Organophosphate pesticide exposure and biomarkers of liver injury/liver function

Abstract

Background and Aims There is little epidemiological evidence linking the exposure of organophosphate pesticides (OPs) to liver function or liver injury in the general population. We used data from the National Health and Nutrition Examination Survey 1999–2012 to investigate the relationship of urinary OPs with biomarkers of liver function/liver injury. Methods The exposures were the concentrations of urinary OP metabolites (dimethyl phosphate [DMP], dimethyl thiophosphate [DMTP], diethyl phosphate [DEP] and diethyl thiophosphate [DETP]). The health outcomes were biomarkers of liver function/liver injury. The multivariable linear regression model, restricted cubic splines (RCSs) analysis and weighted quantile sum (WQS) regression were used to evaluate the relationship between individual or overall exposure of OPs and outcomes. Results Regressions of RCSs suggested linear and positive associations of OP metabolites with aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio (DMP and DEP) and fibrosis‐4 (FIB‐4) index (DMP, DEP and DMTP) (all p–non‐linear values >.05). However, L‐shaped relationships were found between OP metabolites (DMTP and DETP) and blood albumin and total protein (TP) concentrations (both p and non‐linear values <.05). The positive associations of urinary DMP, DEP and DMTP with AST/ALT ratio, and with FIB‐4 score were more pronounced among non‐smokers than smokers, among alcohol drinkers than non‐drinkers and among those with a body mass index (BMI) of ≥25 than participants with a BMI of <25. However, most of the interaction p values were more than .05, indicating no significant interactions between covariates and OPs on outcomes mainly including AST/ALT, FIB‐4, ALB and TP levels. Finally, the WQS indices were positively associated with AST/ALT ratio (p = .014) and FIB‐4 score (p = .002). Conclusions Our study added novel evidence that exposures to OPs might be adversely associated with the biomarkers of liver function/liver injury. These findings indicated the potential toxic effect of OP exposures on the human liver.

Organophosphate pesticides: Another silent liver hazard?

“…Environmental pollutants and pesticides have been involved in causing (and worsening pre‐existing) non‐alcoholic fatty liver disease, the so‐called “toxicant” associated steatohepatitis (TASH) being the typical phenotype of liver injury, as, for instance, has been described in workers of the petrochemical industry majority of whom did not have insulin resistance suggesting that fatty liver was a direct effect of the volatile compounds for which they were exposed to 10 . Although Li and coworkers in a recently published article of similar design found that among a mixture of chemical compounds, organophosphate pesticides were associated with fatty liver measured by the liver steatosis indexes, HSI and USFLI (OR: 1.32, 95% CI 1.15–1.51) 11 , in the present study, however, they did not replicate their previous findings 3 . Instead, a novel and intriguing finding of this study is the association of some urinary OP metabolites with parameters of liver fibrosis and liver dysfunction, which suggest that long‐term exposure to these pesticides might apparently lead to subclinical liver damage severe enough to affect liver function.…”

“…10 Although Li and coworkers in a recently published article of similar design found that among a mixture of chemical compounds, organophosphate pesticides were associated with fatty liver measured by the liver steatosis indexes, HSI and USFLI (OR: 1.32, 95% CI 1.15-1.51) 11 , in the present study, however, they did not replicate their previous findings. 3 Instead, a novel and intriguing finding of this study is the association of some urinary OP metabolites with parameters of liver fibrosis and liver dysfunction, which suggest that long-term exposure to these pesticides might apparently lead to subclinical liver damage severe enough to affect liver function. The mechanisms for which OP exposure would result in liver fibrosis and hepatic dysfunction are elusive.…”

“…Besides, cohort 3 (5488 participants) and cohort 4 (2639 participants) were evaluated for hepatic steatosis index (HSI) and US fatty liver index (USFLI) score, respectively. The authors found that DMP, DEP and DMTP were significantly associated with AST/ALT ratio and FIB‐4 score, as well as that urinary DMTP and DETP concentrations were negatively associated with serum albumin and total protein levels, indicating for the first time a potential toxic effect of ‘long‐term’ OP exposure to human liver 3 …”

“…2 However, the effects of OP on exposed subjects without manifestations of acute toxicity have not been yet investigated in epidemiologically designed studies. In this issue of Liver International, Li et al 3 or dimethyldithiophosphate (DMDTP)], which are eliminated in the urine within 6-24 h after exposure and can be used as a surrogate of OP exposure and biomarkers of liver injury (AST, ALT and ALP and composite fibrosis and steatosis scores) and liver function (bilirubin, total protein and albumin). They used different cohorts; cohort 1 enrolled 5952 participants for the outcomes of ALT, AST, AST/ALT, TBIL, ALB, TP and FIB-4; cohort 2, included 4953 participants for association with ALP.…”

“…The authors found that DMP, DEP and DMTP were significantly associated with AST/ALT ratio and FIB-4 score, as well as that urinary DMTP and DETP concentrations were negatively associated with serum albumin and total protein levels, indicating for the first time a potential toxic effect of 'long-term' OP exposure to human liver. 3 The source of data for the study was the National Health and Nutrition Examination Survey (NHANES). The NHANES is an ongoing, national, cross-sectional series of surveys with multistage complex sampling strategies, representative of the health and nutritional status of the noninstitutionalized civilian (adults and children) United States population.…”