There are species differences in the metabolism of the intermediate, epoxybutene, which is hydrolysed faster to diols in man and glutathione conjugation occurs more quickly in rodents than in man. In vitro studies of diepoxybutane-induced genetic changes in human lymphocytes have shown increased sensitivity with the GSTT1 null genotype. Work on genetic changes in the lymphocytes of workers exposed to 1,3-butadiene is a newly developing research area. The Panel asked whether metabolism occurred anywhere other than the liver and whether there were differences between species and individuals. Dr Shuker noted that the active form could be found bound to haemoglobin, forming adducts.
Mice form the reactive intermediates ten times faster than rats and man.
Man seems to be closer to the rat in terms of effects. It was agreed the Secretariat would find out whether lymphomas occurred in mice or rats . It was noted that it would be important to understand the toxicology and metabolism of 1,3-butadiene. There have been some observations of 1,3-butadiene metabolism in humans at ppm levels. The Chairman thanked Dr Shuker and introduced the epidemiological papers that had been circulated prior to the meeting.