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Bibliography Tag: organophosphates

Pahwa et al., 2012

Pahwa, M., Harris, S. A., Hohenadel, K., McLaughlin, J. R., Spinelli, J. J., Pahwa, P., Dosman, J. A., & Blair, A., “Pesticide use, immunologic conditions, and risk of non-Hodgkin lymphoma in Canadian men in six provinces,” International Journal of Cancer, 2012, 131(11), 2650-2659. DOI: 10.1002/ijc.27522.


Pesticide exposures and immune suppression have been independently associated with the risk of non-Hodgkin lymphoma (NHL), but their joint effect has not been well explored. Data from a case-control study of men from six Canadian provinces were used to evaluate the potential effect modification of asthma, allergies, or asthma and allergies and hay fever combined on NHL risk from use of: (i) any pesticide; (ii) any organochlorine insecticide; (iii) any organophosphate insecticide; (iv) any phenoxy herbicide; (v) selected individual pesticides [1,1′-(2,2,2-trichloroethylidene)bis[4-chlorobenzene]; 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (DDT), malathion, (4-chloro-2-methylphenoxy)acetic acid (MCPA), mecoprop, and (2,4-dichlorophenoxy)acetic acid (2,4-D); and (vi) from the number of potentially carcinogenic pesticides. Incident NHL cases (n = 513) diagnosed between 1991 and 1994 were recruited from provincial cancer registries and hospitalization records and compared to 1,506 controls. A stratified analysis was conducted to calculate odds ratios (ORs) adjusted for age, province, proxy respondent, and diesel oil exposure. Subjects with asthma, allergies, or hay fever had non-significantly elevated risks of NHL associated with use of MCPA (OR = 2.67, 95% confidence interval [CI]: 0.90-7.93) compared to subjects without any of these conditions (OR = 0.81, 95% CI: 0.39-1.70). Conversely, those with asthma, allergies, or hay fever who reported use of malathion had lower risks of NHL (OR = 1.25, 95% CI: 0.69-2.26) versus subjects with none of these conditions (OR = 2.44, 95% CI: 1.65-3.61). Similar effects were observed for asthma and allergies evaluated individually. Although there were some leads regarding effect modification by these immunologic conditions on the association between pesticide use and NHL, small numbers, measurement error and possible recall bias limit interpretation of these results. FULL TEXT


Hertz-Picciotto et al., 2018

Hertz-Picciotto, Irva, Sass, Jennifer B., Engel, Stephanie, Bennett, Deborah H., Bradman, Asa, Eskenazi, Brenda, Lanphear, Bruce, & Whyatt, Robin, “Organophosphate exposures during pregnancy and child neurodevelopment: Recommendations for essential policy reforms,” PLOS Medicine, 2018, 15(10). DOI: 10.1371/journal.pmed.1002671.


• Widespread use of organophosphate (OP) pesticides to control insects has resulted in ubiquitous human exposures.
• High exposures to OP pesticides are responsible for poisonings and deaths, particularly in developing countries.
• Compelling evidence indicates that prenatal exposure at low levels is putting children at risk for cognitive and behavioral deficits and for neurodevelopmental disorders.
To protect children worldwide, we recommend the following:
• Governments phase out chlorpyrifos and other OP pesticides, monitor watersheds and other sources of human exposures, promote use of integrated pest management (IPM) through incentives and training in agroecology, and implement mandatory surveillance of pesticide-related illness.
• Health professions implement curricula on the hazards from OP pesticides in nursing and medical schools and in continuing medical education courses and educate their patients and the public about these hazards.
• Agricultural entities accelerate the development of nontoxic approaches to pest control through IPM and ensure the safety of workers through training and provision of protective equipment when toxic chemicals are to be used. FULL TEXT

Ferre et al., 2018

Ferre, D. M., Quero, A. A. M., Hernandez, A. F., Hynes, V., Tornello, M. J., Luders, C., & Gorla, N. B. M., “Potential risks of dietary exposure to chlorpyrifos and cypermethrin from their use in fruit/vegetable crops and beef cattle productions,” Environmental Monitoring and Assessment, 2018, 190(5), 292. DOI 10.1007/s10661-018-6647-x.


The active ingredients (a.i.) used as pesticides vary across regions. Diet represents the main source of chronic exposure to these chemicals. The aim of this study was to look at the pesticides applied in fruit, vegetable, and beef cattle productions in Mendoza (Argentina), to identify those that were simultaneously used by the three production systems. Local individuals (n = 160), involved in these productions, were interviewed. Glyphosate was the a.i. most often used by fruit-vegetable producers, and ivermectin by beef cattle producers. Chlorpyrifos (CPF) and cypermethrin (CYP) were the only a.i. used by the three production systems. The survey revealed that CPF, CYP, alpha CYP, and CPF+CYP were used by 22, 16, 4, and 20% of the fruit and vegetable producers, respectively. Regarding beef cattle, CYP was used by 90% of producers, CYP + CPF formulation by 8%, and alpha CYP by 2%. The second approach of this study was to search the occurrence of CYP and CPF residues in food commodities analyzed under the National Plan for Residue Control (2012-2015). CYP residues found above the LOD were reported in 4.0% and CPF in 13.4% of the vegetable samples tested, as well as in 1.2 and 28.8%, respectively, of the fruit samples tested. Regarding beef cattle, CYP residues were reported in 2.3% and organophosphates (as a general pesticide class) in 13.5% of samples tested. In conclusion, consumers may be exposed simultaneously to CPF and CYP, from fruits, vegetables, and beef intake. Accordingly, the policy for pesticide residues in food and human risk assessment should account for the combined exposure to CPF and CYP. Moreover, appropriate toxicological studies of this mixture (including genotoxicity) are warranted.

Bradman et al., 2013

Bradman, Asa; Kogut, Katherine; Eisen, Ellen A; Jewell, Nicholas P; Quiros-Alcala, Lesliam; Castorina, Rosemary; Chevrier, Jonathan; Holland, Nina T;  Barr, Dana Boyd; Kavanagh-Baird, Geri; Eskenazi, Brenda, “Variability of organophosphorous pesticide metabolite levels in spot and 24-hr urine samples collected from young children during 1 week,” Environmental Health Perspectives, 2013, 121:118-124. DOI:10.1289/ehp.1104808.


BACKGROUND: Dialkyl phosphate (DAP) metabolites in spot urine samples are frequently used to characterize children’s exposures to organophosphorous (OP) pesticides. However, variable exposure and short biological half-lives of OP pesticides could result in highly variable measurements, leading to exposure misclassification.

OBJECTIVE: We examined within- and between-child variability in DAP metabolites in urine samples collected during 1 week.

METHODS: We collected spot urine samples over 7 consecutive days from 25 children (3-6 years of age). On two of the days, we collected 24-hr voids. We assessed the reproducibility of urinary DAP metabolite concentrations and evaluated the sensitivity and specificity of spot urine samples as predictors of high (top 20%) or elevated (top 40%) weekly average DAP metabolite concentrations.

RESULTS: Within-child variance exceeded between-child variance by a factor of two to eight, depending on metabolite grouping. Although total DAP concentrations in single spot urine samples were moderately to strongly associated with concentrations in same-day 24-hr samples (r approximately 0.6-0.8, p < 0.01), concentrations in spot samples collected > 1 day apart and in 24-hr samples collected 3 days apart were weakly correlated (r approximately -0.21 to 0.38). Single spot samples predicted high (top 20%) and elevated (top 40%) full-week average total DAP excretion with only moderate sensitivity ( approximately 0.52 and approximately 0.67, respectively) but relatively high specificity ( approximately 0.88 and approximately 0.78, respectively).

CONCLUSIONS: The high variability we observed in children’s DAP metabolite concentrations suggests that single-day urine samples provide only a brief snapshot of exposure. Sensitivity analyses suggest that classification of cumulative OP exposure based on spot samples is prone to type 2 classification errors.  FULL TEXT

Nowell et al., 2018

Nowell Lisa H., Moran Patrick W., Schmidt Travis S., Norman Julia E., Nakagaki Naomi, Shoda Megan E., Mahler Barbara J., Van Metre Peter C., Stone Wesley W., Sandstrom Mark W., Hladik Michelle L., “Complex mixtures of dissolved pesticides show potential aquatic toxicity in a synoptic study of Midwestern U.S. streams,” Science of the Total Environment, 613-614, 2018, DOI: 10.1016/j.scitotenv.2017.06.156


Aquatic organisms in streams are exposed to pesticide mixtures that vary in composition over time in response to changes in flow conditions, pesticide inputs to the stream, and pesticide fate and degradation within the stream. To characterize mixtures of dissolved-phase pesticides and degradates in Midwestern streams, a synoptic study was conducted at 100 streams during May–August 2013. In weekly water samples, 94 pesticides and 89 degradates were detected, with a median of 25 compounds detected per sample and 54 detected per site. In a screening-level assessment using aquatic-life benchmarks and the Pesticide Toxicity Index (PTI), potential effects on fish were unlikely in most streams. For invertebrates, potential chronic toxicity was predicted in 53% of streams, punctuated in 12% of streams by acutely toxic exposures. For aquatic plants, acute but likely reversible effects on biomass were predicted in 75% of streams, with potential longer-term effects on plant communities in 9% of streams. Relatively few pesticides in water—atrazine, acetochlor, metolachlor, imidacloprid, fipronil, organophosphate insecticides, and carbendazim—were predicted to be major contributors to potential toxicity. Agricultural streams had the highest potential for effects on plants, especially in May–June, corresponding to high spring-flush herbicide concentrations. Urban streams had higher detection frequencies and concentrations of insecticides and most fungicides than in agricultural streams, and higher potential for invertebrate toxicity, which peaked during July–August. Toxicity-screening predictions for invertebrates were supported by quantile regressions showing significant associations for the Benthic Invertebrate-PTI and imidacloprid concentrations with invertebrate community metrics for MSQA streams, and by mesocosm toxicity testing with imidacloprid showing effects on invertebrate communities at environmentally relevant concentrations. This study documents the most complex pesticide mixtures yet reported in discrete water samples in the U.S. and, using multiple lines of evidence, predicts that pesticides were potentially toxic to nontarget aquatic life in about half of the sampled streams.  FULL TEXT

McDuffie et al., 2001

Helen H. McDuffie, Punam Pahwa, John R. McLaughlin, John J. Spinelli, Shirley Fincham, James A. Dosman, Diane Robson, Leo F. Skinnider and Norman W. Choi, “Non-Hodgkin’s Lymphoma and Specific Pesticide Exposures in Men: Cross-Canada Study of Pesticides and Health,” Cancer Epidemiology, Biomarkers, & Prevention, 2001, 10.


Our objective in the study was to investigate the putative associations of specific pesticides with non-Hodgkin’s Lymphoma [NHL; International Classification of Diseases, version 9 (ICD-9) 200, 202]. We conducted a Canadian multicenter population-based incident, case (n = 517)-control (n = 1506) study among men in a diversity of occupations using an initial postal questionnaire followed by a telephone interview for those reporting pesticide exposure of 10 h/year or more, and a 15% random sample of the remainder. Adjusted odds ratios (ORs) were computed using conditional logistic regression stratified by the matching variables of age and province of residence, and subsequently adjusted for statistically significant medical variables (history of measles, mumps, cancer, allergy desensitization treatment, and a positive history of cancer in first-degree relatives). We found that among major chemical classes of herbicides, the risk of NHL was statistically significantly increased by exposure to phenoxyherbicides [OR, 1.38; 95% confidence interval (CI), 1.06–1.81] and to dicamba (OR, 1.88; 95% CI, 1.32–2.68). Exposure to carbamate (OR, 1.92; 95% CI, 1.22–3.04) and to organophosphorus insecticides (OR, 1.73; 95% CI, 1.27–2.36), amide fungicides, and the fumigant carbon tetrachloride (OR, 2.42; 95% CI, 1.19–5.14) statistically significantly increased risk. Among individual compounds, in multivariate analyses, the risk of NHL was statistically significantly increased by exposure to the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D; OR, 1.32; 95% CI, 1.01–1.73), mecoprop (OR, 2.33; 95% CI, 1.58–3.44), and dicamba (OR, 1.68; 95% CI, 1.00–2.81); to the insecticides malathion (OR, 1.83; 95% CI, 1.31–2.55), 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT), carbaryl (OR, 2.11; 95% CI, 1.21–3.69), aldrin, and lindane; and to the fungicides captan and sulfur compounds. In additional multivariate models, which included exposure to other major chemical classes or individual pesticides, personal antecedent cancer, a history of cancer among first-degree relatives, and exposure to mixtures containing dicamba (OR, 1.96; 95% CI, 1.40–2.75) or to mecoprop (OR, 2.22; 95% CI, 1.49–3.29) and to aldrin (OR, 3.42; 95% CI, 1.18–9.95) were significant independent predictors of an increased risk for NHL, whereas a personal history of measles and of allergy desensitization treatments lowered the risk. We concluded that NHL was associated with specific pesticides after adjustment for other independent predictors. FULL TEXT

Bellinger, 2012

David C. Bellinger, “A Strategy for Comparing the Contributions of Environmental Chemicals and Other Risk Factors to Neurodevelopment of Children,” Environmental Health Perspectives, 2012, 120:4, DOI: 10.1289/ehp.1104170


BACKGROUND: The impact of environmental chemicals on children’s neurodevelopment is sometimes dismissed as unimportant because the magnitude of  the impairments are considered to be clinically insignificant. Such a judgment reflects a failure to distinguish between individual and population risk. The population impact of a risk factor depends on both its effect size and its distribution (or incidence/prevalence).

OBJECTIVE:  The objective was to develop a strategy for taking into account the distribution (or incidence/prevalence) of a risk factor, as well as its effect size, in order to estimate its population impact on neurodevelopment of children.

METHODS: The total numbers of Full-Scale IQ points lost among U.S. children 0–5 years of age were estimated for chemicals (methylmercury, organophosphate pesticides, lead) and a variety of medical conditions and events (e.g., preterm birth, traumatic brain injury, brain tumors, congenital
heart disease).

DISCUSSION: Although the data required for the analysis were available for only three environmental chemicals (methylmercury, organophosphate pesticides, lead), the results suggest that their contributions to neurodevelopmental morbidity are substantial, exceeding those of many nonchemical risk factors.

CONCLUSION: A method for comparing the relative contributions of different risk factors provides a rational basis for establishing priorities for reducing neurodevelopmental morbidity in children. FULL TEXT

De Roos et al., 2003

A J De Roos, S Zahm, K Cantor, D Weisenburger, F Holmes, L Burmeister, and A Blair, “Integrative assessment of multiple pesticides as risk factors for non-Hodgkin’s lymphoma among men,” Occupational and Environmental Medicine, 2003, 60:9, DOI: 10.1136/oem.60.9.e1


METHODS: During the 1980s, the National Cancer Institute conducted three case-control studies of NHL in the midwestern United States. These pooled data were used to examine pesticide exposures in farming as risk factors for NHL in men. The large sample size (n = 3417) allowed analysis of 47 pesticides simultaneously, controlling for potential confounding by other pesticides in the model, and adjusting the estimates based on a prespecified variance to make them more stable.

RESULTS: Reported use of several individual pesticides was associated with increased NHL incidence, including organophosphate insecticides coumaphos, diazinon, and fonofos, insecticides chlordane, dieldrin, and copper acetoarsenite, and herbicides atrazine, glyphosate, and sodium chlorate. A subanalysis of these “potentially carcinogenic” pesticides suggested a positive trend of risk with exposure to increasing numbers.

CONCLUSION: Consideration of multiple exposures is important in accurately estimating specific effects and in evaluating realistic exposure scenarios.  FULL TEXT

Waddell et al., 2001

Waddell BL, Zahm SH, Baris D, Weisenburger DD, Holmes F, Burmeister LF, Cantor KP, Blair A., “Agricultural use of organophosphate pesticides and the risk of non-Hodgkin’s lymphoma among male farmers (United States).,” Cancer Causes Control, 2001, 12:6.


OBJECTIVE: Data from three population-based case-control studies conducted in Kansas, Nebraska, Iowa, and Minnesota were pooled to evaluate the relationship between the use of organophosphate pesticides and non-Hodgkin’s lymphoma (NHL) among white male farmers.

METHODS: The data set included 748 cases of non-Hodgkin’s lymphoma and 2236 population-based controls. Telephone or in-person interviews were utilized to obtain information on the use of pesticides. Odds ratios (OR) adjusted for age, state of residence, and respondent status, as well as other pesticide use where appropriate, were estimated by logistic regression.

RESULTS: Use of organophosphate pesticides was associated with a statistically significant 50% increased risk of NHL, but direct interviews showed a significantly lower risk (OR = 1.2) than proxy interviews (OR = 3.0). Among direct interviews the risk of small lymphocytic lymphoma increased with diazinon use (OR = 2.8), after adjustment for other pesticide exposures.

CONCLUSIONS: Although we found associations between the risk of NHL and several groupings and specific organophosphate pesticides, larger risks from proxy respondents complicate interpretation. Associations, however, between reported use of diazinon and NHL, particularly diffuse and small lymphocytic lymphoma, among subjects providing direct interviews are not easily discounted.

Cabello et al., 2001

Gertrudis Cabello, Mario Valenzuela, Arnaldo Vilaxa, Viviana Durán, Isolde Rudolph, Nicolas Hrepic, and Gloria Calaf, “A Rat Mammary Tumor Model Induced by the Organophosphorous Pesticides Parathion and Malathion, Possibly through Acetylcholinesterase Inhibition,” Environmental Health Perspectives, 2001, 109:5.


Environmental chemicals may be involved in the etiology of breast cancers. Many studies have addressed the association between cancer in humans and agricultural pesticide exposure. Organophosphorous pesticides have been used extensively to control mosquito plagues. Parathion and malathion are organophosphorous pesticides extensively used to control a wide range of sucking and chewing pests of field crops, fruits, and vegetables. They have many structural similarities with naturally occurring compounds, and their primary target of action in insects is the nervous system; they inhibit the release of the enzyme acetylcholinesterase at the synaptic junction. Eserine, parathion, and malathion are cholinesterase inhibitors responsible for the hydrolysis of body choline esters, including acetylcholine at cholinergic synapses. Atropine, a parasympatholytic alkaloid, is used as an antidote to acetylcholinesterase inhibitors. The aim of this study was to examine whether pesticides were able to induce malignant transformation of the rat mammary gland and to determine whether alterations induced by these substances increase the cholinergic activation influencing such transformation. These results showed that eserine, parathion, and malathion increased cell proliferation of terminal end buds of the 44-day-old mammary gland of rats, followed by formation of 8.6, 14.3, and 24.3% of mammary carcinomas, respectively, after about 28 months. At the same time, acetylcholinesterase activity decreased in the serum of these animals from 9.78 +/- 0.78 U/mL in the control animals to 3.05 +/- 0.06 U/mL; 2.57 +/- 0.15 U/mL; and 3.88 +/- 0.44 U/mL in the eserine-, parathion-, and malathion-treated groups, respectively. However, atropine alone induced a significant (p < 0.05) decrease in the acetylcholinesterase activity from the control value of 9.78 +/- 0.78 to 4.38 +/- 0.10 for atropine alone, to 1.32 +/- 0.06 for atropine in combination with eserine, and 2.39 +/- 0.29 for atropine with malathion, and there was no mammary tumor formation. These results indicate that organophosphorous pesticides induce changes in the epithelium of mammary gland influencing the process of carcinogenesis, and such alterations occur at the level of nervous system by increasing the cholinergic stimulation. FULL TEXT

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