Restrospective case-control study of cancer incidence associated with vanadium pentoxide exposure in the mineral processing industry

Abstract

Background Vanadium is an economically important mineral that is mined and processed at several international locations, including South Africa and the USA. Vanadium exists in several oxidative states, of which the pentavalent compounds are usually the most toxic. Vanadium pentoxide (V205) is pentavalent and is generated during various processing and metal alloy manufacturing processes. Occupational exposure may occur via inhalation of V205 fumes and particles, resulting primarily in adverse effects to the respiratory system. Currently, there is no evidence that vanadium is carcinogenic in humans, and it has never been reported in exposed humans. The International Agency for Research in Cancer (IARC) has classified V205 as possibly carcinogenic to humans, based on the increased incidence of bronchiolo-alveolar neo¬plasms observed in male and female mice and male rats in a study by the National Toxicology Program (NTP) of the US Department of Health and Human Services. The NTP study has prompted the international vanadium industry, embodied by Vanitec, the international association of vanadium producers, to request an epidemiological study with the aim of determining the potential association between cancer and occupational V205 exposure. Aim The aim of the study was to conduct a pilot retrospective case-control study to investigate the relationship between cumulative occupational exposure to V2O5 and the risk of developing cancer at two representative vanadium processing plants, one in SA and one in the USA. Methods All cases and controls were sourced from the industry’s current and past employee corps. Employees that could potentially have been exposed to V2O5 in the workplace for a period of at least 5 years were included in the study. Ethics approval for the study was obtained from the Ethics Committee of the University of Pretoria. Participation was on a voluntary basis, and all potentially eligible current workers were invited to participate. As many retirees and former employees as possible were traced and invited to participate, and eligible deceased employees that conformed to the inclusion and exclusion criteria were identified from lists provided by the companies involved. Potential participants were asked to grant informed consent to participate in the study. Health and lifestyle information, information on fuel use in the family home, and a personal job history were obtained by use of a structured questionnaire during a personal interview with a trained interviewer. Interviews were conducted from April to July 2004. The main inclusion criterion for both cases and controls was current or previous employment at the South African, or the USA vanadium processing facility included in the study. The disease case definition was histologically confirmed cancer. Exclusion criteria were: refusal of interview; less than 5 years in employment when V2O5 was produced at the plant; cause of death not ascertained, employment elsewhere in the vanadium industry, and exposure to a known carcinogenic agent during a period of employment elsewhere. Males and females were included and participants were not excluded on the basis of race or ethnicity. Employees of all ages were eligible. Exposure assessment at both plants was based on recorded V2O5 concentrations in personal air samples, the participant’s job history, the history of vanadium processing, the physical structure and work organisation at the processing plants. Historical V2O5 concentrations in air in the workplace were retrospectively estimated for those periods during which personal air sampling was not conducted. Historical concentrations were estimated by extrapolation from current (known) air concentrations, in conjunction with data on annual production volumes, personal experiences of occupational hygienists and plant managers at the plant, and historical records of plant upgrades, controls on emissions, changes in production processes and industrial incidents and accidents, where available at the plants. Exposure was expressed as the cumulative exposure (mg-years/m3) and the mean air concentration (mg/m3) of V2O5 to which participants had been exposed. Study participants were also classified into exposure categories based on their mean exposure concentrations. Results In total, 196 questionnaires were collected from eligible participants. The majority (94.4 per cent) were males. Smoking and the consumption of alcohol was fairly common amongst the study group, with 61 per cent of the participants being current or previous smokers, and 59.5 per cent indicating that they were drinking alcoholic drinks or beverages. The mean age (± SD) of the study group was 52.4 ± 10.2. The annual mean exposure of the study group during the period of employment was 0.02 ± 0.03 mg/m3 V2O5, and the mean cumulative exposure to V2O5 was 0.17 ± 0.46 mg-years/m3. Four (4) cancer cases were confirmed at the South African plant, and 6 at the USA plant: four adenocarcinomas (three each in the prostate and one in the colon); three squamous cell carcinomas (two each in the lung and one skin cancer); one renal cell cancer of the kidney, one seminoma of the testis, and one papillary urothelial cancer of the bladder. The occurrence of prostate and lung cancers were not unusual, giving the presence of risk factors such as relatively advanced age (for prostate cancer) and smoking (for lung cancer). The other types of cancer, and the ages at which cancer was most frequently diagnosed (the mean age at diagnosis of cancer was 58.5) were not remarkably different from those that were prominent in the cancer literature. An unusual cluster of specific types of cancer, or of any prominent and unusual organ involvement not associated with known non-occupational risk factors, was therefore not found in the case group. Conclusion The results of this study fail to indicate a statistically significant association between cancer and various indices of exposure to vanadium pentoxide. This conclusion is subject to a number of limitations and uncertainties arising from the small number of cases available for study, and limited follow-up of some participants. The potential association between exposure and cancer should be tested in a larger study group with more cancer cases, allowing more powerful statistical analyses, ideally multivariate logistic regression analysis. The study has confirmed the feasibility of the retrospective assessment of exposure to vanadium compounds in the vanadium processing industry, providing that the processing plant history covers detail of processing methodologies, physical structures, production volumes and work organisation, and providing that a detailed job history should be available for all potential participants. Confirmation of the cause of death and cancer status of previous employees was not practical in the South African scenario. An open case-control design nested in a prospective cohort should be more successful in the South African scenario, but also more expensive and results will only be available after an extended follow-up period. In the USA scenario tracing of previous employees, and access to cancer registries and death certificates should be more practical, and a retrospective case-control study should be possible. Copyright