Risk assessment for conventional diesel exhaust (before 1990) and lung cancer in a cohort of miners.

Diesel exhaust in the latter half of the 20th century has been found to be a lung carcinogen. Conventional diesel emissions continue in the transportation, mining, construction, and farming industries. From the Diesel Exhaust in Miners Study, a public-use dataset was used to calculate the excess lifetime risk of lung cancer associated with diesel exposure (1947-1997). Excess rates of lung cancer mortality associated with respirable elemental carbon (REC) and possible other mining exposures (e.g., oil mists, explosives emissions) were investigated using Poisson regression methods. Lung cancer mortality declined with increasing employment duration while increasing with cumulative REC and non-diesel exposures, suggesting a strong worker survivor effect. Attenuation of the REC effect was observed with increasing cumulative exposure. After adjustment for employment duration, the excess rate ratio for lung cancer mortality was 0.67 (95% CI = 0.35-0.99) for a 10-year lagged exposure to 200 µg/m3 REC, a typical below-ground exposure in the study mines. At exposures of 200, 10, and 1 µg/m3 REC, the estimated excess lifetime risks, respectively, were 119, 43, and 8.7 per thousand. Analysis of an inception cohort hired after dieselization commenced produced smaller and less certain estimates of lifetime risk. From exposures to conventional diesel engine exhaust common in occupational groups in the past, the excess lifetime risk of lung cancer was more than 5%. Ambient REC exposures in the general population were estimated to confer lifetime risks of 0.14 to 14 per thousand, depending on assumptions made.

Risk assessment for o-toluidine and bladder cancer incidence.

BACKGROUND: Elevated bladder cancer incidence has been reported in a cohort of 1875 workers manufacturing chemicals used in the rubber industry and employed any time during 1946-2006. o-Toluidine (OT), an aromatic amine, was the prime suspect agent. Using the available environmental data and process characterization, previous investigators assigned ranks to volatile chemical air concentrations across time in departments and jobs, reflecting probabilities of exposure and use of personal protective equipment for airborne and dermal exposures. Aniline, another aromatic amine, was present at comparable concentrations and is known to be an animal carcinogen but produced lower levels in post-shift urine and of hemoglobin adducts than OT in a group of workers. METHODS: A quantitative risk assessment was performed based on this same population. In this study, cumulative OT exposures were estimated (a) based on previously assigned ranks of exposure intensity and reported actual exposures in jobs with the highest assigned rank, and (b) directly from the historical environmental sampling for OT. Models of bladder cancer incidence were evaluated taking into account possible healthy worker survivor effects. RESULTS: Under various assumptions regarding workforce turnover, the excess lifetime risk of bladder cancer from OT exposure at 1 ppb was estimated to be in the range 1-7 per thousand. CONCLUSIONS: The current ACGIH TLV and OSHA standards for OT are 2 and 5 ppm, respectively, 1000-fold higher than the exposure estimated here for 1-7 per thousand excess lifetime risk.

Risk Assessment for Toluene Diisocyanate and Respiratory Disease Human Studies.

BACKGROUND: Toluene diisocyanate (TDI) is a highly reactive chemical that causes sensitization and has also been associated with increased lung cancer. A risk assessment was conducted based on occupational epidemiologic estimates for several health outcomes. METHODS: Exposure and outcome details were extracted from published studies and a NIOSH Health Hazard Evaluation for new onset asthma, pulmonary function measurements, symptom prevalence, and mortality from lung cancer and respiratory disease. Summary exposure-response estimates were calculated taking into account relative precision and possible survivor selection effects. Attributable incidence of sensitization was estimated as were annual proportional losses of pulmonary function. Excess lifetime risks and benchmark doses were calculated. RESULTS: Respiratory outcomes exhibited strong survivor bias. Asthma/sensitization exposure response decreased with increasing facility-average TDI air concentration as did TDI-associated pulmonary impairment. In a mortality cohort where mean employment duration was less than 1 year, survivor bias pre-empted estimation of lung cancer and respiratory disease exposure response. CONCLUSION: Controlling for survivor bias and assuming a linear dose-response with facility-average TDI concentrations, excess lifetime risks exceeding one per thousand occurred at about 2 ppt TDI for sensitization and respiratory impairment. Under alternate assumptions regarding stationary and cumulative effects, one per thousand excess risks were estimated at TDI concentrations of 10 - 30 ppt. The unexplained reported excess mortality from lung cancer and other lung diseases, if attributable to TDI or associated emissions, could represent a lifetime risk comparable to that of sensitization.

Preliminary Risk assessment for Acrylamide and Peripheral Neuropathy.

Acrylamide (ACM) is a high-volume industrial chemical with diverse uses in manufacturing, construction and laboratory research. ACM is a well-established neurotoxic agent causing peripheral neuropathy with impairment in the arms and legs of exposed workers, most thoroughly studied in Swedish tunnel workers exposed to ACM grouting. A quantitative risk assessment was performed to assess ACM risk to workers. Using data from a published paper investigating peripheral neuropathies in Chinese chemical workers, estimates of exposure response for vibration perception threshold and nerve conduction velocities were calculated, based on hemoglobin adducts and air concentrations as exposure metrics. The benchmark dose procedure was applied in order to calculate excess risks of impairment, defined as adverse performance exceeding the 95th percentile in unexposed populations, at various concentrations of airborne ACM exposure. Under the assumptions in this risk assessment, after three years of inhalation exposure at 0.3 mg/m3, the excess attributable impairment manifest in vibration perception and nerve conduction velocity is estimated to occur in 1-2% of workers. For 10 years at 0.3 mg/m3 ACM inhalation (equivalent to 3 years at 1.0 mg/m3) the excess prevalence of impairment would be 2-14% of workers, assuming the effect continues to accrue linearly in time. Using published data, the risks of impairment from peripheral neuropathy attributable to exclusively airborne ACM exposure can be predicted for exposure periods less than 10 years. The risks associated with dermal and airborne ACM exposures can be estimated by characterizing working process environments using ACM Hb-adduct levels and possibly monitored with urinary biomarkers.

Risk Assessment for Metalworking Fluids and Respiratory Outcomes.

BACKGROUND: Metalworking fluids (MWFs) are mixtures with inhalation exposures as mists, dusts, and vapors, and dermal exposure in the dispersed and bulk liquid phase. A quantitative risk assessment was performed for exposure to MWF and respiratory disease. METHODS: Risks associated with MWF were derived from published studies and NIOSH Health Hazard Evaluations, and lifetime risks were calculated. The outcomes analyzed included adult onset asthma, hypersensitivity pneumonitis, pulmonary function impairment, and reported symptoms. Incidence rates were compiled or estimated, and annual proportional loss of respiratory capacity was derived from cross-sectional assessments. RESULTS: A strong healthy worker survivor effect was present. New-onset asthma and hypersensitivity pneumonitis, at 0.1 mg/m3 MWF under continuous outbreak conditions, had a lifetime risk of 45%; if the associated microbiological conditions occur with only 5% prevalence, then the lifetime risk would be about 3%. At 0.1 mg/m3, the estimate of excess lifetime risk of attributable pulmonary impairment was 0.25%, which may have been underestimated by a factor of 5 or more by a strong healthy worker survivor effect. The symptom prevalence associated with respiratory impairment at 0.1 mg/m3 MWF was estimated to be 5% (published studies) and 21% (Health Hazard Evaluations). CONCLUSION: Significant risks of impairment and chronic disease occurred at 0.1 mg/m3 for MWFs in use mostly before 2000. Evolving MWFs contain new ingredients with uncharacterized long-term hazards.

Pulmonary Impairment and Risk Assessment in a Diacetyl-Exposed Population: Microwave Popcorn Workers.

OBJECTIVES: The butter flavoring additive, diacetyl (DA), can cause bronchiolitis obliterans (BO) by inhalation. A risk assessment was performed using data from a microwave popcorn manufacturing plant. METHODS: Current employees' medical history and pulmonary function tests together with air sampling over a 2.7-year period were used to analyze forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC). The exposure responses for declining pulmonary function and for possible early onset of BO were estimated using multiple regression methods. Several exposure metrics were investigated; benchmark dose and excess lifetime risk of impairment were calculated. RESULTS: Forty-six percent of the population had less than 6 months exposure to DA. Percent-of-predicted FEV1 declined with cumulative exposure (0.40 per ppm-yr, P < 10) as did percent FEV1/FVC (0.13 per ppm-yr, P = 0.0004). Lifetime respiratory impairment prevalence of one per thousand resulted from 0.005 ppm DA and one per thousand lifetime incidence of impairment was predicted for 0.002 ppm DA. CONCLUSION: DA exposures, often exceeding 1 ppm in the past, place workers at high risk of pulmonary impairment.

Risk assessment for metalworking fluids and cancer outcomes.

BACKGROUND: Metalworking fluids (MWF) are complex mixtures with dermal and inhalation exposure. Published reports reveal excess cancer risk. METHODS: Using published findings exposure response was derived for each attributable cancer site. Aggregate excess lifetime risk was estimated by applying a lifetable calculation. RESULTS: Cancer sites contributing the most attributable cases were larynx, esophagus, brain, female breast, and uterine cervix. With constant workplace MWF exposure of 0.1 mg/m3 over a 45 years working life, the risk of attributable cancer was 3.7% or, excluding the less certain female cancers, 3.1%. CONCLUSION: Substantial cancer risks occurred at 0.1 mg/m3 MWF, one fourth of the current NIOSH recommended exposure limit for MWF total particulate. Because ingredients in current MWF remain from earlier formulations, it is likely that some MWF carcinogenicity persists today. Although important changes have occurred, newer agents are being continually introduced with little or no knowledge of chronic health risks.

Manganese and neurobehavioral impairment. A preliminary risk assessment.

Similar patterns of cognitive and motor deficits have been widely reported from manganese exposures in welding, metallurgical and chemical industry workers. A risk assessment was performed based on studies reported in the literature, extending some earlier work, and deriving new estimates of exposure response and excess risk. Many investigations of manganese neurological effects in humans have insufficient information to derive an exposure response; however, findings from a chemical manufacturer, two smelter and two welder populations permitted application of the benchmark dose procedure for continuous end-points. Small particles and aggregates of condensation fume (condensing vaporized metal, <0.1µm in diameter) appear to have a higher potency per unit mass than larger particles from dusts (>1.0µm). Consideration was given to long-term effects of continuous low exposures that instead of producing increasing toxicity attain a steady-state condition. Impairment was defined as excursions beyond the 5th percentile in a normal population and the concentrations of manganese predicted to result in 1% excess prevalence of impairment over different time periods were calculated. Over five years, exposures resulting in 1% excess prevalence of impairment (for purposes of discussion) were in the vicinity of 10µg/m3 for manganese fume and 25µg/m3 for larger particle dusts. These levels are below current recommendations for occupational limits on manganese exposure in the United States.

Uncompensated consequences of workplace injuries and illness: long-term disability and early termination.

PROBLEM: Costs related to early retirement, termination, or long-term disability could fall outside workers' compensation (WC). METHOD: Statistical models examined early retirement, long-term disability status, or early termination related to WC claims. RESULTS: The WC-associated early-termination rate ratio was 1.20 (95% CI=1.14-1.28) for hourly nonunion employees, 1.05 (95% CI=0.97-1.13) for hourly union employees, and 3.43 (95% CI=3.11-3.79) for salaried nonunion employees. In the manufacturing-durable sector the WC-associated rate ratio was 1.58 (95% CI=1.42-1.76) for hourly nonunion employees and 1.23 (95% CI=1.10-1.38) for union hourly employees. In contrast, in transportation-utilities-communications, the rate ratio was 0.52 (95% CI=0.46-0.59) for hourly nonunion and 1.22 (95% CI=1.08-1.38) for union hourly employees. DISCUSSION: Uncompensated costs of workplace injuries and illnesses may result from adverse events previously compensated by WC. In some workplaces reduced termination rates with prior WC suggests added costs to employers. SUMMARY: Conditions leading to WC claims have cost implications related to early - or delayed - removal from the workforce. IMPACT ON INDUSTRY: Additional costs from work-related injury or illness that are not covered by workers compensation may result from the effect of continuing impairment on the subsequent early termination (or prolonging) of employment. These costs would accrue to both employers and employees and are not generally included in global estimates of the burden of workplace injuries and illnesses.

Possible health benefits from reducing occupational magnetic fields.

BACKGROUND: Magnetic fields (MF) from AC electricity are a Possible Human Carcinogen, based on limited epidemiologic evidence from exposures far below occupational health limits. METHODS: To help formulate government guidance on occupational MF, the cancer cases prevented and the monetary benefits accruing to society by reducing workplace exposures were determined. Life-table methods produced Disability Adjusted Life Years, which were converted to monetary values. RESULTS: Adjusted for probabilities of causality, the expected increase in a worker's disability-free life are 0.04 year (2 weeks) from a 1 microtesla (µT) MF reduction in average worklife exposure, which is equivalent to $5,100/worker/µT in year 2010 U.S. dollars (95% confidence interval $1,000-$9,000/worker/µT). Where nine electrosteel workers had 13.8 µT exposures, for example, moving them to ambient MFs would provide $600,000 in benefits to society (uncertainty interval $0-$1,000,000). CONCLUSIONS: When combined with the costs of controls, this analysis provides guidance for precautionary recommendations for managing occupational MF exposures.

Excess healthcare costs associated with prior workers' compensation activity.

BACKGROUND: Workers compensation (WC) does not fully compensate workplace injuries and illnesses. This work examines whether cost shifting occurs to group health insurance for work-related injuries and illnesses. METHODS: Thomson Reuters MarketScan databases of medical insurance claims were used. WC and other benefit system data, employee status and types of medical insurance coverage were also available. Medical cost was analyzed using two-part models: the first part modeled the monthly probability of a worker having any group health medical claims, and the second part modeled the total monthly cost of those medical claims. Models included an estimate of a worker's annual medical costs prior to a WC claim. The predicted monthly medical costs were derived by retransformation using Duan's smearing factor. RESULTS: Individuals with prior WC claims were more likely to file a group health medical claim compared to those with no prior WC claims (OR = 1.25) and incurred a higher average monthly medical costs (among nonunion hourly men aged 18-34 years with prior WC claims: $203.72 vs. $160.29 with no prior claim, an increase of $43). These increases were observed in all industrial sectors with the service sector having the highest monthly increase ($66). DISCUSSION: The results reveal that individuals with prior WC claims had higher probability of filing a group health medical claim and higher average monthly medical costs in all sectors. This suggests that a part of employer liability costs related to WC gets shifted to the group health medical insurance system.

Exposure-response relationship and risk assessment for cognitive deficits in early welding-induced manganism.

OBJECTIVE: The exposure-response relationship for manganese (Mn)-induced adverse nervous system effects is not well described. Symptoms and neuropsychological deficits associated with early manganism were previously reported for welders constructing bridge piers during 2003 to 2004. A reanalysis using improved exposure, work history information, and diverse exposure metrics is presented here. METHODS: Ten neuropsychological performance measures were examined, including working memory index (WMI), verbal intelligence quotient, design fluency, Stroop color word test, Rey-Osterrieth Complex Figure, and Auditory Consonant Trigram tests. Mn blood levels and air sampling data in the form of both personal and area samples were available. The exposure metrics used were cumulative exposure to Mn, body burden assuming simple first-order kinetics for Mn elimination, and cumulative burden (effective dose). Benchmark doses were calculated. RESULTS: Burden with a half-life of about 150 days was the best predictor of blood Mn. WMI performance declined by 3.6 (normal = 100, SD = 15) for each 1.0 mg/m3 x mo exposure (P = 0.02, one tailed). At the group mean exposure metric (burden; half-life = 275 days), WMI performance was at the lowest 17th percentile of normal, and at the maximum observed metric, performance was at the lowest 2.5 percentiles. Four other outcomes also exhibited statistically significant associations (verbal intelligence quotient, verbal comprehension index, design fluency, Stroop color word test); no dose-rate effect was observed for three of the five outcomes. CONCLUSIONS: A risk assessment performed for the five stronger effects, choosing various percentiles of normal performance to represent impairment, identified benchmark doses for a 2-year exposure leading to 5% excess impairment prevalence in the range of 0.03 to 0.15 mg/m3, or 30 to 150 microg/m3, total Mn in air, levels that are far below those permitted by current occupational standards. More than one-third of workers would be impaired after working 2 years at 0.2 mg/m3 Mn (the current threshold limit value).

Incorporating genetics and genomics in risk assessment for inhaled manganese: from data to policy.

Manganese is an essential nutrient, and a healthy human with good liver and kidney function can easily excrete excess dietary manganese. Inhaled manganese is a greater concern, because it bypasses the body's normal homeostatic mechanisms and can accumulate in the brain. Prolonged exposure to high manganese concentrations (>1mg/m(3)) in air leads to a Parkinsonian syndrome known as "manganism." Of greatest concern are recent studies which indicate that neurological and neurobehavioral deficits can occur when workers are exposed to much lower levels (<0.2mg/m(3)) of inhaled manganese in welding fumes. Consequently, researchers at NIOSH are conducting a risk assessment for inhaled manganese. Novel components of this risk assessment include an attempt to quantify the range of inter-individual differences using data generated by the Human Genome Project and experimental work to identify genetically based biomarkers of exposure, disease and susceptibility. The difficulties involved in moving from epidemiological and in vivo data to health-based quantitative risk assessment and ultimately enforceable government standards are discussed.

Impact of publicly sponsored interventions on musculoskeletal injury claims in nursing homes.

BACKGROUND: The rate of lost-time sprains and strains in private nursing homes is over three times the national average, and for back injuries, almost four times the national average. The Ohio Bureau of Workers' Compensation (BWC) has sponsored interventions that were preferentially promoted to nursing homes in 2000-2001, including training, consultation, and grants up to $40,000 for equipment purchases. METHODS: This study evaluated the impact of BWC interventions on back injury claim rates using BWC data on claims, interventions, and employer payroll for all Ohio nursing homes during 1995-2004 using Poisson regression. A subset of nursing homes was analyzed with more detailed data that allowed estimation of the impact of staffing levels and resident acuity on claim rates. Costs of interventions were compared to the associated savings in claim costs. RESULTS: A $500 equipment purchase per nursing home worker was associated with a 21% reduction in back injury rate. Assuming an equipment life of 10 years, this translates to an estimated $768 reduction in claim costs per worker, a present value of $495 with a 5% discount rate applied. Results for training courses were equivocal. Only those receiving below-median hours had a significant 19% reduction in claim rates. Injury rates did not generally decline with consultation independent of equipment purchases, although possible confounding, misclassification, and bias due to non-random management participation clouds interpretation. In nursing homes with available data, resident acuity was modestly associated with back injury risk, and the injury rate increased with resident-to-staff ratio (acting through three terms: RR = 1.50 for each additional resident per staff member; for the ratio alone, RR = 1.32, 95% CI = 1.18-1.48). In these NHs, an expenditure of $908 per resident care worker (equivalent to $500 per employee in the other model) was also associated with a 21% reduction in injury rate. However, with a resident-to-staff ratio greater than 2.0, the same expenditure was associated with a $1,643 reduction in back claim costs over 10 years per employee, a present value of $1,062 with 5% discount rate. CONCLUSIONS: Expenditures for ergonomic equipment in nursing homes by the Ohio BWC were associated with fewer worker injuries and reductions in claim costs that were similar in magnitude to expenditures. Un-estimated benefits and costs also need to be considered in assessing full health and financial impacts.

Issues in neurological risk assessment for occupational exposures: the Bay Bridge welders.

The goal of occupational risk assessment is often to estimate excess lifetime risk for some disabling or fatal health outcome in relation to a fixed workplace exposure lasting a working lifetime. For sub-chronic or sub-clinical health effects measured as continuous variables, the benchmark dose method can be applied, but poses issues in defining impairment and in specifying acceptable levels of excess risk. Such risks may also exhibit a dose-rate effect and partial reversibility such that effects depend on how the dose is distributed over time. Neurological deficits as measured by a variety of increasingly sensitive neurobehavioral tests represent one such outcome, and the development of a parkinsonian syndrome among welders exposed to manganese fume presents a specific instance. Welders employed in the construction of piers for a new San Francisco-Oakland Bay Bridge in San Francisco were previously evaluated using a broad spectrum of tests. Results for four of those tests (Rey-Osterrieth Complex Figure Test, Working Memory Index, Stroop Color Word Test and Auditory Consonant Trigrams Test) were used in the benchmark dose procedure. Across the four outcomes analyzed, benchmark dose estimates were generally within a factor of 2.0, and decreased as the percentile of normal performance defining impairment increased. Estimated excess prevalence of impairment, defined as performance below the 5th percentile of normal, after 2 years of exposure at the current California standard (0.2 mg/m3, 8 h TWA), ranged 15-32% for the outcomes studied. Because these exposures occurred over a 1-2-year period, generalization to lifetime excess risk requires further consideration of the form of the exposure response and whether short-term responses can be generalized to equivalent 45-year period. These results indicate unacceptable risks at the current OSHA PEL for manganese (5.0 mg/m3, 15 min) and likely at the Cal OSHA PEL as well.

Hexavalent chromium and lung cancer in the chromate industry: a quantitative risk assessment.

The purpose of this investigation was to estimate excess lifetime risk of lung cancer death resulting from occupational exposure to hexavalent-chromium-containing dusts and mists. The mortality experience in a previously studied cohort of 2,357 chromate chemical production workers with 122 lung cancer deaths was analyzed with Poisson regression methods. Extensive records of air samples evaluated for water-soluble total hexavalent chromium were available for the entire employment history of this cohort. Six different models of exposure-response for hexavalent chromium were evaluated by comparing deviances and inspection of cubic splines. Smoking (pack-years) imputed from cigarette use at hire was included in the model. Lifetime risks of lung cancer death from exposure to hexavalent chromium (assuming up to 45 years of exposure) were estimated using an actuarial calculation that accounts for competing causes of death. A linear relative rate model gave a good and readily interpretable fit to the data. The estimated rate ratio for 1 mg/m3-yr of cumulative exposure to hexavalent chromium (as CrO3), with a lag of five years, was RR=2.44 (95% CI=1.54-3.83). The excess lifetime risk of lung cancer death from exposure to hexavalent chromium at the current OSHA permissible exposure limit (PEL) (0.10 mg/m3) was estimated to be 255 per 1,000 (95% CI: 109-416). This estimate is comparable to previous estimates by U.S. EPA, California EPA, and OSHA using different occupational data. Our analysis predicts that current occupational standards for hexavalent chromium permit a lifetime excess risk of dying of lung cancer that exceeds 1 in 10, which is consistent with previous risk assessments.