Lung cancer mortality in workers exposed to sulfuric acid mist and other acid mists.

Mortality patterns were studied in 1,165 workers exposed to sulfuric acid mist and other acid mists (primarily hydrochloric acid mist) in steel-pickling operations. Standardized mortality ratio (SMR) analysis of the full "any acid exposure" cohort (n = 1,165), with the use of U.S. death rates as a standard, showed that lung cancer was significantly elevated, with a mortality ratio of 1.64 [95% confidence interval (CI) = 1.14-2.28, based on 35 observed deaths]. The lung cancer mortality ratio for workers exposed only to sulfuric acid (n = 722) was lower (SMR = 1.39), but further restriction to the time 20 years and more from first employment in a job with probable daily sulfuric acid exposure (approximately equal to 0.2 mg/m3) yielded a mortality ratio of 1.93 (95% CI = 1.10-3.13). An excess lung cancer risk was also seen in workers exposed to acids other than sulfuric acid (SMR = 2.24; 95% CI = 1.02-2.46). When comparison was made to other steel workers (rather than to the U.S. general population) to control for socioeconomic and life-style factors such as smoking, the largest lung cancer excess was again seen in workers exposed to acids other than sulfuric acid (SMR = 2.00; 95% CI = 1.06-3.78). Adjustment for potential differences in smoking habits showed that increased smoking was unlikely to have entirely explained the increased risk. Mortality from causes of death other than lung cancer was unremarkable, with the exception of significantly low rates for deaths due to digestive system diseases.

Disease determinants of sporadic salmonellosis in four northern California counties. A case-control study of older children and adults.

A population-based, case-control study of sporadic salmonellosis was conducted in 1988 and 1989 in four northern California counties. The study included 120 patients and 265 control subjects. Conditional logistic regression analysis (adjusted for age) revealed that patients were more likely to consume undercooked chicken prior to the onset of disease (odds ratio [OR], 23.57; 95% confidence interval [CI], 2.89 to 192.30). Elevated associations were also found with recent travel to foreign countries (OR, 9.69; 95% CI, 3.18 to 29.56), diabetes (OR, 6.29; 95% CI, 1.56 to 25.34), hormonal replacement therapy (principally conjugated estrogen) in older women (OR, 4.20; 95% CI, 1.82 to 9.71), and antibiotic therapy prior to illness (OR, 1.96; 95% CI, 0.86 to 4.37). The problems of studying self-selected cases that may lead to alternative explanations for these findings are also discussed.

Mortality in agricultural workers after compensation claims for respiratory disease, pesticide illness, and injury.

The long-term mortality experience of California agricultural workers who filed workers' compensation claims for respiratory diseases, pesticide illnesses, and injuries between 1946 and 1975 was observed until 1991 and compared to U.S. death rates. The respiratory disease claimants had an elevated relative risk of 3.27 (95% CI 2.09-4.86) for mortality from nonmalignant respiratory diseases (NMRD). Emphysema mortality was particularly high, with a relative risk of 5.94 (95% CI 2.56-11.70). NMRD mortality peaked 5 to 9 years after the claims were filed (relative risk 9.83, 95% CI 4.47-18.57) and was most strongly associated with exposure to wood, rice, coffee, and flour dusts. Among the pesticide illness claimants, mortality from heart disease was slightly elevated in the subcohort with systemic pesticide illness (SMR = 1.32, 95% CI 0.86-1.94). Among the injury claimants, risk was increased for motor vehicle deaths (relative risk 1.62, 95% CI 0.74-3.08). It was concluded that respiratory disease claimants in agriculture have a significantly elevated risk of mortality from respiratory diseases and that the risk is highest (10-fold) 5-9 years after claims are filed.

Mortality of chrome leather tannery workers and chemical exposures in tanneries.

A retrospective mortality analysis was conducted in a cohort of 9,365 individuals employed as of 1940 in two chrome leather tanneries in the United States and followed to the end of 1982. Vital status as of the closing date was determined for over 95% of the cohort. Potential hazardous workplace exposures varied with department and included nitrosamines, chromate pigments, benzidine-based direct dyestuffs, formaldehyde, leather dust, and aromatic organic solvents. Mortality from all causes combined was lower than expected for each tannery, the standardized mortality ratio being 81 for one and 93 for the other. Deaths from cancer of each site, including the lung, were also lower than expected compared to those of either the population of the United States or of local state rates. A significant excess of deaths was observed, however, due to accidental causes in one tannery and cirrhosis of the liver, suicide, and alcoholism in the other. These excesses did not appear to be causally associated with occupational exposures. The findings of this study are consistent with those of the only other mortality investigation of leather tannery employees.

An investigation of mortality from cancer and other causes of death among workers employed at an east Texas chemical plant.

The cause-specific mortality of 2,510 males employed at an east Texas chemical plant was examined in a historical prospective study to evaluate a suspected increase in deaths from multiple myeloma and brain cancer. Potential exposures from chemicals, either used in manufacturing processes or produced during the study period 1952-1977, included the fuel additive tetraethyl lead, ethylene dibromide and dichloride, inorganic lead, and vinyl chloride monomer. Overall mortality for all workers (156 observed vs. 211.14 expected) and for workers first employed between 1952 and 1959 (131 observed vs. 167.33 expected) when tetraethyl lead was the single major product was lower than expected when compared to the United States general population. There were no significant increases in mortality from malignancies or other causes of death. The deficits may be due to the small number of total deaths, and the low power for detecting excess risk of mortality from multiple myeloma (Z1-beta = 27, alpha = .05), brain cancer (Z1-beta = 31, alpha = .05), or other rare causes of death; lack of complete workplace exposure data for production workers; and the absence of historical measurements on the extent of environmental exposure to tetraethyl lead and other chemicals.

Epidemiologic and toxicologic evidence for chronic health effects and the underlying biologic mechanisms involved in sub-lethal exposures to acidic pollutants.

Since the 1880s, a disparate and extensive literature has evolved examining the biologic effects of acidification on cells. More recently, effects on the health of human and other species of acidic agents contained, for example, in pollutants have been suggested, particularly relating to long-term exposures. This paper provides a review of the epidemiologic and toxicologic evidence concerning health effects--particularly carcinogenicity--attributable to sub-lethal acid exposure. Underlying biologic mechanisms that explain adverse health outcomes include pH modulation of toxicity for a number of xenobiotics (including carcinogens, genotoxins, and teratogens), and low-pH-induced changes of cells involving, for example, alterations in mitotic and enzyme regulation. More focused research is recommended to test the relationship between long-term exposures to acidic agents (with a consequent lowered cellular pH) and various health effects.

Suicide, cancer, and other causes of death among California veterinarians, 1960-1992.

Previous studies reporting on mortality patterns in veterinarians have been restricted to deaths among white male veterinarians. In an effort to examine the mortality of male and female veterinarians of all races, we conducted a standardized proportionate mortality ratio (SPMR) analysis of 450 California veterinarians who died between January 1960 and December 1992. In comparison to State of California general population statistics, white male veterinarians had significantly elevated mortality from malignant melanoma of the skin (SPMR 3.47, 95% CI 1.74, 6.94), cancer of the large intestine (SPMR 1.74, 95% CI 1.04, 2.09), rheumatic heart disease (SPMR 3.50, 95% CI 1.90, 6.43), and suicide (SPMR 2.50, 95% CI 1.84, 3.38). White female veterinarians had significantly elevated mortality from suicide (SPMR 5.89, 95% CI 3.02, 11.48). We also examined veterinary mortality for different lengths of time in the profession. Significantly elevated SPMRs were noted for suicide in veterinarians in the profession for less than 30 years; deaths due to malignant melanoma of the skin and rheumatic heart disease in veterinarians in the profession 20 years or more; and cancer of the large intestine in veterinarians in the profession 30 years or more. Because of significant findings in mortality from suicide among veterinarians of both sexes, it was recommended that future studies and efforts toward suicide prevention include both male and female veterinarians.

Mortality of welders, shipfitters, and other metal trades workers in boilermakers Local No. 104, AFL-CIO.

The mortality experience of 8679 members of a metal trades union--men employed in shipyards, metal fabrication shops, small boat yards, and field construction--was studied from 1950 to 1976 by the historical prospective method. Relative to rates for US men of comparable age and race, the risk of death from all causes combined was 0.99. However, excesses of 40 per cent (p < 0.001) and 60 per cent (p < 0.001) occurred for malignant and nonmalignant respiratory disease deaths, respectively, beginning 20 years after first employment. The mortality excesses from malignant and nonmalignant respiratory diseases increased with increasing interval from first employment; and the nonmalignant respiratory disease excess was also related to cumulative exposure. Causes of death that occurred at significantly (p < 0.05) greater than expected rates in specific job classifications included pneumonia in welders, accidents and suicide in shipfitters, and emphysema in burners.

Power considerations in epidemiologic studies of vinyl chloride workers.

Nine retrospective mortality studies of workers exposed to vinyl chloride were reviewed to determine whether differences in their hypothesis testing results might be due to differences in statistical power. Where possible, the power of each study was calculated for cancer of the lung, brain and liver. When power was taken into consideration, the results for liver and brain cancer were found to be consistent with an etiologic role for vinyl chloride. For lung cancer, the data were not consistent with an etiologic role in that two studies with very high power yielded negative results.

Timing and patterns of exposures during pregnancy and their implications for study methods.

Patterns of exposure variability across pregnancy were examined for medical, lifestyle, residential, and occupational exposures in a population-based sample of 357 livebirths from 10 rural California counties. A new measure of variability, the ratio of overall prevalence to time-window-specific prevalence, is introduced. The higher the overall : time window (OTW) ratio, the greater the potential for misclassification when using anytime-during-pregnancy prevalence for an agent that exerts its effect in a smaller time window. Exposures to cigarettes, marijuana, saunas/hot tubs, factors related to location of residence, and some workplace substances tended to be of longer duration. Intertrimester concordance was high (kappa's > 0.8) for smoking, residential proximity to crops, and use of video display terminals; moderately high (kappa's between 0.4 and 0.8) for many occupational exposures; and low (kappa's < 0.4) for illnesses, which tended to be of short duration. The lowest OTW ratios were for smoking and some residential exposures (1.1-1.3), while OTW ratios were much higher for paint applications, influenza, vaginal infections, and ultrasound (reaching, e.g., 4-6). Use of anytime-during-pregnancy exposure indices can bias measures of association between risk factors and adverse pregnancy outcomes, particularly if the OTW ratio is high. Misclassification bias occurs if there is a vulnerable time window during which the exposure exerts its effect. The misclassification can be differential when the average length of gestation of cases is shorter than that of controls. For exposures that vary, investigations of pregnancy outcome should collect as much detail as feasible regarding timing.

Power and detectable risk of seven tests for standardized mortality ratios.

Power and minimum detectable risk are calculated for seven one-sided tests of standardized mortality ratios with Poisson-distributed events. Each test contrasts the number of observed deaths (D) with the number expected (E). Three tests use exact Poisson probabilities: 1) the exact test, which computes a p value as the probability of equaling or exceeding the number of observed events; 2) the optimal randomized exact test which, although not used in practice, serves as a standard for the other statistics; and 3) the exact "mid-p" procedure, which counts only one-half the probability of the observed event. The remaining four tests use normal approximations to the Poisson ("Z statistics"): 4) Z = magnitude of D-E/square root of E; 5) the Z statistic corrected for continuity, Z = (magnitude of D-E)-0.5)/square root of E; 6) a statistic based on a square root transformation, Z = 2(square root of D-square root of E); and 7) a statistic created by Byar, which, when D is greater than E, is Z = square root of 9D[1-1/(9D)-3 square root of D/E]. Power differences among these procedures with one-sided alpha of 0.05, 0.025, and 0.01 are small as long as four or more events are expected. If fewer than four events are expected, the uncorrected Z has unacceptably high type I error. Simple approximations to the power and detectable risk of these tests are evaluated and prove satisfactory. Differences in minimum detectable risk, actual and approximated, are slight for E of 2.0 or more.

Risk of stillbirth from occupational and residential exposures.

OBJECTIVES: To analyse the risk of stillbirth from 12 residential and occupational maternal exposures during pregnancy. METHODS: Stillbirths and neonatal deaths in 1984 within 24 hours of birth from 10 California counties were identified from death certificates. Controls were randomly selected from live births born in 1984 and frequency matched to cases by maternal age and county. Data sources included vital statistics and a self-administered postal questionnaire. Logistic regression and proportional hazards modelling were performed; the proportional hazards considered the truncated opportunity for exposure among cases. Special focus was given to two cause of deaths groups: congenital anomalies (12% of deaths) and complications of the placenta, cord, and membranes (37% of deaths). RESULTS: Occupational exposure to pesticides during the first two months of gestation was positively associated with stillbirths due to congenital anomalies (odds ratio (OR) 2.4, 95% confidence interval (95% CI) 1.0 to 5.9), and during the first and second trimesters with stillbirths due to all causes of death (risk ratios (RR) 1.3-1.4, 95% CI 1.0 to 1.7) and stillbirths due to complications of the placenta, cord, and membranes (RR 1.6-1.7, 95% CI 1.1 to 2.3). Occupational exposure to video display terminals in the third trimester was found to have a modest inverse association with stillbirths (RR 0.7, 95% CI 0.6, 0.9). Home pesticide exposure was positively associated with stillbirths due to congenital anomalies (OR 1.7, 95% CI 1.0 to 2.9). CONCLUSIONS: Occupational exposure to pesticides, especially during early pregnancy, had a clear positive association with stillbirths regardless of cause of death. Methodologically, this study of stillbirths is unique in its analysis of specific causes of death and use of time specific exposure windows.

Risk of stillbirth from medications, illnesses and medical procedures.

Associations between stillbirth and 14 medical exposures during pregnancy were examined using deliveries in 1984 in 10 California counties. Cases (n = 332) were stillbirths and infant deaths within 24 h of birth. Randomly selected live births served as controls (n = 357) and were frequency matched by maternal age and county. Using questionnaire and vital statistics data, logistic regression and proportional hazards modelling were performed with adjustment for potential confounders. The most prevalent exposures were ultrasound (65% of cases, 58% of controls) and acetaminophen (45% of cases, 54% of controls). Prescription pain medication, when taken in the first 2 gestational months, was strongly associated with stillbirths due to congenital anomalies (odds ratio = 7.5, 95% confidence interval [CI] 2.3, 24.1). First and second trimester use of prescription pain or migraine medication was positively associated with all stillbirths (rate ratio [RR] range 1.3-1.6). Fertility drugs were positively associated with stillbirths in total and stillbirths due to complications of the placenta, cord and membranes (RR = 1.8, 95% CI 0.8, 4.1; and RR = 2.5, 95% CI 0.9, 7.2 respectively). No associations were found for aspirin, amniocentesis, diagnostic X-rays or fever, consistent with previous studies. This report is among the few studies of specific causes of stillbirth and medical exposures by gestational time window.

A case-control study of pesticides and fetal death due to congenital anomalies.

We examined the association between late fetal death due to congenital anomalies (73 cases, 611 controls) and maternal residential proximity to pesticide applications in ten California counties. A statewide database of all applications of restricted pesticides was linked to maternal address to determine daily exposure status. We examined five pesticide chemical classes. The odds ratios from logistic regression models, adjusted for maternal age and county, showed a consistent pattern with respect to timing of exposure; the largest risks for fetal death due to congenital anomalies were from pesticide exposure during the 3rd-8th weeks of pregnancy. For exposure either in the square mile of the maternal residence or in one of the adjacent 8 square miles, odds ratios ranged from 1.4 (95% confidence interval = 0.8-2.4) for phosphates, carbamates, and endocrine disruptors to 2.2 (95% confidence interval = 1.3-3.9) for halogenated hydrocarbons. Similar odds ratios were observed when a more restrictive definition of nonexposure (not exposed to any of the five pesticide classes during the 3rd-8th weeks of pregnancy) was used. The odds ratios for all pesticide classes increased when exposure occurred within the same square mile of maternal residence.

A computer program for incidence density sampling of controls in case-control studies nested within occupational cohort studies.

A nested case-control study is a case-control study performed with a cohort study. The nested case-control design is useful because the number of study subjects for whom risk factor information is needed is smaller than in the original cohort study. The approach is especially helpful when collection of data is expensive or time consuming, as when it is necessary to contact subjects or next of kin. Selection of controls in nested case-control studies is best performed with a method called "incidence density" sampling. An approach to incidence density sampling that yields a valid estimate of the rate ratio is sampling without replacement from noncases at the time of case occurrence. To implement this approach, a system of computer programs was written that randomly selects a user defined number of controls for each case. The case-control data produced by this program can be analyzed by conditional logistic regression.

A computer program for analyses of vital statistics-based occupational mortality data.

Routinely collected vital statistics mortality data (death certificate data) on occupation and industry are useful for (1) generating hypotheses about potential occupational hazards and (2) identifying occupational mortality differentials possibly associated with socioeconomic and life-style factors. This paper presents a Fortran program that analyzes occupational mortality using vital statistics and census data. The user can form any desired grouping of age, race, occupation (or industry), and cause of death codes for analysis. The program also allows stratification on social class or other user-defined correlates of occupation such as smoking behavior. Furthermore, program output can be used for Poisson regression analysis of mortality rates.

Case-cohort analysis of agricultural pesticide applications near maternal residence and selected causes of fetal death.

The potential association between fetal death and residential proximity to agricultural pesticide applications was examined in 10 California counties for 1984. A case-cohort analysis utilized 319 cases of selected causes of fetal death other than congenital anomalies and 611 non-cases. A statewide database of all applications of restricted pesticides was linked to maternal address; residential proximity within 1 mile (1.6 km) provided a surrogate for daily exposure. Pesticides were grouped by chemical class and mechanism of acetylcholinesterase inhibition. Multivariate proportional hazards models using time-dependent exposure variables were fit for each pesticide grouping. Overall, pesticides showed no strong association with fetal death. Slightly elevated risks were observed for women who resided near applications of halogenated hydrocarbons, carbamates, estrogenic pesticides, and carbamate acetylcholinesterase inhibitors during the second trimester, with hazard ratios of 1.3 (95% confidence interval (CI): 1.0, 1.8), 1.3 (95% CI: 1.0, 1.8), 1.4 (95% CI: 0.8, 2.5), and 1.3 (95% CI: 1.0, 1.8), respectively. In a month-by-month analysis, elevated risks were observed when exposure occurred during gestational months 3 and 4 for carbamates and carbamate inhibitors and during months 4 and 5 for halogenated hydrocarbons. Since previous studies have relied on personal recall of exposure, major strengths of this study were the objective source for environmental pesticide exposure assessment and the use of data on the timing of exposure.

Asthma mortality in California, 1960-1989. Demographic patterns and occupational associations.

We analyzed asthma mortality rates in California during the years 1960 to 1989. Sex- and race-specific rates were stratified by age group (0 to 4, 5 to 34, 35 to 64, and 65+ yr) and for all ages directly standardized to the 1970 U.S. age distribution. Observed and expected asthma deaths were also calculated by occupation for the period 1979 to 1981 among persons aged 16 to 64 yr using data from the California Occupational Mortality Study. Asthma mortality rates were strongly associated with increasing age, but no consistent differences were observed between men and women. Mortality rates among blacks under age 65 yr were two to four times the corresponding rate among whites between 1960 and 1989, but this difference was not observed for those over age 65. Asthma mortality rates were calculated for Hispanics and Asians from 1985 to 1989. In this time period the asthma mortality rate ratios for Hispanics were 0.4 to 0.8 compared with the age-stratified rates among whites, 0.1 to 0.2 times the black rates in age categories under 65, and 0.5 times the rate for blacks ages 65 and above. Asthma mortality rates among Asians under 65 yr of age were similar to rates for whites, but for Asians 65 yr of age and over the rate ratios for males and females compared with whites were 1.8 and 1.1, respectively. A decrease of approximately 50% in asthma mortality occurred from 1960 to 1970, and a marked increase occurred between 1975 and 1989.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory cancer and other chronic disease mortality among silicotics in California.

Silicotics have increased mortality from tuberculosis (TB) and from nonmalignant respiratory diseases (NMRD), including silicosis and silicotuberculosis. Since the publication of the International Agency for Research on Cancer monograph in 1987 indicating that silica was a probable human carcinogen, there has been an extensive debate about the cancer risks among silicotics. The authors identified 590 claims for silicosis among a registry of lung diseases compiled from California Workers' Compensation cases from 1945 to 1975. Using state vital records, we determined the mortality risks from 1946 to 1991. Our findings confirmed that these claimants had a significantly elevated risk for all causes of death with a standardized mortality ratio (SMR) of 1.30 (95% confidence interval [CI] = 1.18, 1.43); TB had a SMR of 56.35 (95% CI = 41.10, 75.40) and NMRD a SMR of 3.80 (95% CI = 3.11, 4.60). Cancers of the trachea, bronchus, and lung had a SMR of 1.90 (95% CI = 1.35, 2.60). For malignancies of the large intestine, there was a previously unreported SMR of 2.08 (95% CI = 1.14, 3.50). Mortality from all diseases of the heart was significantly less than expected with a SMR of 0.68 (95% CI = 0.55, 0.83); cancers of the prostate and lymphatic system were also significantly low with SMRs of 0.26 (95% CI = 0.03, 0.94) and 0.17 (95% CI = 0.04, 0.97), respectively. Workers with silicosis should be warned about these chronic disease risks, and prevention efforts to control occupational silica dust exposure should become a higher priority.

Lung cancer mortality among nonsmoking uranium miners exposed to radon daughters.

Radon daughters, both in the workplace and in the household, are a continuing cause for concern because of the well-documented association between exposure to radon daughters and lung cancer. To estimate the risk of lung cancer mortality among nonsmokers exposed to varying levels of radon daughters, 516 white men who never smoked cigarettes, pipes, or cigars were selected from the US Public Health Service cohort of Colorado Plateau uranium miners and followed up from 1950 through 1984. Age-specific mortality rates for nonsmokers from a study of US veterans were used for comparison. Fourteen deaths from lung cancer were observed among the nonsmoking miners, while 1.1 deaths were expected, yielding a standardized mortality ratio of 12.7 with 95% confidence limits of 8.0 and 20.1. These results confirm that exposure to radon daughters in the absence of cigarette smoking is a potent carcinogen that should be strictly controlled.