Biomedical subjects

M Potvin

Publications and source records attributed to M Potvin.

40 records · Page 3Linked to original sources

PubMedDate not supplied

Inhalation toxicity study of methanol, toluene, and methanol/toluene mixtures in rats: effects of 28-day exposure.

The inhalation toxicity of methanol and toluene was investigated in rats. Young Sprague Dawley rats of both sexes were exposed to vapors of methanol (300 ppm, 3000 ppm), toluene (30 ppm, 300 ppm) or methanol/toluene (300/30 ppm, 300/300 ppm, 3000/30 ppm, and 3000/300 ppm) six hrs per day, five days/week for four weeks. Control animals inhaled air only. Increased serum alkaline phosphatase activity was observed in males exposed to high-dose toluene, and decreased creatinine was noted in the group exposed to high-dose methanol/toluene. The thyroid gland in females appeared to be a target organ for inhaled methanol, toluene, and methanol/toluene, although the changes were confined to a mild, and occasionally moderate, reduction in follicle size. Histopathological changes of the nasal passages, consisting of subepithelial nonsuppurative inflammation, occurred in higher incidences in rats exposed to methanol/toluene than in those exposed to the individual vapors. Inhalation of methanol, toluene, or methanol/toluene produced no changes in liver weights, hepatic mixed-function oxidases, or serum aspartate transaminase activities, and onlly minimal changes in liver histopathology. The only liver changes were decreased liver weight and increased cytoplasmic density of the periportal areas in females exposed to high-dose methanol/toluene. These data indicated that exposure to methanol, toluene, or a mixture of both produced mild biochemical effects and histological changes in the thyroid and nasal passage. No apparent interactive effects were observed.

Administration, Inhalation↗

PubMedDate not supplied

Short-term inhalation toxicity of methanol, gasoline, and methanol/gasoline in the rat.

Four- to five-week-old male and female Sprague Dawley rats were exposed to vapors of methanol (2500 ppm), gasoline (3200 ppm), and methanol/gasoline (2500/3200 ppm, 570/3200 ppm) six hours per day, five days per week for four weeks. Control animals were exposed to filtered room air only. Depression in body weight gain and reduced food consumption were observed in male rats, and increased relative liver weight was detected in rats of both sexes exposed to gasoline or methanol/gasoline mixtures. Rats of both sexes exposed to methanol/gasoline mixtures had increased relative kidney weight and females exposed to gasoline and methanol/gasoline mixtures had increased kidney weight. Decreased serum glucose and cholesterol were detected in male rats exposed to gasoline and methanol/gasoline mixtures. Decreased hemoglobin was observed in females inhaling vapors of gasoline and methanol/gasoline at 570/3200 ppm. Urine from rats inhaling gasoline or methanol/gasoline mixtures had up to a fourfold increase in hippuric acid, a biomarker of exposure to the toluene constituent of gasoline, and up to a sixfold elevation in ascorbic acid, a noninvasive biomarker of hepatic response. Hepatic mixed-function oxidase (aniline hydroxylase, aminopyrine N-demethylase and ethoxyresorufin O-deethylase) activities and UDP-glucuronosyltransferase activity were elevated in rats exposed to gasoline and methanol/gasoline mixtures. Histopathological changes were confined to very mild changes in the nasal passages and in the uterus, where decreased incidence or absence of mucosal and myometrial eosinophilia was observed in females inhaling gasoline and methanol/gasoline at 570/3200 ppm. It was concluded that gasoline was largely responsible for the adverse effects, the most significant of which included depression in weight gain in the males, increased liver weight and hepatic microsomal enzyme activities in both sexes, and suppression of uterine eosinophilia. No apparent interactive effects between methanol and gasoline were observed.

Animals↗

PubMedDate not supplied

Inhalation toxicity of methanol/gasoline in rats: effects of 13-week exposure.

The subchronic inhalation toxicity of a methanol/gasoline blend (85% methanol, 15% gasoline, v/v) was studied in rats. Sprague Dawley rats (10 animals per group) of both sexes were exposed to vapours of methanol/gasoline at 50/3, 500/30 and 5000/300ppm for 6 hours per day, 5 days per week, for 13 weeks. Control animals inhaled filtered room air only. Control recovery and high dose recovery groups were also included which inhaled room air for an extra 4 weeks following the treatment period. No clinical signs of toxicity were observed in the treatment group and their growth curves were not significantly different from the control. Except for decreased forelimb grip strength in high dose females, no treatment-related neurobehavioural effects (4-6 hours post inhalation) were observed using screening tests which included cage-side observations, righting reflex, open field activities, and forelimb and hindlimb grip strength. At necropsy, the organ to body weight ratios for the liver, spleen, testes, thymus and lungs were not significantly different from the control group. There were no treatment-related effects in the hematological endpoints and no elevation in serum formate levels. Minimal serum biochemical changes were observed with the only treatment-related change being the decreased creatinine in the females. A dose-related increase in urinary ascorbic acid was detected in males after 2, 4 and 8 weeks of exposure, but not after the 12th week, and in females only at week-2. Increased urinary albumin was observed in treated males starting at the lowest dose and at all exposure periods, but not in females. A treatment-related increase in urinary beta 2-microglobulin was detected in males at week-2 only. Except for mild to moderate mucous cell metaplasia in nasal septum B, which occurred more often and with a slightly higher degree of severity in the low dose groups of both sexes, and presence of a minimal degree of interstitial lymphocyte infiltration in the prostate glands in the high dose males. No other significant microscopic changes were observed in the tissues of treated animals. Based on the marked increase in urinary ascorbic acid and albumin in the high dose males and the decreased forelimb grip strength in the high dose females, we concluded that the no-observed adverse effect level (NOAEL) of methanol/gasoline vapour is 500/30 ppm.

Albuminuria↗

PubMedDate not supplied

Multi-center study of two dose levels of paclitaxel with carboplatin in locally advanced and metastatic non-small cell lung cancer (NSCLC).

BACKGROUND: The efficacy and toxicity of the combination of two cytotoxic compounds that are active as single agents in non-small cell lung cancer (NSCLC), paclitaxel (Taxol) and carboplatin (Paraplatin) was investigated in a multicenter, community-based setting. MATERIALS AND METHODS: Two consecutive cohorts of chemonaive patients with stages IIIA/B and IV NSCLC received two dose levels of paclitaxel. The first cohort received 200 mg/m2 over 3 hours (HD) and the second cohort 175 mg/m2 over 3 hours (LD) in combination with a fixed dose of carboplatin. The dose of carboplatin was calculated according to the Calvert formula with an area under the concentration versus time curve (AUC) value of 6 mg/ml/minute. The carboplatin clearance, calculated by the Chatelut formula rather than the glomerulation filtration rate (GFR) +25, was introduced into the Calvert formula. The eligibility criteria were identical for both cohorts throughout the study. Treatment was administered every three weeks. The study endpoints were response rate (RR), toxicity, time to progression (TTP) and survival (S). RESULTS: One hundred and thirty consecutive eligible patients from 36 Belgian institutions were fully evaluable for all study parameters (99 in the HD and 31 in the LD cohort). Myelosuppression was the most prominent side-effect of treatment with comparable results for both cohorts. The worst grade 3-4 leucopenia and neutropenia per patient in the HD versus LD cohort was 34.4 vs 19.3% and 59.2 vs 51.6%, respectively. 10.4% of patients in the HD cohort required hospitalisation for febrile neutropenia (6.2% with and 4.2% without documented bacterial infection), while in the LD cohort the respective figures were 13.7, 10.3 and 3.4%. The most prominent non-hematologic toxicities were alopecia and polyneuropathy, with no major difference between the HD and LD cohort (grade 2 alopecia in 78.1 vs. 83.9% and grade 3 neuropathy in 14.3 vs. 9.7%, respectively). The overall best clinical RR was 31 out of 130 (23.8%) with one complete (CR) and 30 partial responses (PR). The respective RR in the HD and LD cohort was 23.2 and 25.8%. Median TTP and S for all patients was 120 and 248 days, with no apparent difference between the HD and the LD cohort (119 and 254 versus 128 and 222, respectively). The one year survival was 34% in the HD cohort. The 95% confidence intervals for efficacy and toxicity parameters overlapped in both cohorts. CONCLUSION: In this multicenter study, the combination of paclitaxel and carboplatin produced a moderate RR of 23.8% in stages IIIA/B & IV NSCLC. The therapy was generally well tolerated at both doses of paclitaxel. Myelosuppression, neurotoxicity and alopecia were the major therapy-related side-effects. The differences between the two paclitaxel dose cohorts with respect to activity and toxicity were minimal. The use of the Chatelut formula to calculate the carboplatin clearance is feasible, but might have lead to the apparent excess in myelotoxicity in our study compared to other studies which used other methods for estimating renal function.

Adenocarcinoma↗