Chlorpyrifos - HH-RA.org

Bibliography Tag: chlorpyrifos

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.

ABSTRACT:

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

Alavanja et al., 2004

Alavanja, M. C., Dosemeci, M., Samanic, C., Lubin, J., Lynch, C. F., Knott, C., Barker, J., Hoppin, J. A., Sandler, D. P., Coble, J., Thomas, K., & Blair, A.; “Pesticides and lung cancer risk in the agricultural health study cohort;” American Journal of Epidemiology, 2004, 160(9), 876-885; DOI: 10.1093/aje/kwh290.

ABSTRACT:

The authors examined the relation between 50 widely used agricultural pesticides and lung cancer incidence in the Agricultural Health Study, a prospective cohort study of 57,284 pesticide applicators and 32,333 spouses of farmer applicators with no prior history of lung cancer. Self-administered questionnaires were completed at enrollment (1993-1997). Cancer incidence was determined through population-based cancer registries from enrollment through December 31, 2001. A lung cancer standardized incidence ratio of 0.44 (95% confidence interval: 0.39, 0.49) was observed overall, due in large part to a low cigarette smoking prevalence. Two widely used herbicides, metolachlor and pendimethalin (for low-exposed groups to four higher exposure categories: odds ratio (OR) = 1.0, 1.6, 1.2, 5.0; p(trend) = 0.0002; and OR = 1.0, 1.6, 2.1, 4.4; p(trend) = 0.003, respectively), and two widely used insecticides, chlorpyrifos and diazinon (OR = 1.0, 1.1, 1.7, 1.9; p(trend) = 0.03; and OR = 1.0, 1.6, 2.7, 3.7; p(trend) = 0.04, respectively), showed some evidence of exposure response for lung cancer. These excesses could not be explained by previously identified lung cancer risk factors. The usage levels in this cohort are considerably higher than those typically experienced by the general population. An excess risk among spouses directly exposed to pesticides could not be evaluated at this time. FULL TEXT

Zhao et al., 2016

Zhao, Y., Zhang, Y., Wang, G., Han, R., & Xie, X.; “Effects of chlorpyrifos on the gut microbiome and urine metabolome in mouse (Mus musculus);” Chemosphere, 2016, 153, 287-293; DOI: 10.1016/j.chemosphere.2016.03.055.

ABSTRACT:

In this study, the toxic effects of chlorpyrifos (CPF) on the gut microbiome and related urine metabolome in mouse (Mus musculus) were investigated. Mice were exposed to a daily dose of 1 mg kg(-1) bodyweight of CPF for 30 d. As a result, CPF significantly altered the gut microbiota composition in terms of the relative abundance of key microbes. Meanwhile, CPF exposure induced the alterations of urine metabolites related to the metabolism of amino acids, energy, short-chain fatty acids (SCFAs), phenyl derivatives and bile acids. High correlations were observed between perturbed gut microbiome and altered metabolic profiles. These perturbations finally resulted in intestinal inflammation and abnormal intestinal permeability, which were also confirm by the histologic changes in colon and remarkable increase of lipopolysaccharide (LPS) and diamine oxidase (DAO) in the serum of CPF-treated mice. Our findings will provide a new perspective to reveal the mechanism of CPF toxicity. FULL TEXT

Ruden and Grandjean, 2018

Mie, A., Ruden, C., & Grandjean, P.; “Safety of Safety Evaluation of Pesticides: developmental neurotoxicity of chlorpyrifos and chlorpyrifos-methyl;” Environmental Health, 2018, 17(1), 77; DOI: 10.1186/s12940-018-0421-y.

ABSTRACT:

Authorization of pesticides for market release requires toxicity testing on animals, typically performed by test laboratories on contract with the pesticide producer. The latter provides the results and summary to the regulatory authorities. For the commonly used pesticide chlorpyrifos, an industry-funded toxicity study concludes that no selective effects on neurodevelopment occur even at high exposures. In contrast, the evidence from independent studies points to adverse effects of current exposures on cognitive development in children. We reviewed the industry-funded developmental neurotoxicity test data on chlorpyrifos and the related substance chlorpyrifos-methyl. We noted treatment-related changes in a brain dimension measure for chlorpyrifos at all dose levels tested, although not been reported in the original test summary. We further found issues which inappropriately decrease the ability of the studies to reveal true effects, including a dosage regimen that resulted in too low exposure of the nursing pups for chlorpyrifos and possibly for chlorpyrifos-methyl, and a failure to detect any neurobehavioral effects of lead nitrate used as positive control in the chlorpyrifos study. Our observations thus suggest that conclusions in test reports submitted by the producer may be misleading. This discrepancy affects the ability of regulatory authorities to perform a valid and safe evaluation of these pesticides. The difference between raw data and conclusions in the test reports indicates a potential existence of bias that would require regulatory attention and possible resolution. FULL TEXT

Berkowitz et al., 2004

Berkowitz, G. S., Wetmur, J. G., Birman-Deych, E., Obel, J., Lapinski, R. H., Godbold, J. H., Holzman, I. R., & Wolff, M. S.; “In utero pesticide exposure, maternal paraoxonase activity, and head circumference;” Environmental Health Perspectives, 2004, 112(3), 388-391; DOI: 10.1289/ehp.6414.

ABSTRACT:

Although the use of pesticides in inner-city homes of the United States is of considerable magnitude, little is known about the potentially adverse health effects of such exposure. Recent animal data suggest that exposure to pesticides during pregnancy and early life may impair growth and neurodevelopment in the offspring. To investigate the relationship among prenatal pesticide exposure, paraoxonase (PON1) polymorphisms and enzyme activity, and infant growth and neurodevelopment, we are conducting a prospective, multiethnic cohort study of mothers and infants delivered at Mount Sinai Hospital in New York City. In this report we evaluate the effects of pesticide exposure on birth weight, length, head circumference, and gestational age among 404 births between May 1998 and May 2002. Pesticide exposure was assessed by a prenatal questionnaire administered to the mothers during the early third trimester as well as by analysis of maternal urinary pentachlorophenol levels and maternal metabolites of chlorpyrifos and pyrethroids. Neither the questionnaire data nor the pesticide metabolite levels were associated with any of the fetal growth indices or gestational age. However, when the level of maternal PON1 activity was taken into account, maternal levels of chlorpyrifos above the limit of detection coupled with low maternal PON1 activity were associated with a significant but small reduction in head circumference. In addition, maternal PON1 levels alone, but not PON1 genetic polymorphisms, were associated with reduced head size. Because small head size has been found to be predictive of subsequent cognitive ability, these data suggest that chlorpyrifos may have a detrimental effect on fetal neurodevelopment among mothers who exhibit low PON1 activity. FULL TEXT

Thomas et al., 2010b

Thomas, K. W., Dosemeci, M., Coble, J. B., Hoppin, J. A., Sheldon, L. S., Chapa, G., Croghan, C. W., Jones, P. A., Knott, C. E., Lynch, C. F., Sandler, D. P., Blair, A. E., & Alavanja, M. C.; “Assessment of a pesticide exposure intensity algorithm in the agricultural health study;” Journal of Exposure Analysis and Environmental Epidemiology, 2010, 20(6), 559-569; DOI: 10.1038/jes.2009.54.

ABSTRACT:

The accuracy of the exposure assessment is a critical factor in epidemiological investigations of pesticide exposures and health in agricultural populations. However, few studies have been conducted to evaluate questionnaire-based exposure metrics. The Agricultural Health Study (AHS) is a prospective cohort study of pesticide applicators who provided detailed questionnaire information on their use of specific pesticides. A field study was conducted for a subset of the applicators enrolled in the AHS to assess a pesticide exposure algorithm through comparison of algorithm intensity scores with measured exposures. Pre- and post-application urinary biomarker measurements were made for 2,4-D (n=69) and chlorpyrifos (n=17) applicators. Dermal patch, hand wipe, and personal air samples were also collected. Intensity scores were calculated using information from technician observations and an interviewer-administered questionnaire. Correlations between observer and questionnaire intensity scores were high (Spearman’s r=0.92 and 0.84 for 2,4-D and chlorpyrifos, respectively). Intensity scores from questionnaires for individual applications were significantly correlated with post-application urinary concentrations for both 2,4-D (r=0.42, P<0.001) and chlorpyrifos (r=0.53, P=0.035) applicators. Significant correlations were also found between intensity scores and estimated hand loading, estimated body loading, and air concentrations for 2,4-D applicators (r-values 0.28-0.50, P-values<0.025). Correlations between intensity scores and dermal and air measures were generally lower for chlorpyrifos applicators using granular products. A linear regression model indicated that the algorithm factors for individual applications explained 24% of the variability in post-application urinary 2,4-D concentration, which increased to 60% when the pre-application urine concentration was included. The results of the measurements support the use of the algorithm for estimating questionnaire-based exposure intensities in the AHS for liquid pesticide products. Refinement of the algorithm may be possible using the results from this and other measurement studies. FULL TEXT

Hoppin et al., 2002

Hoppin, J. A., Yucel, F., Dosemeci, M., & Sandler, D. P.; “Accuracy of self-reported pesticide use duration information from licensed pesticide applicators in the Agricultural Health Study;” Journal of Exposure Analysis and Environmental Epidemiology, 2002, 12(5), 313-318; DOI: 10.1038/sj.jea.7500232.

ABSTRACT:

Epidemiologists frequently rely on self-reported information regarding a variety of exposures including smoking history, medication use, and occupational exposure because other sources of information are either unavailable or difficult to obtain. One way to evaluate the accuracy of self-reported information is through logic checks using other sources. To assess the quality of the self-reported pesticide product use history of 57,311 licensed pesticide applicators in the Agricultural Health Study (AHS), we compared the self-reported decade of first use and total years of use to the year the pesticide active ingredient was first registered for use. We obtained pesticide active ingredient registration information from the United States Environmental Protection Agency (USEPA) and other publicly available sources for the 52 pesticides on the AHS initial questionnaires administered from 1994 to 1997. Based on the registration year, we assessed 19 pesticides for potential inaccuracies regarding duration of use or decade of first use. When calculating potential total years of use, we did not consider the impact of chemicals being removed from the market, since the possibility for continued use existed. The majority of respondents provided plausible responses for both decade of first use and total duration of use. On average, 1% of the subjects overestimated total possible duration of use, ranging from less than 1% for carbofuran and chlorpyrifos to 5% for imazethapyr. Decade of first use was also reasonably reported, although more subjects did not report decade of first use than duration of use, with an average of 6% of subjects missing decade information for an individual chemical. For subjects who reported a decade of first use, 98% gave plausible responses on average, with overestimates highest for cyanazine, introduced in 1971 (6% reported earlier use), and chlorimuron ethyl, introduced in 1985 (7% reported earlier use). This analysis provided the opportunity to consider only one source of potential overreporting of exposure, and while underreporting may have also occurred, we cannot evaluate its role nor the balance between these potential inaccuracies. While we are unable to validate directly the accuracy of a respondent’s use of pesticides, this analysis suggests that participants provide plausible information regarding their pesticide use. FULL TEXT

Curwin et al., 2007

Curwin, Brian D., Hein, Misty J., Sanderson, Wayne T., Striley, Cynthia, Heederik, Dick, Kromhout, Hans, Reynolds, Stephen J., & Alavanja, Michael C.; “Pesticide dose estimates for children of Iowa farmers and non-farmers;” Environmental Research, 2007, 105, 307-315; DOI: 10.1016/j.envres.2007.06.001.

ABSTRACT:

Farm children have the potential to be exposed to pesticides. Biological monitoring is often employed to assess this exposure; however, the significance of the exposure is uncertain unless doses are estimated. In the spring and summer of 2001, 118 children (66 farm, 52 non-farm) of Iowa farm and non-farm households were recruited to participate in a study investigating potential take-home pesticide exposure. Each child provided an evening and morning urine sample at two visits spaced approximately 1 month apart, with the first sample collection taken within a few days after pesticide application. Estimated doses were calculated for atrazine, metolachlor, chlorpyrifos, and glyphosate from urinary metabolite concentrations derived from the spot urine samples and compared to EPA reference doses. For all pesticides except glyphosate, the doses from farm children were higher than doses from the non-farm children. The difference was statistically significant for atrazine (p<0.0001) but only marginally significant for chlorpyrifos and metolachlor (p=0.07 and 0.1, respectively). Among farm children, geometric mean doses were higher for children on farms where a particular pesticide was applied compared to farms where that pesticide was not applied for all pesticides except glyphosate; results were significant for atrazine (p=0.030) and metolachlor (p=0.042), and marginally significant for chlorpyrifos (p=0.057). The highest estimated doses for atrazine, chlorpyrifos, metolachlor, and glyphosate were 0.085, 1.96, 3.16, and 0.34 μg/kg/day, respectively. None of the doses exceeded any of the EPA reference values for atrazine, metolachlor, and glyphosate; however, all of the doses for chlorpyrifos exceeded the EPA chronic population adjusted reference value. Doses were similar for male and female children. A trend of decreasing dose with increasing age was observed for chlorpyrifos. FULL TEXT

Curwin et al., 2002

Curwin, B., Sanderson, W., Reynolds, S., Hein, M., & Alavanja, M.; “Pesticide use and practices in an Iowa farm family pesticide exposure study;” Journal of Agricultural Safety and Health, 2002, 8(4), 423-433; DOI: 10.13031/2013.10222.

ABSTRACT:

Residents of Iowa were enrolled in a study investigating differences in pesticide contamination and exposure factors between 25 farm homes and 25 non-farm homes. The target pesticides investigated were atrazine, metolachlor, acetochlor, alachlor, 2,4-D, glyphosate, and chlorpyrifos; all were applied to either corn or soybean crops. A questionnaire was administered to all participants to determine residential pesticide use in and around the home. In addition, a questionnaire was administered to the farmers to determine the agricultural pesticides they used on the farm and their application practices. Non-agricultural pesticides were used more in and around farm homes than non-farm homes. Atrazine was the agricultural pesticide used most by farmers. Most farmers applied pesticides themselves but only 10 (59%) used tractors with enclosed cabs, and they typically wore little personal protective equipment (PPE). On almost every farm, more than one agricultural pesticide was applied. Corn was grown by 23 (92%) farmers and soybeans by 12 (48%) farmers. Of these, 10 (40%) grew both soybeans and corn, with only 2 (8%) growing only soybeans and 13 (52%) growing only corn. The majority of farmers changed from their work clothes and shoes in the home, and when they changed outside or in the garage, they usually brought their clothes and shoes inside. Applying pesticides using tractors with open cabs, not wearing PPE, and changing from work clothes in the home may increase pesticide exposure and contamination. Almost half of the 66 farm children less than 16 years of age were engaged in some form of farm chores, with 6 (9%) potentially directly exposed to pesticides, while only 2 (4%) of the 52 non-farm children less than 16 years of age had farm chores, and none were directly exposed to pesticides. Farm homes may be contaminated with pesticides in several ways, resulting in potentially more contamination than non-farm homes, and farm children may be directly exposed to pesticides through farm chores involving pesticides. In addition to providing a description of pesticide use, the data presented here will be useful in evaluating potential contributing factors to household pesticide contamination and family exposure. FULL TEXT

Coble et al., 2011

Coble, J., Thomas, K. W., Hines, C. J., Hoppin, J. A., Dosemeci, M., Curwin, B., Lubin, J. H., Beane Freeman, L. E., Blair, A., Sandler, D. P., & Alavanja, M. C.; “An updated algorithm for estimation of pesticide exposure intensity in the agricultural health study;” International Journal of Environmental Research and Public Health, 2011, 8(12), 4608-4622; DOI: 10.3390/ijerph8124608.

ABSTRACT:

An algorithm developed to estimate pesticide exposure intensity for use in epidemiologic analyses was revised based on data from two exposure monitoring studies. In the first study, we estimated relative exposure intensity based on the results of measurements taken during the application of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) (n = 88) and the insecticide chlorpyrifos (n = 17). Modifications to the algorithm weighting factors were based on geometric means (GM) of post-application urine concentrations for applicators grouped by application method and use of chemically-resistant (CR) gloves. Measurement data from a second study were also used to evaluate relative exposure levels associated with airblast as compared to hand spray application methods. Algorithm modifications included an increase in the exposure reduction factor for use of CR gloves from 40% to 60%, an increase in the application method weight for boom spray relative to in-furrow and for air blast relative to hand spray, and a decrease in the weight for mixing relative to the new weights assigned for application methods. The weighting factors for the revised algorithm now incorporate exposure measurements taken on Agricultural Health Study (AHS) participants for the application methods and personal protective equipment (PPE) commonly reported by study participants. FULL TEXT

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