416-730-1

Endpoint summary

Description of key information

A seven day study and a 28d study in rats (EU B.7, OECD 407) were performed to evaluate the subacute repeated dose toxicity of the test substance. The test substance did not induce any mortalities, abnormalities or clinical symptoms. Based on the results of these studies, the NOEL and the NOAEL of the test substance is 1000 mg/kg bw per day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

Procedure and results

A pre-test and a main study were performed to evaluate the subacute repeated dose toxicity of the test substance in rats. In the pre-study, the test substance was administered orally to a group of three male and three, female rats at 1000 mg/kg/day (at a dosage volume of 10 ml/kg/day), formulated as a 10% w/v suspension in 1 % w/v aqueous methylcellulose (1 % MC). A further group of three male and three female rats received the vehicle (1 % MC) alone as a control. The study started on 14 June 1994 and following seven consecutive days of treatment all animals were killed on Day 8 (21 June 1994). Clinical signs, bodyweight, food consumption, organ weight and macroscopic examinations were recorded for the study.

There were no mortalities. No treatment-related clinical signs were noted for any of the animals throughout the study. The only clinical observation during the study was yellow-coloured faeces on the tray paper for all rats receiving 1000 mg/kg/day. No treatment releated effects on organ weight, water consumption or food consumption were observed. There were no macroscopic abnormalities observed in any rats.

In the main study, the substance was administered by oral gavage, once daily, to three groups of rats for a minimiun for twenty eight consecutive days, at dosage levels of 15, 150 or 1000 mg/kg/day. The test material was prepared as suspensions in 1% w/v aqueous methylcellulose (1% MC) at concentrations of 0.15, 1.5 or 10% w/v and was administered at a dosage volume of 10 ml/kg/day. Control animals received the vehicle (1% MC) alone at the same dose volume (10 ml/kg/day).

All rats of Groups 2 and 3 (15 and 150 mg/kg/day respectively) and five males and five females from each of Groups 1 and 4 (Control and 1000 mg/kg/day respectively) were killed following the fourweek treatment period (Day 32). The remaining animals (five males and five females from Groups 1 and 4) were retained for a two-week recovery period, following which, they were also killed (Day 46).

Bodyweights, food consumption and clinical observations were recorded during the study. Blood and urine samples were taken from all rats shortly prior to termination following the four-week treatment and two-week recovery periods. All animals were killed and subsequently examined macroscopically; specified tissues were then prepared for histopathological examination.

There were no changes seen in the parameters measured in this study namely clinical signs, bodyweights, food consumption, clinical pathology, organ weight analysis, macroscopic or microscopic pathology, that were considered to be related to treatment with the test substance.

Discussion

The test substance did not induce any mortalities, abnormalities or clinical symptoms. The only remarkable finding in the pre-study was a yellow discoloration of faeces. This incidental finding was considered to be due to the presence of the test substance in the faeces and not a manifestation of toxicity. Based on the results of these studies, the NOEL and the NOAEL of the test substance is 1000 mg/kg bw per day.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is notconsidered to be classified for repeated dose toxicity under Directive 67/548/EEC, as amended for the 30th time in Directive 2008/58/EC.

 

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for repeated dose toxicity under Regulation (EC) No. 1272/2008, as amended for the second time in Directive (EC 286/2011).