Occupational cancer in France: epidemiology, toxicology, prevention, and compensation.

This article is a description of the current situation in France with regard to occupational cancer: research, prevention, and occupation. Toxicologic experiments are carried out using (italic)in vitro(/italic) and (italic)in vivo(/italic) tests, particularly using transgenic mice. Several epidemiologic studies have been conducted over the last decades: population-based case-control studies; mortality studies and cancer incidence studies carried out in historical cohorts of workers employed in the industry; and case-control studies nested in occupational cohorts. French ethical aspects of toxicologic and epidemiologic studies are described. The results thus obtained are used to establish regulations for the prevention and the compensation of cancers attributable to occupational exposure. This French regulation for prevention of occupational cancer involves several partners: (italic)a(/italic)) the states authorities, including labor inspectors, responsible for preparing and implementing the labor legislation and for supervising its application, particularly in the fields of occupational health and safety and working conditions; (italic)b(/italic)) the Social Security Organisation for the analysis of present or potential occupational risks based on tests, visits in plants, complaints or requests from various sources, and statistics. These activities are performed within the framework of the general French policy for the prevention of occupational cancer. This organization includes the National Institute for Research and Safety, particularly involved in research in the various fields of occupational risks--animal toxicology, biologic monitoring, exposure measurements epidemiology, psychology, ergonomy, electronic systems and machineries, exposure to chemicals, noise, heat, vibration, and lighting; and (italic)c(/italic)) companies where the regulation defines the role of the plant manager, the occupational physician, and the Health, Safety and Working Conditions Committee (comprising the manager, employees' representatives, the occupational physician, and the safety department) in dealing with any problem regarding safety, occupational hygiene, and working conditions. These organizations along with medical practitioners are involved with the compensation of occupational cancers. The regulation for compensation includes the tables of occupational cancer, the possibility of recognition of a cancer case when the requirements of the tables are not met, and the postprofessional follow-up of workers exposed to a carcinogenic agent.

Effects of coumarin following perinatal and chronic exposure in Sprague-Dawley rats and CD-1 mice.

Coumarin, a naturally occurring substance most frequently used as a fragrance enhancer and stabilizer, was administered in the diet of Sprague-Dawley rats at dose levels of 0, 333, 1000, 2000, 3000, and 5000 ppm or in the diet of CD-1 mice at dose levels of 0, 300, 1000, or 3000 ppm. Rats receiving 333, 1000, and 2000 ppm coumarin were exposed to these dose levels in utero and during the lactational period, then chronically following weaning. Rats in the 3000- and 5000-ppm dose groups and all mice received only postweaning chronic exposure. All male rats were terminated after 104 weeks of postweaning exposure; female rats were terminated after 110 weeks: Male mice were terminated at Week 101 and female mice at Week 109. Among rats, survival was decreased at 333 ppm, but significantly increased among rats in the 3000- and 5000-ppm dose groups. Dramatic dose-related decreases in body weight gain were recorded for rats receiving 2000, 3000, and 5000 ppm, clearly indicating that the MTD (maximum tolerated dose, as indicated by a body weight decrement of greater than 10-15%) was exceeded. Food consumption also was decreased at the three highest dose levels, although body weight decrement was disproportionately large compared to changes in food consumption. Treatment-related decreases in hemoglobin were recorded from Week 6 onward. Minimal treatment-related changes in hematology and clinical chemistry were recorded. Increased liver weights were observed for male and female rats receiving 3000 or 5000 ppm and for females only at 1000 and 2000 ppm. Increased incidences of cholangiofibroma, cholangiocarcinoma, and parenchymal liver cell tumors were observed among male and female rats receiving 5000 ppm. One male rat receiving 3000 ppm developed a cholangiocarcinoma; no tumor increase was observed in males or females at 2000 ppm or below. Coumarin, at a dose clearly exceeding the MTD can, therefore, induce liver tumors in rats, although survival, relative to controls, was increased at the same dose levels. Among mice, a decrease in body weight gain was reported for males in the 1000- and 3000-ppm dose groups during the first 52 weeks of the study. No dose-related abnormalities in clinical signs, clinical pathology, hematology, or gross or microscopic pathology were noted.