Prevention of Risks from Occupational Exposures to Antineoplastic Drugs: Consensus Document.

Ever-increasing numbers of cancer patients have been treated with antineoplastic drugs in the past few years. Among patients treated with these drugs, an increased risk of a "second neoplasm" has been observed, mainly as a function of increased life expectancy. On the basis of this observation, the International Agency for Research on Cancer has classified a number of antineoplastic drugs as carcinogenic or probably carcinogenic for humans. Various categories of workers are at risk for exposure to antineoplastic drugs, absorbing these substances mainly through inhalation or dermal contact. Although the absorbed doses are notably lower than those administered to patients, review of the literature reveals increased risks of spontaneous abortions and chromosomal aberrations in subjects who have worked without adequate protection. A working group, Prevention of Occupational Risks Due to Handling Antineoplastic Drugs in Health Care, was established by the Italian Institute of Prevention and Safety at Work (Istituto Superiore per la Prevenzione e Sicurezza sul Lavoro-ISPESL) in February 1995. This group reviewed the epidemiologic studies and research on cytogenetic indicators of genotoxicity in occupationally exposed subjects. In addition, the group made recommendations for environmental and biological monitoring of exposure and health surveillance, and developed guidelines for primary and secondary prevention. The group's recommendations are summarized in a consensus document, but cannot be considered definitive, since work practices continue to evolve and will have to be examined further in the future. Thus, more research is needed to achieve answers to the questions raised by the working group. The main topics to be addressed are indicated in the consensus document. In particular, it will be necessary to evaluate working conditions nationwide, using standardized protocols for risk assessment, to achieve precise estimates of workers' exposures.

Solubilization of lead from crystal dust in protein solution (pseudointerstitial fluid) and gastric juice.

Since several workers engaged in polishing and engraving crystal articles were found to have higher than average blood levels of lead (560 micrograms/liter, range 80-560 micrograms/liter), we investigated the hypothesis that crystal dust releases lead in the human body. To test the hypothesis, two types of crystal polishing dusts, having different lead contents, were mixed with human serum diluted 1:3 (pseudointerstitial fluid), gastric juice, and phosphate buffer at pH 9. After 14 days of contact, the diluted serum had extracted 0.620% of the lead in the crystal dust (particle size < 20 microns) containing 25.2% lead and 0.425% of that containing 19.9% lead. After 48 hr in gastric juice, 0.235 and 0.556% of the lead was extracted from crystal dusts (unsieved crystal dusts) containing 25.2 and 19.9% lead, respectively. After 28 days in alkaline solution, 0.358 and 0.304% of the lead was extracted respectively from the same two crystal dusts (unsieved crystal dusts).

Toxicity of fungicides containing ethylene-bis-dithiocarbamate in serumless dissociated mesencephalic-striatal primary coculture.

Agricultural exposure to the organomanganese fungicide MANEB (manganese-ethylene-bis-dithiocarbamate) may induce an extrapyramidal syndrome resembling parkinsonism. To evaluate the relative role of manganese (Mn) and ethylene-bis-dithiocarbamate (EBDTC) in the hazard of organomanganese fungicides, we studied the effects of MANCOZEB (Mn-Zinc-EBDTC) and ZINEB (Zinc-EBDTC) on serumless dissociated mesencephalic-striatal primary coculture. High affinity 3H-dopamine (DA) and 14C GABA uptakes as well as immunocytochemical staining of tyrosine hydroxylase (TH)-containing cells were used as specific functional markers of DA and GABA neuron viability. Both MANCOZEB and ZINEB, at 10 and 50 microM concentrations, dose dependently reduced DA and GABA viability parameters. These data suggest that EBDTC rather than Mn may be primarily responsible for the cytotoxicity of organomanganese fungicides on neuronal systems relevant to the pathophysiology of parkinsonism.