Peter S.J. Lees

NTP-CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A.

Robert E. Chapin, Jane Adams, Kim Boekelheide, L. Earl Gray Jr, Simon W. Hayward, Peter S.J. Lees, Barry S. McIntyre, Kenneth M. Portier, Teresa M. Schnorr, Sherry G. Selevan, John G. Vandenbergh, and Susan R. Woskie Pfizer, Inc., Groton, CT University of Massachusetts, Boston, MA Brown University, Providence, RI U.S. Environmental Protection Agency, Research Triangle Park, NC Vanderbilt University Medical Center, Nashville, TN Johns Hopkins University, Baltimore, MD Schering Plough Research Institute, Summit, NJ American Cancer Society, Atlanta, GA National Institute for Occupational Safety and Health, Cincinnati, OH U.S. Public Health Service (Ret), Silver Spring, MD North Carolina State University, Raleigh, NC University of Massachusetts, Lowell, MA

Lung cancer among workers in chromium chemical production

BACKGROUND An elevated risk of lung cancer among workers in chromate production facilities has previously been reported. This excess risk is believed to be the result of exposure to hexavalent chromium. There have been mixed reports about whether trivalent chromium exposure is also associated with an excess lung cancer risk. Previous studies of measured hexavalent chromium exposure and lung cancer risk have not examined cigarette smoking as a risk factor. METHODS A cohort of 2,357 workers first employed between 1950 and 1974 at a chromate production plant was identified. Vital status of the workers was followed until December 31, 1992. Work histories of cohort members were compiled from the beginning of employment through 1985, the year the plant closed. Annual average exposure estimates, based on historical exposure measurements, were made for each job title in the plant for the years 1950-1985. These exposure estimates were used to calculate the cumulative hexavalent chromium exposure of each member of the study population. Following closure of the plant, settled dust samples were collected and analyzed for hexavalent and trivalent chromium. The trivalent/hexavalent concentration ratios in each plant area were combined with historic air-sampling data to estimate cumulative trivalent chromium exposure for each individual in the study cohort. Smoking status (yes/no) as of the beginning of employment and clinical signs of potential chromium irritation were identified from company records. RESULTS Cumulative hexavalent chromium exposure showed a strong dose-response relationship for lung cancer. Clinical signs of irritation, cumulative trivalent chromium exposure, and duration of work were not found to be associated with a risk of lung cancer when included in a proportional hazards model with cumulative hexavalent chromium exposure and smoking. Age-specific data on cumulative hexavalent chromium exposure, observed and expected numbers of lung cancer cases, and person-years of observation are provided. CONCLUSIONS Cumulative hexavalent chromium exposure was associated with an increased lung cancer risk; cumulative trivalent chromium exposure was not. The excess risk of lung cancer associated with cumulative hexavalent chromium exposure was not confounded by smoking status. The current study offers the best quantitative evidence to date of the relationship between hexavalent chromium exposure and lung cancer. Am. J. Ind. Med. 38:115-126, 2000. Published 2000 Wiley-Liss, Inc.

Evaluation of antineoplastic drug exposure of health care workers at three university-based US cancer centers

Objective: This study evaluated health care worker exposure to antineoplastic drugs. Methods: A cross-sectional study examined environmental samples from pharmacy and nursing areas. A 6-week diary documented tasks involving those drugs. Urine was analyzed for two specific drugs, and blood samples were analyzed by the comet assay. Results: Sixty-eight exposed and 53 nonexposed workers were studied. Exposed workers recorded 10,000 drug-handling events during the 6-week period. Sixty percent of wipe samples were positive for at least one of the five drugs measured. Cyclophosphamide was most commonly detected, followed by 5-fluorouracil. Three of the 68 urine samples were positive for one drug. No genetic damage was detected in exposed workers using the comet assay. Conclusions: Despite following recommended safe-handling practices, workplace contamination with antineoplastic drugs in pharmacy and nursing areas continues at these locations.

Wood-burning stoves and lower respiratory illnesses in Navajo children

BACKGROUND Acute lower respiratory illnesses (ALRI) have been associated with exposure to domestic smoke. To examine further this association, a case-control study was conducted among Navajo children seen at the Public Health Service Indian Hospital at Fort Defiance, AZ. METHODS Cases, children hospitalized with an ALRI (n = 45), were ascertained from the inpatient logs during October, 1992, through March, 1993. Controls, children who had a health record at the same hospital and had never been hospitalized for ALRI, were matched 1:1 to cases on date of birth and gender. Home interviews of parents of subjects during March and April, 1993, elicited information on heating and cooking fuels and other household characteristics. Indoor air samples were collected for determination of time-weighted average concentrations of respirable particles (i.e. < 10 microns in diameter). RESULTS Age of cases at the time of admission ranged from 1 to 24 months (median, 7 months); 60% of the cases were male. Matched pair analysis revealed an increased risk of ALRI for children living in households that cooked with any wood (odds ratio (OR), 5.0; 95% confidence interval (CI), 0.6 to 42.8), had indoor air concentrations of respirable particles > or = 65 micrograms/m3 (i.e. 90th percentile) (OR 7.0, 95% CI 0.9 to 56.9), and where the primary caretaker was other than the mother (OR 9, 95% CI 1.1 to 71.4). Individual adjustment for potential confounders resulted in minor change (i.e. < 20%) in these results. Indoor air concentration of respirable particles was positively correlated with cooking and heating with wood (P < 0.02) but not with other sources of combustion emissions. CONCLUSIONS Cooking with wood-burning stoves was associated with higher indoor air concentrations of respirable particles and with an increased risk of ALRI in Navajo children.

Evidence for Dermal Absorption as the Major Route of Body Entry During Exposure of Transformer Maintenance and Repairmen to PCBs

Traditional industrial hygiene assessment of exposure to polychlorinated biphenyls (PCBs) has long focused on air concentrations as a surrogate measure of worker dose. Evidence is presented to support the hypothesis that the dermal and dermal/oral routes of worker PCB exposure are major contributors to total PCB body burden in the group of transformer maintenance and repair personnel studied. Additional evidence is presented to demonstrate the critical role of work practices in determining PCB exposure. These hypotheses challenge the long-held notion of the pre-eminent importance of respiratory exposure to PCBs.

Factors affecting the retention of dust mite allergen on carpet.

Carpeting is one of the most common and perhaps the most important reservoir of aeroallergens and other components of dust found in residential or commercial settings. This research evaluated factors that affect the retention of dust mite allergens on different types of tufted carpet commonly found in homes and offices. Twenty-six types of carpet were custom manufactured as part of a two-stage factorial experiment using 182 carpet samples. Carpets differed with respect to fiber denier, cross-sectional shape, presence of fluorocarbon treatment, carpet style, pile height, and pile density. The major hypothesis tested was that the amount of allergen-containing dust recovered from vacuum samples of tufted carpet sources was dependent on micro (fiber) or macro (construction) retention characteristics of the carpets. Carpet samples were doped in a uniform and reproducible manner using an allergen-containing reference dust. A standardized vacuum surface sampler was used to recover dust from samples. Allergen was assayed using a standard, monoclonal antibody ELISA. Carpet-surface area and presence of fluorocarbon were found to have the largest effects on retention and recovery of dust and allergen. Specifically, fluorocarbon treatment of fibers, square-hollow fiber shape, high-denier fiber, low-pile height in cut-pile carpets, and low-pile density in loop carpets were significantly associated with increased release and recovery of allergen. Results from this study suggest that carpet type be considered for both allergen avoidance and allergy and asthma risk assessment.

Clinical findings of irritation among chromium chemical production workers

BACKGROUND Several reports of workers in chromate production and chromeplating have indicated that exposure to hexavalent chromium is associated with skin and nasal irritation. METHODS A cohort of 2, 357 workers first employed between 1950 and 1974 at a chromate production plant was identified. Clinical findings of irritation were identified by a physician as a result of routine examinations or visits to the medical clinic by members of the cohort. Percentages of the cohort with various clinical findings, the time from hire to occurrence of the first finding, and the mean and median annual hexavalent chromium (measured as CrO(3)) concentration for the job title where the clinical finding first occurred were determined. A proportional hazards model was used to evaluate the relationship between hexavalent chromium exposure and first occurrence of each of the clinical findings. RESULTS Nasal irritation and nasal ulceration were the most common clinical findings reported, occurring in more than 60% of the cohort. The average time to first occurrence of these findings was less than 3 months, whereas the time to first occurrence of the other findings ranged from 10 to 22 months. Median exposure to hexavalent chromium at the time of occurrence for most of the findings was about 20 microg/m(3). The proportional hazards model indicated that ulcerated nasal septum, irritated skin, and perforated eardrum were significantly associated with ambient hexavalent chromium exposure; all clinical findings with the exception of conjunctivitis and irritated skin were associated with the calendar year of hire, with the risk being lower as the calendar year of hire became more recent. Annual average ambient hexavalent chromium concentrations generally dropped in the plant over the period of the study. CONCLUSIONS Workers in the chromate production plant in this study experienced a variety of nasal and skin irritations. Irritated and ulcerated nasal septa, in particular, were quite common clinical findings, occurring in over 60% of the cohort, and they occurred in relatively short periods of time-less than 3 months from date of hire. Annual average concentrations of chromium may not be a good predictor of clinical findings of irritation. Am. J. Ind. Med. 38:127-131, 2000. Published 2000 Wiley-Liss, Inc.

Development of a method to detect and quantify Aspergillus fumigatus conidia by quantitative PCR for environmental air samples

Exposure to Aspergillus fumigatus is linked with respiratory diseases such as asthma, invasive aspergillosis, hypersensitivity pneumonitis, and allergic bronchopulmonary aspergillosis. Molecular methods using quantitative PCR (qPCR) offer advantages over culture and optical methods for estimating human exposures to microbiological agents such as fungi. We describe an assay that uses lyticase to digest A. fumigatus conidia followed by TaqMan™ qPCR to quantify released DNA. This method will allow analysis of airborne A. fumigatus samples collected over extended time periods and provide a more representative assessment of chronic exposure. The method was optimized for environmental samples and incorporates: single tube sample preparation to reduce sample loss, maintain simplicity, and avoid contamination; hot start amplification to reduce non-specific primer/probe annealing; and uracil-N-glycosylase to prevent carryover contamination. An A. fumigatus internal standard was developed and used to detect PCR inhibitors potentially found in air samples. The assay detected fewer than 10 A. fumigatus conidia per qPCR reaction and quantified conidia over a 4−log10 range with high linearity (R2 > 0.99) and low variability among replicate standards (CV=2.0%) in less than 4 h. The sensitivity and linearity of qPCR for conidia deposited on filters was equivalent to conidia calibration standards. A. fumigatus DNA from 8 isolates was consistently quantified using this method, while non-specific DNA from 14 common environmental fungi, including 6 other Aspergillus species, was not detected. This method provides a means of analyzing long term air samples collected on filters which may enable investigators to correlate airborne environmental A. fumigatus conidia concentrations with adverse health effects.

Industry-Wide Study of Mortality of Pulp and Paper Mill Workers

A study of pulp and paper mill workers indicated low risks of death from all causes (standardized mortality ratio (SMR) = 0.74) and all cancers (SMR = 0.81) compared with U.S. rates. The leukemia death rate in workers was not higher than the U.S. rate but was higher than the rate in county populations surrounding mills. Workers whose last jobs were in the finishing areas of the mills had an elevated SMR for liver cancer. An internal comparison of occupational characteristics indicated that workers employed in mills using other chemical pulping operations had significantly elevated mortality from all causes, all cancers, heart disease, lymphomas, and brain cancers. Lung cancer mortality was elevated in mills using kraft pulping. The internal comparisons confirmed the association between work in finishing and the risk of liver cancer. This study was designed to investigate whether pulp and paper mill workers have any risks that would indicate the need for studies detailing exposures.

Time Trends in Exposure Measurements from OSHA Compliance Inspections of the Pulp and Paper Industry

Time trends in employee exposures to the air contaminants measured by the Occupational Safety and Health Administration (OSHA) during compliance inspections of pulp and paper manufacturing facilities conducted between 1979 and 1997 were evaluated based on the measurement results stored in the OSHA Integrated Management Information System (IMIS) database. The IMIS database is among the largest sources of occupational exposure measurements available for occupational health research in the United States. The IMIS database contains the results of 3,568 personal time-weighted average (TWA) measurements for 171 air contaminants made at 524 establishments in Standard Industrial Classification (SIC) 26. An analysis of these measurements revealed an overall decrease in the total number of measurements made per year since 1991, and a decrease in the percentage of measurements by year that exceeded the OSHA permissible exposure limits (PELs). Linear regression analyses detected decreasing trends in the geometric mean concentrations by year for 33 of the 36 agents analyzed.