Tyl R W, Gerhart J M, Myers C B, Marr M C, Brine D R, Gilliam A F, Seely J C, Derelanko M J, Rinehart W E
Research Triangle Institute, North Carolina, USA.
Fundam Appl Toxicol. 1996 Jun;31(2):149-61. doi: 10.1006/faat.1996.0086.
Methylethyl ketoxime (CAS No. 96-29-7; MEKO; 2-butanone oxime), an antioxidant agent used in paints, resins, and adhesives, was tested for reproductive toxicity in a two-generation study with CD (Sprague-Dawley) rats. Thirty-eight-week-old rats/sex/group (F0) were administered MEKO in water, by gavage, at 0, 10, 100, or 200 mg/kg/day (at a dosing volume of 2 ml/kg), 5 days/week for 10 weeks with vaginal cytology evaluation (VCE) of F0 females during the last 3 weeks of the prebreed period. Animals were mated within groups for 3 weeks with dosing during mating, gestation, and lactation for 7 days/week. F0 parents and F1 weanlings, 10/sex/dose, were necropsied (after a 2-week postwean VCE in F0 females) with hematologic evaluation (including methemoglobin) and histology of adult livers, spleens, and reproductive organs. F1 weanlings, 30/sex/dose, were dosed for 11 weeks and mated as described above. Because of poor reproductive performance, not treatment related, F1 animals with no F2a litters were rebred to produce F2b litters. F1 parents and F2a weanlings, 10/sex/dose, were necropsied and evaluated as described above. Inguinal mammary glands were examined histologically from all nonselected F1 and F2 (a and b) female weanlings. Adult toxicity was observed in both generations and both sexes at all doses. Treatment-related parental deaths occurred at 200 mg/kg/day. At 100 and 200 mg/kg/day, parents exhibited dose-related reduced body weights and weight gains, reduced feed consumption, clinical signs of toxicity, and anemia with concomitant extramedullary hematopoiesis and hemosiderosis in livers and spleens (and increased spleen weights). At 10 mg/kg/day, only adult liver and spleen histologic effects were present. There was no evidence of reproductive organ or mammary glad pathology or of reproductive or postnatal toxicity at any dose tested. There was no adult "no observable adverse effect level" (NOAEL) established; the NOAEL for reproductive and postnatal toxicity was at least 200 mg/kg/day for rats in this study.
甲乙酮肟（化学物质登记号：96 - 29 - 7；MEKO；2 - 丁酮肟）是一种用于涂料、树脂和粘合剂的抗氧化剂，在一项对CD（斯普拉格 - 道利）大鼠进行的两代研究中测试了其生殖毒性。38周龄的大鼠/每组/性别（F0）通过灌胃给予水中的MEKO，剂量为0、10、100或200毫克/千克/天（给药体积为2毫升/千克），每周5天，共10周，在繁殖前期的最后3周对F0雌性大鼠进行阴道细胞学评估（VCE）。动物在组内交配3周，交配、妊娠和哺乳期每周给药7天。F0亲代和F1断奶仔鼠，每组/性别/剂量10只，进行尸检（F0雌性大鼠断奶后2周进行VCE），包括血液学评估（包括高铁血红蛋白）以及对成年肝脏、脾脏和生殖器官进行组织学检查。F1断奶仔鼠，每组/性别/剂量30只，给药11周并按上述方法交配。由于生殖性能不佳（与处理无关），没有F2a窝仔的F1动物重新繁殖以产生F2b窝仔。F1亲代和F2a断奶仔鼠，每组/性别/剂量10只，进行尸检并按上述方法评估。对所有未选的F1和F2（a和b）雌性断奶仔鼠的腹股沟乳腺进行组织学检查。在所有剂量下，两代雌雄动物均观察到成年毒性。在200毫克/千克/天出现与处理相关的亲代死亡。在100和200毫克/千克/天，亲代出现剂量相关的体重减轻和体重增加减少、饲料消耗减少、毒性临床症状以及贫血，同时肝脏和脾脏出现髓外造血和含铁血黄素沉着（脾脏重量增加）。在10毫克/千克/天，仅出现成年肝脏和脾脏的组织学效应。在任何测试剂量下均未发现生殖器官或乳腺病理学证据，也未发现生殖或产后毒性。未确定成年动物的“无可见不良反应水平”（NOAEL）；本研究中大鼠生殖和产后毒性的NOAEL至少为200毫克/千克/天。
