Grizzle T B, George J D, Fail P A, Seely J C, Heindel J J
Research Triangle Institute, Research Triangle Park, North Carolina 27709.
Fundam Appl Toxicol. 1994 Jan;22(1):122-9. doi: 10.1006/faat.1994.1015.
4-Vinylcyclohexene (VCH), a dimer of 1,3-butadiene, was evaluated for reproductive toxicity in Swiss (CD-1) mice using the continuous breeding protocol (NTP, 1989). VCH in corn oil was administered by gavage at doses of 0, 100, 250, and 500 mg/kg/day to animals that were housed in same sex pairs for 1 week and then cohabited in breeding pairs for 14 weeks. During cohabitation, newborn litters were euthanized immediately after evaluation on postnatal Day (PND) 0. Litters born after Week 15 were reared until PND 21, when all F0 animals and low- and mid-dose F1 weanlings were humanely killed without a necropsy. At PND 74 +/- 10, control and high-dose F1 animals were cohabited within groups for 1 week and necropsied after delivery of the litters. In F0 breeding pairs, VCH did not affect measures of reproductive competence, including initial fertility, litters per pair, live litter size, or the proportion of pups born alive. Pup weight was decreased (4%) in the high-dose group relative to controls. High-dose F0 females exhibited slight general toxicity, manifested as an 8% difference in body weight compared to controls. VCH did not adversely affect preweaning growth or survival in the F1 generation. VCH had no effect on the reproductive competence of the F1 generation. High-dose F1 adult males and females had decreased body weight. At necropsy, increased relative liver weight (males 9% and females 8%) and sperm motility (although not thought to be biologically significant) were observed in the 500 mg/kg VCH group.(ABSTRACT TRUNCATED AT 250 WORDS)
4-乙烯基环己烯(VCH)是1,3-丁二烯的二聚体,采用连续繁殖方案在瑞士(CD-1)小鼠中评估其生殖毒性(NTP,1989)。将玉米油中的VCH以0、100、250和500 mg/kg/天的剂量通过灌胃给予动物,这些动物先按同性配对饲养1周,然后按繁殖对同居14周。在同居期间,新生仔鼠在出生后第0天评估后立即安乐死。第15周后出生的仔鼠饲养至出生后第21天,此时所有F0动物以及低剂量和中剂量F1断奶仔鼠被人道处死,未进行尸检。在出生后第74±10天,对照组和高剂量F1动物在组内同居1周,产仔后进行尸检。在F0繁殖对中,VCH不影响生殖能力指标,包括初始生育力、每对产仔数、活仔数或活产幼崽比例。高剂量组幼崽体重相对于对照组下降了4%。高剂量F0雌性表现出轻微的全身毒性,表现为体重与对照组相比有8%的差异。VCH对F1代断奶前的生长或存活没有不利影响。VCH对F1代的生殖能力没有影响。高剂量F1成年雄性和雌性体重下降。尸检时,在500 mg/kg VCH组中观察到相对肝脏重量增加(雄性9%,雌性8%)和精子活力增加(尽管认为无生物学意义)。(摘要截断于250字)