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Biomedical subjects

R J Kavlock

Publications and source records attributed to R J Kavlock.

At least 127 records · Page 7Linked to original sources
PubMed1983

The effects of the herbicide 2,4-dichlorophenyl-p-nitrophenyl ether (NIT) on serum thyroid hormones in adult female mice.

The administration of the herbicide 2,4-dichlorophenyl-p-nitrophenyl ether (nitrofen; NIT) to adult female mice by i.p. injection at doses of 500 and 1000 mg/kg/day for 3 days, reduced serum thyroxine (T4) levels. T4 levels were reduced in the high-dosage group by 60% of the control and by 20% in the low-dose group. Serum triiodothyronine (T3) levels were relatively unaffected by NIT treatment at either dose. The animals appeared euthyroid, as body weights were unaffected even though T4 levels were reduced. Liver weights were slightly higher as a result of NIT exposure at both 500 and 1000 mg/kg/day.

Animals↗
PubMed1983

Morphometric, biochemical, and physiological assessment of perinatally induced renal dysfunction.

Three chemicals, known either to alter renal development when administered during fetal development or to affect renal function when administered to adult rats, were administered to Sprague-Dawley rats at critical periods of renal development. Chlorambucil (CHL) was administered ip on d 11 of gestation at doses of 0, 3, and 6 mg/kg; nitrofen (2,4-dichlorophenyl p-nitrophenyl ether) (NIT) was given po on d 8-16 of gestation at 0, 4.17, 12.5, and 25 mg/kg . d; and mercuric chloride (MER) was given sc on postnatal d 1 at 0, 14, and 28 micrograms/pup. To assess the effects of these toxicants on the functional development of the kidneys, a diuresis test with and without antidiuretic hormone was applied on postnatal d 3 (PD 3); a hydropenia test on PD 6; and kidney weights, glomerular counts in midhilar cross sections, and the specific activity of renal alkaline phosphatase were determined on PD 3 and 6. Data from pups with obvious malformations of the kidneys was eliminated from the statistical analyses of the data so that emphasis could be placed on alterations of functional development in individuals with apparently morphologically normal kidneys. CHL retarded the growth and biochemical differentiation of the kidney at 6 mg/kg. Pups from this treatment groups showed an attenuated response to exogenously administered antidiuretic hormone. NIT impaired growth and altered renal morphology at a dose of 12.5 mg/kg . d and altered physiological responses in the absence of anatomical changes at a dose of 4.17 mg/kg . d. MER, at doses near the maximum tolerated, failed to alter any parameter, indicating that the very young animal differs markedly from the adult in response to that compound. The data indicate that relatively simple tests of renal function are useful in the detection of perinatally induced nephrotoxicity.

Age Factors↗
PubMed1983

Effects of prenatal nitrofen exposure on postnatal lung function in the rat.

The herbicide Nitrofen was administered by gavage to pregnant F-344 rats during Days 10 through 13 of gestation. Postnatal lung function was measured in male progeny at 3 and 6 weeks of age. There were no differences in body weight or wet and dry lung weights between control and Nitrofen-exposed rats in either age group. Nitrofen produced no observable effects on lung function at 3 weeks of age. However, by 6 weeks of age the Nitrofen-exposed animals had significant decreases in tidal volume (p less than 0.01), vital capacity (p less than 0.01), total lung capacity (p less than 0.05), and quasi-static lung compliance (p less than 0.01). There was also a mild ventilation inhomogeneity, as indicated by significant increases in the nitrogen washout slope (p less than 0.01) and the moment ratio (p less than 0.05). Histopathology of lung, liver, kidney, and testes was not significantly altered by Nitrofen exposure. These data suggest that prenatal Nitrofen exposure may have an effect on postnatal lung maturation in the rat and could potentially be useful as a model of pulmonary hypoplasia.

Aging↗
PubMed1982

Prenatal exposure to the herbicide 2,4-dichlorophenyl-p-nitrophenyl ether destroys the rodent Harderian gland.

Exposure of mice to the herbicide 2,4-dichlorophenyl-p-nitrophenyl ether during gestation produces abnormalities that are not readily apparent at birth but become obvious as the pups mature. By 2 weeks after birth there are severe intraorbital defects resulting from destruction of the Harderian glands behind the eyes. This effect is noticeable only postnatally because the Harderian gland does not grow or function until after birth.

Abnormalities, Drug-Induced↗
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↗
PubMed1982

Evaluation of renal function in neonatal rats.

The ontogenetic profile of several parameters of neonatal renal development in the rat is presented. Nephrogenesis was observed to continue at a rapid pace between birth and 8 days of age and to be virtually complete by 11 days of age. The activity of alkaline phosphatase, a brush border enzyme, declined during this time period relative to organ growth as a whole. The ability to elaborate a concentrated urine when presented with a period of fluid deprivation was barely present at birth and increased dramatically with age. Finally, the diuresis response to an orally administered water load was detected on the second postnatal day, while the response to antidiuretic hormones was present to a slight degree on the first postnatal day.

Age Factors↗
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

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

Studies on the developmental toxicity of ozone: postnatal effects.

Pregnant rats were exposed to either 0, 1.0, or 1.5 ppm ozone during either mid gestation (Days 9-12) or late gestation (Days 17-20). The dams were allowed to deliver and the early morphological and behavioral development of their pups was monitored. Both exposure regimens transiently reduced neonatal growth rates. The late gestation exposure regimen produced retardations in early reflex development and in open field behavior. Finally, several males from this exposure regimen remained permanently stunted in growth.

Animals↗
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↗
PubMedDate not supplied

Prioritization of NTP reproductive toxicants for field studies.

Population studies that evaluate human reproductive impairment are time consuming, expensive, logistically difficult, and with limited resources must be prioritized to effectively prevent the adverse health effects in humans. Interactions among health scientists, unions, and industry can serve to identify populations exposed to potential hazards and develop strategies to evaluate and apply appropriate controls. This report describes a systematic method for prioritizing chemicals that may need human reproductive health field studies. Rodent reproductive toxicants identified from the National Toxicology Program (NTP) Reproductive Assessment by Continuous Breeding (RACB) protocol were prioritized on the basis of potency of toxic effect and population at risk. This model for prioritization links NTP findings with data from the National Occupational Exposure Survey (NOES) and the Hazardous Substance Data Base (HSDB) or the High Production Volume Chemical Database (HPVC) to prioritize chemicals for their potential impact on worker populations. The chemicals with the highest priority for field study were: dibutyl phthalate, boric acid, tricresyl phosphate, and N, N-dimethylformamide.

Animals↗