Biomedical subjects

A R Schnatter

Publications and source records attributed to A R Schnatter.

At least 19 recordsLinked to original sources

PubMed2001

Using epidemiological studies to check the consistency of the cancer risks predicted by high-dose animal experiments: a methodological review.

Epidemiological studies have been cited in the literature as evidence both for and against the human cancer risks predicted by high-exposure rodent studies. However, there has been little overall consistency in the ways that these animal-to-human comparisons have been made. This review examines some examples of these types of comparisons and describes the methods and techniques used by different investigators. Eleven "key decision areas" that need to be addressed are identified and recommendations for consistent, logical, and statistically appropriate approaches that might be taken to standardize the process are provided. In general, it is suggested that investigators provide the most useful information when they use logical, transparent, and statistically valid comparisons to pursue limited and focused objectives, such as directly testing the validity of an existing regulatory guidance value. Other recommendations include selecting biologically plausible extrapolative models that fit the data and drawing conclusions that are consistent with the study results and objectives.

Animals↗

PubMed2000

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.

Age Factors↗

PubMed2000

A framework for addressing health issues in or near a manufacturing facility.

Clustering of health events in or around industrial facilities sometimes leads to worker and community concerns that plant management or local health professionals must address. We provide an eight-step process to deal with these concerns systematically. We emphasize the use of good scientific practices with managerial oversight for effective worker and community communication. This process is directed to plant management and the local health professional and emphasizes the practical aspects of the investigation.

Contract Services↗

PubMed2000

Updated mortality among diverse operating segments of a petroleum company.

OBJECTIVES: To update mortality for 34 560 employees from diverse operating segments of a Canadian petroleum company; and to investigate potential relations with occupational factors. METHODS: Employees from 1964-83 were linked to the Canadian mortality data base to provide 11 years additional follow up. There were 6760 deaths and 750 683 person-years of follow up compared with 3909 and 428 190, respectively, in the earlier study. Analyses used standardised mortality ratios (SMRs) to compare worker cause specific mortality with the Canadian general population. Duration of employment and latency analyses were performed for causes previously found to be increased in this and other petroleum cohorts, as well as any findings of interest. RESULTS: For the period 1964-94, employees experienced significantly low overall mortality (SMR=0.86 men, SMR=0.80 women). Kidney cancer, which has been increased in some studies of petroleum workers, was not increased. Acute non-lymphocytic leukaemia in exposed operating segments was consistent with the expected or only slightly, non-significantly increased. The most notable finding was increased deaths from mesothelioma among refinery and petrochemical workers (SMR 8.68; 95% confidence interval (95% CI) 5.51 to 13.03), most of whom were long term employees in jobs with presumed exposure to asbestos (mechanical and pipefitters). Deaths from multiple myeloma among marketing and distribution workers, which were previously increased, remained increased (SMR 2.08; 95% CI 0.95 to 3.95) in the update period 1984-94; however, there was no clear pattern by duration of employment or latency. Aortic aneurysms, which also were previously significantly increased among marketing and distribution workers approached the expected in the update period (SMR 1.18; 95% CI 0. 65-1.98). Analyses by duration of employment showed suggestive trends for aortic aneurysms, but earlier studies of this cohort have not found a relation between aortic aneurysms and exposure to hydrocarbons. CONCLUSION: The additional 2851 deaths and 322 493 person-years of follow up strengthened the assessment of mortality patterns relative to occupational factors. With the exception of mesothelioma, no clear work related increases in disease were identified.

Canada↗

PubMed1999

Quantifying uncertainty in a risk assessment using human data.

A call for risk assessment approaches that better characterize and quantify uncertainty has been made by the scientific and regulatory community. This paper responds to that call by demonstrating a distributional approach that draws upon human data to derive potency estimates and to identify and quantify important sources of uncertainty. The approach is rooted in the science of decision analysis and employs an influence diagram, a decision tree, probabilistic weights, and a distribution of point estimates of carcinogenic potency. Its results estimate the likelihood of different carcinogenic risks (potencies) for a chemical under a specific scenario. For this exercise, human data on formaldehyde were employed to demonstrate the approach. Sensitivity analyses were performed to determine the relative impact of specific levels and alternatives on the potency distribution. The resulting potency estimates are compared with the results of an exercise using animal data on formaldehyde. The paper demonstrates that distributional risk assessment is readily adapted to situations in which epidemiologic data serve as the basis for potency estimates. Strengths and weaknesses of the distributional approach are discussed. Areas for further application and research are recommended.

Carcinogens↗

PubMed1997

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.

Accidents, Occupational↗

PubMed1996

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.

Algorithms↗

PubMed1996

Determination of leukemogenic benzene exposure concentrations: refined analyses of the Pliofilm cohort.

Biologic data on benzene metabolite doses, cytotoxicity, and genotoxicity often show that these effects do not vary directly with cumulative benzene exposure (i.e., concentration times time, or c x t). To examine the effect of an alternate exposure metric, we analyzed cell-type specific leukemia mortality in Pliofilm workers. The work history of each Pliofilm worker was used to define each worker's maximally exposed job/department combination over time and the associated long-term average concentration associated with the maximally exposed job (LTA-MEJ). Using this measure, in conjunction with four job exposure estimates, we calculated SMRs for groups of workers with increasing LTA-MEJs. The analyses suggest that a critical concentration of benzene exposure must be reached in order for the risk of leukemia or, more specifically, AMML to be expressed. The minimum concentration is between 20 and 60 ppm depending on the exposure estimate and endpoint (all leukemias or AMMLs only). We believe these analyses are a useful adjunct to previous analyses of the Pliofilm data. They suggests that (a) AMML risk is shown only above a critical concentration of benzene exposure, measured as a long-term average and experienced for years, (b) the critical concentration is between 50 and 60 ppm when using a median exposure estimate derived from three previous exposure assessments, and is between 20 and 25 ppm using the lowest exposure estimates, and (c) risks for total leukemia are driven by risks for AMML, suggesting that AMML is the cell type related to benzene exposure.

Benzene↗

PubMed1996

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-Hodgkin's 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-Hodgkin's 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.

Aged↗

PubMed1996

The relationship between low-level benzene exposure and leukemia in Canadian petroleum distribution workers.

This study was conducted to evaluate the relationship between leukemia occurrence and long-term, low-level benzene exposures in petroleum distribution workers. Fourteen cases were identified among a previously studied cohort [Schnatter et al., Environ Health Perspect 101 (Suppl 6):85-89 (1993)]. Four controls per case were selected from the same cohort, controlling for birth year and time at risk. Industrial hygienists estimated workplace exposures for benzene, without knowledge of case-control status. Average benzene concentrations ranged from 0.01 to 6.2 ppm. Company medical records were used to abstract information on other potential confounders such as cigarette smoking. Odds ratios were calculated for several exposure metrics. Conditional logistic regression modeling was used to control for potential confounders. The risk of leukemia was not associated with increasing cumulative exposure to benzene for these exposure levels. Duration of benzene exposure was more closely associated with leukemia risk than other exposure metrics, although results were not statistically significant. A family history of cancer and cigarette smoking were the two strongest risk factors for leukemia, with cumulative benzene exposure showing no additional risk when considered in the same models. This study is consistent with other data in that it was unable to demonstrate a relationship between leukemia and long-term, low-level benzene exposures. The power of the study was limited. Thus, further study on benzene exposures in this concentration range are warranted.

Adult↗

PubMed1994

Colorectal polyp incidence among polypropylene manufacturing workers.

To follow up earlier findings of increased colorectal cancer and polyp risk among a group of Texas polypropylene manufacturing workers, a second company-sponsored colorectal cancer screening program was conducted. Ninety-four (64%) of the 147 male workers negative for polyps in the first screening were rescreened. Age- and examiner-adjusted incidence rate ratios (IRRs) were modestly elevated for polypropylene manufacturing workers compared with patients screened at the same clinic for total (IRR = 1.31; 90% confidence interval [CI] = 0.84 to 2.03) and adenomatous (IRR = 1.80; 90% CI = 0.68 to 4.78) polyps. However, risk of adenomas among the highest exposed group (early term process/mechanical workers: IRR = 1.77; 90% CI = 0.51 to 6.18) was similar to risk in the least-exposed group (engineer/chemist/administrative workers: IRR = 2.02; 90% CI = 0.56 to 7.31). The modest, nonsignificant excesses and the similarity in risk across job categories does not suggest an occupationally related risk, although small numbers and potential biases preclude making definitive conclusions.

Adenocarcinoma↗

PubMed1994

Colorectal cancer incidence among polypropylene manufacturing workers. An update.

This study updates an earlier investigation that found a sixfold excess incidence of colorectal cancer among polypropylene workers for the period January 1960 to September 1985. The study cohort comprised 412 male workers with at least 6 months employment and 10 years latency. For the extended follow-up period (October 1985 to May 1992), the standardized incidence ratio (SIR) based on state comparison rates was slightly elevated and not statistically significant (SIR = 1.5, 95% confidence interval [CI] = 0.5 to 3.5). A 2.3-fold excess was observed among process workers (95% CI = 0.3 to 8.2), but this was based on only two cases. Risk among process/mechanical workers was greater for short-term workers (< 10 years, SIR = 3.2, 95% CI = 0.7 to 9.2) compared with longer-term workers (> or = 10 years, SIR = 0.7, 95% CI = 0.02 to 4.0). Overall, the update findings do not suggest an occupationally related risk. Possible influences of company-sponsored colorectal cancer screening, the polyolefin unit shutdown, and other factors are discussed.

Aged↗

PubMed1993

A retrospective mortality study among Canadian petroleum marketing and distribution workers.

We conducted a retrospective mortality study among 6672 petroleum marketing and distribution workers from 226 locations throughout Canada. These employees worked for at least 1 year in the marketing distribution segment from 1964 through 1983 or were annuitants as of 1964. Industrial hygienists assigned hydrocarbon (HC) exposure frequency scores for several jobs, departments, and job functions. We computed standardized mortality ratios for the total cohort, HC exposure frequency groups, and tank truck drivers, and we also used Poisson regression techniques to model mortality for selected causes of death according to HC exposure frequency. Results indicate overall mortality below that of the general Canadian population for all marketing distribution workers [Standardized mortality ratio (SMR) = 0.88]. Mortality from aortic aneurysms was significantly elevated in all marketing/distribution workers (SMR = 1.79) but was due to raised mortality in nonexposed workers (SMR = 2.80). Tank truck drivers showed significantly elevated mortality due to leukemia (SMR = 3.35) based on five deaths. The leukemia findings were not evident in the larger group of marketing distribution workers classified as exposed to hydrocarbons (SMR = 1.01). No other cause of death was elevated in truck drivers. The leukemia findings are suggestive of a possible influence due to exposure to HCs in tank truck drivers, although other explanations cannot be ruled out. Other findings of elevated mortality in the marketing distribution group are generally not statistically significant. These included moderately increased mortality due to multiple myeloma, malignant melanoma, and kidney cancer. Small numbers of observed and expected deaths limit concise interpretations for these diseases.

Canada↗

PubMed1992

A retrospective mortality study within operating segments of a petroleum company.

This retrospective mortality study was conducted among 34,597 oil industry workers in diverse operating segments. Employees were traced through Statistics Canada, and overall mortality (SMR = 0.85) was lower than general population rates and similar to other petrochemical cohorts. The most notable finding was a significant excess of malignant melanoma [observed deaths (N) = 16, SMR = 1.87, 95% CI = 1.07, 3.04], which concentrated among upstream workers (N = 6, SMR = 6.00, 95% CI = 2.19, 13.06), and was directly related to employment duration and latency. Specific substances or hydrocarbon (HC) streams could not be implicated, although possible explanations include dermal HC exposure, ultraviolet light exposure, or a synergistic effect between these two factors. Marketing/transportation workers showed a non-significant excess of multiple myeloma (SMR = 1.81), which was also related to employment duration, latency, and commencement of employment before 1950. Lymphatic cancer, skin cancer, and kidney cancer mortality was not elevated in refinery workers, a finding at odds with some previous refinery worker studies. Although the malignant melanoma and possibly the multiple myeloma mortality patterns are consistent with an occupational link, further studies are needed to investigate the relationship of these diseases with particular exposures.

Aortic Aneurysm↗

PubMed1991

An update of mortality due to brain neoplasms and other causes among employees of a petrochemical facility.

In an update of an earlier investigation of brain tumors, mortality patterns were examined for 7849 male employees who worked at a petrochemical plant from 1941 through 1983. The update added 6 years of observation (1978 to 1983). During this period, the brain tumor (BT) mortality risk declined relative to the US population, but continued to be higher than expected in hourly workers (5 observed/3.4 expected). Similar to the earlier studies, BT occurrence was not explained by patterns of production work assignments. Mortality rates for hourly and salaried workers from all causes combined, total cancer and respiratory cancer were lower than US population rates. Lower rates for these causes were also seen for white and nonwhite production and maintenance workers. Liver cancer rates were greater than expected in white production workers (3 observed/1.6 expected) and included two men assigned more than 40 years ago to vinyl chloride-related departments. Mortality rates due to malignant melanoma were elevated in white maintenance workers (5 observed/2.0 expected) and may be explained by heavy sun exposure in outdoor work.

Brain Neoplasms↗

PubMed1990

Mortality surveillance in a large chemical company: the Union Carbide Corporation experience, 1974-1983.

The mortality experience of 88,000 Union Carbide Corporation employees from 1974 to 1983 is presented using a population-based surveillance system. The study included many long-term employees, with most deaths contributed by those retired or terminated. The total population exhibited 30% lower mortality overall and 10% lower cancer mortality, as compared with the general U.S. population. Excesses of benign neoplasms and malignant melanoma of the skin were observed in both hourly and salaried males. Mortality rates for lymphosarcoma and reticulosarcoma were significantly elevated due to higher rates among hourly male employees and a cluster in one location. This same location also exhibited an excess of liver cancer associated with vinyl chloride operations. There were no other significant excesses in the hourly male workers and fewer deaths than expected due to brain cancer, respiratory cancer, and nonmalignant respiratory diseases. Salaried, and particularly hourly, women experienced favorable mortality, although for the women, time since hire was relatively short. Location-specific findings were similar to what had been observed in the company's previously conducted cohort studies. Future value lies in the development of a database that will have greater power to address possible effects of past exposures and outcomes related to more recent lower level exposures.

Cause of Death↗

PubMed1987

Population based mortality surveillance in carbon products manufacturing plants.

The utility of a population based, corporate wide mortality surveillance system was evaluated after a 10 year observation period of one of the company's divisions. The subject population, 2219 white male, long term employees from Union Carbide Corporation's carbon based electrode and specialty products operations, was followed up for mortality from 1974 to 1983. External comparisons with the United States male population were supplemented with internal comparisons among subgroups of the study population, defined by broad job categories and time related variables, adjusting for important correlates of the healthy worker effect. Significant deficits of deaths were observed for all causes and the major non-cancer causes of death. The numbers of deaths due to malignant neoplasms and respiratory cancer were less than, but not statistically different from, expected. There was a non-significant excess of deaths from lymphopoietic cancer, occurring predominantly among salaried employees. When specific locations were examined, operations with potential exposure to coal tar products exhibited a mortality pattern similar to that of the total cohort. The risk for lung cancer was significantly raised (five observed, 1.4 expected) in one small, but older, location which did not involve coal tar products during the period of employment of these individuals, but which historically used asbestos materials for several unique applications. Although these findings are limited by small numbers and a short observation period, the population based surveillance strategy has provided valuable information regarding the mortality experience of the population, directions for future research, and the allocation of epidemiological resources.

Carbon↗

PubMed1983

A cohort mortality study of petrochemical workers.

A historical prospective cohort mortality study was conducted for a cohort of 6,588 white male employees of a Texas petrochemical plant because of a suspected increased incidence of malignant brain tumors. Mortality experience from 1941 to 1977 was determined and compared with that of the general U.S. white male population adjusting for age and time period. Overall and cause-specific standardized mortality ratios were calculated for various subgroups of the population defined by length of employment, latency and payroll status. Significant deficits in total cohort mortality were found for all causes of death, all circulatory diseases, all respiratory diseases and all digestive diseases. Although not statistically significant, fewer deaths were observed (O) than expected (E) for all malignant neoplasms. No statistically significant excess of malignant brain tumors was found in the overall plant population (O/E = 12/7.42 = 1.62). A borderline significant excess of brain cancer deaths was found among hourly employees with more than six months' employment based on 10 observed and five expected deaths. This excess was observed to occur among elderly employees (over 55 years) and in later follow-up years (post-1970). Risk did not appear to be related to length of employment. Because of the nature of the problem that prompted this study, the small number of cases involved and the lack of a suspect agent in the plant that could have produced this excess, insufficient evidence was found to conclude that these tumors were occupationally related.

Age Factors↗