A very small proportion of all chemicals in commerce have occupational exposure limits (OELs) based on quantitative risk assessments which require estimates of exposure-response relationships (XRs). For only 18 of the 94 chemicals declared by NIOSH to be carcinogens were human XRs reported in or calculable from published reports. For the 18 carcinogens, 96 such XRs could be derived (corresponding to chemicals with multiple associated cancer end-points and/or multiple source studies). Twenty-four of 96 XR estimates came directly from reported statistical models (on continuous cumulative exposure), 45 were derived from summary study-population attributes, and 27 came from categorical analyses. Using the 96 XRs, OEL conferring one-per-thousand excess lifetime risk were calculated. OSHA's OEL, permissible exposure limits (PEL) were then compared to OEL derived from the 96 XRs. For 88 of the 96 calculated OELs (for which a corresponding PEL exists) all but 10 fell below the current PEL. Thirty-four OEL estimates were 10- to 100-fold below the PEL and 21 were greater than 100-fold below the PEL. This same pattern was observed using the different methods for deriving XRs. These findings can guide priorities in setting standards and the method is not limited to carcinogens.

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.

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.

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 95(th) 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/m(3), 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/m(3) ACM inhalation (equivalent to 3 years at 1.0 mg/m(3)) 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.

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. Method(s): 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. Result(s): 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(s): 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.

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.

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.

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.

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 yr period were used to analyze FEV1 and FEV1/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 mo exposure to DA. Percent-of-predicted FEV1 declined with cumulative exposure (0.40 per ppm-yr, p < 10) and 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.

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/m(3) 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/m(3) 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.

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, < 0.1mum in diameter) appear to have a higher potency per unit mass than larger particles from dusts (> 1.0mum). 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 10mug/m3 for manganese fume and 25mug/m3 for larger particle dusts. These levels are below current recommendations for occupational limits on manganese exposure in the United States.

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.

Virtually no occupational exposure standards specify the level of risk for the prescribed exposure, and most occupational exposure limits are not based on quantitative risk assessment (QRA) at all. Wider use of QRA could improve understanding of occupational risks while increasing focus on identifying exposure concentrations conferring acceptably low levels of risk to workers. Exposure-response modeling between a defined hazard and the biological response of interest is necessary to provide a quantitative foundation for risk-based occupational exposure limits; and there has been considerable work devoted to establishing reliable methods quantifying the exposure-response relationship including methods of extrapolation below the observed responses. We review of several exposure-response modeling methods available for QRA, and demonstrate their utility with simulated data sets.

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.

We read with great interest the recent publication, Evaluation of electronic cigarette liquids and aerosol for the presence of selected inhalation toxins.1 We are particularly grateful to the authors for recognizing the high rate of chronic obstructive pulmonary disease and of bronchiolitis, specifically, in smokers and for measuring the concentrations of diacetyl (DA) and acetyl propionyl (AP, also known as 2,3-pentanedione) in electronic cigarette (e-cigarette) liquids and aerosols. However, we would like to clarify two issues: | The National Institute for Occupational Safety and Health (NIOSH) draft document, Criteria for a Recommended Standard: Occupational Exposure to Diacetyl and 2,3-Pentanedione, proposes recommended exposure limits (RELs) to reduce the risk of respiratory impairment (decreased lung function) and the severe irreversible lung disease, constrictive bronchiolitis obliterans, associated with occupational exposure to these chemicals. As noted by Farsalinos and co-workers in their limitations section, it is not intended to establish “safe” exposure concentrations for consumers or the general public.1 | The exposure comparisons between e-cigarette users and traditional cigarette smokers and workers use values that are not widely accepted.

The appropriate exposure metrics for characterizing manganese (Mn) exposure associated with neurobehavioral effects have not been established. Blood levels of Mn (B-Mn) provide a potentially important intermediate marker of Mn airborne exposures. Using data from a study of a population of silicon- and ferro-manganese alloy production workers employed between 1973 and 1991, B-Mn levels were modeled in relation to prior Mn exposure using detailed work histories and estimated respirable Mn concentrations from air-sampling records. Despite wide variation in exposure levels estimated for individual jobs, duration of employment (exposure) was itself a strong predictor of B-Mn levels and strongest when an 80-day half-life was applied to contributions over time (t=6.95, 7.44, respectively; p<10-5). Partitioning exposure concentrations based on process origin into two categories: (1) "large" respirable particulate (Mn-LRP) derived mainly from mechanically generated dust, and (2) "small" respirable particulate (Mn-SRP) primarily electric furnace condensation fume, revealed that B-Mn levels largely track the small, fume exposures. With a half-life of 65 days applied in a model with cumulative exposure terms for both Mn-LRP (t=-0.16, p=0.87) and Mn-SRP (t=6.45, p<10-5), the contribution of the large-size fraction contribution was negligible. Constructing metrics based on the square root of SRP exposure concentrations produced a better model fit (t=7.87 vs. 7.44, R2=0.2333 vs. 0.2157). In a model containing both duration (t=0.79, p=0.43) and (square root) fume (t=2.47, p=0.01) metrics, the duration term was a weak contributor. Furnace-derived, small respirable Mn particulate appears to be the primary contributor to B-Mn levels, with a dose-rate dependence in a population chronically exposed to Mn, with air-concentrations declining in recent years. These observations may reflect the presence of homeostatic control of Mn levels in the blood and other body tissues and be useful in assessing Mn exposures for evaluating neurotoxic effects.

The progression of manganism with chronic exposure to airborne manganese (Mn) is not well understood. Here, we further investigate the findings on exposure and neurobehavioral outcomes of workers from a silico- and ferromanganese production plant and non-exposed workers from the same community in 1990 and 2004, using a variety of exposure metrics that distinguish particle size and origin within the range of respirable airborne exposures. Mn exposure matrices for large respirable particulate (Mn-LRP, dust) and small respirable particulate (Mn-SRP, fume), based on process origins, were used together with detailed work histories since 1973 (plant opening), to construct exposure metrics including burdens and cumulative burdens with various clearance half-lives. For three out of eight 1990 neurobehavioral tests analyzed with linear regression models, duration of Mn exposure was the best predictor: Luria-Nebraska Neuropsychological Battery - Motor Scale, Trail-Making B and Finger Tapping. The Luria-Nebraska Motor Scale had the strongest association (t approximately 5.0, p<10-6). For outcomes on three other tests, the duration and Mn-SRP metrics were comparable: Trail Making Test A, Cancellation H and Stroop Color-Word Test (color/word subtest). Delayed Word Recall was best predicted by Mn-SRP (based on square root or truncated air-concentrations). The Word score on the Stroop Color-Word Test was the only outcome for which Mn-LRP was the leading predictor (t=-2.92, p=0.003), while performance on the WAIS-R Digit Span Test was not significantly predicted by any metric. For outcomes evaluated in both 1990 and 2004, a mixed-effect linear regression model was used to examine estimates of within-individual trends. Duration and Mn-SRP were associated with performance on the Luria-Nebraska Motor Scale, as well as with other outcomes that appeared to have both reversible and progressive features, including Trail Making A and B, Cancellation H and Delayed Word Recall. With the mixed-effect model, Digit Span exhibited a significant irreversible association with exposure duration (t=-2.34, p=0.021) and Mn-SRP (square root; t=-2.38, p=0.019) metrics. The strong prediction using duration of exposure is consistent with effective homeostatic regulation of tissue-level Mn in the observed exposure range of respirable Mn (< 0.2mg/m3).

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 (microT) MF reduction in average worklife exposure, which is equivalent to $5,100/worker/microT in year 2010 U.S. dollars (95% confidence interval $1,000-$9,000/worker/microT). Where nine electrosteel workers had 13.8 microT 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.

PROBLEM: Costs related to early retirement or termination, and long-term disability resulting from work-related injury or illness, or their residual effects, could be outside the workers compensation (WC) envelope. METHOD: Using a benefits database providing utilization information for medical insurance and WC, statistical models were fit to determine if the rate of early retirement, long-term disability status, or any early termination depended on a prior WC claim. RESULTS: Rates of early retirement or long-term disability varied widely across industrial sectors and by employee classification likely reflecting variable benefits structures or reporting across employers. For any early termination the WC-associated rate ratio in hourly nonunion employees was 1.20 (95%CI = 1.14-1.28); for hourly union employees the rate ratio was 1.05 (95%CI = 0.97-1.13); for salaried nonunion employees, the rate ratio was 3.43 (95%CI = 3.11-3.79). In the manufacturing-durable sector the WC-associated rate ratio for hourly nonunion employees was 1.58 (95%CI = 1.42-1.76); for union hourly employees the rate ratio was 1.23 (95%CI = 1.10-1.38). In contrast, in the transportation-utilities-communications sector, for hourly nonunion employees the WC-associated rate ratio was 0.52 (95%CI = 0.46-0.59) whereas for union hourly employees the rate ratio was 1.22 (95%CI = 1.08-1.38). DISCUSSION: Prior WC predicts increased early termination in some workplaces but not others. Substantial uncompensated costs of workplace injuries and illnesses may result either from adverse events previously compensated by WC or from uncompensated events in individuals having other, WC-compensated episodes, i.e., workers in higher risk jobs. In other workplaces reduced termination rates with prior WC suggests added costs internalized by employers. SUMMARY: Conditions leading to WC claims appear to have cost implications related to early - or delayed - removal from the workforce. These costs can affect both employees and employers and should be included in estimates of burden of occupational injury and illness.

Diseases associated with specific exposures may have little or no observable background rate in the absence of the exposure. Examples include mesothelioma (environmental asbestos), aplastic anemia (benzene), bronchiolitis obliterans (artificial butter flavorings), Reye’s syndrome (aspirin in children), and angiosarcoma of the liver (vinyl chloride). Relative-rate models of exposure-response produce unstable near-zero baseline risk and unbounded coefficients, especially when age confounding requires baseline age dependence. The same problem arises in a proportional-hazards context. Baseline risk volatility also threatens meta-analyses, a procedure that assumes uniformity. | Using Poisson regression,1 we investigated two methods: (1) fixing the intercept at a small value corresponding to 1% of attributable cases and (2) generating random sets of new cases across observation time independent of any predictor, possibly preempting true cases. Although models can be reliably fit using randomly generated cases, repetition would reduce variability in parameter estimates. We performed simulations with fixed intercepts (1,000) and with simulated populations (100) each with 100 random baselines. Hypothetical populations, constructed iteratively, consisted of 500 subjects with an exposure that could extend up to 200 time units. Exposure duration was random, favoring shorter durations to represent typical environmental or occupational exposures. Individual average exposure levels were randomly assigned and then randomly varied across time. We generated attributable cases with probability proportional to cumulative exposure, at which time follow-up ceased. Numbers of attributable or baseline cases averaged ~60–70. The analyses were implemented using an R algorithm2 that called specific FORTRAN and EPICURE3 steps with an indexing seed for random number generation. Additional information is included in the eAppendix (http://links.lww.com/EDE/A619).

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. (Am. J. Ind. Med. (c) 2012 Wiley Periodicals, Inc.)

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. (Am. J. Ind. Med. (c) 2012 Wiley Periodicals, Inc.)

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 lifting 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 wheelchairs 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 versus availability of equipment, may be needed to better understand the impact of safety equipment on nursing home worker injury rates.

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 mcg/m(3) Cd.

BACKGROUND: Work-related injuries and illnesses in the educational services sector have not been well studied. This analysis examined whether teachers and other school workers are at higher risk of head/chest cold compared to all other workers in the United States. METHODS: Seven years (1998-2004) of National Health Interview Survey data on currently employed workers were combined to provide a basis for estimating the incidence proportion of head/chest cold. RESULTS: The adjusted odds ratio for head/chest cold was significantly elevated for teachers and other workers employed at schools compared to all other workers. When examined by month, an excess of increased head/chest cold risk during the school year suggested that a portion of head/chest cold among teachers and other school workers is attributable to their workplace, perhaps due to close contact with students at school. CONCLUSION: Head/chest cold, a surrogate for acute respiratory infection, was more common among school workers during the school year and less common during July than for all other workers in the United States. Targeted training for school workers and students may be beneficial to reduce work-related exposure to viruses and bacteria that infect the respiratory system.

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.

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/m 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/m, or 30 to 150 mug/m, 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/m Mn (the current threshold limit value).

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. Am. J. Ind. Med. 52:683-697, 2009. (c) 2009 Wiley-Liss, Inc.