Richard A. Lemen

A dose-response analysis and quantitative assessment of lung cancer risk and occupational cadmium exposure.

We performed a quantitative assessment of the risk of lung cancer from exposure to cadmium based on a retrospective cohort mortality study of cadmium-exposed workers. The study population consisted of white male workers who were employed for at least 6 months at a cadmium smelter between January 1, 1940, and December 31, 1969, and who were first employed at the facility on or after January 1, 1926. The study findings were analyzed using a modified life-table analysis to estimate standardized mortality ratios (SMRs), and various functional forms (i.e., exponential, power, additive relative rate, and linear) of Poisson and Cox proportional hazards models to examine the dose-response relationship. Estimates of working lifetime risk (45 years) were developed using an approach that corrects for competing causes of death. An excess in mortality from lung cancer was observed for the entire cohort (SMR = 149, 95% confidence interval (CI) = 95, 222). Mortality from lung cancer was greatest among non-Hispanic workers (SMR = 211, 95% CI = 131, 323), among workers in the highest cadmium exposure group (SMR = 272, 95% CI = 123, 513), and among workers with 20 or more years since the first exposure (SMR = 161, 95% CI = 100, 248). A statistically significant dose-response relationship was evident in nearly all of the regression models evaluated. Based on our analyses, the lifetime excess lung cancer risk at the current Occupational Safety and Health Administration standard for cadmium fumes of 100 micrograms/m3 is approximately 50 to 111 lung cancer deaths per 1000 workers exposed to cadmium for 45 years.

The Worldwide Pandemic of Asbestos-Related Diseases

BACKGROUND Asbestos-related diseases are still a major public health problem. The World Health Organization (WHO) has estimated that 107,000 people worldwide die each year from mesothelioma, lung cancer, and asbestosis. We review what is known about asbestos use, production, and exposure and asbestos-related diseases in the world today, and we offer predictions for the future. Although worldwide consumption of asbestos has decreased, consumption is increasing in many developing countries. The limited data available suggest that exposures may also be high in developing countries. Mesothelioma is still increasing in most European countries and in Japan but has peaked in the United States and Sweden. Although the epidemic of asbestos-related disease has plateaued or is expected to plateau in most of the developed world, little is known about the epidemic in developing countries. It is obvious that increased asbestos use by these countries will result in an increase in asbestos-related diseases in the future.

Exposure-response analysis of risk of respiratory disease associated with occupational exposure to chrysotile asbestos.

OBJECTIVES: To evaluate alternative models and estimate risk of mortality from lung cancer and asbestosis after occupational exposure to chrysotile asbestos. METHODS: Data were used from a recent update of a cohort mortality study of workers in a South Carolina textile factory. Alternative exposure-response models were evaluated with Poisson regression. A model designed to evaluate evidence of a threshold response was also fitted. Lifetime risks of lung cancer and asbestosis were estimated with an actuarial approach that accounts for competing causes of death. RESULTS: A highly significant exposure-response relation was found for both lung cancer and asbestosis. The exposure-response relation for lung cancer seemed to be linear on a multiplicative scale, which is consistent with previous analyses of lung cancer and exposure to asbestos. In contrast, the exposure-response relation for asbestosis seemed to be nonlinear on a multiplicative scale in this analysis. There was no significant evidence for a threshold in models of either the lung cancer or asbestosis. The excess lifetime risk for white men exposed for 45 years at the recently revised OSHA standard of 0.1 fibre/ml was predicted to be about 5/1000 for lung cancer, and 2/1000 for asbestosis. CONCLUSIONS: This study confirms the findings from previous investigations of a strong exposure-response relation between exposure to chrysotile asbestos and mortality from lung cancer, and asbestosis. The risk estimates for lung cancer derived from this analysis are higher than those derived from other populations exposed to chrysotile asbestos. Possible reasons for this discrepancy are discussed.

MORTALITY PATTERNS AMONG HARD ROCK GOLD MINERS EXPOSED TO AN ASBESTIFORM MINERAL

The first suggestion that asbestos could be a carcinogen was made by Lynch and Smith in 1935,l as they had noticed an association between asbestosis and lung cancer. Since then, all forms of commercial asbestos have repeatedly been shown to be carcinogenic in man, and data from animal studies have corroborated these findings. In 1960 Wagner et al.* reported that pleural and peritoneal mesotheliomas occurred among asbestos miners occupationally exposed to crocidolite in certain areas of South Africa. From 1960 to 1973, studies of anthophyllite miners in Finland by Ki lv i l~oto ,~ M e u ~ m a n , ~ and Meurman et aL5 reported significantly increased proportional mortality from bronchogenic carcinoma. In 1972, Selikoff et ~ 1 . ~ demonstrated a sevenfold excess of lung cancer among insulation workers with 20 or more years since their first exposure to amosite asbestos. In 1973, Wagoner et aL7 reported results of a mortality study of asbestos workers occupationally exposed predominantly to chrysotile and demonstrated significant increases in lung cancer and asbestosis. In 1972, the National Institute for Occupational Safety and Health (NIOSH) recommended an occupational standard for asbestos exposure of 2.0 asbestos fibers greater than 5 pm in length per cubic centimeter of air, as an 8-hr time-weighted average daily concentration.R This standard was recommended with the recognition that it would “prevent asbestosis and more adequately guard against asbestos-induced neoplasms.” In developing this standard, NIOSH recognized the need for additional research due to “the lack of epidemiological studies or clinical reports with supporting environmental data in the exposure range that must be considered” and “the lack of definite information on the biologic response of fibers of different size.’’ Further need for research on possible adverse health effects of occupational and nonoccupational exposures to noncommercial asbestos fibers, and asbestos fibers shorter than 5 pm, was brought out at recent court hearings for a mining company in Minnesota and its disposal of taconite tailingsg Expert testimony

CYTOLOGIC OBSERVATIONS AND CANCER INCIDENCE FOLLOWING EXPOSURE TO BCME

The investigative cycle has now advanced full circle. The carcinogenecity of bis(chloromethyl)ether (BCME), initially discovered in laboratory-animal experiments, spurred occupational epidemiological sputum cytology and cancer-incidence studies which demonstrated the carcinogenicity of BCME in humans. In turn, these observations spurred laboratory investigations into the spontaneous formation of BCME. Subsequently, this spontaneous formation of BCME was demonstrated to occur in select industrial settings. These observations on the carcinogenicity of BCME, first in animals and subsequently in man, strongly support the need for animal testing prior to introduction of agents into the environment.

A retrospective cohort mortality study of a phosphate fertilizer production facility

A retrospective cohort mortality study of phosphate fertilizer production workers was undertaken to determine whether this group is at increased risk of dying from any cause, particularly from lung cancer. A total of 3,199 workers who had ever been employed at one facility were included in this investigation. These workers were followed for vital status ascertainment from their first date of employment up to December 1, 1977, or the date of death, whichever occurred first. Overall, no statistically significant elevations in cause-specific mortality were observed for the entire study population. However, when the analysis was stratified by duration of employment, and length of follow-up, a statistically significant (P less than .05) excess in lung cancer mortality was observed among workers with more than 10 yr of employment and follow-up (standardized mortality ratio = 411). Because of the small number of deaths involved, and because we had prior knowledge of a lung cancer cluster at this plant, we believe that these findings should be viewed as suggestive, and that other investigations in plants with similar exposures are needed to clarify whether an occupationally related lung cancer excess truly exists.

Developments in asbestos cancer risk assessment.

BACKGROUND Efforts have been made for 25 years to develop asbestos risk assessments that provide valid information about workplace and community cancer risks. Mathematical models have been applied to a group of workplace epidemiology studies to describe the relationships between exposure and risk. EPAs most recent proposed method was presented at a public meeting in July 2008. METHODS Risk assessments prepared by USEPA, OSHA, and NIOSH since 1972 were reviewed, along with related literature. RESULTS AND CONCLUSIONS None of the efforts to use statistical models to characterize relative cancer potencies for asbestos fiber types and sizes have been able to overcome limitations of the exposure data. Resulting uncertainties have been so great that these estimates should not be used to drive occupational and environmental health policy. The EPA has now rejected and discontinued work on its proposed methods for estimating potency factors. Future efforts will require new methods and more precise and reliable exposure assessments. However, while there may be genuine need for such work, a more pressing priority with regard to the six regulated forms of asbestos and other asbestiform fibers is to ban their production and use.

A Case Study in Avoiding a Deadly Legacy in Developing Countries

a nation, but to the lives of people in the affected country. The transfer of technology from the industrialized world to the developing world involves many risks. Damage to the health and safety of workers and their families may ultimately be the most severe. Countries experiencing industrialization are changed from agrarian disperse populations to urban convergences, often with resultant poverty, malnutrition, inadequate housing, and related diseases. People who are expected to benefit most by industrialization are often the ones most adversely affected.

Ethics, morality, and conflicting interests: how questionable professional integrity in some scientists supports global corporate influence in public health

Abstract Clinical and public health research, education, and medical practice are vulnerable to influence by corporate interests driven by the for-profit motive. Developments over the last 10 years have shown that transparency and self-reporting of corporate ties do not always mitigate bias. In this article, we provide examples of how sound scientific reasoning and evidence-gathering are undermined through compromised scientific enquiry resulting in misleading science, decision-making, and policy intervention. Various medical disciplines provide reference literature essential for informing public, environmental, and occupational health policy. Published literature impacts clinical and laboratory methods, the validity of respective clinical guidelines, and the development and implementation of public health regulations. Said literature is also used in expert testimony related to resolving tort actions on work-related illnesses and environmental risks. We call for increased sensitivity, full transparency, and the implementation of effective ethical and professional praxis rules at all relevant regulatory levels to rout out inappropriate corporate influence in science. This is needed because influencing the integrity of scientists who engage in such activities cannot be depended upon.

Collegium Ramazzini: Comments on the 2014 Helsinki consensus report on asbestos.

The Collegium Ramazzini is an international scientific society that examines critical issues in occupational and environmental medicine with a view towards action to prevent disease and promote health. The Collegium derives its name from Bernardino Ramazzini, the father of occupational medicine, a professor of medicine of the Universities of Modena and Padua in the late 1600s and the early 1700s. The Collegium is comprised of 180 physicians and scientists from 35 countries, each of whom is elected to membership. The Collegium is independent of commercial interests. TheCollegiumRamazzini recognizes thework of the 2014 expert committee convened by the Finnish Institute of Occupational Health (FIOH) to update the 1997 and 2000 Helsinki criteria onAsbestos, Asbestosis, andCancer in light of newadvances in research.Thepublishedconsensus report of the Helsinki Committee [Wolff et al., 2015] and its more extensive on-line version (Helsinki Criteria Update 2014 Asbestos, Asbestosis, and Cancer) provide a valuable synthesis of many aspects of current knowledge of the hazards of asbestos. The Collegium Ramazzini is, however, very concerned about the sections of the 2014 Helsinki consensus report that discuss criteria for pathological diagnosis of the diseases caused by asbestos. The sections of the Helsinki report dealing with pathology diagnosis are based on a selective reading of the medical literature. They rely overly much on certain published articles [Srebro et al., 1995; Butnor et al., 2003; Roggli et al., 2010] while omitting reference to other important and highly relevant information. They are heavily influenced by the outdated and incorrect concept that analysis of lung tissue for asbestos fibers and asbestos bodies can provide data to contradict exposures that are documented in a reliable occupational history. Further, without any explanation the most accepted College of American Pathologists (CAP)-NIOSH 1982 asbestos definition which underwent extensive review and endorsement by NIOSH is now replaced in the 2014 Helsinki criteria by the more restrictive CAP/Pulmonary Pathology Society (PPS) modification which differs especially in the early histological stages of asbestosis and in the higher numbers of asbestos bodies needed to make the pathological diagnosis of asbestosis [Hammar and Abraham, 2015]. Applying the 2014 Helsinki report recommendations on pathology diagnosis will lead to: