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Biomedical subjects

D C Villeneuve

Publications and source records attributed to D C Villeneuve.

At least 37 records · Page 2Linked to original sources
PubMed1991

Short-term dermal toxicity and mutagenicity of coal coprocessing products in the rat.

The present study was conducted to determine the dermal toxicity of coal coprocessing products and to assess their potential health hazards. Groups of 10 male and 10 female Sprague-Dawley rats were administered dermally coal coprocessing products (light gas oil, LGO; heavy gas oil I, HGOI; heavy gas oil II, HGOII) at 1 g/kg body weight/d for 14 d. The control and positive control groups received normal saline and a coal liquefaction product (CLP) at the same dose level, respectively. Treatment with either the three fractions of coprocessing products or CLP caused decreased growth rate and food consumption in animals of both sexes. Liver enlargement occurred in groups treated with HGOI, HGOII, and CLP. Decreased serum glucose was observed in animals of both sexes treated with the three fractions and CLP. Treatment with HGOI and CLP caused an elevation of hepatic microsomal ethoxyresorufin deethylase activity in the rat of both sexes. The three fractions and CLP caused mild anemia. Mild treatment-related histological changes were observed in the liver, spleen, thyroid, bone marrow, and kidney. All three fractions of coprocessing products were tested for their mutagenicity in five strains of Salmonella typhimurium: TA98, TA100, TA1535, TA1537, and TA1538. HGOI, after metabolic activation, was found to be mutagenic in the strains of TA98, TA100, and TA1538. In contrast, HGOII was mutagenic in the five strains with or without metabolic activation. These data indicate that HGOI and HGOII are more toxic than LGO, and should be subjected to further studies to determine their long-term effects.

Administration, Topical↗
PubMed1991

Alteration of primate ovary surface epithelium by exposure to hexachlorobenzene: a quantitative study.

Hexachlorobenzene (HCB) is a fungicide and a pollutant of increasing concern in industrialized regions of the world. Reproductive failure is one of the effects of HCB upon mammals. Alteration of cell shape in the ovary surface epithelium (OSE) of Cynomolgus monkeys following oral administration of HCB was observed in this study. At the lowest dose used, 0.1 mg/kg body weight, a dosage that is associated with follicular degeneration, HCB caused quantifiable changes in length-to-width ratios of OSE. Measurement of cell shape by light microscopy offers a reliable indication of OSE changes induced by HCB.

Animals↗
PubMed1991

Surface epithelium of the ovary following oral administration of hexachlorobenzene to the monkey.

Hexachlorobenzene (HCB) is a toxic and carcinogenic chemical that has been implicated in female reproductive dysfunctions, including destruction of ovarian follicles in primates. The purpose of this study was to determine the effects of HCB on ovary surface epithelium (SE). Gelatin capsules containing HCB mixed with glucose were given to 16 cynomolgus monkeys housed under controlled conditions in dosages of 0.0, 0.1, 1.0, or 10.0 mg/kg body weight daily, for 90 days; the first group served as the control. At necropsy one ovary from each animal was removed, fixed in glutaraldehyde, and processed by conventional methods for examination by transmission electron microscopy. SE from the animals in control group consisted of a single layer of squamous-to-cuboidal cells which possessed microvilli and contained cytoplasm rich in organelles; the nuclei were placed in middle of the cells. Although the types of alteration were similar in the treated groups, the degree of severity increased with increasing dose levels. In the lowest dose group (0.1 mg/kg) tested, stratification of cells was observed in some areas. Many cells were tall columnar, highly irregular in outline, and showed signs of degeneration. The nuclei had migrated toward the apical surface. Cytoplasm contained a large number of lysosomes, and numerous vesicles, which may have been swollen endoplasmic reticulum. In the 10 mg/kg group the affected cells were in advanced stages of degeneration. These observations support the evidence that HCB is a potent reproductive toxicant. Further studies are required to establish the effects of this damage on reproductive performance.

Administration, Oral↗
PubMed1990

A teratological assessment of coal liquefaction products in the rat.

Teratogenicity of coal liquefaction products (CLP) was assessed in the pregnant rat. Three product streams of CLP (medium, hydrotreated medium and heavy fractions) were each administered dermally on Sprague-Dawley rats at doses of 125, 250 or 500 mg kg-1 day-1 from Day 6 through to Day 15 of gestation. Depressed maternal weight gain and reduced number of fetuses resulting from an increased resorption rate, decreased fetal weight and retarded ossification were observed in the group treated with the heavy fraction at a dose of 500 mg kg-1 day-1. The heavy fraction at 500 mg kg-1 day-1 also caused anaemia and increased liver and spleen weights in dams. The dams exposed to the highest dose of three CLP fractions had mild and adaptative hepatic changes consisting of increased cytoplasmic eosinophilia and nuclear anisokaryosis. No treatment-related histological changes were observed in fetuses. None of the fractions demonstrated any teratological effects.

Abnormalities, Drug-Induced↗
PubMed1990

Subchronic oral toxicity of triethyl lead in the male weanling rat. Clinical, biochemical, hematological, and histopathological effects.

This study was designed to ascertain the effects of low level exposure of triethyl lead (3EL) to the male weanling rat. Groups of 20 animals were administered by gavage 3EL at 0.05, 0.10, 0.20, 0.50, and 1.00 mg/kg body wt for 91 days, 5 days/week. Lead acetate (PbHOAC) at 200 mg/kg body wt/day was given as a positive control. Weight gain was reduced in those animals receiving 1.0 3EL. Spleen and kidney weights were elevated in the PbHOAC group. Residues of 3EL and its metabolites diethyl lead (2EL) and lead (Pb) accumulated in a dose-dependent manner in blood, liver, kidney, and brain; 3EL accumulated preferentially in the liver while inorganic lead accumulated in the kidney. Dose-dependent changes occurred in serum calcium which was decreased and in phosphorus which was elevated for all dose groups. Serum cholesterol was elevated in the three highest 3EL groups as was alkaline phosphatase. LDH was lowered in the PbHOAC-treated group but microsomal aniline hydroxylase was elevated. Hematological changes consisted of elevated platelet counts in the 1.0 3EL group and decreased mean corpuscular hemoglobin content and mean corpuscular volume in the PbHOAC-treated group. Treatment related histopathological changes were seen in thyroid, liver, kidney, and bone marrow. Based on these data a no observed adverse effect level for 3EL was set at 0.10 mg/kg/body wt.

Administration, Oral↗
PubMed1990

Toxicological assessment of chlorinated diphenyl ethers in the rat, Part II.

Chlorinated diphenyl ethers (CDE's) are environmental contaminants that have been found in Great Lakes fish. Because of the paucity of toxicity data and potential for human exposure, the present short-term study was conducted to assess their potential toxic effects. Groups of 10 male and 10 female rats were administered the three CDE congeners (2,2',4,4',5-pentachlorodiphenyl ether (PCDE), 2,2',4,4',5,5'-hexachlorodiphenyl ether (HCDE), 2,2',3,4,4',6,6'-heptachlorodiphenyl ether (HPCDE] in diets at levels of 0.5, 5.0, 50 or 500 ppm for a period of 4 weeks. Decreased food consumption was observed with male and female rats fed the diet containing 500 ppm HPCDE. Treatment with the three isomers at the highest dose level produced an increase in liver weight in both sexes. While administration of PCDE produced an increase in hepatic aminopyrine demethylase activity, HCDE caused a significant increase in aminopyrine demethylase, aniline hydroxylase and ethoxyresorufin de-ethylase activities. HPCDE caused a significant increase in ethoxyresorufin de-ethylase activity. HPCDE at the highest dose level also caused a significant reduction in circulating lymphocytes in male rats. The 3 CDE's produced mild and adaptative histological changes in the liver and thyroid, but only HPCDE elicited mild changes in the thymus, bone marrow, and spleen. The above data indicate that HPCDE is immunosuppressive and that all three CDE isomers are considered to be moderately toxic in rats. The no-observable effects levels appear to be between 5-50 ppm in diet (0.36-3.0 mg/kg b.w.) for the three CDE's.

Animals↗
PubMed1989

Toxicological assessment of chlorinated diphenyl ethers in the rat.

Chlorinated diphenyl ethers are environmental contaminants that have been found in Great Lakes fish and birds. Because of their presence in the food chain, and potential for human exposure, the present short-term study was conducted to assess their toxicity. Groups of 10 male and 10 female rats were each given by gavage 2,2',4,4'6-pentachlorodiphenyl ether (CDE1), 2,2',4,4',5,6-hexachlorodiphenyl ether (CDE2) or 2,2',3,3',4,6'-hexachlorodiphenyl ether (CDE3) at dose levels of 0.04, 0.4, 4.0 or 40 mg/kg b.w./day for a period of 28 days. The control group received an equivalent volume of corn oil only (0.5 ml/100 g b.w.). Treatment with the three CDE congeners did not result in suppression of growth rate or food consumption. Increased liver weights were seen in the animals of both sexes fed 40 mg/kg CDE2, in males treated with 40 mg/kg CDE1, and in females with 40 mg/kg CDE3. Hepatic microsomal aminopyrine demethylase activity was significantly higher in the male rats administered 40 mg/kg CDE2, and aniline hydroxylase activity was elevated in the females following the same treatment. Serum glucose, calcium, protein and urea nitrogen of CDE1-treated males were higher than the control. Levels of uric acid, potassium and LDH of CDE3-treated females were also elevated. No hematological changes were observed. Histological examination revealed that the liver and thyroid were the target organs affected by CDE treatment but the morphological changes were mild even at the highest dose level. Changes in the liver consisted of nuclear vesiculation and increased cytoplasmic volume. Alterations in the thyroid were characterized by increased epithelial height and follicular collapse. Based on the data presented above, the 3 CDE congeners can only be considered moderately toxic in the rat.

Animals↗
PubMed1989

Subacute inhalation toxicity of a medium-boiling coal liquefaction product (154-378 degrees C) in the rat [Part III].

The short-term inhalation toxicity of a medium-boiling coal liquefaction product (CLP) was investigated in the rat. Groups of 5 male and 5 female Sprague-Dawley rats were exposed to CLP aerosols at 25 mg/m3 (low dose) or 100 mg/m3 (high dose) 6 h/d, 5 d/w, for 4 wk. The control group was exposed to filtered air while the positive control received diesel fuel aerosols at 100 mg/m3. Male rats exposed to high-dose CLP aerosols exhibited growth depression and increased hepatic aminopyrine demethylase activity compared to control animals. High-dose females had decreased hemoglobin content and hematocrit values. These biochemical and hematological effects were not observed in animals of either sex treated with the diesel fuel. No other biochemical and hematological changes were observed. Mild histological changes occurred in the liver and thyroid of rats treated with CLP and diesel fuel aerosols. Based on the data presented, inhalation of CLP aerosols resulted in toxicological effects that were similar to those caused by dermal exposure.

Administration, Topical↗
PubMed1988

Tissue distribution metabolism and excretion of 2,2',4,4',5-pentachlorodiphenyl ether in the rat.

The tissue distribution, metabolism and excretion of 14C-2,2',4,4',5-pentachlorodiphenyl ether (PCDE) were studied in the rat. Radioactivity was distributed in all tissues examined, with the highest concentrations being found in the fat followed by the skin, liver, kidney and muscle. Most of the radioactivity found in the tissues was due to unchanged PCDE. Decay of PCDE in the blood was fitted to a four-compartment pharmacokinetic model, and the last compartment had a half-life of 5.8 days. A total of 55% and 1.3% of an orally administered dose was excreted in feces and urine, respectively, in 7 days. More than 64% of the fecal radioactivity was due to unchanged PCDE, while hydroxylated PCDE accounted for 23%.

Animals↗
PubMed1988

Reproduction study of toxaphene in the rat.

The purpose of the present study was to investigate in rats the reproductive effects of toxaphene, an insecticidal mixture which has been identified as a pollutant in the Great Lakes ecosystem. Groups of 30 female and 15 male weanling rats were given toxaphene in the diets at 0, 4.0, 20, 100 or 500 ppm in a 1 generation 2 litter reproduction study. Toxaphene treatment at the levels studied had no effects on the litter size, pup weight, fertility, or gestation and survival indices. Toxic effects in the parental rats included depressed weight gain, elevated serum cholesterol, and increased liver and kidney weight and hepatic microsomal enzyme activities. Most of these effects were associated only with 500 ppm toxaphene treatment. Treatment-related histological changes in the liver, thyroid and kidney of adult rats were observed at levels as low as 20 ppm. Based on the data presented, the no observable adverse effect dose of toxaphene was considered to be 4.0 ppm in the diet (0.29-0.38 mg/kg b.w./day depending on the amount of dietary intake).

Aminopyrine N-Demethylase↗
PubMed1988

Dermal toxicity of a medium-boiling (154-378 degrees C) coal liquefaction product in the rat--Part I.

The subchronic dermal toxicity of a medium-boiling coal liquefaction product (CLP, 154-378 degrees C) was investigated in the rat. CLP was applied to the shaved backs of rats at dose levels of 50, 100, 200, or 400 mg/kg body weight.d, 7 d/wk for a period of 13 wk. Control groups received 0.4 ml/kg of normal saline. Signs of dermal irritation were observed at sites of application in males dosed at 200 and 400 mg/kg body weight and were characterized by thickened, focally necrotic and ulcerative skin. All animals survived the full length of the treatment period. Growth depression was observed in males at all dose levels, but no significant decrease in weight gain was observed in females. An increase in liver/body weight ratios was observed in all treatment groups of both sexes. The organ/body weight ratios for the spleen, heart, kidney, and brain were also increased in the upper dose groups of both sexes. Treatment with CLP caused a dose-dependent decrease in hemoglobin and packed cell volume in both sexes of all dose groups. The number of erythrocytes was decreased and that of neutrophils was increased in some CLP-treated groups of both sexes. There was a mild myeloid hyperplasia with increased myeloid/erythroid ratios in the 200- and 400-mg/kg groups of both sexes. Hepatic microsomal ethoxyresorufin deethylase activity was increased in all treatment groups of females, and in males dosed at 100 mg/kg and higher. In the renal tubules mild treatment-related histological changes occurred, which consisted of eosinophilic inclusions, increased cytoplasmic volume, and pyknosis. These changes were noted in the high-dose groups of both sexes. These data indicate that the medium-boiling CLP could produce systemic toxicity when applied dermally at 50 mg/kg body weight.d.

Animals↗
PubMed1988

Dermal toxicity of a high-boiling (bp 250-450 degrees C) coal liquefaction product in the rat--II.

Coal liquefaction products have been considered as an alternate source of energy to replace conventional crude oil. The present study was designed to investigate the dermal toxicity of a heavy fraction of coal liquefaction product (CLP, bp 250-450 degrees C) in the rat. Groups of 10 male and 10 female Sprague-Dawley rats (180-200 g) were treated dermally with CLP at dose levels of 100, 200, 400, or 800 mg/kg body weight.d for 6 wk. The controls were treated with 0.4 ml/kg of normal saline, while the positive control group received 400 mg/kg diesel fuel. Growth suppression was observed in all CLP-treated groups of males; in the females this effect occurred in the two highest dose groups. Diesel fuel at 400 mg/kg also caused growth suppression of a similar magnitude to that of CLP in male rats. Male animals treated with high doses of CLP or diesel fuel had severe skin lesions. Increased liver weights were observed in the diesel fuel-treated as well as all CLP-treated groups of females. The kidney weights of females treated with 400 mg/kg and 800 mg/kg CLP were also higher than control values. Decreased red cell count, hemoglobin, and hematocrit volume occurred in some CLP and diesel fuel groups of both sexes. There was mild bone marrow hyperplasia in rats of both sexes treated with CLP or diesel fuel. Mild histological changes were observed in the thyroid, liver, bone marrow, and skin of rats of both sexes treated with CLP and diesel fuel. Based on the data presented, dermal application of CLP produced systemic toxicity at the dose levels studied, and CLP and diesel fuel possess toxic effects of similar nature and magnitude.

Animals↗
PubMed1988

Trichlorobenzenes: results of a thirteen week feeding study in the rat.

Trichlorobenzenes (TRCBs) are industrial chemicals and environmental pollutants found in Great Lakes fish. The present study was carried out to provide information on the toxic effects of these chemicals in mammals. Groups of male and female weanling rats were fed diets containing TRCB isomers at 1, 10, 100 or 1000 ppm for 13 weeks. The group of males fed 1000 ppm 1,2,3-TRCB diet had reduced weight gain. No other clinical signs of toxicity were observed. Increased relative liver and kidney weights occurred in the highest dose groups of males for all 3 TRCBs. Of the 3 isomers, only 1,2,4-TRCB at 1000 ppm caused increases in hepatic aminopyrine demethylase and aniline hydroxylase activities in male rats, and aminopyrine demethylase in females. Serum biochemical and hematological parameters measured were not affected. All three TRCBs produced histological changes of a moderate degree in the liver and thyroid of male rats at 1,000 ppm. Only 1,3,5-TRCB elicited moderate renal changes in male rats fed 1,000 ppm. Microscopic changes in the females were generally milder than those of the corresponding males. Based on these data it was concluded that the nonobservable adverse effect levels for the three TRCBs were 100 ppm in the diet, or 7.6 approximately 7.8 mg/kg b.w./day depending on the dietary consumption.

Animals↗
PubMed1987

Kinetic parameters of the inhibition of red blood cell aminolevulinic acid dehydratase by triethyl lead and its reversal by dithiothreitol and zinc.

In chronic or acute exposure to triethyl lead, a de novo synthesis of aminolevulinic acid dehydratase (delta-ALAD) in bone marrow and an increased activity in circulating red blood cells can be demonstrated by activating the enzyme with dithiothreitol (DTT) and zinc. We determined the median inhibitory concentration and the apparent inhibition constant for triethyl lead on delta-ALAD. After dosing with triethyl lead, in vivo inhibition of ALAD only occurred at the high dose, but activation analysis in vitro showed increased ALAD activity to be present at all dose levels in a dose-dependent fashion. The use of an activation assay for red blood cell ALAD may have value as a bio-effects monitor of exposure to organic lead.

Animals↗