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Biomedical subjects

N Chernoff

Publications and source records attributed to N Chernoff.

At least 55 records · Page 3Linked to original sources
PubMed1982

An analysis of fetotoxicity using biochemical endpoints of organ differentiation.

The biochemical differentiation of the brain, lungs, liver, and kidneys of the late gestation rat fetus was examined to characterize the immediate implications of retarded growth on fetal development. Initially, the normative profile of development of the brain (weight, DNA content, and protein content), lungs (weight and surfactant accumulation), liver (weight and glycogen deposition), and kidneys (weight, alkaline phosphatase activity, and protein content) was determined on gestation days 19, 20, 21, and 22 (day 1 = finding of sperm in the vaginal smear). Subsequently, five compounds known to induce fetotoxicity (chlorambucil, methyl salicylate, mirex, nitrofen, and toxaphene) were administered during organogenesis, and the effects on organ differentiation were determined in day 21 fetuses. The effects of fetal growth retardation resulting from exposure to exogenous agents were not equally distributed among the organs studied. The liver and kidney appeared more sensitive to insult by these agents than did the brain and lungs.

Animals↗
PubMed1981

Perinatal toxicity of endrin in rodents. II. Fetotoxic effects of prenatal exposure in rats and mice.

The fetotoxic potential of endrin in the CD rat and CD-1 mouse was investigated. Endrin was administered as a solution in corn oil to groups of pregnant animals by gastric intubation at multiple dose levels throughout the period of organogenesis. The dams were sacrificed prior to term and the fetuses were examined for skeletal and visceral anomalies. In addition, maternal livers and fetuses from rats in each dose level were analyzed for endrin content. In the mouse, endrin caused maternal liver enlargement at a dose of 0.5 mg/kg/day and reduced maternal weight gain at a dose of 1.0 mg/kg/day. Fetal weight and skeletal and visceral maturity were adversely affected at a dose of 1.0 mg/kg/day, but no teratogenic effect or embryo lethality was evident even at a dose level that produced maternal lethality (1.5 mg/kg/day). In the rat, endrin markedly reduced maternal weight at doses above 0.150 mg/kg/day but produced no apparent effects on the fetus. The data suggest that species differences in sensitivity to endrin may in part be due to differences in metabolism. Although endrin levels in rat fetuses at a maximally tolerated dosage level resembled those previously reported for the hamster, relatively less 12-ketoendrin was present, paralleling the change in fetal sensitivity.

Animals↗
PubMed1981

Perinatal toxicity of endrin in rodents. III. Alterations of behavioral ontogeny.

The behavioral development of rats and hamsters was observed following perinatal exposure to endrin, a central nervous system teratogen in the hamster but not the rat [1,2]. In the hamster, prenatal exposure to endrin at 1.5 mg/kg/day on days 5-14 of gestation produced a persistent elevation in the locomotor activity. Offspring of treated hamsters ambulated 75% more than controls in the open field at 15 days and 45% more at 20 days of age. Long term observations of locomotor activity in the figure-8 mazes indicated that a significant elevation of this behavior was still present at 125 days of age. Non-locomotor behaviors of the Offspring (including sexual, rearing and running wheel behaviors) were unaffected. The dams repeatedly exposed daily to endrin at 0.75 or 1.5 mg/kg/day were markedly hypoactive using the same testing conditions in which the pups were hyperactive. This dosing regime was toxic to the dams in the 1.5 mg/kg/day dose group, killing more than half of them. In the second experiment, rats exposed perinatally to endrin at 0.15 or 0.30 mg/kg/day were 30% more active than control prior to weaning, but not as adults. These doses did not kill dams or affect the pup survival or growth. The similarity of the behavioral changes noted in the young of both species is suggestive of similar alteration of central nervous system function even though endrin produces gross morphological defects only in the hamster.

Aging↗
PubMed1981

Histopathologic lens changes in mirex-exposed rats.

The early histologic lesions and sequential changes in the development of mirex-induced cataracts were studied in the offspring of lactating female Sherman rats given oral doses of mirex for 5 consecutive days post partum. The earliest histologic change, seen at neonatal day 7, was slight swelling of the individual cortical lens fibers. At day 9, many swollen but intact fibers were observed, and at days 11 and 13, extensive degeneration and necrosis appeared throughout the cortex of the affected lenses.

Animals↗
PubMed1981

Multigeneration study of 1,2,4-trichlorobenzene in rats.

Rats were continuously exposed to 0, 25, 100, or 400 ppm 1,2,4-trichlorobenzene (TCB) in the drinking water, beginning with birth of the F0 generation and continuing through weaning of the F2 generation. The treatment did not affect fertility, growth, viability, locomotor activity, or blood chemical analysis. Adrenal gland enlargement was observed in both the F0 and F1 animals at 95 d of age. To further examine the adrenal enlargement found in the reproduction study, an acute toxicity study was undertaken in which immature females were given ip injections of 0, 250, or 500 mg/kg TCB on 3 consecutive days. It was found that TCB had no estrogenic activity and that the livers and adrenals of treated females were significantly larger than those of controls. Rather than being estrogenic, TCB in this treatment regimen resulted in a decrease in uterine weight. These two studies demonstrate that chronic or acute doses of TCB can produce adrenal enlargement in rats.

Adrenal Glands↗
PubMed1981

The teratogenic potential of cacodylic acid in the rat and mouse.

Cacodylic acid, an organic arsenical herbicide, was administered to time-pregnant albino CD rats and CD-1 mice on days 7-16 of gestation. The compound was given by gastric intubation as a solution in distilled water. Rats received 0, 7.5, 15, 30, 40, 50, or 60 mg/kg/day in 0.2 ml/day intubation volume; mice received 0, 200, 400, or 600 mg/kg/day in 0.1 ml/day. Following maternal sacrifice on day 18 (mice) and 21 (rats), fetuses were weighed and fixed for skeletal and visceral examinations. Fetal and maternal toxicity was observed in both species. In the mouse, maternal toxicity was evident at the lowest dose, while teratogenic response was confined to cleft palate at 400 and 600 mg/kg/day. The effective maternal toxic dose in the rat was 40 mg/kg/day. In this species, incidence of irregular palatine rugae, i.e., ridges that were discontinuous and/or not lying in apposition at the palatal raphe, was significantly (p less than 0.001) dose-related. The results suggest an "apparent no effect level" for this anomaly below 30 mg/kg/day.

Animals↗
PubMed1980

Developmental toxicity of guthion in rats and mice.

The purpose of this study was to assess the effects of Guthion, a pesticide with anticholinesterase activity, on development in rats and mice. A preliminary toxicity study with Guthion indicated that a 35-day LD50 dose for virgin rats and a 10-day LD50 dose for virgin mice was between 4 and 8 mg/kg/day for both species. On the basis of these data, doses of 0, 1.25, 2.5, and 5.0 mg/kg/day were selected for the developmental study, which consisted of two phases. During the first phase, pregnant rats and mice were treated for 10 days starting on gestational day 6. The high dose affected maternal welfare only in rats. Guthion did not significantly increase in a dose-related manner any of the specific anomalies observed in either rats or mice. During the second phase, pregnant rats were treated from gestational day 6 to postpartum day 21. Dams in the high dose group were more sensitive to Guthion later in gestation with the result that deaths and signs of anticholinesterase toxicity increased during this time. Guthion also adversely affected maternal welfare in this group. As a result of Guthion toxicity, only one litter survived until weaning. The inability to dissociate toxicity in adult and developing animals suggests that Guthion has little primary effect on the development of rats or mice.

Abnormalities, Drug-Induced↗
PubMed1979

The fetotoxic potential of municipal drinking water in the mouse.

Mice (CD-1 strain) were placed on diets containing either municipal drinking water (Durham, North Carolina) or water that had been distilled and passed through cartridges to reduce organics and remove inorganics. After a two-week acclimation period, animals were bred and pregnancy confirmed by the presence of a sperm plug. During the 8-month course of the study, approximately 500 pregnant mice were sacrificed on day 18 of gestation and their fetuses examined for visceral and skeletal anomalies. No significant water-related effects were found on any fetal parameter studied except for a 28.1% incidence of supernumerary ribs in the tap-water group as compared to 21.1% in the purified-water group. No differences were noted in the type or occurrence of anomalies between the two groups. A month to month variation was observed in a number of parameters. The degree of variation was similar for the treatment groups, suggesting that these changes might be random fluctuations.

Abnormalities, Drug-Induced↗
PubMed1979

Perinatal toxicity of maneb, ethylene thiourea, and ethylenebisisothiocyanate sulfide in rodents.

The potential of the fungicide maneb and two of its metabolites, ethylenebisisothiocyanate sulfide (EBIS) and ethylene thiourea (ETU), to induce perinatal toxicity in four species of rodents was investigated. The compounds were admininistered to rats and mice during the period of organogenesis, and ETU was also administered to rats and mice during the period of organogenesis, and ETU was also administered by oral gavage for a similar period to hamsters and guinea pigs. Treatment also continued through the lactational period in groups of rats that were allowed to give birth. Fetuses were examined for signs of toxicity, including terata, and neonates for reflex developement and open-field behavior. Maneb produced hydrocephalus in fetuses in litters of rats receiving 480 mg/kg . d. No fetotoxic effects were noted in litters of rats receiving EBIS at doses at high as 30 mg/kg . d. ETU proved to be a potent teratogen in the rat. Among the effects seen at doses of 40 mg/kg . d or greater were hydrocephalus, encephalocele, kyphosis, and various defects of the digits. Neither maneb (up to 1500 mg/kg . d), ETU (up to 200 mg/kg . d), nor EBIS (up to 200 mg/kg . d) elicited signs of fetal toxicity in the mouse. ETU also failed to result in fetal toxicity when administered to the hamster (100 mg/kg . d) or the guinea pig (100 mg/kg . d). Neither maneb nor EBIS produced significant dose-related alterations in the behavioral development of perinatally exposed rat neonates. At doses that also produced neonatal hydrocephalus, ETU produced significant increases in the open-field activity of the neonates. In addition to the perinatal effects noted above, both maneb and EBIS caused maternal limb paralysis in the rat, an effect not noted in the mouse at much higher doses.

Abnormalities, Drug-Induced↗
PubMed1977

Disposition of 14C and/or 74As-cacodylic acid in rats after intravenous, intratracheal, or peroral administration.

The distribution, excretion, and possible metabolism of (14)C- and/or (74)As-cacodylic acid, an organoarsenical herbicide, was studied in rats following a single intravenous injection, intratracheal instillation or oral gavage. Male Sherman rats were dosed at levels ranging from 200 mg/kg to 120 mug/kg. The extent and rate of lung absorption was greater than gastrointestinal absorption. Concentrations in the liver and whole blood were higher after peroral dosing than intravenous administration. Levels observed in plasma and other tissues were similar after all three routes following the absorptive phase. The percent dose found in the whole blood, red blood cells, and plasma was similar for all doses given by these routes. Less than 0.1(1/2) of the administered dose was recovered as (14)CO(2) by any route at 24 hr after administration. Twenty-four hours after intravenous, intratracheal, and peroral administration, 71, 60, and 25%, respectively, was excreted in the urine. After intravenous administration of 200 mg/kg, sufficient (14)C-cacodylic acid was recovered in bile to account for the small amount excreted in the feces. Cacodylic acid is probably not metabolized to inorganic arsenic since the disposition of (14)C and (74)As-cacodylic acid were identical.Kinetic analyses of the plasma curve for (14)C-cacodylic acid (high dose) yielded three half-times; 0.014, 0.214 and 3.42 hr with an apparent volume of distribution of 15.3 ml. Highest initial concentrations were found in the whole blood, muscle, kidney, liver and lung. Levels in all tissues decreased rapidly, but remained high in whole blood. The red blood cells were found to be the major site of body burden of cacodylic acid.

Absorption↗