methylcellulose and Abnormalities--Drug-Induced

A series of studies were conducted to assess Polysorbate 80 (PS80), Propylene Glycol (PG), and Hydroxypropyl-β-Cyclodextrin (HPβCD), when compared with Hydroxypropyl Methylcellulose (MC) in developmental and reproductive toxicology (DART) studies.. In the rat fertility study, 20 mg/kg MC, 10 mg/kg PS80, 1,000 mg/kg PG, 500 mg/kg HPβCD or 1,000 mg/kg HPβCD were administered orally before/during mating, and on gestation Day (GD) 0-7, followed by an assessment of embryonic development on GD 14. In the rat and rabbit teratology studies, the doses of MC, PS80, PG, and HPβCD were the same as those in the fertility study. In these teratology studies, pregnant females were dosed during the period of organogenesis, followed by an assessment of fetal external, visceral, and skeletal development.. In the rat fertility and rat teratology studies, PS80, PG, and HPβCD did not exhibit toxicity, when compared with MC. Similarly, in the rabbit teratology study, there was no PS80 or PG-related toxicity, when compared with MC. However, individual rabbits in the 500 and 1,000 mg/kg HPβCD groups exhibited maternal toxicity, which included stool findings, decreased food consumption, and body weight gain. Furthermore, one rabbit each in the 500 and 1,000 mg/kg HPβCD groups exhibited evidence of abortion, which was considered secondary to maternal toxicity.. Although HPβCD was not well tolerated in rabbits at doses of 500 and 1,000 mg/kg, PS80 and PG were comparable to MC and should be considered for use in developmental and reproductive toxicology studies.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Abnormalities, Drug-Induced; Animals; beta-Cyclodextrins; Dose-Response Relationship, Drug; Eating; Embryo, Mammalian; Female; Hypromellose Derivatives; Methylcellulose; Pharmaceutical Vehicles; Polysorbates; Pregnancy; Propylene Glycol; Rabbits; Rats; Reproduction; Toxicity Tests; Weight Gain

A teratogenicity study was carried out in S1c: SD rats orally administered Hydroxypropylmethylcellulose acetate succinate (HPMCAS), a useful pharmaceutical excipient, at dose levels of 625, 1,250 and 2,500 mg/kg/day for a period of 11 days from day 7 to day 17 of gestation. Two-thirds of the pregnant females in each group were sacrificed on Day 21 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and the postnatal development of the offsprings was observed. The incidences of external, internal, and skeletal anomalies were not significantly increased in the fetuses of any treated groups. HPMCAS caused no effects on parturition, lactation, postnatal growth and reproductive ability of the male and female offspring.

Topics: Abnormalities, Drug-Induced; Administration, Oral; Animals; Body Weight; Bone and Bones; Drinking; Eating; Female; Fetus; Hypromellose Derivatives; Male; Methylcellulose; Organ Size; Pregnancy; Rats; Rats, Inbred Strains; Reproduction; Weaning

A teratological study was carried out in New Zealand White rabbits in order to examine the teratogenic potentiality of HPMCAS, a useful pharmaceutical excipient. HPMCAS was orally administered at dose levels of 625, 1,250 and 2,500 mg/kg/day for a period of 13 days from day 6 to day 18 of gestation. All pregnant females were sacrificed on day 29 of gestation and their fetuses were examined. The administration of HPMCAS during a period of organogenesis produced no embryotoxic and teratogenic effects as well as no influence on behavior, appearance and growth of animals.

Topics: Abnormalities, Drug-Induced; Administration, Oral; Animals; Body Weight; Bone and Bones; Drinking; Eating; Female; Fetus; Methylcellulose; Pregnancy; Rabbits

Topics: Abnormalities, Drug-Induced; Animals; Anti-Infective Agents, Local; Bone and Bones; Carbamates; Cricetinae; Dimethyl Sulfoxide; Disulfiram; Embryo, Mammalian; Female; Fetal Death; Fetus; Guinea Pigs; Methylcellulose; Naphthalenes; Organophosphonates; Pesticides; Pregnancy; Pyrimidines; Rabbits; Thiocarbamates; Thiram; Urea

Topics: Abnormalities, Drug-Induced; Animals; Female; Fetal Death; Male; Maternal-Fetal Exchange; Methylcellulose; Mice; Phenobarbital; Phenytoin; Pregnancy; Pregnancy Complications; Thalidomide; Thioridazine; Tranquilizing Agents; Urethane