Mark J. Nicolich

Use of correlational data to examine the effects of risk perceptions on precautionary behavior.

Abstract The idea that perceptions of high personal risk lead people to adopt precautionary behavior (the “motivational hypothesis”) is mainly tested with correlational data. A review of studies from selective journals reveals a high proportion with methodological and conceptual problems that make them invalid as tests of this hypthesis. Three problems arc emphasized: (1) the misinterpretation of correlations from cross-sectional studies as testing the motivational hypothesis when they actually indicate the accuracy of risk perceptions; (2) the failure to control for prior behavior in prospective studies; and (3) the we of prospective studies in situations of little behavior change. Path models are used to help explain these problems. Recommendations for selecting research designs and for calculating the least problematic correlations are given, along with warnings about the many assumptions needed to interpret even these correlations. Summary Overall, 27 of the 61 cross-sectional analyses listed in Table...

Lymphohaematopoietic malignancies and quantitative estimates of exposure to benzene in Canadian petroleum distribution workers.

OBJECTIVE: To evaluate the relation between mortality from lymphohaematopoietic cancer and long term, low level exposures to benzene among male petroleum distribution workers. METHODS: This nested case control study identified all fatal cases of lymphohaematopoietic cancer among a previously studied cohort. Of the 29 cases, 14 had leukaemia, seven multiple myeloma, and eight non-Hodgkins lymphoma. A four to one matching ratio was used to select a stratified sample of controls from the same cohort, controlling for year of birth and time at risk. Industrial hygienists estimated workplace exposures for benzene and total hydrocarbons, without knowledge of case or control status, for combinations of job, location, and era represented in all work histories. Average daily benzene concentrations ranged from 0.01 to 6.2 parts per million (ppm) for all jobs. Company medical records were used to abstract information on other potential confounders such as cigarette smoking, although the data were incomplete. Odds ratios (ORs) were calculated with conditional logistic regression techniques for several exposure variables. RESULTS: Risks of leukaemia, non-Hodgkins lymphoma, and multiple myeloma were not associated with increasing cumulative exposure to benzene or total hydrocarbons. For leukaemia, the logistic regression model predicted an OR of 1.002 (P < 0.77) for each ppm-y of exposure to benzene. Duration of exposure to benzene was more closely associated with risk of leukaemia than other exposure variables. It was not possible to completely control for other risk factors, although there was suggestive evidence that smoking and a family history of cancer may have played a part in the risk of leukaemia. CONCLUSION: This study did not show a relation between lymphohaematopoietic cancer and long term, low level exposures to benzene. The power of the study to detect low-such as twofold-risks was limited. Thus, further study on exposures to benzene in this concentration range are warranted.

Mortality and cancer morbidity in a cohort of Canadian petroleum workers

Aims: To assess mortality and cancer morbidity in Canadian petroleum workers and explore exposure-response relations for specific petroleum agents. Methods: A total of 25 292 employees hired between 1964 and 1994 were linked to the Canadian tumour registry and national mortality database. Exposure-response trends were assessed for hydrocarbon solvents/fuels, hydrocarbon lubricants, petroleum coke/spent catalyst, and hydrogen sulphide (H2S). Results: External comparison analyses (mortality and incidence) showed deficits for all causes and all malignant neoplasms combined and were consistent with expectation for most malignant and non-malignant sites analysed. Gall bladder cancer mortality was increased among males based on four deaths, but cases had no common job assignments and the increase was focused in workers employed <10 years. Mesothelioma incidence was increased. Most exposure-specific analyses were compromised by small numbers. Statistically significant increases were observed for H2S exposure and a subgroup of accidental deaths as well as for petroleum coke/spent catalyst exposure and lung cancer. While both findings have a degree of biologic plausibility, the H2S association, which exhibited a clearer exposure-response pattern, could be subject to unmeasured confounders. Additionally, interpretation was complicated by the high correlation between hydrocarbon and H2S exposures. With regard to lung cancer, the analysis could not adequately control for smoking, was based on small numbers, and exhibited a tenuous exposure-response pattern. Conclusion: The findings for mesothelioma suggest the need for continued attention to asbestos in the petroleum industry. The relation between accidental deaths and H2S exposure deserves closer scrutiny in similarly exposed populations. Further analyses of lung cancer are underway and will be reported separately.

Retrospective Benzene and Total Hydrocarbon Exposure Assessment for a Petroleum Marketing and Distribution Worker Epidemiology Study

A quantitative exposure-estimating algorithm for benzene and total hydrocarbons was developed for a case control study of petroleum marketing and distribution workers. The algorithm used a multiplicative model to adjust recently measured quantitative exposure data to past scenarios for which representative exposure measurement data did not exist. This was accomplished through the development of exposure modifiers to account for differences in the workplace, the materials handled, the environmental conditions, and the tasks performed. Values for exposure modifiers were obtained empirically and through physical/chemical relationships. Dates for changes that altered exposure potential were obtained from archive records, retired employee interviews, and from current operations personnel. Exposure modifiers were used multiplicatively, adjusting available measured data to represent the relevant exposure scenario and time period. Changes in exposure modifiers translated to step changes in exposure estimates. Though limited by availability of data, a validation exercise suggested that the algorithm provided accurate exposure estimates for benzene (compared with measured data in industrial hygiene survey reports); the estimates generally differed by an average of less than 20% from the measured values. This approach is proposed to quantify exposures retrospectively where there are sufficient data to develop reliable current era estimates and where a historical accounting of key exposure modifiers can be developed, but where there are insufficient historic exposure measurements to directly assess historic exposures.

Peripheral blood effects in benzene-exposed workers.

The hematotoxic effects of benzene exposure may be important in the occurrence of subsequent health effects. We sought to provide further information on peripheral blood effects by studying 928 workers in five factories in and around Shanghai, China exposed to a wide range of benzene concentrations. Specifically, we sought to investigate which blood indices are more strongly related to benzene exposure and which concentration levels of benzene result in peripheral blood changes. Lifestyle habits and demographic information was obtained via questionnaire, and potentially important genetic influences were determined by assessing single nucleotide polymorphisms in four genes (NQO1, MPO, CYP2E1, GSTT1). Weekly benzene exposure estimated from individual monitoring results ranged from 0.07 to 872 mg/m(3) with a median value of 7.4 mg/m(3). Twelve peripheral blood indices were examined. Stronger effects on peripheral blood were seen for red cell indices such as anemia and macrocytosis, albeit at higher (>10 ppm) exposure levels. The most sensitive parameters to benzene appeared to be neutrophils and the mean platelet volume (MPV), where effects were seen for benzene air concentrations of 7.8-8.2 ppm. Toluene exposure is a potential confounder for some peripheral blood effects, pointing to the need to scrutinize levels of both compounds in the occupational environment.

Two-generation reproduction study in rats given di-isononyl phthalate in the diet

The potential reproductive toxicity of di-isononyl phthalate (DINP: CAS RN 68515-48-0) was assessed in one- and two-generation reproductive toxicity studies. Groups of 30 male and female CRL : CD(SD)BR rats were given DINP via dietary administration at levels of either 0.0, 0.5, 1, or 1.5% (one-generation study) or 0.0, 0.2, 0. 4, or 0.8% (two-generation study). There were no changes in any of the classic reproductive parameters, i.e. mating, male or female fertility, fecundity, gestational index, or length of gestation in either study. The overall NOAELs for these effects were the highest Dietary Level (%)s tested, approximately 500 mg/kg/day in the two-generation study and 1000 mg/kg/day in the one-generation study. There were no testicular effects in parental animals exposed as juveniles and young adults at 960 mg/kg/day in the one-generation study. In the two-generation study, there were no testicular effects in either the P(1) males, exposed as juveniles and young adults or the P(2) (F(1)) offspring exposed in utero, through lactation, and continuously to terminal sacrifice. The NOAEL was 470 mg/kg/day. Offspring survival was reduced at the 1.5% level ( approximately 1100 mg/kg/day) but unaffected at the 1% level ( approximately 760 mg/kg/day). There were decreased offspring body weights both at postnatal day (PND) 0 and during lactation; however, the PND 0 effects were only clearly related to treatment at the 1.5% level. Weights of offspring during lactation were significantly reduced but within the historical control range at Dietary Level (%)s below 1%. As there was rapid recovery at the lower levels, even though treatment continued, the toxicologic significance is unclear. Adult survival was unaffected at any level in either study, but weight gain was significantly reduced at the 1% level ( approximately 600 mg/kg/day). Liver and kidney weights were elevated at Dietary Level (%)s above approximately 110 mg/kg/day, consistent with evidence from other studies of peroxisomal proliferation at these levels. This study showed that DINP treatment does not affect fertility or male reproductive development at doses of up to approximately 1000 mg/kg/day.

Influence of parental and biological factors on the male birth fraction in the United States: an analysis of birth certificate data from 1964 through 1988.

OBJECTIVE To determine the role of parental and biological factors on the U.S. male birth fraction from 1964 through 1988. DESIGN Logistic regression on annual U.S. male births by race group. SETTING Population-based data. PATIENT(S) Live births in the United States 1964 through 1988. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Annual U.S. male birth fraction by parental and biological factors. RESULT(S) During the study period, the annual U. S. male birth fraction showed changes based on race group, parental age, and low birth weight. The overall influence of parental age on the U.S. male birth fraction is strong and is stronger in nonwhites than in whites. The U.S. male birth fraction is also strongly influenced by the percentage of low birth weight infants in nonwhites, but not in whites. The male birth fraction declines with increasing age of either parent and with an increase in the percentage of low birth weight infants. CONCLUSION(S) The relative magnitude of influences on the U.S. male birth fraction depend on the race group, which may be a reflection of the range of observed data rather than biological differences. The developed models have reasonable predictive power and are an appropriate first step in understanding the factors influencing the male birth fraction. These types of parental and biological variables should be included in models before examining other exogenous and population level variables.

Genotoxicity of intermittent co-exposure to benzene and toluene in male CD-1 mice.

Benzene is an important industrial chemical. At certain levels, benzene has been found to produce aplastic anemia, pancytopenia, myeloblastic anemia and genotoxic effects in humans. Metabolism by cytochrome P450 monooxygenases and myeloperoxidase to hydroquinone, phenol, and other metabolites contributes to benzene toxicity. Other xenobiotic substrates for cytochrome P450 can alter benzene metabolism. At high concentrations, toluene has been shown to inhibit benzene metabolism and benzene-induced toxicities. The present study investigated the genotoxicity of exposure to benzene and toluene at lower and intermittent co-exposures. Mice were exposed via whole-body inhalation for 6h/day for 8 days (over a 15-day time period) to air, 50 ppm benzene, 100 ppm toluene, 50 ppm benzene and 50 ppm toluene, or 50 ppm benzene and 100 ppm toluene. Mice exposed to 50 ppm benzene exhibited an increased frequency (2.4-fold) of micronucleated polychromatic erythrocytes (PCE) and increased levels of urinary metabolites (t,t-muconic acid, hydroquinone, and s-phenylmercapturic acid) vs. air-exposed controls. Benzene co-exposure with 100 ppm toluene resulted in similar urinary metabolite levels but a 3.7-fold increase in frequency of micronucleated PCE. Benzene co-exposure with 50 ppm toluene resulted in a similar elevation of micronuclei frequency as with 100 ppm toluene which did not differ significantly from 50 ppm benzene exposure alone. Both co-exposures - 50 ppm benzene with 50 or 100 ppm toluene - resulted in significantly elevated CYP2E1 activities that did not occur following benzene or toluene exposure alone. Whole blood glutathione (GSH) levels were similarly decreased following exposure to 50 ppm benzene and/or 100 ppm toluene, while co-exposure to 50 ppm benzene and 100 ppm toluene significantly decreased GSSG levels and increased the GSH/GSSG ratio. The higher frequency of micronucleated PCE following benzene and toluene co-exposure when compared with mice exposed to benzene or toluene alone suggests that, at the doses used in this study, toluene can enhance benzene-induced clastogenic or aneugenic bone marrow injury. These findings exemplify the importance of studying the effects of binary chemical interactions in animals exposed to lower exposure concentrations of benzene and toluene on benzene metabolism and clastogenicity. The relevance of these data on interactions for humans exposed at low benzene concentrations can be best assessed only when the mechanism of interaction is understood at a quantitative level and incorporated within a biologically based modeling framework.

Mortality experience of a young petrochemical industry cohort : 1979-1992 follow-up study of US-based employees

This retrospective study examines the mortality patterns of a relatively young cohort of 81,746 former and current petrochemical company employees. Standardized mortality ratios (SMR) for 1979 through 1992 are generally from about unity to well below unity for major causes and numerous specific causes of death studied by gender/race/job subgroups. Findings of note include a SMR (based on incidence rates) of 1.94 (95% confidence interval [CI], 1.04 to 3.33) for mesothelioma, and a SMR of 1.81 (95% CI, 0.90 to 3.24) for chronic lymphocytic leukemia, both among males hired before 1960. All male semiskilled operatives have a 1.6-fold increase (95% CI, 1.07 to 2.29) in motor vehicle accident deaths, with declining rates since the mid-1980s. The overall SMR for acquired immunodeficiency syndrome (AIDS) is at unity (69 deaths), with excesses in technician and office worker subgroups. Four decedents with lymphoma (code 202.8 in 9th revision ICD) had AIDS as a secondary cause of death, suggesting the need to examine secondary causes when studying lymphopoietic conditions. This routine surveillance activity provides leads regarding the presence or absence of excess mortality risk.

Cumulative effects and threshold levels in air pollution mortality: data analysis of nine large US cities using the NMMAPS dataset.

We examined the existence of thresholds, cumulative effects and the homogeneity of five air pollutants on the relative risk of three mortality outcomes using data from nine major US cities using data from NMMAPS. Overall, PM(10) (usually 200-day accumulation) and ozone (3-day accumulation) were the two important predictors of outcome but their effect was not uniform across the nine cities. Many models exhibited thresholds (25-45 microm g/m(3) for PM(10), and 10-45 ppb for O(3)). Our preliminary exploratory analyses suggest that the use of a linear, no threshold, model for pollution studies is not consistent with the observed data. The heterogeneity in the risk estimates across the nine cities suggests combining the local risk estimates to obtain a national risk estimate may not be justifiable and the estimate is likely to be confounded.