2022/03/31 by Hartwig, Andrea, MAK Commission
#Arbeitsstoff #Dinatriumnitrilotriacetat #Entwicklungstoxizität #Gefahrstoff #Genotoxizität #Harnwege #Kanzerogenität #MAK value #MAK-Wert #Monohydrat #Mononatriumnitrilotriacetat #Nitrilotriacetic acid and its sodium salts #Nitrilotriessigsäure #Nitrilotriessigsäure und ihre Natriumsalze #Spitzenbegrenzung #Toxizität #Trinatriumnitrilotriacetat #Zytotoxizität #carcinogenicity #cytotoxicity #developmental toxicity #disodium nitrilotriacetate #disodium nitrilotriacetate monohydrate #genotoxicity #hazardous substance #maximale Arbeitsplatzkonzentration #maximum workplace concentration #monosodium nitrilotriacetate #nitrilotriacetic acid #peak limitation #substance in the work area #toxicity #trisodium nitrilotriacetate #trisodium nitrilotriacetate monohydrate #urinary tract
paper · doi:10.34865/mb13913e7_1ad
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re-evaluated the Carcinogen Category, the maximum concentration at the workplace (MAK value) and the Pregnancy Risk Group of nitrilotriacetic acid [139-13-9] and its sodium salts [18994-66-6, 15467-20-6, 23255-03-0, 5064-31-3, 18662-53-8]. Available publications and unpublished study reports are described in detail. Nitrilotriacetic acid and its sodium salts cause an increased incidence of carcinomas of the kidneys and urinary tract in rats and mice. Underlying mechanisms are cytotoxicity and, at higher doses, potential indirect genotoxicity. These processes are due to the complex-forming properties of nitrilotriacetic acid. As their thresholds have been examined in detail, nitrilotriacetic acid and its sodium salts are classified in Carcinogen Category 4. A NAEL (no adverse effect level) of 2.3 mg/kg body weight and day for hyperplasia of the urinary bladder epithelium, the most sensitive end point, was estimated for nitrilotriacetic acid from a 2-year study in rats. Based on this NAEL, the MAK value for nitrilotriacetic acid and its sodium salts is set at 2 mg/m3 I as acid. Since the critical effect of nitrilotriacetic acid and its sodium salts is systemic, they are assigned to Peak Limitation Category II. As the half-life of nitrilotriacetic acid in humans is approximately 4 hours, an excursion factor of 4 is set. There is an adequate margin between the NOAEL for developmental toxicity scaled to a concentration at the workplace and the MAK value. Therefore, damage to the embryo or foetus is unlikely when the MAK value is not exceeded and nitrilotriacetic acid and its sodium salts are assigned to Pregnancy Risk Group C. As genotoxicity has been observed only at or near cytotoxic doses, the substance is not regarded as a germ cell mutagen. The contribution of skin contact to systemic toxicity is expected to be relatively slight. Limited data show no sensitization.