Sodium [2-[(2,6-dichlorophenyl)amino]phenyl]acetate

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

2 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

In a 3 month repeated dose oral toxicity study with 4 weeks recovery period, 10 rats per sex and group were treated with doses of 0.5, 2 and 6 mg/kg bw/d of diclofenac sodium salt suitable for read-across. For the dose group receiving 6 mg/kg bw/d, the dose level was increased to 10 mg/kg bw/d from week 10 until the end of the experiment.

Results:

Mortality:In the group receiving 10 mg/kg bw/day, 3/20 animals (2 male and 1 female) died during the study.

Blood Chemistry:Decreases in total protein and albumin were seen at doses > 6 mg/kg bw/d. No changes were found in rats that received 0.5 and 2 mg/kg bw/d.

Haematology:Most rats that received doses of 10 mg/kg bw/d showed a moderate to marked anaemia with high reticulocyte response and raised platelet counts. These animals also had increased total white blood cell counts and raised neutrophil levels. Female rats were more severely affected. By week 17 there was evidence of recovery from these effects, particularly in the males.

Pathology, Macroscopic Findings:Thickening of the wall of the small intestine, perforation of the intestinal tract, intestinal adhesions and focal discolouration of the caecal mucosa were seen in some animals that received doses of 10 mg/kg. Splenic enlargement was also seen in these rats. At the completion of the recovery period thickening of the wall of the small intestine and of the pyloric region of the stomach and focal discolouration of the caecal mucosa were only seen in a few rats which had received doses of 10 mg/kg bw/d. Splenic enlargement was also seen in these rats.

Pathology, Microscopic Findings:Doses > 2 mg/kg caused ulcerative lesions in the gastro-intestinal tract. Associated changes were also noted with minor effects on protein and red and white blood cells. Thrombosis of the endocardium was present in 4 rats receiving a dose of 10 mg/kg bw/d.

Based on the available data, the NOAEL for systemic was considered to be 2 mg/kg bw/d.

Justification for classification or non-classification

According the classification criteria described in REGULATION (EC) No 1272/2008 (CLP), the product has to be classified in the Hazard Class "Repeated Dose Toxicity", CAT 1.