Nephropathy in cadmium workers: assessment of risk from airborne occupational exposure to cadmium.

To assess the quantitative relation between exposure to airborne cadmium and various markers of renal tubular and glomerular function, 45 male workers employed at a plant that recovers cadmium from industrial waste and 32 male hospital workers of similar age and geographical location were examined. Cumulative external exposure to airborne cadmium (dose) was estimated from historical air sampling data, adjusted for respirator use. Increasing cadmium dose was associated with multiple renal tubular functional abnormalities, including reduced reabsorption of beta-2-microglobulin (beta-2), retinol binding protein (RBP), calcium, and phosphate. Serum creatinine concentration also increased with cadmium dose, suggesting impaired glomerular function. Mean systolic and diastolic blood pressures were higher in the cadmium workers than in the unexposed (134 v 120 mm Hg and 80 v 73 mm Hg respectively), but only systolic blood pressure was significantly associated with cadmium dose in multivariate analyses. Cadmium dose remained the most important predictor of serum creatinine concentration after controlling for age, blood pressure, body size, and other extraneous factors. Logistic regression to model the probability (prevalence) of various renal abnormalities with increasing dose of cadmium was used. The probability of multiple tubular abnormalities and raised serum creatinine concentration increased sharply at cumulative cadmium exposures exceeding 300 mg/m3 days, corresponding to working for 4.3 years at the current permissible United States exposure limit for cadmium dust.     

Nephropathy in cadmium workers: assessment of risk from airborne occupational exposure to cadmium

To assess the quantitative relation between exposure to airborne cadmium and various markers of renal tubular and glomerular function, 45 male workers employed at a plant that recovers cadmium from industrial waste and 32 male hospital workers of similar age and geographical location were examined. Cumulative external exposure to airborne cadmium (dose) was estimated from historical air sampling data, adjusted for respirator use. Increasing cadmium dose was associated with multiple renal tubular functional abnormalities, including reduced reabsorption of beta-2-microglobulin (beta-2), retinol binding protein (RBP), calcium, and phosphate. Serum creatinine concentration also increased with cadmium dose, suggesting impaired glomerular function. Mean systolic and diastolic blood pressures were higher in the cadmium workers than in the unexposed (134 v 120 mm Hg and 80 v 73 mm Hg respectively), but only systolic blood pressure was significantly associated with cadmium dose in multivariate analyses. Cadmium dose remained the most important predictor of serum creatinine concentration after controlling for age, blood pressure, body size, and other extraneous factors. Logistic regression to model the probability (prevalence) of various renal abnormalities with increasing dose of cadmium was used. The probability of multiple tubular abnormalities and raised serum creatinine concentration increased sharply at cumulative cadmium exposures exceeding 300 mg/m3 days, corresponding to working for 4.3 years at the current permissible United States exposure limit for cadmium dust.     

基于剂量-反应模型的苯职业暴露健康风险定量评价方法研究

目的 初步建立一种评价职业暴露导致的健康风险的定量方法,为我国职业健康风险的定量研究提供理论依据.方法 根据健康风险评价的基本方法,利用剂量-反应模型计算个体暴露于剂量为d的某物质所导致的致癌概率.暴露物质的人体内剂量与致癌概率间的函数关系可用probit模型、logit模型、Weibull模型、单击模型、多击模型和多阶模型来表达.通过药代动力学分析或人类流行病学数据拟合,可以得到暴露剂量与人体内剂量间的函数关系,将其带入剂量-反应模型,即可得出不同环境浓度下暴露人群的致癌风险.结果 根据测得的环境苯浓度值,分别用2阶模型、单击模型和Weibull模型计算得到的剂量-反应曲线均为直线,2阶模型得出的致癌风险最高,Weibull模型得出的致癌风险最小,苯的平均浓度为7.25 mg/m3时,3个模型对应的风险值分别为7.50×10-4、1.83×10-4、2.31×10-6.结论 初步建立了一种定量评价职业健康风险的方法,可利用此方法对工作场所中的有害物质暴露情况进行分析,得出工人在此环境下的致癌风险.     

A practical guide to dose-response analyses and risk assessment in occupational epidemiology

Dose-response modeling in occupational epidemiology is usually motivated by questions of causal inference (eg, is there a monotonic increase of risk with increasing exposure?) or risk assessment (eg, how much excess risk exists at any given level of exposure?). We focus on several approaches to dose-response in occupational cohort studies. Categorical analyses are useful for detecting the shape of dose-response. However, they depend on the number and location of cutpoints and result in step functions rather than smooth curves. Restricted cubic splines and penalized splines are useful parametric techniques that provide smooth curves. Although splines can complement categorical analyses, they do not provide interpretable parameters. The shapes of these curves will depend on the degree of "smoothing" chosen by the analyst. We recommend combining categorical analyses and some type of smoother, with the goal of developing a reasonably simple parametric model. A simple parametric model should serve as the goal of dose-response analyses because (1) most "true" exposure response curves in nature may be reasonably simple, (2) a simple parametric model is easily communicated and used by others, and (3) a simple parametric model is the best tool for risk assessors and regulators seeking to estimate individual excess risks per unit of exposure. We discuss these issues and others, including whether the best model is always the one that fits the best, reasons to prefer a linear model for risk in the low-exposure region when conducting risk assessment, and common methods of calculating excess lifetime risk at a given exposure from epidemiologic results (eg, from rate ratios). Points are illustrated using data from a study of dioxin and cancer.     

Case-control study on occupational exposure to diesel exhaust and lung cancer risk.

The association between lung cancer and occupations with probable exposure to diesel exhaust (DE) was studied among 2,584 cases and 5,099 hospital controls. The crude odds ratio (OR) for probable exposure was 1.31 (95% confidence interval [CI] 1.09-1.57), but adjustment for smoking and other confounders reduced the estimate to 0.95 (95% CI = 0.78-1.16). Similar results were observed for truck drivers, the only occupational category large enough for separate analysis. Data on self-reported exposure for 477 cases and 946 controls revealed a crude OR of 1.45 (95% CI = 0.93-2.27), which was reduced to 1.21 (95% CI = 0.78-2.02) after controlling for smoking and other confounders. The present results and a review of the literature do not definitively support an etiologic association between DE exposure and elevated lung cancer risk.     

Metallothionein and occupational exposure to cadmium.

The relationship between metallothionein (MT), chronic exposure to cadmium (Cd), and renal function was investigated in 53 men who were occupationally exposed to Cd. The aim was to determine if MT is a potential biological monitor for chronic exposure to Cd which would be useful for preventing Cd nephropathy. In this study MT excretion, serum MT, and serum creatinine concentrations were significantly higher in subjects with abnormal renal function who had been exposed to Cd. MT excretion was also linearly related on an individual basis to protein excretion, beta 2-microglobulin (beta 2-M) excretion, and cumulative time weighted exposure (dose). MT excretion was also a better predictor of dose than either beta 2-M excretion or Cd excretion. The findings suggest that MT is a potential biological monitor for chronic Cd exposure that would be useful for preventing Cd-induced nephropathy. Further studies of non-specific nephropathies and MT are needed to determine if MT is a specific indicator of proximal tubule function secondary to chronic exposure to Cd.     

Crystalline silica exposure and lung cancer mortality in diatomaceous earth industry workers: a quantitative risk assessment

OBJECTIVE—To use various exposure-response models to estimate the risk of mortality from lung cancer due to occupational exposure to respirable crystalline silica dust.
METHODS—Data from a cohort mortality study of 2342 white male California diatomaceous earth mining and processing workers exposed to crystalline silica dust (mainly cristobalite) were reanalyzed with Poisson regression and Cox's proportional hazards models. Internal and external adjustments were used to control for potential confounding from the effects of time since first observation, calendar time, age, and Hispanic ethnicity. Cubic smoothing spline models were used to assess the fit of the models. Exposures were lagged by 10 years. Evaluations of the fit of the models were performed by comparing their deviances. Lifetime risks of lung cancer were estimated up to age 85 with an actuarial approach that accounted for competing causes of death.
RESULTS—Exposure to respirable crystalline silica dust was a significant predictor (p<0.05) in nearly all of the models evaluated and the linear relative rate model with a 10 year exposure lag seemed to give the best fit in the Poisson regression analysis. For those who died of lung cancer the linear relative rate model predicted rate ratios for mortality from lung cancer of about 1.6 for the mean cumulative exposure to respirable silica compared with no exposure. The excess lifetime risk (to age 85) of mortality from lung cancer for white men exposed for 45 years and with a 10 year lag period at the current Occupational Safety and Health Administration (OSHA) standard of about 0.05 mg/m³ for respirable cristobalite dust is 19/1000 (95% confidence interval (95% CI) 5/1000 to 46/1000).
CONCLUSIONS—There was a significant risk of mortality from lung cancer that increased with cumulative exposure to respirable crystalline silica dust. The predicted number of deaths from lung cancer suggests that current occupational health standards may not be adequately protecting workers from the risk of lung cancer.


Keywords: crystalline silica; cristobalite; lung cancer     

Do quantitative exposure assessments improve risk estimates in occupational studies of cancer?

Quantitative assessment of exposure intensity is a difficult process, particularly for jobs held long ago. Despite difficulties, the use of this approach is growing in occupational epidemiology because it is hoped that the estimates will more closely approximate delivered dose than more traditional measures such as duration of exposure. If this assumption is correct, development and use of quantitative exposure estimates should reduce nondifferential exposure misclassification, sharpen exposure-response gradients, and enhance interpretation of study results. In this report, we used two methods to assess the value of quantitative exposure assessments in cancer epidemiology. In one, we surveyed the literature for investigations on occupational cancer that included assessments of both duration and intensity of exposure. The results of this survey indicated that exposure measures based on some measure of intensity of exposure yielded monotonically increasing exposure-response gradients and larger relative risks more often than those based on duration of exposure. Duration of exposure, however, occasionally provided the larger relative risks. In another approach, we found that different measures of exposure to formaldehyde classified subjects quite differently. For example, duration of exposure was unrelated to average exposure and was only weakly associated with exposure intensity or peak exposure. Because different measures of exposure may classify subjects quite differently and because quantitative estimates usually, but not always, yield larger relative risks and sharper exposure-response gradients than other measures of exposure, we believe that the prudent approach in epidemiologic investigations would be to develop quantitative estimates of exposure and to conduct analyses using several different measures of exposure, or combinations such as duration by intensity. Multiple comparisons would, however, increase chance findings. The value of such an approach is twofold. When a true association exists, use of several different measures decreases the chances of an unfortunate selection of an exposure measure that is poorly related to delivered dose, which would tend to produce negative results, and increases the chances of uncovering sharper exposure-response gradients. Use of several exposure measures in investigations that fail to exhibit an association between exposure and disease would be of value because such an approach would provide greater confidence that negative findings were not simply due to exposure misclassification.     

Smoking, occupational exposure to rubber, and lung cancer.

A cohort of 1624 employees (957 men, 667 women) in a rubber factory in Shanghai have been followed up since 1972 and their 12 year mortality experience is presented. The relative risk of lung cancer for smokers was 8.5 for men and 11.4 for women and for rubber workers exposed to curing agents or talc powder 3.2 for men and 4.6 for women.     

Metallothionein and occupational exposure to cadmium

The relationship between metallothionein (MT), chronic exposure to cadmium (Cd), and renal function was investigated in 53 men who were occupationally exposed to Cd. The aim was to determine if MT is a potential biological monitor for chronic exposure to Cd which would be useful for preventing Cd nephropathy. In this study MT excretion, serum MT, and serum creatinine concentrations were significantly higher in subjects with abnormal renal function who had been exposed to Cd. MT excretion was also linearly related on an individual basis to protein excretion, beta 2-microglobulin (beta 2-M) excretion, and cumulative time weighted exposure (dose). MT excretion was also a better predictor of dose than either beta 2-M excretion or Cd excretion. The findings suggest that MT is a potential biological monitor for chronic Cd exposure that would be useful for preventing Cd-induced nephropathy. Further studies of non-specific nephropathies and MT are needed to determine if MT is a specific indicator of proximal tubule function secondary to chronic exposure to Cd.     

Quantitative risk assessment for lung cancer after exposure to bitumen fume

An international cohort of asphalt workers was assembled to study cancer risk after bitumen exposure. This article describes the combination of the exposure assessment with the exposure-response for a quantitative risk assessment for lung cancer mortality within the Dutch component of the study. We identified a retrospective cohort of 3,709 workers with at least one season of employment. Semi-quantitative exposure to bitumen fume was estimated by a job-exposure matrix. Exposure-response relations were fitted by Poisson regression, and excess lifetime risks through age 75 were calculated by a life table method. Working lifetime cumulative exposure to bitumen fume was calculated under different scenarios, representing past and future exposures. For workers with exposures accumulated in the past, excess risks for lung cancer varied from 7.8 to 14.3%. Calculations for future exposures resulted in considerably lower excess risks ranging from 0.6 to 2.6%. The calculated excess risks for lung cancer mortality after working lifetime exposure to bitumen fume depend strongly on when exposure was experienced and to some extent on the exposure-response model chosen, while confounding by smoking cannot be ruled out. Nevertheless, the excess lifetime risk for lung cancer in this Dutch cohort of asphalt workers is above benchmark risks as applied by the Dutch Health Council. Current exposure levels have decreased this risk considerably, but further exposure control may be required.     

金属矿尘接触与肺癌发病的危险度定量评价

本文对大厂矿长坡锡矿1960～1974年井下接尘的工人进行了一次回顾性定群研究。研究队列共1113人,贡献人年26780。观察期间死于肺癌45人,与全国、上海人口比较,SMR分别为2184和519。以累计接尘量作定量评价的结果表明,工人吸入的矿尘与肺癌发病呈明显的剂量—反应关系。用对数线性模型拟合接尘量与吸烟量对肺癌发病的作用,发现接尘量与吸烟量同时引入模型后拟合优度最佳。控制吸烟因素后,不同累计接尘量水平对肺癌发病的相对危险度逐次为4.18、5.20、13.01、16.07;控制接尘量后,不同吸烟量的相对危险度分别为1.74、4.19,接尘量与吸烟量及肺癌发病危险度都呈现剂量—反应关系,表明接尘和吸烟同时为肺癌发病的危险因子。     

苯职业暴露健康风险评价研究及应用

目的对苯暴露的非致癌效应与致癌效应进行职业健康风险的定量评价,为我国职业病危害因素的控制以及职业性肿瘤等严重职业病的预防和管理提供科学依据。方法以某大型化工企业苯乙烯装置为研究对象,采用美国环境保护署(EPA)推荐的健康风险评价四步法,即危害辨识、暴露评价、剂量-反应评价和风险表征,对苯乙烯装置作业工人的苯职业暴露进行健康风险评价。分别以吸入单位风险、参考浓度表示化学毒物的致癌效应、非致癌效应的剂量-反应关系,以危害指数HI(hazard index)、致癌超额风险值(Risktumor)分别对非致癌风险、致癌风险进行表征;针对暴露与风险的不确定性,采用水晶球软件蒙特卡洛模拟方法分析概率分布规律。结果该装置工人84.65%情况下苯导致淋巴细胞计数减少的非致癌效应危害指数HI高于安全阈值1;69.37%的情况下苯导致白血病的超额风险超过了可接受风险水平1.0×10-4。提示风险不可接受,需要采取相应的风险应对措施,降低工人职业健康风险。结论利用职业健康风险评价四步法及蒙特卡洛模拟可以得到非致癌风险、致癌风险值的概率分布及其统计学分布特征,从而为风险管理者提供更准确的信息。