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Objectives: We aimed to develop a method to determine workers' personal exposure levels to N‐(phosphonomethyl)glycine (glyphosate) for their risk assessments. Methods: The proposed method was assessed as follows: recovery, stability of samples on storage, method limit of quantification, and reproducibility. Glyphosate in air was sampled using an air‐sampling cassette containing a glass fiber filter. Ultrapure water was used to extract glyphosate from sampler filters. After derivation with 9‐fluorenylmethyloxycarbonyl chloride, samples were analyzed by high‐performance liquid chromatography using a fluorescence detector. Results: Spiked samples indicated an overall recovery of 101%. After 7 days of storage at 4°C, recoveries were approximately 100%. The method limit of quantification was 0.060 μg/sample. Relative standard deviations representing overall reproducibility, defined as precision, were 1.4%–1.8%. Conclusions: The method developed in this study allows 4‐h personal exposure monitoring of glyphosate at 0.250–500 μg/m3. Thus, this method can be used to estimate worker exposure to glyphosate. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to develop and validate a simple and reliable gas chromatography‐mass spectrometry (GC‐MS) method to simultaneously determine urinary 1‐naphthol (1‐NAP) and 2‐naphthol (2‐NAP) for biological monitoring of occupational exposure to naphthalene. Methods: NAPs were derivatized in situ with acetic anhydride after enzymatic hydrolysis, extracted with n‐hexane, and analyzed using GC‐MS. Validation of the proposed method was conducted in accordance with US Food and Drug Administration guidance. A final validation was performed by analyzing a ClinChek®‐Control for phenolic compounds. Results: The linearity of calibration curves was indicated by a high correlation coefficient (>0.999) in the concentration range 1‐100 μg/L for each NAP. The limits of detection and quantification for each NAP were 0.30 and 1.00 μg/L, respectively. The recovery was 90.8%‐98.1%. The intraday and interday accuracies, expressed as the deviation from the nominal value, were 92.2%‐99.9% and 93.4%‐99.9%, respectively. The intraday and interday precision, expressed as the relative standard deviation, was 0.3%‐3.9% and 0.4%‐4.1%, respectively. The ClinChek® values obtained using our method were sufficiently accurate. Conclusions: The proposed method is simple, reliable, and appropriate for routine analyses, and is useful for biological monitoring of naphthalene exposure in occupational health practice. [ABSTRACT FROM AUTHOR]

Acetoaceto- o -toluidide (AAOT) is made from ortho -toluidine (OTD) and is used for the synthesis of pigments. A report of occupational urinary bladder carcinomas in Japanese workers chronically exposed to OTD and AAOT has recently been published. OTD is a well-known human urinary bladder carcinogen; however, little is known about the toxicity and the carcinogenicity of AAOT. The aim of the present study is to evaluate the toxic effects of AAOT on urinary bladder epithelium. In vitro, the cytotoxicities of AAOT and OTD were evaluated in rat (MYP3) and human (1T1) urothelial cells. The LC50 of AAOT was higher than that of OTD in both MYP cells and 1T1 cells. In vivo, 6-week-old male and female F344 rats were fed diets supplemented with 0%, 1.5%, or 3% AAOT for 4 weeks. Incidences of simple hyperplasia, cell proliferative activity, and γ-H2AX expression, which is a novel marker for the prediction of carcinogenicity, were significantly increased in a dose-dependent manner in the bladder urothelium of male and female rats administered AAOT. Furthermore, in male and female rats administered AAOT, the major urine metabolite of AAOT was OTD. These results demonstrate that AAOT has proliferation-enhancing activity and suggest that OTD metabolized from AAOT may play a pivotal role in the deleterious effects of AAOT in rats. The results of the present study also indicate that AAOT, like other carcinogenic aromatic amines, is likely to be a human bladder carcinogen. [ABSTRACT FROM AUTHOR]

1,2-dichloropropane (1,2-DCP) was reclassified recently by IARC as a Group 1 carcinogen based on epidemiological studies on an outbreak of cholangiocarcinoma in offset-printing workers exposed to 1,2-DCP in Japan. However, the underlying mechanism of 1,2-DCP-induced cholangiocarcinoma remains obscure. A previous whole-genome mutation analysis of cholangiocarcinoma of 4 cases exposed to 1,2-DCP suggested the involvement of activation-induced cytidine deaminase (AID), based on specific signatures of mutation patterns. The objective of the present study is to determine whether exposure to 1,2-DCP induces expression of AID in human cholangiocytes. Human MMNK-1 cholangiocytes, differentiated THP-1 macrophages, and co-cultures of MMNK-1/THP-1 cells were exposed to 1,2-DCP at different concentrations and time intervals. The mRNA expression levels of AID and related genes were quantified by real-time PCR. Protein expression was measured by immunostaining. Alkaline Comet assay was performed to examine DNA damage. The results showed that 1,2-DCP alone did not change AID expression in MMNK-1 cholangiocytes. 1,2-DCP significantly increased pro-inflammatory cytokine TNF-α expression in THP-1 macrophages. TNF-α treatment upregulated expression of AID, NF-κB, and IκB in MMNK-1 cholangiocytes. SN50, a NF-κB inhibitor, significantly downregulated TNF-α-induced AID expression, suggesting the involvement of NF-κB pathway in TNF-α-induced AID expression. Exposure to 1,2-DCP significantly increased AID expression in MMNK-1 cholangiocytes co-cultured with THP-1 macrophages. Comet assay showed that 1,2-DCP-induced DNA damage in MMNK-1 cholangiocytes, as indicated by increased tail DNA% and tail moment, was enhanced when co-cultured with macrophages. The results suggest that inflammatory response of macrophages and consequent aberrant AID expression or DNA damage in the cholangiocytes underlie the mechanism of 1,2-DCP-induced cholangiocarcinoma in humans. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the relationship between cumulative exposure to 1,2-dichloropropane (1,2-DCP) and incidence risk of cholangiocarcinoma among workers in the offset proof-printing section of a small printing company in Osaka, Japan.Methods: We identified 95 workers of a printing company (78 men and 17 women) who had been exposed to 1,2-DCP between 1987 and 2006, and calculated the standardised incidence ratio (SIR) of cholangiocarcinoma from 1987 to 2012. We estimated cumulative exposure to 1,2-DCP and calculated SIRs in four exposure categories. We also calculated incidence rate ratios (RRs) adjusted by sex, age, calendar year and dichloromethane (DCM) exposure for three exposure categories using Poisson regression analysis.Results: Cumulative exposures to 1,2-DCP ranged from 32 to 3433 ppm-years (mean, 851 ppm-years) and the SIR was 1171 (95% CI 682 to 1875). In the analysis of the four exposure categories, SIRs increased significantly in the three highest exposure categories, but not in the lowest category. Adjusted RRs in the middle and high exposure categories were 14.9 (95% CI 4.1 to 54.3) and 17.1 (95% CI 3.8 to 76.2), respectively, in the analysis without lag time, and were 11.4 (95% CI 3.3 to 39.6) and 32.4 (95% CI 6.4 to 163.9), respectively, in the analysis with a 5-year lag. The trend analysis revealed a significant increase in RR in association with increasing cumulative exposure to 1,2-DCP. DCM exposure was not significantly associated with the development of cholangiocarcinoma.Conclusions: The present study demonstrated an exposure-response relationship between exposure to 1,2-DCP and the development of cholangiocarcinoma. [ABSTRACT FROM AUTHOR]