NTA and Fe(III)NTA: differential patterns of renal toxicity in subchronic studies.
Differential patterns in terms of nephropathology and 8-hydroxyguanine formation in the course of oral 28-day studies were observed with nitrilotriacetic acid (NTA) and FeNTA. FeNTA, but not NTA, caused enhanced 8-hydroxyguanine formation in kidney DNA after oral and intraperitoneal administration. Enhanced lipid peroxidation in the kidney homogenate was observed with FeNTA as well as with NTA. For NTA, the low dose (9 mg/kg per day) was without adverse effect. The kidney toxicity of oral FeNTA (50, 200, and 1000 mg/kg per day) was only mild, 50 mg/kg per day; however, it still led to an increased 8-hydroxyguanine content. The relevance of Iron(III) (Fe(III)) or Fe(III)NTA formation as a relevant mediator of NTA-related toxicity was excluded on the basis of these data. Also, a thermodynamic consideration presented here, supports the view that zinc (Zn), and not Fe, is likely to mediate the tubular cell cytotoxicity of NTA.
Leibold
E
E
Department of Product Safety, Regulations, Toxicology and Ecology of BASF Aktiengesellschaft, Ludwigshafen, Germany.
Deckardt
K
K
Mellert
W
W
Potthoff-Karl
B
B
Grundler
O
O
Jäckh
R
R
D000284:Administration, Oral; D000818:Animals; D002614:Chelating Agents / Q000008:administration & dosage / Q000633:toxicity*; D004247:DNA / Q000737:chemistry; D005290:Ferric Compounds / Q000008:administration & dosage / Q000633:toxicity*; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D007263:Infusions, Parenteral; D007668:Kidney / Q000473:pathology*; D015227:Lipid Peroxidation; D008297:Male; D009571:Nitrilotriacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013816:Thermodynamics; D015032:Zinc / Q000494:pharmacology
D002614:Chelating Agents; D005290:Ferric Compounds; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D015032:Zinc; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate