Registration Dossier

Administrative data

Description of key information

Oral (Rat-Wistar, GLP-like): LD50 males = 67 mg/kg, LD50 females = > 25 < 50 mg/kg; LD50 both sexes approx. 36 mg/kg
[Bayer AG, Report No. 18004, 1989-05-16]
Dermal (Rat-Wistar, GLP-like): LD50 males = 1451 mg/kg, LD50 females = > 100 < 500 mg/kg; LD50 both sexes 918 mg/kg
[Bayer AG, Report No. 15809, 1987-05-22]
A further non-GLP, non-Guideline study was conducted in male Wistar rats with a single oral administration of 108 mg/kg TVX 3934 (equivalent to Acemetacin-tert.-butylester) by gavage. TVX 3934 was suspended in Traganth (application volume 5 ml/kg) or Lutrol (application volume 10 ml/kg) and 10 animals per solvent were used. No animal died after administration of TVX 3934 in Traganth and one animal died after administration of TVX 3934 in Lutrol. No LD50 could be defined in this study.
[Troponwerke, Scientific Report No. 51138 F, 1987-03-23]

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
36 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
918 mg/kg bw

Additional information

The acute oral and the acute dermal toxicity of Acemetacin-tert.-butylester was studied in male and female rats in two GLP-like studies to define LD50 -values.

In these studies the acute oral LD50 for both sexes was determined to be approximately 36 mg/kg and the acute dermal LD50 for both sexes was determined to be approximately 918 mg/kg, whereas females seemed to be more susceptible.

In a further study in male rats with single oral application of 108 mg/kg TVX 3934 suspended in Traganth or Lutrol in male rats no mortality was observed in rats treated with TVX 3934 in Traganth and one animal died on day 8 after administration of TVX 3934 in Lutrol. 4/10 animals treated orally with TVX 3934 in Traganth showed ptosis 4 to 6 hours after administration, on the next the no clinical signs could be observed. All animals treated orally with TVX 3934 in Lutrol showed diarrhoe on the first day after administration. In 7/10 animals bloody noses and eyelids were observed on day 2 and 3 after administration and 6/10 animals showed e.g. ruffled fur up to 9 days after administration. From day 10 after administration onwards all surviving animals were without clinical signs.

Justification for classification or non-classification

Based on the study results Acemetacin-tert-butylester has to be classified according to Directive 67/548/EEC and Regulation (EC) No. 1272/2008 (CLP) as toxic in contact with skin and if swallowed (T, R24/25) or as acute oral toxic, category 2 (H300) and acute dermal toxic, category 3 (H311), respectively.