Mark F. Boeniger

INTERPRETATION OF URINE RESULTS USED TO ASSESS CHEMICAL EXPOSURE WITH EMPHASIS ON CREATININE ADJUSTMENTS: A REVIEW

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.

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°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.

Quantification of epithelial cell micronuclei by fluorescence in situ hybridization (FISH) in mortuary science students exposed to formaldehyde.

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.

Community-based intervention to reduce pesticide exposure to farmworkers and potential take-home exposure to their families.

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 μg per pair, respectively (P<0.001)); similarly, median MDA levels in urine were lower among workers who wore gloves (45.3 vs. 131.2 μg/g creatinine, P<0.05). Malathion was detected on clothing (median=0.13 μg/cm2), but not on skin. Workers who ate strawberries had higher malathion dicarboxylic acid levels in urine (median=114.5 vs. 39.4 μg/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.

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.

Biologic markers in hospital workers exposed to low levels of ethylene oxide

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.

Immunologic findings among lead-exposed workers

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.

Formate in urine as a biological indicator of formaldehyde exposure: a review.

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.

Mortality of workers exposed to toluene diisocyanate in the polyurethane foam industry.

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-Hodgkins 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-Hodgkins lymphoma and Hodgkins 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.

Exposure to Protein Aeroallergens in Egg Processing Facilities

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.