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Biomedical subjects

R E Staples

Publications and source records attributed to R E Staples.

At least 37 records · Page 2Linked to original sources
PubMed1980

Influence of n-hexane on embryo and fetal development in mice.

Pregnant outbred albino mice (CD-1) received n-hexane once daily be gavage at doses up to 2.20 g/kg/day on days 6-15 of gestation. Other pregnant mice received higher hexane doses (up to 9.90 g/kg/day), employing a three times a day injection schedule. At the lower, once-daily doses only one dam died and no teratogenic effects occurred. Higher hexane doses (t.i.d.) were toxic: 2 of 25 dams treated with 2.83 g/kg/day, 3 of 34 treated with 7.92 g/kg/day and 5 of 33 treated with 9.90 g/kg/day died. At the 7.92 and 9.90 g/kg/day doses, the average fetal weight was significantly (p less than 0.05) reduced, but the incidence of malformations in treated and vehicle (cotton-seed oil) control groups did not differ significantly. Thus, n-hexane was not teratogenic even at doses toxic to the dam.

Animals↗
PubMed1979

Influence of drinking water -- tap versus purified -- on embryo and fetal development in mice.

Pregnant CD-1 mice drank either chlorinated tap water obtained at NIEHS from the City of Durham, North Carolina municipal water supply or this same water passed in sequence through an organic removal cartridge and a demineralizer, followed by glass distillation. No significant overall differences in the reproductive status of pregnant mice were noted when the two groups were compared. Similarly, no significant overall influence on the incidence of malformed fetuses could be traced to the purity of drinking water. Month by month comparisons indicated that there were three statistically significant differences; all of which indicated improved performance for the mice that drank tap water. When the results for both groups were combined and a month by month comparison was made there was a significant difference in the pregnancy rate for February (68%) as compared with an overall pregnancy rate of 80% and a 79-93% spread for the other months, but the decrease was due to the low incidence of pregnancy in the group that drank the purified water.

Abnormalities, Drug-Induced↗
PubMed1979

Teratogenic potential of inhaled carbon monoxide in mice and rabbits.

Pregnant CF-1 mice and New Zealand rabbits were exposed to carbon monoxide at a concentration of 250 ppm for 7 or 24 hours daily during the period of major organogenesis, days 6 through 15 of gestation in mice and 6 through 18 of gestation in rabbits. Carboxyhemoglobin levels in the range of 10--15% were observed in both species (control animals had 0.7% or less). Carbon monoxide was not found to be teratogenic in either species. In mice, a significant increase in the incidence of some minor skeletal variants was observed. One litter in each of the carbon monoxide-exposed groups of mice was completely resorbed; none of the litters of control mice or of control or exposed rabbits were completely resorbed. The fetuses of mice exposed to carbon monoxide for seven hours daily were heavier than control fetuses, and those exposed for 24 hours daily were lighter than control fetuses. The reason for this result is not known.

Abnormalities, Drug-Induced↗
PubMed1979

Teratogenic potential of dichlorvos given by inhalation and gavage to mice and rabbits.

Dichlorvos (2,2-dichlorovinyl dimethyl phosphate) is an important organophosphate insecticide and anthelmintic with widespread use. The purpose of this study was to evaluate the teratogenic potential of dichlorvos given orally at the maximum tolerated dose to mice (60 mg/kg/day) and rabbits (5 mg/kg/day) and by inhalation in both species at a concentration of 4 microgram/l seven hours daily. Dichlorvos was not found to be teratogenic in either species by either route of administration.

Administration, Oral↗
PubMed1979

Dipterex teratogenicity in the rat, hamster, and mouse when given by gavage.

Dipterex was teratogenic after administration by gavage (t.i.d.) at a dose level of 480 mg/kg-day to the CP rat on days 6 through 15 of gestation, but not when administered only on days 8 or 10 of gestation. A positive teratogenic response also occurred in the hamster after administration on days 7 through 11 of gestation at 400 mg/kg-day; the apparent no-effect level for the criteria studied was 200 mg/kg-day. Embryotoxicity, but not teratogenicity, occurred after administration of 400 mg/kg-day on day 8 of gestation. In both species, the teratogenicity seen was not merely due to reduced maternal food consumption during the period of exposure. The mouse was less susceptible to Dipterex than were the rat and hamster, but a significant increase in the incidence of cleft palates resulted from exposure on days 10 through 14, or on days 12 through 14 of gestation.

Animals↗
PubMed1979

Teratology.

Two categories of collaborative studies are defined. Examples of each type are presented through teratologic studies conducted at the National Institute for Environmental Health Sciences (NIEHS) in collaboration with an Environmental Protection Agency laboratory and a laboratory in the USSR. These studies and the few pertinent studies found in the literature point out the problem of obtaining repeatability and uniformity of results among tests conducted to determine teratogenic potential. Collaborating laboratories should take more time to select the procedures to be used, to standardize the intended protocol in greater detail, to train participating personnel uniformly, and to test for repeatability by use of a known teratogen, before tackling major interests. Establishment of an archives would improve duplication of published results by making available additional pertinent unpublished information. Finally, possible advantages of collaborative studies for the testing of teratogenic potential are offered.

Animals↗
PubMed1979

Embryotoxicity of inhaled sulfur dioxide and carbon monoxide in mice and rabbits.

The embryotoxic and teratogenic potential of sulfur dioxide (SO2) was evaluated in CF-1 and New Zealand rabbits exposed to SO2 alone or in combination with carbon monoxide (CO). The animals inhaled filtered room air (controls), SO2 (mice, 25 ppm; rabbits, 70 ppm), or SO2 plus CO (250 ppm) for 7 hr/day from days 6 through 15 (mice) and from days 6 through 18 (rabbits) of gestation. In both species, inhalation of SO2 resulted in slight toxicity in the dams and an increased incidence of minor skeletal variants among their offspring; exposure to the combination did not potentiate the increased incidence of these variants. A teratogenic effect was not discerned in either mice or rabbits exposed to SO2 alone or in combination with carbon monoxide, but the fetuses of mice exposed to the combination were significantly smaller than those exposed only to SO2.

Abnormalities, Drug-Induced↗
PubMed1979

Embryotoxicity of inhaled sulfuric acid aerosol in mice and rabbits.

The effect of inhaled sulfuric acid (H2SO4) on embryonal and fetal development was assessed in CF-1 mice and in New Zealand white rabbits. Both species were exposed for 7 hr/day to 0, 5, or 20 mg H2SO4/m3 during the period of major organogenesis (mice, days 6 through 15 of gestation; rabbits, days 6 through 18 of gestation). Little evidence of toxicity was seen in the fetuses of mice or rabbits exposed to H2SO4. Slight maternal toxicity was seen at 20 mg H2SO4/m3 in both species. Teratogenicity was not observed in either mice or rabbits exposed to H2SO4.

Administration, Intranasal↗
PubMed1978

Teratogenicity of ethylenethiourea and thyroid function in the rat.

Ethylenethiourea (ETU) was given by gavage at a dose of 40 mg/kg/day from Days 7 through 15 of gestation to hypothyroid and euthyroid rats, and to rats given exogenous thyroxine, to determine whether ETU teratogenicity occurs through alteration of maternal thyroid function. At sacrifice on Day 20 of gestation 84-100% of the fetuses in all groups given ETU were malformed regardless of the thyroid status of the dams. Ten percent of the fetuses of dams thyroparathyroidectomized at 75 days of age that were not given ETU were malformed; no malformations were noted among the fetuses of the other groups not given ETU. Hence, ETU was found to induce teratogenicity in rats but not through alteration of maternal thyroid status. In addition, it was determined that ETU lowered serum thyroxine concentration, that hypothyroidism itself increased the background level of malformations in the rat, and that hypothyroidism qualitatively and quantitatively increased the incidence of specific malformations after ETU administration.

Animals↗
PubMed1978

Teratogenic potential of ethanol in mice, rats and rabbits.

Pregnant CF-1 mice, Sprague-Dawley rats and New Zealand white rabbits were given 15% ethanol in their drinking water during the period of major organogenesis, from day 6 through 15 of gestation in mice and rats and days 6 through 18 of gestation in rabbits. Maximum blood alcohol levels, measured in non-pregnant animals, were about 200 mg percent in mice and 25-50 mg percent in rats and rabbits. Maternal toxicity in the form of decreased liquid intake and decreased maternal body weight occurred in all species during the experimental period. A significant increase in the incidence of external or soft tissue alterations was not observed in the alcohol-exposed groups of any species, but a significant increase in minor skeletal variants was observed in mice and rats. These were probably due to retarded fetal growth rather than to a specific effect of the ethanol. Teratogenic effects were not observed in any of the three species.

Animals↗
PubMed1977

Prenatal toxicity of medroxyprogesterone acetate in rabbits, rats, and mice.

Medroxyprogesterone acetate (MPA) was given once daily sc at 0.1-3,000 mg/kg/day for 3, 6, or 9 consecutive days during gestation days 7 to 15 to CD1 and A/J mice, and New Zealand (NZ) and Dutch Belted (DB) rabbits, and during days 8 to 16 to CD rats. Malformations attributable to MPA did not occur in fetuses of mice or rats exposed to the largest dosage tested. However, 1, 3, or 10 mg/kg on days 13 to 15 to NZ rabbits resulted in 6, 28, and 42% cleft palate, respectively. Comparable cleft palate frequencies were seen in DB offspring.

Abnormalities, Drug-Induced↗
PubMed1976

Developmental toxicity in the rat after ingestion or gavage of organophosphate pesticides (Dipterex, Imidan) during pregnancy.

The structural development of fetuses was altered when Dipterex was administered by diet to pregnant rats from days 6 through 15 of gestation. Major external and skeletal alterations occurred after consumption of 432 or 519 mg/kg body weight per day, only minor skeletal changes occurred in the 375 mg/kg dose group and the incidence of alterations in the 145 mg/kg dose group was not significantly different from that in the pair-fed controls. The malformations seen at the two highest doses did not result directly from the associated decrease in food consumed. Dipterex was not shown to have teratogenic potential when given for the same time span, once daily by gavage, even at levels that produced maternal lethality. Imidan was not teratogenic when similarly given, either by diet at concentrations that resulted in a 45% reduction in food consumption, or by gavage at dose levels that resulted in some maternal lethality. Data collected from pair-fed control females revealed that limitation of food consumption to 13--15 g/rat per day from days 6 through 15 of gestation did not result in increased fetal mortality or stunting. However, fetal weight was reduced slightly, and the incidence of minor skeletal changes was approximately three to four times that among fetuses of control dams that were not pair-fed.

Abnormalities, Drug-Induced↗