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Biomedical subjects

D C Villeneuve

Publications and source records attributed to D C Villeneuve.

At least 19 recordsLinked to original sources
PubMed1992

Hexachlorobenzene (HCB) suppresses circulating progesterone concentrations during the luteal phase in the cynomolgus monkey.

Hexachlorobenzene (HCB) is a known reproductive toxin. However, the full spectrum of its reproductive toxicity is unknown. Consequently, the effect of HCB on serum oestradiol (E2) and progesterone (P4) concentrations during the follicular (days 1-9), periovulatory (days 10-14) and luteal (days 15 to beginning of next menses) phases was investigated in the spontaneously cycling cynomolgus monkey. Adult female cynomolgus monkeys (n = 16) were randomly assigned to one of four treatment groups and orally doses with gelatin capsules containing HCB (0.0, 0.1, 1.0 and 10.0 mg kg-1 body wt. day-1) mixed with glucose. A 10-week acclimitization phase was followed by 13 weeks of dosing. HCB induced a dose-dependent suppression of serum P4 concentrations during the luteal phase. However, circulating levels of P4 were unaffected during the follicular and periovulatory phases of the menstrual cycle. Serum E2 concentrations, body weight, menstrual cycle length and duration of menses were not affected by HCB treatment. The range of menstrual cycle length and duration range of menses, however, were broader in the highest dose group. We conclude that HCB interfers with mechanisms regulating ovarian steroidogenesis and suppresses P4 levels during the luteal phase in the cynomolgus monkey.

Animals↗
PubMed1992

Systemic toxicity of the heavy fraction of a coal coprocessing product in male rats following subchronic dermal exposure.

The systemic toxicity of a coal coprocessing product [heavy gas oil II (HGOII)] following subchronic, dermal exposure in male Sprague-Dawley rats was investigated. HGOII was applied to the dorsal skin daily at doses of 8.7, 20.8, 50.0, or 120.0 mg/kg body weight (bw) for 13 weeks. Another group of rats treated with a medium boiling coal liquefaction product (CLP) served as positive controls. Growth suppression and decreased food consumption were noted in the groups exposed to HGOII at 20.8 mg/kg and higher, and to CLP starting at the third week of treatment. Relative liver, kidney, and brain weights in the 20.8 mg/kg HGOII group and up were higher than those of the control. Increased spleen weight was observed in all HGOII-treated groups. CLP treatment also caused increased relative kidney and brain weights. Serum cholesterol was elevated in the HGOII-treated groups starting at 8.7 mg/kg while increased uric acid and lactate dehydrogenase were observed at 20.8 mg/kg and up. Decreased erythrocyte, hemoglobin, and platelet counts were observed at 20.8 mg/kg and higher. All HGOII-treated groups had elevated reticulocytes. These biochemical and hematological changes were not observed in the CLP-treated group. Mild to marked histological changes were observed in the thyroid, thymus, liver, spleen, and bone marrow of HGOII groups. In contrast, morphological changes were relatively mild in CLP-treated animals. Data from the present study demonstrated that the hematological endpoints were sensitive to the liquid fuels and that HGOII was more toxic than CLP.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1992

Neuropathologic findings in young male rats in a subchronic oral toxicity study using triethyl lead.

This study was undertaken to ascertain the neuropathologic effects of low level exposure of triethyl lead (3EL) to young male rats. Groups of 20 male Sprague-Dawley weanling rats were given 3EL at 0, 0.05, 0.10, 0.20, 0.50, and 1.00 mg/kg body wt for 91 days, 5 days/week by oral gavage. Lead acetate (PbHOAC) was given at 200 mg/kg body wt/day as a positive control. Animals (five or six) were perfused with glutaraldehyde following barbiturate anesthesia at the termination of the experiment. These animals and the remaining members of the group received a thorough gross and microscopic postmortem examination. Sections of the central, peripheral, and autonomic nervous systems were examined and lesions scored. No lesions were noted in the brain, but randomly distributed light microscopic changes of spinal cord Wallerian degeneration were noted to increase in a dose responsive manner (rho = 0.48; p < 0.01), with 3EL administration. Ultrastructural examination of selected sections of the lumbosacral nerves, revealed lesions characterized by reduced neurofilaments and neurotubules, and irregular lamellated axoplasmic dense bodies in all animals receiving lead. Organolead was only detected in animals receiving 3EL, but lead cations were detected in all lead-treated animals. The brain lead levels of 1.00 mg/kg/day and 200 mg Pb acetate positive control animals were equivalent. As distinctive ultrastructural lesions were seen in all rats treated with 3EL, we suggest that the no observed adverse effect level (NOAEL) for 3EL be lowered to less than 0.05 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Absorption and retention of uranium from drinking water by rats and rabbits.

Uranium in the form of uranyl nitrate hexahydrate was administered in drinking water to Sprague-Dawley rats for periods of 28 and 91 d and New Zealand White rabbits for 91 d. The animals consumed food and water ad libitum. Subgroups of rabbits were followed for recovery periods of up to 91 d; 24-h collections of urine and feces were performed for some of the rabbits at various times during the exposure and recovery periods. At the end of the experiment, all animals were sacrificed and femur and kidney samples were analyzed for uranium residues. The results show that both rats and rabbits absorb about 0.06% of ingested uranium in the gastrointestinal (GI) tract. The distribution and retention of uranium in the skeleton and kidneys of rats are comparable to parameters reported for humans. The retention half-time in rabbit bone is substantially longer than for humans. The implications of extrapolating from animal data to effects on humans are discussed.

Animals↗
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↗
PubMed1979

An interactive toxicological data handling system for a PDP-12 computer.

This paper describes a program developed for the cataloguing, storage and retrieval of toxicological data. The user can, through dialogue with the program, enter and update data, and request reports with statistical analyses. The system is written in the FOCAL-12 language for a PDP-12 laboratory computer, and is suitable for a larger number of moderately-sized experiments.

Computers↗