Identification of Trichloroethylene and Its Metabolites in Human Seminal Fluid of Workers Exposed to Trichloroethylene

Abstract

ABSTRACT:We have investigated the potential of the male reproductive tract to accumulate trichloroethylene (TCE) and its metabolites, including chloral, trichloroethanol (TCOH), trichloroacetic acid (TCA), and dichloroacetic acid (DCA). Human seminal fluid and urine samples from eight mechanics diagnosed with clinical infertility and exposed to TCE occupationally were analyzed. In in vivo experimental studies, TCE and its metabolites were determined in epididymis and testis of mice exposed to TCE (1000 ppm) by inhalation for 1 to 4 weeks. In other studies, incubations of monkey epididymal microsomes were performed in the presence of TCE and NADPH. Our results showed that seminal fluid from all eight subjects contained TCE, chloral, and TCOH. DCA was present in samples from two subjects, and only one contained TCA. TCA and/or TCOH were also identified in urine samples from only two subjects. TCE, chloral, and TCOH were detected in murine epididymis after inhalation exposure with TCE for 1 to 4 weeks. Levels of TCE and chloral were similar throughout the entire exposure period. TCOH levels were similar at 1 and 2 weeks but increased significantly after 4 weeks of TCE exposure. Chloral was identified in microsomal incubations with TCE in monkey epididymis. CYP2E1, a P450 that metabolizes TCE, was localized in human and monkey epididymal epithelium and testicular Leydig cells. These results indicated that TCE is metabolized in the reproductive tract of the mouse and monkey. Furthermore, TCE and its metabolites accumulated in seminal fluid, and suggested associations between production of TCE metabolites, reproductive toxicity, and impaired fertility.

Trichloroethylene biotransformation and its role in mutagenicity, carcinogenicity and target organ toxicity

“…TCE metabolism by the oxidative pathway occurs predominantly in the liver [7]. Other tissues including the lungs [8-10], kidneys [11], and male reproductive organs [12, 13] are also sites of CYP-mediated TCE metabolism. Chemical stability of the metabolite is an important determinant of systemic availability and fate.…”

Pulmonary Bioactivation of Trichloroethylene to Chloral Hydrate: Relative Contributions of Cyp2e1, Cyp2f, and Cyp2b1

“…The National Toxicology Program (1990) has estimated that 3.5 million workers are exposed annually to TCE in the United States. Although the current occupational exposure limit for TCE is 50 ppm (American Conference of Governmental Industrial Hygienists, 2004), workers are still exposed to TCE under conditions where adequate protective measures are not in place (National Institute for Occupational Safety and Health, 1978;Forkert et al, 2003). As a result of its versatility and widespread use, TCE has become a prevalent soil and groundwater contaminant (Davidson and Beliles, 1991).…”

A review of analytical methods for the determination of trichloroethylene and its major metabolites chloral hydrate, trichloroacetic acid and dichloroacetic acid

“…These methods include the simultaneous analysis of TCE and its metabolites in several biological matrices, including lung, liver, kidney and blood (Merdink et al, 1998;Muralidhara and Bruckner, 1999). A GC-ECD method also exists for the analysis of TCE in seminal fluids of humans exposed to TCE occupationally (Forkert et al, 2003). There are also several GC-ECD methods for the analysis of HAAs in water LeBel et al, 1997;Dalvi et al, 2000;Benanou et al, 1998;Singer et al, 1995;Krasner et al, 1989) and biological samples (Kim et al, 1999;Wu et al, 2002;Ketcha et al, 1996).…”

“…The authors conclude that this method can be used in future studies to determine the formation of metabolites of TCE in pharmacokinetic studies. Forkert et al (2003) measured levels of TCE, TCEOH, DCA and TCA in the seminal fluid of eight infertile mechanics exposed to TCE occupationally. Semen samples (2 mL) were thawed at the time of analysis, and 1,3-dibromopropane (1 µL) was added as an internal standard.…”