Regulatory toxicity and safety profiling of N-acetyl-L-tryptophan with special emphasis on genotoxicity and male reproductive toxicity via intramuscular route of administration.

The present study was performed to evaluate N-acetyl-L-tryptophan (L-NAT) single-dose acute toxicity in Swiss albino mice and Sprague Dawley rats and 14-day repeated dose toxicity using Swiss albino mice and New Zealand white rabbit models. Genotoxic profiling of L-NAT was established using the AMES, human lymphocyte chromosome dicentric, and human erythrocyte micronuclei assays. The male reproductive toxicity of L-NAT was determined using the rat model. All studies were performed following the OECD guidelines in a GLP-compliant facility. The intramuscular administration of L-NAT as a single dose ≥1500 mg/kg b.wt, in Swiss albino mice and Sprague Dawley rats was observed as 'No-Observed Adverse Effect Level (NOAEL).' Similarly, 14-day repeated dose L-NAT administration (im) up to 1000 mg/kg b.wt in males and females Swiss-albino mice, and up to 750 mg/kg b.wt (im) in New Zealand white rabbits (males and females) was found to be the NOAEL dose. Furthermore, L-NAT treatment to Salmonella typhimurium strains (up to 1.25 mg/plate), human lymphocytes (up to 1.25 mg/plate), and mice (up to 750 mg/kg b.wt) did not demonstrate any observable genotoxicity in terms of mutagenesis, chromosomal aberration, and erythrocyte micronuclei induction, respectively. No significant male reproductive toxicity was evident in the rats in terms of sperm motility, counts, and morphology, seminiferous tubules cellularity, sex organs' absolute and relative weights, and reproductive performance after L-NAT daily dosing up to 600 mg/kg b.wt, for 10 weeks. In view of the above observations, L-NAT may be considered safe and non-toxic within the concentration range used in the present study.