The importance of evaluating specific myeloid malignancies in epidemiological studies of environmental carcinogens.

INTRODUCTION: Although myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) - including chronic myeloid leukemia (CML) - and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are largely clinically distinct myeloid malignancies, epidemiological studies rarely examine them separately and often combine them with lymphoid malignancies, limiting possible etiological interpretations for specific myeloid malignancies. METHODS: We systematically evaluated the epidemiological literature on the four chemical agents (1,3-butadiene, formaldehyde, benzene, and tobacco smoking, excluding pharmaceutical, microbial and radioactive agents, and pesticides) classified by the International Agency for Research on Cancer as having sufficient epidemiological evidence to conclude that each causes "myeloid malignancies." Literature searches of IARC Monographs and PubMed identified 85 studies that we critically assessed, and for appropriate subsets, summarized results using meta-analysis. RESULTS: Only two epidemiological studies on 1,3-butadiene were identified, but reported findings were inadequate to evaluate specific myeloid malignancies. Studies on formaldehyde reported results for AML and CML - and not for MDS or MPN - but reported no increased risks. For benzene, several specific myeloid malignancies were evaluated, with consistent associations reported with AML and MDS and mixed results for CML. Studies of tobacco smoking examined all major myeloid malignancies, demonstrating consistent relationships with AML, MDS and MPN, but not with CML. CONCLUSIONS: Surprisingly few epidemiological studies present results for specific myeloid malignancies, and those identified were inconsistent across studies of the same exposure, as well as across chemical agents. This exercise illustrates that even for agents classified as having sufficient evidence of causing "myeloid malignancies," the epidemiological evidence for specific myeloid malignancies is generally limited and inconsistent. Future epidemiological studies should report findings for the specific myeloid malignancies, as combining them post hoc - where appropriate - always remains possible, whereas disaggregation may not. Furthermore, combining results across possibly discrete diseases reduces the chances of identifying important malignancy-specific causal associations.

An examination of the Environmental Protection Agency risk assessment principles and practices: a brief commentary on section 4.1.3 of the EPA March 2004 Staff Paper.

The US Environmental Protection Agency (EPA) recently issued a Staff Paper that articulates current risk assessment practices. In section 4.1.3, EPA states, "... effects that appear to be adaptive, non-adverse, or beneficial may not be mentioned." This statement may be perceived as precluding risk assessments based on non-default risk models, including the hormetic--or biphasic--dose-response model. This commentary examines several potential interpretations of this statement and the anticipated impact of ignoring hormesis, if present, in light of necessary conservatism for protecting human and environmental health, and the potential for employing alternative risk assessment approaches.

Workplace airborne hexavalent chromium concentrations for the Painesville, Ohio, chromate production plant (1943-1971).

Hexavalent chromium [Cr(VI)] is recognized as an inhalation carcinogen, based primarily on the increased incidence of lung cancer among occupationally exposed workers. To assess the carcinogenic potency of Cr(VI), both the U.S. Environmental Protection Agency and the Occupational Safety and Health Administration have relied on data from a 1930s cohort of workers from the Painesville, Ohio, chromate production plant. However, the exposure information for this cohort has several shortcomings. In an effort to provide better exposure information, we present here recently identified historical exposure data for the Painesville workers. More than 800 measurements of airborne Cr(VI) from 23 newly identified surveys conducted from 1943 to 1971 are presented. The results indicate that the highest Cr(VI) concentrations recorded at the plant occurred in shipping (e.g., bagging of dichromate), lime and ash, and filtering operations, with maximum yearly average Cr(VI) concentrations of 8.9, 2.7, and 2.3 mg/m(3), respectively. The locker rooms, laboratory, maintenance shop, and outdoor raw liquor storage areas had the lowest average Cr(VI) air concentrations over time, with yearly average concentrations that rarely exceeded the historical and current Threshold Limit Value TLV(R) of 0.05 mgCr(VI)/m(3) (0.1 mgCrO(3)/m(3)). Concentrations generally decreased in the plant over time. The average airborne concentration of Cr(VI) in the indoor operating areas of the plant in the 1940s was 0.72 mg/m(3), that from 1957 through 1964 was 0.27 mg/m(3), and that from 1965 through 1972 was 0.039 mg/m(3). Although in some ways limited, these data are of sufficient quality to allow for exposure reconstruction for workers employed at this plant from 1940 to 1972, and to provide the basis for an improved cancer risk assessment.

Lung cancer mortality among chromate production workers.

AIMS: To assess mortality in 1997 among 493 former workers of a US chromate production plant employed for at least one year between 1940 and 1972. METHODS: Cohort members were followed for mortality to 31 December 1997. Standardised mortality ratios (SMRs) were calculated for selected cause specific categories of death including lung cancer. Lung cancer mortality was investigated further by calculation of SMRs stratified by year of hire, duration of employment, time since hire, and categories of cumulative exposure to Cr(VI). RESULTS: Including 51 deaths due to lung cancer, 303 deaths occurred. SMRs were significantly increased for all causes combined (SMR = 129), all cancers combined (SMR = 155), and lung cancer (SMR = 241). A trend test showed a strong relation between lung cancer mortality and cumulative hexavalent exposure. Lung cancer mortality was increased for the highest cumulative exposure categories (> or =1.05 to <2.70 mg/m(3)-years, SMR = 365; > or =2.70 to 23 mg/m(3)-years, SMR = 463), but not for the first three exposure groups. Significantly increased SMRs were also found for year of hire before 1960, 20 or more years of exposed employment, and latency of 20 or more years. CONCLUSIONS: The finding of an increased risk of lung cancer mortality associated with Cr(VI) exposure is consistent with previous reports. Stratified analysis of lung cancer mortality by cumulative exposure suggests a possible threshold effect, as risk is significantly increased only at exposure levels over 1.05 mg/m(3)-years. Though a threshold is consistent with published toxicological evidence, this finding must be interpreted cautiously because the data are also consistent with a linear dose response.

Risk factors for occupational knee related disability among enlisted women in the US Army.

AIMS: To identify sociodemographic and occupational determinants of knee related disability discharge from the US Army among enlisted women, and to investigate effect modification. METHODS: A case-control study of 692 cases of knee related disability discharge and 2080 incidence density matched controls nested within the population of all 244 000 enlisted women on active duty in the US Army, 1980-97. We used logistic regression to identify determinants of disability, stratified to explore effect modification by demographic and work characteristics. RESULTS: The risk of disability discharge was twice as high (odds ratio (OR) 2.4, 95% confidence interval (CI): 1.71 to 3.47) for the oldest (33-60 years) versus the youngest (17-21 years) women. Non-whites had lower risk than whites (OR 0.5, 95% CI: 0.41 to 0.60), as did married (OR 0.7, 95% CI: 0.54 to 0.81) relative to non-married women. Those of lower rank (pay grades E1-E3) were at five times the risk of disability discharge compared to those of higher ranks (pay grades E4-E9, OR 5.0, 95% CI: 2.86 to 8.33), while ORs were highest for those with longer duration of service compared to women on active duty for a year or less (OR 1.4, 95% CI: 0.8 to 2.55 after 12 years). Race modified several effects, including that of rank. Age, duration of service, and pay grade were too highly correlated to draw firm conclusions about their independent modifying effects on risk of disability discharge from the Army. CONCLUSIONS: Sociodemographic factors had larger effects than occupational characteristics on risk of knee related disability discharge from the US Army. Interactions suggest subgroups at differing risk levels that might be targeted for more detailed investigations.

Critical review of the epidemiological literature on the potential cardiovascular effects of occupational carbon disulfide exposure.

OBJECTIVES: Occupational carbon disulfide (CS(2)) exposure has been associated with a variety of health effects since its introduction in the mid-19th century. Much of the epidemiological interest, especially since the 1960s, has focused on associations with cardiac effects. However, considerable differences in study approach, disease outcome, CS(2) exposure level, and control of confounding factors have produced mixed results and conclusions. This critical review presents a synthesis of the most relevant and best quality studies to better understand these associations. METHODS: Using specific criteria to assess methodological and scientific quality, we identified 37 studies with the potential to inform on at least one of the following questions: (1) Has a relationship between CS(2) exposure and coronary heart disease (CHD) mortality been reasonably demonstrated? If so, at what apparent exposure levels has it been observed? (2) Among studies of workers routinely exposed to CS(2) at levels greater than 20 ppm, have any health effects or indicators of CHD been observed consistently? (3) Among occupational groups exposed to CS(2) at levels less than 20 ppm, have any health effects or indicators of CHD been observed consistently? RESULTS: Several CHD-related effects have been examined relative to various levels of occupational CS(2) exposure. Overall, there was remarkably little consistency of CHD effects observed, including CHD mortality. CONCLUSIONS: Although a physiological effect of CS(2) exposure on CHD is plausible, the epidemiological evidence for an association between CS(2) exposure and various cardiac risk indicators is mixed. The only somewhat consistent finding, of CS(2) exposure on total and/or LDL cholesterol level, may be due to residual confounding by other time-dependent risk factors. If real, however, it appears to be of small magnitude and uncertain clinical importance.

Mental health insurance claims among spouses of frequent business travellers.

OBJECTIVES: Following up on two earlier publications showing increased psychological stress and psychosocial effects of travel on the business travellers this study investigated the health of spouses of business travellers. METHODS: Medical claims of spouses of Washington DC World Bank staff participating in the medical insurance programme in 1997-8 were reviewed. Only the first of each diagnosis with the ninth revision of the international classification of diseases (ICD-9) recorded for each person was included in this analysis. The claims were grouped into 28 diagnostic categories and subcategories. RESULTS: There were almost twice as many women as men among the 4630 identified spouses. Overall, male and female spouses of travellers filed claims for medical treatment at about a 16% higher rate than spouses of non-travellers. As hypothesised, a higher rate for psychological treatment was found in the spouses of international business travellers compared with non-travellers (men standardised rate ratios (RR)=1.55; women RR=1.37). For stress related psychological disorders the rates tripled for both female and male spouses of frequent travellers (>or= four missions/year) compared with those of non-travelling employees. An increased rate of claims among spouses of travellers versus non-travellers was also found for treatment for certain other diagnostic groups. Of these, diseases of the skin (men RR=2.93; women RR=1.41) and intestinal diseases (men RR=1.31; women RR=1.47) may have some association with the spouses' travel, whereas others, such as malignant neoplasms (men RR=1.97; women RR=0.79) are less likely to have such a relation. CONCLUSION: The previously identified pattern of increased psychological disorders among business travellers is mirrored among their spouses. This finding underscores the permeable boundary between family relations and working life which earlier studies suggested, and it emphasises the need for concern within institutions and strategies for prevention.

Antisocial behavioral syndromes and return to drug use following residential relapse prevention/health education treatment.

This study compared residential addiction treatment clients meeting full DSM-III-R criteria for antisocial personality disorder (ASPD) with those reporting syndromal levels of antisocial behavior only in adulthood (AABS) on time to and severity of first posttreatment drug use. Antisocial syndrome and selected other mental disorders were assessed using the Diagnostic Interview Schedule, Revised for DSM-III-R, and validity of self-reported posttreatment drug behavior was measured against results of hair analysis. Among subjects followed within 180 days after treatment exit, individuals with ASPD were at modestly increased risk of a first lapse episode compared to those with AABS. However, the two groups did not differ in severity of lapse. Participants with ASPD demonstrated poorer agreement between self-reported posttreatment drug behavior and hair data. These results add to the evidence suggesting that the DSM requirement for childhood onset in ASPD may be clinically important among substance abusers in identifying a severely antisocial and chronically addicted group at elevated risk for early posttreatment recidivism. Our findings support the importance of careful classification of antisocial syndromes among substance abusers and the identification of characteristics of these syndromes that underlie clients' risks for posttreatment return to drug use to provide optimally individualized treatment planning.

Deep venous thrombosis associated with corporate air travel.

BACKGROUND: Deep venous thrombosis (DVT) is commonly seen among bedridden and postoperative patients. Its association with travel may also make DVT an occupational health risk to otherwise healthy business travelers. We estimated the incidence of and risk factors for DVT among 8,189 World Bank employees and a subset of 4,951 international business travelers. METHODS: Occurrence of DVT between 1995 and 1998 was determined using 1) medical insurance claims; 2) Workers' Compensation claims; and 3) intra-office E-mail solicitation followed by interview. For each insurance claim case, 10 controls were randomly selected from among World Bank employees insured during the same month and year as the case's claim was filed, and case-control analyses were performed to identify potential predictors or risk factors for DVT. RESULTS: Thirty individuals filed claims for DVT of the legs (annual incidence rate: 0.9 per 1,000 employees); three of these claims were filed within 30 days after a travel mission. Two employees reported DVT as a Workers' Compensation injury, and five staff with verified DVT participated in interviews. After controlling for age and gender, no association with any travel-related covariate was seen. Results of analyses considering all thrombophlebitis and thromboembolism followed the same pattern. The average annual incidence of DVT occurring within 30 days of mission among traveling staff ranged from 0.10 per 1,000 to 0.25 per 1,000 travelers, depending on the case-finding method. CONCLUSION: No association between DVT and travel was observed after adjustment for gender and age. These results, however, are preliminary, and due to the rarity of DVT, based on small numbers.

Historical cohort study of 10 109 men in the North American vinyl chloride industry, 1942-72: update of cancer mortality to 31 December 1995.

OBJECTIVES: To update and assess mortality from neoplasms to 31 December 1995 among 10 109 men employed in a job exposed to vinyl chloride for at least 1 year between 1942 and 1972 at any of 37 North American factories. Previous analyses indicated associations between employment in vinyl production and increased mortality risk from cancers of the liver and biliary tract, due to increased mortality from angiosarcoma of the liver, and brain cancer. METHODS: Standardised mortality ratio (SMR) analyses, overall and stratified by several work related variables, were conducted with United States and state reference rates. Cox's proportional hazards models and stratified log rank tests were used to further assess occupational factors. RESULTS: 895 of 3191 deaths (28%) were from malignant neoplasms, 505 since the previous update to the end of 1982. Mortality from all causes showed a deficit (SMR 83, 95% confidence interval (95% CI) 80 to 86), whereas mortality from all cancers combined was similar to state referent rates. Mortality from cancers of the liver and biliary tract was clearly increased (SMR 359, 95% CI 284 to 446). Modest excesses of brain cancer (SMR 142, 95% CI 100 to 197) and cancer of connective and soft tissue (SMR 270, 95% CI 139 to 472) were found. Stratified SMR and Cox's proportional hazard analyses supported associations with age at first exposure, duration of exposure, and year of first exposure for cancers of the liver and soft tissues, but not the brain. CONCLUSIONS: Excess mortality risk from cancer of the liver and biliary tract, largely due to angiosarcoma, continues. Risk of mortality from brain cancer has attenuated, but its relation with exposure to vinyl chloride remains unclear. A potentially work related excess of deaths from cancer of connective and soft tissue was found for the first time, but was based on few cancers of assorted histology.

Parental occupational exposures and risk of neuroblastoma: a case-control study (United States).

BACKGROUND: A case-control study was conducted with 183 histologically confirmed neuroblastoma cases aged 0-14 years diagnosed among residents of New York State, excluding New York City, between 1976 and 1987. Three hundred seventy-two controls were selected from the New York State live birth certificate registry and were matched to cases on year of birth. METHODS: Parental occupational exposures at the time of each child's birth were obtained from maternal telephone interviews, successfully completed for 85% of cases and 87% of controls. RESULTS: Odds ratios were significantly elevated for maternal occupation in the service (OR = 2.0, 95% CI = 1.0 4.1) and retail (OR = 2.0, 95% CI = 1.1-3.7) industries and paternal occupation in materials handling (OR = 3.8, 95% CI = 1.1-14.6). Odds ratios were also significantly elevated for maternal report of occupational exposure to acetone (OR = 3.1, 95% CI = 1.7-5.6), insecticides (OR = 2.3, 95% CI = 1.4-3.7), lead (OR = 4.7, 95% CI = 1.3-18.2) and petroleum (OR = 3.0, 95% CI = 1.5-6.1) and paternal exposure to creosote (OR = 2.1, 95% CI = 1.1-4.3), dioxin (OR = 6.9, 95% CI = 1.3-68.4), lead (OR = 2.4, 95% CI = 1.2-4.8), and petroleum (OR = 1.8, 95% CI = 1.1-2.8). CONCLUSIONS: Due to the uncertainty of the biologic plausibility of these associations and the possibility of alternative explanations, these results should be interpreted cautiously.

Video display terminal workstation improvement program: I. Baseline associations between musculoskeletal discomfort and ergonomic features of workstations.

Associations between selected sites of musculoskeletal discomfort and ergonomic characteristics of the video display terminal (VDT) workstation were assessed in analyses controlling for demographic, psychosocial stress, and VDT use factors in 273 VDT users from a large administrative department. Significant associations with wrist/hand discomfort were seen for female gender; working 7+ hours at a VDT; low job satisfaction; poor keyboard position; use of new, adjustable furniture; and layout of the workstation. Significantly increased odds ratios for neck/shoulder discomfort were observed for 7+ hours at a VDT, less than complete job control, older age (40 to 49 years), and never/infrequent breaks. Lower back discomfort was related marginally to working 7+ hours at a VDT. These results demonstrate that some characteristics of VDT workstations, after accounting for psychosocial stress, can be correlated with musculoskeletal discomfort.

Video display terminal workstation improvement program: II. Ergonomic intervention and reduction of musculoskeletal discomfort.

The effects of an ergonomic intervention on musculoskeletal discomfort in 118 video display terminal (VDT) users were assessed 1 year after intervention. The intervention consisted of recommended changes to workstations, which were based on the evaluation of 15 ergonomic characteristics. Compliance with the intervention was at least 75% for most workstation characteristics. Reduction in discomfort was substantial and was highest for the wrist/hand (57%), lower back (43%), and neck/shoulder (41%) severity of discomfort outcomes. Neither compliance with intervention on individual workstation characteristics nor summary intervention scores were associated with reduction in discomfort. Our results demonstrate that although reduction of musculoskeletal discomfort may be observed in the context of an intervention study, it may be difficult to link these benefits to specific interventions.

Case-control study of discharge from the U.S. Army for disabling occupational knee injury: the role of gender, race/ethnicity, and age.

BACKGROUND: Occupational injuries are responsible for more lost time from work, productivity, and working years of life than any other health condition in either civilian or noncombat military sectors. Injuries, not illnesses, are the leading cause of morbidity and mortality among U.S. Army personnel. We examined the separate and joint roles of gender, race/ethnicity, and age in the odds of discharge from the Army for disabling knee injury. METHODS: A total of 860 women and 7868 men were discharged from the Army between 1980 and 1995 for knee-related disability and met all inclusion criteria for this study. All women and a subsample of 1005 men were included in these analyses, along with a simple random sample of three controls per case, stratified by gender, drawn from the population of all active-duty enlisted soldiers in each year from 1980 to 1995. We identified predictors of the occurrence or nonoccurrence of discharge from the Army for disabling knee injury using unconditional multiple logistic regression analyses. RESULTS: We found relations between the risk of knee-related disability and age and race, with marked effect modification by gender. Non-Caucasian men and women were at lower risk than Caucasians at all ages. At most ages, Caucasian women were at higher risk than Caucasian men, and non-Caucasian women were at lower risk than non-Caucasian men. Within race/ethnicity and gender, the risks for men showed an inverted "U" shape with increasing age, and the risks for women showed a "J" shape with increasing age. CONCLUSIONS: Age, race/ethnicity, and gender interactions are important in occupational injury. Differences in risk may be related to differences in work assignments, leisure activities, physical or physiological differences, or the ways in which disability compensation is granted.

Critical review of the epidemiology literature on the potential cancer risks of methylene chloride.

OBJECTIVE: To critically review and summarize the epidemiological evidence published to date on the carcinogenicity of methylene chloride to humans. METHODS: Papers for review were identified through Medline (National Library of Medicine) and were limited to epidemiology studies. Studies were classified using three categories. Primary studies focused on the association between methylene chloride and cancer among occupational cohorts primarily exposed to methylene chloride. Secondary studies identified methylene chloride a priori as a potential exposure of interest, and the investigators either characterized the methylene chloride exposure or described results for the methylene chloride-exposed workers separately. Tertiary studies evaluated cohorts either minimally exposed to methylene chloride or presumed exposed but for which no exposure estimation or separate classification was made. RESULTS: No strong or consistent finding for any site of cancer was apparent despite several studies of large occupational cohorts of workers potentially exposed to high concentrations of methylene chloride. Sporadic and weak associations were reported for cancers of the pancreas, liver and biliary passages, breast, and brain. Although these studies collectively cannot rule out the possibility of any cancer risk associated with methylene chloride exposure, they do support a conclusion of no substantive cancer risk. CONCLUSIONS: Continued follow-up of the established cohorts may elucidate the few and inconsistent relationships reported to date; however, it appears likely that risks associated with methylene chloride exposure, if any, are small and limited to rare cancers. The usefulness of additional cohort studies for the evaluation of cancer risks associated with methylene chloride exposure will depend largely on whether the relevant exposure period has passed and whether exposure characterization (e.g., peak or intermittent exposure or intensity) can be improved.

An occupational cohort mortality study of women in the German rubber industry: 1976 to 1991.

Few previous studies of workers in the rubber industry have focused on women. We examined patterns of mortality among 2871 women employed in one of five German rubber plants for at least 1 year on or after January 1, 1976, and observed through December 31, 1991. All-causes mortality was near that expected (standardized mortality ratio [lsqbSMR], 101; 95% confidence interval [CI], 87 to 118), but cancer mortality was decreased (SMR, 90; 95% CI, 70 to 115). Nevertheless, excesses were observed for mortality from stomach cancer (SMR, 156; 95% CI, 63 to 322), lung cancer (SMR, 140; 95% CI, 56 to 289), and lymphatic system cancers (SMR, 175; 95% CI, 48 to 448). Stronger associations were observed among sub-cohorts defined by time period hired. Despite limited numbers of deaths, modest excesses of mortality due to specific cancers were observed and are consistent with previous studies.

Risk factors for psychological stress among international business travellers.

OBJECTIVES: This study investigated sources of self reported psychological stress among international business travellers at the World Bank, following up on a previous study showing that travellers submitted more insurance claims for psychological disorders. Hypotheses were that work, personal, family, and health concerns, as well as time zone travel, contribute to travel stress. METHODS: A travel survey was developed from focus groups and consisted of questions about these potential sources of travel stress. Surveys were sent to a random sample of staff, stratified by number of travel missions, age range, and sex. Canonical correlation analyses estimated the association between key survey items on sources of stress and two measures of travel stress. RESULTS: 498 staff completed the survey. More than a third reported high to very high travel stress. Correlations between predictors and travel stress showed that social and emotional concerns (such as impact of travel on family and sense of isolation) contributed the most to such stress, followed by health concerns, and workload upon return from travel. Surprisingly, time zone travel did not contribute to the self reported stress of these travellers. There were few modifiers of stress, although respondents suggested that a day of rest after travel and reduced workloads would help. CONCLUSIONS: The current study confirms clinical impressions about several correlates of travel stress. Similar research with travellers in other organisations could help to determine whether the findings from this study are valid and what measures can be taken to reduce the psychological health risks to travellers.

Antisocial behavioral syndromes among residential drug abuse treatment clients.

We compared residential addictions treatment clients meeting full criteria for antisocial personality disorder (ASPD+) with those reporting syndromal levels of antisocial behavior only in adulthood (AABS+) on demographics, antisocial symptomatology, drug history, axis I comorbidity and characteristics of index treatment episode. We examined these issues in the sample as a whole, as well as separately in male and female respondents. Among both men and women, ASPD+ initiated their antisocial behavior earlier, met more ASPD criteria and endorsed more violent symptoms, than AABS+. Male ASPD+ also met criteria for more lifetime axis I diagnoses and reported more years of drug involvement than male AABS+. Trends were observed toward poorer retention in treatment among ASPD+ than among AABS+ participants of both genders randomized to a planned duration of 180 days, but retention did not differ between ASPD+ and AABS+ randomized to a planned duration of 90 days. Our findings, which replicate and extend previously published results, carry potential implications for treatment programming and for the nosology of ASPD.

Workplace risk factors for cancer in the German rubber industry: Part 1. Mortality from respiratory cancers.

OBJECTIVES: To determine the cancer specific mortality by work area among active and retired male workers in the German rubber industry. METHODS: A cohort of 11,663 male German workers was followed up for mortality from 1 January 1981 to 31 December 1991. Cohort members were classified as active (n = 7536) or retired (n = 4127) as of 1 January 1981 and had been employed for at least one year in one of five study plants producing tyres or technical rubber goods. Work histories were reconstructed with routinely documented "cost centre codes" which were classified into six categories: I preparation of materials; II production of technical rubber goods; III production of tyres; IV storage and dispatch; V maintenance; and VI others. Standardised mortality ratios (SMRs) adjusted for age and calendar year and 95% confidence intervals (95% CIs), stratified by work area (employment in respective work area for at least one year) and time related variables (year of hire, lagged years of employment in work area), were calculated from national reference rates. RESULTS: SMRs for laryngeal cancer were highest in work area I (SMR 253; 95% CI 93 to 551) and were significant among workers who were employed for > 10 years in this work area (SMR 330; 95% CI 107 to 779). Increased mortality rates from lung cancer were identified in work areas I (SMR 162; 95% CI 129 to 202), II (SMR 134; 95% CI 109 to 163), and V (SMR 131; 95% CI 102 to 167). Mortality from pleural cancer was increased in all six work areas, and significant excesses were found in work areas I (SMR 448; 95% CI 122 to 1146), II (SMR 505; 95% CI 202 to 1040), and V (SMR 554; 95% CI 179 to 1290). CONCLUSION: A causal relation between the excess of pleural cancer and exposure to asbestos among rubber workers is plausible and likely. In this study, the pattern of excess of lung cancer parallels the pattern of excess of pleural cancer. This points to asbestos as one risk factor for the excess deaths from lung cancer among rubber workers. The study provides further evidence for an increased mortality from laryngeal cancer among workers in the rubber industry, particularly in work area I.