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PubMedDate not supplied

[State of the lymphoid tissue of tracheobronchial lymph nodes in rats after incorporation in respiratory organs of low-transportable Pu-239].

After single inhalation exposure of rats to low transportable 239Pu the alpha-irradiation doses in tracheo-bronchial lymph nodes (TBLN) were one order of magnitude lower than those in lung. The reduction of cell population in TBLN was observed in late (12-18 month after) post-inhalation period. Dose-response curve for the reduction (as a whole for 12 month) were presented as a line function. Functional abilities of these cells were less damaged and observed in different periods after inhalation. As one of the probable mechanisms of different radiation damage to cells in TBLN population, a variety in their spatial distribution is discussed.

Administration, Inhalation↗
PubMed1982

Distribution, retention and dosimetry of plutonium and americium in the rat, dog and monkey after inhalation of an industrial-mixed uranium and plutonium oxide aerosol.

This study provides information on patterns of radiation dose in laboratory animals after inhalation exposure to an aerosol of one form of mixed uranium and plutonium oxide. The aerosol contained a mixture of UO2 and 750 degrees C heat-treated PuO2 obtained from the ball milling operation in a mixed-oxide fuel fabrication process. Americium-241 from the decay of 241Pu was also present in the PuO2 matrix. Fischer-344 rats, Beagle dogs, and Cynomolgus and Rhesus monkeys inhaled aerosols re-generated from dry mixed oxide powders with particle size distribution characteristics similar to those observed in samples collected at the industrial site. Clearance from the lung and distribution in other tissues of the plutonium from this UO2 + PuO2 admixture was similar to what has been observed for PuO2 from laboratory-produced aerosols. The UO2-PuO2 aerosol was relatively insoluble in the lungs of all species. Monkeys and rats cleared plutonium and americium from their lungs faster than dogs. Very little plutonium or americium translocated within the first 2 yr after exposure to tissues other than tracheobronchial lymph nodes. The greater accumulation of plutonium and americium in the tracheobronchial lymph nodes of dogs as compared to monkeys and rats combined with the more rapid initial clearance of these radionuclides from the lungs of rats and monkeys suggests that errors could result from using data from a single animal species to estimate risk to humans from inhalation of these industrial aerosols.

Aerosols↗
PubMed2006

Micronuclei, DNA single-strand breaks and DNA-repair activity in mice exposed to 1,3-butadiene by inhalation.

We investigated single-strand breaks and endonuclease III-sensitive sites in DNA along with gamma-irradiation-specific DNA-repair activity in hepatocytes and frequencies of micronuclei in polychromatic bone-marrow erythrocytes of male NMRI mice (2 months old, weight 30-35 g) during sub-acute inhalation exposure to 1,3-butadiene (28 days, 500 mg/m3) and up to 28 days after the exposure. Concentrations of 1,3-butadiene in blood, an indicator of internal exposure, moderately increased during the exposure period. The most interesting finding was that gamma-irradiation-specific DNA-repair activity gradually increased during exposure, being significantly higher compared with control levels on days 7 and 28 of exposure (P = 0.005 and 0.035, respectively), reaching a maximum on day 1 after the termination of exposure (P = 0.003) and then returning to control levels. A significant correlation between gamma-irradiation-specific DNA-repair activity and the concentration of 1,3-butadiene in blood (R = 0.866, P = 0.050) supports a possible induction of DNA-repair activity by the exposure to 1,3-butadiene and formation of its metabolites. The initial increase in micronucleus frequency (micronuclei per 1000 cells) in the exposed mice continuously decreased from 20.4 +/- 5.1 (day 3) to 15.1 +/- 3.2 (day 28) within the exposure period, and subsequently from 12.4 +/- 5.1 to 4.6 +/- 1.6 in the period following termination of the 1,3-butadiene exposure, while micronucleus frequencies in control animals were significantly lower (from 1.7 +/- 1.5 to 4.2 +/- 0.8).

Administration, Inhalation↗
PubMed1988

Kinetics of the bronchoalveolar leucocyte response in rats during exposure to equal airborne mass concentrations of quartz, chrysotile asbestos, or titanium dioxide.

The kinetics of the bronchoalveolar response was assessed in rats exposed, at equal airborne mass concentration (10 mg/m3), to titanium dioxide--a non-pathogenic dust--and the two pathogenic mineral dusts quartz and chrysotile asbestos. Rats were killed at intervals over a 75 day exposure period and groups of rats exposed for 32 and 75 days after recovery for two months. Bronchoalveolar lavage was carried out and the lavage fluid characterised for cellular content, macrophage activation, and concentrations of free total protein, lactate dehydrogenase, and N-acetyl-beta-D-glucosaminidase. Inhalation exposure to the two pathogenic dusts resulted in an increased number of leucocytes, macrophage activation, and increased levels of free enzymes and total protein. The pattern and magnitude of the responses to quartz and chrysotile differed. Chrysotile caused less inflammation than quartz, and the main cellular response peaked around the middle of the period of dust exposure whereas the highest levels of enzymes occurred towards the end. The difference in timing suggests that macrophages were not available for lavage towards the end of the exposure, owing to their playing a part possibly in deposition of granulation tissue. Quartz caused a greater cellular and enzyme response than chrysotile, particularly towards the end of the dust exposure phase. There was a noticeable progression of inflammation in the quartz exposed groups left to recover for two months, but not in the chrysotile recovery groups.

Animals↗
PubMed1997

Effects of ozone on macrophage adhesion in vitro and epithelial and inflammatory responses in vivo: the role of cytokines.

Inhalation exposure to ozone (O3) is known to induce epithelial and inflammatory changes in the lungs, characterized by neutrophilia and changes in epithelial permeability. Several cell types and their soluble mediators, including interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), are involved in the evolution of these responses. In this study, we have compared the effects of the combination of anti-IL-1 alpha and anti-TNF-alpha on in vitro and in vivo responses to inhaled O3. Male, Sprague-Dawley rats were exposed, nose-only, to 0.8 ppm O3 for 3 h and the in vitro and in vivo parameters were measured 8-12 h following exposure. The in vitro studies revealed that the adherence of inflammatory cells, primarily macrophages, harvested from the lungs of O3-exposed rats to cultured lung epithelial cells (ARL-14) was significantly greater than the adherence of macrophages from air-exposed controls. Furthermore, this adherence was significantly reduced in antibody-treated cells as compared to cells treated with preimmune rabbit serum. In vivo, elevations were found in the percentage of neutrophils in bronchoalveolar lavage fluid (BALF), transport of 99mTc-diethylenetriaminepentaacetate (DTPA) across the tracheal epithelium, and concentrations of total protein and albumin in BALF following O3 exposure. However, these effects were not significantly altered by treatment with the anti-IL-1 alpha/anti-TNF-alpha combination. Therefore, it was concluded that O3 affects the early stages of the inflammatory response, particularly with respect to macrophage activation and adherence to epithelial cells, and that this early response may be mediated by IL-1 alpha and/or TNF-alpha. The results also suggest that the in vivo effects of O3 are controlled by complex mechanisms involving factors other than IL-1 alpha and TNF-alpha, even though these cytokines are capable of modifying macrophage function as revealed by the in vitro adherence studies.

Administration, Inhalation↗
PubMed2005

Exposure to vapors, gas, dust, or fumes: assessment by a single survey item compared to a detailed exposure battery and a job exposure matrix.

BACKGROUND: Occupational exposure assessment often relies upon subject report. We examined the characteristics of self-reported exposure in respondents' longest held job to vapors, gas, dust, or fumes (VGDF) compared to other measures of exposure risk. METHODS: We analyzed data from 1,876 respondents from a national US population-based telephone survey designed to estimate the association between occupational factors and chronic disease of the airways. We tested a single VGDF item against responses to a 16-item battery assessing specific inhalation exposures and against a job exposure matrix (JEM). We analyzed all of these measures for their association with adult-onset asthma after excluding subjects with COPD or asthma with onset before age 18. RESULTS: VDGF (single item) was reported by 744 (40%) subjects; any of the 16 exposures by 899 (48%); and an intermediate or high exposure likelihood job by JEM was assigned to 682 (36%). The sensitivity of the VGDF item measured against the 16-item battery was 69%; the specificity was 88%; (classification agreement kappa=0.58); against the JEM classification the sensitivity was 64% and specificity 74% (kappa=0.37). The relative odds (OR) for adult-onset asthma associated with various measures of exposure were: VGDF, 1.7 (95% Confidence Interval [CI] 1.0-2.8; P=0.04); any of the 16 exposures, 1.6 (95% CI 1.0-2.7; P=0.06), and intermediate or high by JEM, 1.2 (0.7-2.1; P>0.50). CONCLUSIONS: A single VGDF survey item appears to delineate exposure risk at least as well as a multiple-item battery assessing such exposures; it has modest agreement with a JEM-based exposure categorization.

Aged↗
PubMed1987

Inhalation toxicity of ribavirin in suckling ferrets.

Ribavirin is a broad-spectrum antiviral agent useful for treatment of infants. To study the effects in developing mammalian lungs, four groups of jill ferrets and their litters were given whole body inhalation exposures for 6 h a day for 10 or 30 consecutive days to concentrations of 0 (vehicle control), 162, 355 or 620 mg/m3. The effects, including special lung observations in suckling kits, were evaluated after exposures at weaning and at puberty. First the high dose, then the mid dose jills developed lactation failure. Probably due to nutritional deficiency, approximately half of the mid dose and three quarters of the high dose kits were found dead or killed whilst moribund. There were no test compound-related deaths in the control or low dose level groups. Reductions in body weight gain were observed in both 10 and 30 day exposed kits, and high dose kits actually lost weight as exposure continued. Some recovery was apparent in survivors. Some discoloration of the liver was seen in malnourished kits at necropsy. There were no gross or histopathologic lesions in the lungs or tracheas of suckling ferrets attributable to the test material. Ribavirin exposure had no effect on the lavageable cell pool, while lung DNA to protein ratios showed a mild, reversible, proliferative response in smaller kits. There were no differences in lung function between controls and low dose kits of either group. Effects seen in the higher dose groups are due to differences in size. While there may have been a real dose-related enlargement of alveolar diameters at 40 days of age, this disappeared in males by puberty and did not seem toxicologically significant in females. The low dose, which corresponds to an exposure dose 4 to 6 times that used clinically, appeared to be a no-effect level.

Administration, Inhalation↗
PubMed2001

Carcinogenic risk of toluene diisocyanate and 4,4'-methylenediphenyl diisocyanate: epidemiological and experimental evidence.

Diisocyanates are highly reactive compounds widely used, for example, in the production of polyurethane foams, elastomers, paints, and adhesives. The high chemical reactivity of these compounds is also reflected in their toxicity: diisocyanates are one of the most important causes of occupational asthma but also other adverse effects, such as irritation and toxic reactions, have been described in exposed subjects. One of the open questions is whether occupational isocyanate exposure is a carcinogenic hazard. The few epidemiological studies available have been based on young cohorts and short follow-up and are not conclusive. Toluene diisocyanate (TDI) has been classified as carcinogenic in animals on the basis of gavage administration studies, but no conclusions are available on inhalation exposure. For 4,4'-methylene diphenyldiisocyanate (MDI) there is suggestive evidence for carcinogenicity in rats. The possible carcinogenic mechanism of TDI and MDI is not clear. Both chemicals have been positive in a number of short-term tests inducing gene mutations and chromosomal damage. The reactive form could be either the diisocyanate itself or may derive from the metabolic activation of the aromatic diamine derivatives formed by hydrolysis. TDI and MDI react with DNA in vivo and in vitro. However, the structure of the adducts has not been identified. Especially from the in vivo experiment it is not known if the adducts are a product from the reaction with the isocyanate or the corresponding amine. In conclusion, both TDI and MDI are highly reactive chemicals that bind to DNA and are probably genotoxic. The alleged animal carcinogenicity of TDI and MDI would suggest that occupational exposure to these compounds is a carcinogenic risk. The few epidemiological studies available have not, however, been able to clarify if TDI and MDI are occupational carcinogens.

Animals↗
PubMedDate not supplied

Giant cell interstitial pneumonia in a hard-metal worker. Cytologic, histologic and analytical electron microscopic investigation.

A case of biopsy-proven giant cell interstitial pneumonia in a patient with occupational exposure to hard-metal dust is reported. Bronchial washings performed several days prior to open-lung biopsy yielded an almost exclusive population of nonpigmented alveolar macrophages and pleomorphic, phagocytic multinucleated giant cells. Microorganisms, viral inclusions in the giant cells, epithelioid histiocytes and well-formed granulomas were not seen. This cytologic picture strongly suggests the presence of giant cell interstitial pneumonia in a patient with restrictive lung disease, particularly when exposure to hard-metal dust is known or suspected. A specific diagnosis early in the course of the disease may facilitate removal of the individual from the workplace and forestall the development of end-stage interstitial fibrosis. Additionally, the working environment may be modified to minimize inhalational exposure. Recognition of this entity by the cytopathologist may direct diagnostic efforts toward accurate histologic evaluation and the identification of particulates by microprobe analysis of either cellular or biopsy material.

Adult↗
PubMed1998

Carbon disulfide neurotoxicity in rats: VII. Behavioral evaluations using a functional observational battery.

The neurobehavioral consequences of inhalational exposure to carbon disulfide (CS2) were evaluated as part of a joint project between the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency. Behavioral changes in rats were measured using a functional observational battery (FOB), which is a series of observations and manipulations designed to assess the neuronal integrity of autonomic, motor, sensory, and integrative functions. Young adult male and female Fischer-344 rats were exposed to one of four CS2 concentrations (0, 50, 500, or 800 ppm, six hours/day, five days/week) and tested at the end of one of several exposure durations (two, four, eight, or 13 weeks). All rats were also tested before exposure began to obtain baseline values. Neuromuscular deficits which were more pronounced in the hindlimbs, e.g., decreased strength and gait alterations, were detected in rats of both sexes. These changes were closely related to CS2 concentration and exposure duration, with mild gait changes evident after only two weeks of exposure. Other effects, mostly observed at 13 weeks, included decreased responsiveness to a visual stimulus and mild tremors. Reactivity in response to handling was generally increased, and excitability in the open field was decreased, in rats tested after the shorter exposures (two and four weeks). Thus, the exposure-concentration and -duration characteristics of the neuromotor syndrome produced by CS2 were detected and defined using the FOB. These studies provide a more complete evaluation of rats under these CS2 exposure conditions, which can then be used to compare with other mechanistic-related endpoints from this collaborative study.

Administration, Inhalation↗
PubMed2004

The EXPOLIS study: implications for exposure research and environmental policy in Europe.

Exposure analysis is a crucial part of effective management of public health risks caused by pollutants and chemicals in our environment. During the last decades, more data required for exposure analysis has become available, but the need for direct population based measurements of exposures is still clear. The current work (i) describes the European EXPOLIS study, designed to produce this kind of exposure data for major air pollutants in Europe, and the database created to make the collected data available for researchers (ii) reviews the exposure analysis conducted and results published so far using these data and (iii) discusses the implications of the results from the point of view of research and environmental policy in Europe. Fine particle (with 37 elements and black smoke), nitrogen dioxide, volatile organic compounds (30 compounds) and carbon monoxide inhalation exposures and exposure-related questionnaire data were measured in seven European cities during 1996-2000. The EXPOLIS database has been used for exposure analysis of these pollutants for 4 years now and results have been published in approximately 30 peer-reviewed journal papers, demonstrating the versatility, usability and scientific value of such a data set. The multipollutant exposure data from the same subjects in the random population samples allows for analyses of the determinants, microenvironments and sources of exposures to multipollutant mixtures and associations between the different air pollutants. This information is necessary and useful for developing effective policies and control strategies for healthier environment.

Adult↗
PubMed2003

Elemental mercury poisoning in occupational and residential settings.

In its elemental form, mercury is the only metal that is in a liquid state at room temperature. It readily volatilizes at standard temperature and pressure, and its presence in open containers can result in biologically significant air concentrations in unventilated or poorly ventilated spaces. In recent years, elemental mercury has proven to be a potential source of toxicosis through either unintentional exposure or exposure resulting from inappropriate handling of liquid mercury acquired from school science laboratories or abandoned industrial facilities or warehouses. The shiny, silvery appearance of mercury in its liquid form makes it particularly enticing to children, and its insolubility in water and tendency to form beads when disturbed add to its mystique. This paper presents two case studies in which excessive exposure to elemental mercury vapor has resulted in adverse health effects in the exposed individuals: one in the workplace and one in a residential setting. These case studies serve to emphasize that primary care physicians, public health officials, and science educators need to recognize the potential risk posed by inhalation exposure to mercury vapors, and health practitioners need to be able to recognize the health signs and symptoms of such exposure. Public health professionals and those in charge of public and private education facilities should also be keenly aware of the necessity of prompt mitigation of human exposure should a spill or other mercury exposure scenario occur.

Adolescent↗
PubMed1994

Retrospective analysis of calls to poison control centers resulting from exposure to the insect repellent N,N-diethyl-m-toluamide (DEET) from 1985-1989.

This study analyzed 9,086 human exposures involving N,N-diethyl-m-toluamide--containing insect repellents that were reported to Poison Control Centers from 1985-1989. Nearly two-thirds of those exposed had no adverse effects or only experienced minor symptoms that resolved rapidly. Symptoms were more likely to occur after ocular or inhalation exposures and least likely to occur if the product was ingested. The only reported death occurred in a patient who suicidally ingested 8 oz of an insect repellent containing N,N-diethyl-m-toluamide. Five patients may have experienced a serious or potentially life-threatening effect but the poison center record did not provide unequivocal substantiation of the effect or clearly establish N,N-diethyl-m-toluamide as the causative agent. From the analysis of those patients calling Poison Control Centers, it appears the risk of serious medical effects with the labeled use of N,N-diethyl-m-toluamide-containing insect repellents is low in comparison with its reported annual use by about 30% of Americans. For patients contacting Poison Control Centers, the occurrence of adverse effects appears to be related to the route of exposure rather than age or gender of the patient or the concentration of N,N-diethyl-m-toluamide in the product.

Adolescent↗
PubMed2002

The risk to the United Kingdom population of zinc cadmium sulfide dispersion by the Ministry of Defence during the "cold war".

OBJECTIVES: To estimate exposures to cadmium (Cd) received by the United Kingdom population as a result of the dispersion of zinc Cd sulfide (ZnCdS) by the Ministry of Defence between 1953 and 1964, as a simulator of biological warfare agents. METHODS: A retrospective risk assessment study was carried out on the United Kingdom population during the period 1953-64. This determined land and air dispersion of ZnCdS over most of the United Kingdom, inhalation exposure of the United Kingdom population, soil contamination, and risks to personnel operating equipment that dispersed ZnCdS. RESULTS: About 4600 kg ZnCdS were dispersed from aircraft and ships, at times when the prevailing winds would allow large areas of the country to be covered. Cadmium released from 44 long range trials for which data are available, and extrapolated to a total of 76 trials to allow for trials with incomplete information, is about 1.2% of the estimated total release of Cd into the atmosphere over the same period. "Worst case" estimates are 10 microg Cd inhaled over 8 years, equivalent to Cd inhaled in an urban environment in 12100 days, or from smoking 100 cigarettes. A further 250 kg ZnCdS was dispersed from the land based sites, but significant soil contamination occurred only in limited areas, which were and have remained uninhabited. Of the four personnel involved in the dispersion procedures (who were probably exposed to much higher concentrations of Cd than people on the ground), none are suspected of having related illnesses. CONCLUSION: Exposure to Cd from dissemination of ZnCdS during the "cold war" should not have resulted in adverse health effects in the United Kingdom population.

Air Pollution↗
PubMed1987

Decalin-induced nephrotoxicity: light and electron microscopic examination of the effects of oral dosing on the development of kidney lesions in the rat.

Male and female Fischer 344 rats were given decalin by oral gavage for 5 or 12 consecutive days in order to determine whether oral dosing would result in light microscopically evident renal effects that were comparable to those that have been observed after inhalation exposure. Decalin (in corn oil vehicle) was administered at doses of 0, 0.1, 0.5, 1.0 or 2.0 g/kg body weight to male rats, and 0, 1.0, 1.5, 1.75 or 2.0 g/kg to female rats. Biopsies of the kidneys of selected control and high-dose male rats were taken for examination by electron microscopy. Sections of kidneys from all control and treated rats were examined by light microscopy. The kidneys of all male control rats contained minimal levels of hyaline droplets within the cytoplasm of proximal convoluted tubule (PCT) epithelial cells. Decalin-induced alterations in the kidneys of male rats included an exacerbation of the hyaline droplet/globule levels found in controls and the formation of granular casts in the outer zone of the renal medulla. The exacerbated formation of hyaline droplets was characterized light microscopically by a marked dose-related increase in the number and size of individual droplets/globules and ultrastructurally by a marked increase in the size range of, and the presence of crystalline inclusions in, the PCT epithelial cell phagolysosomal populations. No other ultrastructural alterations occurred that differentiated treated male rats from control males. The formation of granular casts was dose and time related, occurring in 60% of male rats given 0.5 g decalin/kg for 12 days and in 100% of those given 1.0 g decalin/kg for 12 days. Light microscopy revealed no differences between the kidneys of control and decalin-treated female rats, and no hyaline droplets or granular casts were observed in the kidneys of any female rat killed after 5 or 12 days. These results were in agreement with those of inhalation studies and provide additional evidence that the formation of hyaline droplets in response to exposure to volatile hydrocarbons may be unique to the male rat.

Administration, Oral↗
PubMed1986

Enhanced interleukin 1 production by alveolar macrophages and increase in Ia-positive lung cells in silica-exposed rats.

Inhalation exposure to silica dust enhanced interleukin 1 (IL-1) production by alveolar macrophages (AM), which is attributable to an increase in Ia-positive lung cells. While the proportion of Ia-positive cells in lavaged bronchoalveolar cells (BAC) was much lower (0-3%) in unexposed control rats, about a third of the rats that inhaled silica showed higher proportions (8.0-18.5%); these were designated "Ia-high" exposed animals. The number of total cells, Ia-positive cells and lymphocytes in BAC was significantly increased (P less than 0.05, P less than 0.001, and P less than 0.001, respectively) in these "Ia-high" exposed animals, compared to the control animals. Adherent AM populations obtained from BAC preparations also contained significantly higher (P less than 0.001) proportions of Ia-positive cells in the "Ia-high" exposed animals. When these adherent AM cultures were stimulated with lipopolysaccharide, IL-1 activity of the culture supernatants was enhanced and was significantly higher (P less than 0.001) in the "Ia-high" exposed rats, compared to the control animals. These results indicate that silica-exposure can induce populational changes in lung cells and also activation of AM associated with the increase in Ia-positive cells.

Animals↗
PubMed1986

Inhibition of the acute toxicity of methyl chloride in male B6C3F1 mice by glutathione depletion.

Previous data have demonstrated that methyl chloride (MeCl) is toxic to B6C3F1 mice under both acute and chronic exposure conditions, and that conjugation of MeCl with glutathione (GSH) is a key step in the metabolism of MeCl. This study examined the role of GSH in mediating the acute toxicity of MeCl to liver, kidney, and brain of male B6C3F1 mice. The lethal effects of a single 6-hr inhalation exposure of B6C3F1 males to 2500 ppm MeCl were completely prevented by pretreatment with the GSH synthesis inhibitor, L-buthionine-S,R-sulfoximine (4 mmol L-BSO/kg, ip 1.5 hr prior to MeCl exposure). GSH levels (measured as nonprotein sulfhydryl) in liver and kidney were depleted to 19 and 25% of control values, respectively, at the start of the exposure; the ratio of dead/exposed mice during the 18-hr postexposure declined from 14/15 mice to 0/10. Also, the LC50 for MeCl increased from 2200 to 3200 ppm in male mice pretreated with BSO. The hepatic toxicity of MeCl was detected by increased alanine aminotransferase (ALT) activities in serum 18 hr after a 6-hr exposure to 1500 ppm MeCl (2147 +/- 1327 IU/liter vs 46 +/- 6 in controls). Liver toxicity was inhibited when B6C3F1 males were depleted of GSH prior to MeCl exposure by BSO pretreatment (43 +/- 2), fasting (100 +/- 47), or injection of diethyl maleate (42 +/- 16). The effects of GSH depletion on MeCl toxicity to brain and kidney were determined in B6C3F1 males exposed to 1500 ppm MeCl 6 hr/day, 5 days/week for 2 weeks, with and without daily pretreatment with 2 mmol L-BSO/kg. This dose of BSO depleted hepatic and renal GSH by 28 and 60%, respectively, at the start of MeCl exposure. BSO-pretreated mice were protected from the central nervous system toxicity of MeCl, as assessed by microscopic examination of the granule cell layer of the cerebellum. BSO pretreatment also inhibited the renal toxicity of MeCl as measured by incorporation of [3H]thymidine ([3H]TdR) into renal DNA, an indicator of cell regeneration after cortical necrosis. [3H]TdR incorporation was 105 +/- 10,337 +/- 40, and 60 +/- 15 dpm/microgram DNA in nonexposed controls, MeCl, and MeCl + BSO treatment groups, respectively. These results indicate that GSH is an important component in the toxicity of MeCl to multiple organ systems in B6C3F1 mice. Reaction of MeCl with GSH appears to constitute a mechanism of toxication, contrary to the role usually proposed for GSH in detoxifying xenobiotics.

Animals↗