A 4-week toxicity study of methionine in male rats.
To examine 4-week toxicity of l-methionine (methionine), 5-week-old Fisher strain male rats were fed on diets containing 0, 0.1, 0.3, 0.9, 2.7 (w/w) of added methionine. Although no deaths were recorded, the highest dose of methionine (2.7% [w/w] of diet) reduced food intake and significantly suppressed growth rate. Growth suppression was characterized by an increase in hemolysis, splenic, and hepatic accumulation of hemosiderin, hemolytic anemia, and promotion of hematopoiesis. Other changes observed in the highest methionine intake group were a decrease in white blood cell count, thymus atrophy, and histological abnormalities in the adrenal gland and testis. Small, but significant, growth suppression, accompanied by some minor changes in plasma biochemical parameters, was also seen in rats fed on a test diet containing 0.9% (w/w) of additional methionine. Thus, no-observed-adverse-effect-level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) of diet-added methionine were determined at 0.3% and 0.9% (w/w), corresponding to 236 and 705 mg/kg/d body weight, respectively. Since the basal diet contained protein-bound methionine at 0.5% (w/w), NOAEL and LOAEL of total dietary methionine were estimated at 0.8% and 1.4% (w/w) of diet.
Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan.
Keigi
K
Chin
Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan.
Sakino
S
Toue
Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan.
Yasuko
Y
Kawamata
Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan.
Akiko
A
Watanabe
Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan.
Tadashi
T
Miwa
Quality Assurance & External Scientific Affairs Dept., Ajinomoto Co., Inc., Tokyo, Japan.
Miro
M
Smriga
Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan ryosei_sakai@ajinomoto.com.
Ryosei
R
Sakai
D000311:Adrenal Glands / Q000378:metabolism / Q000473:pathology; D000743:Anemia, Hemolytic / Q000209:etiology; D000821:Animal Feed / Q000009:adverse effects*; D000818:Animals; D000855:Anorexia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D019587:Dietary Supplements / Q000009:adverse effects*; D006130:Growth Disorders / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006486:Hemosiderosis / Q000209:etiology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008715:Methionine / Q000506:poisoning*; D019055:No-Observed-Adverse-Effect Level; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D011916:Rats, Inbred F344; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D013249:Sternum; D013737:Testis / Q000378:metabolism / Q000473:pathology; D059551:Toxicity Tests, Subacute
D008715:Methionine
LOAEL; NOAEL; methionine; safety