On-line sources of toxicological information in Canada.

This paper will provide an overview of the on-line resources available in toxicology in Canada. It will describe a brief history of The Society of Toxicology of Canada, with reference to other societies and also provide information on education, research and other resources related to toxicology. Toxicology in Canada emerged as a distinct and vibrant discipline following the thalidomide tragedy of the 1960s.

Municipal firefighter exposure groups, time spent at fires and use of self-contained-breathing-apparatus.

Background: Previous studies have found significant associations between firefighting and cancer.

Methods: Fires, vehicle movement, and firefighter job assignment were determined, and storage and distribution of self-contained-breathing-apparatus (SCBAs) were tracked for 12 months. Time spent at fires and use of SCBAs were calculated.

Characterization of volatile organic compounds in smoke at municipal structural fires.

The objective of this study was to characterize volatile organic compounds (VOCs) found at municipal structural fires in order to identify sources of long-term health risks to firefighters, which may be contributing factors in heart disease and cancer. Firefighters collected air into evacuated Summa canisters inside burning buildings at nine municipal structural fires under conditions where they judged that at least some firefighters might remove their self-contained breathing apparatus masks. Volatile organic compounds were identified and quantified for 144 target compounds using cryogenic preconcentration and gas chromatography/mass spectral detection (GC/MSD) methodology operating in selected ion monitoring mode.

Characterization of volatile organic compounds in smoke at experimental fires.

Significant associations between firefighting and cancer have been reported; however, studies finding toxic products of combustion at municipal fires have been limited by (1) technical difficulties encountered at the scene of working fires, (2) the lack of a coherent sampling strategy, and (3) the absence of verified sampling methods. The objective of the present study was to characterize the presence of volatile organic compound (VOC) combustion products in fire smoke. Air samples from experimental fires burning various materials commonly found at structural fires were collected into evacuated Summa canisters and analyzed for 144 target VOCs using cryogenic preconcentration and gas chromatography/mass spectroscopy (GC/MSD) methodology.

Pesticide use in developing countries.

Chemical pesticides have been a boon to equatorial, developing nations in their efforts to eradicate insect-borne, endemic diseases, to produce adequate food and to protect forests, plantations and fibre (wood, cotton, clothing, etc.). Controversy exists over the global dependence on such agents, given their excessive use/misuse, their volatility, long-distance transport and eventual environmental contamination in colder climates.

Our changing perspectives on benefits and risks of pesticides: a historical overview.

The introduction of chemical pesticides following WW II ushered in the era of the "quick fix" for any aqricultural, forestry and human health problems. Scenarios of use, misuse, abuse and environmental contamination can be presented for any class of pesticide, culminating in dependence on these chemicals for increased production of food and fibre and improved health. With time, sophisticated agents having unique, target-specific mechanisms of action evolved but at increased cost(s) to crop production.

Tentative explanatory variable of lung dust concentration in gold miners exposed to crystalline silica.

Introduction: The first objective of the study was to investigate the relationships between quantitative lung mineral dust burdens, dust exposure history, and pathological fibrosis grading in silicotic workers. The second objective was to evaluate the association between particle size parameters, concentration of retained silica particles and the severity of the silicosis. Sixty-seven paraffin-embedded lung tissue samples of silicotic patients were analyzed.

Carbon monoxide and water vapor contamination of compressed breathing air for firefighters and divers.

Compressed breathing air, used in self-contained breathing apparatus (SCBA) by firefighters and other categories of workers as well as by recreational and commercial divers, is prepared with the aid of high-pressure compressors operating in the range of 5000 psig. There have been reports of unexplained deaths of SCUBA divers and anecdotal accounts of decreased time to exhaustion in firefighters using SCBAs. Compressed breathing air has been found to contain elevated levels of carbon monoxide (CO) and water vapor that are consistent with carboxyhemoglobin (COHb) poisoning and freezing of the user's regulator on the breathing apparatus.

Protective antioxidant mechanisms in rat and guinea pig tissues challenged by acute exposure to cigarette smoke.

Cellular damage from reactive intermediates formed during xenobiotic biotransformation is prevented by the presence of adequate levels of antioxidant chemicals in the tissues. Equally important for cell protection is the rate at which these chemicals are replaced if tissue stores are depleted. The present experiments, using adult male Sprague-Dawley rats and Hartley guinea pigs, were conducted to ascertain what effects mainstream (MS) and sidestream (SS) tobacco smoke would have on the water-soluble, cytoplasmic antioxidants, ascorbic acid (AA) and reduced glutathione (GSH).

Abiotic transformations and decomposition kinetics of 4-carbamoyl-2'-[(hydroxyimino)methyl]-1,1'-(oxydimethylene)-bis(pyridin ium chloride) in aqueous phosphate buffers.

The rate of disappearance of 4-carbamoyl-2'-[(hydroxyimino)methyl]-1,1'-(oxydimethylene) bis (pyridinium chloride) (HI-6) from aqueous phosphate buffers (pH 3.0-9.1) was both pH and temperature sensitive.

Chemical management of forest pest epidemics: a case study.

The management of insect epidemics in large tracts of forest is difficult given the climatic conditions encountered, the topography of the forested land, the nature of the forest, the types of chemical and/or biological insecticides registered for use, and the technologies available for insecticide application. Since 1952, the province of New Brunswick, Canada, has been heavily involved in attempting to control an epidemic of the eastern spruce budworm (Choristoneura fumiferana. Clemens) that has ravaged the coniferous softwoods of eastern Canada and the United States.

Kinetics, distribution, and biotransformation of the chemical HI-6 in the rat, dog, and rhesus monkey.

Disposition of the bis-pyridinium mono-oxime, HI-6, following intramuscular injection in rats (200 mg/kg bw), beagle dogs (10 and 50 mg/kg bw), and rhesus monkeys (50 mg/kg bw) revealed that the oxime was absorbed rapidly and completely from the site of injection, was distributed rapidly in the tissues, and that tissue concentrations decreased below the limits of detection by 4 h after treatment. No overt signs of toxicity were observed in any species at the concentrations given. Tissue analysis for HI-6 and degradation products was conducted by extraction followed by ion-pair, reverse phase, HPLC chromatography.

Disposition and elimination of BIOLF-143, an antiviral agent, in the rabbit.

BIOLF-143, (N-(dimethylamino)methylene-9- [[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine), an experimental, purine-based, acyclic nucleoside was administered by iv or ip injection to adult, male and female, albino New Zealand rabbits in order to determine: (1) the pharmacokinetic disposition, (2) the route and rate of excretion, (3) the biotransformation, and (4) the acute toxicity of the agent. HPLC analysis of blood plasma concentrations of BIOLF-143 was conducted following iv injections of 50 or 100 mg/kg and ip injections of 250 mg/kg. Tissue levels of BIOLF-143 were analyzed at 60 min following an ip injection of 100 mg/kg.

Evaluation of exposure of health care personnel to ribavirin.

Reports that ribavirin was teratogenic in animals raised concerns of female health care personnel about possible occupational exposure during the care of infants having respiratory syncytial virus infections. Under simulated operational conditions, experiments were conducted to measure ribavirin residues in room air, in surface wipe samples, and in personal sampling devices worn by volunteers. There was exposure to a dispersible dust, presumably dried ribavirin, deposited inside the croupette or hood and on the bedding.

Acetaminophen metabolism in vivo by pregnant, fetal, and neonatal guinea pigs.

Acetaminophen (50 mg/kg body weight) was administered by iv injection to pregnant guinea pigs (60-65 days of gestation) and by ip injection to cesarean-derived term (67 days of gestation) pups. At suitable time intervals after treatment, the concentrations of drug, glucuronide (GLU), and sulfate (SO4) in blood plasma, urine, and bile were measured by high-performance liquid chromatography (HPLC). At 60-65 days of gestation, guinea pig fetuses formed both GLU and SO4, an approximate ratio of 2:1 being observed with mean concentrations of the order of 43 and 27 micrograms/mL being measured for GLU and SO4, respectively at 180 min post-treatment.

Subacute inhalation of cigarette smoke by pregnant and lactating rodents: AHH changes in perinatal tissues.

To study the transplacental acquisition of tobacco smoke products and the effects on fetal tissue enzymes, pregnant rats, guinea pigs, and hamsters were exposed to freshly generated cigarette smoke via a nose-only inhalation system on a daily basis through the latter one-third (guinea pigs) or latter half (rats, hamsters) of the gestational period. Following euthanasia on the day of parturition, microsomal aryl hydrocarbon hydroxylase (AHH) activities were determined in the lungs, livers, and kidneys of both dams and fetuses. The possible acquisition of tobacco smoke products via the milk was studied by exposing lactating dams to cigarette smoke daily for either 4 or 14 days (rats), 4 or 7 days (guinea pigs), or 10 days (hamsters), with analysis of tissues from the euthanized pups for AHH.

Drug disposition and biotransformation in the developing beagle dog.

The ability of developing male and female beagle pups to biotransform and eliminate drugs was studied by administering single intravenous doses of acetaminophen (50 mg/kg body wt), phenobarbital (15 mg/kg body wt), or phenytoin (15 mg/kg body wt) to the same groups of dogs (n = 6-8/drug) at 4, 10, 20, 40, and 60 days of age. At suitable intervals after treatment, small (1.0 ml) blood samples were obtained via the jugular vein and centrifuged and the plasma was recovered and stored at -20 degrees C to await analysis.

The acute toxicity of BIOLF-143 in the rat.

BIOLF-143, an experimental, purine-based acyclic nucleoside, was administered by iv or ip injection to young, adult, male and female Sprague-Dawley rats in order to determine the (1) pharmacokinetic disposition, (2) route and rate of excretion, and (3) acute toxicity. HPLC analysis of plasma, hepatic, and renal tissue levels was conducted following iv injections of 50 and 100 mg/kg and ip injections of 500 mg/kg. Metabolism/excretion studies were conducted following ip injections of BIOLF-143 (100 mg/kg).

Hexahydrocarbon effects on intermediate filament organization in human fibroblasts.

We reported previously that 2,5-hexanedione (2,5-HD), the neurotoxic metabolite of methyl-n-butylketone (MnBK) and n-hexane, induced aggregation of intermediate filaments of the vimentin type in cultured fibroblasts. To determine if these findings have relevance to the mechanism by which these hexacarbons induce their filamentous axonopathy, it was necessary to show that only those hexacarbon analogues that induce focal accumulation of neurofilaments in nerve fibers do aggregate intermediate filaments in fibroblasts. We report here that the nonneurotoxic hexacarbons, 1,6-hexanediol and 2,4-hexanedione (2,4-HD), had no primary effect on intermediate filament distribution in fibroblasts, although the profound, nonspecific cytotoxicity of the latter controverted comparisons with equimolar, effective concentrations of 2,5-HD.

An assessment of the neurotoxic potential of fenitrothion in the hen.

The potential of single, toxic doses of fenitrothion (O,O-dimethyl O-(4-nitro-m-tolyl)phosphorothioate) to elicit delayed neurotoxicity in the adult White Leghorn hen was compared to the effects produced following similar treatment with the known neurotoxin, tri-o-tolyl phosphate (TOTP). Hens (2.0-2.

A subchronic inhalation toxicity study of a Matacil formulation in the albino rat.

The subchronic toxicity of a new formulation of Matacil (aminocarb) was assessed by exposing male and female Sprague-Dawley rats via a nose-only technique to a respirable (2.0- to 4.1-microns diameter) aerosol at chamber concentrations of 22.

Acetaminophen in the guinea pig: metabolite identification in blood, urine, and bile.

The biotransformation of single acute oral doses of acetaminophen (100 mg/kg body weight) in adult male guinea pigs was studied by collecting serial blood, urine, and bile samples post-treatment and identifying and quantitating the concentrations of parent drug and excretory products by high performance liquid chromatography. The plasma half-life (beta t/2) (mean +/- SD) of acetaminophen was 1.87 +/- 0.