PubMed HealthSearch

Biomedical subjects

L W Rampy

Publications and source records attributed to L W Rampy.

9 recordsLinked to original sources

Methylene chloride: a 2-year inhalation toxicity and oncogenicity study in rats.

Male and female Sprague-Dawley rats were exposed to 0, 50, 200, or 500 ppm methylene chloride for 6 hr/day, 5 days/week for 2 years. Blood carboxyhemoglobin levels were elevated in a dose-dependent (less than linear) manner in rats exposed to 50-500 ppm methylene chloride. Histopathologic lesions related to methylene chloride exposure were confined to the liver and mammary tissue of rats. An increased incidence of hepatocellular vacuolization was observed in male and female rats exposed to 500 ppm methylene chloride. Female rats exposed to 500 ppm methylene chloride also had an increased incidence of multinucleated hepatocytes and number of spontaneous benign mammary tumors/tumor-bearing rat (adenomas, fibromas, and fibroadenomas with no progression toward malignancy); the incidence of benign mammary tumors in female rats exposed to 50 or 200 ppm methylene chloride was comparable to historical control values. No increase in the number of any malignant tumor type was observed in rats exposed to concentrations as high as 500 ppm methylene chloride. Additional groups of female rats were exposed to 500 ppm methylene chloride for the first 12 months or the last 12 months of the 24-month study. The response observed in female rats exposed to 500 ppm for the first 12 months was the same as that observed in female rats exposed to 500 ppm for 2 years. Conversely, the response observed in female rats exposed to 500 ppm during the last 12 months of the study was similar to that observed in control animals. Based upon the results of this study, the no-adverse-effect level for chronic inhalation exposure of Sprague-Dawley rats was judged to be 200 ppm methylene chloride.

Administration, Inhalation

Chronic toxicity and oncogenicity study on inhaled vinylidene chloride in rats.

Male and female Sprague-Dawley rats (Spartan substrain) were exposed to vinylidene chloride (VDC) by inhalation for 18 months to assess chronic toxicity and oncogenic potential of the subject test material. Interim sacrifices were performed at 1, 6, and 12 months. Rats were exposed to VDC concentrations of 10 and 40 ppm for 6 hr/day, 5 days/week for the first 5 weeks of the study. Based upon the absence of observable treatment-related effects among rats sacrificed after 1 month of exposure, the exposure concentrations were increased to 25 and 75 ppm VDC. Exposures were continued at these concentrations through the 18th month of the study after which the surviving animals were held until 24 months and then sacrificed. Cytogenetic evaluations were performed on a separate group of animals, four rats/sex, exposed to 0, 25, or 75 ppm VDC for 6 months. There were no exposure-related changes in the following parameters: mortality, appearance and demeanor, body weight data, clinical chemistry determinations, hematologic evaluations, urinalysis, or cytogenetic evaluation of bone marrow preparations. A target organ effect, characterized by hepatocellular fatty change in the midzonal region of the hepatic lobule which was minimal in severity, was observed in both male and female rats of both the 25- and 75-ppm exposure groups as early as the 6-month interim sacrifice. The midzonal fatty change was also observed at the 12-month sacrifice but no indication of progression of this lesion in either severity or incidence was apparent. During the last 6 months of the study, after exposures had been discontinued, this effect was no longer discernible; therefore this alteration was readily reversible. The incidences of several tumors and/or tumor types were statistically increased or decreased in VDC-exposed rats when compared to their respective control groups; none of these differences were judged to be attributable to VDC exposure.

Animals

Embryotoxicity of inhaled benzene in mice and rabbits.

The effect of inhaled benzene on embryonal and fetal development was assessed in mice and rabbits. CF-1 mice and New Zealand white rabbits were exposed to 0 or 500 ppm of benzene for 7 hr per day from days 6 through 15 (mice) and 6 through 18 (rabbits) of gestation. Little evidence of maternal toxicity was seen in either species. Although some signs of embryonal toxicity were observed in both mice and rabbits, a teratogenic effect was not discerned in either species inhaling 500 ppm of benzene.

Aerosols

Induction of pulmonary carcinoma in rats by chronic inhalation of dust from pulverized asbestos pipe covering.

Rats and hamsters were exposed to the dust of pulverized asbestos pipe covering at an average concentration of 85 mg/m(3) for 6 h/d, 5 d/wk, for 7 mo, followed by a lifetime observation period. In rats, the pulmonary responses were alveolar adenomatous proliferation, nonprogressive fibrosis, squamous metaplasia, and a substantial incidence of pulmonary carcinoma formation. A smaller group of hamsters exposed under these conditions experienced an earlier onset of mortality than control hamsters, which were not subjected to the exposure regimen. Although this prevented conclusive evaluation of the pulmonary response in this species, no pulmonary neoplasms were noted in the surviving hamsters.

Animals

Interim results of two-year toxicological studies in rats of vinylidene chloride incorporated in the drinking water or administered by repeated inhalation.

Male and female Sprague-Dawley rats were exposed to vinylidene chloride (VDC) orally or by inhalation in 2-year toxicological studies. Interim results are included in this report. VDC was given in the drinking water at mean +/- S.D. concentrations of 0, 68 +/- 13, 106 +/- 22, and 220 +/- 35 ppm which produced mean +/- S.D. dosage levels of 0, 5.9 +/- 0.6, 10.0 +/- 1.2, and 19.3 +/- 2.7 mg/kg for male rats and 0, 7.5 +/- 0.4, 12.6 +/- 1.1, and 25.6 +/- 2.4 mg/kg for female rats. Forty-eight rats/sex/VDC level and 80 rats/sex in the control group were used in the 2-year study with an interim kill of an additional 10 rats/sex/level at 90 days. In the inhalation study, rats were exposed to 0, 10, or 40 ppm of VDC vapor 6 hr/day, 5 days/week for 5 weeks, after which the exposure levels were changed to 0, 25, and 75 ppm of VDC. Exposure continued for a total of 18 months and the rats held for observation an additional 6 months. Interim kills occurred at 1, 6 and 12 months. A separate 90-day study using 20 rats/sex/level was conducted at 0, 25, and 75 ppm of VDC vapor. There were 86 rats/sex/level in the 2-year portion of the study. The parameters monitored were: body weight, food and water consumption (drinking water study only), hematology, clinical chemistries, cytogentics of bone marrow cells (inhalation study only), mortality, terminal organ weights, and gross and histopathology. Based on interim kills and gross pathologic observations, the main conclusions are: increased cytoplasmic vacuolation of hepatocytes was seen in the livers of rats given 200 ppm VDC in drinking water or 25 or 75 ppm VDC vapor by inhalation; based on gross tumor count, tumor incidence in VDC-exposed rats was not greater than controls.

Animals