Developmental toxicity studies in Crl:CD (SD) rats following inhalation exposure to trichloroethylene and perchloroethylene

Abstract

The potential for trichloroethylene (TCE) and perchloroethylene (PERC) to induce developmental toxicity was investigated in Crl:CD (SD) rats whole-body exposed to target concentrations of 0, 50, 150 or 600 ppm TCE or 0, 75, 250 or 600 ppm PERC for six hours/day, seven days/week on gestation day (GD) 6-20 and 6-19, respectively. Actual chamber concentrations were essentially identical to target with the exception of the low PERC exposure level, which was 65 ppm. The highest exposure levels exceeded the limit concentration (2 mg/L) specified in the applicable test guidelines. Maternal necropsies were performed the day following the last exposure. Dams exposed to 600 ppm TCE exhibited maternal toxicity, as evidenced by decreased body weight gain (22% less than control) during GD 6-9. There were no maternal effects at 50 or 150 ppm TCE and no indications of developmental toxicity (including heart defects or other terata) at any exposure level tested. Therefore, the TCE NOEC for maternal toxicity was 150 ppm, whereas the embryo/fetal NOEC was 600 ppm. Maternal responses to PERC were limited to slight, but statistically significant reductions in body weight gain and feed consumption during the first 3 days of exposure to 600 ppm, resulting in a maternal NOEC of 250 ppm. Developmental effects at 600 ppm consisted of reduced gravid uterus, placental and fetal body weights, and decreased ossification of thoracic vertebral centra. Developmental effects at 250 ppm were of minimal toxicological significance, being limited to minor decreases in fetal and placental weight. There were no developmental effects at 65 ppm.

Human Health Effects of Trichloroethylene: Key Findings and Scientific Issues

“…Some studies identified significant treatment-related increases in the overall incidence of cardiac anomalies at environmentally relevant exposure levels (e.g., Johnson et al 2003, 2005), whereas others reported no excess cardiac abnormalities at much higher dose levels (e.g., Carney et al 2006; Fisher et al 2001). Several methodological factors may contribute to differences across study outcomes, such as the route of administration, test substance purity, test species or strain, timing of dosing or fetal evaluation, procedures used in dissecting and examining fetal hearts, statistical approaches applied to data evaluation, and generally uncharacterized interlaboratory variation.…”

Early lifestage exposure and potential developmental susceptibility to tetrachloroethylene

“…In a study designed to examine the effects of perc on fertility, female rats were exposed to inhaled perc for 2 hours/day, 5 days/week for 2 weeks and the oocytes extracted; the percentage of fertilized oocytes in vitro was reduced in perc-treated females as compared with controls (Berger and Horner, 2003). However, this study found no effect from exposure in drinking water, and other studies in rats also found no change in fertility (Carney et al, 2006;Tinston, 1994). An earlier study reported an increase in fertility of female rats exposed to perc (Carpenter, 1937).…”

“…In experimental animals, exposure to perc caused decreased birth weight (Tinston, 1994) and decreased fetal body weight in some studies of rats (Carney et al, 2006;Szakmáry et al, 1997) and mice (Schwetz et al, 1975). However, no effect on birth weight was found in other studies of mice (Szakmáry et al, 1997), rats (Hardin et al, 1981;Schwetz et al, 1975), and rabbits (Hardin et al, 1981;Szakmáry et al, 1997).…”

“…In one in vitro study, exposing rat embryos to perc resulted in increased mortality, malformations, delayed growth and differentiation, with a doseresponse observed (Saillenfait et al, 1995). However, no difference was seen in the corpora lutea/dam, implantations/dam, resorptions/litter, and pre-or postimplantation loss in rats (Carney et al, 2006), and pre-or post-implantation loss was not seen in rats and rabbits (Hardin et al, 1981).…”

“…Skeletal retardation and malformations were increased after maternal inhalation exposure in rats (Carney et al, 2006;Szakmáry et al, 1997) and mice (Schwetz et al, 1975;Szakmáry et al, 1997). Internal organ malformations were significantly increased in mice (Schwetz et al, 1975;Szakmáry et al, 1997).…”