Comparison of the dominant lethal effects of acrylonitrile and acrylamide in male Fischer 344 rats

Abstract

Acrylonitrile (ACN) and acrylamide (AA), structurally similar vinyl monomers, are both animal carcinogens. ACN is weakly mutagenic in bacteria and induces sister-chromatid exchange, unscheduled DNA synthesis and cell transformation in cells in culture. AA induces chromosomal aberrations in bone marrow, blood and germ cells in vivo, and dominant lethal mutations in the germ cells of male mice and rats. In the current study, the ability of AA and ACN to induce dominant lethal mutations in the germ cells of male Fischer 344 rats was compared. Three groups of 50 males were gavaged daily for 5 days with ACN (60 mg/kg in normal saline), AA (30 mg/kg in normal saline) or vehicle only; an additional group of 20 males received a single i.p. injection of 0.2 mg/kg triethylenemelamine (TEM) on the afternoon of day 5. Starting 1 day after exposure, each male was bred to one female per week for 4 weeks (TEM-exposed group) or 10 weeks (ACN, AA and control groups). Mating rates were reduced only during week 1 in the TEM-treated group; pregnancy rates were reduced only during week 2 in the AA-exposed group and week 4 in the TEM-treated group. Females were necropsied 13 days after the end of the appropriate mating week and the amount of pre- and post-implantation loss calculated. ACN treatment of male rats induced no increases in either pre- or post-implantation loss in females in any of the 10 weeks post-exposure examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Scientific Opinion on acrylamide in food

“…Based upon the concordance of tumour sites between AA and GA, it can be concluded that carcinogenic activity of AA is due to its metabolic conversion to GA. (2012). These previous evaluations referred to several studies reporting on the reproductive and developmental toxicity of orally administered AA Sakamoto and Hashimoto, 1986;Smith et al, 1986;Working et al, 1987;Sublet et al, 1989;Chapin et al, 1995;Tyl et al, 2000a,b). AA did not significantly affect mating performance in female rats, e.g.…”

Induction of micronuclei in bone marrow and sperm head abnormalities after combined exposure of mice to low doses of X-rays and acrylamide

“…A lower frequency of pregnant females obtained after exposure of spermatozoa to AA and X-rays + AA [14] can be compared to a higher frequency of sperm head abnormalities, because malformed spermatozoa are not able to fertilize. Also, the results of other AA studies suggest that the late spermatids and spermatozoa are the most susceptible to damage [13,15,17,[44][45][46] . In previous studies, a significant increase in micronucleus frequency in bone marrow was observed 24 h after treatment with 50-100 mg/kg bw of AA [4,6,7].…”

“…Several authors have found positive effects in micronucleus tests in spermatids of rodents [9][10][11][12]. AA causes dominant lethal mutations in mice [8,[13][14][15] and in rats [16,17], and produces increases in malformed sperm heads [18].…”

Carcinogenicity and Other Health Effects of Acrylonitrile with Reference to Occupational Exposure Limit.

“…Leonard et al (1981) 68) reported that AN had negative results in both micronucleus test using murine erythrocytes and dominant lethal test using germs cells from male mice. Working et al (1987) 69) also showed in dominant lethal test that oral administration to rats at dose levels up to 60 mg/ kg/day resulted in negative results.…”