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A 4-week toxicity study of methionine in male rats
Keigi Chin1, Sakino Toue1, Yasuko Kawamata1
1Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan.
Abstract:
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.
Insights
High methionine intake in rats caused growth suppression and anemia. The no-observed-adverse-effect-level (NOAEL) for added methionine was 0.3%, with a lowest-observed-adverse-effect level (LOAEL) of 0.9%.
Area of Science:
- Toxicology
- Nutritional Science
- Animal Studies
Background:
- Methionine is an essential amino acid crucial for various physiological functions.
- Understanding methionine's toxicity is vital for establishing safe dietary levels in animal nutrition and human health.
- Previous research has indicated potential adverse effects of excessive methionine supplementation.
Purpose of the Study:
- To determine the toxicological profile of L-methionine (methionine) in male rats over a 4-week period.
- To establish the no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) for added methionine in the diet.
- To assess the impact of varying methionine doses on growth, hematology, and organ histology.
Main Methods:
- Male Fisher strain rats (5 weeks old) were fed diets with 0, 0.1, 0.3, 0.9, or 2.7% (w/w) added methionine for 4 weeks.
- Body weight, food intake, hematological parameters, and plasma biochemistry were monitored.
- Histopathological examination of spleens, livers, thymus, adrenal glands, and testes was performed.
Main Results:
- The highest dose (2.7% added methionine) significantly reduced food intake and growth rate, causing hemolytic anemia, hemosiderin accumulation, and stimulated hematopoiesis.
- This high dose also led to decreased white blood cell count, thymus atrophy, and adrenal/testicular abnormalities.
- A dose of 0.9% added methionine caused minor growth suppression and slight changes in plasma biochemistry.
Conclusions:
- The NOAEL for added methionine was determined to be 0.3% (w/w) of the diet, and the LOAEL was 0.9% (w/w).
- These levels correspond to 236 mg/kg/day and 705 mg/kg/day body weight, respectively.
- The estimated NOAEL and LOAEL for total dietary methionine were 0.8% and 1.4% (w/w), considering the basal diet's protein-bound methionine.
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