Report Date: November 1988
The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. For more information, see the Explanation of Levels of Evidence for Developmental Toxicity. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
Acetone, an aliphatic ketone, is a ubiquitous industrial solvent and chemical intermediate; consequently, the opportunity for human exposure is high. The potential for acetone to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 440, 2200, or 11000 ppm, and in Swiss (CD-1) mice exposed to 0, 440, 2200, and 6600 ppm acetone vapors, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and ~32 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation, and rats on 6-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects.
Pregnant rats did not exhibit overt symptoms of toxicity other than statistically significant reductions for the 11000 ppm group in body weight. (14, 17, 20 dg), cumulative weight gain from 14 dg onward, uterine weight and in extragestational weight gain. (EGWG - maternal body weight [20 dg] uterine weight - maternal body weight [0 dg.) Mean body weights of treated virgin females were also reduced, but not significantly. There were no maternal deaths and the mean pregnancy rate was greater than or equal to 93% in all groups. No affect was observed in the mean liver or kidney weights of pregnant dams, the organ to body weight ratios, the number of implantations, the mean percent of live pups/litter, the mean percent of resorptions/litter, or the fetal sex ratio. However, fetal weights were significantly reduced for the 11000-ppm exposure group relative to the 0-ppm group. The incidence of fetal malformations was not significantly increased by gestational exposure to acetone vapors, although the percent of litters with at least one pup exhibiting malformations was greater for the 11000-ppm group than for the 0-ppm group, 11.5 and 3.8%, respectively. The diversity of malformations observed in the 11000-ppm group was greater than that found in the lower dose groups or in the 0-ppm group.
There was no increase in the incidence of fetal variations, reduced ossification sites, or in the mean incidence of fetal variations per litter.
Analysis of rat plasma samples 30 min post-exposure showed an increase in plasma acetone levels which correlated with increasing exposure concentration. Acetone levels dropped to control levels by 17 h post-exposure for all exposure groups except the 11000-ppm group. Plasma acetone-levels for this group were still slightly elevated with respect to the controls at 17 h post-exposure. The concentration of plasma acetone levels at either 30 min or 17 h post exposure did not increase over gestation regardless of the exposure concentration. Neither exposure to acetone vapor, nor advancing gestation resulted in alterations of the plasma levels for the other two ketone bodies, acetoacetic acid and b-hydroxybutyric acid, with respect to control animals.
Swiss (CD-1) mice exhibited severe narcosis at the 11000-ppm acetone concentration; consequently, the high exposure concentration was reduced to 6600 ppm acetone after one day of exposure. No further overt signs of toxicity were observed and there were no maternal deaths. No treatment- related effects on maternal or virgin body weight, maternal uterine weight, or on EGWG were noted in mice. There was a treatment-correlated increase in liver to body weight ratios in pregnant dams which may have been indicative of an induction of the P450-monooxygenase enzyme system.
The mean pregnancy rate for all mated mice was greater than or equal to 85% in all groups. There was no effect on the number of implantations per dam, on any other reproductive indices, or on the fetal sex ratio. Developmental toxicity was observed in mice in the 6600 ppm exposure group as; 1) a statistically significant reduction in fetal weight, and 2) a slight, but statistically significant increase in the percent incidence of late resorptions. However, the increase in the incidence of late resorptions was not sufficient to cause a decrease in the mean number of live fetuses per litter. The incidence of fetal malformations or variations in mice was not altered by exposure to acetone vapors at any of the levels employed.
It may be concluded from the results of this study that the 2200-ppm acetone level was the no observable effect level in both the Sprague-Dawley (CD) rat and the Swiss (CD-1) mouse for developmental toxicity. Furthermore, since only minimal maternal toxicity was observed at 11000 ppm acetone for rats and 6600 ppm acetone for mice, it is possible that the actual maternal NOEL is somewhat greater than 2200 ppm.