Abnormal liver function associated with occupational exposure to dimethylformamide and glutathione S-transferase polymorphisms.

Dimethylformaide (DMF) is a major solvent predominately used in synthetic leather and resin production. Many human and animal studies have linked the cause of hepatoxicity to DMF. Previously, the authors demonstrated the significant dose-response relationship between abnormal liver function tests and DMF exposure and the interaction with hepatitis B virus (HBV) infection in Taiwanese workers. Because the toxic effect of various chemicals can be modified by metabolic traits, the study also investigated the influence of the glutathione S-transferases (GSTM1 and GSTT1) on the toxic effect of DMF. The average DMF exposure concentration was 23.87 ppm (range 5.2-86.6 ppm) in the high-exposure (>/=5 ppm) group and 2.41 ppm (range 0.9-4.3 ppm) in the low-exposure (<5 ppm) group. There were 13 of 44 (29.6%) abnormal liver function tests (elevations of either glutamate oxaloacetate transaminase (GOT) or glutamate pyruvate transaminase (GPT)) among the high DMF exposure workers, two of 22 (9.1%) abnormal liver function tests among the low DMF exposure workers. Chronic liver disease as determined by ultrasonography was present in seven of 44 (15.9%) high DMF exposure workers, and 0 of 22 (0%) low DMF exposure workers. There were 11 of 34 (32.4%) abnormal liver function tests among the GSTT1 null genotype workers, and four of 32 (12.5%) abnormal liver function tests among the GSTT1-positive genotype workers. Compared with the low DMF exposure workers, the adjusted odds ratio and 95% confidence intervals for abnormal liver function tests was 6.78 (0.94-48.7) for the high DMF exposure workers. Compared with the GSTT1-positive genotype workers, the adjusted odds ratio and 95% confidence intervals for abnormal liver function tests was 4.41 (1.15-16.9) for the GSTT1 null genotype workers. Compared with the low DMF group with GSTT1-positive genotype workers, the odds ratio (adjusted for HBV status) of abnormal liver function test was 12.38, 95% CI=(1.04-146.9) for the high DMF group with GSTT1 null genotype workers. This study indicates that abnormal liver function and chronic liver disease are associated with DMF exposure, and there are more than multiplicative interaction effects on abnormal liver function tests between the DMF exposure and the GSTT1 genotype.

Biological monitoring of environment exposure to safrole and the Taiwanese betel quid chewing.

A rapid and sensitive biological monitoring (BM) method for assessing exposure to the environmental carcinogen safrole has been developed. The method is an isocratic high-performance liquid chromatographic (HPLC) analysis of urinary dihydroxychavicol (DHAB) and eugenol, the urinary metabolites of safrole. Good linearity, precision, and accuracy were demonstrated. A recovery of 98.8 +/- 5.4% (SD, n = 3) was found for DHAB and 84.1 +/- 3.4% (n = 3) for eugenol. The quantitation limits of the method were 8 ng for DHAB and 10 ng for eugenol. The validity of the method was demonstrated by a linear dose-response relationship observed in rats given oral doses of safrole at 30, 75, and 150 mg/kg body weight. The method was also used to monitor the environmental exposure to the Taiwanese betel quid (TBQ) chewing, because TBQ used in Taiwan not only contains areca (betel) nut, slaked lime, and catechu but also Piper betle inflorescence or its leaves. Both of the latter have a high content of safrole. The feasibility of the method to monitor TBQ chewing was demonstrated by an analysis of 153 spot human urine samples. The results showed that the p value of the nonparametric group comparison was < 0.001 for DHAB and 0.832 for eugenol. The TBQ chewers also exhibited a significantly higher rate of urinary DHAB (but not eugenol) than the nonchewers with an odd ratio of 3.47 (95% CI, 1.61-7.51). However, when only the eugenol-positive subjects were taken into analysis, the ratio rose to 24.38 (95% CI, 3.00-197.90).

Decreased white blood cell counts in semiconductor manufacturing workers in Taiwan.

OBJECTIVES: To assess the systematic health effects on the liver, kidney, and haematological function tests of workers in semiconductors in Taiwan. METHODS: 926 workers of a semiconductor plant in Taiwan in July 1995 were investigated. Complete blood tests including liver, kidney, and haematological functions were available from 227 workers. RESULTS: There was a significantly lower mean (SD) white blood cell (WBC) count in male workers of photolithography (5870 (1190)/mm(3), p=0.003) and implantation (6190 (1150)/mm(3), p=0.018) than that of male control workers (7350 (1660)/mm(3)). There was a significantly higher prevalence of leukopenia in male photolithography workers (6 of 20; 30%) than in male control workers (1 of 18; 5.6%), the crude odds ratio (OR) was 7.3 (95% confidence interval (95% CI) 1 to 55.6), and the multivariate adjusted OR was 8.1 (95% CI 0.83 to 78.3). The tests for serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma glutamyl transferase (RGT), and creatinine were not significant among male workers. Female workers in photolithography had abnormal SGPT and RGT of borderline significance, the multivariate adjusted ORs were 9.6 (95% CI 0.86 to 107) and 6.35 (95% CI 0.53 to 75.8), respectively. CONCLUSIONS: This study suggests that leukopenia is a potential health effect in male fabrication workers of the semiconductor industry. The tasks of the process, maintenance, and equipment engineers which consisted mostly of men put them at risk for intermittent short term peak exposure to glycol ethers, ionising radiation, arsenic, or other toxins. The findings of this medical surveillance are significant; however, a further investigation of the aetiological factors and the subsequent health effects is necessary.