The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program (NTP). The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP in March 2009 (see http://ntp.niehs.nih.gov/ntp/Test_info/NTP_DevTox20090405.pdf). The findings and conclusions for this study should not be construed to represent the views of the NTP or the US Government.
Developmental Toxicity Evaluation of 1,1,1-Trichloroethane (CAS No. 71-55-6) Administered in Drinking Water to CD® Rats
NTP Study T0179
1,1,1-Trichloroethane (TCEN), a saturated, lipophilic trichlorinated hydrocarbon, was evaluated for teratologic effects in COBS CD® (SD) BR outbred albino rats using an experimental design similar to but more extensive than that reported by Dapson et al. (1984). TCEN was administered in the drinking water at target concentrations of 3, 10, or 30 ppm, using 0.05% Tween 80® as an emulsifying agent. The doses chosen were expected to give a dose-response for cardiac malformations, based on findings reported by Dapson et al. (1984), that cardiac malformations significantly increased in rat offspring after exposure to 10 ppm TCEN. Two control groups, one receiving deionized/filtered water and the other receiving a vehicle control solution containing 0.05% Tween 80® were included. Groups of male and female breeders received either one of the control solutions or 3, 10, or 30 ppm TCEN for 14 consecutive days prior to cohabitation and for up to 6 days during cohabitation. Sperm-positive females continued to be exposed to the formulations throughout gestation. On gd 20, females were killed and the uterine contents were examined.
The effects of TCEN administered in the drinking water at target concentrations of 3, 10, or 30 ppm were evaluated in males and females after exposure prior to and during the cohabitation period (max. 6 days), and in females following exposure throughout gestation to scheduled sacrifice on gd 20. The following results were obtained:
- No significant adverse effect on body weight, food consumption, or water consumption for males or females during the premating period.
- No evidence of maternal toxicity throughout the gestational period.
- No adverse effect on any measure of developmental toxicity.
- No increase in malformations in term fetuses evaluated on gd 20.
- It was difficult to formulate the TCEN drinking water solutions, and TCEN content declined over a 72-hour period. These problems seriously limited attempts at estimating the true level of exposure of the animals to the test chemical. Thus, TCEN consumption was based on time-weighted averages of TCEN concentration in the formulations, based on stability data.
- Planned analysis of adult and fetal blood for TCEN concentration provided no meaningful results because the limit of detection (50 ng/ml) was too high. This level was chosen based on the Dapson et al. (1984), report which indicated blood levels of 200 ng/ml after exposure to 10 ppm TCEN. This information had been printed incorrectly and was later corrected to 30 ng/ml (Dapson, personal communication) after the present study was completed. Preliminary pharmacokinetic data (Appendix X) suggest that a limit of detection at least 10-fold lower than what was used in the present study would be required to quantify TCEN levels in the blood.
Thus, continuous exposure to TCEN in the drinking water at target concentrations up to 30 ppm, as tested in the present study, caused no significant toxicity in the parental generation as well as no developmental toxicity. The average exposure levels over the entire study, based on the combined time-weighted average concentration of TCEN in the formulations for the premating and gestational periods were 2.5, 6.5 and 18.6 ppm TCEN for the 3, 10, and 30 ppm groups, respectively. The exposure levels in the present study were higher than that reported by Dapson et al. (1984), yet no cardiac abnormalities [specifically atrial hypoplasia and/or displacement, as reported by Dapson et al. (1984) ] were observed.
Report Date: September 23, 1987