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.

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.

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.

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.