The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
Methacrylamide (MACR), a congener of acrylamide, was tested for reproductive toxicity, neurotoxicity, and dominant lethal effects in Swiss CD-1 mice using the Continuous Breeding protocol. MACR was one of a series of structural congeners chosen to represent a varying degrees of reproductive and neural toxicities. MACR was previously reported to have more neurotoxicity than reproductive toxicity. A dose-range-finding study was used to identify concentration levels that were expected to produce only slight neurotoxicity: 0, 24, 80, 240 ppm in drinking water for up to 27 weeks. Water consumption was unchanged by MACR; consumption of MACR was calculated at nearly equal to 4, 15, and 49 mg/kg for the F0 mice.
Methacrylamide induced no changes in fertility or pup endpoints at any dose in F0 animals. There were no treatment-related differences in body weights. Grip strength was variably changed, and significantly (12%) increased in males at wk 15. Consistent with the lack of reproductive effects in Task 2, MACR produced no change in the dominant lethal test after Task 2. In the absence of detectable effects on fertility endpoints, Task 3 (crossover mating to determine the affected sex) was not conducted. At necropsy, sperm concentration was reduced by 21% at 80 ppm, and sperm motility was reduced by nearly equal to 42% at 240 ppm.
In the F1 animals, there was slight neurotoxicity at pnd (post-natal day) 21, measured as decreases in forelimb grip strength in males (26% - 29%) and hindlimb grip strength (12 - 31%). These decrements in grip strength were not apparent by week 5, nor were they seen again as the animals matured. At cohabitation at nearly equal to pnd 74, male body weights were significantly reduced nearly equal to 5% in all treated groups. In the F1 mating trial, there were no treatment-related effects on any reproductive endpoint, nor were any necropsy endpoints meaningfully altered.
In summary, MACR at these concentrations was without effect on F0 body weights, neurotoxicity, or reproduction, and had only transient effects on body weight and grip strength in F1 mice, with no alterations in fertility of the F1's.