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Carcinogenicity

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NCI (1977) reported a 18-month study using male and female B6C3F1 mice. The animals were offered concentrations of 0.75 and 1.5% via the diet. Survival was comparable in treated and control animals. Renal interstitial fibrosis and tubular dilatations were frequent. Increases in the frequency of renal tubular cell neoplasms (RCN, kidney + urinary tract), adenoma and carcinoma, were observed in males, and of transitional and squamous cell carcinoma (TCC, urinary bladder) in females; other tumours were increased, too: phaeochromocytomas (PhC, adrenal gland) and hepatoadenomas (HA) in females.

 

Another NCI study (1977) were done using male and female Fischer-344 rats. The study duration was 18 months, too. Concentrations offered were 0.75 and 1.5% via the diet. Renal interstitial fibrosis and tubular dilatations were frequent. Increases in the frequency of renal tubular cell neoplasms (RCN, kidney and urinary tract), adenoma and carcinoma, were observed in males, and transitional and squamous cell carcinoma (TCC, urinary bladder) in females; other tumours were increased, too: phaeochromocytomas (PhC, adrenal gland) and hepatoadenomas (HA) in females. PhC spontaneously formed are frequent in this strain. The incidence of hepatic neoplastic nodules was strikingly higher than generally noted in those rats receiving Na.3.NTA.H2O, but not considered NTA related. Revision of slides from both, the group having received 1.5% H3.NTA for 18 months followed by a 6-month recovery period and a test group having received 2% of Na3.NTA for 24 months suggested that a recovery period has interupted the sequence of events leading to renal neoplasms.

 

BASF (2006) tested Trilon ES 9964 (CAS: 5064-31-3) in a combined chronic toxicity/carcinogenicity study. Male and female Wistar rats were used in this experiment. For comparison, NTA was offered at a concentration of 20000 ppm via the diet for 12 and 24 months. For both substances, the target organ was the kidney. Both substances caused chronic nephropathy, pigment storage and cytoplasmatic vacuolation in tubular epithelial cells, and (multi-)focal tubular hyperplasia. Incidence and severity of these findings were higher in males than in females or, the finding occurred in males, only. The effect after treatment with Trilon A 92 R was more severe than the effect observed after treatment with Trilon ES 9964 / Pulver and resulted in some males in a secondary hyperparathyroidism followed by osteodystrophia fibrosa. Furthermore, after treatment with Trilon A 92 R, severe changes occurred in the renal pelvis. While after treatment with Trilon ES 9964/Pulver nodular or papillary hyperplasia of the transitional cell epithelium was only observed in few males, many males and few females showed this finding by treatment with Trilon A 92 R. Remarkable after treatment with Trilon A 92 R was the occurrence of a chronic fibrotic and partly necrotising pyelitis, considered as responsible for the occurrence of mesenchymal tumors observed in six males. Further target organs after treatment with Trilon A 92 R were the ureter, vessels in the pancreas, mesentery, testes, and epididymides. The severe findings in kidneys and vessels are considered causal for the increased number of male decedents.

Justification for classification or non-classification

Classification proposal: R40; GHS: Carc. Cat. 2