Four-week oral toxicity study of three metabolites of nitrobenzene in rats.
Our previous studies have shown that major metabolites of nitrobenzene in bovine and fowl were p-nitrophenol, p-aminophenol, and p-nitroaniline. There are few reports about the subacute toxicity of the three metabolites. The aim of this study was to investigate the subacute toxicity of these compounds. A suspension containing three metabolites at 50, 25, and 5 mg kg(-1) body weight was administrated introgastrically to Sprague-Dawley rats of both sexes for 4 weeks. All four groups survived to the end of the 4-week treatment period. Compared to the control group, there was a significant difference in body-weight increases in rats administered nitrobenzene metabolites at 50 and 25 mg kg(-1) (P < 0.01). ALT, AST, ALP, T-CHO, TP, albumin, and creatinine were significantly increased in the 50-mg kg(-1) group and tended to increase in the 25-mg kg(-1) group, compared with controls. There was no significant difference in glucose between treatment groups and controls. RBC counts and concentration of Hb decreased significantly in the 50- and 25-mg kg(-1) groups, compared with controls, whereas WBC and Ret counts increased in the 50- and 25-mg kg(-1) groups and LYM only in the 50-mg kg(-1) group. There were no significant differences in MONO and neutrophil counts, compared with controls. Methemoglobin concentrations were significantly increased on day 21 of treatment in the 50-mg kg(-1) group and on day 28 in the 25- and 50-mg kg(-1) groups. The subacute toxicity was characterized by lesions affecting the liver, kidneys, spleen, cerebellum, and hematopoietic system.
Wang
Guixia
G
College of Veterinary Medicine, Northeast Agriculture University, Harbin, China.
Zhang
Xiuying
X
Yao
Chunzhu
C
Tian
Meizhan
M
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000627:Aminophenols / Q000633:toxicity*; D000814:Aniline Compounds / Q000633:toxicity*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D008297:Male; D008706:Methemoglobin / Q000378:metabolism; D009578:Nitrobenzenes / Q000378:metabolism; D009596:Nitrophenols / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism
D000627:Aminophenols; D000814:Aniline Compounds; D009578:Nitrobenzenes; D009596:Nitrophenols; D012709:Serum Albumin; C019498:4-nitroaniline; D008706:Methemoglobin; D002784:Cholesterol; D003404:Creatinine; C036077:nitrobenzene; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; C026729:4-aminophenol; C024836:4-nitrophenol