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Analysis of markers of exposure to polymeric methylene-diphenyl diisocyanate (pMDI) in rats: a comparison of dermal and inhalation routes of exposure.

Rats received polymeric methylenediphenyl-diisocyanate (pMDI) or a mixture of methylenediphenyl-4,4'-diamine (4,4'-MDA) and amino-di(aminophenylmethylene)-benzene (3-core MDA) by single inhalation or dermal exposure. The ratio of 4,4'-MDA and 3-core MDA used in this study mirrored that of 4,4'-MDI and 3-core MDI present in pMDI. The yields of the corresponding markers of exposure in hydrolyzed blood (Hb-adducts) and urine were determined. For the inhalation exposure, rats were acutely exposed for a duration of 6 h to 3.7 mg pMDI/m3 and 2.7 mg MDA/m3, respectively. Furthermore, C x t products of approximately 1200 mg pMDI/m3 x h were examined, ranging from 3 h x 6.2 mg/m3, 1.5 h x 12.7 mg/m3, 45-min x 25.1 mg/m3, and 23-min x 58.1 mg/m3. Additional groups of rats received equimolar doses of pMDI and MDA by epicutaneous exposure, i.e., 100 mg pMDI/kg bw, equivalent to approximately 50 mg 4,4'-MDI/kg bw and 34 mg 3-core MDI/kg bw or 79 mg MDA-mixture/kg bw, equivalent to 46 mg 4,4'-MDA/kg bw and 33 mg 3-core-MDA/kg bw. The biomarkers measured in this study suggest that the kind and yield of biomarkers are dependent on the route of exposure and differ markedly for MDI and MDA. This isocyanate appears to undergo reactions specific to the site of first contact (e.g., formation of adducts, conjugates and/or polyureas), suggesting that these markers of 'total body burden' can neither predict the local dose at that site nor does it provide any means to identify the route receiving the most critical dose. Similarly, it appears that the formation of biomarkers is governed by reactions requiring an intact isocyanate group rather than hydrolysis. In contrast, for MDA this type of portal-of-entry specificity was not observed. Moreover, trace amounts of diamines available to dermal contact, with respect to the isocyanate, may cause false-positive readings. Thus, in spite of the recognized advantages of biomonitoring to identify cryptic exposures not readily detected by conventional analytical sampling procedures, in regard to pMDI this technique appears to be potentially biased to overestimate exposure, i.e., results obtained from integrating dosimeters of exposure need to be verified by adequate air monitoring.

Administration, Cutaneous↗

Applicator exposure to acetochlor based on biomonitoring.

Biomonitoring was used to assess the combined dermal, oral, and inhalation exposure associated with the agricultural use of Harness Plus, an emulsifiable concentrate formulation of the herbicide acetochlor. Twenty Spanish farmers handled and applied acetochlor to maize in the spring of 2003, following the product label recommendations. Open- and closed-cabin applications were equally represented. Urine was collected during six consecutive days, starting the day prior to application. Daily composites were analyzed for 2-ethyl-6-methyl-aniline, a common chemophore representing the major urinary acetochlor metabolites. All applicators showed detectable concentrations in urine after application. Although, the open-cabin applicators treated fewer hectares, they showed significantly higher exposure compared to the closed-cabin applicators (average exposure: 0.004 and 0.002 mg/kg bw/day, respectively). Linear regression analysis suggested that untracked incidents had a significant impact on the total exposure. Other events that may have contributed to the observed exposure are repair of faulty equipment, accidental spillages, splashes, and inadequate use of protective gloves. The average margins of exposure (MOE) for farmers ranged from 23,000 (open cabin) to about 44,000 (closed cabin). For professional applicators the MOEs were 10-fold lower. These MOEs clearly indicate that no adverse health effects should be expected from agricultural acetochlor applications.

Administration, Oral↗

Partition coefficients for benzene in human skin.

The contribution of benzene to body burden after skin absorption compared with that due to inhalation absorption is of potential interest in the setting and interpretation of benzene (inhalation) exposure standards. However, an understanding of the quantitative relationship between skin and inhalation absorption, under different exposure conditions, is required. Such knowledge may be gained through physiological based pharmacokinetic (PBPK) modeling. The intake of benzene to the body via inhalation has been studied extensively. Physiological parameters enabling the calculation of amounts of benzene entering the blood stream per unit time are readily available for use in a PBPK model. Unfortunately, some data (i.e., partition coefficients) that would enable biologically plausible calculation of amounts of benzene entering the blood stream via skin absorption in a PBPK model are not available. Hence, the aim of this research was to determine partition coefficients across the epidermal and dermal layers of human skin so that these could be used within a PBPK model to determine quantitatively the flow rate of benzene per unit time through intact skin into the blood stream. The partition coefficients found for blood substitute: viable epidermis and blood substitute: dermis were, respectively, 2.4 and 11.2. Partition coefficients for benzene : stratum corneum (4.2), whole skin : blood substitute (2.2), benzene : water (109/126), and benzene : blood substitute (55/59) also were determined for the purposes of validating the blood substitute: viable epidermis and blood substitute : dermis partition coefficients.

Benzene↗

Silica induced early fibrogenic reaction in lung of mice ameliorated by Nyctanthes arbortristis extract.

OBJECTIVE: To investigate the pharmacological effect of Nyctanthes arbortristis (NAT) leaf extract in the prevention of lung injury induced by silica particles. METHOD: Lung injury was induced in Swiss mice through inhalation exposure to silica particles (< 5 mu) using a Flow Past Nose Only Inhalation Chamber at the rate of -10 mg/m3 respirable mass for 5 h. Lung bronchoalveolar lavage (BAL) fluid collected between 48 and 72 h was subjected to protein profiling by electrophoresis and cytokine evaluation by solid phase sandwich ELISA. Lung histopathology was performed to evaluate lung injury. RESULTS: Inhalation of silica increased the level of tumor necrosis factor-alpha (TNF-alpha), and of the 66 and 63 kDa peptides in the BAL fluid in comparison to sham-treated control. Pre-treatment of silica exposed mice with NAT leaf extract significantly prevented the accumulation of TNF-alpha in the BAL fluid, but the 66 and 63 kDa peptides remained unchanged. The extract was also effective in the prevention of silica-induced early fibrogenic reactions like congestion, edema and infiltration of nucleated cells in the interstitial alveolar spaces, and thickening of alveolar septa in mouse lung. CONCLUSION: NAT leaf extract helps in bypassing silica induced initial lung injury in mice.

Administration, Oral↗

Size selective dustiness and exposure; simulated workplace comparisons.

A simulated workplace study was conducted to investigate the relation between inhalation exposure and dustiness determined with a rotating drum dustiness tester. Three powders were used in the study, i.e. magnesium stearate, representing a very dusty powder, and aluminium oxide and calcium carbonate, representing low and very low dusty powders, respectively. Two scenarios of handling small volume of powders were included; sweeping/cleaning and scooping/weighing/adding. Size-selective dust exposure was assessed using MultiDust (dual-fraction) IOM and RespiCon sampling heads. For the present operation scenarios, dustiness showed itself to be the major determinant of exposure and explained approximately 70% of the exposure variances. The ratios of respirable and inhalable fractions as determined by dustiness tests were comparable with the ratios observed for exposure. The results emphasize the relevance of dustiness as a parameter to characterize substances according to potential for exposure.

Air Pollutants, Occupational↗

A stochastic exposure assessment model to estimate vanadium intake by beef cattle used as sentinels for the South African vanadium mining industry.

This paper presents an environmental exposure assessment model for estimating chronic intake of vanadium (a transition metal) by cattle farmed extensively in areas contaminated by vanadium pollutants. The exposure model differs from most other models in several ways: (1) it does not rely heavily on extrapolating information from the point source (e.g. stack height, exit velocity, exit diameter) to the point of exposure. (2) It incorporates the physiological constraints of the species exposed. (3) It takes into account oral as well as inhalation exposure. (4) It addresses terrain, by using measurements at the point of exposure. (5) It accounts for existing background concentrations of pollutants and pollutants from multiple sources. (6) It uses a stochastic process with distribution functions to account for variability in the data over time. Environmental inputs into the model included aerial fall-out sample vanadium (n=566), unwashed grass sample vanadium (n=342) and soluble soil sample vanadium (n=342). Physiological cattle inputs were derived from two cohorts of Brahman-cross sentinel cattle (n=30). The model provided an estimate of the chronic external exposure dose of vanadium for two separate groups of cattle grazing over a 5-year period (1999-2004) immediately adjacent (median dose=2.14mg vanadium/kg body weight/day) and 2km away (median dose=1.07mg/kg/day) from a South African vanadium-processing plant, respectively. The final output of the model is a distribution curve of the probable vanadium intake based on the variability within the inputs over the 5-year period of the study. The model is adaptable enough for application to other transition metals and species (including man), and could be used as an alternative to plume-dispersion modelling.

Air Pollutants↗

Physiological pharmacokinetic modeling of inhaled trichloroethylene in rats.

The pharmacokinetics of trichloroethylene (TCE) was characterized during and following inhalation exposures of male Sprague-Dawley rats. The blood and exhaled breath TCE time-course data were used to formulate and assess the accuracy of predictions of a physiologically based pharmacokinetic (PB-PK) model for TCE inhalation. Fifty or 500 ppm of TCE was inhaled by unanesthetized rats of 325-375 g for 2 hr through a miniaturized one-way breathing valve. Repetitive samples of the inhaled and exhaled breath streams, as well as arterial blood, were collected concurrently during and for 3 hr following the exposures and analyzed for TCE by headspace gas chromatography. Respiratory rates and volumes were continuously monitored and used in conjunction with the pharmacokinetic data to delineate uptake and elimination profiles. Levels of TCE in the exhaled breath attained near steady-state soon after the beginning of exposures, and were then directly proportional to the inhaled concentration. Exhaled breath levels of TCE in rats were similar in magnitude to values previously published for TCE inhalation exposures of humans. Levels of TCE in the blood of the 50 ppm-exposed animals also rapidly approached near steady-state, but blood levels in the 500 ppm-exposed animals rose progressively, reaching concentrations 25- to 30-fold higher than in the 50 ppm group during the second hour of exposure. The 10-fold increase in inhaled concentration resulted in an 8.7-fold increase in cumulative uptake, or total absorbed dose. These findings of nonlinearity indicate that metabolic saturation ensued during the 500 ppm exposure. The PB-PK model was characterized as blood flow-limited with TCE eliminated unchanged in the exhaled breath and by saturable liver metabolism. The uptake and elimination profiles were accurately simulated by the PB-PK model for both the 50 and 500 ppm TCE exposure levels. Such a model may be quite useful in risk assessments in predicting internal (i.e., systemically absorbed) doses of TCE and other volatile organics under a variety of exposure scenarios.

Administration, Inhalation↗

A five year evaluation of acute exposures to phenol disinfectant (26%).

A five year retrospective review of all exposures to a high concentration phenol disinfectant (Creolin Disinfectant 26% phenol) reported to a regional poison center located 96 cases, with 16 cases lost to follow up. There were 60 oral-only exposures, 7 dermal-only exposures and 12 oral/dermal exposure. One patient was an inhalation exposure. Fifty-two cases (65%) were evaluated in a hospital. Eleven patients with oral exposures (14%) experienced rapid CNS depression, but no seizures occurred. Vomiting, coughing, and stridor was noted in 14, 7 and 4 patients respectively. Burns were noted in 17 of 72 (24%) patients with oral exposure and 5 of 19 (26%) with dermal exposure. Seventeen patients underwent endoscopy. Tissue sloughing was noted in one case. All other burns were first degree. No cardiovascular complications occurred. Twenty-eight patients (35%) were followed at home via telephone with one episode of vomiting and one episode of dermal irritation occurring. CNS toxicity from exposure to a high concentration phenol containing cleaning product appears to be rapid in onset. The absence of serious toxicity and major chemical burns in this series does not eliminate concern with the corrosive and systemic risks of phenol poisoning.

Administration, Cutaneous↗

Effects of ozone exposure: a comparison between oral and nasal breathing.

Mode of inhalation, by nose or by mouth, as a determinant of pulmonary toxicity to acute inhalant exposure has been investigated incompletely. This communication addresses whether there are significant differences in toxic pulmonary responses to acute ozone (O3) exposure between differing modes of inhalation (nasal vs. oral breathing). Changes in the results of pulmonary function tests and symptomatology of healthy young adults were compared following both exclusive nose and exclusive mouth breathing during a 30-min exposure to approximately 0.4 ppm O3 under conditions of moderate continuous exercise. In this single-blind, randomized, crossover study, no significant differences in either the results of pulmonary function tests or in symptomatology were found between the two modes of inhalation.

Adult↗

Olefinic hydrocarbons: a first risk estimate for ethene.

The exhalation of ethene oxide by rats exposed to ethene now allows a first estimate of the genotoxic risk of ethene on a pharmacokinetic basis. The distribution (Keq, Kst) of ethene oxide under conditions of inhalation of ethene oxide, or high levels of ethene and consideration of the saturation behaviour of metabolism of ethene lead to the conclusion that inhalation exposure of rats to 1000 ppm ethene or more would theoretically correspond to about 7.5 ppm ethene oxide exposure. Available carcinogenicity data for inhaled ethene oxide were utilized into a comparison of the genotoxic risks of low levels of ethene oxide and ethene. It has been shown that consideration of ethene as a "simple asphyxiant" is inappropriate. The new intended TLV of 1 ppm for ethene oxide would be consistent with a TLV of 100 ppm for ethene.

Animals↗

N-terminal globin adducts as biomarkers for formation of butadiene derived epoxides.

The aim of this review is to summarize our recent data on butadiene (BD) derived hemoglobin adducts as biomarkers for the internal formation of the individual epoxides formed by butadiene (BD). It is well known that BD is oxidized by cytochrome P450s to several epoxides that form DNA and protein adducts. 1,2-Epoxy-3-butene (EB), 1,2;3,4-diepoxybutane (DEB) and 1,2-epoxy-3,4-butanediol (EB-diol) form N-(2-hydroxy-3-butenyl)-valine (HB-Val), N,N-(2,3-dihydroxy-1,4-butadiyl)-valine (pyr-Val) and N-(2,3,4-trihydroxybutyl)-valine (THB-Val) adducts, respectively. The analysis of HB-Val and THB-Val by the modified Edman degradation and GC-MS/MS has generated valuable insights into BD metabolism across species. In addition, a recently established method for the analysis of pyr-Val has been proven to be suitable for detection of pyr-Val in rodents exposed to BD as low as 1 ppm. These technologies have been applied to study a wide range of exposures to BD, EB, DEB, and 3-butene-1,2-diol as a precursor of EB-diol in male and female mice and rats. Altogether the data have shown that BD metabolism is species and concentration dependent, consistent with metabolism and carcinogenesis data. Mice form much more HB-Val and pyr-Val than rats, especially at low exposures. After 10 days of inhalation exposure to 3 ppm BD, mice formed 12.5-fold more pyr-Val than rats. In contrast, the amounts of THB-Val were similar in mice and rats exposed to 3 or 62.5 ppm BD. Furthermore, it appears that the formation of THB-Val is supralinear in mice and rats due to saturation of metabolic activation pathways. Gender differences in metabolism are less well established. One study with male and female rats exposed to 1000 ppm BD for 90 days demonstrated a 1.6-, 3.5- and 2.0-fold gender difference in formation of HB-Val, pyr-Val and THB-Val, respectively, with females being more efficient in epoxide formation. The analyses of BD derived protein adducts correlate well with the observed species and gender differences in BD-carcinogenesis and suggest that DEB may indeed be the most important metabolite.

Animals↗

Miotic tolerance to sarin vapor exposure: role of the sympathetic and parasympathetic nervous systems.

O-isopropyl methylphosphonofluoridate, also known as sarin or GB, is a highly toxic organophosphorous compound that exerts its effect by inhibiting the enzyme acetylcholinesterase. While the effects of a single exposure to GB vapor are well characterized, the effects of multiple exposures to GB vapor are less clear. Previous studies in the rat and guinea pig have demonstrated that multiple exposures result in tolerance to the miotic effect of nerve agents. The aim of the present study was to examine potential mechanisms responsible for tolerance to the miotic effect of GB vapor that has been observed in the rat after multiple exposures. Multiple whole-body inhalation exposures to GB vapor were conducted in a dynamic airflow chamber. Exposures lasted 60 min and each of the three exposures occurred at 24-h intervals. The results of the present study demonstrate that the alpha-adrenergic antagonist phentolamine and the beta-adrenergic receptor antagonist propranolol did not affect the development of tolerance to the miotic effect of GB vapor, suggesting that enhanced sympathetic tone to the eye is not responsible for the observed tolerance. Administration of atropine before the first exposure prevented the tolerance to the miotic effect of GB vapor after the third exposure, suggesting that the tolerance is the result of muscarinic receptor desensitization secondary to receptor stimulation. The present study extends the findings of previous studies to strengthen the hypothesis that the miotic tolerance observed in the rat upon repeated exposure to nerve agents is due to desensitization of muscarinic acetylcholine receptors located on the pupillary sphincter.

Adrenergic alpha-Antagonists↗

Significance of durability of mineral fibers for their toxicity and carcinogenic potency in the abdominal cavity of rats in comparison with the low sensitivity of inhalation studies.

At the same time that carcinogenicity of very thin glass fibers after intrapleural and intraperitoneal (ip) administration was demonstrated (1,2) researchers found that gypsum fibers and HCI-leached chrysotile fibers were easily soluble in the peritoneal cavity. This led to the conclusion that the chemical composition of fibers was not responsible for the carcinogenesis but that the degree of carcinogenic potency of a fiber depended on the extent to which it retained its fibrous structure. A thin glass fiber with a low biodurability did not induce tumors after ip injection of a high dose, although the ip test had been criticized for being "overly sensitive." The ip model has been the most successful for determining carcinogenicity of inorganic fibers and establishing dose-response relationships; but to determine the possibilities and limitations of this test model, very high doses of nonfibrous silicon carbide and of a slightly durable glass fiber type were injected ip in Wistar rats. No obviously acute or chronic toxic effect was observed in 90 weeks, but there was a 40% incidence of serosal tumors in the group treated with glass fibers. A pilot study on the persistence of slag fibers in the omentum of rats after ip injection showed a half-time of about 1 year. It was calculated that an ip injection of 10(9) fibers would lead to a concentration of fiber numbers in the ash of the omentum in the same range as the concentration in the lung after 2 years of inhalation exposure. The long-term inhalation study with fibers in rats has been called the "gold standard" for risk characterization.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

Toxicity and pathogenicity of Metarhizium anisopliae var. acridum (Deuteromycotina, Hyphomycetes) and fipronil to the fringe-toed lizard Acanthodactylus dumerili (Squamata: Lacertidae).

Reptiles in arid and semiarid zones are frequently exposed to insecticides sprayed to control locusts and grasshoppers. We evaluated the toxicity and pathogenicity of new biological and chemical control agents to the fringe-toed lizard Acanthodactylus dumerili in Mauritania, West Africa. A mycoinsecticide based on spores of the entomopathogenic fungus Metarhizium anisopliae var. acridum (isolate IMI 330189, Green Muscle) was tested at high challenge concentrations, using three exposure routes. Thirty-minute inhalation exposure to 3.9 x 10(8) viable conidia/L had no adverse effect. Locomotor activity, feeding activity, food consumption, body weight, and liver-to-body weight ratio were similar among treatments. Gross necropsy revealed no pulmonary lesions, hyphal mats, clumps of spores, or other abnormalities associated with fungal infections. Oral exposure to an oil-miscible flowable concentrate administered at approximately 10(7) viable conidia/g body weight had no effect on locomotor activity, food consumption, and body weight of survivors. However, two of the treated lizards died within one week of exposure. Feeding activity (sexes pooled) and relative liver mass of female survivors were significantly reduced. This was also observed in lizards treated with deactivated (nonviable) conidia, indicating an inherent toxicity of the formulation. Limited necropsy examination at four weeks posttreatment revealed that one lizard treated with viable spores had developed a pulmonary mycetoma that contained a clump of viable spores and fungal mycelium. The toxicity of mycotoxins was tested by feeding mycosed nymphs of desert locust Schistocerca gregaria to lizards. An average consumption of 231 mg (females) or 260 mg (males) nymphs/g body weight showed no adverse effect for any of the endpoints. No risk due to the pathogen is anticipated at recommended field application rates. The second agent tested was fipronil (Adonis), a phenylpyrazole insecticide. A single dose of 30 microg fipronil/g body weight was administered via contaminated prey or stomach instillation. The percentage of dead or moribund lizards at four weeks posttreatment was 62.5% in animals fed contaminated prey and 42.0% in gavaged animals. In both tests, survivors showed significantly reduced feeding activity, food consumption, body weight, and organ-to-body-weight ratios (liver and/or fat body). The high toxicity of fipronil to lizards was not previously known, suggesting that follow-up studies (e.g., subacute dietary tests) are needed to provide adequate data for risk assessment.

Animals↗

Does the Harvard/U.S. Environmental Protection Agency Ambient Particle Concentrator change the toxic potential of particles?

Inhalation exposure to urban air particles is known to increase morbidity in humans and animals. Our group utilizes the Harvard/U.S. Environmental Protection Agency Ambient Particle Concentrator (HAPC) to generate concentrated aerosols of outdoor air particles for experimental exposures. We have reported increased pathologic responses to inhalation of concentrated urban air particles and identified silicon (as silicate) as an element associated with many of these responses. Using silicate-rich Mt. St. Helen's volcanic ash (MSHA), we exposed three groups of Sprague-Dawley rats by inhalation for 6 hr to filtered air, MSHA, or MSHA passed though the HAPC. Twenty-four hours following exposure, bronchoalveolar lavage was performed to assess total cell count, differential cell count, protein, lactate dehydrogenase, and n-beta-glucosaminidase levels. Peripheral blood was examined for packed cell volume, total protein, total white cells, and differential cell count. Morphologic studies localized particles in the lung and assessed pulmonary vasculature. No significant differences were observed among any of the groups in any parameter measured including morphometric analysis of pulmonary vasoconstriction. Scanning electron microscopy and X-ray analysis identified particles as silicates typical of MSHA throughout the lung. These findings suggest that particles passing through the HAPC have no change in their toxic potential in an exposure setting where particle deposition in the lung has occurred.

Aerosols↗

Measurement of urinary methoxyphenols and their use for biological monitoring of wood smoke exposure.

A urinary assay for methoxyphenols was developed for the biological monitoring of wood smoke exposure. Methoxyphenols in 10-ml samples of urine were extracted after acid hydrolysis using XAD in a solid-phase extraction cartridge. The methoxyphenols were eluted with ethyl acetate and then analyzed by gas chromatography/mass spectrometry. Specific chemicals quantified were guaiacol, 4-methylguaiacol, 4-ethylguaiacol, 4-propylguaiacol, syringol, 4-methylsyringol, 4-ethylsyringol, vanillin, eugenol, and syringaldehyde. Recoveries ranged from 60 to 90%, with coefficients of variation of < or =20%. Background levels of the compounds were measured in 21 nonsmoking adults. Guaiacol, 4-methylguaiacol, eugenol, and vanillin were detected in all subjects. An experimental feeding of a commercial wood smoke flavoring demonstrated that methoxyphenols were rapidly and efficiently eliminated in urine. Preliminary field studies demonstrated that urinary excretion rates of some methoxyphenols increased after inhalation exposure to wood smoke.

Adult↗

Comparative assessment of three in vitro exposure methods for combustion toxicity.

A comparative assessment of three approaches for the use of human cells in vitro to investigate combustion toxicity was conducted. These included one indirect and two direct (passive and dynamic) exposure methods. The indirect method used an impinger system in which culture medium was used to trap the toxicants, whilst the direct exposure involved the use of a Horizontal Harvard Navicyte Chamber at the air/liquid interface. The cytotoxic effects of thermal decomposition products were assessed using the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay (Promega) on a selection of human cells including: HepG2, A549 and skin fibroblasts. A small scale laboratory fire test using a vertical tube furnace was designed for the generation of combustion products. Polymethyl methacrylate (PMMA) was selected as a model polymer to study the cytotoxic effects of combustion products. NOAEC (no observable adverse effect concentration), IC10 (10% inhibitory concentration), IC50 (50% inhibitory concentration) and TLC (total lethal concentration) values were determined from dose response curves. Assessment using the NRU (neutral red uptake) and ATP (adenosine triphosphate) assays on human lung derived cells (A549) was also undertaken. Comparison between in vitro cytotoxicity results against published toxicity data for PMMA combustion and predicted LC50 (50% lethal concentration) values calculated from identified compounds using GCMS (gas chromatography mass spectrometry) was determined. The results suggested that the indirect exposure method did not appear to simulate closely exposure via inhalation, whilst exposure at the air/liquid interface by using the dynamic method proved to be a more representative method of human inhalation. This exposure method may be a potential system for in vitro cytotoxicity testing in combustion toxicity.

Adenosine Triphosphate↗

Operator exposure when applying amenity herbicides by all-terrain vehicles and controlled droplet applicators.

A total of 33 surveys of amenity herbicides took place during 1998-1999. These surveys concentrated on two application methods: all-terrain vehicles (ATVs) and controlled droplet applicators (CDAs). The purpose of these surveys was to measure surface deposition and potential inhalation exposure of the operators to the spray fluid used. This paper recommends that the following indicative values should inform risk assessments for these types of application. ATV: The potential dermal exposure (PDE) to spray fluid (21 sample sets) ranged between 0.7 and 6.8 ml/h of spray fluid, median 2.0 ml/h based on patch samplers. Exposure to the hands, as collected on cotton gloves, ranged between 0.6 and 13.6 ml/h, median 3.0 ml/h. Potential exposure to spray fluid by inhalation was found in 85% of the samples, range 7-37 mg/m(3), median of non-zero values at 16 mg/m(3). CDA: The PDE to spray fluid (12 sample sets) ranged between 0.003 and 0.826 ml/h of fluid, median 0.133 ml/h, based on patch samplers. Exposure to the hands, as collected on cotton gloves inside protective gloves, ranged up to 0.06 ml/h, median 0.004 ml/h, and on socks ranged up to 0.05 ml/h, median 0.001 ml/h. Potential exposure by inhalation was low: detected in just 33% of the samples, range 0.02-0.61 mg/m(3), median 0.12 mg/m(3).

Air Pollutants, Occupational↗