Limited lactational transfer of acrylamide to rat offspring on maternal oral administration during the gestation and lactation periods.
To evaluate the developmental exposure effects of acrylamide (ACR) on the nervous and male reproductive systems, pregnant Sprague-Dawley rats were given ACR at 0, 25, 50 or 100 ppm in the drinking water from gestational day 6 to postnatal day (PND) 21 and histopathological assessment was performed at PND 21. Exposure levels in offspring were examined by measurement of free ACR and hemoglobin (Hb)-ACR adducts on PND 14, and compared with maternal levels on PND 21. Additionally, a group of offspring that received ACR at 50 mg/kg by intraperitoneal injections directly three times a week from PND 2 to 21 was subjected to analysis for comparison with maternal exposure groups. Although maternal neurotoxicity was evident at 100 ppm, no changes suggestive of neurotoxicity or testicular toxicity were observed in their offspring except for growth retardation evident as lowered body weights. In contrast, offspring given ACR intraperitoneally exhibited obvious neurotoxicity, but not testicular damage. Free ACR in serum and milk was detected in neither dams nor their offspring. The level of ACR-Hb adducts in offspring was one tenth or less than that in dams. In summary, although preweaning rats have susceptibility to ACR-induced neurotoxicity, the internal level of ACR in offspring exposed through maternal oral administration is insufficient to induce neurotoxicity and testicular toxicity due to limited lactational transfer.
Takahashi
Miwa
M
Division of Pathology, National Institute of Health Sciences, Setagaya, Tokyo, Japan.
Shibutani
Makoto
M
Nakahigashi
Jun
J
Sakaguchi
Natsumi
N
Inoue
Kaoru
K
Morikawa
Tomomi
T
Yoshida
Midori
M
Nishikawa
Akiyoshi
A
D020106:Acrylamide / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D002531:Cerebellum / Q000187:drug effects; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007774:Lactation / Q000097:blood; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D008892:Milk / Q000737:chemistry; D009420:Nervous System / Q000187:drug effects*; D009498:Neurotoxins / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects; D012671:Seminiferous Tubules / Q000187:drug effects; D012668:Trigeminal Ganglion / Q000187:drug effects
D006454:Hemoglobins; D009498:Neurotoxins; D020106:Acrylamide