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6 Tumor Incidence Data Used in Recalculations of Carcinogenic Potency for 19 Chemicals in the NRC Report

6 Tumor Incidence Data Used in Recalculations of Carcinogenic Potency for 19 Chemicals in the NRC Report

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Public policy with respect to pesticides has relied on the results of high-dose, rodent cancer tests as the major source of information for assessing potential cancer risks to humans. This chapter critically examines the assumptions, methodology, results, and implications of cancer risk assessments of pesticide residues in the diet. The analyses pr...

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... Some chronic diseases are due to the effects of pesticides (Tago et al., 2014), as a result of: (i) direct exposure to farmers, (ii) indirect exposure to members of a farming community, and (iii) consumption of pesticide residues in food, water, fish, and herbal preparations (Gold et al., 2001;W. J. Ntow et al., 2008b;. ...
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The high patronage of herbal medicinal products in Ghana for the treatment of diverse disease conditions raises concerns about patient safety, given that much of the raw materials for production are obtained from the wild or farmlands potentially exposed to varied agrochemical residues. Therefore, the work sought to investigate the contamination of herbal medicinal products with pesticide residues and assess the potential risk posed to patients. As a result, validated gas chromatography with mass spectrometry as a detector was used to determine forty-two pesticides in thirty herbal medicinal products. The performance parameters of the method such as linearity, accuracy, and precision were found as acceptable. Pesticide residues such as chlorpyrifos and/or bifenthrin were found in 4/30 herbal medicinal products. Specifically, 3/30 herbal medicinal products contained only one pesticide, while 1/30 was contaminated with both pesticide residues. The levels of pesticide residue contamination ranged between 2.5 and 5.0 µg/kg. The acute hazard quotient and chronic hazard quotient for the two pesticide residues were evaluated and ranged between 0.21 and 0.92% and between 8.21 × 10⁻⁴ and 5.88 × 10⁻³%. The detected pesticide residue levels are below the maximum residue limit values, which may not cause acute and chronic health risks due to intake of the selected herbal medicinal product. Nevertheless, patient safety and potential public health risk can be reduced by regular monitoring, and regulation of pesticide residue levels in herbal medicinal products.
... 13 Herein we collected a database of pesticides annotated with multiple toxicological endpoints, named PESTIMEP (PESTicide Multiple EndPoint), and explored the relations of experimental toxicity values measured at different species and at different routes of administration. 2,14 In addition, we analyzed the pesticide profile by MOA of the PPDB database. Further information of PESTIMEP and PPDB databases is provided in the Materials and methods section of this work. ...
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The continuous use of compounds contained in commodities such as processed food, medicines, and pesticides, demands safety measures, in particular, those in direct contact with humans and the environment. Safety measures have evolved and regulations are now in place around the globe. In the case of pesticides, attempts have been made to use toxicological information to inform of potentially harmful compounds either across species, on different routes of exposure, or entirely new chemicals. The generation of models, based on statistical and molecular modeling studies, allow for such predictions. However, the use of these models is framed by the available data, the experimental errors, the complexity of the measurement, and available computational algorithms, among other factors. In this work, we present the methodologies used for extrapolation across different species and routes of administration and show the appropriateness of developing of predictive models of pesticides based on its type and mode of action. The analyses include comparisons based on structural characteristics and physicochemical properties. Whenever possible, the scope and limitations of the methodologies are discussed. We expect that this work will serve as a useful introductory guide of the tools employed in the toxicity assessment of agrochemical compounds.
... Pese a la importancia de los plaguicidas en los cultivos, su uso y manejo inadecuado representa riesgos para la salud humana y la contaminación ambiental. Asociado con la exposición a plaguicidas en el ser humano se han reportado síntomas como dolores de cabeza, náuseas, mareos o pérdida del conocimiento (Abhilash & Singh, 2009;McCauley et al., 2006;Ngowi, Mibise, Ijani, London & Ajayi, 2007), carcinogénesis (Abhilash & Singh, 2009;Andreotti et al., 2009;Bassil et al., 2007;Cockburn et al., 2011;Gold, Slone, Ames & Manley, 2001), disrupción endócrina (Bretveld, Thomas, Scheepers, Zielhuis & Roeleveld, 2006;Colborn & Carroll, 2007), asma y diversos síntomas respiratorios (Faria, Facchini, Gastal & Tomasi, 2005), entre otros efectos a corto, mediano y largo plazo (Alavanja, Hoppin & Kamel, 2004;Araújo, Nogueira & Augusto, 2000;Damalas & Eleftherohorinos, 2011;Durkin, 2010;Ritter, Goushleff, Arbuckle, Cole & Raizenne, 2006;Weiss, Amler & Amler, 2004;Zhao et al., 2008). ...
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Sugarcane crop involves a wide variety of pesticides. Therefore, there is a need to know their status of use and to identify their health risk on the occupationally exposed population. The aim was to identify pesticides used during the last 30 years on this agroecosystem, in the Irrigation District 035 “La Antigua”, Veracruz, Mexico, and its potential effects on human health. A search of historical data along with a sur- vey among farmers in the Modelo and Gloria mills were carried out in 2011. Twenty-eight different active ingredients have been applied from 1980 to 2012. Carbofuran and monocrotophos as well as herbicides, such as triazine, 2, 4-D and monosodium methyl arsenate, had been the most common used insecticides. Pesticides used are closely related to induce immune and endocrine disruption, damage to the peripheral and central nervous systems, and carcinogenesis in humans.
... [3][4][5] Organophosphate pesticides are the major class of agricultural chemicals commonly used in controlling a wide range of pests in field crops, fruits, and vegetables. 6 Chlorpyrifos (CPF; O,O-diethyl O-3,5,6-trichloropyridin-2-yl phosphorothioate) is a colorless to white crystalline solid organophosphate insecticide. Due to the risks posed by CPF to human health, the US Environmental Protection Agency in the year 2000 placed restriction to its domestic applications. ...
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Exposure to pesticide chlorpyrifos (CPF) has been implicated in reproductive deficits in both humans and animals. Diphenyl diselenide (DPDS) is an organoselenium compound widely reported to elicit potent pharmacological activities in several chemically-induced toxicity and disease models. However, there is paucity of scientific information on the influence of DPDS on CPF-induced reproductive dysfunction. The present study investigated the influence of DPDS on CPF-induced functional changes along the hypothalamic-pituitary- testicular axis in rats. CPF was administered alone at 5 mg/kg body weight or orally co-treated with DPDS at 2.5 and 5 mg/kg body weight for 35 consecutive days. Results showed that DPDS co-treatment significantly (p < 0.05) abrogated CPF-induced oxidative stress by increasing the antioxidant enzymes activities and glutathione content, decreasing the hydrogen peroxide and lipid peroxidation levels in the hypothalamus, testes and epididymis of the treated rats. Moreover, DPDS co-treatment significantly ameliorated CPF-induced histological alterations in the hypothalamus, testes and epididymis of the treated rats. Besides, the significant augmentation of luteinizing hormone, follicle-stimulating hormone and testosterone levels as well as the testicular activities of acid phosphatase, alkaline phosphatase and lactate dehydrogenase by DPDS was accompanied by an increase in sperm quality and quantity in the treated rats. Taken together, DPDS abrogates CPF mediated toxicity along the hypothalamic-pituitary-testicular axis in rats via inhibition of lipid peroxidation, enhancement of antioxidant enzymes activities and testicular function. Thus, DPDS may be a possible chemoprotective drug candidate against CPF-induced male reproductive deficits in humans.
... pesticides should be given proper instruction on the use of protective clothing and have facilities to wash their hands after touching containers. The premises where pesticides are stored and sold must have good ventilation to prevent any build up of pesticide vapor in the air (Gold et al. 2001). ...
... Many employers were trained but were not permanently working in the shop while permanent workers (sellers) were untrained and improperly dressed. Very few of them were wearing any adequate personal protective clothing during clean up, reconditioning or packaging, or when entering the store as recommended (Gold et al. 2001;Workcover 2006). It is important to note that some women sell pesticides during pregnancy or with children crawling around. ...
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In Bamenda and peripheral zones, studies have been focused on the effects of pesticides on farmers (pesticide users) while nothing has been done to assess the exposure of sellers to pesticides. This study aimed at evaluating the exposure of pesticide sellers in the same area. Thirty-two questionnaires were administered to 32 pesticide sellers systematically selected, and chi-square was used for statistical analysis. From each shop, a respondent was chosen among the workers according to its daily time spent in the workplace. The results showed that there is similarity between sellers in Bamenda and peripheral area; one active ingredient (metalaxyl) and one formulation (beauchamp) sold are not registered; throat irritation, headaches, fatigue, skin irritation, eye irritation, and difficulty in breathing with more cases of nose irritation were symptoms observed; pesticides are stored either in the shops or in warehouses; safety measures generally applied are sitting outside the shop, taking medicated charcoal and the use of protective clothing; 56% have less than 5 years experience. Permanent pesticide sellers are then exposed to chronic intoxication in Bamenda and neighboring zones. Employers should make use of protective clothing in their shops when manipulating pesticides in the application of safety measures.
... However, indiscriminate use of pesticides has led to varying degree of deleterious effects in non-target organisms such as fishes, birds and mammals, especially humans (Ecobichon 1996). Blood disorders, brain and nerve damage, paralysis, emphysema, asthma, cancer, birth defects and infertility have reportedly been linked to low residual amount of pesticides (Gold et al. 2001). Being a reactive compound, pesticide tends to form covalent bonds with various nucleophilic centres of cellular biomolecules such as DNA (Poletta et al. 2009), resulting in cancer and other chronic diseases (Meinert et al. 2000). ...
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Background: Cypermethrin (Cyp), a synthetic pyrethroid developed for agricultural and public health applications, has become harmful to the environment and mammalian life owing to indiscriminate use. Aim: This study aimed to investigate the protective effect of the methanolic extract of Jatropha gossypifolia leaves against Cyp-induced genotoxicity in rats using alpha-lipoic acid (α-LA) as standard drug. Method: Fifty-six male Wistar rats, assigned to eight groups of seven animals each, were treated orally for 28 days as follows - Group 1: only corn oil (Control); Group 2: 20 mg/kg body weight (b.wt) of Cyp; Groups 3, 4 and 5: Cyp + 50 mg/kg b.wt of J. gossypifolia, Cyp + 100 mg/kg b.wt of J. gossypifolia and Cyp + 50 mg/kg b.wt of α-LA, respectively; Groups 6, 7 and 8: J. gossypifolia (50 mg/kg b.wt), J. gossypifolia (100 mg/kg b.wt) and α-LA (50 mg/kg b.wt), respectively. The P53 was assayed for using the plasma, while the micronucleus assay was carried out on the bone marrow. Results: Results showed that exposure to Cyp significantly increased the number of micronucleated polychromatic erythrocytes (86.70%) as well as p53 concentration in both the liver and plasma (200.00% and 125.53%) compared to the control. Co-administration with methanolic extract of J. gossypifolia leaves significantly reversed these alterations in a dose-dependent manner. Conclusion: The methanolic extract of J. gossypifolia leaves has the potential to ameliorate Cyp-induced genotoxicity in rats, and also, the toxicological evaluations of the plant extract and α-LA showed that it is relatively safe for use at the doses investigated.
... This is similar to cases reported by Sonchieu [16] [33] can be applied to limit contamination of food. This ignorance will surely lead to developing non-communicable diseases such as cancer as described by Gold et al. [34] and Margaret et al. [35] as a result of non-respect of spraying parameters such as doses, date before harvesting, among others [4, 36,37]. Contamination of these foods can also be attributed to microorganisms whose development is facilitated because of high water content increasing their perishability [26]. ...
... Despite the questions that have been raised about their relevance to pesticide registration, 11,12 Ames mutagenicity tests 13 remain a major regulatory hurdle that must be passed early in agrochemical pesticide development. Though hundreds of thousands of these assays have been done, the majority of the results obtained are not publicly available. ...
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Pesticides must be effective to be commercially viable but they must also be reasonably safe for those who manufacture them, apply them, or consume the food they are used to produce. Animal testing is key to ensuring safety, but it comes late in the agrochemical development process, is expensive, and requires relatively large amounts of material. Surrogate assays used as in vitro models require less material and shift identification of potential mammalian toxicity back to earlier stages in development. Modern in silico methods are cost‐effective complements to such in vitro models that make it possible to predict mammalian metabolism, toxicity and exposure for a pesticide, crop residue or other metabolite before it has been synthesized. Their broader use could substantially reduce the amount of time and effort wasted in pesticide development. This contribution reviews the kind of in silico models that are currently available for vetting ideas about what to synthesize and how to focus development efforts; the limitations of those models; and the practical considerations that have slowed development in the area. Detailed discussions are provided of how bacterial mutagenicity, human CYP (cytochrome P450) metabolism, and bioavailability in humans and rats can be predicted.
... High levels of residual pesticides in food may result in adverse effects on human health. Several pathologies such as cancers, neurodegenerative diseases, or reproductive disorders are suspected of being connected to exposure to pesticides (Gold et al. 2001;Yarita et al. 2014;Nougadère et al. 2014). ...
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Soybean production is responsible for a great amount of pesticides applied in Brazil. In the last years, an increase of soy-based beverage consumption and a higher concern about pesticide residues in food occurred. A simple, fast, and efficient multiresidue method based on the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method was developed for simultaneous determination of 39 pesticides and two plant growth regulators in soy-based beverages by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The clean-up procedure was established based on central composite design (CCD), using response surface methodology (RSM). For the optimization of the clean-up step, different amounts of sorbents in dispersive solid phase extraction (d-SPE) were evaluated. Validation results were satisfactory, considering that the optimized method presented recoveries between 70 and 112 %, with RSD lower than 19 % for spike levels between 10 and 50 μg L−1. The method limit of detection (LOD) and quantification (LOQ) ranged from 3 to 8 and 10 to 25 μg L−1, respectively. The proposed method combines the advantages of QuEChERS and UHPLC-MS/MS and proved to be suitable for the pesticide multiresidue determination in soy-based beverages in routine laboratory analyses.
... However, the abuse of these substances resulted in pollution and ecosystems imbalance. Several studies reported a causal relationship between their use and the increase of cancers and congenital disorders in humans (Gold et al., 2001;Sanborn et al., 2007). In concentrations of organic tomatoes had higher vitamin C, carotenoids and polyphenol contents (except for chlorogenic acid) than conventional tomatoes. ...
Chapter
Carotenoids are a diverse group of colored pigments, tetraterpenes, or have in its structure 40 carbon atoms, are found naturally in plants, algae, fungi and bacteria. Lycopene is the predominant carotenoid in tomatoes, giving colors ranging from yellow to red and has no provitamin A activity. However, it is a very powerful antioxidant and its intake in the human diet is associated with the prevention of various diseases. Biosynthesis of lycopene in plants is discussed in this chapter. Since the common base of the synthesis of all carotenoids with isopentenyl diphosphate units and isomer thereof (dimetilanil diphosphate), to the dehydrogenation of phytoene, from which the lycopene is produced. Moreover, various genera of yeast also have the ability to produce carotenoids. In the case of conventional yeast Saccharomyces cerevisiae, that can accumulate in their cells lots of lycopene, due to the carbon flow to the ergosterol biosynthetic pathway to be partially directed to the production of carotenoid.