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Biomedical subjects

R E Schroeder

Publications and source records attributed to R E Schroeder.

14 recordsLinked to original sources

Reproductive and developmental toxicity studies of a linear alkylbenzene mixture in rats.

Alkylate 215, a mixture of linear decyl- to tridecylbenzenes, is an intermediate in the manufacture of detergent sulfonates. A two-generation reproduction study and a developmental toxicity study were conducted using single daily doses given by gastric intubation in a corn oil vehicle. In the reproduction study, groups of 30 rats/sex/group were given doses of 0, 5, 50, or 500 mg/kg/day. F0 animals received a 10-week premating treatment period and were then mated to produce a single litter; F1 adults were selected from the F1 litters. F1 animals were dosed for 11 weeks before mating to produce a single litter. Adults and weaned pups received a gross postmortem examination. Histopathology studies were conducted on reproductive tissues, tissues with gross lesions, and the pituitary gland taken from each adult in the control and high dose groups. In the developmental toxicity study, groups of 24 mated female rats were given 0, 125, 500, or 2000 mg/kg/day on Days 6 through 15 of gestation. Dams were terminated on gestation Day 20 and fetuses were examined for external, soft tissue, and skeletal defects. Results of the reproduction study were as follows. At 50 mg/kg/day, pup weights were decreased at Day 7 in the F1 litter. At 500 mg/kg/day, decreases were found in the F0 females in premating and early lactation weight gains; in both generations in premating weight gains in males and in weight gains during gestation in females; and in litter size, pup viability at birth, Day 0-4 survival, and pup weights on Days 14 and 21. The NOAEL for reproductive effects was 5 mg/kg/day. The developmental toxicity study found effects on several parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Developmental toxicity of dimethylformamide in the rat following inhalation exposure.

Dimethylformamide (DMF) is a widely used industrial solvent. DMF has been reported to be a developmental toxin when given to rodents by injection or following dermal administration. In this study, groups of pregnant rats were exposed by inhalation to either 0 (control), 30, or 300 ppm DMF from gestation day 6 through 15. In the 300 ppm rats, both maternal weight gain during gestation and fetal weights were lower than those of the controls. Fetal resorptions were not increased in this group. No significant differences among either maternal or fetal rats were seen in the 30 ppm group compared to controls. Both fetal and maternal toxicity were noted at 300 ppm and the no observed effect level under these experimental conditions was 30 ppm for both the dams and the conceptuses. DMF did not produce malformations in the rat fetus even at a level that was toxic to the dam.

Abnormalities, Drug-Induced

A study of developmental toxicity of hydroquinone in the rabbit.

To obtain information on potential developmental toxicity, hydroquinone (HQ) was administered to pregnant New Zealand White rabbits (18 mated per dose group) in aqueous solution (0, 25, 75, or 150 mg HQ/kg/day) by gavage on Gestation Days (GD) 6 to 18. Caesarean sections were performed on GD 30. Doses of 75 and 150 mg/kg/day adversely affected feed consumption and/or body weights of dams during the treatment period. At these doses, however, treatment-related effects were not evident from physical observations, liver and kidney weights, premature delivery incidence, and caesarean sectioning data. The NOEL for maternal toxicity was 25 mg/kg/day. In the 150 mg/kg/day dose group, total incidences of external, visceral, and skeletal findings for fetuses did not differ statistically from controls. Slight, statistically insignificant, increases were found, however, in the incidences of ocular and minor skeletal malformations (micro-ophthalmia, vertebral/rib defects, angulated hyoid arch) on both a per fetus and a per litter basis. Under the conditions of this study, HQ at 150 mg/kg/day produced minimal developmental alterations in the presence of maternal toxicity. The NOEL for developmental toxicity was 75 mg/kg/day.

Animals

Subchronic inhalation toxicity and reproductive assessment in rats of three chlorinated propenes.

Groups of 15 male and 15 female Sprague-Dawley rats were exposed to 1 of 3 chloropropene (2,3-Di = DCP; 1,2,3-Tri = TRCP; and 1,1,2,3-Tetra = TECP) vapors to provide information on repeated exposures and the potential for reproductive impairment by the most likely route of occupational exposure. Target exposure concentrations were 0, 1, 5, and 15 ppm, 6 h/d, 5 d/wk for 13 wk. The following parameters were evaluated: pharmacotoxic signs, survival, body weights, hematology, clinical blood chemistry, urine analysis, gross and histopathology (over 40 tissues/rat), organ weights, and selected weight ratios. Signs of nasal irritation were noted in rats exposed to 15 ppm of either DCP or TRCP but not TECP. Small decreases in overall body weight were observed in female rats exposed to 15 ppm TCP. An increase (approximately 15%) in spleen weight, with no corresponding histopathological or clinical findings, was observed in 15 ppm DCP-treated male rats. No other effects considered related to treatment were observed following exposure to any of the three chlorinated propenes. Additional groups of 10 male and 20 female Sprague-Dawley rats were exposed to DCP, TRCP, or TECP vapors at target concentrations of 0, 1, or 5 ppm for 6 h/d, 5 d/wk for a 10-wk premating period, a mating period, and the first 14 d (females only) of gestation. Females were allowed to deliver litters and the offspring were evaluated during a 21-d lactation period. Mating, pregnancy, and fertility indices were generally comparable among all test groups, although female mating and pregnancy indices of both DCP-treated females were lower than expected in the regular and postrecovery reproduction phase. No effects were seen on pup survival, sex distribution, body weights, organ weights, and ratios. A modest reduction in pup body weights was observed following TECP exposure but was attributed to large litter size. No treatment-related effects were seen following necropsy of adults or weanlings, nor were such effects noted following microscopic evaluation of gonads from parental animals.

Administration, Inhalation

Chronic toxicity, oncogenic potential, and reproductive toxicity of p-nitroaniline in rats.

Dose levels for these studies were selected mainly on the basis of subchronic studies, although consideration was also given to workplace exposure levels and proposed mechanism of tumor formation with structurally similar compounds. For the chronic study, groups of 60 male and 60 female Sprague-Dawley CD (Registered Trademark of Charles River Breeding Laboratories, Portage, MI) rats were given 0, 0.25, 1.5, or 9.0 mg/kg/day paranitroaniline (PNA) by gavage in corn oil for a period of 2 years. Parameters monitored included clinical observations, ophthalmoscopic exams, body weights, food consumption, hematology, clinical chemistry, and urinalysis at regular intervals throughout the study. All gross lesions and over 40 tissues were examined histologically for all control and high-dosage-level animals. Gross lesions, spleens, and livers of low- and mid-dosage groups were also examined histologically. For the reproduction study, groups of 15 male and 30 female rats, designated as F0 generation, were given PNA at the same levels as the chronic study for 14 weeks prior to mating and during mating, gestation, and lactation. Selected groups of 15 male and 30 female rats of the F1 generation received the same dose of PNA for 18 weeks prior to mating and during mating, gestation, and lactation. F2 pups were observed through weaning at which time they were euthanized. Observations made during the study included body weights, food consumption, mating and fertility indices, pup and litter survival indices, and histopathology of selected tissues. In the chronic study, except for a slight decrease in survival of high-dose male rats late in the study, survival in all treated groups was comparable to controls. Blood methemoglobin levels were elevated in the mid- and high-dosage groups, while slight anemia was observed in the high-dosage group also. Spleen weights were significantly increased in the high-dosage groups. An accumulation of brown pigment was observed in the cytoplasm of the sinusoidal macrophages or littoral cells of the liver and in the reticuloendothelial cells of the spleen. No treatment-related increase in tumor incidence was observed. In the reproduction study, no consistent pattern of effect from treatment between the F0 and F1 generation was seen in mating, pregnancy, or fertility indices. Thus, administration of PNA at levels which produced significant methemoglobinemia and low-level anemia in the rat and histological changes in the spleen produced no tumors or reproducible effects on reproductive performance.

Aniline Compounds

Evaluation of the subchronic and reproductive effects of a series of chlorinated propanes in the rat. I. Toxicity of 1,2,3-trichloropropane.

Repeated inhalation exposure and 1-generation reproduction studies have been conducted in the rat to address the adequacy of the 10 ppm occupational exposure limit established for 1,2,3-trichloropropane (TriCP). Groups of 5 rats per sex were exposed for 6 h/d, 5 d/wk up to 4 wk to target TriCP concentrations of 0-900 ppm. Nine of 10 rats died after a single exposure at 900 ppm. Additional deaths were seen in the 300 (1 death) and 600 (3 deaths) ppm test groups. Mean body weights for all TriCP-treated groups were lower than control values. Liver weights were increased in animals of both sexes at 600 ppm and lower. For females ovary weights for the 300 and 600 ppm groups and spleen weights for the 300 ppm group were lower than those of controls. Males exhibited decreased testes weights only at the 600 ppm TriCP level (not evaluated at 900 ppm). Results of a 13-wk exposure, 6 h/d, 5 d/wk of 15 rats/sex.group to TriCP target vapor concentrations of 5, 15, or 50 ppm also resulted in liver weight increases at all test levels. Histopathologic examination showed hepatocellular hypertrophy in male rats at all TriCP levels. Other microscopic findings related to treatment in rats exposed to 15 ppm and to 5 ppm TriCP included lung hyperplasia (both sexes) and splenic extramedullary hematopoiesis (females only) and parallel observed organ weight increases. No treatment-related deaths were observed in this study, nor were there apparent effects on the hematology or clinical chemistries. Group mean body weights at 50 ppm (both sexes) and 15 ppm (females only) TriCP were reduced when compared to controls. In a 13-wk follow-up study in rats at 0, 0.5, and 1.5 ppm TriCP, no gross or microscopic findings related to treatment were found. Groups of 10 male and 20 female rats were exposed 6 h/d, 5 d/wk to 0, 5, or 15 ppm TriCP vapor during premating and mating. Females also were exposed during gestation. Low mating performance was observed in all groups of female rats including the controls, although fewer females in the 15-ppm group mated than in other study groups. Mating and fertility indices of male rats in both treated and control groups were generally low. All measured progeny indices appeared unaffected by treatment. A follow-up study of the same design was conducted at levels of 0, 0.5, and 1.5 ppm TriCP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Evaluation of the subchronic and reproductive effects of a series of chlorinated propanes in the rat. II. Toxicity of 1,2,2,3-tetrachloropropane and 1,1,2,2,3-pentachloropropane.

Comparative subchronic and reproductive toxicity studies by inhalation exposure were conducted with 1,2,2,3-tetrachloropropane (TECP) and 1,1,2,2,3-pentachloropropane (PCP). Groups of 5 male and 5 female CD rats were exposed 6 h/d, 5 d/wk for 4 wk to either TECP or PCP at target concentrations of 0, 100, 300, 600, or 900 ppm (single exposure only). Deaths occurred at and above 300 ppm PCP and 600 ppm TECP. Significant irritation of mucosal tissue was attributed to vapors of TECP and PCP. Lower group mean body weights of surviving male rats of all groups were observed after 4 wk of exposure to TECP. Liver, kidney, and ovary weights were affected by PCP treatment. Groups of 15 male and 15 female CD rats were exposed to target vapors of 0-50 ppm TECP or PCP for 6 h/d, 5 d/wk for 13 wk. Irritation about the nose and eyes was observed at all TECP, but not with PCP, test levels. Liver weights were increased at and above 5 ppm in all groups of TECP-treated males. Kidney weights were also elevated in male rats at 15 and 50 ppm PCP and females from the 50 ppm PCP group. Degenerative changes in these two corresponding tissues were seen at and above 5 ppm TECP and PCP. A treatment level of 1.5 ppm TECP or PCP was without systemic effect clinically or pathologically. Groups of 10 male and 20 female CD rats were exposed 6 h/d, 5 d/wk for a premating, mating, or gestation (F only) period to target levels of 0, 5, or 15 ppm TECP or PCP. No treatment-related effects were seen in the PCP study. While mating performance overall was poor in the TECP study, female mating performance of the 15 ppm TECP-exposed group appeared lower than control. In a follow-up study with TECP using the same study design, no effects on female or male fertility or fecundity or on offspring were seen up to 1.5 ppm TECP.

Animals

A two-generation reproduction study with monochlorobenzene vapor in rats.

Groups of 30 male and 30 female Sprague-Dawley CD rats, designated as the F0 generation, were exposed to vapor of monochlorobenzene (MCB) at target concentrations of 0, 50, 150, or 450 ppm for 10 weeks prior to mating and during mating, gestation, and lactation. The progeny of the F0 generation was designated as the F1 generation and groups of 30 male and 30 female F1 animals were exposed to the same concentrations of MCB as the F0 parents. Exposure of F1 animals was initiated 1 week postweaning and lasted 11 weeks prior to mating and through mating, gestation, and lactation. All F2 pups were observed through weaning at which time they were killed. Observations made during the study included body weights, food consumption, mating and fertility indices, pup and litter survival indices, and histopathology of selected tissues. No mortality was observed during the course of this study. Body weights and food consumption for all treated groups were comparable to controls during the growth period. Maternal body weight data during gestation and lactation were also comparable between the control and treated groups. Mating and fertility indices for males and females for both generations appeared unaffected by treatment. Pup and litter survival indices for all treated groups were comparable to those of controls. Hepatocellular hypertrophy and renal changes (tubular dilation with eosinophilic material, interstitial nephritis, and foci of regenerative epithelium) were observed among F0 and F1 male rats exposed to 150 and 450 ppm MCB.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation

Methyl tertiary butyl ether inhalation in rats: a single generation reproduction study.

Male rats exposed to target concentrations of methyl tertiary butyl ether (MtBE) at 300, 1300 and 3400 ppm for 6 hours/day, 5 days/week for 12 weeks were mated to female rats exposed to the same concentrations for a 3-week period. Exposures continued through the mating period and the females continued exposures during gestation and from days 5-21 lactation of the litters (F1a) (no exposures days 0-4 lactation). A second litter (F1b) was produced under the same mating and post mating exposure regimen. No adverse effect of treatment was observed with the adult animals (Fo) throughout the in-life portion of the study. The only remarkable finding was an increased incidence of dilated renal pelves in the low- and high-dose females (Fo). All gonad weights, male accessory reproductive organ weights, organ-to-body weight ratios and reproductive organ histopathology were unremarkable upon comparison of treated animals with air sham controls. The mating indices and fertility indices in exposed animals for both mating intervals (F1a and F1b) were not significantly different from controls. Pregnancy rates were comparable between treated and control females for the first litter interval (F1a) but were slightly lower (not statistically significant) than control on the second litter interval (F1b). Treated animal mean gestation length and the mean number of pups at birth were not statistically different from controls. The pup viability indices at birth were comparable for control and treated groups for the F1a generation, but the mid- and high-dose groups displayed a slight statistically significant decrease in the F1b generation; the decrease was not considered to be biologically significant and perhaps not treatment-related. Litter survival indices were comparable between control and treated groups for both litter intervals. Pups of mid- and high-dose females had slightly lower (not statistically significant) mean weights at days 14 and 21 of lactation but this was not considered treatment-related. The most frequent post-mortem observation for pups sacrificed at day 21 of lactation was dilated renal pelves. This did not appear to be related to treatment. It is concluded that MtBE inhalation in rats results in little adverse reproductive toxicity as shown in a two litter, one generation reproduction assay in rats.

Administration, Inhalation

Satisfaction of patients in two Air Force family practice programs.

This study was carried out to determine of patients enrolled in family practice clinics were satisfied with their care and to ascertain if there was a difference in the level of satisfaction between two groups of family practice patients: one group at a teaching medical center and the other at a general acute care community hospital. The overwhelming majority of family practice patients surveyed were extremely satisfied with the care they were receiving. The prime reasons for this satisfaction were physician continuity (having one physician for the whole family), personal attention, and having levels of satisfaction between the groups at a teaching and a non-teaching facility. Overall, families that had received preventive health instructions from their physician had a stronger desire to remain with family practice and had fewer dislikes about the program than did the group of patients who had not received any preventive health instructions from their physician.

Aerospace Medicine