DNA adducts in granulocytes of hospital workers exposed to ethylene oxide.

BACKGROUND: Ethylene oxide (EtO), an important industrial chemical intermediate and sterilant, is classified as a human carcinogen. Occupational EtO exposure in many countries is regulated at 1 ppm (8-hr TWA), but levels of EtO-DNA adducts in humans with low occupational EtO exposures have not been reported. METHODS: We examined the formation of N7-(2'-hydroxyethyl)guanine (N7-HEG), a major DNA adduct of EtO, in 58 EtO-exposed sterilizer operators and six nonexposed workers from ten hospitals. N7-HEG was quantified in granulocyte DNA (0.1-11.5 microg) by a highly sensitive and specific gas chromatography-electron capture-mass spectrometry method. Cumulative exposure to EtO (ppm-hour) was estimated during the 4-month period before the collection of blood samples. RESULTS: There was considerable inter-individual variability in the levels of N7-HEG with a range of 1.6-241.3 adducts/10(7) nucleotides. The mean levels in the nonexposed, low (< or =32 ppm-hour), and high (>32 ppm-hour) EtO-exposure groups were 3.8, 16.3, and 20.3 adducts/10(7) nucleotides, respectively, after the adjustment for cigarette smoking and other potential confounders, but the differences were not statistically significant. CONCLUSIONS: This study has demonstrated for the first time, detectable levels of N7-HEG adducts in granulocytes of hospital workers with EtO exposures at levels less than the current U.S. standard of 1 ppm (8-hr TWA). A nonsignificant increase in adduct levels with increasing EtO exposure indicates that further studies of EtO-exposed workers are needed to clarify the relationship between EtO exposure and N7-HEG adduct formation.

An FTIR investigation of isocyanate skin absorption using in vitro guinea pig skin.

Isocyanates may cause contact dermatitis, sensitization and asthma. Dermal exposure to aliphatic and aromatic isocyanates can occur in various exposure settings. The fate of isocyanates on skin is an important unanswered question. Do they react and bind to the outer layer of skin or do they penetrate through the epidermis as unreacted compounds? Knowing the kinetics of these processes is important in developing dermal exposure sampling or decontamination strategies, as well as understanding potential health implications such exposure may have. In this paper the residence time of model isocyanates on hairless guinea pig skin was investigated in vitro using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectrometry. Model isocyanates tested were octyl isocyanate, polymeric hexamethylene diisocyanate isocyanurate (pHDI), polymeric isophorone diisocyanate isocyanurate (pIPDI) and methylenediphenyl diisocyanate (MDI). Isocyanates in ethyl acetate (30 microL) were spiked directly on the skin to give 0.2-1.8 micromol NCO cm(-2) (NCO = -N=C=O), and absorbance of the isocyanate group and other chemical groups of the molecule were monitored over time. The ATR-FTIR findings showed that polymeric isocyanates pHDI and pIPDI may remain on the skin as unreacted species for many hours, with only 15-20% of the total isocyanate group disappearing in one hour, while smaller compounds octyl isocyanate and MDI rapidly disappear from the skin surface (80+% in 30 min). Isocyanates most likely leave the skin surface by diffusion predominantly, with minimal reaction with surface proteins. The significance of these findings and their implications for dermal exposure sampling and isocyanate skin decontamination are discussed.

Urinary hexane diamine to assess respiratory exposure to hexamethylene diisocyanate aerosol: a human inhalation study.

The use of urinary hexane diamine (HDA) as a biomarker to assess human respiratory exposure to hexamethylene diisocyanate (HDI) aerosol was evaluated. Twenty-three auto body shop workers were exposed to HDI biuret aerosol for two hours using a closed exposure apparatus. HDI exposures were quantified using both a direct-reading instrument and a treated-filter method. Urine samples collected at baseline, immediately post exposure, and every four to five hours for up to 20 hours were analyzed for HDA using gas chromatography and mass spectrometry. Mean urinary HDA (microg/g creatinine) sharply increased from the baseline value of 0.7 to 18.1 immediately post exposure and decreased rapidly to 4.7, 1.9 and 1.1, respectively, at 4, 9, and 18 hours post exposure. Considerable individual variability was found. Urinary HDA can assess acute respiratory exposure to HDI aerosol, but may have limited use as a biomarker of exposure in the workplace.

Federal government regulation of occupational skin exposure in the USA.

There are at least 14 federal regulations and three agencies that are involved in the regulation of occupational skin exposures in the USA. The Environmental Protection Agency (EPA) requires the reporting of health effects information on chemicals, and such information is used to assess the risks of human and environmental exposure. The health effects information and any resulting risk assessments are generally available to the public. A fair amount of this information relates to skin irritation, sensitization, and dermal absorption. The EPA can require the submission of new data necessary for it to carry out its risk assessments, and has the authority to ban hazardous chemicals for certain uses. The Food and Drug Administration (FDA) regulates the correct labeling of cosmetics and requires safety and efficacy data on new products that are claimed to have preventive or health benefits. Commercial distribution of topical skin-care and protection products, therefore, can be potentially scrutinized by the FDA, which can control the use of hazardous chemicals in such products. The Occupational Safety and Health Administration (OSHA) has the most direct contact with workplaces through its field inspection compliance activity, which is directed at the reduction of workplace injuries and illnesses. Our analysis suggests that although considerable amounts of health effects information is generated and available, such information may not always be adequately conveyed to the end users of chemical products. In addition, the most effective and practical means of preventing exposure is often not apparent or generally known. Current regulations may have created a reliance on use of chemical protective equipment that may not always be the best approach to protecting workers. Lack of performance criteria that are measurable has hampered industry from objectively assessing skin exposures. This lack of performance criteria or guidance has also hindered the implementation of prevention strategies and a critical assessment of their effectiveness. Better guidance from regulatory agencies directed at performance-based control of occupational skin hazards is presently needed.

Methods for assessing risks of dermal exposures in the workplace.

The skin as a route of entry for toxic chemicals has caused increasing concern over the last decade. The assessment of systemic hazards from dermal exposures has evolved over time, often limited by the amount of experimental data available. The result is that there are many methods being used to assess safety of chemicals in the workplace. The process of assessing hazards of skin contact includes estimating the amount of substance that may end up on the skin and estimating the amount that might reach internal organs. Most times, toxicology studies by the dermal route are not available and extrapolations from other exposure routes are necessary. The hazards of particular chemicals can be expressed as "skin notations", actual exposure levels, or safe exposure times. Characterizing the risk of a specific procedure in the workplace involves determining the ratio of exposure standards to an expected exposure. The purpose of this review is to address each of the steps in the process and describe the assumptions that are part of the process. Methods are compared by describing their strengths and weaknesses. Recommendations for research in this area are also included.

A critique of assumptions about selecting chemical-resistant gloves: a case for workplace evaluation of glove efficacy.

Wearing chemical-resistant gloves and clothing is the primary method used to prevent skin exposure to toxic chemicals in the workplace. The process for selecting gloves is usually based on manufacturers' laboratory-generated chemical permeation data. However, such data may not reflect conditions in the workplace where many variables are encountered (e.g., elevated temperature, flexing, pressure, and product variation between suppliers). Thus, the reliance on this selection process is questionable. Variables that may influence the performance of chemical-resistant gloves are identified and discussed. Passive dermal monitoring is recommended to evaluate glove performance under actual-use conditions and can bridge the gap between laboratory data and real-world performance.

In-use testing and interpretation of chemical-resistant glove performance.

Issuing gloves to workers is the most common approach to protecting against skin contact with hazardous chemicals. Typically, glove materials are selected and duration of wear is estimated based on comparisons of laboratory test data. Those who select the glove materials often fail to verify their selections by testing the glove during actual use. This failure poses a common but potentially serious hazard to workers. Although methods are available for assessing permeation rates during actual use, such testing is unlikely without acceptable exposure guidance criteria for decision making. This document reviews methods for testing glove performance during actual use and suggests an approach for estimating acceptable exposure guidance criteria for evaluation of chemicals that are systemically absorbed. It is the authors' opinion that as of now an approach to estimating exposure criteria for chemical irritants and sensitizers may not be feasible. With available data resources, acceptable glove exposure criteria could be generated for use in assessing the risk of using specific gloves for handling many compounds in occupational settings.

Indoor particles and symptoms among office workers: results from a double-blind cross-over study.

BACKGROUND: We studied the effects of removing small airborne particles in an office building without unusual contaminant sources or occupant complaints. METHODS: We conducted a double-blind crossover study of enhanced particle filtration in an office building in the Midwest United States in 1993. We replaced standard particle filters, in separate ventilation systems on two floors, with highly efficient filters on alternate floors weekly over 4 weeks. Repeated-measures models were used to analyze data from weekly worker questionnaires and multiple environmental measurements. RESULTS: Bioaerosol concentrations were low. Enhanced filtration reduced concentrations of the smallest airborne particles by 94%. This reduction was not associated with reduced symptoms among the 396 respondents, but three performance-related mental states improved; for example, the confusion scale decreased (-3.7%; 95% confidence limits (CL) = -6.5, -0.9). Most environmental dissatisfaction variables also improved; eg, "stuffy" air, -5.3% (95% CL = -10.3, -0.4). Cooler temperatures within the recommended comfort range were associated with remarkably large improvement in most outcomes; for example, chest tightness decreased -23.4% (95% CL = -38.1, -8.7) for every 1 degrees C decrease. CONCLUSIONS: Benefits of enhanced filtration require assessment in buildings with higher particulate contaminant levels in studies controlling for temperature effects. Benefits from lower indoor temperatures need confirmation.