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Table 1.
Tumor incidence in male and female Sprague-Dawley rats exposed to acrylonitrile by
inhalation (Maltoni et al., 1977)
Tumor type
Tumor incidence
Acrylonitrile concentration (ppm)
0 5 10 20 40
mammary tumors (females) 5/30 10/30 7/30 10/30 7/30
mammary tumors (males) 1/30 0/30 1/30 4/30 4/30
nonglandular forestomach papillomas (males) 0/30 1/30 2/30 0/30 3/30
skin carcinomas (females) 0/30 4/30 1/30 1/30 1/30
The authors claimed that these results indicated a “border-line carcinogenic effect”. US EPA (1983)
noted that low sensitivity of this study due to the low concentrations of acrylonitrile used and the short
duration of acrylonitrile exposure (12 months). Additionally, male and female Sprague-Dawley rats
(40/sex/group) were exposed to 0 or 5 mg/kg body weight acrylonitrile by gavage 3 times/week for 52
weeks. On spontaneous death, a moderate increase in the incidence of female rat mammary gland
tumors and nonglandular forestomach tumors was noted. US EPA (1983) commented that although the
observation period was relatively short (52 weeks) and only a single dose level was used, this study
provides additional evidence for the carcinogenicity of acrylonitrile.
A three-generation reproductive study on the effect of acrylonitrile exposure in male and female Charles
River rats [CRL:COBS CD (SD) BR] was conducted by Litton-Bionetics, Inc. for the Chemical
Manufacturers Association (Beliles et al., 1980; reviewed by US EPA, 1983). The rats and their
offspring were exposed to drinking water containing 0, 100 or 500 ppm acrylonitrile starting 15 days
post-weaning and were mated after 100 days. After delivery of two litters, the animals were exposed
to acrylonitrile for approximately 45 weeks. After exposure, all animals in generations F 0 , F 1 b and F 2 b
were sacrificed and examined histologically. Second-generation rats in the 500 ppm exposure group
demonstrated a significant increase in the incidence of astrocytomas and Zymbal gland tumors. Tumor
incidence data are listed in Table 2.
Table 2.
Tumor incidence data in Charles River rats during a three-generation reproductive
study (Beliles et al., 1980)
Tumor type Generation Tumor incidence
Acrylonitrile dose (ppm)
0 100 500
astrocytomas F 0 0/19 1/20 2/25
F 1 b 0/20 1/19 4/17
F 2 b 0/20 1/20 1/20
Zymbal gland F 0 0/19 0/20 1/25
F 1 b 0/20 2/19 4/17
F 2 b 0/20 0/20 3/20
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