Biomedical subjects

J Cocker

Publications and source records attributed to J Cocker.

At least 19 recordsLinked to original sources

PubMed2006

Assessing isocyanate exposures in polyurethane industry sectors using biological and air monitoring methods.

Isocyanates, as a chemical group, are considered to be the biggest cause of occupational asthma in the UK. Monitoring of airborne exposures to total isocyanate is costly, requiring considerable expertise, both in terms of sample collection and chemical analysis and cannot be used to assess the effectiveness of protection from wearing respiratory protective equipment (RPE). Biological monitoring by analysis of metabolites in urine can be a relatively simple and inexpensive way to assess exposure to isocyanates. It may also be a useful way to evaluate the effectiveness of control measures in place. In this study biological and inhalation monitoring were undertaken to assess exposure in a variety of workplaces in the non-motor vehicle repair sector. Companies selected to participate in the survey included only those judged to be using good working practices when using isocyanate formulations. This included companies that used isocyanates to produce moulded polyurethane products, insulation material and those involved in industrial painting. Air samples were collected by personal monitoring and were analysed for total isocyanate content. Urine samples were collected soon after exposure and analysed for the metabolites of different isocyanate species, allowing calculation of the total metabolite concentration. Details of the control measures used and observed contamination of exposed skin were also recorded. A total of 21 companies agreed to participate in the study, with exposure measurements being collected from 22 sites. The airborne isocyanate concentrations were generally very low (range 0.0005-0.066 mg m(-3)). A total of 50 of the 70 samples were <0.001 mg m(-3), the limit of quantification (LOQ), therefore samples below the LOQ were assigned a value of 1/2 LOQ (0.0005 mg m(-3)). Of the 70 samples, 67 were below the current workplace exposure limit of 0.02 mg m(-3). The highest inhalation exposures occurred during spray painting activities in a truck manufacturing company (0.066 mg m(-3)) and also during spray application of polyurethane foam insulation (0.023 mg m(-3)). The most commonly detected isocyanate in the urine was hexamethylene diisocyanate, which was detected in 21 instances. The geometric mean total isocyanate metabolite concentration for the dataset was 0.29 micromol mol(-1) creatinine (range 0.05-12.64 micromol mol(-1) creatinine). A total of 23 samples collected were above the agreed biological monitoring guidance value of 1.0 micromol mol(-1) creatinine. Activities that resulted in the highest biological monitoring results of the dataset included mixing and casting of polyurethane products (12.64 micromol mol(-1) creatinine), semi-automatic moulding (4.80 micromol mol(-1) creatinine) and resin application (3.91 micromol mol(-1) creatinine). The biological monitoring results show that despite low airborne isocyanate concentrations, it was possible to demonstrate biological uptake. This tends to suggest high sensitivity of the biological monitoring method and/or that in some instances the RPE being used by operators was not effective or that absorption may have occurred via dermal or other routes of exposure. This study demonstrates that biological monitoring is a useful tool when assessing worker exposure to isocyanates, providing a more complete picture on the efficacy of control measures in place than is possible by air monitoring alone. The results also demonstrated that where control measures were judged to be adequate, most biological samples were close to or < 1 micromol mol(-1) creatinine, the agreed biological monitoring benchmark.

Air Pollutants, Occupational↗

PubMed2006

Biomonitoring for chromium and arsenic in timber treatment plant workers exposed to CCA wood Preservatives.

This study reports a survey of occupational exposure to copper chrome arsenic (CCA) based wood preservatives during vacuum pressure timber impregnation. The survey involved biological monitoring based on analysis of chromium and arsenic in urine samples collected from UK workers. The aim of the study was to determine the extent of occupational exposure to arsenic and chromium in the UK timber treatment industry. The objectives were to collect and analyse urine samples from as many workers as possible, where CCA wood preservatives might be used, at 6 monthly intervals for 2 years. In addition, to investigate day-to-day variations in urinary excretion of chrome and arsenic by collecting and analysing three samples a week for 3 weeks in subsets of workers and controls (people not occupationally exposed). All urine samples were analysed for chromium and inorganic arsenic. To investigate any residual interference every sample was accompanied by a short questionnaire about recent consumption of seafood and smoking. The analytical methods for arsenic used a hydride generation technique to reduce interference from dietary sources of arsenic and also a technique that would measure total arsenic concentration in urine. The main findings show that workers exposed to CCA wood preservatives have concentrations of inorganic arsenic and chromium in urine that are significantly higher than those from non-occupationally exposed people but below biological monitoring guidance values that would indicate inhalation exposure at UK occupational exposure limits for chromium and arsenic. The effects of consumption of seafood on urinary arsenic were not significant using the hydride generation method for inorganic arsenic but were significant if 'total' arsenic was measured. The 'total' arsenic method could not distinguish CCA workers from controls and is clearly unsuitable for assessment of occupational exposure to arsenic. There was a significant increase in the urinary concentration of chromium in workers over the four sample collection rounds indicating increasing exposure to chromium during the 2 years of the study. This unexpected finding may be worth further investigation. Overall, the study demonstrated the utility of biological monitoring for assessment of occupational exposure to chromium and arsenic.

Arsenic↗

PubMed2006

Biological monitoring for trimethylbenzene exposure: a human volunteer study and a practical example in the workplace.

This paper presents data from both a human volunteer study looking at exposure to 1,3,5-trimethylbenzene (TMB) and an occupational hygiene study of a printing firm using screen wash containing technical grade TMB. The biomarkers measured were TMB in blood and breath, and urinary dimethylbenzoic acids (DMBAs). The volunteer (N = 4) study showed that TMB was rapidly absorbed into the bloodstream reaching a mean level of 0.85 micromol l(-1) during a 4 h exposure to 25 p.p.m. TMB. There was little decline 1 h post-exposure possibly indicating storage of TMB in adipose tissue. Breath TMB levels peaked within an hour of exposure commencing and averaged 137 nmol l(-1) during exposure. Elimination of TMB in breath was biphasic with an initial half-life of 60 min. Peak excretion of urinary DMBA occurred 4-8 h after the end of exposure and averaged 40 mmol mol(-1) creatinine. Elimination of DMBA in urine was biphasic with half-lives of 13 and 60 h indicating that accumulation of body burden throughout the working week is likely if exposure is repeated. The occupational hygiene study demonstrated an excellent correlation between personal air TMB levels and post-shift urinary DMBA levels (r = 0.997) collected on the third working day. The regression equation from this study indicates that 8 h exposure to 25 p.p.m. TMB would result in a urinary DMBA level of 206 mmol mol(-1) creatinine. All workers showed pre-shift levels of DMBA from exposure to TMB on previous days. Both urinary DMBA and breath TMB levels can be used as biomarkers of TMB exposure. Urine samples should be taken post-shift towards the end of the working week as significant body burden accumulation throughout the working week can be expected. Breath sampling is more suited to task or single-shift monitoring.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2005

Physiologically based pharmacokinetic modelling of human exposure to 2-butoxyethanol.

A physiologically based pharmacokinetic (PBPK) model describing the disposition of 2-butoxyethanol (2-BE) was developed in order to predict the urinary concentration of its major metabolite, butoxyacetic acid (BAA) under a range of exposure scenarios. Based on Corley et al. [Corley, R.A., Bormett, G.A., Ghanayem, B.I., 1994. Physiologically based pharmacokinetics of 2-butoxyethanol and its major metabolite, 2-butoxyacetic acid, in rats and humans. Toxicol. Appl. Pharmacol. 129, 61-79], the model included such features as multiple entry routes into the body, varying workload conditions, metabolism in the liver and elimination of free BAA in urine by glomerular filtration and acid transport. A bladder compartment simulating the fluctuations in metabolite concentration in urine caused by micturition formed a novel aspect of the model. Good agreement between model predictions and existing experimental data of total BAA levels in the blood and urine over various exposure conditions were observed. The mechanistically based PBPK model allowed comparison of disparate studies and also enabled the prediction of urinary concentrations of BAA post-shift. By calculating the total amount of BAA, any inter-individual variability in conjugation is taken into account. This led us to conclude that a biological monitoring guidance value should be proposed for total rather than free BAA with a value of 250 mmol/mol of creatinine (post-shift), based on an 8h exposure to 25 ppm 2-BE at resting working conditions.

Environmental Exposure↗

PubMed2005

Internal contamination of gloves: routes and consequences.

The effect of internal glove contamination was investigated using N-methyl pyrrolidone (NMP) as a biological marker to assess systemic absorption when wearing internally contaminated gloves, and when not wearing gloves but subjected to the same challenge contaminant. The routes by which the insides of gloves become contaminated were also investigated. The area of dermal contamination was quantified using a fluorescent tracer dye and a surface monitoring fluorimeter. The main routes of internal glove contamination were found to be self-contamination, cuff entry and failed gloves. Wearing internally contaminated gloves led to higher systemic absorption than was gained from the equivalent skin contamination when not wearing gloves. Repeat wetting of fingers with aqueous NMP, when gloves were not worn, gave higher systemic absorption than the equivalent continuous exposure, probably due to the low volatility of NMP leading to increased concentration and longer residence time on the skin.

Environmental Monitoring↗

PubMed2004

Biotransformation of chlorpyrifos and diazinon by human liver microsomes and recombinant human cytochrome P450s (CYP).

The cytochrome P450 (CYP)-mediated biotransformation of the organophosphorothioate insecticides chlorpyrifos and diazinon was investigated. Rates of desulphuration to the active oxon metabolite (chlorpyrifos-oxon and diazinon-oxon) and dearylation to non-toxic hydrolysis products were determined in human liver microsome preparations from five individual donors and in recombinant CYP enzymes. Chlorpyrifos and diazinon underwent desulphuration in human liver microsome with mean Km = 30 and 45 microM and V(max) = 353 and 766 pmol min(-1) mg(-1), respectively. Dearylation of these compounds by human liver microsome proceeded with Km = 12 and 28 microM and V(max) = 653 and 1186 pmol min(-1) mg(-1), respectively. The apparent intrinsic clearance (V(max)/Km) of dearylation was 4.5- and 2.5-fold greater than desulphuration for chlorpyrifos and diazinon, respectively. Recombinant human CYP2B6 possessed the highest desulphuration activity for chlorpyrifos, whereas CYP2C19 had the highest dearylation activity. In contrast, both desulphuration and dearylation of diazinon were catalysed at similar rates, in the rank order CYP2C19 > CYP1A2 > CYP2B6 > CYP3A4. Both organophosphorothioates were more readily detoxified (dearylation) than bioactivated (desulphuration) in all human liver microsome preparations. However, the role of individual CYP enzymes in these two biotransformation pathways varied according to the structure of the organophosphorothioate, which was reflected in different activation/detoxification ratios for chlorpyrifos and diazinon. Variability in activity of individual CYP enzymes may influence interindividual sensitivity to the toxic effects of chlorpyrifos and diazinon.

Aged↗

PubMed2003

Factors affecting the extent of dermal absorption of solvent vapours: a human volunteer study.

OBJECTIVES: We have previously reported that solvent vapours can be absorbed through the skin and that the extent varies markedly and depends on the chemical. For some chemicals, the extent of absorption is significant, e.g. for 1-methoxy-2-propanol dermal absorption accounts for up to 14% of the total absorbed dose after 8 h exposure at the OES. We have conducted a second study using 2-butoxyethanol to investigate the influence of temperature, humidity and clothing on the dermal absorption of vapours. As for the first study, the extent of dermal absorption was determined by biological monitoring to measure the resultant body burden of the chemical. METHODS: Four volunteers were exposed on nine occasions. For eight of these exposures they wore air-fed half-masks to supply clean air for the inhalation route. The 'baseline' conditions (one 'whole body' and one 'skin only' exposure) were 25 degrees C, 40% relative humidity with volunteers wearing shorts and T-shirt. For each subsequent exposure, a single parameter was changed: humidity (60%, 65%), temperature (20 degrees C, 30 degrees C) or clothing (minimal and overalls). Finally, a 'industrial scenario' was conducted where volunteers wore overalls over their shorts and T-shirts and environmental conditions reflected high temperature and high humidity (30 degrees C, 60%), such as might be encountered in a tank-cleaning operation or similar. RESULTS: Results show that 'baseline' dermal absorption of 2-butoxyethanol vapour was, on average, 11% of the total absorbed dose. Higher temperature (30 degrees C, mean 14%, P = 0.03) and greater humidity (65% RH, mean 13%, P = 0.1) increased dermal absorption. The wearing of whole-body overalls did not attenuate absorption (mean 10%). By combining several factors together in the 'industrial scenario', dermal absorption of vapours was significantly increased with a mean of 39% of the total absorbed dose. CONCLUSIONS: The work has shown that dermal absorption of vapours can be significant and that environmental conditions may affect the absorption. Some types of protective clothing may not be suitable to reduce absorption. The possibility of dermal absorption of vapours should be considered particularly for workers in high vapour concentration conditions where control of exposure relies on respiratory protection.

Adult↗

PubMed2002

Biological monitoring of exposure to organophosphate pesticides.

Organophosphates (OPs) are readily absorbed through the skin and biological monitoring is an essential component of any comprehensive assessment of exposure. This paper presents a summary of our experience in a wide range of occupational studies. Additionally, we have conducted studies of non-occupational exposure and human volunteer studies looking at the kinetics of chlorpyrifos, propetamphos, diazinon and malathion. In non-occupationally exposed people, 95% of urinary alkyl phosphates do not exceed 72 micromol/mol creatinine. In occupationally exposed people, the corresponding 95th percentile of total urinary alkyl phosphates is 122 micromol/mol creatinine. In volunteer studies with 1 mg oral doses of chlorpyifos, diazinon and propetamphos the mean peak values were 160, 750 and 404 micromol/mol creatinine, respectively, and were not associated with any reduction in blood cholinesterase activity. The levels of OP metabolites seen in urine from workers potentially exposed to OPs are generally low and unlikely to cause significant reduction in blood cholinesterase activity.

Biomarkers↗

PubMed2002

Exposure to the organophosphate diazinon: data from a human volunteer study with oral and dermal doses.

Biological monitoring of occupational exposure to diazinon is possible by the determination of blood cholinesterase activity and by the measurement of metabolites in urine. However, there is little data to aid in the interpretation of results. This study gave oral (11 microg kg(-1) (36 nmol kg(-1)) body weight) and occluded dermal (100 mg (329 micromol)) doses of diazinon to five volunteers and analysed blood and urine samples for plasma and erythrocyte cholinesterase and urinary dialkyl phosphate (DAP) metabolites of diazinon: diethyl phosphate (DEP) and diethyl thiophosphate (DETP). Following oral and dermal exposure, peak urinary DAP levels occurred at 2 and 12 h, respectively. The apparent urinary elimination half-lives of DAP metabolites following oral and dermal exposure were approximately 2 and 9 h, respectively. Approximately 60% of the oral dose and 1% of the dermal dose was excreted as urinary DAP metabolites, with 90% of the dermal dose being recovered from the skin surface. On a group basis, there was no statistically significant mean depression in plasma or erythrocyte cholinesterase when compared with pre-exposure levels for either dosing experiment. The observed elimination kinetics of diazinon metabolites suggest a biological monitoring strategy for occupational exposure to diazinon based on urine samples collected at the end of shift.

Administration, Cutaneous↗

PubMed2002

Oral and dermal exposure to propetamphos: a human volunteer study.

Propetamphos ((E)-O-2-isopropylcarbonyl-1-methylvinyl-O-methylethyl phosphoramidothioate) is an organophosphate pesticide (OP) and has been used as an active ingredient in sheep dip where there is the potential for significant dermal exposure during dipping. Biological monitoring of exposure to propetamphos has until recently relied on the measurement of cholinesterase activity in plasma. Following the development of a novel method for the determination of propetamphos metabolites in urine, it is now possible to biologically monitor exposure using urine samples. This paper describes a human volunteer study involving oral and dermal exposure to propetamphos.

Administration, Cutaneous↗

PubMed2001

Identification of a possible biomarker for colophony exposure.

Colophony is known to cause occupational asthma and dermatitis. Biological monitoring may be useful in assessing exposure. This paper describes a method for the analysis of dehydroabietic acid in urine and its potential use as a marker of colophony exposure. The method involves hydrolysis, solvent extraction, derivatization and analysis by gas chromatography-mass spectrometry. Twenty-eight workers from a soldering factory in South Africa were monitored. Results showed that levels of dehydroabietic acid in urine may be correlated with a subjective assessment of exposure.

Abietanes↗

PubMed2001

The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazone.

The effects of acute administration of dietary levels of ethanol and the garlic oil extract, diallyl sulphide (DAS), on cytochrome P450 2E1 (CYP2E1) activity in volunteers were studied using the selective probe substrate, chlorzoxazone (CZX). The ratio of the CZX metabolite 6- hydroxychlorzoxazone (6-OHCZX) to CZX was taken to indicate CYP2E1 activity. The mean differences between the baseline and DAS-treated (0.2 mg/kg) CYP2E1 activities were significantly different (two-tailed p value = 0.0242, n = 8). Likewise, the mean differences between the baseline and ethanol-treated (0.8 g/kg) CYP2E1 activities were also significantly different (two-tailed p value = 0.0005, n = 7). The reduction in in vivo CYP2E1 activity by DAS is consistent with reported inhibition observed in vitro. The marked reduction in CYP2E1 activity following acute ingestion of ethanol is consistent with a competitive inhibition mechanism of CZX metabolism. The inhibitory effect of DAS maybe additive with daily consumption of Allium vegetables in particular. This may explain the lower 6-OHCZX/CZX metabolic ratios measured in various European and Mexican cohorts and is consistent with the lower incidence of stomach, liver and colon cancers observed in southern Europeans.

Administration, Oral↗

PubMed2000

The in vitro percutaneous penetration of chlorpyrifos.

Chlorpyrifos is a widely used organophosphate pesticide. In order to study the pharmacokinetics of the penetration of chlorpyrifos through human skin we measured the percutaneous penetration of chlorpyrifos through human skin using an in vitro flow through apparatus. The chlorpyrifos was applied to the skin as a commercial concentrate or as a reference standard dissolved in ethanol. There was a significant difference (P=0.03) between the rate of penetration from the commercial concentrate (9.0 nmoles cm(-2) h(-1)) and that from the reference standard (4.9 nmoles cm(-2) h(-1)). Each experiment was run for 24 h. The recoveries from experiments where chlorpyrifos was applied to the skin as a commercial concentrate and as a reference standard dissolved in ethanol were, respectively, in total 91 and 87% of the applied dose of which 15 and 10% was recovered from the skin, 56 and 66% was recovered from the surface of the skin and 20 and 11% was recovered from the receptor fluid. There was a significant difference in the recoveries from the skin but there was no significant difference in the recoveries from the surface of the skin. We concluded that the majority of a dermal dose of chlorpyrifos was still present at or in the surface of the skin 24 h after application of a dermal dose. Because chlorpyrifos was recovered from the skin after 24 h, it is possible that the skin could act as a reservoir and release chlorpyrifos over a longer period. We also conclude that the solvent vehicle for chlorpyrifos can affect the rate of penetration of the pesticide.

Administration, Cutaneous↗

PubMed1999

Estimation of the dermal absorption of m-xylene vapor in humans using breath sampling and physiologically based pharmacokinetic analysis.

A physiologically-based pharmacokinetic model, containing a skin compartment, was derived and used to simulate experimentally determined exposure to m-xylene, using human volunteers exposed under controlled conditions. Biological monitoring was conducted by sampling, in exhaled alveolar air and blood, m-xylene and urinary methyl hippuric acid concentrations. The dermal absorption of m-xylene vapor was successfully and conveniently studied using a breath sampling technique, and the contribution to m-xylene body burden from the dermal route of exposure was estimated to be 1.8%. The model was used to investigate the protection afforded by an air-fed, half-face mask. By iteratively changing the dermal exposure concentration, it was possible to predict the ambient concentration that was required to deliver the observed urinary excretion of methylhippuric acid, during and following inhalation exposure to 50 ppm m-xylene vapor. This latter extrapolation demonstrates how physiologically-based pharmacokinetic modeling can be applied in a practical and occupationally relevant way, and permitted a further step not possible with biological monitoring alone. The ability of the model to extrapolate an ambient exposure concentration was dependent upon human metabolism data, thereby demonstrating the mechanistic toxicological basis of model output. The methyl hydroxylation of m-xylene is catalyzed by the hepatic mixed function oxidase enzyme, cytochrome P450 2E1 and is active in the occupationally relevant, (<100 ppm) exposure range of m-xylene. The use of a scaled-up in vitro maximum rate of metabolism (Vmaxc) in the model also demonstrates the increasingly valuable potential utility of biokinetic data determined using alternative, non-animal methods in human chemical-risk assessment.

Administration, Cutaneous↗

PubMed1999

Oral and dermal absorption of chlorpyrifos: a human volunteer study.

OBJECTIVES: To determine the kinetics of elimination of urinary dialkylphosphate metabolites after oral and dermally applied doses of the organophosphate pesticide chlorpyrifos to human volunteers and to determine whether these doses affected plasma and erythrocyte cholinesterase activity. METHOD: Five volunteers ingested 1 mg (2852 nmol) of chlorpyrifos. Blood samples were taken over 24 hours and total void volumes of urine were collected over 100 hours. Four weeks later 28.59 mg (81567 nmol) of chlorpyrifos was administered dermally to each volunteer for 8 hours. Unabsorbed chlorpyrifos was washed from the skin and retained for subsequent measurement. The same blood and urine sampling regime was followed as for the oral administration. Plasma and erythrocyte cholinesterase concentrations were determined for each blood sample. The concentration of two urinary metabolites of chlorpyrifos--diethylphosphate and diethyl-thiophosphate--was determined for each urine sample. RESULTS: The apparent elimination half life of urinary dialkylphosphates after the oral dose was 15.5 hours and after the dermal dose it was 30 hours. Most of the oral dose (mean (range) 93% (55-115%)) and 1% of the applied dermal dose was recovered as urinary metabolites. About half (53%) of the dermal dose was recovered from the skin surface. The absorption rate through the skin, as measured by urinary metabolites was 456 ng/cm2/h. Blood plasma and erythrocyte cholinesterase activity did not fall significantly during either dosing regime. CONCLUSION: An oral dose of chlorpyrifos was readily absorbed through the skin and almost all of the dose was recovered as urinary dialkylphosphate metabolites. Excretion was delayed compared with the oral dose. Only a small proportion of the applied dose was recovered during the course of the experiment. The best time to collect urine samples for biological monitoring after dermal exposure is before the shift the next day. The amounts of chlorpyrifos used did not depress acetyl cholinesterase activity but could be readily detected as urinary dialkylphosphate metabolites indicating that the urinary assay is a more sensitive indicator of exposure.

Administration, Cutaneous↗

PubMed1999

Biological monitoring to assess exposure from use of isocyanates in motor vehicle repair.

OBJECTIVES: To develop a method for the measurement of a metabolite of hexamethylene diisocyanate (HDI), an isocyanate, and use it to assess the exposure of sprayers employed in motor vehicle repair shops. METHODS: Urine samples were taken from sprayers wearing personal protective equipment and spraying in booths or with local exhaust ventilation, from bystanders, and from unexposed subjects. Samples were analyzed for a metabolite of HDI, hexamethylene diamine (HDA), by gas chromatography-mass spectrometry (GC-MS). RESULTS: HDA was detected in four sprayers and one bystander out of 22 workers. No HDA was detected in the urine of unexposed subjects. CONCLUSIONS: Exposure to isocyanates still occurs despite the use of personal protective equipment and the use of a booth or extracted space. Health surveillance is likely to be required to provide feedback on the adequacy of controls even if such precautions are used and to identify cases of early asthma. Biological monitoring can provide a useful additional tool to assess exposure and the adequacy of controls in this group of exposed workers.

Automobiles↗

PubMed1999

Dermal route in systemic exposure.

To evaluate risk from dermal exposure, the amount of material on the skin must first be measured. The potential for dermal uptake must then be assessed for the potential health effects from systemic exposure. No standard methods exist for studying these processes, and published data are not comparable because of the different techniques used. Future validated methodology should provide a sound scientific basis for risk assessment. Methods for measuring skin and surface contamination will require development of reference contaminated surfaces and skin as part of quality control procedures. Biological monitoring is a valuable tool in the assessment of dermal absorption, in contributing to the validation of in vitro techniques, and in risk assessment and management. It will be necessary to conduct detailed investigations to support risk assessment for dermal exposure. Ultimately, predictive models will be established for exposure and for dermal absorption to support a generic approach and allow risk assessment strategies appropriate to actual workplace situations.

Environmental Monitoring↗

PubMed1998

Dermal uptake of solvents from the vapour phase: an experimental study in humans.

The control of exposure to hazardous substances in the workplace has traditionally focused on uptake via the inhalation route. Control of skin uptake has generally been considered for solids and liquids but the potential for uptake from vapours and gases has received relatively little attention. The current work was undertaken to establish a methodology to study the dermal uptake from vapours and to provide new and comparative information on a range of substance vapours. Groups of human volunteers were exposed to a small range of substances either 'whole body' or via the skin only. Substances (xylene, toluene, tetrahydrofuran [THF], methyl ethyl ketone [MEK] and 1-methoxypropan-2-ol [M2P]) were selected on the basis of their predicted dermal uptake from the vapour phase; their industrial use and potential for occupational exposure; the existence of a health-based occupational exposure limit; the availability of an analytical technique(s) for the substance and/or metabolite(s); and as representatives of chemical classes. Exposures were for four hours generally at the level of the UK Occupational Exposure Standard. Uptake was assessed by monitoring of parent or metabolite in blood, single breath or urine following exposure. Uptake of xylene, toluene and THF vapours via the skin under the conditions of this study was estimated to contribute around 1-2% of the body burden received following whole body (including inhalation) exposure. MEK showed more uptake via the skin, contributing around 3-3.5% of the body burden. Most dermal uptake was seen for the glycol ether M2P for which estimates of between 5-10% of whole body exposure body burden were obtained. The results of this and other studies indicate that uptake of vapours across the skin can occur but that for some substances (e.g., xylene, toluene, THF) this is likely to contribute little to the body burden. For other substances, such as the glycol ethers, skin uptake from vapours may be an important contributor to total uptake, particularly in situations where respiratory protective equipment is used to control inhalation exposure.

Administration, Cutaneous↗