Bibliography Tag: organophosphates

Schütze et al. 2021

Andre Schütze, Pilar Morales-Agudelo, Meghan Vidal, Antonia M. Calafat, Maria Ospina.; “Quantification of glyphosate and other organophosphorus compounds in human urine via ion chromatography isotope dilution tandem mass spectrometry;” Chemosphere, 2021, 274; DOI: 10.1016/j.chemosphere.2020.129427.


Organophosphorus pesticides are the most used pesticides in the United States. Most organophosphorus pesticides are composed of a phosphate (or phosphorothioate or phosphorodithioate) moiety and a variable organic group. Organophosphorus pesticides are scrutinized by regulatory bodies and agencies because of their toxicity or suspected carcinogenicity. Upon exposure, organophosphorus pesticides and their metabolites eliminate in urine; these urinary biomarkers are useful to evaluate human exposure. We developed a method using stable isotope dilution, ion chromatography tandem mass spectrometry for quantification in urine of 6 O,O-dialkylphosphates, metabolites of organophosphorus insecticides, and glyphosate, the most used herbicide in the United States. With simple and minimal sample preparation, the analytical method is selective and sensitive (limits of detection are 0.2-0.8 μg/L), accurate (>85%) and precise (relative standard deviation <20%), depending on the analyte. To assess the suitability of the method in real exposure scenarios, we analyzed samples collected anonymously from subjects with suspected exposure to pesticides (n = 40) or who had been on an organic diet (n = 50). We detected glyphosate in 80% of subjects reporting an organic diet and in 78% of those with suspected glyphosate exposure; concentrations ranged from <0.2 to 28.6 μg/L. Median concentrations were 0.39 μg/L for the organic diet group and 0.40 μg/L for individuals with suspected exposure. Interestingly, interquartile ranges were considerably higher among those reporting pesticide exposure (0.63 μg/L) than those consuming organic diets (0.42 μg/L). These data suggest that the method meets typical validation benchmark values and is sensitive to investigate background exposures in the general population. FULL TEXT

Rauh et al., 2012

Rauh, V. A., Perera, F. P., Horton, M. K., Whyatt, R. M., Bansal, R., Hao, X., Liu, J., Barr, D. B., Slotkin, T. A., & Peterson, B. S.; “Brain anomalies in children exposed prenatally to a common organophosphate pesticide;” Proceedings of the National Academy of Sciences, 2012, 109(20), 7871-7876; DOI: 10.1073/pnas.1203396109.


Prenatal exposure to chlorpyrifos (CPF), an organophosphate insecticide, is associated with neurobehavioral deficits in humans and animal models. We investigated associations between CPF exposure and brain morphology using magnetic resonance imaging in 40 children, 5.9-11.2 y, selected from a nonclinical, representative community-based cohort. Twenty high-exposure children (upper tertile of CPF concentrations in umbilical cord blood) were compared with 20 low-exposure children on cortical surface features; all participants had minimal prenatal exposure to environmental tobacco smoke and polycyclic aromatic hydrocarbons. High CPF exposure was associated with enlargement of superior temporal, posterior middle temporal, and inferior postcentral gyri bilaterally, and enlarged superior frontal gyrus, gyrus rectus, cuneus, and precuneus along the mesial wall of the right hemisphere. Group differences were derived from exposure effects on underlying white matter. A significant exposure x IQ interaction was derived from CPF disruption of normal IQ associations with surface measures in low-exposure children. In preliminary analyses, high-exposure children did not show expected sex differences in the right inferior parietal lobule and superior marginal gyrus, and displayed reversal of sex differences in the right mesial superior frontal gyrus, consistent with disruption by CPF of normal behavioral sexual dimorphisms reported in animal models. High-exposure children also showed frontal and parietal cortical thinning, and an inverse dose-response relationship between CPF and cortical thickness. This study reports significant associations of prenatal exposure to a widely used environmental neurotoxicant, at standard use levels, with structural changes in the developing human brain.  FULL TEXT

Potera, 2015

Potera, C.; “Tracking organophosphates: new method for assessing long-term dietary exposures;” Environmental Health Perspectives, 2015, 123(5), A135; DOI: 10.1289/ehp.123-A135.


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Tang et al., 2021

Tang, J., Wang, W., Jiang, Y., & Chu, W.; “Diazinon exposure produces histological damage, oxidative stress, immune disorders and gut microbiota dysbiosis in crucian carp (Carassius auratus gibelio);” Environmental Pollution, 2021, 269, 116129; DOI: 10.1016/j.envpol.2020.116129.


Diazinon is a common organophosphate pesticide widely used to control parasitic infections in agriculture. Excessive use of diazinon can have adverse effects on the environment and aquatic animal health. In the present study, the toxic effects of diazinon on the histology, antioxidant, innate immune and intestinal microbiota community composition of crucian carp (Carassius auratus gibelio) were investigated. The results showed that diazinon at the tested concentration (300 mug/L) induced gill and liver histopathological damages. Hepatic total superoxide dismutase (T-SOD), catalase (CAT), and glutathione S-transferase (GST) activities significantly decreased (P < 0.05) by 32.47%, 65.33% and 37.34%, respectively. However, the liver tissue malondialdehyde (MDA) content significantly (P < 0.05) increased by 138.83%. The 300 mug/L diazinon significantly (P < 0.05) downregulated the gene expression of TLR4, MyD88, NF-kB p100 and IL-8 but had no significant effect TNF-alpha (P = 0.8239). In addition, the results demonstrated that diazinon exposure could affect the intestinal microbiota composition and diversity. Taken together, the results of this study indicated that diazinon exposure can cause damage to crucian carp, induce histopathological damage in gill and liver tissues, oxidative stress in the liver, and innate immune disorders and alter intestinal microbiota composition and diversity.

Sheppard et al., 2020

Sheppard, L., McGrew, S., & Fenske, R. A.; “Flawed analysis of an intentional human dosing study and its impact on chlorpyrifos risk assessments;” Environment International, 2020, 143, 105905; DOI: 10.1016/j.envint.2020.105905.


In March 1972, Frederick Coulston and colleagues at the Albany Medical College reported results of an intentional chlorpyrifos dosing study to the study’s sponsor, Dow Chemical Company. Their report concluded that 0.03 mg/kg-day was the chronic no-observed-adverse-effect-level (NOAEL) for chlorpyrifos in humans. We demonstrate here that a proper analysis by the original statistical method should have found a lower NOAEL (0.014 mg/kg-day), and that use of statistical methods first available in 1982 would have shown that even the lowest dose in the study had a significant treatment effect. The original analysis, conducted by Dow-employed statisticians, did not undergo formal peer review; nevertheless, EPA cited the Coulston study as credible research and kept its reported NOAEL as a point of departure for risk assessments throughout much of the 1980’s and 1990’s. During that period, EPA allowed chlorpyrifos to be registered for multiple residential uses that were later cancelled to reduce potential health impacts to children and infants. Had appropriate analyses been employed in the evaluation of this study, it is likely that many of those registered uses of chlorpyrifos would not have been authorized by EPA. This work demonstrates that reliance by pesticide regulators on research results that have not been properly peer-reviewed may needlessly endanger the public. FULL TEXT

Christensen et al., 2016

Christensen, C. H., Barry, K. H., Andreotti, G., Alavanja, M. C., Cook, M. B., Kelly, S. P., Burdett, L. A., Yeager, M., Beane Freeman, L. E., Berndt, S. I., & Koutros, S.; “Sex Steroid Hormone Single-Nucleotide Polymorphisms, Pesticide Use, and the Risk of Prostate Cancer: A Nested Case-Control Study within the Agricultural Health Study;” Frontiers in Oncology, 2016, 6, 237; DOI: 10.3389/fonc.2016.00237.


Experimental and epidemiologic investigations suggest that certain pesticides may alter sex steroid hormone synthesis, metabolism or regulation, and the risk of hormone-related cancers. Here, we evaluated whether single-nucleotide polymorphisms (SNPs) involved in hormone homeostasis alter the effect of pesticide exposure on prostate cancer risk. We evaluated pesticide-SNP interactions between 39 pesticides and SNPs with respect to prostate cancer among 776 cases and 1,444 controls nested in the Agricultural Health Study cohort. In these interactions, we included candidate SNPs involved in hormone synthesis, metabolism or regulation (N = 1,100), as well as SNPs associated with circulating sex steroid concentrations, as identified by genome-wide association studies (N = 17). Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. We translated p-values for interaction into q-values, which reflected the false discovery rate, to account for multiple comparisons. We observed a significant interaction, which was robust to multiple comparison testing, between the herbicide dicamba and rs8192166 in the testosterone metabolizing gene SRD5A1 (p-interaction = 4.0 x 10(-5); q-value = 0.03), such that men with two copies of the wild-type genotype CC had a reduced risk of prostate cancer associated with low use of dicamba (OR = 0.62 95% CI: 0.41, 0.93) and high use of dicamba (OR = 0.44, 95% CI: 0.29, 0.68), compared to those who reported no use of dicamba; in contrast, there was no significant association between dicamba and prostate cancer among those carrying one or two copies of the variant T allele at rs8192166. In addition, interactions between two organophosphate insecticides and SNPs related to estradiol metabolism were observed to result in an increased risk of prostate cancer. While replication is needed, these data suggest both agonistic and antagonistic effects on circulating hormones, due to the combination of exposure to pesticides and genetic susceptibility, may impact prostate cancer risk. FULL TEXT

Hoppin et al., 2002

Hoppin, Jane A., Umbach, David M, London, Stephanie J., Alavanja, Michael, & Sandler, Dale P.; “Chemical Predictors of Wheeze among Farmer Pesticide Applicators in the Agricultural Health Study;” American Journal of Respiratory and Critical Care Medicine, 2002, 165, 683-689; DOI: 10.1164/rccm.2106074.


Pesticides may contribute to respiratory symptoms among farmers. Using the Agricultural Health Study, a large cohort of certified pesticide applicators in Iowa and North Carolina, we explored the association between wheeze and pesticide use in the past year. Self-administered questionnaires contained items on 40 currently used pesticides and pesticide application practices. A total of 20,468 applicators, ranging in age from 16 to 88 years, provided complete information; 19% reported wheezing in the past year. Logistic regression models controlling for age, state, smoking, and history of asthma or atopy were used to evaluate associations between individual pesticides and wheeze. Among pesticides suspected to contribute to wheeze, paraquat, three organophosphates (parathion, malathion, and chlorpyrifos), and one thiocarbamate (S-ethyl-dipropylthiocarbamate [EPTC]) had elevated odds ratios (OR). Parathion had the highest OR (1.5, 95% confidence interval [CI] 1.0, 2.2).

Chlorpyrifos, EPTC, paraquat, and parathion demonstrated significant dose–response trends. The herbicides, atrazine and alachlor, but not 2,4-D, were associated with wheeze. Atrazine had a significant dose–response trend with participants applying atrazine more than 20 days/year having an OR of 1.5 (95% CI 1.2,1.9). Inclusion of crops and animals into these models did not significantly alter the observed OR. These associations, though small, suggest an independent role for specific pesticides in respiratory symptoms of farmers. FULL TEXT

Pardo et al., 2020

Pardo, L. A., Beane Freeman, L. E., Lerro, C. C., Andreotti, G., Hofmann, J. N., Parks, C. G., Sandler, D. P., Lubin, J. H., Blair, A., & Koutros, S.; “Pesticide exposure and risk of aggressive prostate cancer among private pesticide applicators;” Environmental Health, 2020, 19(1), 30; DOI: 10.1186/s12940-020-00583-0.


BACKGROUND: Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men in developed countries; however, little is known about modifiable risk factors. Some studies have implicated organochlorine and organophosphate insecticides as risk factors (particularly the organodithioate class) and risk of clinically significant PCa subtypes. However, few studies have evaluated other pesticides. We used data from the Agricultural Health Study, a large prospective cohort of pesticide applicators in North Carolina and Iowa, to extend our previous work and evaluate 39 additional pesticides and aggressive PCa.

METHODS: We used Cox proportional hazards models, with age as the time scale, to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between ever use of individual pesticides and 883 cases of aggressive PCa (distant stage, poorly differentiated grade, Gleason score >/= 7, or fatal prostate cancer) diagnosed between 1993 and 2015. All models adjusted for birth year, state, family history of PCa, race, and smoking status. We conducted exposure-response analyses for pesticides with reported lifetime years of use.

RESULTS: There was an increased aggressive PCa risk among ever users of the organodithioate insecticide dimethoate (n = 54 exposed cases, HR = 1.37, 95% CI = 1.04, 1.80) compared to never users. We observed an inverse association between aggressive PCa and the herbicide triclopyr (n = 35 exposed cases, HR = 0.68, 95% CI = 0.48, 0.95), with the strongest inverse association for those reporting durations of use above the median (>/= 4 years; n = 13 exposed cases, HR=0.44, 95% CI=0.26, 0.77).

CONCLUSION: Few additional pesticides were associated with prostate cancer risk after evaluation of extended data from this large cohort of private pesticide applicators.


Curl et al., 2015

Curl, C. L., Beresford, S. A., Fenske, R. A., Fitzpatrick, A. L., Lu, C., Nettleton, J. A., & Kaufman, J. D.; “Estimating pesticide exposure from dietary intake and organic food choices: the Multi-Ethnic Study of Atherosclerosis (MESA);” Environmental Health Perspectives, 2015, 123(5), 475-483; DOI: 10.1289/ehp.1408197.


BACKGROUND: Organophosphate pesticide (OP) exposure to the U.S. population is dominated by dietary intake. The magnitude of exposure from diet depends partly on personal decisions such as which foods to eat and whether to choose organic food. Most studies of OP exposure rely on urinary biomarkers, which are limited by short half-lives and often lack specificity to parent compounds. A reliable means of estimating long-term dietary exposure to individual OPs is needed to assess the potential relationship with adverse health effects.

OBJECTIVES: We assessed long-term dietary exposure to 14 OPs among 4,466 participants in the Multi-Ethnic Study of Atherosclerosis, and examined the influence of organic produce consumption on this exposure.

METHODS: Individual-level exposure was estimated by combining information on typical intake of specific food items with average OP residue levels on those items. In an analysis restricted to a subset of participants who reported rarely or never eating organic produce (“conventional consumers”), we assessed urinary dialkylphosphate (DAP) levels across tertiles of estimated exposure (n = 480). In a second analysis, we compared DAP levels across subgroups with differing self-reported organic produce consumption habits (n = 240).

RESULTS: Among conventional consumers, increasing tertile of estimated dietary OP exposure was associated with higher DAP concentrations (p < 0.05). DAP concentrations were also significantly lower in groups reporting more frequent consumption of organic produce (p < 0.02).

CONCLUSIONS: Long-term dietary exposure to OPs was estimated from dietary intake data, and estimates were consistent with DAP measurements. More frequent consumption of organic produce was associated with lower DAPs.


Hernandez et al, 2013

Hernandez, A. F., Parron, T., Tsatsakis, A. M., Requena, M., Alarcon, R., & Lopez-Guarnido, O.; “Toxic effects of pesticide mixtures at a molecular level: their relevance to human health;” Toxicology, 2013, 307, 136-145; DOI: 10.1016/j.tox.2012.06.009.


Pesticides almost always occur in mixtures with other ones. The toxicological effects of low-dose pesticide mixtures on the human health are largely unknown, although there are growing concerns about their safety. The combined toxicological effects of two or more components of a pesticide mixture can take one of three forms: independent, dose addition or interaction. Not all mixtures of pesticides with similar chemical structures produce additive effects; thus, if they act on multiple sites their mixtures may produce different toxic effects. The additive approach also fails when evaluating mixtures that involve a secondary chemical that changes the toxicokinetics of the pesticide as a result of its increased activation or decreased detoxification, which is followed by an enhanced or reduced toxicity, respectively. This review addresses a number of toxicological interactions of pesticide mixtures at a molecular level. Examples of such interactions include the postulated mechanisms for the potentiation of pyrethroid, carbaryl and triazine herbicides toxicity by organophosphates; how the toxicity of some organophosphates can be potentiated by other organophosphates or by previous exposure to organochlorines; the synergism between pyrethroid and carbamate compounds and the antagonism between triazine herbicides and prochloraz. Particular interactions are also addressed, such as those of pesticides acting as endocrine disruptors, the cumulative toxicity of organophosphates and organochlorines resulting in estrogenic effects and the promotion of organophosphate-induced delayed polyneuropathy. FULL TEXT