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At least 433 records · Page 24Linked to original sources
PubMed1990

Comparative toxicity of arsine gas in B6C3F1 mice, Fischer 344 rats, and Syrian golden hamsters: system organ studies and comparison of clinical indices of exposure.

In order to examine possible species differences in response to arsine exposure, multiple inhalation studies consisting of acute (1-day), subacute (14- and 28-day), and subchronic (90-day) exposures to this agent were conducted using three different species of rodents. Evaluations of hematopoietic organs and alterations in the heme biosynthetic pathway were the focus of these studies. Species used were B6C3F1 mice (exposed 1, 14, or 90 days), Fischer 344 rats (exposed 14, 28, or 90 days), and Syrian Golden hamsters (exposed 28 days). All arsine exposures were at concentrations of 0.5, 2.5, or 5.0 ppm except for 90-day studies, in which concentrations were lowered to 0.025, 0.5, or 2.5 ppm. No changes in body weight gain were observed in either sex of mice or hamsters. The only decrease in body weight gain occurred in male rats exposed to 5.0 ppm arsine for 28 days. Significant exposure-related increases in relative spleen weights occurred in both sexes of mice and rats in the 0.5 (except 14-day female rats), 2.5, and 5.0 ppm exposure groups from all studies and in hamsters in the 2.5 and 5.0 ppm exposure groups. Generally, increases in relative liver weight occurred in fewer exposure groups and were of a lesser magnitude than increases in spleen weight. Other parameters affected included decreased packed cell volumes (mice, rats, and hamsters), hematology profiles (rats), and an increase in delta-aminolevulinic acid dehydratase activity in all species. Arsenic content was measured in livers of rats after 90 days of exposure. Concentrations increased in relation to atmospheric concentrations of arsine. Histopathologic changes included increased hemosiderosis and extramedullary hematopoiesis in spleen and intracanalicular bile stasis (mice only) in liver. Additionally, bone marrow hyperplasia was observed in rats. Effects on other organs were not observed, suggesting that the hematopoietic system is the primary target for arsine. In conclusion, we have determined that the effects of arsine exposure upon mice, rats, and hamsters are similar. Most importantly, even though no effects on the hematopoietic system were observed following a single exposure to 0.5 ppm arsine which is 10 times the Threshold Limit Value (TLV) set by the American Conference of Governmental Industrial Hygienists, repeated exposure to 0.025 ppm (one-half the TLV) caused a significant anemia in rats.

Administration, Inhalation↗
PubMed1992

The effect of exposure pattern on the accumulation of particles and the response of the lung to inhaled particles.

We hypothesized that a rapid rate of delivery of particles to the lung would overwhelm the normal clearance mechanisms of the lung and result in a higher lung burden of particles and a greater inflammatory response than a slower rate of particle delivery. F344/N rats were exposed over a 12-week period to the same weekly concentration times time product of carbon black (CB) particles, but at three different exposure rates: 3.5 mg/m3, 16 hr/day, 7 days/week; 13 mg/m3, 6 hr/day, 5 days/week; or 98 mg/m3, 4 hr/day, 1 day/week. The intermediate exposure rate was chosen to mimic an occupational work week and to give an 8-hr, time-weighted average exposure equal to the threshold limit value (TLV) for nuisance dusts of the American College of Governmental Industrial Hygienists (10 mg/m3). Pure CB has a lower TLV, 3.5 mg/m3, than nuisance dusts, but this is based on avoidance of excessive dirtiness in the workplace, not on the toxicity of CB. Lung burdens of CB were measured after 3, 6, 9, and 12 weeks of exposure and at 4, 8, 12, 16, and 24 weeks after the exposure ended. The inflammatory response was quantified by analysis of bronchoalveolar lavage fluid (BALF) after 6 and 12 weeks of exposure and at 1, 12, and 24 weeks after exposure. The histopathology of the lung was evaluated at the end of the exposure and at 24 weeks after the exposure. Acquired lung burdens were between 3 and 4 mg/lung at the end of the exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1985

Interpretation of cell toxicity data for the estimation of potential irritation.

Three cytotoxicity assays were evaluated using 57 chemicals of various classes (inorganic and organic metal salts, solvents, detergents, reagents, drugs) which have widely different mechanisms of cytotoxicity. Baby hamster kidney fibroblasts (BHK-21/C13) and early (Keller) and late (MRC-5) passage human fibroblasts were used to measure cell detachment, cloning efficiency, and growth inhibition under subconfluent culture conditions. For the majority of chemicals, for which comparisons were made, the ranking order was roughly the same in all three tests and with all three cell types. However, for some chemicals specific growth effects could either be detected or excluded because the relationship between the data from the detachment assay and that from one of the growth assays was characteristically altered. The ranking order resulting from our in vitro data correlated better with threshold limit values for human workroom air (TLV/TWA) than with LD50 values (rat, oral). Correlations with data from Draize skin and eye irritation tests were not determined since the available in vivo values were derived using various different scoring systems. However, when our in vitro data were used to divide the chemicals into three crude classes, (i) non-irritant, (ii) mild to moderate irritant, or (iii) strong irritant or corrosive, and the results were compared with the known irritation potential for skin and mucous membranes derived from human exposure data, the in vitro data were more than 80% predictive of the in vivo classifications.

Animals↗
PubMed1986

Toxicological evaluation of hydrochlorofluorocarbon 142b.

Groups of 110 rats of each sex were exposed by whole-body inhalation to 0, 1000, 10,000 or 20,000 ppm (v/v) of hydrochlorofluorocarbon 142b (CFC 142b or 1-chloro-1, 1-difluoroethane) for 6 hr/day, 5 days/wk for 104 wk (ten rats from each group were killed after 52 wk) in a combined chronic toxicity and oncogenicity study. Concurrently, ten male rats per group were exposed to the same concentrations for 13 wk in a bone-marrow cytogenicity study and another ten male rats per group were exposed for 15 wk in a dominant lethal study. No toxicologically significant compound-related effects were observed in behaviour, appearance, growth, clinical pathology, or gross and microscopic pathology. Respiratory infection and consequently higher than expected mortality during the first year did not compromise the studies or conclusions but may have contributed to the intergroup differences in the numbers of chromosome breaks and acentric fragments. No evidence for mutagenic potential was seen in either the dominant lethal or the cytogenetic assays. These data indicate the very low toxicity of CFC 142b with respect to chronic effects and genotoxic and oncogenic potential. The toxicological profile of CFC 142b is similar to that of other chlorofluorocarbons that have been assigned a threshold limit value (TLV) of 1000 ppm as a workplace 8-hr time-weighted average by the American Conference of Governmental Industrial Hygienists.

Animals↗
PubMedDate not supplied

Decreased level of lysozyme in rabbit lung lavage fluid after inhalation of low nickel concentrations.

Six rabbits were exposed for 4 months (5 days/week, 6 h/day) and 6 rabbits for 8 months to approx. 0.1 mg/m3 of metallic nickel dust (U.S. threshold limit value (TLV) 1 mg/m3). Another 8 rabbits were exposed for 4-6 weeks (5 days/week, 6 h/day) to 0.3 mg/m3 (as Ni) of nickel chloride (U.S. TLV 0.1 mg/m3). After exposure lungs were lavaged. Concentration of lysozyme in the lavage fluid was estimated with the lyso-plate technique (agar plates with heat-killed Micrococcus lysodeikticus) after macrophages had been removed. All 3 exposed groups had markedly lower concentrations of lysozyme than corresponding controls. Mean values in controls and exposed rabbits were: for 4 months metallic nickel dust exposure 2.3 and less than or equal to 0.04 microgram/ml; for 8 months metallic nickel dust exposure 1.4 and less than or equal to 0.5 microgram/ml; and for nickel chloride exposure 1.9 and less than or equal to 0.4 microgram/ml.

Animals↗
PubMed1989

Persistent effects of neonatal toluene exposure on regional brain catecholamine levels and turnover in the adult male rat.

Effects of neonatal toluene exposure (80 ppm, day 1-7, 6 h/day) have been studied on regional brain catecholamine levels and utilization, and on serum levels of hypophyseal and adrenocortical hormones in the adult male rat. Catecholamine levels were measured by quantitative histofluorimetry in the forebrain and hypothalamus and by high pressure liquid chromatography with electrochemical detection in the substantia nigra. Catecholamine utilization was evaluated from the decrease in catecholamines seen after tyrosine hydroxylase inhibition using alpha-methyl-p-tyrosine methyl ester hydrochloride (alpha MT, 250 mg/kg, i.p., 2 h). Serum levels of thyroid stimulating hormone, corticosterone, aldosterone, prolactin and luteinizing hormone were measured by radioimmunoassays. Neonatal toluene exposure produced a reduction of dopamine levels and utilization selectively in the olfactory tubercle and substantia nigra of the adult rat. Furthermore, neonatal toluene exposure produced a significant reduction in the noradrenaline levels and utilization in the substantia nigra and an increase of noradrenaline utilization selectively in the subependymal layer of the median eminence and of the magnocellular part of the paraventricular hypothalamic nucleus. The serum hormone levels were not significantly influenced by neonatal toluene exposure as evaluated in adulthood. However, the alpha MT induced increase in serum prolactin levels was reduced following neonatal exposure to toluene. Neonatal toluene treatment was also found to alter the responses of the catecholamine neurons to subacute toluene exposure in adulthood. In some of the dopamine nerve terminal systems of the forebrain and in the dopamine cell body containing area of the substantia nigra neonatal toluene exposure appears to have made the dopamine neurons insensitive to adult subacute toluene exposure. In the hypothalamic noradrenaline nerve terminal systems, there were even reversed responses to subacute toluene exposure. The present results indicate that neonatal toluene exposure in doses at the threshold limit value produces persistent changes in dopamine and noradrenaline neurons of the forebrain, hypothalamus and substantia nigra in the presence of a relatively intact neuroendocrine system. In addition, neonatal toluene exposure appears to diminish or even counteract the responses to subacute toluene treatment in adulthood.

Administration, Inhalation↗
PubMed1995

Pulmonary toxicity of nickel subsulfide in F344/N rats exposed for 1-22 days.

Repeated inhalation of nickel subsulfide (Ni3S2) by F344/N rats for 3 months results in chronic active inflammation in the lung and atrophy of the olfactory epithelium. The primary purpose of this study was to determine early responses of the respiratory tract to inhaled Ni3S2 in rats and to track the course of development of such lesions in rats exposed for up to 22 days. A secondary purpose was to obtain an improved estimate of the half-time for clearance of Ni from Ni3S2-exposed lungs. Groups of F344/N rats were exposed to 0, 0.6 or 2.5 mg Ni3S2/m3, 6 h/day for 1-22 days. Histopathological changes in nose and lung, as well as biochemical and cytological changes in lung, as measured in bronchoalveolar lavage fluid (BALF) and lung tissue, alveolar macrophage (AM) viability and Ni concentration in lung were evaluated. Inflammatory lung lesions in rats exposed to 2.5 mg Ni3S2/m3 peaked in intensity after 4 days of exposure. Minimal degeneration of the olfactory epithelium was noted in the 2.5 mg Ni3S2/m3-exposed rats after day 4 of exposure, with atrophy of the olfactory epithelium occurring in rats killed at 22 days. Lactate dehydrogenase, beta-glucuronidase and total protein in BALF were significantly elevated within 7 days of exposure while alkaline phosphatase activity was significantly depressed. AM viability was significantly reduced after 2 days of exposure. Concentrations of Ni in lung increased rapidly during the first 7 days of exposure, but more slowly thereafter. Lung burden data from this and a previous study suggest a clearance half-time for Ni of 3.5-8 days. Results indicate that Ni3S2 is relatively soluble in lung and inhalation of concentrations near the current Threshold Limit Value of 1 mg Ni/m3 can produce detrimental changes in the respiratory tract of rats after only a few days of exposure.

Administration, Inhalation↗
PubMed1996

Butadiene inhalation accelerates arteriosclerotic plaque development in cockerels.

1,3-Butadiene (BD), a gas widely used in the rubber industry, is also present in automotive exhaust and in the vapor phase of environmental tobacco smoke (ETS; approximately 400 micrograms/cigarette). The threshold limit value (TLV) for BD which was 10 ppm, has now been reduced to 2 ppm. Extensive investigations of workers have identified very few statistically significant increases in BD-associated cancer mortality. However, two studies have reported increased BD-associated mortality from arteriosclerotic heart disease in black workers in the BD rubber industry. The cockerel is a sensitive animal model for studying effects of environmental agents on arteriosclerosis development. Previous studies showed that inhaled environmental levels of ETS significantly accelerate arteriosclerosis. Surprisingly, the carcinogen-rich tar fraction of ETS was ineffective. The elevated risk of death from arteriosclerotic heart disease in black BD workers and the high BD level in the vapor phase of ETS, raised the question of whether BD would accelerate arteriosclerosis in cockerels. Here, cockerels breathed either 20 ppm BD or filtered air (6 h/day, 80 days). Blinded measurements showed no differences between groups in plaque frequency or location. However, plaque sizes were significantly larger in BD-treated cockerels than in controls--results nearly identical to those reported earlier for ETS-exposed vs. air-exposed cockerels. This indicates that BD may contribute to the atherogenicity of ETS and provides experimental support for the recent reduction in the TLV for BD.

Administration, Inhalation↗
PubMed1980

Titanium retention in mice.

Intraperitoneal (i.p.) and intravenous (i.v.) injection of 44Ti in a chloride solution into mice produced no detectable translocation in body fluids. There was no obvious interorgan exchange up to 16 days after injection. The whole body biological retention half-lives had a mean of 642 days for both routes, another indication of 44Ti's insolubility in body fluids. Absorption from the gastrointestinal (g.i.) tract after administration by stomach tube was negligible. The threshold limit value (TLV) for titanium in air, based upon nuisance dust, is acceptable based upon the results of this study.

Animals↗
PubMed1981

Sensory irritation caused by various industrial airborne chemicals.

A short inhalation experiment was performed on mice using 22 industrial airborne irritants. The parameter chosen as an index of sensory irritation was the reflex decrease in respiratory rate. For each compound, systematic determination of the concentration associated with a 50% decrease in the respiratory rate (RD50) permitted, on the basis of the same end point, a comparison of their relative potencies. The possibility of using the obtained data as initial guidelines to establish acceptable Threshold Limit Values (TLVs) in the workplace was examined.

Air Pollutants↗
PubMed1982

Toluene and telencephalic dopamine: selective reduction of amine turnover in discrete DA nerve terminal systems of the anterior caudate nucleus by low concentrations of toluene.

The present study demonstrates reductions of dopamine (DA) turnover in various areas of the anterior nucleus caudate of rat by toluene at concentrations lower than the current OSHA threshold limit value (100 ppm). Thus, toluene at low concentrations may produce disturbances in dopaminergic mechanisms of the basal ganglia probably leading to functional changes in sensory-motor integration. The increases in DA turnover in the cholecystokinin (CCK)-DA terminals of the subcortical limbic system induced by high concentrations of toluene may be part of the neurochemical basis for its abuse as a euphoric agent in man.

Animals↗
PubMed1984

Response of the upper respiratory tract of the rat to white spirit vapour.

The threshold limit value (TLV) adopted by industry for white spirit is that of Stoddard's solvent and is currently set at 100 ppm (525 mg/m3). Exposure of rats to atmospheres containing an average of 214 mg/m3, 4 h/day, for 4 consecutive days resulted in irritation of the membranes lining the upper respiratory tract but only minimal signs of lung injury. Histopathological changes were observed in the nasal cavity, trachea and larynx and included loss of cilia, mucous and basal cell hyperplasia and squamous metaplasia. These results suggest that in man exposure to white spirit at or around the TLV may result in irritation of the upper respiratory tract.

Animals↗
PubMed1985

Effects of toluene inhalation on pulmonary host defenses of mice.

The potential hazards of exposure to vapor-phase toluene on pulmonary host defenses were evaluated. Mice exposed to concentrations ranging from 2.5-500 ppm, including the threshold limit value level of 100 ppm, exhibited increased susceptibility to respiratory infection with Streptococcus zooepidemicus. The no-measurable-effect level for single, as well as for 5 exposures was 1 ppm. Significantly decreased pulmonary bactericidal activity was observed after single exposures to 500, 250, 100 and 2.5 ppm toluene, and after 5 daily 3-h exposures to 1.0 ppm of toluene. A 20-exposure study with toluene at 1 ppm produced no changes in either of the 2 assays.

Animals↗
PubMed1989

Evaluation of the subacute nephrotoxicity of cyclohexane and other industrial solvents in the female Sprague-Dawley rat.

The subacute nephrotoxicity of more than 20 industrial solvents has been compared in female Sprague-Dawley rats. The animals were given 5 i.p. injections of the solvents per week for 2 weeks at doses ranging from 1/20 to 1/5 of the i.p. or oral LD50 and the urinary excretion of N-acetyl-beta-D-glucosaminidase, beta 2-microglobulin and albumin was determined. Under these experimental conditions, two solvents, cyclohexane and styrene, were found to cause some tubular injury as evidenced by a statistically significant increase of beta 2-microglobulinuria. At the same dose, styrene was more tubulotoxic than cyclohexane but the opposite was observed when the solvents were administered proportionally to their LD50. The increased beta 2-microglobulinuria caused by cyclohexane was both time- and dose-dependent. It was not accompanied by changes in the glomerular filtration rate and the renal plasma flow, but at the highest dose (1.5 g/kg) the renal concentrating ability was depressed. These renal tubular effects can most likely be ascribed to cyclohexanol, the main metabolite of cyclohexane. As cyclohexane is a widely used industrial solvent with a relatively high threshold limit value (TWA-TLV: 300 ppm) it might represent an underestimated risk for the renal function of exposed populations.

Albuminuria↗
PubMed1995

Biological monitoring and standard setting in the USA: a critical appraisal.

Occupational exposure limits (OELs) issued in the US by the Occupational Safety and Health Administration (OSHA) require measurements of toxic substances in air rather than in biological samples. Most of OSHA's limits were adopted from the 1968 list of the American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Values (TLVs). Although there are no formal requirements to monitor exposures to these substances, it is implicit in the standards that air sampling will be performed. Of the 13 OELs which OSHA has set de novo, 2 (i.e., those for lead and cadmium) require biomonitoring after air sampling has identified the heavily exposed workers. OSHA appears to value biomonitoring in some circumstances but has apparently not found a consistent rationale for using biomarkers to set and enforce its standards. This paper discusses 2 valuable features of biomarkers which should be exploited by OSHA to further its regulatory agenda. The first relates to controversies associated with dose rate which have come into play in setting short-term exposure limits (STELs) when acute effects do not provide the necessary justification. OSHA has not provided evidence that its STELs are needed to reduce the risks of disease (as in the cases of benzene and ethylene oxide). By investigating the exposure-biomarker relationship, it is possible to determine whether the rate of exposure has any influence on the uptake and elimination of toxic substances and, therefore, whether STELs is needed. This is illustrated with data from 2 studies on styrene exposure. The second feature concerns biomonitoring as the primary means of exposure assessment in situations where the biomarker is accumulated over months or years (as in the cases of lead and cadmium). Using data from the lead-battery industry, it is shown that 'correct' compliance decisions are more likely to arise from evaluation of blood lead measurements than from traditional air monitoring.

Chemistry, Clinical↗
PubMed1992

Simultaneous high-performance liquid chromatographic determination of urinary metabolites of benzene, nitrobenzene, toluene, xylene and styrene.

A high-performance liquid chromatographic method is described for the simultaneous determination of six urinary metabolites of several aromatic chemicals: phenol (from benzene), hippuric acid (from toluene), 3-methylhippuric acid (from xylene), mandelic and phenylglyoxylic acid (from styrene) and 4-nitrophenol (from nitrobenzene). Reversed-phase liquid chromatography was performed in an isocratic mode at 1 ml/min on a 5-microns C18 column using two mobile phases: (A) acetonitrile-1% phosphoric acid (10:90); (B) acetonitrile-1% phosphoric acid (30:70). Phase A separates the six metabolites well, but phase B allows to a more rapid and reproducible simultaneous determination of phenolic compounds than phase A. For these compounds a prior enzymic hydrolysis step using Helix pomatia juice is performed to hydrolyse their sulphate and glucuronate conjugates. The reproducibility and the specificity are both excellent. Furthermore, the method is rapid, economical and easily automated. The proposed method appears very suitable for the routine monitoring of workers exposed to these chemicals on the basis of the biological threshold limit values.

Benzene↗
PubMed1988

Semen quality in workers producing reinforced plastic.

A comparison of semen parameters from 25 workers at a reinforced plastic production plant and from 46 age-matched male fertility patients was carried out. For a period of more than three months before the semen analyses, the 25 workers had been exposed to styrene and acetone in concentrations exceeding the Danish threshold limit values. Serum concentrations of follicle stimulating and luteinizing hormones, semen sample volume, and concentration of sperm showed no differences between the two groups. Significant differences between the two groups were found in the percentage of live sperm, immotile sperm, and normal sperm. The reinforced plastic plant workers showed, in terms of semen quality, better values in the percentages of live sperm and immotile sperm, whereas they had a reduced percentage of normally shaped sperm. It was found that the reinforced-plastic workers had increased percentages of the amorphous and the pyriform sperm head shapes as compared to the fertility clientele. In sperm midpiece and sperm tail defects, the two groups showed similar values. From the data it could be concluded that work with production of reinforced plastic might result in an increase in the number of abnormal sperm heads.

Acetone↗
PubMedDate not supplied

An ethologist's approach to behavioural toxicology.

Ethology, the biology of behaviour, is briefly introduced, and a review is presented of two ethological methods applied to toxicology. (1) When elements in the behaviour of rats in a social situation are objectively observed, chemically-induced changes in several kinds of behaviour can be detected at low doses. Changes are specific and repeatable in long-term experiments. Effects of nicotine at a 'smoking' dose, or trichloroethylene at the Threshold Limit Value, were reversible; limited tolerance developed to methyl mercury dicyandiamide. (2) An 'Exploration-Thirst' method is simple enough for use as a screen. It was compared with conventional toxicological methods for 30 compounds in routine screening (20 acute intraperitoneal, 10 subacute inhalation). Both ethological methods are sensitive enough to estimate 'no-effect' doses. They also distinguish non-specific toxic effects (consistent with the animal's equivalent of 'feeling ill') from various more specific CNS effects comparable to those of human experience.

Animals↗