National Toxicology Program

Inhalation Development Toxicology Studies: Acetonitrile (CAS No.75-05-8) in Rats

NTP Study: TER91039

ABSTRACT

Acetonitrile is a volatile liquid used primarily as a solvent in extractive distillation and crystallization of pharmaceutical and agricultural products. The potential for acetonitrile to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 100, 400, or 1200 ppm acetonitrile, 6 hours/day, 7 days a week. Each of the four treatment groups consisted of 10 non-pregnant females (for comparison), 10 positively mated females for a distribution study evaluating maternal blood for acetonitrile and cyanide, and ~33 positively mated females for evaluating developmental toxicity. Rats were exposed for 14 consecutive days (6-19 days of gestation [dg] for pregnant animals). The day of sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained on 20 dg. Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Acetonitrile and cyanide concentrations were determined in the maternal blood of the rats (~6/group) on 8 and 18 dg.

Exposure of rats to these concentrations of acetonitrile resulted in mortality in the 1200 ppm group (2133 pregnant females; 1/10 non-pregnant females), and the 400 ppm group (1/33 pregnant females). However, there were no treatment-related effects upon body weights or reproduction indices at any exposure level, nor was there a significant increase in the incidence of fetal malformations or variations. The only effect observed in the fetuses was a slight, but not statiscally significant, exposurecorrelated increase in the incidence of supernumerary ribs.

Determination of acetonitrile and cyanide concentrations in maternal rat blood showed that acetonitrile concentration in the blood increased with exposure concentration for all exposed maternal rats. Detectable amounts of cyanide in the blood were found only in the rats exposed to 1200 ppm acetonitrile (~2 micrograms of cyanide per gram of blood).

In summary, the two highest exposure concentrations were maternally lethal to some rats; however, there was no reduction in body weights, body weight gains, or clinical signs of toxicity in surviving pregnant or non-pregnant rats. The no-observable-adverse-effect-leveI (NOAEL) for acetonitrile with respect to developmental toxicity in this study was the highest exposure concentration, 1200 ppm. The maternal NOAEL was 100 ppm.

Report Date: February 1994

NTIS# DE94-008272

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