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Final Report on the Safety Assessment of Acrylates Copolymer and 33 Related Cosmetic Ingredients
Abstract
Ingredients in the Acrylates Copolymer group all contain the monomers acrylic acid or methacrylic acid or one of their salts or esters. These ingredients are considered similar in that they are uniformly produced in chemical reactions that leave very little residual monomer. Although residual acrylic acid may be as high as 1500 ppm, typical levels are 10 to 1000 ppm. There is sufficient odor if residual monomers are present to cause producers to keep levels as low as possible. These ingredients function in cosmetics as binders, film formers, hair fixatives, suspending agents, viscosity-increasing agents, and emulsion stabilizers. Concentrations may be as high as 25% if used as a binder, film former, or fixative; or as low as 0.5% if used as a viscosity-increasing agent, suspending agent, or emulsion stabilizer. These very large polymers exhibit little toxicity. In rabbits and guinea pigs, Acrylates Copolymer did produce irritation, but no evidence of sensitization was found. The principle concern regarding the use of these polymer ingredients is the presence of toxic residual monomers. In particular, although 2-ethylhexyl acrylate was not genotoxic, it was carcinogenic when applied at a concentration of 21% to the skin of C3H mice. Lower concentrations (2.5%) and stop-dose studies at high concentrations (43%) were not carcinogenic. 2-Ethylhexyl acrylate was not carcinogenic in studies using NMRI mice. Whether an increase in carcinogenesis was seen or not, there was evidence of severe dermal irritation in these 2-ethylhexyl acrylate studies. Another concern regarding residual monomers was inhalation toxicity. Although the acrylic acid monomer is a nasal irritant, exposure to the monomer from use of these polymers in cosmetic formulations would always be less than the established occupational exposure limits for nasal irritation. Although there appears to be a huge variation in the mix of monomers used in the synthesis of these polymers, they are similar in that the polymers, except for dermal irritation, are not significantly toxic, and residual monomer levels are kept as low as possible. Although the monomers may be toxic, the levels that would be found in cosmetic formulations are not considered to present a safety risk. Accordingly, these Acrylate Copolymers are considered safe for use in cosmetic formulations when formulated to avoid irritation.
... Acrylate monomers are the building blocks for producing acrylic polymers and copolymers, and these polymers and copolymers are used for numerous applications, including paint formulations, adhesives, packaging, cosmetic products, synthetic flavoring, industrial coatings, leather finishes, plastics, and textiles (IARC, 1986(IARC, , 1994(IARC, , 1999NTP, 2004;Zondlo Fiume, 2002). Acrylate monomers are based on acrylic acid and consist of esters of increasing carbon length (Autian, 1975): ...
... End-consumer products can contain residual acrylate monomers in food packaging, and other industrial and commercial products such as adhesives; however, only trace levels of acrylic acid and its esters (as a result of polymerization) have been detected (OECD, 2002(OECD, , 2003(OECD, , 2004. Residuals of ethyl-and 2-ethylhexyl acrylate have been found in copolymers used for cosmetic products (Zondlo Fiume, 2002). The levels of monomers found in cosmetic formulations were reported as ≤20 ppm for ethyl acrylate and < 100 ppm to 1000 ppm for 2-ethylhexyl acrylate; however, these levels were not considered to present a safety risk (Zondlo Fiume, 2002). ...
... Residuals of ethyl-and 2-ethylhexyl acrylate have been found in copolymers used for cosmetic products (Zondlo Fiume, 2002). The levels of monomers found in cosmetic formulations were reported as ≤20 ppm for ethyl acrylate and < 100 ppm to 1000 ppm for 2-ethylhexyl acrylate; however, these levels were not considered to present a safety risk (Zondlo Fiume, 2002). ...
Lower alkyl acrylate monomers include methyl-, ethyl-, n-butyl-, and 2-ethylhexyl acrylate. These acrylates are used in the manufacture of acrylic polymers and copolymers for plastics, food packaging, adhesives, and cosmetic formulations. Although there is limited potential for human environmental exposure, occupational exposure can occur via inhalation and dermal contact. Recently, new genotoxicity data have been generated, along with in silico and in vitro read-cross analyses, for these acrylates. The availability of high-throughput screening (HTS) data through the ToxCast™/Tox21 databases allows for consideration of computational toxicology and organization of these data according to the ten key characteristics of carcinogens. Therefore, we conducted a comprehensive review to evaluate the mechanistic, toxicokinetic, animal, and human data, including HTS data, for characterizing the potential carcinogenicity, mutagenicity, and genotoxicity of these acrylates. Toxicokinetic data demonstrate that these acrylates are metabolized rapidly by carboxylesterase hydrolysis and conjugation with glutathione. HTS data demonstrated an overall lack of bioactivity in cancer-related assay pathways. Overall, the genotoxicity and mutagenicity data support a cytotoxic, non-genotoxic mechanism for these acrylates. Cancer bioassay studies conducted by the oral, dermal, and inhalation pathways in animal models with these acrylates did not show any increase in tumor incidence, with two exceptions. At high doses, and secondary to chronic site-of-contact irritation and corrosion, rodent forestomach tumors were induced by oral gavage dosing with ethyl acrylate, and skin tumors were observed following chronic dermal dosing with 2-ethylhexyl acrylate in C3H/HeJ inbred mice (a strain with deficiencies in wound healing), but not in the outbred NMRI strain. For both dermal and forestomach cancers, tumorigenesis is secondary to high doses and long-term tissue damage, hown to be reversible. With evidence that these chemicals are not genotoxic, and that they cause forestomach and dermal tumours through chronic irritation and regenerative proliferation mechanisms, these acrylates are unlikely to pose a human cancer hazard.
... If you are pregnant or lactating, please are trying to find recommendation from your medical doctor previously than the utilization of any product with zinc oxide [1,5,9,23]. It is used as an emulsion stabilizer, pacifying agent, and foam boosting surfactant, as well as an aqueous and non-aqueous viscosity-increasing agent [32]. Mineral Oil 7% Mineral oil has been shown to improve skin softness and barrier function better than some other emollients. ...
... A humectant meaning it holds and binds water, and these properties mean that it is ideal when it comes to keeping water in the skin. It also works as an emollient which means it can moisturize and soothe the skin, as well as help, protect it from environmental factors HA 1% Mentioned before It is used as an emulsion stabilizer, pacifying agent, and foam boosting surfactant, as well as an aqueous and non-aqueous viscosity-increasing agent [32]. Mineral Oil 7% Mineral oil has been shown to improve skin softness and barrier function better than some other emollients. ...
... 15 Furthermore, toxicological studies referred to the soluble silicon derivative as safe, with no genotoxic for use in living beings. 16,17 Objective of the study Our primary objective of this study was to evaluate the correlation between metric parameters and laboratory assessments of patients undergoing oral supplementation of silicon. ...
... Finally, none of our patients complained of side effects due to silicon administration, confirming available data on safeness and security of silanol. 16,17 These effects we observed could be linked to the strengthening of hair sheets and strand, since both of them have a high level of silicon and its role as factor contributing to skin resistance is well established. ...
Objectives: We evaluated the correlation between metric parameters and laboratory assessments of hair taken from patients undergoing oral supplementation of orthosilicic acid. Material and methods: 34 women aged between 17 and 57 years received an oral dose of 30 mg of orthosilicic acid for five months. Hair samples (pre and post-treatment) were obtained from an area of 1 cm² on the occipital protuberance and submitted to ultrasound bath in a distilled water solution. After that, we tested this water using spectrophotometric technique for measuring the hair ability to preserve proteins during physical stress. Hair growth was also assessed every month, before treatment and during treatment. We applied a questionnaire addressing the perception of patients about their hair. Results: 83% of patients believed that there was overall improvement of hair quality after treatment. 79.41% of patients exhibited increasing in hair growth rate and this increase was of 37.6%. Protein loss analysis showed a improvement in hair quality. Conclusion: We suggest that orthosilicic acid has a beneficial role in the hair, leading to a faster growth rate and an increase in resistance to aggression.
... It facilitates the disposal of bodily fluids and prevents spills and is intended to increase patient hygiene and comfort, as well as reducing the workload of care staff for cleaning bodily fluid spills. Although the manufacturer advises against direct use on skin and in body orifices, as well as in children's toys, the chemical mixture has been well studied and is considered to be safe [3]. Eye irritation has been described for sodium polyacrylate in animal studies, but other toxicological or irritant effects have not been observed. ...
Background
Super-absorbent polymers (SAPs) possess the ability to absorb large amounts of water and are widely used in medical settings. Commonly used in vomit bags to contain fluids, reduce spillage, and enhance bedside hygiene, SAPs are generally regarded as safe and non-toxic. However, we report a tragic incident where the accidental ingestion of SAPs led to fatal asphyxiation, highlighting a critical safety concern.
Case presentation
A 76-year-old female suffering from advanced Alzheimer’s dementia was brought to the emergency department following a fall with cervical trauma. Following a complaint of nausea, she was given a vomit bag containing a sachet of approximately 9 g of SAP. Thirty minutes later, she was found deceased in the waiting area, with a grayish, half-hardened gel blocking her oropharynx and remnants of a chewed SAP sachet. Pathological analysis confirmed death by asphyxiation caused by the SAP expanding in her oropharynx upon contact with saliva.
Conclusions
This case emphasizes the potential dangers of SAPs when accidentally ingested and it is imperative that such products are kept out of reach of vulnerable populations. In cases of airway obstruction, there are no specific treatments available. Laryngoscopy may be impossible, necessitating the prompt consideration of an emergency tracheotomy. Experimental data suggest the use of an aerosol of warm alkaline hydrogen peroxide solution to dissolve these obstructive foreign bodies, but further studies are needed to validate its use in emergency situations.
... All processing instructions must be strictly followed to ensure biocompatibility. One risk to not following manufacturer's instructions is the risk of insufficiently cured or polymerized acrylates (the resin used to create the part) as acrylates are a recognized health concern [17][18][19]. ...
Background
Low temperature vaporized hydrogen peroxide sterilization (VH2O2) is used in hospitals today to sterilize reusable medical devices. VH2O2 sterilized 3D printed materials were evaluated for sterilization, biocompatibility and material compatibility.
Materials & methods
Test articles were printed at Formlabs with BioMed Clear™ and BioMed Amber™, and at Stratasys with MED610™, MED615™ and MED620™. Sterilization, biocompatibility and material compatibility studies with 3D printed materials were conducted after VH2O2 sterilization in V-PRO™ Sterilizers. The overkill method was used to evaluate sterilization in a ½ cycle. Biocompatibility testing evaluated the processed materials as limited contact (< 24-hours) surface or externally communicating devices. Material compatibility after VH2O2 sterilization (material strength and dimensionality) was evaluated via ASTM methods and dimensional analysis.
Results
3D printed devices, within a specific design window, were sterile after VH2O2 ½ cycles. After multiple cycle exposure, the materials were not cytotoxic, not sensitizing, not an irritant, not a systemic toxin, not pyrogenic and were hemo-compatible. Material compatibility via ASTM testing and dimensionality evaluations did not indicate any significant changes to the 3D printed materials after VH2O2 sterilization.
Conclusion
Low temperature vaporized hydrogen peroxide sterilization is demonstrated as a suitable method to sterilize 3D printed devices. The results are a subset of the data used in a regulatory submission with the US FDA to support claims for sterilization of 3D printed devices with specified materials, printers, and device design ¹.
... The MW between Cross-links is a parameter that characterizes the average distance between cross-linking points in the polymer network. Since acrylic monomer conversion is reported to reach full conversion [24,25], it was reasonably assumed that the acrylic conversion was completed. Under this hypothesis, the MW between Cross-links can be calculated by dividing the average molecular weight of the monomers (M av ) by the number of acrylic groups per molecule (c) [26], as shown in Equation (4): ...
In the field of encapsulation, microcapsules containing perfume have emerged as effective vehicles for delivering active ingredients across various applications. The present study employed a multivariate analysis framework to examine polyacrylate microcapsules for household products synthesized using different acrylate monomers. The advanced multivariate approach allowed us to quantify critical properties such as the Molecular Weight between Cross-links (MWc), mechanical attributes, Encapsulation Efficiency (EE), and On-Fabric delivery. It is worth noting that the mechanical properties were gauged using a novel nanoindentation technique, which measures the Rupture Force per unit diameter (RFD). Both Encapsulation Efficiency and On-Fabric delivery were assessed using GC-MS. Our findings identified the optimal microcapsule system as one synthesized with 100% aromatic hexafunctional urethane acrylate, showcasing a 94.3% Encapsulation Efficiency and an optimal RFD of 85 N/mm. This system achieved an exemplary On-Fabric delivery rate of 307.5 nmol/L. In summary, this research provides crucial insights for customizing microcapsule design to achieve peak delivery efficiency. Furthermore, by designing acrylic monomers appropriately, there is potential to reduce the amount of active ingredients used, owing to enhanced delivery efficiency and the optimization of other microcapsule properties. Such advancements pave the way for more environmentally friendly and sustainable production processes in the fast-moving consumer goods industry.
... PAA is a white powder that is composed of acrylic acid monomers that are repeatedly linked together to form a so-called polymer structure, and by using a crosslinking agent to induce covalent crosslinking of multiple linear molecules, the polymer is made more polymeric, forming a complex three-dimensional structure [8]. Since PAA is an organic chemical that has water absorbency and thickening properties when dissolved in water, it is used in various products in daily use-from diapers, shampoos, and cosmetics to food additives-and is a highly safe substance that is widely used in general society [9]. In Japan, however, inflammation and fibrosis of the interstitium around the airways have been reported in workers handling PAAs that are water-absorbing crosslinked polymer compounds [5][6][7]. ...
We conducted intratracheal instillations of polyacrylic acid (PAA) with crosslinking and non-crosslinking into rats in order to examine what kinds of physicochemical characteristics of acrylic-acid-based polymers affect responses in the lung. F344 rats were intratracheally exposed to similar molecular weights of crosslinked PAA (CL-PAA) (degree of crosslinking: ~0.1%) and non-crosslinked PAA (Non-CL-PAA) at low and high doses. Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months post-exposure. Both PAAs caused increases in neutrophil influx, cytokine-induced neutrophil chemoattractants (CINC) in the bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in the lung tissue from 3 days to 6 months following instillation. The release of lactate dehydrogenase (LDH) activity in the BALF was higher in the CL-PAA-exposed groups. Histopathological findings of the lungs demonstrated that the extensive fibrotic changes caused by CL-PAA were also greater than those in exposure to the Non-CL- PAA during the observation period. CL-PAA has more fibrogenicity of the lung, suggesting that crosslinking may be one of the physicochemical characteristic factors of PAA-induced lung disorder.
... All published studies on the toxicity of acrylate-based SAPs have shown that these substances have a positive toxicological profile and can be considered environmentally compatible as such [169][170][171][172][173][174] . The influence of polyacrylates on microbial communities of forest soils has been studied by Carbellas et al. by incubating the polyacrylate copolymer Firesorb in the soil [ 175 , 176 ]. ...
Superabsorbent polymers (SAPs) play important roles in our daily life, as they are applied in products for hygiene, agriculture, construction, etc. The most successful commercially used types of SAPs are acrylate-based, which include poly(acrylic acid)s, poly(acrylamide)s, poly(acrylonitrile)s and their salts. The acrylate-based SAPs have superior water-absorbent properties, but they have high molecular weight and in addition an entirely carbon atom-based and cross-linked backbone. These factors endow them with poor (bio)degradability, which has a devastating impact on the environment where such SAP-containing materials may end up at the end of their lifetime. Furthermore, the raw materials for production of acrylate-based SAPs are mostly petroleum-based. From the viewpoint of sustainability, a bio-based resource would be the ideal candidate to replace the fossil-based ones. To overcome the shortcomings of the existing SAPs, bio-based and degradable SAPs are required. This review will then cover the following topics: (1) the technology development history and state-of-the-art of current SAPs; (2) the product designing principles of SAPs; (3) an in-depth introduction and discussion of the structural characteristics and properties of different kinds of SAPs derived from both fossil or renewable resources and (4) novel polycondensate-based, potentially biodegradable SAPs with promising industrial applicability.
... The curing conditions control the mechanical properties and the degradation behavior. In free radical photocuring, the formation of aliphatic backbones, the toxicity of photoinitiators and residual acrylates and methacrylates, are major limitations in developing biodegradable and biocompatible photocurable polyesters [124][125][126][127]. Therefore, alternatives inspired by naturally occurring photosensitive cross-linkers are appealing since these compounds additionally exhibit reversible photocuring (e.g., cinnamate and coumarin groups) and allow controlled degradation [128][129][130]. ...
Bio-based polyol polyesters are biodegradable elastomers having potential utility in soft tissue engineering. This class of polymers can serve a wide range of biomedical applications. Materials based on these polymers are inherently susceptible to degradation during the period of implantation. Factors that influence the physicochemical properties of polyol polyesters might be useful in achieving a balance between durability and biodegradability. The characterization of these polyol polyesters, together with recent comparative studies involving creative synthesis, mechanical testing, and degradation, have revealed many of their molecular-level differences. The impact of the polyol component on the properties of these bio-based polyesters and the optimal reaction conditions for their synthesis are only now beginning to be resolved. This review describes our current understanding of polyol polyester structural properties as well as a discussion of the more commonly used polyol monomers.
... Acrylic monomers serve as reactants for polymers and copolymers. Following a curing process, the polymers and copolymers have a number of unique physical and chemical properties including durability, weather resistance, color stability, and high gloss that make them indispensable for numerous applications [69][70][71][72]. ...
Some chemicals act as human carcinogens in various organ systems including the skin. Mice have been an ideal model to study a wide variety of chemical carcinogens because the pathogenesis in that species often mirrors that in humans. However, different mouse strains vary in their susceptibility to these agents. Thus, reliance on a single strain may lead to inaccurate findings. 2-Ethylhexyl acrylate (2-EHA) is an acrylate used as a co-monomer in the production of polymer resins for adhesives, latex paints, cross-linking agents, finishes for textiles and leather, and paper coatings. Monomer exposure may occur in occupational settings where it is produced or used; the only exposure that may occur to consumers or construction personnel is trace amounts in the final polymer product. There are no reports of cancer in humans caused by exposure to 2-EHA. However, 2-EHA has been reported to cause cancer in one strain of mice. This is an important issue since recommendations about its safety in humans depend, in part, on information derived from animal studies. We reviewed the literature on the preclinical effects of acrylates on skin carcinogenesis in C3H/HeJ mice, which can be criticized because of peculiarities in the immunological composition of that strain, the lack of rigorous histopathologic characterization of tumors that developed, the high doses of 2-EHA that were used for evaluation, and the lack of reproducibility in a second strain of mice. The C3H/HeJ mouse model is not ideal as it has a mutation in Toll-like receptor 4 (TLR4) that impairs its innate and adaptive immune responses. Inconsistencies in the histological evaluation of tumors induced in C3H/HeJ mice provide further evidence that the tumorigenic effect of 2-EHA was strain specific, a result of chronic inflammation during the promotion stage and/or a skewed immune response caused by the TLR4 mutation. In conclusion, 2-EHA has not convincingly been demonstrated to have skin carcinogenic activity to date. More relevant mouse models that mimic human squamous cell carcinoma, basal cell carcinoma, and melanoma with amounts that do not exceed a maximum tolerated dose are needed to assess the carcinogenic effects of 2-EHA.
... End use applications include adhesives, packaging and multilayer films. BA showcases superior photostability and is a preferred monomer where weatherability, with emphasis on low temperature applications especially at high altitudes, and sunlight resistance are required [24,29,30]. ...
Acrylates are the esters, salts and conjugate bases of acrylic acid with its derivatives. They are made from acrylate monomer, which usually comprises of esters which contains vinyl groups, that is two carbon atoms that are double-bonded to each other, and directly attached to the carbonyl carbon of the ester group. Acrylates possess very diverse characteristic properties ranging from super-absorbency, transparency, flexibility, toughness and hardness, among others. These kinds of materials are used in sundry applications such as diapers, cosmetics, orthopedics, paints and coatings, adhesives, textiles, and many biomedical applications such as contact lenses and bone cements. This book chapter highlights the characteristic properties and applications of acrylates, its derivatives and copolymers.
... The durability of the hydrogel coating to maintain the new configuration effect of the hair was assessed through fourth washing processes. The most of polymeric materials are known to be non-toxic/non-irritable in contact with skin (Fiume, 2002;Pemberton and Lohmann, 2014). ...
Hydrogel coating was explored to modulate the shape of keratin hair fiber. The motivation was the development of an eco-friendly methodology with non-toxic chemicals to modulate keratin fiber. Polymeric hydrogel of acrylic acid and N-N-dimethylacrylamide was prepared by free-radical polymerization in aqueous solution, using nano-alumina particles as crosslinker and potassium persulfate as an initiator. Physico-chemical properties of the hydrogel was investigated by Fourier transformer infrared spectrum (FTIR), thermal analysis and swelling ratio behavior. After hydrogel coating, morphological modification was observed from straight to curly hair effect. The influence of hydrogel coating on hair fiber was evaluated by perming efficiency supported by X-ray diffraction and morphological characterization (SEM and AFM). The durability of hydrogel coating was tested until four wash processes maintaining around 65% the new configuration of the hair fiber.
... An effective substance used in the production of cryogels is the cross-linked polymer sodium polyacrylate (PSA). PSA has the ability to absorb 800 times its weight of distilled water or 300 times its weight of tap water [13,28]. The remarkable osmotic nature of the polymer is often used in baby diapers and, when combined with water in correct proportion, takes the appearance and consistency of snow. ...
Through an extensive scoping review, we systematically captured a broad corpus of published literature and identified seven water filtration devices utilizing nanomaterials and low-cost filter matrices with potential to provide potable water for users via POU filtration units that are deemed sustainable. Major criteria examined for acceptable filters include: (i) construction and design, (ii) microbial disinfection efficacy, and (iii) sustainability and challenges. Moreover, various reoccurring themes are noted throughout our findings, including cost-effectiveness, real-application disinfection efficacy, and ease of use at the individual level.
... The exemption has also resulted in the fact that not all polymers have an EC number and information on polymers is limited within the REACH system. For example, a frequent used type of microplastic in cosmetic products is Acrylates Copolymer, which is a group of polymers containing monomers acrylic acid or methacrylic acid or one of their salts or esters [23]. As an ingredient for cosmetic products, Acrylates Copolymer is included in CosIng, the EC Cosmetic ingredient database for information on substances and ingredients [24]. ...
As part of the EU Plastics Strategy, the European Commission has initiated the restriction process regarding intentionally added microplastics under REACH (acronym of the EU chemical regulation). A restriction dossier is compiled by ECHA according the provisions of REACH. Not only environmental and health risk assessments have to be made, but a large part of the dossier concerns socio-economic analyses and evaluations of risk management options, in order to justify a Union-wide restriction. The procedure reflects the multiple objectives of REACH: protection of human health and the environment, but also the functioning of the internal market. Although the precautionary principle is incorporated in REACH, it plays a less than subordinate role. The process of restriction offers interested parties the possibility to present information and evidence. For the restriction dossier on microplastics is of utmost importance that all available evidence is provided. When less data is available, restriction seems to be less likely.
... At the same time, petroleum-derived monomers are usually toxic and pose a potential health risk to personnel exposed to these materials. For instance, exposure to acrylic monomers can lead to clinical symptoms and some of the monomers are possibly carcinogenic to humans [13][14][15]. To create safer products and work environments, it is essential to pursue less toxic alternatives to the monomers used currently. ...
The polymer industry is dominated by the use of petroleum-based feedstock and, as a result of increased awareness, the related environmental consequences have provided the impetus for change. Emulsion polymerization is considered to be a more sustainable technique for the manufacture of polymeric materials because of its use of water as a dispersing medium. To further improve the sustainability of emulsion polymerization technology, the “12 principles of green chemistry and engineering” were used as a guideline for design of a greener process. The most obvious and effective approach is to use renewable, biobased feedstock in emulsion polymerization formulations. In addition, maximizing energy efficiency, preventing waste and pollution, and minimizing the potential for accidents also figure prominently.
... During the synthesis of SAPs, sodium hydroxide (NaOH) or potassium hydroxide (KOH) is used to neutralize AA (Zohuriaan-Mehr and Kabiri, 2008). The final products of SAPs may contain 16% Na þ when 70% AA is neutralized with NaOH, and the concentration of unconsumed free AA may be as high as 1500 mg kg À 1 (Fiume, 2002). Although AA has low toxicity to animals (Staples et al., 2000), its toxicity to plants has not been reported yet. ...
Superabsorbent acrylate polymers (SAPs) have been widely used to maintain soil moisture in agricultural management, but they may cause damage to plants, and the mechanisms are not well understood. In this study, seed germination, soil pot culture, hydroponic experiments, and SAPs degradation were conducted to investigate damage characteristics and mechanisms associated with SAPs application. The Results showed that SAPs inhibited maize growth and altered root morphology (irregular and loose arrangement of cells and breakage of cortex parenchyma), and the inhibitory effects were enhanced at higher SAPs rates. After 1h SAP hydrogels treatment, root malondialdehyde (MDA) content was significantly increased, while superoxide dismutase (SOD) and catalase (CAT) content were significantly decreased. Hydroponics experiment indicated that root and shoot growth was inhibited at 2.5mgL(-1) acrylic acid (AA), and the inhibition was enhanced with increasing AA rates. This effect was exacerbated by the presence of Na(+) at a high concentration in the hydrogels. Release and degradation of AA were enhanced at higher soil moisture levels. A complete degradation of AA occurred between 15 and 20 days after incubation (DAI), but it took longer for Na(+) concentration to decrease to a safe level. These results indicate that high concentration of both AA and Na(+) present in the SAPs inhibits plant growth. The finding of this study may provide a guideline for appropriate application of SAPs in agriculture.
... The number of polyacrylates have a rapid increase owing to various monomer types. Moreover, acrylates polymers exhibit little toxicity although the monomers may be toxic (20). At present, these polyacrylates have been widely used in the fields of binders, film formers, suspending agents, viscosity-increasing agents, emulsion stabilizers, dental restorative materials and biomaterials (21). ...
The aims of this paper are to investigate the inherent relationship between the structures of the polyacrylates and release behaviors as drug carriers in the transdermal drug delivery systems. Three model polyacrylates compounds were synthesized by radical polymerization. Three polymer materials were characterized by Fourier transform infrared, differential scanning calorimeter and cytotoxicity, and the release behaviors of drug molecules transporting through the polymers membranes were tested. Moreover, the effects of the polymers’ structures on the permeability were studied by molecular dynamic simulation. The simulation results showed that higher chains mobility and larger fractional free volume of the polymer membranes resulted in higher permeation rates. By comparing the monomers’ structure in the polymer materials, it was found that the polymer chains’ mobility decreases, and permeation rate correspondingly decreases with the increase in the amount and volume of side groups on the double bonds.
... These materials without graphite are referred to as copolymers without filler. Alkyl acrylate monomers are widely used in the skin care industry and after polymerization have low toxicity (22). ...
Significance
We have successfully fabricated very unique ultraflexible temperature sensors that exhibit changes in resistivity by six orders of magnitude or more for a change in temperature of only 5 °C or less. Our approach offers an ideal solution to measure temperature over a large area with high spatial resolution, high sensitivity of 0.1 °C or less, and fast response time of 100 ms. Indeed, such a large change of resistivity for our sensors can significantly simplify the readout circuitry, which was the key to demonstrate, to our knowledge, the world’s first successful measurement of dynamic change of temperature in the lung during very fast artificial respiration. Furthermore, we have demonstrated real-time multipoint thermal sensing using organic transistor active-matrix circuits.
... The negligible amounts of monomers in drug-containing UV-cured films (Table 3) show that such UV-curable formulations can be used as topical nail medicines, especially if a formulationfree margin is left around the nail to avoid contact with the skin, as the monomers (but not the polymer) have the potential of causing allergic contact dermatitis (Zondlo Fiume, 2002 Gel formulaƟon (prior to UV-curing) Polymer film (aŌer UV-curing) Fig. 2. FT-IR spectra of solvent-free and drug-free monomer formulation and the resulting polymer film after UV-curing. ...
Nail diseases are common, cause significant distress and treatments are far from successful. Our aim was to investigate the potential of UV-curable gels - currently used as cosmetics - as topical drug carriers for their treatment. These formulations have a long residence on the nail, which is expected to increase patient compliance and the success of topical therapy. The gels are composed of the diurethane dimethacrylate, ethyl methacrylate, 2-hydroxy-2-methylpropiophenone, an antifungal drug (amorolfine HCl or terbinafine HCl) and an organic liquid (ethanol or NMP) as drug solvent. Following its application to a substrate and exposure to a UVA lamp for 2minutes, the gel polymerises and forms a smooth, glossy and amorphous film, with negligible levels of residual monomers. No drug-polymer interactions were found and drug loading did not affect the film's properties, such as thickness, crystallinity and transition temperatures. In contrast, the organic solvent did influence the film's properties; NMP-containing films had lower glass transition temperatures, adhesion and water resistance than ethanol-based ones. Water-resistance being a desired property, ethanol-based formulations were investigated further for stability, drug release and ungual permeation. The films were stable under accelerated stability testing conditions. Compared to terbinafine, amorolfine was released to a greater extent, had a higher ungual flux, but a lower concentration in the nailplate. However, both drugs were present at considerably high levels in the nail when their MICs are taken into account. We thus conclude that UV-curable gels are promising candidates as topical nail medicines.
Copyright © 2015. Published by Elsevier B.V.
... SAPs are widely used in many products such as in diapers, feminine napkins, gel actuators, water blocking tapes, medicine for drug delivery systems, absorbent pads, soils for agriculture and horticulture etc, where water absorbency and retention is important ( Bacalski et al., 2003; Alexander, 1994; Brown et al., 1982). Published studies on the toxicity of SAPs on an acrylate basis have shown these substances have a positive toxicological profile and can be considered environmentally compatible (Fiume, 2002; Haselbach et al., 2000; Hamilton, 1995). Staymoist (SM) was identified at the CSIR–SARI laboratories as equivalent to AgraGel for all intents and purposes. ...
Intermittent droughts have in recent years become more frequent and more prolonged in the Guinea savannah agro-ecological zone (GSZ) due to climate change, contributing to increasingly severe yield losses of maize (Zea mays L.), a key food crop in Ghana. The goal of this work was to minimize the negative impact of drought induced soil water stress on maize productivity in the GSZ through the integrated use of early drought tolerant cultivars of maize (Dorke SR and Dodzi), the application of soil conditioner staymoist (SM) and NPK (15-15-15) fertilizer. Experiments were carried out during the period of 2010-2011 cropping seasons at Council for Scientific and Industrial Research-Savannah Agricultural Research Institute (CSIR-SARI), Ghana. A trial comprised five treatments laid in a randomized complete block design with four replicates. The treatments were: T1-No SM+No NPK (Control); T2-0 kg/ha SM+NPK; T3-7.5 kg/ha SM+NPK, T4-15 kg/ha SM+NPK and T5-22.5 kg/ha SM+NPK. Dorke SR generally out yielded Dodzi in grain and stover yields and in total biomass accumulation in all five treatments. Dodzi grain yields for T 3, T 4 and T 5 were 1176, 1559 and 1734 kg/ha, respectively while Dorke SR grain yields for the same treatments were 1386, 1865 and 1971 kg/ha respectively, which were all significantly (P<0.05) higher than the treatments without SM (T 1 and T 2) for both cultivars. Dodzi total biomass yields for T 3, T 4 and T 5 were 3148, 3591 and 3885 kg/ha respectively while Dorke SR total biomass accumulation for the same treatments were 4970, 6909 and 7302 kg/ha respectively, which were all significantly (P<0.05) higher again than the treatments without SM (T 1 and T 2). The results obtained indicate that relatively small amounts of SM were required together with recommended maize fertilization rate to alleviate drought spells and improve maize yields. The optimum treatment was 15 kg/ha SM+NPK. Beyond this rate positive profit declined.
... This is probably in part due to potential absorption of dendritic systems into systemic circulation, which has been observed with other dendrimer systems [17]. The LD 50 of acrylate polymers was reported to be greater than 2g/kg in rats [18]. Anionic G6.5 dendrimers demonstrated similar trends where we did not observe signs of toxicity as 500mg/kg after oral dosage in mice. ...
Poly(amidoamine) (PAMAM) dendrimers have been evaluated for the influence of surface functionality and size on the epithelial barrier of the gut with the goal of identifying safe carriers that can be used for oral drug delivery. Limited studies are conducted to date, however, to assess the toxicity of PAMAM dendrimers in vivo when administered by the oral route. The goal of this research was to conduct an oral acute toxicity study of PAMAM dendrimers as a function of size and charge in immune competent CD-1 mice. Maximum tolerated doses (MTD) of PAMAM dendrimers as a function of size and surface functionality were established and clinical signs of toxicity monitored. Results demonstrate that positively charged dendrimers caused more toxicity, whereas their anionic counterparts were tolerated at ten times higher doses. Severe signs of toxicity observed for large (G7) cationic amine- or hydroxyl-terminated dendrimers include hemobilia and spleenomegaly. The MTD for these dendrimers ranged from 30mg/kg to 200mg/kg. Anionic G6.5 or smaller molecular weight carboxyl-, amine-, or hydroxyl-terminated dendrimers (G3.5-COOH, G4-NH(2), G4-OH) on the other hand were tolerated at doses of up to 500mg/kg (300mg/kg in some cases) with minimal or no signs of toxicity. Establishing the MTD of orally delivered PAMAM dendrimers and the influence of surface functionality and size on toxicity aids in the rational design of PAMAM-drug conjugates for oral drug delivery applications.
... The cellular internalization of nanoparticles has also been reported (Naha et al. 2010a), a phenomenon supported by Leslie Singka who found reduced levels of prostaglandin E 2 (PGE 2 ) in skin dosed with MTX-loaded nanogel (Singka et al. 2010). Additionally, it was reported that some unreacted (residual) monomers could possibly remain even after being purified, typically in the range of 10-1000 ppm for polymers used in cosmetic products (Zondlo 2002). However, after assessment, the Cosmetic Ingredient Review (CIR) Expert Panel considered the reported levels as safe to be used in cosmetic formulations. ...
Abstract Stimulus-responsive nanogels have potential as carriers for drugs targeting the skin. It is important to estimate the biocompatibility of such materials with the skin since they are directly in contact upon application and may induce irritation or inflammation. In the current work, blank (drug-free) polyN-isopropylacrylamide (polyNIPAM), poly(NIPAM copolymerised butyl acrylate) [poly(NIPAM-co-BA)], and poly(NIPAM copolymerized acrylic acid)(5%) [poly(NIPAM-co-AAc)(5%)] nanogels were dosed onto freshly excised porcine ear skin membranes and the effects on the expression on cyclooxygenase-2 (COX-2) determined ex vivo by Western blotting. Modulated COX-2 expression was indicative that the material had penetrated the skin and keratinocytes of the viable epidermis. The poly(NIPAM-co-BA) nanogel was found to exert a proinflammatory response when applied topically, as reflected by 67% higher COX-2 expression relative to the control treatment (p 0.0035). The data obtained for the poly(NIPAM-co-AAc)(5%) nanogel, on the other hand, indicated no significant modulation in the expression of COX-2 (p 0.1578), suggest the particles are compatible with skin. This was even the case in the presence of co-administered aqueous citric acis solution. Overall the data support the use of the multi-responsive poly(NIPAM-co-AAc)(5%) nanogel for triggered or controlled topical drug delivery applications.
... The adaptability of the molecular imprinting technology to the drug delivery field also requires the consideration of safety and toxicological concerns. The device will enter into contact with sensitive tissues; therefore, it should not be toxic, neither should its components, residual monomers, impurities or possible products of degradation [63,64]. Therefore, to ensure biocompatibility it might be more appropriate to attempt to adapt the imprinting technique to already tested materials instead of creating a completely new polymeric system. ...
The application of the molecular imprinting technology in the design of new drug delivery systems (DDS) and devices useful in closely related fields, such as diagnostic sensors or biological traps, is receiving increasing attention. Molecular imprinting technology can provide polymeric materials with the ability to recognize specific bioactive molecules and with a sorption/release behaviour that can be made sensitive to the properties of the surrounding medium. In this review, an introduction to the imprinting technology presenting the different approaches in preparing selective polymers of different formats is given, and the key factors involved in obtaining of imprinted binding sites in materials useful for pharmaceutical applications are analysed. Examples of DDS based on molecularly imprinted polymers (MIPs) can be found for the three main approaches developed to control the moment at which delivery should begin and/or the drug release rate; i.e., rate-programmed, activation-modulated or feedback-regulated drug delivery. This review seeks to highlight the most remarkable advantages of the imprinting technique in the development of new efficient DDS as well as to point out some possibilities of adapting the synthesis procedures to create systems compatible with both the relative instable drug molecules, especially of peptide nature, and the sensitive physiological tissues with which MIP-based DDS would enter into contact when administered. The prospects for future development are also analysed.
Background:
Acrylate polymers and cross-polymers (ACPs) are frequently used cosmetic ingredients. The British Society for Cutaneous Allergy (BSCA) and the UK Cosmetic, Toiletry and Perfumery Association (CTPA) collaborated to investigate the allergenic potential of three commonly-used ACPs.
Objectives:
The objective of this study is to determine the prevalence of allergic contact dermatitis (ACD) to three ACPs: glyceryl acrylate/acrylic acid co-polymer, sodium polyacrylate, and acrylates/C10-30 alkyl acrylate cross-polymer (Carbopol®).
Materials and methods:
The BSCA prospectively audited data collected from 20 centres in the UK and Ireland between 1st September 2021 and 1st September 2022. Patients with suspected ACD to (meth)acrylates, with facial dermatitis, or consecutive patients, were patch tested to glyceryl acrylate/acrylic acid co-polymer 10% aqueous (aq.) sodium polyacrylate 2% aq., and to acrylates/C10-30 alkyl acrylate cross-polymer 2% aq. (Carbopol®). The frequencies of positive, irritant, and doubtful reactions were recorded.
Results:
In total, 1302 patients were patch tested. To glyceryl acrylate/acrylic acid co-polymer, there was one doubtful reaction in a patient allergic to multiple (meth)acrylates, and one irritant. To sodium polyacrylate, there were four irritant reactions, one doubtful, and one positive reaction; in all cases, relevance was unknown and there was no demonstrable (meth)acrylate allergy. There were no reactions to Carbopol®.
Conclusions:
Sensitisation to these concentrations of the three tested ACPs is rare. Elicitation of dermatitis in (meth)acrylate-sensitised patients by exposure to these three ACPs appears unlikely.
The global acrylate monomers market is projected to reach approximately USD 12 billion by the year 2027. The rapid growth is based on the broad range of application of acrylates from routine household uses and cosmetics/personal care to industrial and surgical/dental applications. With the steep increase in volume and broad use of these products comes increased likelihood of exposure and the potential for adverse effects. Hence, this chapter focuses mainly on the hazard profiles, potential exposure scenarios, and exposure control measures for the various chemical classes of these acrylates. Each section within this chapter integrates scientific, regulatory, and epidemiological information collected from publicly available peer‐reviewed publications and databases maintained by recognized regulatory agencies in various jurisdictions.
Occurrence of volatile organic compounds (VOCs) such as benzene in personal care products is a topic of public health concern. Sunscreen products are extensively used to protect skin and hair from UV radiation from sun light. Nevertheless, little is known about exposure doses and risks of VOCs present in sunscreens. In this study, we determined the concentrations of and exposure to three VOCs, namely benzene, toluene and styrene, in 50 sunscreen products marketed in the United States. Benzene, toluene and styrene were found in 80 %, 92 % and 58 %, respectively, of the samples analyzed at mean concentrations of 45.8 ng/g (range: 0.007-862 ng/g), 89.0 ng/g (range: 0.006-470 ng/g) and 161 ng/g (range: 0.006-1650 ng/g), respectively. The mean dermal exposure doses (DEDs) to benzene, toluene and styrene in children/teenagers were 68.3, 133 and 441 ng/kg-bw/d, respectively, whereas those in adults were 48.7, 94.6 and 171 ng/kg-bw/d, respectively. The cancer risk from benzene concentrations present in 22 sunscreen products (44 % of the samples) on children/teenagers and 19 sunscreen products (38 %) on adults, exceeded the acceptable benchmark risk level (1.0 × 10-6). This is the first study to comprehensively assess the concentrations of and risks to benzene, toluene and styrene present in sunscreen products.
A structure-activity study was conducted to identify the structural characteristics underlying the adjuvant activity of straight (i.e. non-crosslinked) polyacrylate polymers (PAAs) in order to select a new PAA adjuvant candidate for future clinical development. The study revealed that the adjuvant effect of PAA was mainly influenced by polymer size (Mw) and dose. Maximal effects were obtained with large PAAs above 350 kDa and doses above 100 μg in mice. Small PAAs below 10 kDa had virtually no adjuvant effect. HPSEC analysis revealed that PAA polydispersity index and ramification had less impact on adjuvanticity. Heat stability studies indicated that residual persulfate could be detrimental to PAA stability. Hence, this impurity was systematically eliminated by diafiltration along with small Mw PAAs and residual acrylic acid that could potentially affect product safety, potency and stability. The selected PAA, termed SPA09, displayed an adjuvant effect that was superior to that of a standard emulsion adjuvant when tested with CMV-gB in mice, even in the absence of binding to the antigen. The induced immune response was dominated by strong IFNγ, IgG2c and virus neutralizing titers. The activity of SPA09 was then confirmed on human cells via the innate immune module of the human MIMIC® system.
Acrylates (acrylic esters) are versatile monomers that are widely used in polymer formulations because of their highly reactive α,β-unsaturated carboxyl structure. Commonly used acrylates such as butyl acrylate are known to emit a strong unpleasant odour, and the monomers are therefore potential off-odorants in acrylic polymers. However, up to now, the odour properties of structurally related acrylic esters have not been characterised in detail. To obtain deeper insights into the smell properties of different acrylates, we investigated the relationship between the molecular structure and odour thresholds as well as the odour qualities of 20 acrylic esters, nine of these synthesised here for the first time. The OT values of 16 acrylates fell within the range from 0.73 to 20 ng/Lair, corresponding to a high-odour activity. Moreover, sec-butyl acrylate and 2-methoxyphenyl acrylate showed even lower OT values of 0.073 and 0.068, respectively. On the other hand, the OT values of the hydroxylated acrylates 2-hydroxyethyl acrylate and 2-hydroxypropyl acrylate were 5–244 times higher than those of the other compounds, demonstrating that the presence of a hydroxyl group obviously favours odour inactivity.
Poly(meth)acrylates were introduced to the pharmaceutical market in 1954 for the use in oral dosage forms in order to replace time-consuming sugar coatings on tablets in the beginning, closely followed by more functional versions in order to create taste masked and protective coatings or enteric-coated as well as extended release-coated particles, but also for the creation of extended release matrix structures.
Newer developments cover the field of multilayered coatings for longer drug release, specific release profiles or a more precise targeting for regional drug release. Especially the latter can be influenced successfully by the addition of specific ions inside such coated dosage forms in order to create modified/pulsed drug release profiles for improved therapies.
Disposable diapers for adults are widely used in many parts of the developed world to safely and effectively manage urinary and fecal incontinence. Their usage is relatively uncommon in the developing world, although adult diapers are manufactured and exported from and used in India and China, to a limited extent. It is estimated that 90–95 % of adult incontinence diapers that are used in developed nations are of the disposable kind. These products are in direct contact with the skin of the individual when worn, and given that adult diapers are changed three times a day on average, an incontinent adult may be exposed to approximately a thousand disposable diapers per year. This manuscript provides an overview of the application of quantitative risk assessment principles to the safety evaluation of adult care disposable diapers.
This is a safety assessment of alumina and aluminum hydroxide as used in cosmetics. Alumina functions as an abrasive, absorbent, anticaking agent, bulking agent, and opacifying agent. Aluminum hydroxide functions as a buffering agent, corrosion inhibitor, and pH adjuster. The Food and Drug Administration (FDA) evaluated the safe use of alumina in several medical devices and aluminum hydroxide in over-the-counter drugs, which included a review of human and animal safety data. The Cosmetic Ingredient Review (CIR) Expert Panel considered the FDA evaluations as part of the basis for determining the safety of these ingredients as used in cosmetics. Alumina used in cosmetics is essentially the same as that used in medical devices. This safety assessment does not include metallic or elemental aluminum as a cosmetic ingredient. The CIR Expert Panel concluded that alumina and aluminum hydroxide are safe in the present practices of use and concentration described in this safety assessment.
Disposable diapers for adults are widely used in many parts of the developed world, to safely and effectively manage urinary and fecal incontinence. Their usage is relatively uncommon in the developing world, although adult diapers are manufactured and exported from and used in India and China, to a limited extent. It is estimated that 90-95% of adult incontinent diapers that are used in developed nations are of the disposable kind. These products are in direct contact with the skin of the individual when worn, and given that adult diapers are changed three times a day on average, an incontinent adult may be exposed to approximately a thousand disposable diapers per year.
Methacrylate allergies are more common among dental personal and nail technicians. Beauticians who do not use artificial nails nor provide this service for their customers usually do not belong to a risk group. Here we report on a 43-year-old beautician presenting with lid eczema related to the use of a face mask. In the present case there was a strong positive patch test reaction to EGDMA, HEMA and HPMA. We suspect that the patients was sensitized due to methacrylic monomers in a temporary restoration material, but relapsed by exposure to acrylic residues in a facial mask preparation. Although (meth)acrylates are commonly used in cosmetics sensitisation is rather rare, but nevertheless may be responsible for allergic contact dermatitis in single patients.
The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of 62 dimethicone crosspolymer ingredients as used in cosmetics. These ingredients function mostly as absorbents, bulking agents, film formers, hair-conditioning agents, emollient skin-conditioning agents, slip modifiers, surface modifiers, and nonaqueous viscosity-increasing agents. The Panel reviewed available animal and human data related to these polymers and addressed the issue of residual monomers. The Panel concluded that these dimethicone crosspolymer ingredients are safe in the practices of use and concentration as given in this safety assessment.
Biomolecular interactions (antigen-antibody, enzyme-substrate and drug-receptor) have been investigated due to their selective nature. Thus, since 1940, the search for synthetic materials presenting specific binding sites has been increasing. Nowadays, they are well established in different science areas such as pharmacy, analytical chemistry, biochemistry, among others, being the referred materials called molecularly imprinted polymers-MIP. Although the largest applications of MIP are found in the separations science field, few applications of these polymers have been reported as drug delivery systems-DDS. Such applications have been promising due to the feasibility of the MIP synthesis. However, the clinical use of the MIP as DDS is still not observed, probably due to its recent application, as well as extensive tests necessary for its approval as a new pharmaceutical form. In this way, this work aims to present the most recent progresses in the use of MIP as DDS, reinforcing the most significant aspects of this application (potentialities and limitations), as well as classifying and detailing such systems.
As interações biomoleculares (antígeno-anticorpo, enzima-substrato e fármaco-receptor) há muito tempo têm despertado o interesse de diversos pesquisadores quanto à sua natureza seletiva. Nesse contexto, principalmente a partir de 1940, observa-se uma crescente busca por materiais sintéticos dotados de sítios seletivos de reconhecimento. Hoje, esses materiais encontram-se bem estabelecidos em diversas áreas da ciência como farmácia, química analítica, bioquímica, dentre outras, e são rotineiramente intitulados como polímeros impressos molecularmente (molecularly imprinted polymers-MIP). Embora sua maior aplicação esteja voltada às técnicas de extração/separação, alguns trabalhos têm empregado os MIP como matrizes em sistemas de liberação controlada de fármacos (drug delivery system-DDS), devido ao caráter promissor de tal aplicação e pela facilidade de obtenção desses materiais. Entretanto, o emprego clínico de MIP como DDS ainda é inexistente em decorrência de sua recente aplicação e também pelos extensivos testes que precedem a aprovação de um novo sistema de liberação controlada de fármaco. O objetivo deste trabalho é apresentar os mais recentes avanços no emprego de MIP como DDS reforçando os aspectos mais significativos dessa aplicação, bem como classificando e detalhando esses sistemas quanto aos mecanismos pelos quais o fármaco é liberado.
The application of superabsorbent polymers (SAPs) and/or biochars to stressed lands offer solutions to several critical ecological, energy and economic challenges posed by degraded lands due to human activities. These substances are like, 'artificial humus' as they are hydrophilic and contain carboxylic groups (SAPs) which enable them to bind cations and water and sequester carbon from air to reverse global warming (biochars). Several research studies using these substances point to their ability to increase the plant-available water in the soil which enables the plants to survive longer with water shortage, increase soil fertility and agricultural yields, improve soil structure, aeration and water penetration, reduce use of synthetic fertilisers and pesticides, reduce nitrous oxide and methane emission from soil, reduce nitrate and farm chemicals leaching into watersheds, convert green and brown wastes into valuable resources, and reduce the evapotranspiration rate of the plants. SAPs and biochars induce a significantly higher growth rate in plants; they bind heavy metals and mitigate their action on plants as well as mitigate the effects of salinity. This paper reviews what is known about these claims and considers the wider environmental implications of the adoption of these processess. The intention is not just to summarise the current knowledge but also to identify gaps that require further research.
About 3.5 billion ha of land, which amounts to almost 30% of the total solid land of the world, has been degraded by human activities. The ecological restoration of these lands is a major challenge for mankind since they are the only option left for increasing the amount of arable land and producing food for the ever growing worldwide population. One common feature of these degraded lands is the fact that their organic soil matter is degraded also. Rainfall therefore, changes from a blessing to a menace since it is not kept in the soil and therefore causes erosion. A solution for the restoration of these lands could be the application of superabsorbent polymers (SAPs) to these soils. These substances are like ‘artificial humus’ as they are hydrophilic and contain carboxylic groups. This enables them to bind cations and water. They have the following advantages for the restoration of degraded lands. They increase the plant available water in the soil which enables the plants to survive longer under water stress. SAP amendment to soils reduces the evapotranspiration rate of the plants. They induce a significantly higher growth rate in plants growing on SAP amended soil. They bind heavy metals and mitigate their action on plants. They mitigate the effects of salinity. The benefits of SAP amendment to soils substantially outweigh their costs.
An in situ photopolymerization-coating technique was applied to wrap the pellets surface with a pH-sensitive hydrogel layer made from acrylic acid and hydrophobic acrylate monomers. Powdered cellulose (Elcema® P100) and poly(vinylpyrrolidone) (Kollidon® 30) pellets containing theophylline were prepared by extrusion–spheronization, sprayed with an ethanol:water 50:50 v/v solution of the monomers, the cross-linker (N,N′-methylenebis(acrylamide)) and the initiator (Irgacure® 2959), and immediately irradiated at 366 nm. The composition of coating mixture and the time of irradiation were optimized using oscillatory rheometry and analyzing the swelling and the drug release behaviour of the resultant hydrogels. When acrylic acid:lauryl acrylate 88:12 molar ratio was used, the coating did not significantly change the shape, size, or friability of the pellets, but remarkably modified theophylline release profiles. The thicker the coating layer, the better the pH-dependent control of drug release.
Aqueous polymer dispersions are important raw materials used in a variety of industrial processes. They may contain particles with diameters ranging from 10 to 1500 nm. Polymer exposure alone may cause pulmonary lesions after inhalation exposure. Polymer dispersions with increased proportions of nano-sized particles are being developed for improved material characteristics, and this may pose even increased pulmonary hazards upon potential inhalation exposure. In a 5-day screening study, male rats were nose-only exposed to aerosols generated from 2 dispersions of acrylic ester polymers with identical chemical composition but different nano-sized particle proportions at particle concentrations of 3 and 10 mg/m³. Immediately and 19 days after the end of inhalation, necropsies were conducted with major emphasis on respiratory tract histopathology. Three and 23 days after the end of inhalation, bronchoalveolar lavage was performed to screen for early pulmonary injury and inflammation. In contrast to the adverse effects known for other materials in short-term inhalation studies, none of the tested preparations of acrylic ester polymers elicited any adverse effect at the end of the inhalation or postinhalation periods. No shift in toxicity could be observed by the increased proportion of nano-sized polymer particles. Under the conditions of this study, the no observable adverse effect levels for both preparations were >10 mg/m³, that is 2- to 3-fold beyond current nuisance dust threshold limit values.
Baby diapers are complex products consisting of multiple layers of materials, most of which are not in direct contact with the skin. The safety profile of a diaper is determined by the biological properties of individual components and the extent to which the baby is exposed to each component during use. Rigorous evaluation of the toxicological profile and realistic exposure conditions of each material is important to ensure the overall safety of the diaper under normal and foreseeable use conditions. Quantitative risk assessment (QRA) principles may be applied to the safety assessment of diapers and similar products. Exposure to component materials is determined by (1) considering the conditions of product use, (2) the degree to which individual layers of the product are in contact with the skin during use, and (3) the extent to which some components may be extracted by urine and delivered to skin. This assessment of potential exposure is then combined with data from standard safety assessments of components to determine the margin of safety (MOS). This study examined the application of QRA to the safety evaluation of baby diapers, including risk assessments for some diaper ingredient chemicals for which establishment of acceptable and safe exposure levels were demonstrated.
It is generally thought that residual unpolymerized (meth)acrylic monomers commonly found in pressure sensitive adhesive tapes for medical use may cause dermal irritation, but a systematic study has never been carried out. Therefore, we assessed the potential dermal irritating effect of residual (meth)acrylic monomers. We studied seven acrylic monomers, acrylic acid (AA), methyl acrylate (MA), ethyl acrylate (EA), n-butyl acrylate (n-BA), n-hexyl acrylate (n-HA), 2-ethylhexyl acrylate (2-EHA) and 2-hydroxyethyl acrylate (HEA), as well as three methacrylic monomers, methacrylic acid (MAA), methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (2-HEMA). We first examined their cytotoxic effect on a cultured dermis model using the MTT method to determine their EC(50) and then performed a primary irritation test in rabbits using the monomers at three different concentrations (i.e., EC(50) , one-tenth EC(50) and 10 times EC(50)). Marked variations were found in cytotoxic and dermal irritating activities among the (meth)acrylic monomers tested. HEA exhibited the most potent dermal irritation having the lowest erythema dose (the concentration which gives a primary dermal irritation index of 1.00) of 460 ppm. But the other monomers exhibited less potent dermal irritation (lowest erythema doses > or =1000 ppm). For the monomers, significant correlation was found between cytotoxic activity and in vivo dermal irritating activity. Our results show that residual unpolymerized (meth)acrylic monomers in adhesive tapes are unlikely to induce skin irritation except for HEA. This study also suggests that cultured skin models are extremely useful as a screening method for chemical substances that could potentially cause dermal irritating activity.
Molecular imprinting technology has an enormous potential for creating satisfactory drug dosage forms. Although its application in this field is just at an incipient stage, the use of MIPs in the design of new drug delivery systems (DDS) and devices useful in closely related fields, such as diagnostic sensors, is receiving increasing attention. Examples of MIP-based DDS can be found for the three main approaches developed to control the moment at which delivery should begin and/or the drug release rate, i.e. rate-programmed, activation-modulated, or feedback-regulated drug delivery. The utility of these systems for administering drugs by different routes (e.g. oral, ocular or transdermal) or trapping undesired substances under in vivo conditions is discussed. This review seeks to highlight the more remarkable advantages of the imprinting technique in the development of new efficient DDS as well as pointing out some possibilities to adapt the synthesis procedures to create systems compatible with both the relative instable drug molecules, especially of peptide nature, and the sensitive physiological tissues with which MIP-based DDS would enter into contact when administered. The prospects for future development are also analysed.
Immunization of two specific regions of the murine GI tract of two types of mice with ovalbumin (OVA) encapsulated in microbeads with two different pH-sensitive coatings allowed a more precise analysis of this compartment of the mucosal immune system. Acute, chronic and pervasive immunization protocols were utilized in an attempt to stimulate specific types of immunity. Chronic immunization potentiated antibody isotypes influenced by type 2 T helper cells (T(h)2). Pervasive immunization of both regions of the GI tract mimicked chronic immunization, stimulating high levels of OVA-reactive IgE. Acute immunization was best able to potentiate isotypes influenced by type 1 T helper cells (T(h)1) and a sequential segregated immunization protocol allowed the targeting of T(h)1-like memory responses.
Unscheduled DNA synthesis was observed in primary rat liver cell cultures treated with members of five different classes of chemical procarcinogens requiring enzymatic activation as well as with a direct-acting carcinogen. In total, ten carcinogens and one related analog not commonly accepted as carcinogenic were active, while one weak carcinogen and four noncarcinogens were inactive. The production of unscheduled DNA synthesis by this spectrum of chemical carcinogens indicates that these cultures have substantially retained the metabolic capability of liver for activating diverse procarcinogens. Thus, such cultures may be useful for detecting the ability of chemicals to interact with DNA and, thereby, assigning them priority for consideration as potential cancer-causing agents.
In a chronic study conducted by the National Toxicology Program (NTP), gavage administration of 100 or 200 mg ethyl acrylate (EA)/kg/day, 5 days/week, to F344 rats and B6C3F1 mice resulted in a significant dose-dependent increase in the incidence of squamous cell papillomas and carcinomas of the forestomach of both sexes of rats and mice. No increase in the incidence of tumors was observed at any other site in these rats. Chemically-induced cell proliferation is currently thought to play a role in the development and progression of chemically-induced neoplasia. Therefore, a stop-study was initiated where 100 or 200 mg EA/kg (in corn oil) was administered daily, 5 days/week, for 13 weeks. Rats sacrificed at the end of the treatment regimen had severe epithelial hyperplasia of the forestomach. No lesions were observed in the glandular stomach or liver of EA-treated rats. Forestomach hyperplasia induced by EA included upward and downward cell proliferation. However, forestomachs of rats treated for 13 weeks and sacrificed 8 weeks after the last EA dose exhibited a significant decline in the incidence and severity of forestomach mucosal hyperplasia. Histopathologic evaluation of forestomachs of EA-treated rats (13 weeks) which were allowed a 19-month-recovery (with no exposure to EA) showed further decline in the incidence and severity of mucosal cell hyperplasia. These results indicate that gavage administration of EA to rats results in extensive and sustained forestomach mucosal hyperplasia. The sustainability of forestomach hyperplasia is apparently dependent on the continued exposure of rats to ethyl acrylate, and regressed after cessation of dosing. Furthermore, although enough post-treatment time was allowed for tumors to develop after cessation of EA administration, forestomachs exhibited a nearly complete recovery with no increased incidence of papillomas or carcinomas. It, therefore, remains to be determined what duration of exposure or other factors are critical for reversibility or progression of EA-induced forestomach mucosal hyperplasia to neoplasia.
Following oral dosing of [2,3-14C]acrylic acid (AA; 4, 40, or 400 mg/kg) and [2,3-14C]ethyl acrylate (EA; 2, 20, or 200 mg/kg), the dosed radioactivity was rapidly excreted, with 50–75% of the dose for both compounds eliminated within 24 hr. The primary excretory metabolite for both compounds is carbon dioxide, accounting for 44–68% of the dose. HPLC analysis of the urine of AA- and EA-dosed animals indicated the presence of 3-hydroxypropionic acid. The detection of this metabolite suggests the incorporation of AA into propionic acid metabolism and may explain the rapid evolution of carbon dioxide from AA and EA. HPLC analysis of urine from EA-dosed rats revealed the presence of two metabolites derived from glutathione conjugation, N-acetyl-S-(carboxyethyl)cysteine and N-acetyl-S-(carboxyethyl)cysteine ethyl ester. The excretion of the N-acetyl cysteine derivatives of EA, expressed as a percentage of the dosed compound, decreased in a dose-dependent manner that may be attributed to the depletion of glutathione in organs primarily responsible for glutathione conjugation. No significant decrease in hepatic nonprotein sulfhydryl (NPSH) content was observed following oral dosing with EA at 2–200 mg/kg. However, the depletion of NPSH content at the dosing site, forestomach, and glandular stomach, decreased significantly between 0.02 and 0.2% EA in the dose solution (2 and 20 mg/kg). This observation would suggest that the dosing site represents a significant site of conjugation for relatively low doses of EA. Treatment with the carboxylesterase inhibitor, tri-o-cresyl phosphate (TOCP), 18 hr prior to acrylate dosing potentiated the depletion of hepatic nonprotein sulfhydryls, emphasizing the dominance of hydrolysis as a systemic detoxifying mode in this species. In contrast to EA, AA did not significantly decrease NPSH content in the liver, blood, or forestomach at oral doses of <8% AA in the dose solution (400 mg/kg), although a significant depletion of NPSH was observed in the glandular stomach at doses >0.08% (4 mg/kg). No conjugation involving the double bond of AA could be detected in in vitro reactions with glutathione or in the in vivo metabolites, suggesting a secondary effect of AA on NPSH content in these organs. The weights of the forestomach and glandular stomach increased with AA dose, reflecting gross edema and inflammation. With EA this effect on organ weight was only demonstrated in the forestomach, and the response was increased when hydrolysis of EA was inhibited with TOCP. The effect of AA or EA on stomach weight and NPSH content may be attributed to the concentration of these local irritants in the dose solution at the site of dosing.
The developmental toxicities of seven acrylates were studied in Sprague-Dawley rats after inhalation exposure for 6 h/day, during days 6 to 20 of gestation. The exposure concentrations were: for acrylic acid, 50, 100, 200, or 300 ppm; for methyl acrylate, 25, 50, or 100 ppm; for ethyl acrylate, 25, 50, 100, or 200 ppm; for butyl acrylate, 100, 200, or 300 ppm; for ethylhexyl acrylate, 50, 75, or 100 ppm; for hydroxyethyl acrylate, 1, 5, or 10 ppm; and for hydroxypropyl acrylate, 1, 5, or 10 ppm. No treatment-related increases in embryo/fetal mortality or fetal malformations were observed after exposure to any of these acrylates. Fetal toxicity, indicated by reduced fetal body weight, was observed after exposure to 300 ppm acrylic acid, 100 ppm methyl acrylate, 200 ppm ethyl acrylate, and 200 or 300 ppm butyl acrylate in the presence of overt signs of maternal toxicity. While there was evidence of maternal toxicity, no significant developmental toxic effects were observed after exposure to ethylhexyl acrylate, hydroxyethyl ac-rylate, or hydroxypropyl acrylate at any concentration. These results indicate that inhaled acrylic acid, methyl acrylate, ethyl acrylate, butyl acrylate, ethylhexyl acrylate, hydroxyethyl acry-late, and hydroxypropyl acrylate are not selectively toxic to the embryo or fetus.
During 64 months (1977 to 1983), twelve dermatologists from various sections of the United States studied a total of 713 patients with cosmetic dermatitis out of an estimated total of 13,216 patients with contact dermatitis. The number of patients seen for all causes during this period was 281,100. An important finding was that half of the patients or physicians were unaware that a cosmetic was responsible for their dermatitis. Skin care products, hair preparations (including colors), and facial makeup were responsible for the majority of the reactions. The most important objective was identification of causative ingredients. Eighty-seven percent of the subjects had patch tests. Fragrance, preservatives (Quaternium-15, formaldehyde, imidazolidinyl urea, and parabens), p-phenylenediamine, and glyceryl monothioglycolate were the most frequently identified allergic sensitizers, in that order. In addition to the clinical data, the study permitted assessment of the frequency of cosmetic reactions, although the data may not be entirely representative of the country at large because of the special interests of the dermatologists involved.
Differential Thermal Analysis (DTA) can be used to identify some of the organic polyelectrolytes and polymeric flocculating agents. Results are presented for certain polysaccharides, polyacrylates, and polyacrylamide.
Di(2-ethylhexyl)phthalate and 33 other phthalates, ethylhexanol derivatives, and related chemicals were tested for mutagenicity in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 without metabolic activation and in the presence of rat and hamster liver S-9 metabolic activation systems. No mutagenic activity was seen with any of the chemicals tested.
Azulene is an extract from the volatile oil of several perennial herbs and is detected in tobacco smoke. It functions as a skin conditioning agent in cosmetic formulations, including hair dyes. Azulene is reported to be used in a wide range of cosmetic formulations, but these reported uses are likely to be uses of guaiazulene, a chemically related colorant, because there are currently no suppliers of Azulene to the cosmetics industry. The anti-inflammatory action of Azulene has been demonstrated in several animal studies. Effects at the cellular level are reported to include inhibition of respiration and growth, but no effect on ciliary activity or membrane permeability. Relatively low oral toxicity was seen in acute animal studies. Azulene was not mutagenic in an Ames test, with and without metabolic acfivation. An allergic response to Azulene was noted in one case report. These data were clearly insufficient to support the safety of Azulene in cosmetics. Additional data needed to make a safety assessment include: methods of manufacture and impurities, especially naphthalenes; current concentration of use; skin penetration, if there is significant skin penetration, then both a 28-day dermal toxicity study to assess general skin and systemic toxicity and a reproductive and developmental toxicity study are needed; one genotoxicity study in a mammalian system, if positive, then a 2-year dermal carcinogenesis study using National Toxicology Program methods is needed; skin irritation and sensitization in animals or humans; and ocular toxicity.
Polyvinylpyrrolidone (PVP) is a linear polymer of 1-vinyl-2-pyrrolidone monomers used as a binder, emulsion stabilizer, film former, hair fixative, and suspending agent-nonsurfactant. The molecular weight of the polymer ranges from 10,000 to 700,000. PVP K-30, with an average molecular weight of 40,000, is typically used in cosmetic formulations. The highest concentration reported to be used is 35%. There was no significant absorption of PVP K-30 given orally to rats, and the acute oral LD50 was >100 g/kg for rats and guinea pigs. Neither toxic effects nor gross lesions were found in rats maintained for two years on a diet containing 10% PVP K-30. Short-term PVP inhalation studies produced mild lymphoid hyperplasia and fibroplasia in rats, but no inflammatory response. In animal studies, no evidence of significant ocular irritation, skin irritation, or skin sensitization was found at PVP-iodine solution concentrations of 10%. While PVP-iodine is not a cosmetic ingredient, these negative findings were considered to support the safety of the PVP component. Undiluted PVP K-30 was not a dermal irritant or sensitizer in clinical tests. No developmental toxicity was seen in vehicle controls where PVP was used as a vehicle for another agent. In certain assay systems, PVP was genotoxic, but was negative in the majority of studies. Orally administered PVP significantly decreased the rate of bladder tumors in mice exposed to bracken fern. Several studies tested the carcinogenicity of subcutaneous implants of particulate PVP in rats, mice, and rabbits. Although the majority of these studies conducted in rats were positive, tumors (sarcomas) were localized to the site of implantation. Based on the available data, it was concluded that PVP is safe as used in cosmetics.
Pregnant Sprague-Dawley rats (5 per group) were exposed in a pretest to 0, 225, and 450 ppm acrylic acid (AA) and in a main study (30 per group) to 0, 40, 120, and 360 ppm acrylic acid. Exposures were for 6 hr/day, during Days 6 to 15 of gestation (period of organogenesis), with further observation up to Day 20 after mating. Maternal toxicity occurred in animals exposed at 450 and 225 ppm in the pretest. At 360 ppm in the main study maternal toxicity consisted of sensory irritation (discharge from the eyes, snout wiping, and restless behavior) with significant reductions in body weight (p < 0.01), body weight gain (p < 0.01), and food consumption (p < 0.01) relative to that of chamber controls. Effects on body weight and body weight gain were dose-related and when corrected for uterus weight were significant in animals exposed to 120 ppm (p < 0.01), with an effect on body weight gain also at 40 ppm (p < 0.05), indicating a minimal maternal toxic effect. There were no signs of group-related trends or significant differences between groups in terms of numbers of preimplantation losses, live fetuses, or resorptions, and no signs of group-related differences in the incidences of abnormalities, variations, or retardations in the fetuses in terms of general appearance and the condition of the internal organs or the skeletons. It is concluded that under the experimental conditions of the main study acrylic acid vapor at concentrations between 40 and 360 ppm had no embryotoxic teratogenic effects on Sprague-Dawley rats. Maternal toxicity was minimal at 40 ppm, clearer at 120 ppm, and more pronounced at 360 ppm.
Elimination of phosphates from detergents alone, is insufficient to solve the eutrophication problem. Nevertheless, the endeavors of the detergent industry are aimed at finding phosphate subsitutes. Novel approaches for at least a partial replacement of detergent phosphates have been found by using water-soluble organic complexing agents as well as heterogeneous organic or inorganic ion exchangers. So far, a large-scale replacement is not possible. It is not justifiable until all technical requirements are met with and safety with regard to man, animals, plants and drinking water has been established.
Ethyl acrylate or methyl methacrylate have been added to the drinking water of rats in concentrations of 0, 6–7, 60–70, and 2000 ppm for a period of two years. On the basis of fluid and food consumption observations, these concentrations of the test materials were estimated to be equivalent to about 10, 100, and 3000 ppm in the food. Mortality was unaffected. Body weights of female rats receiving 2000 ppm of ethyl acrylate in the water were significantly depressed or bordered on this throughout the study, and this concentration also significantly depressed body weights of males through the first year. Similar depression among rats receiving 2000 ppm of methyl methacrylate did not last beyond the first few weeks. Depressed food consumptions tended to parallel the periods of depressed growth. For both materials, fluid consumptions were significantly lower in rats receiving 2000 ppm. Hematologic values and urine concentrations of protein and reducing substances varied within normal limits for all groups of rats. Organ to body weight ratios were comparable for all groups except for significantly elevated kidney ratios in female rats receiving 2000 ppm of methyl methacrylate. Histopathologic findings revealed no lesions attributable to either test material.
Multifunctional acrylates are being used increasingly as replacements for solvents, and occupational and general population exposure to this structural class is expanding. Four multi-functional acrylates and acrylic acid were tested for mutagenicity in the Salmonella typhimurium and mouse lymphoma L5178Y TK+/−assays. In the Salmonella assay, two of the compounds (trimethylolpropane triacrylate and trimethylolpropane trimethacrylate) showed weakly positive results with a single tester strain (TA1535) in the presence of hamster liver S9; the other three compounds were negative. All five compounds were negative in the Salmonella assay without S9 activation. In the mouse lymphoma assay, two of the compounds (acrylic acid and ethylene glycol diacrylate) were positive in both the presence and the absence of S9, one compound was positive only in the presence of S9 (ethylene glycol dimethacrylate), and one compound was positive only in the absence of S9 (trimethylolpropane triacrylate).
Data on allergic contact dermatitis from acrylates and 4 patients sensitized during routine patch testing are reported. During 1982–1985, we used 7 different acrylates for tests. 1 patient out of 22 (=4.5%) was sensitized to ethyl acrylate and butyl acrylate (1% pet.). Since September 1985, we have used a commercial (meth)acrylate series containing 28 substances. 3 of 24 patients tested became sensitized to ethyl acrylate, 2-hydroxyethyl acrylate and 2-hydroxypropyl acrylate (0.5% pet.). Because active sensitization with acrylates can be very harmful, it may be necessary to use lower concentrations than recommended. Currently, we test ethyl acrylate, 2-hydroxyethyl acrylate and 2-hydroxypropyl acrylate at 0.167% pet.
The results and data from the testing of 255 chemicals for mutagenicity in Salmonella are presented. All chemicals were tested under code using a preincubation modification of the Salmonella/microsome test in the absence of exogenous metabolic activation and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters.
The conditions for obtaining representative, adult rat hepatocyte primary cell cultures were improved such that viable yields
of 50% of the liver were produced which gave rise to cultures representing 30% of the liver. The survival of the cultures
in various media was compared revealing that in complex media, particularly containing galactose, survival was improved.
An in vivo method for screening drugs, food additives, and other chemicals that might cause chromosomal aberrations has been tested. It is reliable, easy, and very much more rapid than the traditional method.
To clarify the mutagenic activity of individual smoke components, 239 compounds, representative of the gaseous and semivolatile phases of tobacco smoke, were assayed for mutagenicity towards 4 histidine-requiring mutants of Salmonella typhimurium (TA 98, TA 100, TA 1535 and TA 1537). All compounds were tested qualitatively both with and without metabolic activation using a liver fraction (S-9) from Aroclor 1254 or methylcholanthrene induced rats. Without S-9, only 2,3-dimethylindole and 2,3,5-trimethylindole showed mutagenic activity that was not enhanced by hte metabolic activation system. 2,6-Diaminotoluene and coronene, which like the above compounds are not documented carcinogens were found to be mutagenic for strain TA 98 with S-9. Mutagenic activity was also observed for the previously known mutagens benz[a]pyrene, chrysene, benz[a]-anthracene, perylene and β-naphthylamine, on exposure to strains TA 98 and/or TA 100 with S-9.
The analysis of NA-5 and NA-6, copolymers of acrylic acid and N-vinylpyrrolidone obtained by the method of radical copolymerization, indicated that these copolymers, while having no toxicity characteristic of polyacrylic acid known to be a powerful agent for stimulating immunogenesis, increased the migration of stem cells, and the processes of T and B lymphocyte spreading, as well as sharply enhanced the effect of interaction between T and B lymphocytes and partially replaced the helper function of T cells; all these actions finally enhanced immune response in the body. A decrease in the toxicity of copolymers was found to be in linear relationship with the percentage of the links of acrylic acid, whereas the adjuvant activity of the copolymers remained unchanged.
The current status of the L5178Y/TK+/- leads to TK-/- mouse-lymphoma mutagenicity assay is described. Dose-survival-mutagenic response data are shown for 43 chemicals. Mutagenicity and cytotoxicity in the presence or absence of non-induced and/or Aroclor-induced rat-liver S-9 are compared for most of these chemicals, 25 of these for which usuable carcinogenicity data exist have been used to construct an approximately linear relationship between oncogenic potency in vivo and mutagenic potency in this system in vitro; linearity between these two endpoints extends over a greater than 100,000-fold range in potencies. Several carcinogens which are negative or difficult to detect in the standard Ames assay are mutagenic in this mammalian cell system. These include natulan, sodium saccharin (lot S-1022), p,p'-DDE (metabolite of DDT), dimethylnitrosamine, diethylnitrosamine and diethylstilbestrol. Characterization of the TK-/- mutants suggests that two mutagenic mechanisms contribute to their final yield. Large-colony TK-/- mutants probably represent point or gene mutations affecting the TK locus. In addition, a class of small-colony TK(/- mutants are described and characterized as being heritably growth-deficient; this and other properties suggest that these small-colony TK-/- mutants originate by a heritable and viable chromosomal aberration. Most carcinogens and mutagens tested produce both classes of TK-/- mutants in this system; the relative proportions of small- and large-colony mutants are both mutagen- and dose-dependent. Comparative studies have been done at the rapidly-expressing TK locus and the slowly-expressing HGPRT locus in these cells. Several carcinogens detected at the TK locus are non- or very weakly mutagenic at the HGPRT locus. This findings is consistent with the induction of slow-growing specific locus mutants by a chromosomal mechanism and their subsequent dilution during this long expression time.
The conditions for obtaining representative, adult rat hepatocyte primary cell cultures were improved such that viable yields of 50% of the liver were produced which gave rise to cultures representing 30% of the liver. The survival of these cultures in various media was compared revealing that in complex media, particularly containing galactose, survival was improved.
Polyacrylic acid (PAAC), lipopolysaccharide (LPS), dextran sulphate (DS) and purified protein derivative of tubercle bacilli (PPD), compounds mitogenic for B lymphocytes in vitro, suppressed the immune response of mice to SRBC in vivo, when injected 4-2 days before immunization. The same compounds enhanced the immune response when injected half an hour before immunization of the animals with a suboptimal antigen dose. A subsequent injection of PAAC given shortly before immunization, abolished the immunosuppressive effect expected by pretreatment of the animals with either PAAC or LPS. A second injection of LPS abolished the immunosuppressive effect of LPS only. The results indicate that when B lymphocytes react with a mitogen in the absence of a particular antigen, they temporarily lose their capacity to respond to antigen.
A rat-liver microsomal system in vitro has been used to activate two indirectly acting carcinogens, DMN and DEN. On activation, both compounds were extremely potent in inducing chromosomal aberrations as well as sister chromatid exchanges in Chinese hamster cells. The implications of these findings and the potential utility of this technique to detect mutagens/carcinogens are discussed.
Acrylic acid (AA) and its esters are used extensively for the production of a variety of polymers. Despite their ubiquitous nature, little has been reported on the metabolism of the parent acid. The metabolites of AA may be volatile, unstable, polar, and thus difficult to isolate. Therefore, 13C NMR was used to help identify and compare directly the urinary metabolites of both 99% 13C-enriched AA and propionic acid (PA). Male Sprague-Dawley rats received [1,2,3-13C]AA (400 mg/kg in water p.o.) or an equimolar dose of [1,2,3-13C]propionate together with a radioactive tracer, [2,3-14C]AA, or [1-14C]propionate, respectively, and excreta were collected for 72 hr. For both acids, expiration of 14CO2 was the major route of elimination of radiolabel (approximately 80%). Approximately 6% of the dose was excreted in the urine. Urine was analyzed directly using proton-decoupled 13C and two-dimensional 13C homonuclear correlated NMR spectroscopy. The urine from AA-treated rats revealed major signals, the intensity of which was time-dependent, from at least five 13C-enriched metabolites of AA. Signals have been assigned to 3-hydroxypropionic acid, N-acetyl-S-(2-carboxyethyl)cysteine, and N-acetyl-S-(2-carboxyethyl)cysteine-S-oxide by comparison with spectra of authentic standards. No unchanged AA was detected. In contrast, the spectra of urine from a propionate-treated rat revealed only a few minor 13C-enriched signals that were assigned to methylmalonic acid. No unchanged PA was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
The alkaline elution assay were applied for testing DNA damage of forestomach squamous epithelium in male F344 rat after oral administration of ethyl acrylate (EA), a forestomach carcinogen. The animals were starved for 18 hr and then given a single oral dose of EA. No DNA damage were observed by EA at the concentration of 0.1-4.0%. The weights of the forestomach increased with EA dose, reflecting edema and inflammation, but that of glandular stomach did not change with its dose.
Induction of mitotic chromosome loss could be demonstrated for the dialdehyde glyoxal, the diketones 2,3-butanedione and 2,3-hexanedione, ethyl and methyl carbamate, ethyl acrylate, dibromoacetonitrile, 2-hydroxypropionitrile and formaldehyde, but only when they were combined with subacute concentrations of propionitrile, which is a strong inducer of chromosomal malsegregation. The same chemicals did not induce mitotic chromosome loss when applied in pure form. However, glyoxal, ethyl acrylate, dibromoacetonitrile and formaldehyde when applied in pure form also induced mitotic recombination. Respiratory deficiency was induced, in the absence of propionitrile, by these recombinogenic agents and also by 2,3-hexanedione and 2-hydroxypropionitrile which are not recombinogenic.
Acrylic acid was tested for gene mutations in the in vitro CHO/HGPRT assay, for chromosome aberrations in CHO cells in culture, and for potential to induce unscheduled DNA synthesis in rat hepatocytes in culture. In vivo assays performed included the Drosophila sex-linked recessive lethal assay by both the feeding and injection routes, the in vivo cytogenetic assay in rat bone marrow cells after both a 1-day and 5-day oral dosing regimen, and a dominant lethal assay in mice by both an acute and 5-day dosing regimen. All results were negative (non-mutagenic) except for the in vitro chromosome aberration assay. This latter result is consistent with the previously reported possible clastogenic activity suggested by the results of the mouse lymphoma L5178Y TK locus assay in which a predominance of small-colony mutants was observed (Moore et al., Environmental and Molecular Mutagenesis 1988, 11, 49-63). The rapid clearance of acrylic acid in animals and the weight of evidence of genetic toxicity testing, including negative in vivo data in both somatic and germ cells, indicate a lack of genetic toxicity of acrylic acid in vivo.
The Chinese hamster ovary (CHO) assay, which measures newly induced mutations at the hypoxanthine-guanine phosphoribosyltransferase (hgprt) locus, has been widely used for mutagenesis testing. The insensitivity of the standard assay to some genotoxic agents has been speculated to be due to the relatively small number of cells used in the assay. In the present study, we have compared the standard monolayer assay with a suspension adapted CHO assay that uses cell numbers comparable to that of the L5178Y mouse lymphoma assay. Nine compounds, ethyl methanesulfonate (EMS), methyl methanesulfonate (MMS), 2-methoxy-6-chloro-9-[3-(ethyl-2-chloroethyl)-aminopropylamino]-acridine 2HCl (ICR 170), methyl acrylate, ethyl acrylate, tetraethylene glycol diacrylate, trimethylolpropane triacrylate, 2-ethylhexyl acrylate and dicyclopentenyloxyethyl methacrylate were evaluated in the monolayer and suspension assays. Both assays gave the same overall qualitative results for the test compounds. There were some quantitative differences in the mutant frequency for the three compounds found to be mutagenic (EMS, MMS and ICR 170). The acrylates (many of which appear to exert their genotoxic effect through a clastogenic mechanism) were negative in both test systems. The use of the suspension assay did not improve the ability of the hgprt locus to detect the genotoxicity of the acrylates. Thus, increasing the number of cells does not improve the ability of the CHO/HGPRT assay to detect compounds that act primarily by a clastogenic mechanism.
Over the past several years, we have been evaluating the mutagenicity and clastogenicity of compounds capable of Michael-type
reactions. These compounds, including acryla-mide, several acrylate and methacrylate esters, vinyl sulfones, and phorone,
have been evaluated using TK+/−-3.7.2C mouse lymphoma cells. Mutagenic chemicals induced increases in the number of small colony tk− deficient mutants. This suggested a clastogenic mechanism which was confirmed by demonstrating increases in aberrations and
micronucleus frequencies in cultured cells. Vinyl sulfone was found to be the most effective chemical mutagen with induction
of genotoxic effects at concentrations as low as 0.25 μg/ml. The other compounds also produced positive results, but at higher
concentrations. Since these compounds are known to deplete glutathione, phorone, a model gluta-thione depleter, was examined
and found to produce similar effects as the other compounds in mouse lymphoma cells. These results suggest that the direct-acting
Michael-type reaction has activity relevant to producing a genotoxic effect. Since acrylamide has been found to be a potent
germ cell mutagen, this mechanism may be also relevant in the induction of heritable mutagenic risk.
The Prenatal Inhalation Toxicity of Acrylic Acid in Rats. Klimisch, H.-J., and Hellwig, J. (1991). Fundam Appl Toxicol. 16, 656–666. Pregnant Sprague–Dawley rats (5 per group) were exposed in a pretest to 0, 225, and 450 ppm acrylic acid (AA) and
in a main study (30 per group) to 0, 40, 120, and 360 ppm acrylic acid. Exposures were for 6 hr/day, during Days 6 to 15 of
gestation (period of organogenesis), with further observation up to Day 20 after mating. Maternal toxicity occurred in animals
exposed at 450 and 225 ppm in the pretest. At 360 ppm in the main study maternal toxicity consisted of sensory irritation
(discharge from the eyes, snout wiping, and restless behavior) with significant reductions in body weight (p < 0.01), body weight gain (p < 0.01), and food consumption (p < 0.01) relative to that of chamber controls. Effects on body weight and body weight gain were dose-related and when corrected
for uterus weight were significant in animals exposed to 120 ppm (p < 0.01), with an effect on body weight gain also at 40 ppm (p < 0.05), indicating a minimal maternal toxic effect. There were no signs of group-related trends or significant differences
between groups in terms of numbers of preimplantation losses, live fetuses, or resorptions, and no signs of group-related
differences in the incidences of abnormalities, variations, or retardations in the fetuses in terms of general appearance
and the condition of the internal organs or the skeletons. It is concluded that under the experimental conditions of the main
study acrylic acid vapor at concentrations between 40 and 360 ppm had no embryotoxic teratogenic effects on Sprague-Dawley
rats. Maternal toxicity was minimal at 40 ppm, clearer at 120 ppm, and more pronounced at 360 ppm.
Multifunctional acrylates are being used increasingly as replacements for solvents, and occupational and general population exposure to this structural class is expanding. Four multifunctional acrylates and acrylic acid were tested for mutagenicity in the Salmonella typhimurium and mouse lymphoma L5178Y TK+/-assays. In the Salmonella assay, two of the compounds (trimethylolpropane triacrylate and trimethylolpropane trimethacrylate) showed weakly positive results with a single tester strain (TA1535) in the presence of hamster liver S9; the other three compounds were negative. All five compounds were negative in the Salmonella assay without S9 activation. In the mouse lymphoma assay, two of the compounds (acrylic acid and ethylene glycol diacrylate) were positive in both the presence and the absence of S9, one compound was positive only in the presence of S9 (ethylene glycol dimethacrylate), and one compound was positive only in the absence of S9 (trimethylolpropane triacrylate).
The clastogenicity of ethyl acrylate (EA) was examined in vivo by injecting i.p. five male C57BL/6 mice per dose group with either 125, 250, 500 or 1000 mg/kg EA dissolved in saline. Controls received solvent only. Acrylamide (100 mg/kg), because of its similarity in structure and mode of action to EA, was used as a positive control. Twenty-four hours after injection, the animals were anesthetized and the spleens aseptically removed. Splenocytes were isolated on density gradients and cultured with concanavalin A to stimulate cell division. In half the cultures bromodeoxyuridine was added at 21 h for analysis of chromosome aberrations (CAs) in first division cells and sister chromatid exchange (SCE) in second division cells. In the remaining cultures cytochalasin B was added to produce binucleated cells for scoring of micronuclei (MN). There was no significant increase in SCE or CAs at any of the doses of EA examined. At the highest dose examined (1000 mg/kg), EA did cause a small but significant increase in binucleated cell MN. Acrylamide caused an increase in MN and SCEs in splenocytes. Because others have found EA to be clastogenic in vitro, isolated splenocytes were exposed to a wide range of concentrations of EA during the G0 stage of the cell cycle or 23 h after mitogen stimulation during the late G1 or early S phase of the cell cycle. Although EA was toxic for both exposure regimens, significant increases in chromatid-type aberrations were found only when the target cells were treated 23 h after mitogenic stimulation. No statistically significant increase in SCE frequency was found after either treatment regimen. These data suggest that EA is only clastogenic at near toxic concentrations during a specific stage of the cell cycle.
No exposure-related clinical signs or lesions of systemic toxicity and no oncogenic responses were observed in male and female Sprague-Dawley rats exposed by inhalation to methyl acrylate (MA) or n-butyl acrylate (BA) vapours, at concentrations of 0, 15, 45 and 135 ppm. The rats were whole-body-exposed 6 hr/day, 5 days/wk, for 24 consecutive months. There was a 6-month post-exposure observation period for subgroups of BA-exposed rats. Atrophy of the neurogenic epithelial cells and hyperplasia of reserve cells were observed in the nasal mucosa of all MA- and BA-exposed groups. These changes were dose related and mainly affected the anterior part of the olfactory epithelium. Opacity and neovascularization of the cornea were seen in all MA-exposed groups and in the group exposed to 135 ppm BA. These toxic effects of the olfactory epithelium and cornea were attributed to the known irritancy of MA and BA. In the BA subgroups kept for a 6-month post-exposure observation, reconstructive effects, such as replacement of altered olfactory epithelium with respiratory epithelium, and partial regression of corneal neovascularization were observed.
The effectiveness of four in vitro short-term tests (STT) for genetic toxicity, induction of mutations in Salmonella (SAL) and mouse lymphoma L5178Y cells (MLA), and induction of sister chromatid exchanges (SCE) and chromosome aberrations (ABS) in Chinese hamster ovary cells that are used for predicting rodent carcinogenicity were examined. The in vitro results were compared with the results from 41 rodent carcinogenicity studies performed by the National Toxicology Program. The predictive values of, and interrelationships among, the STT for these 41 chemicals were similar to those previously reported for 73 chemicals and confirm those earlier results [Tennant RW, Margolin BH, Shelby MD, Zeiger E, Haseman JK, Spalding J, Caspary W, Resnick M, Stasiewicz S, Anderson B, Minor R (1987): Science 236:933-941]. Because of this similarity among the two datasets, the chemicals were combined into a single dataset of 114. The results with 114 chemicals show that SAL had the lowest sensitivity (.48) and the highest specificity (.91), whereas MLA had the highest sensitivity (.72) and the lowest specificity (.40). The concordances of the test results with rodent carcinogenicity were .66, .61, .59, and .59, for SAL, ABS, SCE, and MLA, respectively. Salmonella was the most predictive for carcinogenicity; 89% of the chemicals mutagenic in SAL were carcinogenic in rodents, however a negative result in any or all of the STT was not indicative of noncarcinogenicity. The STT results reported here show good agreement with the potential electrophilicity of the chemicals, and the majority of carcinogens that are undetected by the STT do not have an electrophilic structure. There was no complementarity among the tests and no combination of the four tests was more effective than any single test for predicting carcinogenicity.
An artificial immune complex consisting of IgG covalently bound to polyacrylic acid (PAIGP) was prepared and investigated for its influence on a number of immunological reactions attributed to natural immune complexes. PAIGP consumed complement in a fast reaction. Complement consumption was complete after 10 min of incubation of guinea-pig serum with PAIGP. The concentration of PAIGP for 50% consumption was 2.3 micrograms/ml. PAIGP induced a chemiluminescence response in human peripheral polymorphonuclear leukocytes. This response was elicited in the absence and presence of serum and in whole blood. The response was maximal for leukocytes in the absence of serum and rather low in whole blood. The induction of chemiluminescence by PAIGP was inhibited by monoclonal antibodies to one of the Fc receptors of leukocytes (anti-Leu 11B), while unrelated antibodies had no influence on the chemiluminescence induced by PAIGP. PAIGP also stimulated the production of superoxide anion by polymorphonuclear leukocytes. The efficacy of PAIGP in stimulation of superoxide production was comparable to phorbol myristate acetate (PMA) and opsonized zymosan. PAIGP induced the discharge of elastase, a constituent of the azurophile granules of PMN leukocytes. Here, PAIGP was a rather weak stimulus compared to opsonized zymosan. PMA proved unable to induce elastase release. Thus, PAIGP induced a number of biological reactions usually brought about by naturally occurring antigen antibody complexes.
Male F344/N rats were dosed with ethyl acrylate (EA) either by daily gavage or in the drinking water for 2 weeks. The gavage dose levels were 0, 2, 10, 20, 50, 100, and 200 mg/kg; the drinking water dose concentrations were 0, 200, 1,000, 2,000, and 4,000 ppm (corresponding to 0, 23, 99, 197, and 369 mg/kg/day, respectively). In those animals dosed by gavage, irritation of the forestomach increased in incidence and severity over the 20-200 mg/kg dose range. In those animals dosed with EA in the drinking water, a much lower incidence of forestomach irritation and less severe lesions were observed at corresponding dose levels. No lesions were observed in the glandular stomach from either of the 2 modes of oral administration. Following 2 weeks of gavage dosing with EA, the total non-protein sulfhydryl (NPSH) content of the forestomach and glandular stomach, and the NPSH concentration of the liver were determined 2-24 hr after the last gavage dose. Animals dosed at 200 mg/kg reached approximately 11% of the initial NPSH content in the forestomach at 6 hr after dosing. NPSH depletion of this magnitude has been associated with cytotoxicity of other tissues in other studies. By contrast, either the glandular stomach nor liver were depleted of NPSH to levels generally associated with toxicity. These observations are consistent with the conclusion that bolus dosing of EA induces severe depletion of critical cellular thiols in the forestomach with toxic consequences, but not in the glandular stomach or liver. Changing the mode of oral administration for EA to continued small doses in the drinking water allowed efficient detoxification and did not induce sulfhydryl depletion or comparable forestomach toxicity at the same daily body burden.
Three linear polycarboxylate compounds, two linear polyacrylates (90,000 MW and 4,500 MW) and one linear polyacrylate-maleate copolymer (12,000 MW), were tested for their teratogenic potential in female Sprague Dawley rats. These polymers, which were tested as sodium salts, are used as dispersing agents in detergent formulations at levels of 1-5%. All compounds were administered by gavage during organogenesis (days 6-15 of pregnancy). No adverse effects on development were seen with any of the three compounds at any of the doses tested. The highest dose, and therefore the minimum no-effect dose, for the three linear polymers was 1125 mg/kg/day for the 90,000 MW polyacrylate, 3000 mg/kg/day for the 4,500 MW polyacrylate, and 6670 mg/kg/day for the polyacrylate-maleate copolymer. Based on these data, these compounds are not developmentally toxic, even at very high dose levels.
A carcinogenicity bioassay of 2-ethylhexyl acrylate (2-EHA) was conducted by applying 25 microliters 86.5%, 21%, or 2.5% 2-EHA in acetone three times a week to the clipped dorsal skin of male C3H/HeJ mice (80 per group) over their lifetime. Another group was treated with a 43% 2-EHA solution for 24 weeks and thereafter observed for lifetime (stop-test). An untreated group and a group that received only the diluent acetone served as controls. Treatment-related changes in the skin indicative of irritation (scaling, scabbing, hyperkeratosis, hyperplasia) were found in all 2-EHA-treated groups. These lesions were reversible in the 43% group immediately after treatment was stopped, and in the 2.5% group after the 11th week of treatment. Only in the 86.5% and 21% test groups showing chronic irritative skin damage was there a high incidence of nepolastic skin lesions (papillomas, carcinomas, and melanomas) with no dose dependency. In contrast, no skin tumors were found in the control groups, in the group treated with 2.5% 2-EHA for lifetime or in the group treated with 43% 2-EHA for about 6 months and observed for lifetime.
Two linear polymers of acrylic acid (average molecular weight = 2,000 and 4,500) and one linear copolymer of acrylic and maleic acids (average molecular weight = 12,000) were tested for mutagenicity with the Salmonella mammalian microsome assay, the L5178Y mouse lymphoma assay at the TK locus, an unscheduled DNA synthesis assay in primary cultures of rat hepatocytes, and either an in vitro cytogenetic assay with CHO cells or the bone marrow micronucleus assay in mice. The results of all the assays were uniformly negative for the three polymers.
We report ethyl acrylate to be inactive as a micronucleus-inducing agent in the bone marrow of mice following its i.p. injection in either corn oil or water. These data contrast with a strong positive response in this assay reported earlier. This discrepancy is discussed.
Recent reports by several laboratories indicate that not all non-essential target loci are equally capable of detecting chromosomal mutations. The present study was undertaken to determine if both the tk locus in mouse lymphoma cells and the hgprt locus in Chinese hamster ovary (CHO) cells can be used to quantitate chromosomal mutations. Seven known mutagens for the tk locus were selected. These compounds were evaluated in the mouse lymphoma assay and in a suspension adapted CHO assay for their mutagenicity. In addition to the specific locus mutagenesis analysis, mouse lymphoma and CHO cells were evaluated for the frequency of gross chromosome aberrations. From these investigations, it appears that only those compounds [2-methoxy-6-chloro-9-(3-[ethyl-2-chloroethyl] aminopropylamino)-acridine-dihydrochloride (ICR 170), ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS)] that induce significant numbers of large-colony thymidine kinase (TK) mutants also induce significant numbers of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) mutants. The four acrylates evaluated (methyl acrylate, ethyl acrylate, trimethylolpropane triacrylate and tetraethyleneglycol diacrylate) induced almost exclusively small-colony TK mutants and very few if any HGPRT mutants. Aberration analysis revealed that both the mouse lymphoma and CHO cells responded to the clastogenicity of the compounds (except for ICR 170 which was not positive in CHO cells) and that neither cell line was clearly more sensitive than the other to the clastogens tested. It is significant that the four acrylates give little or no evidence of genotoxicity when evaluated using selection for HGPRT-deficient mutants, yet are clearly clastogenic to the same cells in the same experiment. These results are consistent with the hypothesis that the hgprt locus may not be useful as a marker to evaluate the clastogenic component of a genotoxic compound. The present study adds to the increasing number of studies that support the view that the hemizygous nature of the hgprt locus permits the recovery of mutations primarily affecting the function of a single gene; whereas the heterozygous nature of the tk locus permits the recovery of both single gene and chromosomal mutations.
Nine acrylate/methacrylate esters were tested for the induction of mutations, aberrations and micronuclei in cultured L5178Y mouse lymphoma cells without exogenous activation. With the exception of 2-ethylhexyl acrylate, and dicyclopentenyloxyethyl methacrylate which produced equivocal mutagenic responses, the other seven compounds (2-hydroxyethyl acrylate, dicyclopentenyloxyethyl acrylate, tetraethylene glycol diacrylate, tetraethylene glycol dimethacrylate, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, and pentaerythritol triacrylate) produced positive mutagenic responses with different potencies. For the mutagenic acrylates/methacrylates, primarily small-colony, trifluorothymidine (TFT)-resistant mutants were induced, suggesting a clastogenic mechanism that was supported by increased aberrations and micronucleus frequencies (except for trimethylolpropane trimethacrylate which was positive for aberration but not micronucleus induction). Generally, it was found that multifunctional compounds (esters with greater than 1 functional vinyl group) required lower concentrations than monofunctional compounds to induce maximal cytotoxic, mutagenic, and clastogenic responses. In addition, acrylates were generally more potent than their corresponding methacrylates. This information and these comparative activities will provide some guidance for setting priorities of concern for hazard consideration for acrylate/methacrylate ester compounds.
Adverse effects, involving a combination of hypotension and widespread haemorrhages, as well as evidence of vascuiiar and other tissue dissociation, associated with various systemic malfunctions (cyanosis, cardiac arrhythmias, neuromuscular disorder and death) were observed in the rat, from parenteral administration of a high‐molecular‐weight soluble polymer, sodium polyacrylate (EN21). Experiments to elucidate the mechanism of this effect involved comparisons with a low‐molecular‐weight sodium polyacrylate (EN5), either drug being given to groups of 5–8 rats, male or female, in doses of 5–100 mg/kg i.v., i.p. or s.c., or up to 100 mg/kg p.o. Effects were observed visually up to the death of the animals, and these plus survivors killed after 10 h were prosected for macroscopic and histopathological examination of internal organs. Characteristic EN21 effects were only observed in animals treated by the i.p. and i.v. routes, death occurring in 4–10 h or rapidly (1 h) after i.v. dosage. No such effects were observed from ENS by any dose or route. There were no differences between effects in male and female animals.
In rats anaesthetized with sodium pentobarbitone and cannulated for blood pressure recording (arterial and venous), no hypertensive effects were observed to explain haemorrhagic effects. Instead, i.v. and i.p. injections gave depressor effects, insidious in the latter case, with a precipitous fall only in the delayed terminal stage. Effects were accompanied by cardiac arrhythmias. Depressor effects were prevented by prior treatment of the animals with calcium chloride solution. These effects could not be evoked by EN5, nor by injection of methylcellulose solutions of equivalent high viscosity. It is suggested that, in the absence of pressor effects, haemorrhages must be explained by vascular fragility (angiostaxis), associated with disintegration of other tissues (e.g. intestinal villi). Other malfunctions, too rapid to be dependent on loss of blood, could be explained in terms of hypocalcaemia.
It is suggested that localization of this viscous, high‐molecular‐weight material in vascularized compartments, together with its known ability to form insoluble precipitates with calcium, leads to the operation of a calcium ‘sink’. Resulting hypocalcaemia would explain neuromuscular and cardiac malfunctions, while radical loss of tissue calcium could lead to decrease in cellular adhesion. Resultant loss of tissue integrity could be consistent with observed haemorrhage and disintegrative lesions.
Acrylic acid (AA), ethyl acrylate (EA) and n-butyl acrylate (BA) are widely used in the production of plastics, coatings and acrylic fibres. Occupational exposure occurs primarily via inhalation and/or skin contact.
In chronic inhalation experiments EA and BA did not induce neoplastic changes in rats and mice (Klimisch and Reininghaus 1984; Miller et al. 1985). Additional investigations showed that AA and BA were not carcinogenic in mice after chronic dermal application (De Pass et al. 1984). However, recently other authors reported a weak carcinogenic potential of AA and BA after chronic dermal administration to mice (Cote et al. 1986). The conditions of the latter study lead to the suggestion that the observed tumours had developed secondarily due to the local irritating and corrosive properties of AA and BA.
This view is supported by the negative results of AA, EA and BA in the conventional Ames test (Waegemaekers and Bensink 1984). Mutagenicity data in mammalian cell systems of EA were equivocal (Henschler 1986) and were lacking for AA and BA. For this reason the mutagenic potential of AA and BA was investigated in Syrian hamster embryo fibroblasts (SHE cells). DNA repair (UDS assay), chromosomal changes (micronucleus assay) and morphological transformation were chosen as biological endpoints.
Butyl acrylate (BA) is one of the major monomers used in the manufacture of polymers and resins. Because little is known regarding its metabolic fate in animals, it was of interest to study the metabolism and disposition of BA in the rat. After oral administration, butyl [2,3-14C]acrylate was rapidly absorbed and metabolized. The acrylate moiety was metabolized primarily to CO2, accounting for elimination of up to 75% of the administered radiolabel. Elimination in urine and feces accounted for approximately 10 and 2% of the dose, respectively. Initial clearance of radioactivity from the tissues was very rapid and then decreased to a negligible rate 2 hr after iv administration. Total radioactivity in the major tissues was relatively constant from 2 to 24 hr. The majority of the radioactivity in the blood at 24 hr was found to be covalently bound to the protein fraction of the red blood cell membranes. There was some evidence of a first-pass effect when BA was administered by gavage because iv administration resulted in less metabolism to CO2 and quantitative differences in urinary metabolites. The two major metabolites in urine were identified as N-acetyl-S-(2-carboxyethyl)cysteine and N-acetyl-S-(2-carboxyethyl)cysteine-S-oxide. Results of this study indicated that the major portion of a BA dose was hydrolyzed to acrylic acid, which was further metabolized to compounds available for oxidative metabolism. Radiolabeled carbons from the BA molecule were excreted as CO2 or incorporated in trace amounts into lipids, proteins, and other products of de novo synthesis. A smaller portion of the BA dose was conjugated with endogenous glutathione.(ABSTRACT TRUNCATED AT 250 WORDS)
The disposition of methyl [2,3-14C]-acrylate (MA) and 2-ethylhexyl [2,3-14C]-acrylate (EHA) following intraperitoneal and oral administration to rats has been studied. The 14C found in the tissues was mainly associated with liver, kidneys and lungs. Loss of 14C from these tissues occurred fairly rapidly, excluding the rats given EHA intraperitoneally. Most of the administered acrylates underwent rapid metabolism and excretion with expired air (more than 50% of the dose and urine (10-50% of the dose). Significant differences in the rates of 14C loss from tissues and excretion occurred after intrapritoneal administration of MA and EHA. A possible cumulation of EHA in the organism was suggested.