ToxSci Advance Access originally published online on August 13, 2004
Toxicological Sciences 2004 82(1):237-249; doi:10.1093/toxsci/kfh249
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Toxicological Sciences vol. 82 no. 1 © Society of Toxicology 2004; all rights reserved.
The Effects of Feed Restriction during in Utero and Postnatal Development in Rats
Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan 48674
Received April 15, 2004; accepted June 24, 2004
This study determined the effects of feed restriction (FR) during in utero and postnatal life on standard reproductive toxicity and developmental immunotoxicity end points. Groups of 26 time-mated CD rats were fed various amounts of Purina 5002 diet from gestation day 7 through lactation. Control rats were fed once per day in amounts based on historical control feed consumption data, while the amounts fed to the FR groups were reduced by 10% (10% FR), 30% (30% FR), or 50% (50% FR) relative to controls. Selected F1 weanlings were necropsied on postnatal day (PND) 22, assessed for immunotoxicity end points between PND 22 and 27 or PND 52 and 56, or maintained on FR through PND 70. Thereafter, half the remaining F1 rats in each group were fed ad lib (recovery subgroup), while the rest continued on FR. Both subgroups were necropsied at 21 weeks of age. In the 10% FR group, slight decreases in maternal body weight had no effect on F1 offspring body weights, but did decrease F1 liver weights. FR at the 30% level reduced maternal body weights by 10–20%, reduced F1 offspring body weights by as much as 21%, caused changes in numerous weanling organ weights, but did not affect reproductive or immune system function. Dams in the 50% FR group were 17–32% lighter than controls, resulting in F1 body weights that were 12–47% lower than controls. F1 estrous cycle length was increased, puberty was delayed by 6 days (males and females), and anogenital distance, epididymal sperm counts, and all organ weights were decreased in this group. Antibody responses were unaffected despite decreased spleen and thymus weights. Essentially all effects of feed restriction showed evidence of reversibility.
Key Words: reproductive toxicity; developmental toxicity; maternal toxicity; developmental immunotoxicity.
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