Quantitative analysis of organophosphate pesticides and dialkylphosphates in duplicate diet samples to identify potential sources of measured urinary dialkylphosphates in Japanese women.

Increased levels of dialkylphosphates (DAP) in maternal urine are associated with a variety of adverse developmental outcomes in children. Although urinary DAP levels are usually considered to be a marker of exposure to organophosphate (OP) pesticides, excretion of DAP may also increase by ingesting preformed DAP. To date, no study has quantitatively assessed the possible contribution of the dietary intake of preformed DAP and OP pesticides to urinary levels of DAP. Therefore, we aimed to estimate the levels of 6 DAPs and 84 OP pesticides in duplicate diet samples and urine samples collected from 73 women living in urban areas of Japan in 2018. DAP and OP pesticides were detected in 94% and 45% of diet samples, while DAP was detected in 100% of urinary samples, respectively. The average daily intake of preformed DAP was significantly higher than that of parent OP pesticides in our participants. Dimethylphosphate and diethylphosphate were predominant in the preformed DAP, and the estimated average daily intake of total amount of DAP was 78.3 nmol. Fruits and vegetables were the major dietary sources of DAP. Dietary intake of DAP was positively associated with urinary DAP levels, suggesting that a considerable amount of urinary DAP was derived from ingesting preformed DAP. Our results show that attributing urinary DAP levels exclusively to OP pesticide exposure would result in a substantial overestimation of the exposure level. Therefore, the urinary levels of DAP may not be suitable for evaluating OP pesticide exposure in the general urban population.

Inhalation exposure to 2-ethyl-1-hexanol causes hepatomegaly and transient lipid accumulation without induction of peroxisome proliferator-activated receptor alpha in mice.

2-Ethyl-1-hexanol (2EH) is a volatile organic compound known to cause sick building syndrome. However, 2EH-induced hepatotoxicity has been mainly evaluated in experiments orally administering 2EH as a metabolite of di(2-ethylhexyl) phthalate. To evaluate the hepatotoxicity risk of 2EH as an indoor air pollutant, we exposed 10-wk-old male ICR mice to 2EH by inhalation for 8 h/d, 5 d/wk for 3 months (0, 20, 60, or 150 ppm) or 6 months (0, 0.5, 10, or 100 ppm). In both experiments, relative liver weights significantly increased in the highest exposure groups. The 3-month exposure increased histopathological lipid droplets in the liver in a dose-dependent manner, hepatic triglyceride at all exposure levels, hepatic phospholipid at 150 ppm, and microsomal triglyceride transfer protein at 60 and 150 ppm; however, these changes were not observed following the 6-month of exposure. Following the 3-month exposure, alanine transaminase and peroxisomal bifunctional proteins, known markers of liver injury and peroxisome proliferation, respectively, remained unaltered. Therefore, in the present study, the inhalation concentration range of 2EH induced a toxic hypertrophic change, revealing a limited role of peroxisome proliferator-activated receptor alpha (PPARα). The liver weights may have presumably increased via a mechanism independent of PPARα activation.

Development of a strategic approach for comprehensive detection of organophosphate pesticide metabolites in urine: Extrapolation of cadusafos and prothiofos metabolomics data of mice to humans.

OBJECTIVES: The comprehensive detection of environmental chemicals in biospecimens, an indispensable task in exposome research, is advancing. This study aimed to develop an exposomic approach to identify urinary metabolites of organophosphate (OP) pesticides, specifically cadusafos and prothiofos metabolites, as an example chemical group, using an original metabolome dataset generated from animal experiments. METHODS: Urine samples from 73 university students were analyzed using liquid chromatography-high-resolution mass spectrometry. The metabolome data, including the exact masses, retention time (tR ), and tandem mass spectra obtained from the human samples, were compared with the existing reference databases and with our original metabolome dataset for cadusafos and prothiofos, which was produced from mice to whom two doses of these OPs were orally administered. RESULTS: Using the existing databases, one chromatographic peak was annotated as 2,4-dichlorophenol, which could be a prothiofos metabolite. Using our original dataset, one peak was annotated as a putative cadusafos metabolite and three peaks as putative prothiofos metabolites. Of these, all three peaks suggestive of prothiofos metabolites, 2,4-dichlorophenol, 3,4,5-trihydroxy-6-(2,4-dichlorophenoxy) oxane-2-carboxylic acid, and (2,4-dichlorophenyl) hydrogen sulfate were confirmed as authentic compounds by comparing their peak data with both the original dataset and peak data of the standard reagents. The putative cadusafos metabolite was identified as a level C compound (metabolite candidate with limited plausibility). CONCLUSIONS: Our developed method successfully identified prothiofos metabolites that are usually not a target of biomonitoring studies. Our approach is extensively applicable to various environmental contaminants beyond OP pesticides.

Cumulative exposure assessment of neonicotinoids and an investigation into their intake-related factors in young children in Japan.

Exposure levels of neonicotinoids (NEO) in young children remain unknown, despite their widespread use and the plausible vulnerability of toddlers to environmental toxicants. Herein we aimed to clarify the exposure levels and sources of NEOs in young Japanese children. Disposable diapers were collected from 1036 children (16-23 months old) participating in an adjunct study of the Japan Environment and Children's Study between 2015 and 2016. Six NEOs and one metabolite in urine extracted from a diaper from each child were analyzed using high-performance liquid chromatography-tandem mass spectrometry. A relative potency factor approach was used to assess the cumulative exposure to NEOs equivalent to dinotefuran levels (DINRPF). The 95th percentile urinary concentration of DINRPF was 157 µg/L and 380 µg/g creatinine (Cr). Receiver operating characteristic curve analyses for the propensity scores of the possible exposure-related factors revealed that the discriminatory powers determining whether Cr-adjusted and Cr-unadjusted DINRPF concentrations exceeding the 95th percentile values were higher for the amount of each foodstuff ingested on the survey day (areas under the curve were 0.62 and 0.75, respectively) than for the exposure-related behaviors (0.60 and 0.71, respectively) or for mothers' attitudes toward food selection and preparation (0.54 and 0.57, respectively). Use of a mosquito coil, insect repellent, and mothproof net for a screen door, and playing on a lawn were associated with increased urinary NEO levels (odds ratio [OR]: 2.0-2.9), while care about the child's nutritional balance by mothers reduced urinary NEO levels (OR: 0.23-0.41). To the best of our knowledge, this is the first study that dealt with urinary concentrations and possible exposure sources of NEOs in a large number of young children. Attention to the children's behavior and diet might result in the reduction of a high exposure to NEOs in young children.