Sherry G. Selevan

A Study of Occupational Exposure to Antineoplastic Drugs and Fetal Loss in Nurses

In a case--control study, we examined the relation between fetal loss and occupational exposure to antineoplastic drugs in nurses in 17 Finnish hospitals. The pregnancies studied occurred in 1973 through 1980 and were identified using three national sources: the Central Register of Health Care Personnel, the Hospital Discharge Registry, and policlinic data. Each nurse with fetal loss was matched with three nurses who gave birth. Data on health and exposure were obtained by self-administered, mailed questionnaires; a response rate of 87 per cent was achieved after three mailings. A statistically significant association was observed between fetal loss and occupational exposure to antineoplastic drugs during the first trimester of pregnancy: odds ratio = 2.30 (95 per cent confidence interval, 1.20 to 4.39). Analyses suggested associations between fetal loss and cyclophosphamide, doxorubicin, and vincristine, although the independent effect of each individual drug could not be specifically identified, since many nurses reported handling more than one of these agents. The results of this study, combined with existing data on animals and human beings, suggest that caution be exercised in the handling of these valuable drugs.

The mortality of lead smelter workers: an update

OBJECTIVES Mortality studies of lead workers have shown excesses of nonmalignant renal disease and cerebrovascular disease. Animal studies and one human study have shown excess kidney cancer. We have updated a mortality study of male lead smelter workers (n = 1990). METHODS An analysis was conducted using standard life table techniques. The updated analysis added 11 years of follow-up and 363 new deaths. RESULTS The original study had found elevated but nonsignificant risks for kidney cancer, stroke, and nonmalignant renal disease, probably attributable to lead exposure. Deaths from accidents and nonmalignant respiratory disease were significantly elevated, but probably not as a result of lead exposure. In the updated study, no new deaths from nonmalignant renal disease occurred (9 observed, standardized mortality ratio = 1.21). Three more deaths from kidney cancer were observed, yielding a standardized mortality ratio of 1.93 (9 observed, 95% CI = 0.88, 3.67), which increased for those who had worked in areas with the highest lead exposure (8 observed, standardized mortality ratio = 2.39, 95% CI = 1.03, 4.71). Cerebrovascular disease remained elevated for those with more than 20 years of exposure (26 observed, standardized mortality ratio = 1.41, 95% CI = 0.92, 2.07). CONCLUSIONS This cohort with high lead exposure showed a diminishing excess of death from nonmalignant renal disease, a continued excess from kidney cancer, and an excess of cerebrovascular disease only in those with longest exposure to lead.

Overview of a Workshop on Quantitative Models for Developmental Toxicity Risk Assessment

A workshop was held to discuss potential advancements to improve the precision of risk estimates for developmental toxicity. This paper presents an overview of the discussions at the workshop, focusing on the risk assessment process and science policy considerations important in the use of quantitative models. Some of the pertient biological considerations are reviewed, particularly those related to the repair capacity of the developing organism and how this affects the concept of a threshold for developmental toxicity effects, as well as the maternal and litter influences on developmental toxicity outcomes. Finally, the current status of use of quantitative approaches is described, possible short-term approaches are discussed, and future research needs in this area are outlined.