Long-term toxicity/carcinogenicity study of L-histidine monohydrochloride in F344 rats.
The long-term toxicity and carcinogenicity of histidine, an essential amino acid for most animal species, were examined in Fischer 344 (F344) rats. Groups of 50 males and 50 females were given L-histidine monohydrochloride (HMHC) in their diet at concentrations of 0 (control), 1.25 and 2.5% for 104 wk; these dose levels were selected on the basis of the results of a subchronic toxicity study, in which body weights were depressed and formation of sperm granulomas in the epididymis was histologically evident in males fed 5.0% HMHC. All surviving rats were killed at wk 107. Increases in red blood cell count, haemoglobin value and haematocrit level were observed in male rats given 2.5% HMHC. A variety of tumours developed in all groups, including the control group, but all the neoplastic lesions were histologically similar to those known to occur spontaneously in this strain of rats, and no statistically significant increase in the incidence of any tumor was found in the treated groups of either sex. Thus, it was concluded that, under the present experimental conditions, HMHC is not carcinogenic in F344 rats.
Ikezaki
S
S
Division of Pathology, National Institute of Health Science, Tokyo, Japan.
Nishikawa
A
A
Furukawa
F
F
Enami
T
T
Mitsui
M
M
Tanakamaru
Z
Z
Kim
H C
HC
Lee
I S
IS
Imazawa
T
T
Takahashi
M
M
D000284:Administration, Oral; D000311:Adrenal Glands / Q000187:drug effects / Q000254:growth & development; D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D006639:Histidine / Q000008:administration & dosage / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000254:growth & development; D008297:Male; D009369:Neoplasms / Q000139:chemically induced; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D013047:Specific Pathogen-Free Organisms; D015430:Weight Gain / Q000187:drug effects
D006639:Histidine