Phosphine is an important fumigant in the grain industry and has been reported to be genotoxic in occupationally exposed fumigators. This study reports on the effects of phosphine inhalation exposure at up to, and exceeding, occupational relevant levels in a subchronic (0.3, 1.0 and 4.5 ppm, 13 weeks) and a short term repeated-dose (5.5 ppm, 2 weeks) study in both sexes of Balb-c mice. The following end-points were examined: micronucleus induction in bone marrow, peripheral blood, spleen lymphocytes and skin keratinocytes, mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in lymphocytes, and weight gain and relative organ weights (kidneys, lungs, liver, heart, brain and spleen). After subchronic exposure, there was a highly significant negative linear correlation between proportional weight gain and exposure in both sexes (multiple linear regression, r = -0.56, P < 0.0001), with female mice showing a greater effect. Females also showed an increase in relative organ weights at the highest test dose, in contrast to males where there was a slight decrease. A statistically significant increase in micronucleus frequency was seen in the bone marrow and spleen lymphocytes of both sexes, but only at the highest concentration. The short term repeated-dose study revealed a slight decrease in weight gain in both sexes, with a greater effect in females. It is concluded that phosphine is weakly genotoxic in both sexes of mice, and has an effect on weight gain. However, the weak genotoxic effect may not be biologically significant as it was seen only in the subchronic study and only at the highest test concentration of 4.5 +/- 0.8 ppm (approaching the LD50). Although such exposure conditions are unlikely to be encountered in an occupational environment, caution should continue to be exercised in the use of phosphine until more data become available.

Phosphine has been claimed to cause chromosomal damage at exposures close to the current time weighted average exposure standard of 0'3 ppm (0.4 mg/m3). The current study involved 31 phosphine fumigators and 21 controls during the high fumigation season. All were volunteers and were evaluated for genotoxicity variables, including micronuclei in peripheral blood lymphocytes and urine mutagenicity. In parallel, all fumigators and 17 controls were evaluated--for full haematology, multiple biochemical analysis, whole blood organochlorines, and whole blood and serum cholinesterase activity. The results for-micronuclei showed no significant differences between fumigators and controls, but detected a strong association between age and increased frequency of micronuclei. Measurement of urine mutagenicity did not show any significant difference between fumigators and controls, but did show increased excretion of mutagens in smokers. All haematological and biochemical variables were within normal ranges, except for some nonspecific changes in biochemistry. At monitored occupational exposures of < 2-4 ppm/h our results show no association between phosphine exposure and genotoxic or toxicological effects in fiunigators. (Occup Environ Med 1994;51:700-705)

RESUMO -As drogas citostáticas são substâncias citotóxicas destinadas a causar disfun são celular. Seu mecanismo de ação envolve interação com DNA, RNA na sfntese protei ca de células vivas, normais ou cancerosas. São também atribufdos a elas um potencial para mutagenicidade, carcinogenicidade, assim como efeitos teratogênicos. Alguns tra balhadores hospitalares estão potencialmente expostos a essas drogas. Propõe-se reco mendações para minimizar os riscos ocupacionais causados pelas mesmas, apresentan do algumas medidas de controle relativamente simples, de forma a adequarem-se à reali dade da maioria dos hospitais brasileiros.ABSTRACT -The cytostatic drugs are cytostatoxic substances and c' 3signed to cause cell dysfunction. Their mechanism of action involves interaction with DNA, RNA on pro tein synthesis in living cells, normal or cancerous. Though these actions the potencial for mutagenic, carcinogenic or teratogenic effects are possible. Some' people who work in hospital are frequentely exposed to these drugs. Recomended have done to minimized the occupational risks that produced by then, some forms to control a little simple are showed to adapt to reality of the majority of Brasilian hospital.