富马酸二甲酯慢性毒性与致癌性研究

给４４０只Ｗｉｓｔａｒ大鼠喂饲含０、１２５、２５０、５００及１０００ｐｐｍ富马酸二甲酯（ＤＩＭＥＦＵ）的饲料２４个月。实验结果，各实验组与对照组相比，食物利用率、掺入量、生长、一般表现、列亡率及平均寿命均无显著性差异。血液学检查仅个别指标出现差别，但波动在正常范围。１０００ｐｐｍ组动物血清ＧＰＴ、ＧＯＴ及肝、肾脏器系数呈现持续性改变。病理组织学检查表明各组非肿瘤性及肿瘤性病变发生率与饲料中ＤＩＭＥ

CHRONIC TOXICITY AND CARCINOGENICITY STUDY ON DIMETHYL FUMARATE IN RATS

Groups of 44 male and 44 female Wistar rats were given foods containing dimethyl fumarate (DIMEFU) at 0,125,250,500 or 1000 ppm for 2yr.Six rats from each group were necropsied for haematological,clinical biochemical tests and histopathological examination after 6,12 and 24 months.Growth rate,food utilization and consumption,general appearance and mortality were same in treated and control groups.The mean lifespan of rats given DIMEFU was not significantly different to that of controls.No treatment-related effect was observed in haematological indexes at any stage of the study.At 12 and 24 months,serum level of glutamic-pyruvic transaminase and glutamic-oxalacetic transaminase in high dose groups (1000 ppm and sometimes 500 ppm) were significantly higher than the controls.The incidence and severity of non-neoplastic and neoplastic growth were unrelevant to the level of DIMEFU in the feed. The maximum no-observed-effect level of DIMEFU was 250 ppm,and an acceptable daily intake of DIMEFU for humans of 0.25mg/kg body weight/day is suggested.