[Reproductive and developmental toxicity studies of tazobactam/piperacillin or tazobactam (2)--Teratological study in rats with intravenously administration].

Tazobactam (TAZ) is a newly developed beta-lactamase inhibitor and piperacillin (PIPC) is an antibiotics which is used in clinical field widely. The combination of TAZ and PIPC (TAZ/PIPC), which is combined with TAZ and PIPC at rate of 1:4, has been developed because of PIPC is unstable to various beta-lactamases. Teratogenic potential were studied in rats given daily intravenous doses of TAZ/PIPC (625, 1250, 2500 or 3750 mg/kg/day) or TAZ (125, 500 or 3000 mg/kg/day).

[Reproductive and developmental toxicity studies of tazobactam/piperacillin or tazobactam(1)--Fertility and general reproduction study in rats with intraperitoneal administration].

Tazobactam (TAZ) is a newly developed beta-lactamase inhibitor and piperacillin (PIPC) is an antibiotics which is used in clinical field widely. The combination of TAZ and PIPC (TAZ/PIPC), which is combined with TAZ and PIPC at rate of 1:4, has been developed because of PIPC is unstable to various beta-lactamases. Fertility and general reproductive performance were studied in rats given daily intraperitoneal doses of TAZ/PIPC (200, 800 or 1600 mg/kg/day) or TAZ (40, 160 or 640 mg/kg/day).

Behavioral evaluations in developmental toxicity testing: MARTA survey results.

During 1991, the Middle Atlantic Reproduction and Teratology Association (MARTA) conducted a survey of laboratories performing behavioral evaluations as part of GLP developmental toxicity studies. This survey was conducted to determine the extent to which an "industry standard" had evolved for behavioral test batteries. The most commonly used developmental parameters were eye opening, pinna unfolding, and sexual maturation (physical landmarks); surface righting, pupil constriction, and nonautomated acoustic startle (reflexive landmarks).

Critical developmental periods for effects on male rat genitalia induced by finasteride, a 5 alpha-reductase inhibitor.

The conversion of testosterone to 5 alpha-dihydrotestosterone by the enzyme 5 alpha-reductase is inhibited by finasteride. In a study in which maternal dosing with finasteride commenced on Gestational Day 15 and terminated on Postpartum Day 21, there were 13 and 27% decreases in anogenital distance of male pups on Postnatal Day 1 at 0.03 and 3 mg/kg/day, respectively.

Developmental variation of the diaphragm and liver in Fischer 344 rats.

The nature and frequency of a developmental variation of the diaphragm and liver in Fischer 344 rats are described. Totals of 20, 98 and 55 (25 for caesarean-sectioning and 30 for natural delivery) mated female rats were used for Experiments 1, 2, and 3, respectively. Each rat was intubated (gavage) with either an aqueous suspension of 0.

Currently used alternatives to the Chernoff-Kavlock short-term in vivo reproductive toxicity assay.

The Chernoff-Kavlock assay was initially designed to identify developmental toxins within a relatively short time frame, using a mammalian system. Although it has been used for initial prioritization of multiple agents studied concurrently or for dosage-range evaluations, it has not gained wide usage in a commercial setting. As proposed, use of the Chernoff-Kavlock assay in an industrial setting is relatively inefficient, in terms of animal usage and data produced, when compared with available alternative study designs.

Detection of prenatal effects on learning as a function of differential criteria.

The role of appropriate criteria for detecting prenatal effects on learning was evaluated in Crl:COBS CD (SD)BR rats using a two-choice spatial discrimination escape paradigm. Alcohol was the prenatal treatment, as it has been reported to produce learning deficits in rats. The offspring of dams which consumed either a lab chow diet or isocaloric liquid diets containing 0%, 17.

The effect of paternal alcohol consumption on fetal development in mice.

The purpose of this study was to evaluate the effect of chronic paternal alcohol consumption on fetal growth and development in C3H mice. Male mice were pair-fed isocaloric liquid diets containing either 30%, 20%, or 0% ethanol-derived calories, or given free access to lab chow. After four weeks of treatment, all males were allowed to mate with untreated females.

Effects of acute alcohol exposure during selected days of gestation in C3H mice.

This investigation was designed to evaluate the teratogenic potential of a single alcohol exposure on one of nine specific days of gestation using a mouse model. C3H mice were intubated with alcohol on either Day 7, 8, 9, 10, 11, 12, 14, 16, or 18 of pregnancy in a dose of 0.0, 2.

Alcohol sensitivity in female mice: effect of ovariectomy.

This study tested the hypothesis that decreased estrogen levels accomplished by removing the ovaries affect the response to acutely administered alcohol in female mice. Sensitivity to alcohol was measured in ovariectomized, sham-operated, and non-surgical control C3H/HEN mice. Each animal received an IP injection of alcohol (3.

Department of Psychology, State University of New York at Albany.

The effects of prenatal alcohol on learning and retention of passive avoidance and discriminated shock escape were examined in offspring of rats who consumed isocaloric liquid diets containing either 35, 17.5 or 0% ethanol derived calories (EDC) or lab chow during pregnancy. Alcohol exposed progeny required more trials to reach criterion during passive avoidance acquisition and had shorter second trail latencies into the shock compartment than did controls.

Decreased ethanol consumption as a function of pregnancy and lactation in C57BL mice.

The effects of pregnancy and lactation on alcohol consumption were examined in the C57BL mouse. Pregnant mice were given a two-bottle choice between water and 10% w/v alcohol solution from Day 5 of pregnancy, through two weeks of lactation, and an additional four weeks following the removal of nursing pups. Alcohol consumption was expressed in terms of g absolute ethanol per kg body weight and as an alcohol preference ratio (ml alcohol/ml total fluid).

Nose-poking and head-dipping behaviors in rats prenatally exposed to alcohol.

In three experiments pregnant female rats consumed liquid diets containing various amounts of the total calories in the form of ethanol. In the first study, offspring of these females were tested in a nose-poking paradigm. The frequency of this response was found to be a direct function of the level of alcohol exposure in utero.

Lack of response inhibition in rats prenatally exposed to alcohol.

Offspring of mothers who consumed either 32, 19, 8, or 0% of their daily caloric intake in the form of ethanol during pregnancy were tested for passive avoidance. At 18 days of age, the number of trials to criterion and the within-group variability were direct functions of the amount of ethanol consumed by the mother during pregnancy. At 41--53 days of age, alcohol-treated pups still required more trials to criterion than controls and had faster speeds into the shock compartment on the first trial.

Hypnotic susceptibility to various depressants in rats selected for differential ethanol sensitivity.

MA rats, bred for greater motor impairment following subhypnotic doses of ethanol, were found to be more sensitive to the hypnotic effects of phenobarbital and chloral hydrate than were LA rats. In addition, the previously reported finding of a difference between the two lines of rats in duration of loss of righting reflex following a hypnotic dose of ethanol was replicated. The results are discussed in terms of a phenotypic difference in central nervous systems sensitivity to a range of sedative-hypnotics.

Response perseveration in rats exposed to alcohol prenatally.

Pregnant female rats consumed liquid diets containing either 35, 17, or 0% of the total calories as ethanol. Offspring of these females were tested for spontaneous alternation at 21 days of age and for reversal learning in a T-maze shock-escape paradigm at 20--21 days of age. In the spontaneous alternation test, rats exposed to alcohol prenatally took more trials than controls to enter the goal compartment opposite to that initially entered.

Differential tolerance to pentobarbital in rats bred for differences in alcohol sensitivity.

Two lines of rats bred for differences in motor impairment following alcohol treatment were also found to be differentially affected by sodium pentobarbital in three experiments. The most affected (MA) animals, bred for sensitivity to alcohol, showed a decrement in stabilimeter activity at doses of 8 mg and 16 mg pentobarbital per kg body weight. The least affected (LA) animals, bred for insensivity to alcohol, were affected only by the higher dose, at which the resulting impairment was still less than that of the MA group.

Effects of initial tolerance on acquired tolerance to alcohol in two selectively bred rat strains.

The extent to which initial sensitivity to alcohol influences acquired tolerance was investigated in two selectively bred rat lines. These two lines have been selectively bred for differences in initial sensitivity to alcohol. The most affected (MA) line shows about a 90% reduction in motor activity following a 1.