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KMID : 0379520070230040391
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한국독성학회지
2007 Volume.23 No. 4 p.391 ~ p.403
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Repeated Dose and Reproductive/Developmental Toxicities of Acetanilide in Rats
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Chung Moon-Koo
Baek Sung-Soo
Lee Sang-Hee
Kim Hyun-Mi
Choi Kyung-Hee
Han Sang-Seop
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Abstract
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The study was conducted to assess the repeated dose and reproduction and developmental toxicities of acetanilide, an intermediate for drug production, as a part of OECD Screening Information Data Set (SIDS) program. The test agent was administered by gavage at dose levels of 0, 22, 67, 200 and 600 ㎎/㎏ to Sprague-Dawley rats (12/group/sex) during pre-mating and mating period for males(up to 30 days) and females and pregnancy and early lactation period for females (up to 39~50 days). At 22 ㎎/㎏, decreases in HGB, HCT (males) and MCHC (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow (both sexes) were observed. At 67 ㎎/㎏, salivation (males), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC (males), increases in MCV (males) and spleen weight (males), hyperplasia of spleen red pulp and femur bone marrow (both sexes) were observed. At 200 ㎎/㎏, decreases in locomotor activity and salivation (both sexes), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and increases in MCV, MCH, BUN, T-BIL (males), enlargement of spleen (both sexes), increased weight of spleen (males), hyperplasia of spleen red pulp and femur bone marrow and extramedullary hematopoiesis of liver (both sexes), atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. At 600 ㎎/㎏, decreases in locomotor activity, cyanosis (both sexes), reddish tear, and salivation (males), mortality (4 out of 12 females), decreased body weight (females), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC and increases in WBC, MCV, MCH, reticulocyte, neutrophil, lymphocyte, monocyte, AST, ALT, BUN, T-BIL, ALB, Ca and A/G ratio (males), enlargement of spleen, increased weights of spleen (both sexes), liver (males), kidney and ovary, decreased weights of thymus (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow and extramedullary hematopoiesis of liver (both sexes), and atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. Regarding the reproduction and development toxicities, there were no treatment- related changes in precoital time, mating index, fertility index and pregnancy index at all doses tested. At 22 and 67 ㎎/㎏, there were no adverse effects on all the parameters observed. At 200 ㎎/㎏, decreased body weight of pups (day 4 p.p.) were observed. At 600 ㎎/㎏, decreased body weight of pups (day 0 and 4 p.p.) and viability index (day 4 p.p.), increased incidence of newborns dead or with abnormal clinical signs were observed. The results suggest that the NOAELs for general toxicity are ＜ 22 ㎎/㎏, LOAELs are 22 ㎎/㎏ and the NOAELs for reproductive toxicity are 67 ㎎/㎏.
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KEYWORD
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Acetanilide, Combined repeated dose toxicity study with the reproductive/developmental toxicity screening test, Rats
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