Safety assessment of gamma-glutamylcysteine sodium salt.
γ-Glutamylcysteine (GGC) is a relatively unexplored option for the treatment of chronic glutathione depletion related disorders that involve down regulation of GGC synthetase. High purity GGC (sodium salt) has only recently become available and, given its reactive capacity, required an investigation of its safety profile. In this report, GGC sodium salt was demonstrated to be safe according to Organisation for Economic Cooperation and Development (OECD) toxicology protocols for acute and repeated doses. No mortalities or adverse effects were observed in Wistar rats following the acute oral (gavage) administration of 2000mg sodium GGC /kg body weight. No animal deaths occurred with daily administration (1000mg/kg sodium GGC) over 90days, with a post trial 28day observation period. GGC had no significant effect on feed consumption, body weights, physical appearance, neurological behaviour and urine chemistry. No consistent significant differences between treatment groups were observed in haematological and clinical chemistry parameters. Similarly, no post-mortem necroscopically identified abnormalities could be attributed to GGC. Based on these observations, sodium GGC can be classed as not acutely toxic at 2000mg/kg, with a no-observed-adverse-effect level (NOAEL) of at least 1000mg/kg/day for systemic toxicology from repeated dose oral gavage administration.
Biospecialties International P/L, 57 Tourle St., Mayfield, NSW, Australia.
S D
SD
Chandler
M H
MH
Zarka
S N
SN
Vinaya Babu
Y S
YS
Suhas
K R
KR
Raghunatha Reddy
W J
WJ
Bridge
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000633:toxicity*; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D004151:Dipeptides / Q000008:administration & dosage / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D005260:Female; D006403:Hematologic Tests; D008136:Longevity / Q000187:drug effects; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D017208:Rats, Wistar; D018570:Risk Assessment; D018675:Toxicity Tests; D015430:Weight Gain
D000975:Antioxidants; D004151:Dipeptides; C017341:gamma-glutamylcysteine