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.

Continuous NHANES survey data for environmental ambient and occupational hazard identification-feasibility and preliminary findings for osteoporosis and kidney disease.

The Continuous NHANES Survey provides detailed health and environmental chemical burden information on the U.S. population. As of 2012, there were data for 72,000 participants. Based on single biomarker determinations, cumulative burdens were estimated. Because age distributions would differ comparing ambient environmental and occupational exposures, a procedure to distinguish ambient from likely occupational exposures was applied. Associations are reported for osteoporosis and kidney disease-related outcomes with cadmium, lead, and other metals. Cumulative cadmium burden (from blood cadmium, ambient and occupational) was a strong predictor of bone fracture risk and ambient tungsten also had a positive association. Cumulative lead (ambient and occupational) had a negative ("protective") association with fractures as did mercury (occupational). Bone mineral density was statistically significant and similarly predicted by metal exposures. Kidney disease was significantly associated with cumulative lead burdens from both the estimated ambient and occupational sources and with ambient blood cadmium but was most strongly associated with cumulative occupational uranium burden. Systolic blood pressure statistically significantly increased with cumulative ambient and occupational lead (blood) burden and with ambient cadmium and cobalt. Diastolic blood pressure was significantly associated with several cadmium and cobalt metrics along with ambient and occupational cumulative burdens for lead. For environmental substances with burden half-lives measured in years, NHANES offers opportunities for hypothesis generation and confirmation.

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.

Associations between exposure to ethylene oxide, job termination, and cause-specific mortality risk.

BACKGROUND: Previous analyses of mortality were conducted in a large cohort of ethylene oxide (EtO) exposed workers employed at 13 sterilization facilities throughout the U.S. and followed from the start of operation through 1998. Statistically significant elevated mortality was reported from hematopoietic cancer in men and breast cancer in women compared to the general population. Possible healthy worker survivor bias was not addressed. METHODS: To examine survivor bias in this cohort, employment termination was analyzed with statistical models stratified on sex and race that included age, employment duration, and cumulative EtO exposure. To reduce survivor bias employment duration was included in Poisson regression model specifications for estimating standardized mortality ratios for several cancer outcomes. RESULTS: Strong statistically significant effects of unlagged cumulative EtO exposure were observed on rate of employment termination, indicating potential healthy worker survivor effect bias. Adjustment for employment duration in analyses of mortality resulted in statistically significant and stronger associations between cumulative EtO exposure and lung cancer, female breast cancer and hematopoietic cancer. There was a striking reduction in nonmalignant respiratory disease mortality risk with increasing employment duration with a further (nonsignificant) reduction with cumulative EtO, suggesting that EtO itself is driving termination of workers with respiratory morbidity even though the average EtO exposures in this population were generally far below odor and acute irritancy thresholds. CONCLUSIONS: Important survivor bias was present in this EtO cohort and may be present in many occupational settings involving irritant exposures.

A Simple Toxicokinetic Model Exhibiting Complex Dynamics and Nonlinear Exposure Response.

Uncertainty in model predictions of exposure response at low exposures is a problem for risk assessment. A particular interest is the internal concentration of an agent in biological systems as a function of external exposure concentrations. Physiologically based pharmacokinetic (PBPK) models permit estimation of internal exposure concentrations in target tissues but most assume that model parameters are either fixed or instantaneously dose-dependent. Taking into account response times for biological regulatory mechanisms introduces new dynamic behaviors that have implications for low-dose exposure response in chronic exposure. A simple one-compartment simulation model is described in which internal concentrations summed over time exhibit significant nonlinearity and nonmonotonicity in relation to external concentrations due to delayed up- or downregulation of a metabolic pathway. These behaviors could be the mechanistic basis for homeostasis and for some apparent hormetic effects.

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.

Bayesian Quantile Impairment Threshold Benchmark Dose Estimation for Continuous Endpoints.

Quantitative risk assessment often begins with an estimate of the exposure or dose associated with a particular risk level from which exposure levels posing low risk to populations can be extrapolated. For continuous exposures, this value, the benchmark dose, is often defined by a specified increase (or decrease) from the median or mean response at no exposure. This method of calculating the benchmark dose does not take into account the response distribution and, consequently, cannot be interpreted based upon probability statements of the target population. We investigate quantile regression as an alternative to the use of the median or mean regression. By defining the dose-response quantile relationship and an impairment threshold, we specify a benchmark dose as the dose associated with a specified probability that the population will have a response equal to or more extreme than the specified impairment threshold. In addition, in an effort to minimize model uncertainty, we use Bayesian monotonic semiparametric regression to define the exposure-response quantile relationship, which gives the model flexibility to estimate the quantal dose-response function. We describe this methodology and apply it to both epidemiology and toxicology data.

Extended follow-up of lung cancer and non-malignant respiratory disease mortality among California diatomaceous earth workers.

OBJECTIVES: Millions of workers worldwide are employed in occupations involving potentiality hazardous exposure to crystalline silica. The diatomaceous earth industry can have particularly high exposures, but there is a lower likelihood of simultaneously occurring confounding exposures. We extended follow-up for diatomaceous earth industry workers previously studied for mortality. METHODS: The cohort included 2342 white men who were employed for at least 1 year at a diatomaceous earth plant in Lompoc, California beginning in 1942. Workers' vital status was updated using the National Death Index through 2011, an extension of 19 years from earlier studies. Detailed work history and quantitative air monitoring measurements estimated exposure intensity. Cox proportional hazards modelling estimated HRs and 95% CIs. SMRs were calculated. RESULTS: Elevated mortality was observed by quartile of cumulative crystalline silica exposure for lung cancer (HR=2.03, 95% CI 1.07 to 3.85, highest quartile, unlagged) and non-malignant respiratory disease (NMRD) (HR=3.59, 95% CI 1.94 to 6.67, highest quartile, unlagged), although trends were not statistically significant. Associations were attenuated when adjusted for smoking and asbestos exposure. Mortality from NMRD was significantly increased over the entire follow-up compared to the general population (SMR=1.37, 95% CI 1.17 to 1.60). An increase for lung cancer was confined to the earlier follow-up (SMR=1.29, 95% CI 1.01 to 1.61). CONCLUSIONS: The risk of lung cancer and NMRD mortality remained elevated, although generally non-significant, and exposure-response trends with cumulative crystalline silica persisted on extended follow-up of this cohort. The findings support a generally consistently observed aetiological relation between crystalline silica and lung cancer.

Silicosis exposure-response in a cohort of tin miners comparing alternate exposure metrics.

BACKGROUND.: The detailed lung radiographic response to silica exposure has not been described. In estimating the exposure-response relationship in silicosis with statistical models, the absence of baseline (unattributable) risk can disable relative-rate estimation or produce widely varying estimates. This obstructs identification of optimum exposure metrics and invalidates comparisons and meta-analyses, which assume a common background rate. METHODS.: A cohort of 3,000 Chinese tin miners with more than 1,000 cases of silicosis was analyzed for the period 1961-1994. Regular surveillance documented three stages of silicosis. To examine the exposure-response relationship, the intercept in relative-rate models was fixed to correspond to 1% of the observed silicosis rate. Exposure metrics for contributions in different time-windows were simultaneously evaluated, as were burden and cumulative burden metrics. RESULTS.: Silica exposures that most contributed to silicosis onset occurred in the period 5-10 years prior (excess annual rate per 10 mg-year/m(3) , ER = 0.158, 95% CI = 0.125-0.192, or 16% per year). During 10-20 year prior, the excess rate contribution was much smaller (ER = 0.048, 95% CI = 0.037-0.060) but larger again during 20-30 year prior to onset (ER = 0.112, 95% CI = 0.098-0.126). For advanced silicosis, all time periods contributed about equally to the rate of onset. CONCLUSIONS.: Reliable estimates of parameters were observed, demonstrating exposure contributions over time. Burden metrics with different half-lives suggested some reversibility for silicosis onset with a half-life of 20 years. Advanced silicosis was best predicted with a cumulative burden metric which was consistent with prior observations that previously deposited silica continues to cause pulmonary damage.

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.

Cadmium and lung cancer mortality accounting for simultaneous arsenic exposure.

OBJECTIVES: Prior investigations identified an association between airborne cadmium and lung cancer but questions remain regarding confounding by arsenic, a well-established lung carcinogen. METHODS: A cadmium smelter population exhibiting excess lung cancer was re-analysed using a retrospective exposure assessment for arsenic (As), updated mortality (1940-2002), a revised cadmium (Cd) exposure matrix and improved work history information. RESULTS: Cumulative exposure metrics for both cadmium and arsenic were strongly associated making estimation of their independent effects difficult. Standardised mortality ratios (SMRs) were modelled with Poisson regression with the contribution of arsenic to lung cancer risk constrained by exposure-response estimates previously reported. The results demonstrate (1) a statistically significant effect of Cd independent of As (SMR=3.2 for 10 mg-year/m(3) Cd, p=0.012), (2) a substantial healthy worker effect for lung cancer (for unexposed workers, SMR=0.69) and (3) a large deficit in lung cancer mortality among Hispanic workers (SMR=0.27, p=0.009), known to have low lung cancer rates. A supralinear dose-rate effect was observed (contribution to risk with increasing exposure intensity has declining positive slope). Lung cancer mortality was somewhat better predicted using a cadmium burden metric with a half-life of about 20-25 years. CONCLUSIONS: These findings support an independent effect for cadmium in risk of lung cancer mortality. 1/1000 excess lifetime risk of lung cancer death is predicted from an airborne exposure of about 2.4 µg/m(3) Cd.

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.

Worker injuries and safety equipment in Ohio nursing homes.

A survey of Ohio nursing homes was conducted in 2007 to examine whether injury rates were related to facility characteristics and availability of safety equipment. The median rate of injury in the 898 facilities was 5.7 injuries per 100 workers per year. Although 95% of the facilities had written resident lift-ing policies, only 22% of these were zero-lift policies. Gait transfer belts(99%) and portable total-lift hoists(96%) were common, whereas ceiling-mounted total-lift hoists were rarely reported (7%). In a multivariable analysis, injury rate ratios increased with the proportion of residents using wheel-chairs and were lower in smaller facilities. Facilities without a lifting policy had a higher estimated injury rate than facilities without such a policy; however, none of the safety equipment was associated with significant changes in injury rates. More information, such as frequency of use and access to ver-sus availability of equipment, may be needed to better understand the im-pact of safety equipment on nursing home worker injury rates.

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.

Cancer morbidity of foundry workers in Korea.

Foundry workers are potentially exposed to a number of carcinogens. This study was conducted to describe the cancer incidence associated with employment in small-sized Korean iron foundries and to compare those findings to the Korean population. Cancer morbidity in 208 Korean foundries was analyzed using the Standardized Incidence Ratio (SIR) and Standardized Rate Ratio (SRR). Overall cancer morbidity in foundry workers (SIR=1.11, 95% confidence interval [CI]=1.01-1.21) was significantly higher than that of Korean general population. Lung cancer (SIR=1.45, 95%CI=1.11-1.87) and lymphohematopoietic cancer (SIR=1.58, 95%CI=1.00-2.37) in production workers were significantly high compared to Korean general population. Stomach cancer in fettling (SRR=2.10, 95%CI=1.10-4.01) and lung cancer in molding (SRR=3.06, 95%CI=1.22-7.64) and in fettling (SRR=2.63, 95%CI=1.01-6.84) were there significant elevations compared to office workers. In this study, statistically significant excess lung cancer was observed in production workers comparing to Korean general population and office workers. Also, cancer morbidity of overall cancer, lung cancer and stomach cancer was significantly increased with duration of employment at ten and more years comparing to Korean general population. These findings suggest in causal association between exposure to carcinogens during foundry work and cancer morbidity.

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.

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.