Benzene and aplastic anaemia

Le Noire & Claude reported the first case of benzene-associated leukemia in humans . Further demonstration of the toxic effects of benzene in humans and animal models was provided by Selling in 1916 and Weiskotten in 1916 and 1920 .Selling described how benzene attacked the entire blood- forming system, which he ascribed to aplasia induction, and stressed its leucopenic effects . Some physicians were inspired by the leucopenic effects of benzene to use it for the treatment ofleukaemia. Koranyi gave patients an oral dose of 3-5 g benzene daily and although the patients initially improved, they later developed fatal aplastic anaemia . In the US, Rochner et al. used benzene to treat chronic myeloid leukemia, but again reported problems with haematotoxicity.

In the 1950s and 1960s, further cases of benzene- induced aplastic anaemia were reported throughout the world. In 1956, Savilahti described haematological abnormalities in 107 of 147 Finnish shoe factory workers; concentrations of benzene in this factory were as high as 400 p.p.m. Persistent cytopenias were observed in a follow-up study of these workers performed by Hernberg et al. In 1960 in Japan, Hirokawa reported that 50% of the employees in factories utilizing benzene exhib- ited haematological abnormalities and cases of aplastic anaemia were described . Further, organic solvents were suspected as a causative factor in producing 612% of the aplastic anaemia.

  A nationwide investigation of benzene poisoning was performed in China for workers exposed between 1972 and 1987. It was found that in small factories, especially in the shoe manufactur- ing industry, the incidence of aplastic anaemia in workers exposed to benzene was 5.8 times that in the general population . In a study of 222 workers involved in the production of shoes, 35 individuals developed benzene-related haemato- logical abnormalities in approximately 6 months, with 4 of them developing aplastic anaemia . Exposure levels for these workers were believed to be in the range 50-350 p.p.m. 

 Dose response :

The central premise of modern toxicology is that the dose makes the poison. Although the exposure data available on many of the historical studies of benzene toxicity in humans is sparse, it does provide an approximation of the doses required to produce benzene-induced aplastic anemia. In patients with leukemia and very heavily exposed benzene workers receiving gram quantities of benzene on a daily basis, it appears that aplastic anaemia or pancytopenia may be produced in more than 1 in 10 individuals. In individuals receiving hundreds of milligrams of benzene per day, this incidence decreases to approximately 1 in 100. The ability of benzene to produce aplastic anemia then appears to drop precipitously in workers exposed to lower doses; however, cases of aplastic anaemia are still observe. 

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