Article

Final Report on the Safety Assessment of Sodium p-Chloro-m-Cresol, p-Chloro-m-Cresol, Chlorothymol, Mixed Cresols, m-Cresol, o-Cresol, p-Cresol, Isopropyl Cresols, Thymol, o-Cymen-5-ol, and Carvacrol

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Abstract

Sodium p-Chloro-m-Cresol, p-Chloro-m-Cresol (PCMC), Mixed Cresols, m-Cresol, o-Cresol, p-Cresol, Isopropyl Cresols, Thymol, Chlorothymol, o-Cymen-5-ol, and Carvacrol are substituted phenols used as cosmetic biocides/preservatives and/or fragrance ingredients. Only PCMC, Thymol, and o-Cymen-5-ol are reported to be in current use, with the highest concentration of use at 0.5% for o-Cymen-5-ol in perfumes. The use of PCMC in cosmetics is restricted in Europe and Japan. Cresols can be absorbed through skin, the respiratory tract, and the digestive tract; metabolized by the liver; and excreted by the kidney as glucuronide and sulfate metabolites. Several of these cresols increase the dermal penetration of other agents, including azidothymidine. In acute oral toxicity studies, LD50 values were in the 200 to 5000 mg/kg day-1 range across several species. In short-term studies in rats and mice, an o-Cresol, m-Cresol, p-Cresol or m-Cresol/p-Cresol mixture at 30,000 ppm in the diet produced increases in liver and kidney weights, deficits in liver function, bone marrow hypocellularity, irritation to the gastrointestinal tract and nasal epithelia, and atrophy of female reproductive organs. The no observed effect levels (NOEL) of o-Cresol was 240 mg/kg in mink and 778 mg/kg in ferrets in short-term feeding studies, with no significant dose-related toxicity (excluding body weight parameters). In mice, 0.5% p-Cresol, but neither m-Cresol nor o-Cresol, caused loss of pigmentation. Short-term and subchronic oral toxicity tests performed with various cresols using mice, rats, hamsters, and rabbits resulted in no observed adverse effect levels (NOAELs) for mice of 625 ppm and rats of 50 mg/kg day-1, although the NOEL was 2000 ppm in a chronic study using rats. In rabbits, < or =160 mg/kg PCMC was found to produce irritation and erythema, but no systemic effects. Hamsters dosed with 1.5% p-Cresol in diet for 20 weeks had a greater incidence of mild and moderate forestomach hyperplasia as compared to the control. Acute inhalation toxicity studies using rats yielded LC50 values ranging from >20 mg/m(3) for o-Cresol to >583 mg/m(3) for PCMC. No deaths were recorded in mice given o-Cresol at 50 mg/m(3). Cats exposed (short-term) to 9 to 50 mg/m(3) of o-Cresol developed inflammation and irritation of the upper respiratory tract, pulmonary edema, and hemorrhage and perivascular sclerosis in the lungs. Rats exposed (subchronic) to o-Cresol at 9 mg/m(3) had changes in leukocytes, spinal cord smears, nervous activity, liver function, blood effects, clinical signs, and neurological effects. In guinea pigs, exposure to 9 mg/m(3) produced changes in hemoglobin concentrations and electrocardiograms (EKGs). Rats exposed (subchronic) to 0.05 mg/m(3) Mixed Cresols by inhalation exhibited central nervous system (CNS) excitation, denaturation of lung protein, and decreased weight gain. All cresols appear to be ocular irritants. Numerous sensitization studies have been reported and most positive reactions were seen with higher concentrations of Cresol ingredients. Developmental toxicity is seen in studies of m-Cresol, o-Cresol, and p-Cresol, but only at maternally toxic levels. In a reproductive toxicity study of a mixture of m-Cresol and p-Cresol using mice under a continuous breeding protocol, 1.0% caused minimal adult reproductive and significant postnatal toxicity in the presence of systemic maternal toxicity. The o-Cresol NOAEL was 0.2% for both reproductive and general toxicity in both generations. Cresol ingredients were generally nongenotoxic in bacterial, fruit fly, and mammalian cell assays. Thymol did not induce primary lung tumors in mice. No skin tumors were found in mice exposed dermally to m-Cresol, o-Cresol, or p-Cresol for 12 weeks. In the trypthan blue exclusion assay, antitumor effects were observed for Thymol and Carvacrol. Clinical patch testing with 2% PCMC may produce irritant reactions, particularly in people with multiple patch test reactions, that are misinterpreted as allergic responses. o-Cresol, p-Cresol, Thymol, Carvacrol, and o-Cymen-5-ol caused no dermal irritation at or above use concentrations. In two predictive patch tests, PCMC did not produce a sensitization reaction. Overall, these ingredients are not significant sensitizing or photosensitizing agents. The Cosmetic Ingredient Review (CIR) Expert Panel noted some of these ingredients may increase the penetration of other cosmetic ingredients and advised cosmetic formulators to take this into consideration. The CIR Expert Panel concluded that the toxic effects of these ingredients are observed at doses higher than would be available from cosmetics. A concentration limitation of 0.5% was chosen to ensure the absence of a chemical leukoderma effect. For p-Cresol and Mixed Cresols (which contain p-Cresol), the Panel considered that the available data are insufficient to support the safety of these two ingredients in cosmetics. Studies that would demonstrate no chemical leukoderma at concentrations of use of p-Cresol and Mixed Cresols, or would demonstrate a dose response from which a safe concentration could be derived, are needed.

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... 26 The median lethal dose (MLD) of CAR in rats is 810 mg/kg/bodyweight (BW) by oral gavage, while the MLD of CAR in mice is 80 and 73.30 mg/kg/BW, by intravenously (i.v.) or intraperitoneally (i.p.) administration, respectively. 27 In addition, i.p. administration of 33.3 mg/kg/BW CAR in mice showed no adverse effects, and at 50 mg/kg/ BW had nonspecific effects, but at higher doses (110-233.3 mg/kg/BM) showed ataxia, decreased spontaneous motor activity and somnolence prior to death in mice. ...
... mg/kg/BM) showed ataxia, decreased spontaneous motor activity and somnolence prior to death in mice. 27 It has been reported that over 80% of uncapsulated CAR is absorbed or metabolized in duodenum and stomach. Encapsulation of CAR in Ca-alginate microcapsules could effectively reduce its early absorption in the upper GI tract after oral administration. ...
... In mice, LD50 was 80.00, 73.30, and 680 mg/kg when administered i.v. or i.p. and subcutaneously, respectively. 27 Orally, LD50 of CAR in rats was 810 mg/ kg. 72 LD50 CAR was 0.31 g/kg in dogs when i.v. ...
Article
Carvacrol (CAR) showed various pharmacological and therapeutic effects in different disorders. In the current article, the experimental and clinical effects of CAR on respiratory, allergic, and immunologic disorders are described. Various databases, including PubMed, Science Direct, and Scopus, were searched regarding the effects of CAR on respiratory and allergic disorders until the end of October 2021. CAR showed the relaxant effect, with various possible mechanisms suggesting the bronchodilatory effect in obstructive pulmonary diseases. The preventive effects of CAR on experimental animal models of respiratory diseases were shown through mechanisms such as antioxidant, immunomodulatory, and anti‐inflammatory. CAR also showed therapeutic potential on lung cancer, lung infections, and allergic and immunologic disorders. Clinical studies also revealed therapeutic effects of CAR on asthma, sulfur‐mustard‐induced lug disorders, and some other allergic and immunologic diseases. Pharmacological and therapeutic effects of CAR indicate possible remedy effects of this agent in the treatment of respiratory, allergic, and immunologic diseases.
... 2-Phenylpropanoic acid is known to possess preservative property and acts as one of the components in dentistry [1][2] formulations. Studies supported hydrazides to possess [3][4][5] anti-tubercular activity. ...
... The melting points of the compounds are uncorrected and were determined using Stuart SMP11 melting point apparatus. The proton magnetic resonance were recorded by Bruker 300 MHz instrument employing CDCl solvent, δ value scale in ppm as chemical 3 shift relative to tetramethylsilane being internal standard. The infrared spectra were recorded over Shimadzu FT-IR 8300 -1 instrument in KBr, in between 400 to 4000 cm . ...
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2-Phenylpropanoic acid and oxadiazoles are known to possess antimicrobial potential. 2- phenylpropanehydrazide (2), a derivative of methyl 2-phenylpropionate, on cyclization with aromatic acids offered new 2-aryl-5-(1-phenylethyl)-1,3,4-oxadiazole derivatives (3a-e). The new oxadiazole derivatives were characterized by elemental analysis and spectral studies. All the newly synthesized compounds were screened for their antimicrobial potential. The compounds 3dand 3e possessing electron-withdrawing groups displayed highest antimicrobial activities.
... Tanto la pasta dental como el colutorio utilizados contenían, entre otros ingredientes, o-cymen-5-ol, cloruro de zinc, glicirrizato potásico, nitrato potásico e ion fluoruro. La eficacia y tolerabilidad del o-cymen-5-ol (0,6%) y el cloruro de zinc (0,1%) en el tratamiento de la gingivitis han sido evaluados previamente de forma extensa con resultados muy positivos, con reducciones de placa, gingivitis y sangrado a las 6 semanas, y respecto a las pastas dentífricas convencionales formuladas con fluoruro de sodio/sílice, del 13,2%, 12,3% y 18,5% respectivamente [9][10][11][12]34,35 . Aunque estas reducciones son inferiores a las conseguidas en nuestro estudio (41%, 21% y 70% respectivamente), es importante destacar que nuestras valoraciones se hicieron respecto de la situación inicial de los voluntarios antes de comenzar a usar el producto, no frente a otro producto. ...
... Parece claro que la asociación de una pasta dental a un colutorio para el tratamiento de la gingivitis y la hiperestesia dental ofrece datos más positivos que el uso de una pasta dental sin asociar a un colutorio, tal como se puede observar al comparar los resultados del presente estudio frente a los de estudios previos en los que solo se utilizó una pasta dental 12 . En cuanto a la tolerabilidad, existen numerosos datos toxicológicos que respaldan la seguridad del o-cymen-5-ol en pastas de dientes a concentraciones del 0,1% 10,11,34,35 . En el presente estudio, y según la evaluación del odontólogo, ninguno de los voluntarios mostró alteración de las encías, dientes o mucosa como consecuencia del uso de los productos. ...
Article
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Introduction: Gingivitis and dental hyperesthesia do not usually occur at the same time. The aim of this study is to evaluate the combined efficacy of a toothpaste and mouthwash to deal with both situations simultaneously.Methods: A proof of concept study in which 20 volunteers with gingivitis and dental hyperesthesia used for 42 days a tooth-paste and mouthwash containing, among other compounds, o-cymen-5-ol, zinc chloride, glycyrrhizinate dipotassium, potas-sium nitrate, and fluoride ion.Results: 42 days after starting the use of the products, there was a statistically significant decrease in the plaque index (41%), gingival index (21%), and bleeding index (70%). Tactile hyperesthesia was reduced by 87% and air hyperesthesia by 52%. No volunteer showed alteration of gums, teeth or mucosa. The composition and diversity of the microbiome was not affected. Overall, both investigators and volunteers perceived an improvement from baseline.Conclusions: The combination of toothpaste and mouthwash significantly decreased plaque, gingival inflammation, bleed-ing, and dental hypersensitivity, without producing any adverse event and preserving the microbiota of the mouth
... 10 Moreover, the acute and short-term in vivo toxicity data on thymol, which are most relevant to the practical safety evaluation, together with its high LD50 values in a wide range of animal species, indicate a high safety level of thymol. 11 Also, the time-tested safety of thymol can be attested to by the long history of using thymol-containing herbs worldwide for centuries. 12 Therefore, thymol is widely used as a food additive, preservative, and cosmetic product. ...
... [13][14][15] Based on previous studies, the range of safe concentrations of thymol in rats extends between 10-100 mg per kg body weight. 11,12,16,17 Due to its lipophilic properties, thymol has been reported to easily cross the bloodbrain barrier, improve the antioxidant status in the brain and exert protective effects on neurons. 18 Previous studies have documented the protective and therapeutic effects of thymol on the brain. ...
Article
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In the present study, we aimed to delineate the neuroprotective potential of thymol (THY) against neurotoxicity and cognitive deterioration induced by thioacetamide (TAA) in an experimental model of hepatic encephalopathy (HE). Rats received TAA (100 mg kg-1, intraperitoneally injected, three times per week) for two weeks. THY (30 and 60 mg kg-1), and Vit E (100 mg k-1) were administered daily by oral gavage for 30 days after HE induction. Supplementation with THY significantly improved liver function, reduced serum ammonia level, and ameliorated the locomotor and cognitive deficits. THY effectively modulated the alteration in oxidative stress markers, neurotransmitters, and brain ATP content. Histopathology of liver and brain tissues showed that THY had ameliorated TAA-induced damage, astrocyte swelling and brain edema. Furthermore, THY downregulated NF-kB and upregulated GFAP protein expression. In addition, THY significantly promoted CREB and BDNF expression at both mRNA and protein levels, together with enhancing brain cAMP level. In conclusion, THY exerted hepato- and neuroprotective effects against HE by mitigating hepatotoxicity, hyperammonemia and brain ATP depletion via its antioxidant, anti-inflammatory effects in addition to activation of the CREB/BDNF signaling pathway.
... Studies performed on the mice model have revealed poor liver function, increased liver and kidney weights, nasal epithelia and atrophy of female reproductive organs as a consequence of p-cresol administration at doses of 30,000 ppm in the diet [54]. Although the majority of the scientific reports on pulegone toxicity relate to rodent models, valuable results were obtained for research based on the human livers of five patients. ...
... Usage of the plants can cause allergic reactions or medical accidents. Particular attention should be paid to them by pregnant women due to the fact that a significant number of terpenes reveal teratogenic toxicity or changes in reproductive organs [54]. A characteristic feature of terpenes is their aromatic character which results in essential oils consisting of these compounds being commonly used in cosmetics and household products. ...
Article
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Monoterpenes make up the largest group of plant secondary metabolites. They can be found in numerous plants, among others, the Lamiaceae family. The compounds demonstrate antioxidative, antibacterial, sedative and anti-inflammatory activity, hence, they are often employed in medicine and pharmaceuticals. Additionally, their fragrant character is often made use of, notably in the food and cosmetic industries. Nevertheless, long-lasting studies have revealed their toxic properties. This fact has led to a detailed analysis of the compounds towards their side effects on the human organism. Although most are safe for human food and medical applications, there are monoterpene compounds that, in certain amounts or under particular circumstances (e.g., pregnancy), can cause serious disorders. The presented review characterises in vitro and in vivo, the toxic character of selected monoterpenes (α-terpinene, camphor, citral, limonene, pulegone, thujone), as well as that of their original plant sources and their essential oils. The selected monoterpenes reveal various toxic properties among which are embryotoxic, neurotoxic, allergenic and genotoxic. It is also known that the essential oils of popular plants can also reveal toxic characteristics that many people are unaware of.
... In vivo studies report adverse effects of acute and prolonged oral exposure to carvacrol and thymol in mice, rats, and rabbits (Andersen 2006). The LD 50 for oral exposure to carvacrol and thymol in rats is 810 mg/kg bw and 980 mg/kg bw, respectively. ...
... Acute toxic effects after oral exposure in mice, rats and rabbits. Skin irritation after acute dermal exposure in mice Andersen (2006) Thymol food spoilage bacteria, yeasts, and fungi (Tippayatum and Chonhenchob 2007;De Souza et al. 2014). Eugenol antimicrobial activity has been associated with the ability of its hydroxyl group to disrupt the cytoplasmic membrane and the cell wall, and to interact with proteins, to result in intracellular content leakage and the disruption of the proton motive force (Hyldgaard et al. 2012). ...
Article
Phenolic compounds carvacrol, thymol, eugenol and vanillin are four of the most thoroughly investigated essential oil components given their relevant biological properties. These compounds are generally considered safe for consumption and have been used in a wide range of food and non-food applications. Significant biological properties, including antimicrobial, antioxidant, analgesic, anti-inflammatory, anti-mutagenic or anti-carcinogenic activity, have been described for these components. They are versatile molecules with wide-ranging potential applications whose use may substantially increase in forthcoming years. However, some in vitro and in vivo studies, and several case reports, have indicated that carvacrol, thymol and eugenol may have potential toxicological effects. Oxidative stress has been described as a main mechanism underlying their cytotoxic behavior, and mutagenic and genotoxic effects have been occasionally observed. In vivo studies show adverse effects after acute and prolonged carvacrol and thymol exposure in mice, rats and rabbits, and eugenol has caused pulmonary and renal damage in exposed frogs. In humans, exposure to these three compounds may cause different adverse reactions, including skin irritation, inflammation, ulcer formation, dermatitis or slow healing. Toxicological vanillin effects have been less reported, although reduced cell viability after exposure to high concentrations has been described. In this context, the possible risks deriving from increased exposure to these components for human health and the environment should be thoroughly revised.
... Subcutaneous treatment was preferred over dietary supplementation or oral gavage to avoid the possible conversion of 4-cresol by gut bacteria or enterocytes, to control permanent delivery of 4-cresol over a long period, and to reduce the stress induced by animal handling that gavage requires. This delivery method also avoided the possible toxic effects of this volatile compound that are observed at much higher doses (240-2,000 mg/kg/day) on neurological function, liver function, and respiratory epithelium (Andersen, 2006). As expected, mice fed an HFD rapidly gained more weight than did mice fed a control diet and developed fasting hyperglycemia and marked glucose intolerance (Figures 2A-2F). ...
... It is naturally present in food (smoked foods, tomatoes, asparagus, dairy products), drinks (coffee, black tea, wine), cigarette smoke, wood burning, and surface waters and groundwater (https:// www.atsdr.cdc.gov/), and can be synthesized from phenol found in the environment and absorbed by ingestion, inhalation, or dermal contact. Lethal dose (LD 50 ) for 4-cresol given orally ranges from 200 to 5,000 mg/kg/day (Andersen, 2006). Irritation to the respiratory epithelium and deteriorated liver function can be caused by dietary exposure to doses of 4-cresol (240-2,000 mg/kg/day), which are much higher than those used in our in vivo (0.5 mg/kg/day) and in vitro (10 nM) studies. ...
Article
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Exposure to natural metabolites contributes to the risk of cardiometabolic diseases (CMDs). Through metabolome profiling, we identify the inverse correla- tion between serum concentrations of 4-cresol and type 2 diabetes. The chronic administration of non- toxic doses of 4-cresol in complementary preclinical models of CMD reduces adiposity, glucose intoler- ance, and liver triglycerides, enhances insulin secre- tion in vivo, stimulates islet density and size, and pancreatic b-cell proliferation, and increases vascu- larization, suggesting activated islet enlargement. In vivo insulin sensitivity is not affected by 4-cresol. The incubation of mouse isolated islets with 4-cresol results in enhanced insulin secretion, insulin content, and b-cell proliferation of a magnitude similar to that induced by GLP-1. In both CMD models and isolated islets, 4-cresol is associated with the downregulated expression of the kinase DYRK1A, which may mediate its biological effects. Our findings identify 4-cresol as an effective regulator of b-cell function, which opens up perspectives for therapeutic applications in syndromes of insulin deficiency.
... Phenols are the chemical entities that are widely employed in dentistry, pharmaceutical formulations, food preservatives, [1][2][3] disinfectant, antioxidants and antiseptics. ...
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Chloroxylenol and imines are the known potent antimicrobial entities. 2-(4-Chloro-3,5-dimethylphenoxy)acetohydrazide (2), prepared from ethyl 2-(4-chloro-3,5-dimethylphenoxy)acetate (1), on treatment with aromatic aldehydes offered N-substituted benzylidene-2-(4-chloro-3,5-dimethylphenoxy)acetamides (3a-e). The 1 structures of new compounds were characterized by elemental analysis, FTIR, H-NMR, and Mass spectral data. Synthesized compounds were evaluated for antibacterial and antifungal potential. Among newly synthesized compounds, compound 3e incorporated with high electronegative group, exhibited maximum antimicrobial potential.
... Carvacrol, whose toxic effect has not been reported, accelerates breast cancer cell death according to researches (Arunasree 2010;Babili et al. 2011). Regardless of the type of cancer, carvacrol treatment gives similar results (Andersen 2006). Lung, oral cancer, and brain tumor cells were reported to die when treated with carvacrol (Liang and Lu 2012;Ozkan and Erdogan 2012;Liang et al. 2013). ...
Article
In this study, the potential of aromatic Origanum species belonging to Lamiaceae family to prevent and treat cancer was investigated. Since aromatic plants contain phytochemicals such as essential oils, phenolic acids, terpenoids, flavonoids, alkaloids, vitamins, enzymes and minerals with beneficial biological activities, they have become more interesting and important in medicine, pharmacy and industry. Publications/research between 1950 and 2022 were screened to investigate the effects of Origanum species on cancer, and the effects of their extracts and essential oils in cancer prevention and treatment. Essential phytochemicals found in plants provide efficacy in the prevention and treatment of many diseases. Besides, the essential oils found in these plant extracts are another reason that makes them important. Therefore, it is preferred in traditional medicine in the fight against many diseases as well as cancer. Essential oils of Origanum species mainly contain monoterpenes such as p-cymene, carvacrol, thymol and γ-terpinene. Since these compounds exhibit anticancer properties, Origanum species are becoming the plants of choice in the fight against cancer. In this context, Origanum majorana L. Origanum vulgare and Origanum munzurense are promising species, considering the composition of their extracts and essential oil.
... In general, oral, intravenous (iv), intramuscular (im), and subcutaneous (sc) administration are possible routes for medication delivery. Effects and toxicity of PDAs have mostly been conducted by oral administration, sc or iv injections [11][12][13] . A very limited number of reports documented intraperitoneal (ip) injection of PDAs in the mouse model, mainly to explore their beneficial health effects. ...
Article
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With increasing antibiotic resistance, the use of plant derived antimicrobials (PDAs) has gained momentum. Here, we investigated the toxicity of trans-cinnamaldehyde, eugenol, and carvacrol after intramuscular injection in mice. Two doses of each PDA—300 and 500 mg/kg body weight—and vehicle controls were injected into the muscle of the right hind limb of CD-1 adult mice (n = 8/treatment). Ten physical/behavioral parameters were monitored hourly for 2 h and twice daily for 4 days post-injection together with postmortem examination of leg muscles and organs. Within the first 2 days of carvacrol treatment, one male died in each dose level and a third male receiving 500 mg/kg was removed from the study. No mortality was seen with any other treatment. Among all 81 parameters examined, significant higher relative liver weights (300 and 500 mg/kg eugenol groups; P < 0.05) and relative kidney weights (300 mg/kg carvacrol group; P < 0.001) were observed. Taken together, little to mild toxicity was seen for trans-cinnamaldehyde and eugenol, respectively, while carvacrol exerted more toxicity in males. This study lays the foundation for future extensive work with large sample size, varied treatment durations, and additional treatment levels.
... Where, thyme essential oil contains subspecies between 5% and 75% of carvacrol [3]. Carvacrol has antimicrobial activity against several diverse bacterial and strains [4]. Moreover, to these incredible benefits, thyme also contains many vitamins (A, C, E, K, and B6) and minerals (calcium, iron, phosphorous, manganese and magnesium) as well as omega-3 and omega-6. ...
... Finally, Andersen (2006) concluded that thymol did not induce primary lung tumors in mice, caused no dermal irritation, and is not a ...
... Although the in vitro genotoxic potential of carvacrol and eugenol has been reported using V79, Caco-2, and mouse lymphoma cells (Llana-Ruiz-Cabello et al., 2014b;Maisanaba et al., 2015;Maralhas et al., 2006), these results are still limited. In vivo toxicity studies are scarce, and potential adverse effects after acute and prolonged exposure to carvacrol, thymol and eugenol have appeared in different species (Andersen, 2006;Nejad et al., 2017). In humans, it is known that exposure to carvacrol, thymol and eugenol is able to cause allergic reactions because skin irritation, ulcer formation, dermatitis or reduced healing have been reported (Kamatou et al., 2012;Salehi et al., 2018). ...
Article
The extensive use of essential oil components in an increasing number of applications can substantially enhance exposure to these compounds, which leads to potential health and environmental hazards. This work aimed to evaluate the toxicity of four widely used essential oil components (carvacrol, eugenol, thymol, vanillin) using the in vivo model Caenorhabditis elegans. For this purpose, the LC50 value of acute exposure to these components was first established; then the effect of sublethal concentrations on nematodes’ locomotion behaviour, reproduction, heat and oxidative stress resistance and chemotaxis was evaluated. The results showed that all the components had a concentration-dependent effect on nematode survival at moderate to high concentrations. Carvacrol and thymol were the two most toxic compounds, while vanillin had the mildest toxicological effect. Reproduction resulted in a more sensitive endpoint than lethality to evaluate toxicity. Only pre-exposure to carvacrol and eugenol at the highest tested sublethal concentrations conferred worms oxidative stress resistance. However, at these and lower concentrations, both components induced reproductive toxicity. Our results evidence that these compounds can be toxic at lower doses than those required for their biological action. These findings highlight the need for a specific toxicological assessment of every EOC application.
... m-Cresol can be absorbed through the respiratory tract and excreted as glucuronide and sulfate metabolites. In a 28-day study involving rats and mice, excessive m-cresol caused irritation in the gastrointestinal tract and nasal epithelia [33]. Weber et al. found that m-cresol could activate P38 and JNK signaling pathways and promote the chemokine MCP-1 to induce a pro-in ammatory response [34]. ...
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Background: Despite the availability of inhaled corticosteroid-formoterol treatment, asthma in some patients is poorly controlled. Kechuanting acupoint sticking therapy may regulate immunological functions to improve asthma. In this study, we focused on the effect of Kechuanting acupoint sticking therapy on disease control and the characteristics of serum metabolites in asthma patients treated with long-term inhaled corticosteroid-formoterol. Methods: We enrolled healthy controls (n=30) and asthma patients treated with inhaled corticosteroid-formoterol for at least 6 months (n=30) and evaluated asthma control, lung function, and airway inflammation after treatment with Kechuanting acupoint sticking therapy (in asthma patients at baseline and week 6). Gas chromatography-mass spectrometry was used to analyze the serum samples of the two groups. Results: Asthma control test scores, forced expiratory volume in one second, and peak expiratory flow increased (P<0.01) at week 6 in the inhaled corticosteroid-formoterol+ Kechuanting acupoint sticking therapy group, while the level of fractional exhaled nitric oxide did not change significantly (P=0.359). Among the 46 significant metabolites in the asthma patients and healthy controls (at baseline), 12 were restored after 6 weeks of inhaled corticosteroid-formoterol+ Kechuanting acupoint sticking therapy treatment and 8 (e.g., glycine, sucrose, and glycerol) were correlated with the clinical characteristics. Conclusions: Kechuanting acupoint sticking therapy improved asthma control in patients treated with long-term inhaled corticosteroid-formoterol, and the serum metabolomic pathway analysis demonstrated the association of Kechuanting acupoint sticking therapy with carbohydrate, glycerolipid, and amino acid metabolism. Trial registration: https://www.chictr.org.cn, ChiCTR1800016644.
... Such components, for example carvacrol, thymol and β-caryophyllene, can penetrate the intestinal mucosa, cross the epithelial wall into deeper layers and will thereby affect various cellular and intestinal physiological functions. Due to their chemogenetic action, processes such as gene expression can be affected (Andersen, 2006;Bimczok et al., 2008;Walter & Bilkei, 2004). ...
Article
Full-text available
Pig production depends on a health and performance balance. An approach to improve intestinal health is the oregano essential oil (OEO) supplementation within a conventional diet. Intestinal integrity regulating effects, for example gene expression, of some feed ingredients are important key factors for that balance. We hypothesized that OEO affects the expression of genes associated with pigs' intestinal integrity. In four trials, a total of 86 pigs have been used. From weaning, the 'treated' group (n = 42) was additionally fed an oregano flavour additive [1500 mg/kg (7.5% pure OEO)] within the basal diet. The 'control' group (n = 44) was kept under identical environmental conditions, except the OEO. At age of 6 months, pigs were slaughtered with an average weight of 111.1 ± 10.9 kg. In addition to automatically generated 'Fat-o-Meter' (AutoFOM) data, carcass quality factors have been measured manually. Valuable cuts of meat, such as ham and belly, were significantly reduced in the OEO group. Effects of OEO on pigs' haematologic parameters were very limited. For transcriptome analysis, the most interesting microarray expression results have been listed in a table (topTable). Selected genes were technically validated by qPCR. As a result, few significant differences in animal development and meat quality have been found between the OEO treated and the control group. Depending on OEO supplementation, we found 93 differently regulated genes in the jejunal tissue (70 up, 23 down) and 60 in the ileal tissue (48 up, 12 down). Just three genes (GRIN3B [glutamate ionotropic receptor NMDA type subunit 3B], TJP1/ZO-1 [tight junction protein ZO-1] and one uncharacterized gene) were affected by OEO both in jejunum and ileum. qPCR validation revealed AKT serine/threonine kinase 3 (AKT3), Interferon (IFN) -ε, -ω, tight junction protein (TJP1)/ZO-1 (ZO-1) to be upregulated in the jejunum and C-C motif chemokine ligand 21 (CCL21) was upregulated in the ileum of pigs that were supplemented with OEO. OEO supplementation had limited effects on pigs' performance traits. However, we were able to demonstrate that OEO alters the expression of genes associated with adaptive immune response in pigs' small intestine. These findings help to explain OEOs' beneficial impact on pigs' intestinal integrity.
... These species are generally enriched source of phenolics, α-pyrone and acetophenones derivatives responsible for its biological activities (Kladar et al., 2015). It was established that phenols and its derivatives are toxic to humans and animals due to the formation of phenoxyl radicals (Andersen, 2006). Salvia species are also characterized by different secondary metabolite constituents responsible for their bioactivities (Simmonds and Blaney, 1992). ...
... Absinthin shows biological activity and has proved to be a promising anti-inflammatory agent (44). Carvacrol has antimicrobial activity against different bacteria (45). Linalool is used as a flea, fruit fly, and cockroach insecticide (46). ...
Article
Every year, millions of people worldwide get sick with gastrointestinal diseases such as heartburn. Certain herbs contribute to the alleviation of heartburn, nausea, and improvement of digestion. Moreover, these herbs do not have as many side effects as synthetic drugs. As a health problem and one of the challenging issues in medical sciences, heartburn is common in children and adults worldwide. Hence, in the present study, we tried to report medicinal plants used in cultures and traditions of different regions of Iran to treat heartburn in children and adults. In this review study, articles of Iranian ethnobotanical sources were searched with the keywords of ethnobotanics, heartburn, children, adult, medicinal plants, and Iran. Journal articles published from 2010 to 2019 in several Iranian and International databases, including ISI Web of Science, PubMed, Scopus, ISC, Magiran, were searched to find relevant articles and information. Anethum graveolens L., Punica granatum L., Mentha pulegium, Thymus kotschyanus Boiss. & Hohen., Achillea millefolium, Ocimum basilicum, Nigella sativa , etc., are the plants used in different parts of Iran to treat heartburn.
... Moreover, its lipophilic nature facilitates stronger interaction with the fungal cell membrane which leads to altering the permeability of the cell membrane and hence, increase the movement of macromolecules across the cell membrane [8][9][10]. Additionally, thymol was shown to possess a strong antimutagenic effect, antitumor properties, and can be used in the treatment of actinomycosis, cystic echinococcosis (a zoonotic disease) onycholysis (separation or loosening of a fingernail or toenail from its nail bed) [11][12][13][14]. Hydro-alcoholic solution of thymol was also used in the treatment of ringworm and hookworm infections in the United States [15]. ...
Article
The current investigation aimed to prepare and characterize the inclusion complex of thymol with hydroxypropyl-β-cyclodextrin (HP-β-CD) to uniformly incorporate in hydrogel system for its topical application. An inclusion complex of thymol with HP-β-CD was formulated through different methods viz. physical mixture, kneading, and co-precipitation. Phase solubility study was carried out to find the stability constant of complex. Further, the inclusion complex of thymol with HP-β-CD was characterized by DSC, FT-IR, and ¹H-NMR spectroscopy. The molecular docking studies were also performed to understand the molecular interactions of stable supra-molecular host-guest inclusion complex of thymol with HP-β-CD. After that inclusion complex was incorporated in carbopol 940 hydrogel and evaluated for its drug content, pH, homogeneity, rheological behavior, and in-vitro release. The phase solubility graph demonstrated AL type correlation with apparent stability constant (K1:1) of 370 M⁻¹. The inclusion complex formulated by the co-precipitation technique exhibited the highest dissolution rate (98.73%) of thymol as compared to kneading and physical methods. The DSC, FT-IR and ¹H-NMR spectroscopic analysis confirmed the formation of inclusion complex between thymol and HP-β-CD. The molecular docking study has confirmed that the binding affinity of thymol with the HP-β-CD was -9.6 kcal/mol, indicating desirable stability of the prepared inclusion complex. The diffusion flux of thymol in a form of inclusion complex was found to be approximately 4.4 folds higher as compared to that of thymol in the hydrogel system for topical administration. The in vitro release of thymol from carbopol 940 hydrogel system exhibited a sustained release profile with thixotropic behaviour. The thymol in a form of inclusion complex was found to be stable in the developed hydrogel system according to ICH guidelines. Therefore, incorporation of thymol in form of inclusion complex in hydrogel system is an effective approach to improve its biopharmaceutical performance for topical administration.
... Gap-junction inhibitor, cytotoxic [56]. Safe for use, no negative effect reported at the tested concentration (0.1%) [57]. ...
Article
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Background: DNA-RNA compounds have shown promising protection against cell oxidative stress. This study aimed to assess the cytotoxicity, protective, or preventive effect of different experimental formulations on oral epithelia's oxidative stress in vitro. Methods: Reconstituted human oral epithelia (RHOE) were grown air-lifted in a continuous-flow bioreactor. Mouthwashes and gels containing DNA-RNA compounds and other bioactive molecules were tested on a model of oxidative stress generated by hydrogen peroxide treatment. Epithelia viability was evaluated using a biochemical MTT-based assay and confocal microscopy; structural and ultrastructural morphology was evaluated by light microscopy and TEM. Results: DNA-RNA showed non-cytotoxic activity and effectively protected against oxidative stress, but did not help in its prevention. Gel formulations did not express adequate activity compared to the mouthwashes. Excipients played a fundamental role in enhancing or even decreasing the bioactive molecules' effect. Conclusion: A mouthwash formulation with hydrolyzed DNA-RNA effectively protected against oxidative stress without additional enhancement by other bioactive molecules. Active compounds, such as hyaluronic acid, β-Glucan, allantoin, bisabolol, ruscogenin, and essential oils, showed a protective effect against oxidative stress, which was not synergistic with the one of DNA-RNA. Incorporation of surfactant agents showed a reduced, yet significant, cytotoxic effect.
... In earlier studies, the antioxidant, hepatoprotective and immunostimulatory activities of ZMEO have been documented [34,52]. Previous studies also confirmed that thymol and carvacrol as the main components of ZMEO are safe compounds [53]. ...
Article
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Background Novel and more efficient compounds are urgently required for medical treatment of cystic echinococcosis (CE). Germinative cell culture of Echinococcus granulosus could be used for anti-echinococcosis agent tests and other biological studies on CE. This study was performed to establish an in vitro cell culture model for E. granulosus germinative cells and to evaluate the lethal effect of Zataria multiflora essential oil (ZMEO) on the cultured cells. Methods The inner surface of germinal layers of CE cysts was scraped, and the obtained materials were trypsinized to obtain a suspension of single germinative cells. Medium 199 was used as the basic culture medium and was supplemented with fetal bovine serum, 2-mercaptoethanol, l -cysteine, l -glutamine, glucose, sodium pyruvate, hydatid fluid, amphotericin B and antibiotics. The cells were cultured at a concentration of 10 ⁴ cells/ml of culture medium and incubated at 37 °C. The culture medium was replaced every 7 days. Chemical composition of ZMEO was identified by GC-MS analysis. ZMEO was tested at concentrations of 0.5–8 mg/ml. Viability of the cells was assessed by trypan blue exclusion assay. Results A significant increase in the cell number was evident at 20, 30 and 45 days after cultivation. At 45 days of cultivation, the number of cells was approximately five-fold higher than on the first day. In GC-MC analysis, carvacrol, p -cymene, g-terpinene and thymol were found to be the main compounds of ZMEO. The lethal effect of ZMEO on the germinative cells at concentrations of 6, 7 and 8 mg/ml was 100% after 60, 25 and 7 min of exposure, respectively. Conclusions At 45 days of cultivation, the cell concentration was suitable for the desired in vitro experiments. A high lethal effect of ZMEO on the germinative cells of E. granulosus may be considered an opportunity for the introduction of a novel, more effective and safer therapeutic agent for treatment of CE using an herbal product. Graphic abstract
... Meanwhile, I60 had a lower MIC for S. aureus (0.6 mg mL − 1 ) than for E. coli (1.2 mg mL − 1 ). The results of GC-MS show the presence of simple phenols, it is known that these compounds have antimicrobial properties [65]. However, they are not the only compounds, present in fractions, that inhibit the growth of bacteria. ...
Article
Pyrolytic lignin is the water-insoluble fraction of the bio-oil from rapid pyrolysis. The separation of pyrolytic lignin can improve the extraction of monophenols. Studies reveal the efficacy of phenolic aromatic compounds derived from lignin as antioxidants and as antimicrobials. In this study, we used aqueous acetone solutions to improve the fractionation of eucalypt pyrolytic lignin. Experiments to obtain the pyrolytic lignin were carried out based on a central composite factorial design, and the characterizations were performed by GPC, NMR, FTIR, TGA, GC-MS, antioxidant assays, and antibacterial activity analysis. The most soluble fraction resulted in a more homogeneous fraction, concentrating phenolic, carboxylic, and lower molecular weight compounds. The anti-oxidant activity was mainly attributed to phenolic compounds with methoxy substituents. Pyrolytic lignin fractions also showed antimicrobial action against Staphylococcus aureus and Escherichia coli.
... Preservative o-Cymen-5-ol Substitute of parabens Safe for use, no negative effect reported at the tested concentration (0.1%) [57]. ...
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Background: DNA-RNA compounds have shown promising protection against cell oxidative stress. This study aimed to assess the cytotoxicity, protective, or preventive effect of different experimental formulations on oral epithelia’s oxidative stress in vitro. Methods: Reconstituted human oral epithelia (RHOE) were grown air-lifted in a continuous-flow bioreactor. Mouthwash and gels containing DNA-RNA compounds and other bioactive molecules were tested on a model of oxidative stress generated by hydrogen peroxide treatment. Epithelia viability was evaluated using a biochemical MTT-based assay and confocal microscopy; structural and ultrastructural morphology was evaluated by light microscopy and TEM. Results: DNA-RNA showed non-cytotoxic activity and effectively protected against oxidative stress, but not in its prevention. Gel formulation did not express adequate activity compared to the mouthwash. Excipients played a fundamental role in enhancing or even decreasing the bioactive molecules’ effect. Conclusion: A mouthwash formulation with hydrolyzed DNA-RNA effectively protected against oxidative stress without additional enhancement by other bioactive molecules. Active compounds such as hyaluronic acid, β-Glucan, allantoin, bisabolol, ruscogenin, and essential oils showed a protective effect against oxidative stress, which was not synergistic with the one of DNA-RNA. Surfactant agents showed harmful activity against oral epithelia.
... Carvacrol (CARV) is a phenol monoterpene phytochemical mainly found in aromatic plants of the Lamiaceae family (Baser 2008). It is approved for human consumption by the Federal Drug Administration (FDA) and the Council of Europe and is widely used as flavoring, preservative, and fragrance in food and cosmetic industries (Suntres et al. 2015;Andersen 2006). More recently, studies have reported its multiple pharmacological activities, including anti-bacterial, anticarcinogenic, antioxidant, anti-inflammatory, cardioprotective, and neuroprotective (Friedman 2014). ...
Article
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Carvacrol (CARV) is a phytochemical widely used as flavoring, preservative, and fragrance in food and cosmetic industries. CARV is able to cross the blood–brain barrier (BBB) and has demonstrated protective potential against neurodegenerative diseases by several mechanisms, including antioxidant, anti-inflammatory, anticholinesterase, and antiapoptotic effects. However, it is not known whether CARV is able to modulate axonal and synaptic plasticity, crucial events in cognition, memory, and learning. Abnormalities in axonal and synaptic plasticity, low levels of neurotrophins, and bioenergetic failure have been associated with the pathogenesis of neurodegenerative diseases, including Parkinson’s (PD) and Alzheimer’s diseases (ADs). Small lipophilic molecules with neurotrophic activity might be able to restore the axonal and synaptic networks that are lost in neurodegenerative processes. Therefore, this study investigated the neurotrophic potential of CARV in PC12 cell-based neuronal model. Carvacrol induced neurite outgrowth by activating the NGF high-affinity trkA receptor and the downstream PI3K-AKT and MAPK-ERK pathways, without depending on NGF. In addition, CARV increased the expression of proteins involved in neuronal plasticity (β-tubulin III, F-actin, 200-kDa neurofilament, GAP-43 and synapsin-I) and improved bioenergetics (AMPKα, p-AMPKα, and ATP). Our study showed, for the first time, a promising neurotrophic mechanism of CARV that could be beneficial in neurodegenerative and neurological diseases.
... Carvacrol is used as a microbicidal agent, and fragrance ingredient in cosmetic formulations (Andersen, 2006). Carvacrol is generally considered safe for consumption. ...
Article
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The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in December 2019, resulting in the coronavirus disease-19 (COVID-19) pandemic. Coronaviruses are solely accountable for rising mortality and socioeconomic saddles. Presently, there are few repurposed drugs such as remdesivir or favipiravir approved for the treatment of COVID-19, although vaccines and plasma therapy is also subject to emergency approval. However, some potential natural treatments and cures have also been proposed. Molecules of natural origin showed therapeutic importance such as antiviral, anti-inflammatory, and antioxidant activity, and could be useful drug candidates for treating COVID-19. In recent years, essential oils have shown promising therapeutic effects against many viral diseases. Carvacrol is one of the monoterpene phenol with abundant presence in essential oils of many aromatic plants, including thyme and oregano. It is being used as food flavoring, additive, and preservatives. Carvacrol is also used as a fragrance in cosmetic products. A number of research studies have shown biological actions of carvacrol with its therapeutic potential is of clinical significance. The in vitro and in vivo studies have shown multiple pharmacological properties such as anticancer, anti-fungal, anti-bacterial, anti-oxidant, anti-inflammatory, vasorelaxant, hepatoprotective, and spasmolytic. This review highlights the various biological and pharmacological properties of carvacrol within the scope of COVID-19.
... Mezzoug et al. [23] mentioned that carvacrol and thymol, as essential oils were detected to have a powerful antimutagenic effect. Furthermore, Andersen [24], assured that thymol has antitumor activity. ...
Chapter
With the rapid growth of the poultry sector, a major human health concern is noticed relating to the excessive and uncontrolled abuse of antibiotics, which leads to the development of antibiotic-resistant bacteria. Antibiotics are used in sub-therapeutic doses as antimicrobial agents for rapid growth performance in poultry and for prevention of diseases. For this reason, there is a need to develop alternatives to antibiotics. The beneficial effects of plants and plant extracts that have traditional use are evaluated in many studies. The most common beneficial effects of these plants and their extracts are stimulating endogenous digestive enzymes and antioxidants. Essential oils (EOs) have a wide variety of effects, including antimicrobial, antioxidants, and digestive stimulant activities. Essential oils have been demonstrated to positively affect growth performance, gut health, and meat quality, but the responses are inconsistent. The inconsistencies have been related to the species/subspecies of the plant, harvest time, geographical location, and plant part used that can affect the EOs structure. The oils undergo a patented micro fusion process that creates a surface area of oil droplets that is 20 times greater than other commercially available oilsthus increasing the stability and effectiveness of the oils. The EOs exhibit high antioxidant activity, which is attributed to its two main phenols, carvacrol, and thymol. Conclusively, essential oils can be used in poultry nutrition, but still need more studies, especially metabolism, and the optimum dose in various poultry species. F o r p e r s o n a l p r i v a t e u s e o n l y N o t b e d i s t r i b u t e d o r u p l o a d e d t o a n y o n e o r a n y w h e r e 202 Natural Feed Additives Used in the Poultry Industry
... Mezzoug et al. [23] mentioned that carvacrol and thymol, as essential oils were detected to have a powerful antimutagenic effect. Furthermore, Andersen [24], assured that thymol has antitumor activity. ...
Chapter
With the rapid growth of the poultry sector, a major human health concern is noticed relating to the excessive and uncontrolled abuse of antibiotics, which leads to the development of antibiotic-resistant bacteria. Antibiotics are used in sub-therapeutic doses as antimicrobial agents for rapid growth performance in poultry and for prevention of diseases. For this reason, there is a need to develop alternatives to antibiotics. The beneficial effects of plants and plant extracts that have traditional use are evaluated in many studies. The most common beneficial effects of these plants and their extracts are stimulating endogenous digestive enzymes and antioxidants. Essential oils (EOs) have a wide variety of effects, including antimicrobial, antioxidants, and digestive stimulant activities. Essential oils have been demonstrated to positively affect growth performance, gut health, and meat quality, but the responses are inconsistent. The inconsistencies have been related to the species/subspecies of the plant, harvest time, geographical location, and plant part used that can affect the EOs structure. The oils undergo a patented micro fusion process that creates a surface area of oil droplets that is 20 times greater than other commercially available oilsthus increasing the stability and effectiveness of the oils. The EOs exhibit high antioxidant activity, which is attributed to its two main phenols, carvacrol, and thymol. Conclusively, essential oils can be used in poultry nutrition, but still need more studies, especially metabolism, and the optimum dose in various poultry species. F o r p e r s o n a l p r i v a t e u s e o n l y N o t b e d i s t r i b u t e d o r u p l o a d e d t o a n y o n e o r a n y w h e r e 202 Natural Feed Additives Used in the Poultry Industry
... Octanoic acid (Caprylic Acid) is a type of beneficial saturated medium-chain fatty acid with anti-inflammatory, antibacterial, antifungal and antiviral properties (29,30) . Carvacrol was reported to has antimicrobial activity against different 25 periodontopathic bacteria and strains, and fungi such as R. solani, F. moniliforme, P. capsici and S.clerotirum (31) .Thus B. sacra gum oleo resin was selected to be tested as endodontic irrigant for smear layer removal. ...
... The result revealed that depression occurs within 10 min of carvacrol administration, coma, and death of animals within 1 h to 3 days. Administration of the essential oil carvacrol in rabbits, rats, and dogs exhibited the non-toxic nature, although the detailed information was not documented (Budavari 1989;Livingston 1921;Andersen 2006;Ghorani et al. 2019). But some reports showed the toxic behavior of the test drug carvacrol in Osborne-Mendel rats and mice, where depression, ataxia, decreased spontaneous motor activity, somnolence, coma, and death were observed (Jenner et al. 1964;Viana et al. 1981) Detail reports of animal acute toxicity studies have been enlisted in Table 13.1. ...
Chapter
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Carvacrol (cymophenol) has been reported to be the major component of aromatic plant essential oils belonging to the Labiatae family, such as Origanum vulgare and Thymus vulgaris. It is a phenolic moiety containing monoterpenoid compound, chemically known as 5-isopropyl-2-methyl phenol. Carvacrol is used in food products both as a flavoring component and as preservative. Current research is being directed to establish a potent compound carvacrol with diverse pharmacological activities, such as antioxidant, antifungal, antimicrobial, anti-inflammatory, anticancer, hepatoprotective, anti-spasmodic, anti-parasitic, and insecticidal activities. There are various derivatives of carvacrol, which possess antimicrobial action against microbial pathogens. The carvacrol phenolic group does have a good antimicrobial and anti-oxidative function. Its hydrophobic nature is owing to the existence of benzene ring and methyl and isopropyl substituents helped the moiety to bind with guanine present in DNA. This review is based upon an evaluation of the existing data or knowledge regarding the extraction of carvacrol, chemical composition of the potent derivatives synthesized from carvacrol, their pharmacological and toxicological effects. This chapter documents the above-mentioned activities and strived to critically assess the molecular pathway involved in the action of carvacrol.
... mg/kg) showed that mice experienced ataxia, decreased spontaneous motor activity and somnolence prior to death. (Andersen, 2006). However, studies on the effectiveness of carvacrol against testicular tissue damage are quite limited (Aksu et al., 2016;Daggulli et al., 2014;Shoorei et al., 2019). ...
Article
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Diabetes mellitus, which causes many complications, also adversely affects reproductive system in men. Studies reported that natural antioxidants are effective in reducing important complication risks caused by diabetes. Carvacrol is an antioxidant phenolic monoterpene compound with therapeutic effect in various diseases found in essential oils of aromatic plants such as pepper, wild bergamot and thyme. We aimed to investigate the effects of carvacrol on diabetes‐induced reproductive damage in male rats by evaluating the Nrf2/HO‐1 pathway and Nf‐kB‐mediated apoptosis/inflammation and spermatological parameters. For this purpose, 74 Wistar albino male rats were used. The diabetes model was performed using single‐dose intraperitoneal injection of streptozotocin 55 mg/kg. Rats were fed with carvacrol 75 mg/kg/daily/gavage for 4 and 8 weeks. Rats were divided into four groups: control group, diabetic group, carvacrol group which fed with carvacrol and the diabetic group which fed with carvacrol. It was determined that carvacrol significantly decreased malondialdehyde levels, Bax,COX‐2,Nf‐kB protein expression levels, Bax/Bcl‐2 ratio and significantly increased glutathione peroxidase, catalase activities, Bcl‐2, Nrf2,HO‐1 protein expression levels and it was determined that had a positive effect on spermatological parameters. In conclusion, the negative effects of diabetes in the male reproductive system can be prevented and/or reduced by giving carvacrol.
... The result revealed that depression occurs within 10 min of carvacrol administration, coma, and death of animals within 1 h to 3 days. Administration of the essential oil carvacrol in rabbits, rats, and dogs exhibited the non-toxic nature, although the detailed information was not documented (Budavari 1989;Livingston 1921;Andersen 2006;Ghorani et al. 2019). But some reports showed the toxic behavior of the test drug carvacrol in Osborne-Mendel rats and mice, where depression, ataxia, decreased spontaneous motor activity, somnolence, coma, and death were observed (Jenner et al. 1964;Viana et al. 1981) Detail reports of animal acute toxicity studies have been enlisted in Table 13.1. ...
... Mice receiving 33.3 mg/kg CARV (intraperitoneal) showed no adverse effects and at a dose of 50 mg/kg, nonspecific effects were exhibited, however at higher doses (110-233.3 mg/kg CARV) mice experienced ataxia, decreased spontaneous motor activity, and somnolence prior to death [32]. Furthermore, vasorelaxant actions induced by CARV were not relateto putative toxic effects [20]. ...
Article
Carvacrol (CARV), has been shown to possess various pharmacological properties, especially in the treatment of cardiovascular diseases. We evaluated the antihypertensive effect of the CARV free and encapsulation of CARV in β‐cyclodextrin (CARV/β‐CD), and whether CARV/β‐CD is able to improve the antihypertensive effects of CARV free in spontaneously hypertensive rats (SHR). The rats were randomly divided into 4 groups, each treated daily for 21 days and the mean arterial pressure and heart rate was measured every 5 days: group 1 (Wistar‐vehicle solution); group 2 (SHR‐vehicle); group 3 (SHR‐CARV 50 mg/kg/day) and group 4 (CARV/β‐CD 50 mg/kg/day). After 21 days of treatment, the mesenteric artery from treated animals was tested for phenylephrine (Phe) and sodium nitroprusside (SNP) sensitivity. In addition, administration of CARV/β‐CD induced important antihypertensive activity when compared with the uncomplexed form, reducingthe progression of arterial hypertension in SHR. Moreover, pharmacological potency to Phe in the SHR‐CARV and CARV/β‐CD groups was increased, approaching values expressed in the wistar‐vehicle. Furthermore, CARV/β‐CD reduced the production of the pro‐inflammatory mediator, IL‐1β, and increased anti‐inflammatory cytokine, IL‐10. Together, these results produced evidence that the encapsulation of CARV in β‐CD can improve cardiovascular activity, showing potential anti‐inflammatory and antihypertensive effects.
... CFRSearch.cfm?FR=172.515). In recent decades, it has been proposed as a natural preservative for the food industry (Burt 2004) and as a disinfectant, fungicide, and fragrance ingredient in cosmetic formulations and in health-related products (Andersen 2006). It is interesting to note that the strong antimicrobial efficacy of its vapors compared to that of the solution suggests further advantageous perspectives (Inouye et al. 2001;Nostro et al. 2009;Mandras et al. 2016). ...
Article
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The current demand for new antimicrobial systems has stimulated research for the development of poly(lactic acid)/carvacrol (PLA/CAR)-based materials able to hinder the growth and spread of microorganisms. The eco-friendly characteristics of PLA and cytocompatibility make it very promising in the perspective of green chemistry applications as material for food and biomedical employments. The broad-spectrum biological and pharmacological properties of CAR, including antimicrobial activity, make it an interesting bioactive molecule that can be easily compounded with PLA by adopting the same techniques as those commonly used for PLA manufacturing. This review critically discusses the most common methods to incorporate CAR into a PLA matrix and their interference on the morphomechanical properties, release behavior, and antimicrobial activity of systems. The high potential of PLA/CAR materials in terms of chemical-physical and antimicrobial properties can be exploited for the future development of food packaging, coated medical devices, or drug delivery systems.
... The Food and Drug Administration approved carvacrol as a safe food additive, 4 and it is safe for topical use. 5 Carvacrol has attracted attention as a potential therapeutic based on its anti-inflammatory, 6,7 antioxidant, 8 antibacterial, 9 and antifungal 10 activities. Moreover, several studies showed analgesic effects of carvacrol in animal pain models: antinociceptive activity following intraperitoneal injection in rats subjected to formalin test 11 ; inhibition of formalin-induced neurogenic and inflammatory pain after intraperitoneal injection in mice 8 ; and decreased writhing responses from acetic acid-, formalin-or glutamate-induced pain in orally treated mice. ...
Article
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Carvacrol is the predominant monoterpene in essential oils from many aromatic plants. Several animal studies showing analgesic effects of carvacrol indicate potential of carvacrol as a new medication for patients with refractory pain. Voltage-gated sodium channels (Nav) are thought to have crucial roles in the development of inflammatory and neuropathic pain, but there is limited information about whether the analgesic mechanism of carvacrol involves Nav. We used whole-cell, two-electrode, voltage-clamp techniques to examine the effects of carvacrol on sodium currents in Xenopus oocytes expressing α subunits of Nav1.2, Nav1.3, Nav1.6, Nav1.7, and Nav1.8. Carvacrol dose-dependently suppressed sodium currents at a holding potential that induced half-maximal current. The half-maximal inhibitory concentration values for Nav1.2, Nav1.3, Nav1.6, Nav1.7, and Nav1.8 were 233, 526, 215, 367, and 824 μmol/L, respectively, indicating that carvacrol had more potent inhibitory effects towards Nav1.2 and Nav1.6 than Nav1.3, Nav1.7, and Nav1.8. Gating analysis showed a depolarizing shift of the activation curve and a hyperpolarizing shift of the inactivation curve in all five α subunits following carvacrol treatment. Furthermore, carvacrol exhibits a use-dependent block for all five α Nav subunits. These findings provide a better understanding of the mechanisms associated with the analgesic effect of carvacrol.
... Cresols such as phenol, 2-methyl-(o-cresol), phenol, 3-methyl-(m-cresol) and phenol, 4-methyl-(p-cresol) are among the phenols identified in oils. These compounds have antiseptic activity but have also shown moderate toxicity [59] and can be found in the coal tar [26]. Hydroquinone present in oil-2 has been used in the treatment of various hyperpigmentation skin disorders [60]. ...
Article
Pyrolytic products have been historically used as a therapeutic treatment for psoriasis, a dermatological inflammatory disease. However, little is known about the mechanisms involved in their pharmacological activity. The main goals of this work were to characterize pyrolytic fractions derived from Amphipterygium adstringens bark, a plant used in Mexican traditional medicine, and to study the effects of pyrolytic oils as anti-IL-17 agents on HaCaT keratinocytes. A. adstringens biomass and pyrolytic fractions were first characterized by proximate, elemental analysis, FTIR, Py-GC-MS, GC-MS, UV-fluorescence and HPLC-DAD to determine its physicochemical composition. Toxicity of pyrolytic oils was further assessed on HaCaT keratinocytes by the MTT method and the non-cytotoxic concentrations were used to determine their effects on IL-8 production of IL-17-stimulated HaCaT keratinocytes. The result obtained show that pyrolytic oils are very rich in phenols, some of them recognized by their anti-inflammatory properties. Pyrolytic oils showed significant inhibitory effects on IL-8 production, suggesting that they could be potentially explored for treating IL-17 driven dermatological diseases such as psoriasis.
... Toxicity studies of Carvacrol are limited (Suntres et al., 2015). In the mouse, it was estimated that the median lethal doses for intravenous and intraperitoneal administration were 80.0 and 73.3 mg/kg of body weight, respectively (Andersen, 2006). White it was not the purpose here to establish an LD50 for im administration of carvacrol, 3 of the 8 male mice died with 300-500 mg/kg (2.0-3.33 mM) while all females did not exhibit toxicity, suggesting a high tolerance from im administration. ...
Article
Plant derived antimicrobials (PDAs) such as trans-cinnamaldehyde, eugenol and carvacrol, possess strong antibacterial properties yet are generally regarded as safe. In the current crisis of antibiotic resistance, the use of PDAs as alternatives to prevent and control bacterial infections in livestock has gained momentum. The inhibitory effects of PDAs on common bacteria such as C.difficile, Listeria, Salmonella have been widely studied. PDAs have also been found effective in wall-less bacteria such as Mycoplasma, for which common antibiotics are not effective and vaccines are not always effective. In animal husbandry, PDAs can be potentially added in feed to metaphalactively prevent bacteria infection, but they could also be potentially used to treat infection in the form of an injectable. Previous reports of PDA injection were focus on toxicity or effectiveness after intraperitoneal administration in the mouse model. Here we investigated the toxicity trans-cinnamaldehyde, eugenol and carvacrol after intramuscular in mice. Two levels of control (DMSO) and each PDAs were injected into the hind limbs of CD-1 mice of 7-8 weeks of age. Mice were monitored for weight, eating, behavior, appearance, and foot/leg changes for 2 hours post-injection and twice daily for the next 4 days. The liver, kidney and hind limb were observed for discoloration, swelling, size (mm), weight (g), and relative weight (percentage of organ weight/body weight). A total of 13 parameters were studied for each treatment group. Significant differences between controls and treated were only observed for the relative liver weight at 3.04 mM eugenol (p
... These species are generally enriched source of phenolics, α-pyrone and acetophenones derivatives responsible for its biological activities (Kladar et al., 2015). It was established that phenols and its derivatives are toxic to humans and animals due to the formation of phenoxyl radicals (Andersen, 2006). Salvia species are also characterized by different secondary metabolite constituents responsible for their bioactivities (Simmonds and Blaney, 1992). ...
... In these constituents, thymol (2-isopropyl-5-methylphenol), and its isomer carvacrol (2-methyl-5-(1-methylethyl)-phenol) were identified as the major components of Jordanian and Saudi Origanum respectively. These isomeric phytomolecules have widespread applications in various fields including pharmaceutical, food and cosmetic industries (Javed et al. 2013;Sobczak et al. 2014;Venturini et al. 2002;Andersen 2006;Suntres et al. 2015). ...
Article
Full-text available
Essential oils (EOs) from the stems and leaves of Origanum vulgare L. grown in Saudi Arabia and Jordan were analyzed by gas chromatography-mass spectrometry (GC-MS) and GC-flame ionization detector (FID) techniques on two different columns (polar and nonpolar). A detailed phytochemical analysis led to the identification of 153 constituents of these essential oils. Both Saudi and Jordanian plants are classified by chemotypes rich in cymyl-compounds. However, the Saudi Origanum contains carvacrol as the major component and is, thus, characterized as a carvacrol chemotype, while the Jordanian Origanum contains thymol as the major component, and, thus, it is classified as a thymol chemotype. In addition, the antimicrobial activities of the studied EOs and their major components, including carvacrol and thymol, were evaluated against various Gram-positive and Gram-negative microorganisms. All the tested compounds exhibited significant antimicrobial activity against all the tested bacteria. Among them, thymol demonstrated superior activity against all the tested organisms, followed by carvacrol. Moreover, results on oil composition and oil yield of O. vulgare L. from different parts of the world is compared in detail with the present outcomes.
Article
In this study, we evaluated the efficacy of combinations of the terpenes carvacrol, thymol, and menthol on Dermanyssus gallinae under in vitro (direct contact and vapour efficacy assays) and in-use conditions. Combinations investigated in vitro included carvacrol-menthol, thymol-menthol, carvacrol-thymol, and carvacrol-thymol-menthol. Results from contact efficacy studies showed that carvacrol-thymol-menthol was the most efficacious compared to the other combinations (P < 0.05), killing 100% of the mites when at a concentration of 0.5 μg/mL. Thymol-menthol showed the weakest acaricidal activity with an approximate 80% mortality rate at a concentration of 2 μg/mL. Based on the results of the vapour efficacy assay, all tested combinations appear to exert their acaricidal efficacy not only through direct contact, but also by fumigant action. A subsequent in-field efficacy investigation in a cage system laying farm was carried out to confirm the miticidal activity of the carvacrol-thymol-menthol combination. A formulation based on the triple combination of carvacrol-thymol-menthol diluted 1:40 in water was sprayed, with 1-week interval, in an 8000-laying hen farm, in presence of hens. The number of mites were counted by monitoring traps for 21 days through the study. The number of mites in the treated group decreased until day 5 after the first spray, but increased on days 5 and 7. However, after the second spray on day 7, the number of mites showed a significant decrease on day 10. This terpene-based combination which showed promising in vitro and in field miticidal activity can be a step forward in greening the future of pest management, also producing residue-free eggs.
Chapter
Oleoresin is a mixture of volatile and nonvolatile components available in whole extract of natural herb or spice. It principally comprises essential oils and resin. Lemongrass oleoresins come from the Cymbopogon species, which grow in the tropical and subtropical regions of the world. Oleoresin of lemongrass is a dark green-colored viscous liquid having a characteristic lemon aroma and flavor and is mostly used as a flavoring ingredient. The lemon prefix in the lemongrass specifies the characteristic lemon-like odor, which is due to the availability of citral content (mixture of two isomeric aldehydes, geranial and neral). It has been utilized in synthesizing flavors, perfumes, cosmetics, detergents, and in the food and pharmaceutical industries. Different methods are used to extract the lemongrass essential oil, but steam distillation is the most suitable method as it doesn’t alter the quality of the obtained oil. The chemical composition of lemongrass oil varies depending on its extraction methods, genetic differences, harvest period, photoperiod, plant age, farming practices, and geographical origin. Lemongrass essential oil has shown several biological activities, including antimicrobial, antifungal, antiprotozoan, antioxidant, antidiarrheal, antimutagenic, antiinflammatory, antimalarial, antinociceptive, antihepatotoxic activities, etc. Lemongrass oil is a potent food preservative because of its extraordinary antifungal and antibacterial activities.
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Background Since ancient times, humankind has used plants for its flavor, essence and especially for medical purposes in addition to food source. Turkey, due to its geographical location, is home to many varieties of species of medicinal and aromatic plants. Aromatic and medicinal plants produce essential oils in the form of secondary metabolites. These essential oils are being used in food, cosmetic and pharmaceutical industries. Due to the various side effects of synthetic agents, the use of essential oils as antimicrobial agents comes to the fore. Objective The purpose of this study was to determine the essential oil composition of Thymbra spicata L. var. spicata collected from Gaziantep Region of Turkey and to evaluate its antimicrobial efficacy against microorganism species commonly encountered in food, cosmetic and pharmaceutical industries. Methods In this study, the antimicrobial effect of volatile oil obtained from dried leaves of Thymbra spicata L. var. spicata traditionally known as Zahter was investigated. For this purpose, volatile oil was obtained from leaves of the plant by steam vapor distillation method. Antimicrobial efficacy tests were conducted against microorganisms; Staphylococcus aureus, Enterococcus hirae, Enterococcus faecalis, Listeria monocytogenes, Escherichia coli, Klebsiella pneumoniae, Proteus hauseri, Pseudomonas aeruginosa, Salmonella typhimurium and Candida albicans. Results Result of the experiments showed that the volatile oil obtained from Thymbra spicata L. var. spicata had a cidal effect on selected pathogenic microorganisms even at low concentrations. Conclusion This study showed that the high carvacrol content of the T. spicata L. var. spicata grown in the Gaziantep region of Turkey is a promising source of antimicrobial raw materials in the pharmaceutical, cosmetic and food industries.
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Background Thymol and carvacrol as natural essential oils and phenol compounds are components derived from some medicinal plants, such as thyme and oregano species. Objectives The increasing demands in organic and healthy meat and egg consumption in human society have made it necessary to consider alternative natural compounds for the replacement of chemical compounds in poultry production. The chemical compounds can remain in meat and eggs and cause complications in human health. Therefore, these natural compounds can be fed with a higher safety in poultry production with specific effects. In this regard, the role of thymol and carvacrol as natural compounds in the poultry production has been discussed in the review. Methods In this study, by searching for keywords related to thymol and carvacrol in poultry production in Google Scholar database, the articles related to different aspects of the biological effects of these two phytogenes in poultry production were selected and analyzed. Results A review of previous studies has shown that thymol and carvacrol possess a wide range of biological activities, including antibacterial, antiviral, antioxidant, anti-inflammatory, modulating of immunity response and regulating of the gut microbial population. Also, in meat type chickens can promote growth and influence feed utilization. The beneficial effect of this compound was evaluated in hepatic toxicity and demonstrated as a hepatoprotective compound in chickens. Furthermore, these compounds can affect the behavior of layers and influence egg composition, eggshell thickness, and the sensory quality of eggs. Conclusion It seems that with the increasing demand for healthy protein products, these compounds can be used to improve performance as a substitute alternative for chemical compounds in healthy poultry farms.
Article
Carvacrol, a naturally occurring aromatic compound, is known to have medicinal properties. However, the experimental vapour–liquid equilibria (VLE) data reported in literature are limited to vapour pressures up to the normal boiling point and heats of vapourization at three relatively low temperatures. As knowledge of VLE data is essential for the design of efficient separation processes, a molecular simulation technique is employed in conjunction with a force field (where the potential functions and parameters have been obtained entirely from literature) to predict the coexistence properties, including densities, at elevated temperatures. Process simulation software employed to design separation processes generally employ the equation of state approach which requires as input the critical state properties and acentric factor (which are not reported in literature for carvacrol) and are determined to be Tc = 7065 K, Pc = 333 bar, Vc = 50316 cc/mol and ω = 0.485 in this work. The numbers in subscript indicate the uncertainties in the last digit(s). Additionally, the structure of the coexisting liquid phase has also been investigated at the molecular level using the intermolecular site-site radial distribution functions and number integrals to determine the extent of hydrogen-bonding.
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Nowadays, almost 300 essential oils (EOs) are commonly traded in the world market, with a prediction to be worth over $14 billion in 2024. EOs are natural preservatives for food products in order to reduce the activity of pathogenic microorganisms, therefore their use as an antioxidant or a preservative in foods has been encouraged. They are not only considered as antimicrobial or flavoring agents, but are also incorporated into food packaging materials. There are several types of EOs which have been approved as food additives by the Food and Drug Administration. Hence, it is important to use safe EO products to minimize possible adverse effect risks such as nausea, vomiting, necrosis, nephropathy, mucous membrane, and skin irritation. This review article gives information about some EOs that are used in the food industries and the types of some allergenic compounds and biocides which could make the EOs hazardous or may cause allergenic reactions in the human body. Besides, some analysis techniques of possible allergenic compounds or biocides in EOs were introduced and supported with the most relevant studies. The overall conclusion from the study is that pregnant women, patients taking drugs (e.g., diabetics) or the having a history of allergy are the most prone to be affected from EO allergenic components. As regards to biocides, organochlorine and organophosphorus types of pesticides that are carried over from the plant may be found mostly in EOs. The most common allergic reaction is skin sensitization and irritation if the EO components are oxidized during storage or transportation. Moreover, drug interactions are one of the other possible adverse effect. Hence, determination of biocides and possible allergenic component concentrations is an essential factor when they are used as a preservative or flavoring agent. The most prominent analysis techniques are gas and liquid chromatography because most of the allergens and biocides are mainly composed of volatile components. Practical Application Determining of the essential oil's content will be crucial if oils are used for food preservation or flavoring because they may have some hazardous effects, such as nausea, vomiting, necrosis and nephropathy. Therefore, after applying them to the food products, consumers (especially pregnant women) should be informed about their concentration levels and their possible adverse effects are taken into account when they are consumed over toxic limit. For this reason, we reviewed in our study that some allergenic components, biocides and toxic limits of EOs to be used in food products. In addition to this, recent analytical techniques have been explained and discussed which methods are suitable for analysis.
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Bitki ve bitkisel materyaller veteriner fitoterapi ve etnoveteriner hekimlik uygulamaları içerisinde önemli bir yere sahiptir. Bitkiler tarafından sentezlenen bazı biyoaktif kimyasal bileşenler medikal etkilere sahiptir. Ancak bu bitki ve bitkisel materyallerin kullanımları; teşhisteki yanlışlıklar, doz ayarlama güçlüğü, geleneksel kullanımlarına dair yazılı kayıt ve bilimsel çalışmaların yetersizliği, düşük hijyen koşulları ve toplandığı bölgeye, mevsime, kullanılan kısmına ve elde edildiği yönteme göre sahip oldukları kimyasal kompozisyonlarının değişmesi gibi nedenlere bağlı olarak zehirlen-meler meydana getirebilmektedir. Çalışma kapsamında Hatay bölgesinde yetişen, veteriner fitoterapi ve etnoveteriner hekimliğinde de kullanılan Thymbra spicata var. spicata L., Rosmarinus officinalis L. ve Laurus nobilis L. bitkilerinin içerdikleri biyoaktif kimyasal maddelerin kompozisyonları belirlenmiştir. Solvent ekstraksiyonu yöntemiyle elde edilen bitki ekstraksiyonlarının kimyasal kompozisyonları gaz kromatografisi kütle spektrofotometresi (GC-MS) ile belirlendi. Analiz sonucunda R. officinalis L. ve L. nobilis L.’in ana bileşenleri sırasıyla %38.91 ve %33.70 oranlarında 1,8-sineol (ökaliptol) olarak tespit edildi. T. spicata var. spicata L.’nın ana bileşeni ise karvakrol (%48.82) olarak belirlendi. Bu bileşenlerin antimikrobiyal, antienflamatuar ve antioksidan etkileri yanında karaciğer, böbrek, pankreas ve testis gibi organ hasarları, DNA iplik kopmaları ve solunum problemleri gibi istenmeyen ve zehirli etkilere de yol açtığı bildirilmiş-tir. Bu nedenle hayvan sağlığında da kullanılan tıbbi bitki ve bitkisel materyallerin ana bileşen ve oranının bilinmesinin potansiyel toksik etkilerin önlenebilmesi açısından önemli olduğu düşünülmektedir. Plants and herbal substances have an important place in veterinary phytotherapy and ethnoveterinary med-icine applications. Some bioactive chemical compounds synthesized by plants have medical effects. However, the use of these plants and herbal materials can cause poisoning due to wrong identification, difficulty in adjusting its dosage, insufficiency of written records and scientific studies on their traditional use, poor hygienic conditions in preparation and variation in their chemical composition according to the region, where and the season when they are gathered, their used part, and their extraction method. In our study, it was aimed to determine the chemical compositions and to toxi-cologically evaluate the major compounds of T. spicata var. spicata L., Rosmarinus officinalis L., and Laurus nobilis L. grown in Hatay region and used in veterinary phytotherapy and ethnoveterinary medicine. Chemical compositions of plants contents obtained by solvent extraction method were determined by gas chromatography mass spectrophotom-etry (GC-MS) analysis. The major components of R. officinalis L. and L. nobilis L. were determined as 1,8-cineol (eucalyptol), in rates of 38.91%, and 33.70% respectively. The major component of T. spicata var. spicata L. was deter-mined as carvacrol (48.82%). While these components have antimicrobial, anti-inflammatory and antioxidant effects, it has also been reported to cause undesirable and toxic effects such as organs damages (liver, kidney, pancreas and testes etc.), DNA thread breaks and respiratory problems. For this reason, it is thought that knowing the major compo-nents and their ratios of medicinal plants and materials used in animal health is important in terms of preventing poten-tial toxic effects.
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In this work, Thauera sp. DO isolated from sludge and sediment utilized p-chlorocresol and some related compounds as the sole carbon and energy sources under both aerobic and anaerobic conditions. The pathways for p-chlorocresol in the isolate under each condition were different. Under the aerobic condition, p-chlorocresol was degraded via two separate pathways. The first was the reductive dehalogenation reaction, in which the substrate was transformed to m-cresol followed by the catechol degradation pathway, and the second aerobic pathway for p-chlorocresol was the methyl oxidation to 4-chlorobenzoate. Under the anaerobic conditions, p-chlorocresol was rapidly dechlorinated in the first step to m-cresol, followed by sevaral steps prior to the complete degradation. The determination of p-chlorocresol degradation in liquid media by whole cells showed that 100% and 85% of the substrate (0.3 mM) were transformed within 12 h under aerobic and anaerobic conditions, respectively, while nearly 100% of this compound was degraded within 6 h using the two-stage anaerobic–aerobic degradation process. These results show a novel method to increase the degradation rates of p-chlorocresol using the anaerobic process followed by the aerobic process.
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Abstract Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on an essential oil extracted from Origanum vulgare ssp. hirtum (Link) Ietsw. when used as a sensory feed additive for all animal species. Analysis of the oil identified 13 components accounting for > 99% of the oil, with carvacrol being the prevalent (78%). The FEEDAP Panel concludes that the proposed use level of 150 mg/kg complete feed is safe for ornamental fish. For the other species, the calculated maximum safe concentration of the essential oil in complete feed was 22 mg/kg for chickens for fattening, 33 mg/kg for laying hens, 30 mg/kg for turkeys for fattening, 40 mg/kg for piglets, 48 mg/kg for pigs for fattening, 63 mg/kg for sows, 57 mg/kg for dairy cows, 100 mg/kg for veal calves, 88 mg/kg for cattle for fattening, sheep, goats and horses, 35 mg/kg for rabbits, 101 mg/kg for salmonids, 106 mg/kg for dogs, and 18 mg/kg for cats. No concerns for consumer safety were identified following the use of the additive up to the maximum safe concentration in feed. The additive is considered as irritant to skin and eyes and a potential skin and respiratory sensitiser. Use in animal husbandry of the essential oil extracted from O. vulgare ssp. hirtum is not expected to pose a risk for the environment. Since oregano and its preparations are recognised to flavour food and their function in feed would be essentially the same, no further demonstration of efficacy is considered necessary for the essential oil.
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The optimum pH for growth for eight toxigenic strains of Aspergillus was recorded at pH 6 in unamended potato dextrose broth medium. Significantly less mycelial growth was observed at pH 4 and 8, respectively, for all of the fungal strains. In the presence of 1.0 mM of thymol, mycelial growth was completely inhibited at pH 4, 6, and 8 for all of the fungal strains. Carvacrol, at the same concentration, completely inhibited the growth of the fungi only at pH 4 and 8. At lower concentrations (0.1 and 0.5 mM), in the presence of thymol or carvacrol, partial mycelial inhibition at all pH levels was observed with significantly less mycelial growth at pH 4 and 8. Copyright © International Association of Milk, Food and Environmental Sanitarians.
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Laboratory evaluation of the efficacy of soil phase photodegradation of recalcitrant hazardous organic components of wood treating wastes is described. The photodecomposition of anthracene, biphenyl, 9H-carbazole, m-cresol, dibenzofuran, fluorene, pentachlorophenol, phenanthrene, pyrene and quinoline under UV and visible light was monitored over a 50-day reaction period in three test soils. Methylene blue, riboflavin, hydrogen peroxide, peat moss and diethylamine soil amendments were evaluated as to their effect on the enhancement of compound photoreaction rates in the test soil systems. Dark control samples monitored over the entire study period were utilized to quantify non-photo mediated reaction losses. Compounds losses in both the dark control and irradiated samples were found to follow first order kinetics, allowing the calculation of first order photodegradation reaction rate constants for each test soil/compound combination. Degradation due to photochemical activity was observed for all test compounds, with compound photolytic half-lives ranging from 7 to approximately 180 days. None of the soil amendments were found to improve soil phase photodegradation, although photosensitization by anthracene was shown to significantly enhance the rate of photodegradation of the other test compounds. Soil type, and its characteristic of internal reflectance, proved to be the most significant factor affecting compound degradation rates suggesting the necessity for site specific assessments of soil phase photodegradation potential.
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ABSTRACT Essential oils of various plant species rich in carvacrol have several ethnomedical uses for various diseases in Turkey. Carvacrol, which was obtained by fractional distillation of Origanum onites L. Essential oil was tested for lung tumors induced by DMBA in rats in vivo and it was found to have strong antitumor activity at 0.1 mg.kg-1 i.p. Although the mechanism of action of antitumor activity of carvacrol was not investigated in this study, evidences for an inhibitory effect on angiogenesis were observed. Keywords: Carvacrol, Antitumor activity. ÖZET Karvakrol’ce zengin çeşitli bitkilerin uçucu yağları, Türkiye’de çeşitli etnomedikal amaçlarla kullanılmaktadır. Origanum onites L. Uçucu yağından fraksiyonlu distilasyon tekniği ile elde edilen karvakrol’un (0.1 mg.kg-1 i.p.), sıçanlarda DMBA ile oluşturulan pulmoner tumorigenez üzerinde kuvvetli bir inbitör etkiye sahip olduğu bulunmuştur. Karvakrolun antitümör etlisinin mekanizması bu çalışmada araştırılmamış ise de, anjiyojenez üzerinde etkiye sahip olabileceğine ilişkin veriler elde edilmiştir. Anahtar Kelime: Karvakrol, Antitümor etki
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Swine prostate extract (Robaveron) was given to pregnant rabbits to examine its effects on dams and their fetuses. The drug was given subcutaneously at dose levels of 10, 5, 1 ml/kg once daily from day 6 to 18 of gestation. Moreover the solvent (0.3% m-Cresol) was given at dose levels of 10 ml/kg as well as the drug treated rabbits. On the observation of dams, mean body weight, water consumption and general behavior were not influenced by Robaveron. Food consumption was decreased after day 14 of gestation in the 30 ml/kg group and the solvent group. No difference was observed in each groups on the number of implantation, resorption, dead fetus, live fetus and external anomaly. Average number of implantation and body weight were decreased in the solvent group. On the skeletal observation of fetus, there were 2 anomalies (Dumbell shaped Th7, split L7-Th7 and Fused Car 9-10) in the 5 ml/kg group and 1 anomaly (Asymmetry Th10-12) in the 1 ml/kg group. No difference was observed in each group as to the skeletal development and variation. On the visceral observation of fetus, there was no influence in each group.
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Swine prostate extract (Robaveron) was given to ICR-SLC strain mice to examined its teratogenic effects on dams, their fetuses and offsprings. The drug was given subcutaneously at doses of 5, 10, 20 ml/kg/day to pregnant mice daily from the 6th to 15th days of gestation; m-cresol was similarly given to the solvent group, and saline to control group. No influence of the drug was observed on mean body weight or general behavior during pregnancy. No difference was observed in the mean number of implantations, live fetuses, mean body weights and fetal mortality in any of the groups. There were no differences between the control group and the treated groups in the rates of external and skeletal anomality except for a slight increase in club foot and lumber ribs; ossification also did not differ from that of the control group. Malformations of visceral organs were not observed in any of the groups. No effect of Robaveron was observed on the postnatal development of the offspring up to the 5th week after birth.
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High speed liquid chromatographic analysis of isopropylmethylphenol (3-methyl-4-isopropylphenol) on Nucleosil 5NH2 (5μm, Macherey-Nagel) was studied. The condition was as follows; column size: 4mm i.d.×250mm, detector: fluorescence spectrophotometer (exciting wavelength: 280nm and fluorescence wavelength: 305nm), eluent: 10% ethanol-hexane, flow rate: 1.16ml/min. column temperature: 40°C. Determination was carried out successfully by using thymol or estradiol as an internal standard. The plots of peak height ratio vs. amount ratio (isopropylmethylphenol-thymol or estradiol) were linear between 2.5ppm to 12.5ppm. The experimentally prepared hair tonic and cream were diluted (1:100) with ethanol and dehydrated with anhydrous sodium sulfate. Thymol (5ng/μl) or estradiol (20ng/μl) was incorporated into this mixture as an internal standard. The averaged recoveries from hair tonic and cream ranged 100.5% to 100.6% and c. v. (%) were 1.25 to 1.02, respectively. This method is very simple, accurate and selective, therefore it is applicable to determine isopropylmethylphenol in cosmetic products at routin analyses. © 1980, The Japan Society for Analytical Chemistry. All rights reserved.
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More than 200 mono- and sesquiterpenes were evaluated by agar diffusion plate tests for their ability to inhibit the growth of three postharvest pathogenic fungi: Penicillium digitatum, P. italicum, and P. ulaiense. Major fungicidal action was observed in phenolic components like carvacrol and related homologue molecules. Etherified components like anethole, methyl chavicol and safrole exhibited less fungicidal action. Monoterpene hydrocarbons gave poor results. Fungicidal action against the three species often differed in degree of strength. Some components showed a strong fungicidal as well as fungistatic action, others only a fungistatic action. The inhibition of many components lasted for several months. In others a regression was observed as early as one week after initial scoring.
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The retention characteristics of thirty nine phenols have been investigated on aluminium-backed RP-18 F(254s) plates using a variety of mobile phase systems. The visual and photometric detection limits of the compounds have also been determined. The special suitability of reversed phase TLC for the screening of drinking water samples for pollution by phenols has been shown by analysis of two spiked tap water samples.
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The goal of the synthetic fuels industry is simply to convert the solid energy resource, coal, into more readily usable forms such as liquid or gaseous fuels. Additional possibilities exist in the conversion of synfuels gases into petroleum-like products such as waxes, oils and the whole array of products that are now derived from petroleum. A viable synthetic fuels industry is a distinct possibility: such an industry provided fuel for the Axis powers during World War II. A synthetic fuels industry based upon similar German technology is now providing energy for South Africa, which currently finds difficulty in importing sufficient petroleum. The USA and othr Western countries are currently devoting large sums of money and technical resources to further development and refining of second, third and further generations of coal conversion technology. Refs.
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The book provides, in a single source, hazard-analysis information for nearly 13,000 common industrial and laboratory materials. New sections have been added to this edition to refiect the increased interest in pollution and health hazards. For public, academic and special libraries. -- AATA
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1. Antibacterial activity of 32 kinds of pure terpenes was examined against Bacillus subtilis, Salmonella enteritidis, Staphylococcus aureus, Pseudomonas aeruginose, Proteus morganii and Escherichia coli. It was thereby found that carvacrol, thymol, isoborneol, vanilline and salicylaldehyde show antibacterial activity in dilutions 2,000 or over. 2. There was no difference in antibacterial activity according to the number of double bonds in the cyclohexane ring and introduction of a ketone radical to form cyclohexenone also had no effect on antibacterial activity. 3. Derivatives of thymol, carvacrol, eugenol, isoborneol, and vanillin, in which a hydroxyl had been introduced and directly bonded to the cyclohexane ring, showed antibacterial activity in dilutions 2,000 or over. 4. It was presumed that addition of vanilla or eugenol as an essence to fish ham or fish sausage would be effective for the preservation of these food products. © 1960, The Japanese Society of Fisheries Science. All rights reserved.
Article
Concentrations of eugenol and carvacrol in ethanolic extracts of cloves and savory, respectively, were determined quantitatively by GC. Both compounds were exclusively responsible for the antifungal action of these spices against Cladosporium herbarum and Penicillium glabrum. Other constituents showed no or insignificant activity.
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An open epicutaneous test (OET) is proposed for the detection of Skin Irritation and Contact Hypersensitivity induced in Guinea Pigs. Thirty-two compounds described in the literature as being Allergenic for man were tested in the guinea pig by the OET technique, and for the purpose of comparison, by three other techniques, namely the Draize Test (DT), the Maximization Test (MT) and a test with Freund's Complete Adjuvant (FCAT). In the OET, a high degree of correlation was found between the allergenicity of the tested compounds for the guinea pig and for man.
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The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.c. 9604 et seq.], as amended by the Supeliund Amendments and Reauthorization Act (SARA) [Pub. L. 99-499], requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly with the U.S. Environmental Protection Agency (USEPA), ill order of priority, a list of hazardous substances most commonly fOlmd at facilities on the CERCLA National Priorities List (NPL) (42 U.S. C. 9604(i)(2)); prepare toxicological profiles for each substance included on the priority list ofhazardous substances, and ascertain in the toxicological profiles, significant human exposure levels (SHELs)for hazardous substances in the environment, and the associated acute, subacute, alld chronic health effects (42 U.s.c. 9604(i)(3)); and assure the initiation ofa research prog ram tofill identified data needs associated with the substances (42 U.S.c. 9604(i)(5)). The A TSDR Minimal Risk Levels (MRLs) were developed as an initial response to the mandate and to provide screening levels for health assessors and other responders to identify contaminants and potential health effects that may be of concern at hazardous waste sites and releases. An MRL is an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration of exposure. 1n this paper, we describe ATSDR s current approach for deriving MRLs for priority hazardous substances. The MRLs for a particular substance are published in the toxicological profile for that substance. A listing ofthe current published MRL.v as ofDecember 1997 is also provided.
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A 28-year-old woman working in an aviary, complained of red swollen eyelids each time she had to wash chicken incubators. It lasted for several hours, so that she had to leave the job. For washing the incubators, she used 2 detergent disinfectants - Prophyl® and Polydesine®. She was patch tested with the Standard Series, with her cosmetics and with the 2 detergents (10% water), which were all negative. Open tests with readings at 30 min with Propyl® (20% water) elicited an urticarial wheal; at the time we were preparing the solution for the test, the patient developed eyelid oedema and erythema. The 2 active principles of Propyl® are p-chloro-m-cresol (PCMC) and o-benzyl-p-chlorophenol (OBPCP). These 2 products were diluted 1% and 10% in water: ethanol (1:1) and were tested with open and prick tests, with the following results: PCMC open test (1%) neg, (10%) +++; prick test (1%) +?, (10%) +++; OBPCP open test (1%) neg, (10%) neg; prick test (1%) neg, (10%) neg. After the urticarial wheal, tests with chlorocresol produced superficial necrosis, which could also be observed on the eyelids at the same time. Tests in 10 controls elicited a slight erythema in a few patients, but never oedema or necrosis. Chlorocresol has not so far been reported as causing contact urticaria, either immunologic or not. The high concentration needed to induce the urticairal reaction is unusual, as well as the superficial necrosis which resulted. However, the quite similar clinical picture which was elicited simultaneously and the negative controls, made us consider it as a case of contact urticaria.
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The antignawing activity of the steam distillate ofThujopsis dolabrata S. et. Z. var.hondai sawdust against mice was evaluated using a wire-dipping method. This method is suitable for measuring repellent activities of chemicals and plant-derived materials. The steam distillate of theThujopsis sawdust was shown to have potent antignawing activity. Three terpenoid compounds with antignawing activity were isolated from the steam distillate of theThujopsis sawdust: thujopsene, carvacrol, andβ-thujaplicine. Carvacrol exhibited the most potent repellent activity. As a naturally occurring repellent, carvacrol could be useful as new preventive agent against various kinds of damage caused by rodents.
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Toluene (TOL) is one of the most widely used organic solvents in the workplace. Recently, the permissible exposure limit to TOL has been reduced from 100 to 50 ppm by the American Conference of Governmental Industrial Hygienists. Urinary hippuric acid (HA) is not recommended for monitoring the exposure to low ambient concentrations of TOL. Despite the fact that there are other potential indicators of exposure to TOL, there is still no consensus on which one is the most reliable for use on a large scale. This study was undertaken to describe how three indicators of TOL exposure—namely, HA and o-cresol (o-CR) in urine—and unchanged TOL in alveolar air (TOL-A) relate to graded exposure levels of TOL in human volunteers. In addition, the potential impact of simultaneous exposure to xylene (XYL) and TOL exposure on indicators of exposure to TOL was investigated in view of the known metabolic interference between these two solvents. Four adult nonsmoking volunteers were exposed (7 hours) to various concentrations of TOL (10, 20, 30, 50, and 100 ppm). On three other occasions, the volunteers were exposed to three different binary mixtures containing TOL and XYL. The concentrations of HA and o-CR were determined in urine samples collected during and after exposures, whereas TOL was measured in end-exhaled (alveolar) air samples collected at 30-minute intervals during and after exposure. There was a good correlation between TOL exposure and the urinary levels of HA, especially in samples collected during the last 4 hours of exposure (3 to 7 hours) (r = 0.87). The urinary levels of o-CR were also well correlated with TOL exposure for samples collected during the last 4 hours of exposure (r = 0.81) and for samples collected during the 17 hours following exposure (r = 0.88). However, at low exposure concentrations of TOL (i.e., 10 ppm), the excretion (3 to 7 hours) of HA (e.g., 0.23 ± 0.02 mmol/mmol creatinine) was only slightly above the mean background level measured before exposure (0.22 ± 0.06 mmol/mmol creatinine), while that of o-CR was clearly above background (0.12 ± 0.03 versus 0.04 μmol/mmol creatinine in one subject). TOL-A was strongly correlated with exposure concentrations of TOL when measured at the end (r = 0.99), or even 30 minutes after cessation of exposure (r = 0.97). Results of the present study confirm that HA cannot be used to monitor low exposure to TOL and suggest that o-CR and TOL-A are sensitive enough to be used for that purpose. Among three indicators of exposure, only o-CR was significantly affected (reduction of ∼20 to 30% in amount excreted) by simultaneaous exposure to XYL at a total mixture concentration not exceeding approximately 100 ppm, whereas HA and TOL-A remained unaltered. In conclusion, this study shows that TOL-A and o-CR can be used to monitor exposure to low levels of TOL. It also shows that, between these two indicators, o-CR may be especially sensitive to metabolic interferences resulting from coexposure to other solvents sharing similar metabolic pathways, even at exposure levels below exposure limits for mixtures of solvents.
Article
The inhibitory and lethal effects of synthetic versions of compounds found in common herbs and spices were compared on a food spoilage yeast Debaromyces hansenii. Separate treatments of trans‐anethole, carvacrol, eugenol, and thymol were investigated in potato dextrose broth (PDB) suspension cultures. Inhibitory activity was studied for all compounds at concentrations of 25, 50, 75, and 100 ppm over a 55 h incubation while lethality was investigated for trans‐anethole, carvacrol, and thymol at 100 and 125 ppm over a four day incubation. All compounds exhibited at least minor inhibitory activity at a concentration of 25 ppm. During the 55 h incubation period, the minimum concentration for total inhibition by trans‐anethole was 75 ppm, while that for carvacrol and thymol was 100 ppm. The maximum level of eugenol examined, 100 ppm, did not completely inhibit outgrowth. Growth curve data were described by the logistic equation which provided for quantitative comparison of inhibition. Lethality was achieved with trans‐anethole, carvacrol, and thymol at 100 and 125 ppm as determined by colony forming units (CFU) on potato dextrose agar (PDA) over four days incubation. These findings demonstrate an approach for quantitatively describing inhibition and evaluating the lethal effects of synthetic versions of plant metabolites on D. hansenii. This research may prove useful in future studies identifying active compounds, determining their effective concentrations, and providing strategies for the development of food applications.
Article
Absorption cross sections of 24 volatile and non-volatile derivatives of benzene in the ultraviolet (UV) and the infrared (IR) regions of the electromagnetic spectrum have been determined using a 1080l quartz cell. For the UV a 0.5m Czerny-Turner spectrometer coupled with a photodiode array detector (spectral resolution 0.15nm) was used. IR spectra were recorded with an FT-IR spectrometer (Bruker IFS-88, spectral resolution 1cm-1). Absolute absorption cross sections and the instrument function are given for the UV, while for the IR, absorption cross sections and integrated band intensities are reported.The study focused primarily on the atmospherically relevant methylated benzenes (benzene, toluene, o-xylene, m-xylene, p-xylene, 1,2,4-trimethylbenzene, 1,3,5-trimethylbenzene, ethylbenzene, styrene) and their ring retaining oxidation products (benzaldehyde, o-tolualdehyde, m-tolualdehyde, p-tolualdehyde, phenol, o-cresol, m-cresol, p-cresol, 2,3-dimethylphenol, 2,4-dimethylphenol, 2,5-dimethylphenol, 2,6-dimethylphenol, 3,4-dimethylphenol, 3,5-dimethylphenol, 2,4,6-trimethylphenol and (E,Z)- and (E,E)-2,4-hexadienedial).The UV absorption cross sections reported here can be used for the evaluation of DOAS spectra (Differential Optical Absorption Spectroscopy) for measurements of the above compounds in the atmosphere and in reaction chambers, while the IR absorption cross sections will primarily be useful in laboratory studies on atmospheric chemistry, where FT-IR spectrometry is an important tool.
Article
Summary Sulfate-reducing bacterial enrichments were obtained from a shallow anoxic aquifer for their ability to metabolize eithero-, m-, orp-cresol. GC/MS and simultaneous adaptation experiments suggested that the anaerobic decomposition ofp-cresol proceeds by the initial oxidation of the aryl methyl group to formp-hydroxybenzoic acid. This intermediate was then converted to benzoic acid. Benzoic acid and a hydroxybenzaldehyde were also found in spent culture fluids from ano-cresol-degrading enrichment culture. This result, in addition to others, suggested thato-cresol may also be anaerobically degraded by the oxidation of the methyl substituent. An alternate pathway for anaerobicm-cresol decomposition might exist. Enrichment cultures obtained with eitherp- oro-cresol degraded both of these substrates but notm-cresol. In contrast, am-cresol enrichment culture did not metabolize theortho orpara isomers. Anaerobic biodegradation in all enrichment cultures was inhibited by molybdate and oxygen, and was dependent on the presence of sulfate as a terminal electron acceptor. The stoichiometry of sulfate-reduction and substrate depletion by the various enrichment cultures indicated that the parent cresol isomers were completely mineralized. This result was confirmed by the conversion of14C-labeledp-cresol to14CO2. These results help clarify the fate of alkylated aromatic chemicals in anoxic aquifers.
Article
SUMMARYp-Cresol has been identified as the active chemical in a laundry-ink responsible for the previously reported contact depigmentation of hair in agouti CBA/J mice. p-Cresol has been shown to induce depigmentation of both skin and hair in agouti as well as black mice. In the agouti mice there were bands and whorls, as well as plaques of white hair. However, the most striking finding was an occult hair depigmentation wherein the new hair shafts were white except for the tips. Such pigment-loss was not apparent on surface examination of the fur, becoming evident only on parting the hairs. All of these patterned hair pigment losses have been related to a unique sensitivity of the follicular melanocytes to the toxic effect of p-cresol during the earliest days of new hair formation, that is, during the initial anagen phase.
Article
The toluene metabolite p-cresol was rapidly detected and determined using a silicone membrane source adapted for a VG ZAB-2F mass spectrometer. This compound came from hydrolysed urine, extracted with an organic solvent and dissolved in 1-propanol, giving an average value of 11 ± 1 μg ml−1 for unexposed workers.
Article
A simple TLC separation and semi-quantitative visual determination method was used to analyse the volatile phenols in the waste water of the petroleum industry and the grain irrigated by the waste water. The phenol in the rice irrigated by the water that contained phenol for artificial preparation was also studied. A preliminary conclusion was obtained, that the grain could absorb volatile phenols from irrigation water.