Thompson D J, Dyke I L, Molello J A
Toxicol Appl Pharmacol. 1984 Feb;72(2):245-54. doi: 10.1016/0041-008x(84)90309-0.
The antineoplastic drug hexamethylmelamine (HMM) was evaluated for effects on reproduction and postnatal development in the rat and on embryonal and fetal development in the rat and rabbit. Daily po treatment of male rats for 62 days with doses of 0, 10, 20, or 40 mg/kg/day resulted in testicular atrophy, reduced fertility, and a possible dominant lethal mutagenic effect at the higher two dose levels. Alterations in morphology and function of the beta cells of the pancreatic islets were observed after treatment of males for more than 28 days with 20 or 40 mg/kg/day. The same dose levels administered to female rats for 14 days prior to breeding and through Day 13 or 20 of gestation had no adverse effects on fertility, but the highest dose was embryocidal and postnatal survival was decreased at both the 20- and 40-mg/kg/day dose levels. Similar effects on postnatal survival were observed when the drug was administered by gavage to rats during the last week of gestation and throughout the lactation period. Treatment of pregnant rats throughout organogenesis (Days 6 to 15) or for 4-day intervals during organogenesis (Days 6 to 9, 9 to 12, or 12 to 15) with po doses ranging from 20 to 80 mg/kg/day resulted in decreased body weight gain and food consumption, an increased resorption rate in dams receiving 80 mg/kg/day on Days 6 to 9, and decreased fetal weights at all dose levels and most treatment intervals. The incidence of minor skeletal defects was increased among litters of HMM-treated groups. Major fetal malformations were limited in number but were considered treatment related. Treatment of pregnant rabbits po on Days 6 to 18 of gestation with doses of 0, 20, 40, or 60 mg/kg/day did not result in an embryocidal or teratogenic effect. Treatment with 60 mg/kg/day did, however, result in decreased kit weights, indicating a mild embryo-fetotoxic effect.
对抗肿瘤药物六甲蜜胺（HMM）进行了评估，观察其对大鼠生殖及出生后发育以及对大鼠和家兔胚胎及胎儿发育的影响。雄性大鼠每日经口给药，剂量分别为0、10、20或40mg/kg/天，持续62天，结果显示在较高的两个剂量水平下出现睾丸萎缩、生育力下降以及可能的显性致死诱变效应。雄性大鼠用20或40mg/kg/天处理超过28天后，观察到胰岛β细胞的形态和功能发生改变。在雌性大鼠交配前14天及整个妊娠期的第13天或第20天给予相同剂量水平的药物，对生育力没有不良影响，但最高剂量具有胚胎毒性，在20和40mg/kg/天剂量水平下出生后的存活率均降低。在妊娠最后一周及整个哺乳期经口灌胃给予该药物时，对出生后的存活率也观察到类似影响。在整个器官形成期（第6至15天）或在器官形成期内每隔4天（第6至9天、第9至12天或第12至15天）给怀孕大鼠经口给药，剂量范围为20至80mg/kg/天，结果导致体重增加和食物摄入量减少，在第6至9天接受80mg/kg/天的母鼠中吸收率增加，在所有剂量水平和大多数处理间隔下胎儿体重均降低。六甲蜜胺处理组的窝仔中轻微骨骼缺陷的发生率增加。严重的胎儿畸形数量有限，但被认为与治疗有关。在妊娠第6至18天给怀孕家兔经口给药，剂量分别为0、20、40或60mg/kg/天，未产生胚胎毒性或致畸作用。然而，60mg/kg/天的处理确实导致仔兔体重下降，表明有轻微的胚胎 - 胎儿毒性作用。
