Reproductive toxicity

Exposure to tetrachloroethylene may pose a reproductive hazard. However, due to study design or the small number of cases, the relationship of impaired fertility or adverse reproductive outcome to tetrachloroethylene exposure cannot be adequately evaluated (van der Gulden and Zielhuis, 1989; BUA, 1996; ATSDR, 1997).


Exposure to tetrachloroethylene may have subtle effects on sperm quality but it is not known whether the effects are associated with changes in fertility. In the study by Eskenazi et al. (1991a) the average sperm concentration was the same in dry cleaners and controls. The proportion of abnormal forms was also similar, but sperm of dry cleaners were significantly more likely to be round and less likely to be narrow. These effects were related to dose and expired air tetrachloroethylene concentrations. Average sperm motility was similar in both groups, but the sperm of dry cleaners tended to swim with greater amplitude of head displacement. In multiple regression analysis the expired air concentration was a significant predictor of this effect. The sperm linearity swim path was decreased in dry cleaners and this was significantly negatively correlated with exposure concentration (Eskenazi et al., 1991a). Rachootin and Olsen (1983) reported a slightly higher but nonsignificant risk of abnormal sperm in men exposed to dry cleaning chemicals, compared to infertile men with conditions unlikely to be caused by their occupation.

In a study using various animal species there were slight degenerative changes in the germinal epithelium in the testes of guinea pigs exposed to 1,600 ppm tetrachloroethylene on eight occasions. Testicular changes in the other species were not reported (Rowe et al., 1952).

In a study of female workers exposed to tetrachloroethylene, there was an increased risk of almost all menstrual disorders, but particularly premenstrual syndrome and menorrhagia, compared to controls. However, the study was limited by small size and absence of exposure measurements (Zielhaus et al., 1989). A study of female workers found that during the proliferative phase of the menstrual cycle tetrachloroethylene exposed workers had increased serum prolactin concentrations compared to controls. However, in both groups the values were within the normal range. Increased prolactin levels did not correlate with air (median 15 ppm, ranges 1-67 ppm) or blood (median 145 mg/l, range 12-864 mg/l) tetrachloroethylene concentrations or duration of exposure (Ferroni et al., 1992). A Danish investigation of infertile couples and their occupations found an association of increased risk of hormonal disturbances and delayed conception in women working in dry cleaning establishments (Rachootin and Olsen, 1983).


A number of studies have shown that exposure to tetrachloroethylene is associated with an increase in spontaneous abortions (Hemminki et al., 1980; Kyyrönen et al., 1989; Olson et al., 1990; Windham et al., 1991; Lindbohm et al., 1992; Doyle et al., 1997). Other studies have found no association between tetrachloroethylene exposure and increased risk of spontaneous abortion (Bosco et al., 1987; McDonald et al., 1987; Taskinen et al., 1989; Ahlborg, 1990; Eskenazi et al., 1991b). However, some of these studies were not specifically designed to measure the association of spontaneous abortion to solvent exposure and the numbers in the other studies were small. The risk of spontaneous abortion may depend on the exposure concentration. Doyle et al. (1997) postulate that the results of these studies of tetrachloroethylene exposed workers suggest that exposure to high concentrations may increase the risk of spontaneous abortion, but that there is no risk in workers with lower levels of exposure.

A study in rats exposed to 300 ppm tetrachloroethylene found no evidence of embryotoxicity, fetotoxicity or teratogenicity. In mice there was delayed ossification of skull bones and split sternebrae (Schwetz et al., 1975), which could be interpreted as teratogenic effects. However, evaluation of these findings is difficult because the number of animals used was too small and no indication is given of the number of fetuses affected within each litter (NIOSH, 1976; Barlow and Sullivan, 1982).


Using a physiologically based pharmacokinetic (PBPK) model, Fisher et al. (1997) determined that when a lactating woman is exposed to the theshold limit value, the concentration of tetrachloroethylene in breast milk will exceed the Environmental Protection Agency (EPA) non-cancer drinking water ingestion rates for children, and may therefore pose a hazard to nursing infants. Tetrachloroethylene excreted in breast milk caused obstructive jaundice and hepatomegaly in a 6 week old infant (Bagnell and Ellenberger, 1977).

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