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Exposure during the manufacture of pesticides is of particular concern due to their toxicity and because little is known about worker exposure, since most studies have focused on end-use application within agriculture or buildings. Even though dermal exposure can be expected to dominate for pesticides, little is known about workplace dermal exposures or even appropriate methods for their assessment. The current study begins to address this gap by evaluating alternative methods for assessing dermal exposure at a chemical manufacturing plant. For this pilot study, eight workers were recruited from a U.S. plant that produced the pesticide cypermethrin. Exposure was evaluated using three approaches: (1) survey assessment (questionnaire), (2) biological monitoring, and (3) workplace environmental sampling including ancillary measurements of glove contamination (interior and exterior). In each case, cypermethrin was quantified by enzyme-linked immunosorbent assay (ELISA). Environmental measurements identified two potential pathways of cypermethrin exposure: glove and surface contamination. Workplace exposure was also indicated by urine levels (specific gravity adjusted) of the parent compound, which ranged from 35 to 253 μg/L (median of 121 μg/L) with no clear trend in levels from pre- to post-shift. An exploratory analysis intended to guide future studies revealed a positive predictive association (Spearman correlation, p ≤ 0.10) between post-shift urine concentrations and a subset of survey questions evaluating worker knowledge, attitudes, and perceptions (KAP) of workplace dermal hazards, i.e., personal protective equipment self-efficacy, and inverse associations with behavior belief and information belief scales. These findings are valuable in demonstrating a variety of dermal exposure methods (i.e., behavioral attributes, external contamination, and biomarker) showing feasibility and providing measurement ranges and preliminary associations to support future and more complete assessments. Although these pilot data are useful for supporting design and sample size considerations for larger exposure and health studies, there is a need for validation studies of the ELISA assay for quantification of cypermethrin and its metabolites in urine.

The US EPA Worker Protection Standard requires pesticide safety training for farmworkers. Combined with re-entry intervals, these regulations are designed to reduce pesticide exposure. Little research has been conducted on whether additional steps may reduce farmworker exposure and the potential for take-home exposure to their families. We conducted an intervention with 44 strawberry harvesters (15 control and 29 intervention group members) to determine whether education, encouragement of handwashing, and the use of gloves and removable coveralls reduced exposure. Post-intervention, we collected foliage and urine samples, as well as hand rinse, lower-leg skin patch, and clothing patch samples. Post-intervention loading of malathion on hands was lower among workers who wore gloves compared to those who did not (median=8.2 vs. 777.2 microg per pair, respectively (P<0.001)); similarly, median MDA levels in urine were lower among workers who wore gloves (45.3 vs. 131.2 microg/g creatinine, P<0.05). Malathion was detected on clothing (median=0.13 microg/cm(2)), but not on skin. Workers who ate strawberries had higher malathion dicarboxylic acid levels in urine (median=114.5 vs. 39.4 microg/g creatinine, P<0.01). These findings suggest that wearing gloves reduces pesticide exposure to workers contacting strawberry foliage containing dislodgeable residues. Additionally, wearing gloves and removing work clothes before returning home could reduce transport of pesticides to worker homes. Behavioral interventions are needed to reduce consumption of strawberries in the field.

This article describes the laboratory assessment of a hand and surface wipe sampling method for polycyclic aromatic hydrocarbons (PAHs). The analytical method employed extraction of the wipe samples into dimethyl sulfoxide (DMSO) and high-performance liquid chromatography (HPLC) flourometric detection of pyrene, a predominant PAH in used gasoline engine oils (UGEO). Recovery of pyrene was evaluated for two different sampling media by first contaminating the hands of a small number of volunteers with UGEO, followed by applying a small amount of corn oil to the palms, and by wiping the skin with a Whatman cellulostic filter paper or a polyester fabric wipe (i.e., Alpha wipes). In summary, using either Whatman or Alpha wipes, the mean recovery of pyrene from the UGEO that was applied to the hands and contained within three consecutive wipes was 69% and 54%, respectively. However, the relative recovery of the first to second wipe was on average 47% and 75% for the two media, respectively. These results indicate that the Alpha wipes were more efficient at recovering pyrene in the first wipe but less efficient overall when all three consecutive samples were included. Even though this sampling was performed in a controlled laboratory environment, the minimum and maximum amount of pyrene recovered in the individual composite samples using either method spanned a range of twofold. Overall, intra-and interpersonal variability, as measured by coefficient of variation, were 22% and 19%, respectively, and were not statistically different by type of media used. This method was used in a pilot field survey to sample the hands of 18 automotive repair technicians and 18 office workers. Detectable amounts of pyrene (>0.2 microg/sample) were found on the hands of 61% and 0% of these two groups, respectively, with the highest measured quantity equal to 1.06 microg. Samples from the upper surfaces of automobile motors were generally low to nondetectable (<0.027 microg/sample), while the median value of 0.047 mkcrlg/50 cm(2)(CV = 160%) and up to 0.640 microg were found on the drip pans.

Hand contamination by toxic agents such as lead presents a potentially significant health hazard to workers if the contamination is transferred to the mouth by food, smoking, or touching the mouth. One method to sample the mass of contamination on hands is to wipe the skin and analyze the wipe media for the analyte. Several commercially available, prewetted wipe media were evaluated and compared. The Palintest and Wash'n Dri media are made of cellulose fiber; the Ghost wipe is made of a nonwoven polyvinyl alcohol fiber. ASTM test method E1792 for surface lead sampling provides some specified minimum requirements and some general, nonspecific criteria that these media should meet. However, no objective determination of the performance or characteristics of these different wiping media were found in the open literature for sampling lead on hands, particularly relating to typical collection efficiency. To test the recovery of lead oxide dust collected from two hands, two different loading levels were used for each wipe medium. Four successive wipes were collected and analyzed individually. The results of this study indicate that only about 52-62% of the total lead loading is recovered with the first wipe, but that up to 75% recovery could be obtained by combining all three successive wipes. This study also describes testing several physical aspects of these wipes that included tensile strength, wetness, and drying rate, which are characteristics that are not specified by ASTM E1792. The results indicate a higher fragility among the cellulosic wipes, less moisture content, and higher drying rates than the Ghost wipe. This information should be helpful when selecting a wipe material that is best suited for an environmental or industrial hygiene surface or skin sampling task and might also be useful for improving such media in the future.

Objective: The aim of this study was to investigate the percutaneous penetration of lead oxide (PbO) powder and the effect of rapid skin decontamination with two different detergents., Methods: Franz cells were used to study in vitro PbO skin penetration through human skin during a 24-hour period. The tests were performed without or with decontamination using either Ivory Liquid soap or a new experimental cleanser 30 minutes after the start of exposure., Results: We confirm that PbO can pass through the skin with a median penetration of 2.9 ng/cm (25-75th percentiles 0.35-6). The cleaning procedure using Ivory Liquid soap significantly increased skin penetration with a median value of 23.6 ng/cm (25-75th percentiles 12-47.1; Mann-Whitney U test, P = 0.0002), whereas the new experimental cleanser only marginally increased penetration (7.1 ng/cm)., Conclusions: Our results indicate that it is necessary to prevent skin contamination from occurring because a short contact can increase skin content and penetration even if quickly followed by washing. This study demonstrated that PbO powder can pass through the skin and that skin decontamination done after 30 minutes of exposure did not decrease skin absorption occurring over 24 hours and stresses the need to prevent skin contamination when using toxic substances.

The utility of solid phase extraction (SPE) for concentrating four organophosphate insecticides from solutions of water and sodium dioctyl sulfosuccinate, a surfactant, was evaluated. Reverse phase (C18, octadecyl bonded silica) sorbent in the form of a disk was the SPE medium evaluated. Chlorpyriphos, malathion, and diazinon, but not acephate, were retained on and eluted from the SPE disks. For pesticides that were retained on SPE disks, recoveries from the disks were equal to or higher than recoveries achieved by solvent partitioning. Dislodgeable foliar residues of acephate were successfully concentrated for analysis by lyophilization of water-surfactant solutions. Recoveries of pesticides from SPE disks stored at -15 degrees C for one week were equal to or higher than those of pesticides stored in water-surfactant for one week at -15 degrees C. Malathion- and diazinon-fortified samples in watersurfactant and on SPE disks were prepared in one state and shipped for analysis in another state. Pesticides in the water-surfactant samples were concentrated by solvent partitioning and were underestimated by 41% (diazinon) and 16% (malathion). Conversely, diazinon samples on the SPE disks were on average underestimated by 3% and malathion was overestimated by an average of 55%. The overestimation of malathion was attributed to a matrix effect during analysis associated with the presence of surfactant, which was retained on and subsequently eluted from the SPE disks. The retention of surfactant by the SPE disks and its subsequent elution may considerably limit their usefulness in determination of dislodgeable foliar residues.

The aim of the study was to assess the use of 3M porous polymer extraction discs (3M Empore sorbent filters) for detection of chemical permeation of protective clothing. Analysis of some commonly used solvents on 3M Empore sorbent filters was performed for methanol, acetone, trichloroethylene (TriCE), and toluene by solvent desorption and gas chromatography. All solvents exhibited >98 percent adsorption on the filters at a spiking level of 1.8 microL for each solvent. Solvent recovery for the system was calculated for each solvent, ranging from 72-94 percent (RSD < or = 4.0%) for all solvents over the spiking range 0.2-1.8 microL. The modified ASTM F739 method was used to determine breakthrough times for five protective glove materials (polyvinyl chloride, natural rubber, polymerized alkene, nitrile, and nitrile butyl rubber) using the model solvents as test chemicals. Breakthrough times for each type of protective glove were determined, and found to range from 36 s to 9 min for acetone, from 142 s to 52 min for methanol, from 18 s to 12 min for TriCE, and from 32 s to 28 min for toluene. The quantitative mass of the solvents on the filters at the time of breakthrough detection ranged from 150-159, 157-166, 570-581, and 371-382 microg/cm2 for acetone, methanol, TriCE, and toluene, respectively. The sorbent filter should find utility in collecting chemical permeation samples through protective gloves in both laboratory and field studies for quantitative analysis.

Proteinaceous materials in the air can be highly allergenic and result in a range of immunologically mediated respiratory effects, including asthma. We report on the largest evaluation of exposure to date of airborne egg protein concentrations in an egg breaking and processing plant that had cases of occupational asthma. Personal air samples for egg protein were analyzed in duplicate on each PTFE filter using two analytical methods: (1) a commercial assay for non-specific total protein, and (2) indirect competitive inhibition assay using an ELISA method to quantify specific egg protein components. The highest concentrations were found in the egg washing room (mean exposure 644 microg/m3) and breaking room (255 microg/m3), which were also the areas where the risk of being sensitized was the greatest. There was excellent quantitative agreement between the airborne concentrations of total protein and sum of the specific protein antigens (ovalbumin, ovomucoid, and lysozyme). The correlation coefficient of the log-transformed data from the two methods was 0.88 (p < 0.0001). Size-selective sampling also indicated that most of the aerosol was capable of reaching the small airways. The methods described can be utilized to evaluate employee exposure to egg proteins. Exposure documentation, coupled with recommended exposure reduction strategies, could facilitate prevention of future employee sensitization and allergic respiratory responses by identifying high-exposure jobs and evaluating control measures.

Ethylene oxide (EtO) is a genotoxic carcinogen with widespread uses as an industrial chemical intermediate and sterilant. We examined the effects of glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) genotypes on the levels of N-(2-hydroxyethyl)valine (HEV) adducts in the erythrocytes and sister chromatid exchange (SCE) in lymphocytes from a group of 58 operators of sterilizers that used EtO and nonexposed workers from nine hospitals in the United States and one hospital in Mexico City. Cumulative exposure to EtO was estimated during the 4-month period before the collection of blood samples. Results showed that EtO exposure was significantly associated with the levels of HEV adducts and SCE after adjusting for cigarette smoking and other potential confounders. A significantly higher HEV adduct level (0.17 +/- 0.03 versus 0.08 +/- 0.01, mean +/- SE; P = 0.02) but lower SCE frequency (5.31 +/- 0.39 versus 6.21 +/- 0.17; P = 0.04) was observed in subjects with homozygous deletion of the GSTT1 gene (null genotype) as compared with those with at least one copy of the gene (positive genotype). In multiple regression analysis, the GSTT1-null genotype was associated with an increase in HEV adduct level (beta = 1.62; P = 0.02) and a decrease in SCE frequency (beta = -1.25; P = 0.003) after adjusting for age, gender, race, education, cigarette smoking, and EtO exposure status. The inverse SCE-GSTT1 relationship remained unchanged when SCE was further examined in relation to HEV adducts as an indicator of the internal EtO dose. The GSTM1 genotype was not associated with the level of either HEV adduct or SCE. These data indicate that the GSTT1-null genotype is associated with increased formation of EtO-hemoglobin adducts in relation to occupational EtO exposure, suggesting that individuals with homozygous deletion of the GSTT1 gene may be more susceptible to the genotoxic effects of ETO: The unexpected finding of decreased SCEs, which is less clear, may be attributed to the nonchemical specificity of this end point and the lack of expression of the GSTT1 enzyme in lymphocytes.

Hand wash and skin wipes are major techniques that have been used for dermal exposure sampling. Both techniques remove chemicals either deposited on or transferred to the skin contaminant layer by a combination of chemical and mechanical actions. The paper overviews identified methods and techniques, with emphasis on sampling parameters and sampling efficiency. It is concluded that identified sampling protocols, including sampling techniques, deviate at possible key issues, which hampers comparisons of study results. It is recommended to conduct sampling efficiency studies prior to field sampling, under conditions that are quite similar to conditions of exposure regarding exposure process, levels of skin loading, and time of residence of the compound on the skin. Harmonization of sampling protocols will be a first step in creating a database for better understanding the influence of sampling parameters on the performance of removal techniques to assess dermal exposure.

This study compared four solvents (1-propanol, polyethylene glycol [avg. MW 400], 10% Ivory Liquid and water, and D-TAM) for their ability to remove selected pesticides from an in vitro porcine skin model using a solvent-moistened wipe. Wipes were performed 90 min after pesticide was applied to the skin. The four pesticides selected (glyphosate, alachlor, methyl parathion, and trifluralin) were chosen because of their differences in water solubility. This study also determined whether pretreatment of skin with a solvent prior to pesticide application would either increase or decrease recovery of the pesticide. Recovery efficiencies for all solvents and pesticides were affected by the amount of contaminant on the skin. Although pesticide recoveries from all four solvents were similar (range: 45-57%), on average 1-propanol had significantly higher recoveries, followed by soap and water. There was no significant difference between polyethylene glycol, and D-TAM. When skin was pretreated with any of the four solvents before pesticide application, the recoveries of the more water soluble compounds, glyphosate and alachlor, decreased. When pretreatment with solvent preceded application of trifluralin, the pesticide with the lowest water solubility, recoveries increased. 1-Propanol or soap and water were more effective in removing pesticides from skin than polyethylene glycol or D-TAM, but the amount of pesticide recovered from skin was affected by the chemical characteristics of the pesticide (such as water solubility) and the amount of pesticide originally on the skin. This study provides information useful to the interpretation of skin wipe sample results collected in field studies.

A comprehensive panel of immune parameters was evaluated among 145 lead-exposed workers with a median blood lead level (BLL) of 39 micrograms/dL (range: 15-55 micrograms/dL) and 84 unexposed workers. After adjusting for covariates, we found no major differences in the percentage of CD3+ cells, CD4+ T cells, CD8+ T cells, B cells, or NK cells between lead-exposed and unexposed workers, although the association between lead exposure and the number of CD4+ T cells was modified by age. We also found no differences between exposed and unexposed workers in serum immunoglobulin levels, salivary IgA, C3 complement levels, or lymphoproliferative responses. However, among exposed workers, the percentage and number of B cells were positively associated with current BLL, serum IgG was negatively associated with cumulative lead exposure, and the percentage and number of CD4+/CD45RA+ cells were positively associated with cumulative lead exposure. We found no evidence of a marked immunotoxic effect of lead at the exposure levels studied, although some subtle differences in immunologic parameters were noted.

O6-Alkylguanine-DNA alkyltransferase (AGT) activity was assessed in peripheral blood lymphocytes among 23 mortuary science students before and after 9 weeks in a laboratory course in techniques of embalming. Formaldehyde exposure was established by environmental monitoring. The average air concentration of formaldehyde during embalming was about 1.5 ppm. At the pre-exposure sampling, baseline DNA repair capacity tended to be reduced in subjects who reported a prior history of embalming (p = 0.08). From pre- to post-exposure, 17 subjects decreased in DNA repair capacity, while only 6 increased (p < 0.05). Analysis of variance, including adjustment for age, sex, and smoking status, confirmed these findings. Among the eight subjects who had no embalming experience during the 90 days before study, seven had decreased and one had increased AGT activity during the period of study (p < 0.05). For those with prior embalming experience, 10 subjects decreased in AGT activity, while 5 increased (p < 0.05). Although the major chemical exposure in embalming practice was to formaldehyde, no clear link was established between amount of formaldehyde exposure and AGT activity.

A micronucleus assay employing fluorescence in situ hybridization (FISH) with a centromeric probe was used on specimens of exfoliated buccal and nasal cells collected from mortuary science students exposed to embalming fluid containing formaldehyde. FISH labeling allowed micronuclei (MN) containing a whole chromosome (centromere-positive, MN+) to be differentiated from those containing only chromosomal fragments (centromere-negative, MN-). Each student was sampled before and after the 90 day embalming class. We determined if an increase in MN frequency could be attributed to formaldehyde exposure and was specific to either MN+ or MN-. In buccal cells, total MN frequency was significantly increased from 0.6/1000 to 2/1000 (p = 0.007) following the course, whereas in nasal cells it was not (2 and 2.5/1000, respectively, p = 0.2). Cells with multiple MN were present only in samples taken after exposure to embalming fluid. Although the baseline frequency was higher for MN+ in both buccal (0.4/1000 for MN+ and 0.1/1000 for MN-) and nasal cells (1.2/1000 for MN+ and 0.5/1000 for MN-), the increase in MN frequency was greater for MN-, (9-fold, p = 0.005 for buccal cells; 2-fold, p = 0.03 for nasal cells) than for MN+ (> 2-fold, p = 0.08 for buccal cells; no change, p = 0.31 for nasal cells) in both tissues. Thus, the primary mechanism of micronucleus formation appeared to be chromosome breakage. This finding is consistent with known clastogenic properties of formaldehyde, the component of embalming fluid most likely responsible for micronucleus induction.

Objective: To evaluate cancer mortality among United States workers exposed to toluene diisocyanate (TDI) in the manufacture of polyurethane foam., Methods: This cohort mortality study included 4611 men and women employed in four polyurethane foam plants for at least three months between the late 1950s and 1987. The mortality experience of the cohort was then compared with that of the general United States population., Results: Current and past industrial hygiene data indicated that air concentrations in 1984-5 were below the current United States standard of 0.04 mg/m3 but exceeded the standard before 1980. Mortality ratio (SMR) 2.78, 95% confidence interval (95% CI) 0.57-8.13) and non-Hodgkin's lymphoma (SMR 1.54, 95% CI 0.42-3.95) were increased, but not significantly. There was one male breast cancer. However, breast cancer was not increased in women (SMR 0.74). No other cancer category had an increased number of deaths compared with the general population. Only non-Hodgkin's lymphoma and Hodgkin's disease showed a possible relation with time since first employment and no cancer death category showed a strong relation with duration of employment. Mortality from non-malignant respiratory disease was not increased (SMR 0.86)., Conclusions: This young cohort has few deaths and short follow up. The findings are therefore not conclusive. Further years of follow up will enable better evaluation of mortality.

Objectives: To identify potential occupational risk factors, this study examined the occupational occurrence of various neurodegenerative diseases., Methods: Death certificates from 27 states in the National Occupational Mortality Surveillance System were evaluated for 1982 to 1991. Proportionate mortality ratios were calculated by occupation for presenile dementia, Alzheimer's disease, Parkinson's disease, and motor neuron disease., Results: Excess mortality was observed for all four categories in the following occupational categories: teachers; medical personnel; machinists and machine operators; scientists; writers/designers/entertainers; and support and clerical workers. Clusters of three neurodegenerative diseases were also found in occupations involving pesticides, solvents, and electromagnetic fields and in legal, library, social, and religious work. Early death from motor neuron disease was found for firefighters, janitors, military personnel, teachers, excavation machine operators, and veterinarians, among others., Conclusions: Neurodegenerative disease occurs more frequently in some occupations than in others, and this distribution, which may indicate occupational risk factors, should be further investigated.

Room ozonization has been in widespread use to "freshen" indoor air for more than 100 years. This use is sometimes promoted with the claim that ozone can oxidize airborne gases, and even particulates, to simple carbon dioxide and water vapor. Aside from whether ozone can improve indoor air quality, the potentially deleterious consequences to public health of overexposure to ozone are of concern. The literature on both allegations is reviewed. It indicates that ozone is not a practical and effective means of improving indoor air quality, especially in light of its potentially serious risk to health.

Women comprise the majority of workers exposed to ethylene oxide during sterilization of medical instruments and supplies. This article evaluates molecular, cytogenetic, and hematologic effects of ethylene oxide on 68 women workers employed in nine hospitals in the United States and one hospital in Mexico. Workers were classified by three exposure categories: none (0), low (> 0-32 ppm-hrs), and high (> 32 ppm-hrs). Hematologic effects were evaluated using complete blood count with differential, which has been questioned as a test for screening ethylene oxide-exposed workers. A statistically significant decrease in hematocrit (n = 0.02) and hemoglobin (P = 0.03) levels, an increase in lymphocyte percentages (P = 0.04), and a relative decrease in neutrophil percentages (P = 0.03) with exposure were observed in US workers. The absolute number of lymphocytes, however, showed no relationship with exposure. No statistically significant results were seen for Mexican workers, although hematocrit decreased with exposure. An exposure-response relationship for the percentage for lymphocytes (positive) and neutrophils (negative) in US subjects and for neutrophils (positive) in Mexican subjects was seen. No overall relation with exposure was observed for total number of white cells. Molecular and cytogenetic results are also reported for the 68 women, who constitute a subgroup from a previous report. US women workers showed a statistically significant exposure-response relationship for ethylene oxide and hemoglobin adducts (P = 0.0002) and sister chromatid exchanges (P = 0.001). For micronuclei, the difference (P = 0.02) between low and high exposure was statistically significant. In Mexican workers, an exposure-response relationship was observed (P = 0.002) for hemoglobin adducts but not for sister chromatid exchanges or micronuclei.

We conducted a cross-sectional environmental and medical survey of 355 male sugarcane workers in Hawaii to determine whether exposure to biogenic silica fibers (BSF) affected their respiratory health. Exposures to BSF ranged from nondetectable to more than 0.700 BSF/mL and varied by job and department. Respiratory symptoms, chest radiograph findings, and pulmonary function were not associated with BSF exposures. Cigarette smoking was associated with respiratory symptoms and pulmonary obstruction. Fifteen workers had pleural thickening or pleural plaques and 3 of these workers were exposed to BSF for more than 10 years. BSF exposure does not appear to influence the respiratory health of sugarcane workers; however, further study is warranted.

This paper reviews the process of elimination of creatinine (CRE), and the limitations presented when using it to express urine concentrations. This literature review leads to three conclusions: (1) CRE excretion is subject to wide fluctuations due to specific internal and external factors; (2) the use of CRE to correct chemical concentrations in urine will not necessarily improve the correlation to the exposure dose for all chemicals (it may, in fact, worsen the result); and (3) other means of expressing urine concentration may offer greater accuracy towards estimating individually absorbed dose.

The effect of low-level exposure to formaldehyde on oral, nasal, and lymphoycte biological markers was studied prospectively in a group of 29 mortician students who were about to take a course in embalming. During the 85-day study period, the subjects performed an average of 6.9 embalmings and had average cumulative formaldehyde exposures of 14.8 ppm-h, with an average air concentration of 1.4 ppm during embalming. Since the average time spent embalming was 125 min, formaldehyde exposures calculated as an 8-h time-weighted average were 0.33 ppm on days when embalmings were done, which was less than the Occupational Safety and Health Administration permissible exposure limit of 0.75 ppm. Epithelial cells from the buccal area of the mouth showed a 12-fold increase in micronucleus frequency during the study period, from 0.046 +/- 0.17/1000 cells preexposure to 0.60 +/- 1.27/1000 cells at the end of the course (P < 0.05). Nasal epithelial micronuclei increased 22%, from 0.41 +/- 0.52/1000 cells to 0.50 +/- 0.67/1000 cells (P = 0.26). In blood cells, the frequency of micronucleated lymphocytes increased 28%, from 4.95 +/- 1.72/1000 cells to 6.36 +/- 2.03/1000 cells (P < 0.05), while sister chromatid exchanges decreased 7.5% (P < 0.05). A dose-response relationship was observed between cumulative exposure to formaldehyde and increases in buccal micronuclei in the 22 male subjects but not in the 7 female subjects. We conclude that low-level exposure to formaldehyde is associated with cytogenetic changes in epithelial cells of the mouth and in blood lymphocytes. These cytogenetic effects may be useful as markers of biologically effective dose.

Operators of hospital sterilizers that use ethylene oxide were studied to determine if there was a relationship between exposure and a battery of biological markers. A total of 73 workers from nine hospitals in the United States (U.S.) and one hospital in Mexico City was evaluated for ethylene oxide exposure during four months prior to collection of peripheral blood. The frequency of hemoglobin adducts (p = 0.0006) and sister-chromatid exchanges (SCEs) (p = 0.002) increased with cumulative exposure to ethylene oxide in U.S. subjects when controlling by regression analysis for various confounding factors, including cigarette smoking. Hemoglobin adducts, but not SCEs, were also increased in Mexican subjects (p = 0.0012). Chromosomal micronuclei showed no consistent relationship with exposure. The U.S. study participants were classified by four-month cumulative exposure levels of 10 ppm-h (n = 8), greater than 0 to 32 ppm-h (n = 32) and greater than 32 ppm-h (n = 11) of ethylene oxide exposure. The group with an exposure of greater than 32 ppm-h had an increased frequency of hemoglobin adducts (p = 0.002) and SCEs (p = 0.0001) compared to the nonexposed group. The estimated mean of the 8-h time-weighted average (8-h TWA) exposure levels for the highest U.S. exposure group (greater than 32 ppm-h) was 0.16 +/- 0.007 ppm (mean +/- SD). A similar exposure-related differential was observed in the Mexican subjects for hemoglobin adducts (p = 0.04) but not for SCEs. The latter finding may have been due to longer shipping times for the specimens in the cytogenetic assays. The estimated mean of the 8-h TWA exposure levels for the highest Mexican exposure group (greater than 32 ppm-h) was 0.48 +/- 0.08 ppm. This study is the third to suggest that exposures less than the U.S. OSHA standard of 1 ppm 8-h TWA result in biochemical and biologic changes. It is not known whether these changes may be indicative of increased risk of disease; however, they do appear to reflect exposure to relatively low levels of ethylene oxide. The exact meaning of these changes is unknown.

A retrospective cohort mortality study with 5529 nitroglycerin, 4989 dinitrotoluene, and 5136 unexposed workers compared the mortality of the exposed groups with that of the United States population and that of the unexposed group with life-table analysis and Poisson regression. Mortality from ischemic heart disease was close to that expected, and mortality from cerebrovascular disease was slightly less than that expected, for the workers with both nitroglycerin and dinitrotoluene exposure and for those with dinitrotoluene exposure only. A significant interaction between age and nitroglycerin exposure was detected in the Poisson regression analyses for ischemic heart disease, particularly for workers actively exposed to nitroglycerin. The rate ratio for the workers under 45 years of age and actively exposed to nitroglycerin was 3.30 (95% confidence interval 129-8.48). This study did not show a chronic effect of nitroglycerin or dinitrotoluene exposure on cardiovascular disease risk. Potential biases related to the company's medical screening program may have limited the ability to detect chronic cardiovascular effects.

In conjunction with industrial hygiene surveys, mutagenicity studies were performed for the airborne contaminants in three polyurethane manufacturing plants. Airborne particles were collected on glass-fiber filters with Hi-Vol pumps from different locations in each plant. Gases were collected in multiple-sorbent cartridges. The collected airborne particles and sorbent cartridges were extracted with organic solvents. Each extract was tested for mutagenic activity using Salmonella typhimurium TA98 and TA100. The results showed that airborne particles from all three plants are mutagenic to TA98 with or without S9 activation. The mutagenicity with S9, however, was two to four times higher than that without S9. None of the samples of gases collected on sorbent cartridges showed mutagenic activity.

Benzidine (Bzd) and monoacetylbenzidine (MoAcBzd) were found in the urine of workers exposed to benzidine-based azo dyes. A colorimetric screening method, based on the reaction of extracted free aromatic amines with 2,4,6-trinitrobenzene-sulfonic acid (TNBS), was used with a specific electron-capture gas chromatographic (EC-GC) method. Alkaline hydrolyzable conjugates of Bzd and 2,4-diaminoazobenzene (DiAmAzBz) were found together with free DiAmAzBz and traces of 3,3'-dimethylbenzidine (DiMeBzd) and 3,3'-dimethoxybenzidine (DiMxBzd). The presence of a known human bladder carcinogen (Bzd) and its metabolites in the urine of workers exposed to benzidine-based azo dyes is a cause for concern.

The presence of a small amount of endogenously derived formate in human urine is normal; however, formate derived from the metabolism of formaldehyde, several other industrial compounds and some pharmaceuticals may elevate the urine formate concentration above the normally expected values. This elevation in the urine formate concentration presents the possibility of using this as a tool for monitoring exposure to chemicals. Unfortunately, the use of urine formate as a technique for monitoring personal chemical exposure has yet to be evaluated. This review identifies several potentially important variables that could alter the extent to which formate is eliminated through the urine and that could affect the accuracy of using urine formate concentration as an indicator of chemical exposure. Some potentially important confounders that have been identified, but not evaluated adequately, include dietary intake, nutritional status and exposure to cigarette smoke. Furthermore, the metabolism and elimination kinetics have yet to be adequately demonstrated in humans. Without having controlled for potential confounders in previous pharmacokinetic studies, it is unknown whether or not the large range and variation observed in human studies is due to the confounders or to innate individual variability. Given the poor understanding of the normal variation of formate concentration in the urine, the use of it as a biological indicator of chemical exposure becomes questionable. Without appreciable skin penetration, as in this case, the reliance upon air monitoring alone may be more practical. The evidence at this time suggests that the use of urine formate to monitor chemical exposure offers a broad opportunity for investigative research. At the present time, however, the interpretation of urine formate concentration in samples obtained from workers would be difficult.