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Determinants of exposure to inhalable particulate, wood dust, resin acids, and monoterpenes in a lumber mill environment.

In a lumber mill in the northern inland region of British Columbia, Canada, we measured inhalable particulate, resin acid, and monoterpene exposures, and estimated wood dust exposures. Potential determinants of exposure were documented concurrently, including weather conditions, tree species, wood conditions, jobs, tasks, equipment used, and certain control measures. Over 220 personal samples were taken for each contaminant. Geometric mean concentrations were 0.98 mg/m3 for inhalable particulate, 0.49 mg/m3 for estimated wood dust, 8.04 micrograms/m3 for total resin acids, and 1.11 mg/m3 for total monoterpenes. Multiple regression models for all contaminants indicated that spruce and pine produced higher exposures than alpine fir or mixed tree species, cleaning up sawdust increased exposures, and personnel enclosure was an effective means of reducing exposures. Sawing wood in the primary breakdown areas of the mill was the main contributor to monoterpene exposures, so exposures were highest for the barker operator, the head rig operator, the canter operator, the board edgers, and a roving utility worker in the sawmill, and lowest in the planer mills (after kiln drying of the lumber) and yard. Cleaning up sawdust, planing kiln-dried lumber, and driving mobile equipment in the yard substantially increased exposures to both inhalable particulate and estimated wood dust. Jobs at the front end of the sawmill where primary breakdown of the logs takes place had lower exposures. Resin acid exposures followed a similar pattern, except that yard driving jobs did not increase exposures.

Air Pollutants, Occupational↗

A comparison of the predicted risks of developing osteosarcoma for dogs exposed to 238PuO2 based on average bone dose or endosteal cell dose.

Dose-response relationships observed in laboratory animals can be used to identify possible human risk factors and may also be used in a quantitative manner when human data are not available. This paper presents an analysis of the dose dependency of osteosarcoma incidence in beagle dogs given a single inhalation exposure to a monodisperse aerosol of 238PuO2. We were particularly interested in comparing the predicted risks that were based on average bone dose with those based on endosteal cell dose and in evaluating the advantages of using a more biologically relevant cell-specific dose in risk estimation. The endosteal cell dose was calculated using the method of Marshall et al. (Health Phys. 35, 91-101, 1978), as extended to account for exposure by inhalation. The relationship between dose and time to tumor was analyzed by the proportional hazards regression model. The probability of developing osteosarcoma was strongly dependent on dose for dogs receiving low doses, but this was not true for dogs receiving high doses. The predicted risk based on endosteal cell dose was not consistently higher or lower than the risk based on average bone dose at various times after exposure, because the relationship between these two doses was not linear with respect to time. Also, as a result of the nonlinear relationship between these two doses, the risk estimated based on endosteal cell dose would not be a fixed factor of that based on the average dose. Random errors in the measured initial lung burden had a relatively large impact on the predicted risk based on endosteal cell dose, and the difference between the estimated risk of developing osteosarcoma based on endosteal cell dose and that based on average bone dose is likely to be within the error margins of the estimated risks.

Administration, Inhalation↗

An assessment of dermal exposure to semi-synthetic metal working fluids by different methods to group workers for an epidemiological study on dermatitis.

BACKGROUND: Assessment of exposure assessment to metal working fluids (MWF) has almost exclusively focused on inhalation exposure. AIMS: To assess levels of, and factors affecting, dermal and inhalation exposure to semi-synthetic MWF, and to identify suitable dermal exposure grouping schemes among metal workers for an epidemiological survey on dermatitis of hands, forearms, and head. METHODS: A cross-sectional survey was conducted in four metal working machining departments of a truck manufacturing plant, estimating dermal and inhalation exposure levels to semi-synthetic metal working fluids (SMWF) in machine operators. Dermal exposure levels to SMWF were estimated by three different methods for dermal exposure assessment (VITAE, surrogate skin pad method, and a semi-quantitative dermal exposure assessment method (DREAM)). RESULTS: The identified factors affecting dermal exposure were similar for the three methods, although differences were found for estimated variability in dermal exposure levels between groups, within groups (among workers), and from day to day. With the VITAE method differences in exposure levels were detected between workers that were not detected with the surrogate skin pad method, and only partly with the DREAM method. CONCLUSIONS: Considering the additional effort and costs that use of the VITAE method entailed, the observational semi-quantitative DREAM method appeared to be more efficient for grouping of dermal exposure levels for the epidemiological study on dermatitis.

Cross-Sectional Studies↗

Biochemical changes in different brain areas after toluene inhalation.

Exposure to toluene causes both reversible and irreversible changes in the central nervous system. The effects of toluene inhalation on some specific enzymes and glutamate and GABA receptor binding in defined parts of the rat brain were studied following several exposure schemes. The activities of the transmitter synthesizing enzymes glutamic acid decarboxylase (GAD), choline acetyltransferase (ChAT) and aromatic amino-acid decarboxylase (AAD) were used as markers for permanent loss of neuronal activity. Catecholaminergic neurons showed a 50% reduction in the brain stem after 4 weeks exposure to 250 and 1000 ppm toluene. Following 500 ppm of toluene, 16 h/day for 3 months, a general increase in the activities was seen. This is most probably due to a reduction in total protein content, to which the activities were related. The neurotransmitters glutamate and GABA had their specific receptor binding increased in most of the brain areas studied, but decreased in some areas. The glial enzyme, glutamine synthetase, had its activity increased in the cerebellar hemisphere following 4 weeks exposure to 1000 ppm. This suggests that glial cells in the area may have proliferated, a frequent phenomenon following CNS damage.

Administration, Inhalation↗

Chemical pneumonitis following household exposure to hydrofluoric acid.

A previously healthy 26-year-old woman developed hemorrhagic alveolitis and adult respiratory distress syndrome (ARDS) following use of a hydrofluoric acid-containing household cleaning agent. Exposure was inhalational in nature. The circumstances and possible mechanism of chemical pneumonitis from low-dose inhalational exposure to hydrofluoric acid are discussed.

Adult↗

Inhalation studies of Mt. St. Helens volcanic ash in animals. III. Host defense mechanisms.

The effects of inhalation exposure of mice or rats to 9.4 mg/m3 volcanic ash, 2.5 mg/m3 SO2, or both on host defense mechanisms were assessed. Cytologic changes in pulmonary lavage fluid included an increase in percentage polymorphonuclear leukocytes due to SO2 exposure and an increase in eosinophils due to ash. SO2 and ash also produced decreases in percentage alveolar macrophages. In the case of ash-exposed animals, this decrease was offset by an increase in lymphocytes. Total cell counts and viability were not affected by any of the exposures. Pulmonary clearance mechanisms were affected in that there were both decreased alveolar macrophage phagocytic capability following ash and ash + SO2 exposures and depressed ciliary beat frequency attributable to ash exposure. None of the inhalation exposures caused increases in susceptibility to an immediate or 24 hr postexposure aerosol challenge with Streptococcus. However, intratracheal instillation of both fine- and coarse-mode volcanic ash caused slight but significant increases in mortality due to bacterial challenge 24 hr after the instillation. The phytohemagglutinin-induced blastogenic response of splenic lymphocytes from exposed animals did not differ significantly from that of control lymphocytes, although the lipopolysaccharide-induced blastogenic response was enhanced. Ash exposure had no effect on susceptibility to murine cytomegalovirus. In summary, volcanic ash alone or in combination with SO2 had only minimal effects on certain host defense mechanisms.

Air Pollutants↗

Public health benefits of compliance with current E.U. emissions standards for municipal waste incinerators: a health risk assessment with the CalTox multimedia exposure model.

The Angers municipal solid waste incineration plant, in operation since 1974, was upgraded in 2000 to comply with new European standards. This article discusses the risks associated with past and present emissions from the incinerator and its nearby furnace. Emissions of SO(2), HCl, particulate matter, lead, mercury, cadmium and dioxins were studied. We characterised the risks associated with exposure via inhalation and ingestion of locally grown products, before and after the upgrade. Emissions were estimated from regulatory measurements, and ambient air concentrations estimated with a Gaussian dispersion model. The CalTox multimedia model was used to calculate concentrations in the food chain. Food intake rates came from a nationwide survey. Inhalation exposure to respiratory irritants produced a hazard ratio less than 1 in all scenarios, except for SO(2) in the immediate neighbourhood of the incinerator, before the change in furnace fuel and in case of high-pressure weather conditions. The individual excess risk of cancer was less than 10(-6) and the hazard ratios for metals were less than 1. Before compliance, the average dioxin exposure attributable to the incinerator accounted for roughly one quarter of the average total exposure from traffic and other combustion activities. Although the corresponding hazard ratio was less than 1, the individual lifetime excess risk, assuming no change in emissions, was 2 x 10(-4). After compliance, all hazard ratios and future individual lifetime excess risks appear minimal. These results are consistent with environmental data and other studies, but many uncertainties remain, such as intermedia transfer coefficients for dioxins. Nevertheless compliance has vastly reduced the probability of health effects.

Air Pollutants↗

Dose-response relationships and threshold levels in skin and respiratory allergy.

A literature study was performed to evaluate dose-response relationships and no-effect levels for sensitization and elicitation in skin- and respiratory allergy. With respect to the skin, dose-response relationships and no-effect levels were found for both intradermal and topical induction, as well as for intradermal and topical elicitation of allergenic responses in epidemiological, clinical, and animal studies. Skin damage or irritation may result in a significant reduction of the no-effect level for a specific compound. With respect to the respiratory tract, dose-response relationships and no-effect levels for induction were found in several human as well as animal studies. Although dose-response relationships for elicitation were found in some epidemiological studies, concentration-response relationships were present only in a limited number of animal studies. Reported results suggest that especially relatively high peak concentrations can induce sensitization, and that prevention of such concentrations will prevent workers from developing respiratory allergy. Moreover, induction of skin sensitization may result in subsequent heightened respiratory responsiveness following inhalation exposure. The threshold concentration for the elicitation of allergic airway reactions in sensitized subjects is generally lower than the threshold to induce sensitization. Therefore, it is important to consider the low threshold levels for elicitation for recommendation of health-based occupational exposure limits, and to avoid high peak concentrations. Notwithstanding the observation of dose-response relationships and no-effect levels, due to a number of uncertainties, no definite conclusions can be drawn about absolute threshold values for allergens with respect to sensitization of and elicitation reactions in the skin and respiratory tract. Most predictive tests are generally meant to detect the potential of a chemical to induce skin and/or respiratory allergy at relatively high doses. Consequently, these tests do not provide information of dose-response relationships at lower doses such as found in, for example, occupational situations. In addition, the observed dose-response relationships and threshold values have been obtained by a wide variety of test methods using different techniques, such as intradermal exposure versus topical or inhalation exposure at the workplace, or using different endpoints, which all appear important for the outcome of the test. Therefore, especially with regard to respiratory allergy, standardized and validated dose-response test methods are urgently required in order to be able to recommend safe exposure levels for allergens at the workplace.

Allergens↗

Health and ecological effects of adiponitrile.

Adiponitrile (ADN) has moderate acute toxicity with an oral LD50 in rats of 100 to 500 mg/kg and a 4-hr LC50 in rats of 1.71 mg/L (vapor plus aerosol). ADN produced slight eye but no skin irritation in rabbits. Repeated exposures by inhalation produced changes in the hematologic profile with effects seen at 100 or 300 mg/m3. The hematologic changes were reversible upon cessation of further inhalation exposures. Dogs fed up to 500 ppm (equivalent to 12-15 mg/kg) showed no effects but 1,000 ppm produced vomiting and nausea which limited further testing at that concentration. ADN was not a genetic toxin, developmental toxin, reproductive toxin nor did it produce an increase in tumors in a 2-yr drinking water study in rats. Human experience reports are limited to one accidental poisoning case and a few skin exposures resulting in transient irritation and inflammation. ADN is rapidly absorbed and excreted by mammals, and is metabolized to some extent although unchanged ADN is readily detected in urine, and does not bioaccumulate.

Adolescent↗

Health risks of PCB spills from electrical equipment.

The Southern California Edison Company (SCE) has instituted a series of control strategies designed to minimize human exposure to polychlorinated biphenyls (PCBs) in electrical equipment used on its system. This paper describes a method of analyzing PCB risks using conservative estimates of human intake of PCBs originating from accidental spills from electrical equipment. The PCB releases from the Edison system were determined. The fate of these releases in soil, air, and water was analyzed to determine how much material reaches human receptors. The air and water pathways were determined to be the most likely candidates for the exposure and risk considerations. PCB intake via ingestion of soil at the spill site was neglected as an exposure pathway. Equipment spills without controls resulted in at the most 2 ng/day human intake of PCBs via the water exposure pathway. This was determined to be negligible in comparison with intake rates used in conjunction with the setting of food tolerance levels based on fish being the main dietary pathway of human exposure. The inhalation exposure of the hundred or so persons in the immediate vicinity of a spill was determined to equal the PCB intakes of the fish-eating subpopulation analyzed by the Food and Drug Administration for 2 ppm tolerance standard in the case of no controls or cleanup. Current cleanup procedures assure that even the persons in the immediate area are well below the intake of the subjects in the fish contamination analysis. All exposures were well below a "virtual safe dose" level estimated in the fish tolerance study.

California↗

Response of rats to low levels of sarin.

The purpose of this study was to determine whether exposure to levels of sarin causing no overt clinical signs would cause more subtle, adverse health effects that persisted after the exposure ended. Inhalation exposures of male Fischer 344 rats to 0, 0.2, or 0.4 mg/m(3) of sarin for 1 h/day for 1, 5, or 10 days under normal (25 degrees C) and heat-stressed (32 degrees C) conditions were completed and observations were made at 1 day and 1 month after the exposures. The sarin exposures had no observed effects on body weight, respiration rate, and minute volume during exposure nor in body temperature and activity during the 30-day recovery period. There was no evidence of cellular changes in brain determined by routine histopathology nor of any increase in apoptosis. Brain mRNA for interleukin (IL)-1beta, tumor necrosis factor-alpha, and IL-6 was increased in a dose-dependent manner. Autoradiographic studies demonstrated that M1 cholinergic receptor site densities were unchanged at 1 day after repeated exposures with or without heat stress. At 30 days, there was a decrease in M1 receptors in the olfactory tubercle (with and without heat), and, with heat stress, M1 sites also decreased in a dose-dependent manner in the frontal cortex, anterior olfactory nucleus, and hippocampus. M3 receptor sites were not affected by sarin exposure alone. In the presence of heat stress, there was an upregulation in binding site densities in the frontal cortex, olfactory tubercle, anterior nucleus, and striatum immediately after exposure, and these effects persisted at 30 days. Although red blood cell acetylcholinesterase (AChE) was not greatly inhibited by the 1-day exposure, there were 30 and 60% inhibitions after repeated exposures at the low and high doses, respectively. Histochemical staining for AChE demonstrated that sarin exposure alone reduced AChE in the cerebral cortex, striatum, and olfactory bulb. Sarin exposure under heat stress reduced AChE staining in the hippocampus, an area important for memory function. Thus, repeated exposures under heat-stress conditions, to levels of sarin that would not be noticed clinically, resulted in delayed development of brain alterations in cholinergic receptor subtypes that may be associated with memory loss and cognitive dysfunction.

Acetylcholinesterase↗

Effects of concentrated ambient particles on normal and hypersecretory airways in rats.

Epidemiological studies have reported that elevated levels of particulate air pollution in urban communities are associated with increases in attacks of asthma based on evidence from hospital admissions and emergency department visits. Principal pathologic features of chronic airway diseases, like asthma, are airway inflammation and mucous hypersecretion with excessive amounts of luminal mucus and increased numbers of mucus-secreting cells in regions of the respiratory tract that normally have few or no mucous cells (ie, mucous cell metaplasia). The overall goal of the present project was to understand the adverse effects of urban air fine particulate matter (PM2.5; < or = 2.5 pm in aerodynamic diameter)* on normal airways and airways compromised with airway inflammation and excess mucus. Our project was specifically designed to (1) examine the chemical and physical characteristics of PM2.5 and other airborne pollutants in the outdoor air of a local Detroit community with a high incidence of childhood asthma; (2) determine the effects of this community-based PM2.5 on the airway epithelium in normal rats and rats compromised with preexisting hypersecretory airway diseases (ie, animal models of human allergic airway disease--asthma and chronic bronchitis); and (3) identify the chemical or physical components of PM2.5 that are responsible for PM2.5 -induced airway inflammation and epithelial alterations in these animal models. Two animal models of airway disease were used to examine the effects of PM2.5 exposure on preexisting hypersecretory airways: neutrophilic airway inflammation induced by endotoxin challenge in F344 rats and eosinophilic airway inflammation induced by ovalbumin (OVA) challenge in BN rats. A mobile air monitoring and exposure laboratory equipped with inhalation exposure chambers for animal toxicology studies, air pollution monitors, and particulate collection devices was used in this investigation. The mobile laboratory was parked in a community in southwestern Detroit during the summer months when particulate air pollution is usually high (July and September 2000). We monitored the outdoor air pollution in this community daily, and exposed normal and compromised rats to concentrated PM2.5 from this local urban atmosphere. Rats in the inhalation studies were exposed for 1 day or for 4 or 5 consecutive days (10 hours/day) to either filtered air (controls) or concentrated ambient particles (CAPs) delivered by a Harvard ambient fine particle concentrator. Rats were killed 24 hours after the end of the exposure. Biochemical, morphometric, and molecular techniques were used to identify airway epithelial and inflammatory responses to CAPs. Lung lobes were also either intratracheally lavaged with saline to determine cellular composition and protein in bronchoalveolar lavage fluid (BALF) or removed for analysis by inductively coupled plasma-mass spectrometry (ICPMS) to detect retention of ambient PM2.5--derived trace elements. The Harvard concentrator effectively concentrated the fine ambient particles from this urban atmosphere (10-30 times) without significantly changing the major physicochemical features of the atmospheric particles. Daily CAPs mass concentrations during the 10-hour exposure period (0800-1800) in July ranged from 16 to 895 microg/m3 and in September ranged from 81 to 755 microg/m3. In general, chemical characteristics of ambient particles were conserved through the concentrator into the exposure chamber. Single or repeated exposures to CAPs did not cause adverse effects in the nasal or pulmonary airways of healthy F344 or BN rats. In addition, CAPs-related toxicity was not observed in F344 rats pretreated with bacterial endotoxin. Variable airway responses to CAPs exposure were observed in BN rats with preexisting allergic airway disease induced by OVA sensitization and challenge. Only OVA-challenged BN rats exposed to CAPs for 5 consecutive days in September 2000 had significant increases in airway mucosubstances and pulmonary inflammation compared to saline-challenged/air-exposed control rats. OVA-challenged BN rats that were repeatedly exposed to CAPs in July 2000 had only minor CAPs-related effects. In only the September 5-day exposure protocol, PM2.5 trace elements of anthropogenic origin (La, V, and S) were recovered from the lung tissues of CAPs-exposed rats. Recovery of these specific trace elements was greatest in rats with OVA-induced allergic airway disease. Additional laboratory experiments using intratracheal instillations of ambient PM2.5 samples were performed to identify bioactive agents in the CAPs to which rats had been exposed in the inhalation exposure component. Because the most pronounced effects of CAPs inhalation were found in BN rats with OVA-induced allergic airways exposed in September, we used ambient PM2.5 samples that were collected on 2 days during the September CAPs inhalation exposures to use for instillation. Ambient PM2.5 samples were collected, fractionated into soluble and insoluble species, and then compared with each other and with total PM2.5 for their effects in healthy BN rats and those with OVA-induced allergic airway disease. Intratracheal instillation of the insoluble fraction of PM2.5 caused mild neutrophilic inflammation in the lungs of healthy rats. However, total PM2.5 or the soluble or insoluble fractions instilled in rats with OVA-induced airway inflammation did not enhance the inflammation or the airway epithelial remodeling that was evident in some of the BN rats exposed to CAPs by inhalation. Therefore, the results from this instillation component did not suggest what fractions of the CAPs may have been responsible for enhancing OVA-induced airway mucosubstances and pulmonary inflammation observed in the inhalation exposure component. In summary, inhaled CAPs-related pulmonary alterations in the affected OVA-challenged rats appeared to be related to the chemical composition, rather than the mass concentration, to which the animals were exposed. Results of the trace element analysis in the lungs of CAPs-exposed BN rats exposed in September suggested that air particles derived from identified local combustion sources were preferentially retained in allergic airways. These results demonstrate that short-term exposures to CAPs from this southwestern Detroit community caused variable responses in laboratory rats and suggest that adverse biological responses to ambient PM2.5 may be associated more closely with local sources of particles and weather patterns than with particle mass.

Air Pollutants↗

Determinants of inhalable dust exposure in the European carbon black manufacturing industry.

A large study to investigate the respiratory health effects of occupational exposure to carbon black in the European carbon black manufacturing industry commenced in 1987. During the study, a large amount of personal occupational exposure data was collected. This article describes the empirical models used to study the determinants of inhalable dust exposure, using data from 16 factories collected in the third and last cross-sectional phase of this study. Information on activities during the measurements was collected using short job category-specific questionnaires. In addition, questionnaires were completed by factory representatives on the implementation of control measures and changes in production process since the first cross-sectional phase. Mixed effects analyses of variance models were used to identify determinants of exposure, while taking into account the within- and between-worker (random) variance components. The results of these models show that, for any job category, factory is a strong predictor of exposure in this industry. These differences could not be explained entirely by factors such as age of the factory or the control measures implemented since the first phase of the study. Surprisingly, implementation of local exhaust ventilation systems had an effect that was counterintuitive; for example, in warehouses where local exhaust ventilation systems had been implemented, higher dust exposure levels were found compared to those where such control measures had not been installed since the first cross-sectional survey. Season appeared to have some effect on exposure for some job titles, with generally relatively low exposures being found in the summer. Finally, a number of activities were identified that caused higher levels of dust exposure, most notably "changing of filters" and "clean-up of carbon black spills."

Air Pollutants, Occupational↗

Characterization of exposure to inhalable flour dust in Swedish bakeries.

Bakery workers are at risk of developing respiratory symptoms, such as asthma and rhinitis. Exposure to inhalable flour dust in 12 Swedish bakeries was therefore determined: concentrations of airborne inhalable flour dust were measured with the IOM personal inspirable dust sampler and the particle size distribution assessed using the IOM personal inspirable aerosol spectrometer, and the fractions of alpha-amylase, water-soluble protein and total protein in flour dust were determined. A total of 129 measurements were performed of which 77 were repeated measurements. There was a clear hierarchy in geometric mean exposure among bakery workers, with in descending order doughmakers (5.46 mg m-3), bread-formers (2.69 mg m-3), oven workers (1.17 mg m-3), and packers and confectionery workers (0.53 mg m-3). The repeated measurements revealed that within each task group there were considerable differences in mean exposure among the workers: this was demonstrated by geometric standard deviations of between-worker variance of 1.63-1.77. Partitioning of the total variability of inhalable flour dust exposure showed that the task group was the principal source of variance, accounting for 61-69% of the total variability. The optimum grouping strategy was independent of whether the oven workers and the packers were assigned to the same or to different task groups. The doughmakers and the bread-formers are two clearly distinguishable exposure groups with largely overlapping exposure distributions. On average, the flour dust contained 9% total protein, 2.3% water-soluble protein and 0.03% alpha-amylase. The inhalable flour dust was characterized by a substantial proportion of particles with a d(ac) above 10 microns. It was estimated that the thoracic subfraction contributed 39% to the total mass of inhalable dust, and the respirable subfraction 19%.

Dust↗

Should styrene be sampled on the left or right shoulder?--An important question in employee self-assessment.

A self-operated personal sampling technique called 'self assessment of exposure' (SAE) has been suggested as an easy method for collecting inhalation exposure data, as the workers themselves are performing the sampling. Employers and employees have raised the question of whether a different estimate of the air concentration is likely to be obtained depending on whether the sampler is fastened at the left or the right shoulder. In order to answer this question, the exposure to styrene vapour in two different small enterprises within the reinforced plastics industry was measured. Seven workers participated and the air sampling was performed by diffusive sampling. We observed no statistically significant difference in the determined air concentration of styrene between the left and right shoulder (P = 0.878). The results strongly indicate that the fastening of a sampler on the left or right shoulder does not produce a difference in the estimation of the inhalation exposure. SAE can thus be used to collect reliable exposure data of styrene vapour. The reliability of SAE will most certainly inspire occupational hygienists, physicians and other experts to involve the workers in repeated exposure measurements. Taking the exposure variability into account, repeated measurements are crucial when evaluating acute and chronic health effects following inhalation exposure to gases and vapours from chemical hazards.

Air Pollutants, Occupational↗

Development of acute inhalation reference exposure levels (RELs) to protect the public from predictable excursions of airborne toxicants.

Uniform guidelines have been developed for the derivation of 1-h acute inhalation reference exposure levels (RELs) applicable to the general public exposed routinely to hazardous substances released into the environment. Existing acute exposure guidance values developed by other organizations have been examined, and strengths and weaknesses in these existing guidelines have been identified. The results of that examination have led to the development of a reproducible and resource-intensive methodology to calculate acute inhalation RELs for 41 prioritized chemicals. Approaches to estimating levels protective against mild and severe acute effects are discussed in this report. The default methodology is the no-observed-adverse-effect level (NOAEL)/uncertainty factor (UF) approach using mainly reports in the peer-reviewed toxicological and medical literature. For two well-studied chemicals, ammonia and formaldehyde, the data allowed a benchmark dose (or concentration) methodology, as a departure from the default options, to be used. However, better human dose-response data from, for example, improved workplace monitoring correlated with symptoms, and more extensive epidemiological studies are needed before the departure from default approaches can be expanded to more substances.

Air Pollutants↗

Assessment of the hepatotoxicity of acute and short-term exposure to inhaled p-xylene in F-344 rats.

Due to the ubiquitous presence of p-xylene in air and the existing uncertainty regarding its hepatotoxic potential, we examined the effect of acute and short-term exposure to inhaled p-xylene on the liver. Male F-344 rats were exposed to 0 or to 1600 ppm p-xylene, 6 h/d, for 1 or 3 d. Exposure to inhaled p-xylene caused no histopathological evidence of hepatic damage and had little or no effect on the serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, ornithine carbamyl transferase, alkaline phosphatase, and total bilirubin. Exposure to p-xylene for 1 or 3 d resulted in an increase in relative liver weight on d 1 post-exposure. The concentration of hepatic cytochrome P-450 was increased by both p-xylene exposure regimens on d 1 postexposure and had returned to control levels by d 3 following the single p-xylene exposure and by d 2 following the 3-d exposure. These observations provide consistent evidence that acute and short-term exposure to 1600 ppm p-xylene by inhalation did not produce overt hepatotoxicity but resulted in a significant increase in the concentration of hepatic cytochrome P-450, the principal enzyme system involved in the metabolic biotransformation of xenobiotics.

Administration, Inhalation↗