Exposure to organophosphorus insecticides and increased risks of health and cancer in US women

https://doi.org/10.1016/j.etap.2020.103474Get rights and content

Highlights

  • High urinary organophosphate levels increase risk of cardiovascular disease of US women aged 60-85.

  • High urinary organophosphate levels increase risk of asthma of US women aged 1-39.

  • High urinary organophosphate levels increase risk of breast and total cancers of US women.

  • High urinary organophosphate levels increase risk of prostate cancer of smoking men in the US.

Abstract

Results of this paper provide evidence that chronic long-term exposure to organophosphorus insecticides poses a significantly higher health risk for US women than for men, based on dialkylphosphate biomarker data from NHANES cycles 2003-2012. The risk of cardiovascular disease for female non-smokers aged 60-85 years in the highest dimethylthiophosphate (DMTP) urinary concentration quartile is 3.0 (odds ratio, OD = 3.0, 95%CI 1.4-6.4) times higher than that in the lowest quartile. Women with higher urinary DMTP concentrations also have significantly higher risk of asthma at the ages 6-39 years and an apparently higher risk of chronic bronchitis at the ages 60-85. Overall cancer risk is significantly higher for female non-smokers aged 60-85 years in the higher urinary DMTP quartiles (OD = 2.7, 95% CI 1.3-5.9). Increasing risks of breast cancer for female smokers and prostate cancer for male smokers aged 60-85 years with higher exposure to organophosphorus insecticides in the US are also significant.

Introduction

Organophosphorus (OP) compounds are a group of insecticides widely used for pest control on crops in agriculture and on livestock and for other commercial purposes (EPA, 2017; Ragnarsdottir, 2000). OP insecticides account for about 30% of the global insecticide market (i.e., agricultural, home and garden, industry, commercial, and government) (EPA, 2017). Because of health concerns, household domestic use of most OP insecticides has been phased out, following the implementation of the Food Quality Protection Act of 1996. Exposure to OP insecticides can induce free radical production and consequent lipid peroxidation (Akhgari et al., 2003; Altuntas et al., 2002) which can induce DNA damage (Dizdaroglu et al., 2002; Kang, 2002). For adults, long-term exposure to both small and large doses of OP insecticides can increase the risk for developing respiratory and reproductive problems, diabetes (Montgomery et al., 2008), cardiovascular disease (CVD) (Georgiadis et al., 2018; Hung et al., 2015; Sekhotha et al., 2016), Parkinson's disease (Manthripragada et al., 2010), and Alzheimer's disease (Hayden et al., 2010; Weichenthal et al., 2010). For children, OP exposure has been related to developmental problems, including decreased IQ and ADHD (Bouchard et al., 2010; Bouchard et al., 2011). OP exposure has also been actively studied for the risk for multiple types of cancer for agricultural applicators (Alavanja et al., 2004; Bonner et al., 2010; Mahajan et al., 2006).

However, research on the exposure to OP insecticides for non-agricultural US populations and the health impact on women in the United States has been relatively limited (Burns et al., 1998; Cecchi et al., 2012; Engel et al., 2017). Consequently, knowledge on the potential impact of OP exposure on the broad health of the overall population, especially of US women, are still inadequate (Lerro et al., 2015). The aim of this study was to examine the relation of OP exposure and broad health risk, including cancer risk for the US population with a particular focus on women. Our study uses urinary concentrations of the most commonly detected OP metabolite in the US population as an indicator of OP exposure to examine the relation of this exposure to the frequency of prescription drug usage; the occurrence of general health issues such as asthma, bronchitis, CVD, and the incidence of cancer reported in the US National Health and Nutrition Examination Survey (NHANES). Metabolites of OP insecticides have been used regularly as indicators of OP exposure in US agricultural and related populations studies (Arcury et al., 2016; Barr et al., 2005; Barr et al., 2011; Das et al., 2001).

Section snippets

Data

The National Center for Health Statistics of the Centers for Disease Control and Prevention (NCHS/CDC) conducted the NHANES studies. NHANES is designed to measure the health and nutrition status of the civilian, noninstitutionalized U.S. population. NHANES participants were selected based on their age, sex, and racial/ethnic background through a complex statistical process using the most current census information. Urine specimens were collected from participants 6–85 years of age during one of

Sex difference and age trends of urinary DMTP concentrations and health risks

The overall geometric mean (GM) of urinary concentration of DMTP in women (GM = 2.00 ug/l, 95%CI 1.89-2.11) are 1.01 (95% CI, 0.98-1.03) times of that of men (GM = 1.99 ug/l, 95%CI 1.87-2.11) (Fig. 1). GMs of Urinary DMTP level of three age groups (between 6 and 59 years) of women are higher than that of men while GM of urinary DMTP level of age group 60-85 years of women is smaller than that of men. The ratios of GM of DMTP values are 1.01 (95% CI, 0.98-1.03) and 0.94 (95% CI, 0.91-0.97)

Discussion

Sex differences in drug metabolism have been extensively studied (Skett, 1988). Sex differences are found in drug absorption, distribution and excretion. Many cytochrome P450 enzymes show a sex-dependent difference in activity. Experimental studies have found that some drugs were metabolized by certain isoforms of cytochrome P450 at much higher rates in male rats than in female (Kato, 1974). Varied metabolic rates related to hormonal regulation of the production of drug metabolizing enzymes are

Limitations of the study

This study has several limitations. Variations in LOD of DMTP measurement between 2003 and 2012 in NHANES lab affect the accuracy of the result. Though statistics of urinary DMTP measurements of spot data might reflect chronic long-term exposure of population, they are not the actual long-term measurement and can be further complicated as they can be derived from exposure to the preformed environmental metabolite as well as the parent OP insecticide. Possible errors can be introduced during the

Conclusions

Urinary DMTP levels, as an indicator of OP exposure, of women in the United States are higher than that of men. Women have a greater health risk of OP toxicity than men between 2003 and 2012. CVD risk, including that of congestive heart failure, coronary heart disease, angina/angina pectoris, heart attack and stroke for female non-smokers of advanced ages (60-85 years) at the two highest OP exposure quartiles are 2.3 and 3.0 times higher than that of women at the lowest OP exposure quartile,

CRediT authorship contribution statement

Hongbing Sun: Conceptualization, Methodology, Data curation, Investigation, Formal analysis, Writing - original draft, Writing - review & editing. Michael Leo Sun: Data curation, Investigation, Writing - review & editing. Dana Boyd Barr: Methodology, Formal analysis, Validation, Writing - review & editing.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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