2'-chloroacetoacetanilide

Endpoint summary

Description of key information

Key study similar to OECD Guideline 401, Bio Toxicity lab 1976: LD50 male rats 11'600 mg/kg bw 
Several supporting studies similar to OECD 401:
1. Hoechst 209/78, Vehicle Propandiol 1,2, LD50 male rats 3'780 mg/kg bw
2. Hoechst 897/77, Vehicle Polyglycol 400, LD50 female rats 4'580 mg/kg bw
3. Hoechst 843 & 845/77, Vehicle Polyglycol 400, LD50 male rats 4'800 mg/kg bw and female rats 5'600 mg/kg bw
4. Hoechst 842/77, Vehicle Starch slime 2%, LD50 female rats 4'860 mg/kg bw
5. Hoechst 844 & 846/77, Vehicle Starch slime 2%, LD50 female and male rats 4'300 mg/kg bw
A further supporting study was performed by Consultox Laboratories Ltd. for Lonza Ltd. in year 1973 with three different species. The following 
animals were used in these investigation: 
Mice: Tylers original strain, weighing approx. 20g
Rats: Female Wistar rats weighing approx. 200g
Rabbits: New Zealand White weighing approx. 2kg
Vehicle: was aqueous solution of Tween 80 or distilled water
Administration: By gavage using metal cannulae for mice and rats and a rubber stomach catheter for rabbits.
LD50 in mice = 1'900 (1'460-2'470) mg/kg bw
LD50 in rats between 2'500 and 5'000 mg/kg bw
LD50 in rabbits between 2'500 and 5'000 mg/kg bw
In a further acute toxicity study the Methemoglobin formation was determined in male cats. The study was performed in year 1965.
At doses of 100 mg/kg and 500 mg/kg the test item has generated methemoglobin in the male cats.
At doses of 500 mg/kg both cats died.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

3 780 mg/kg bw

Additional information

The acute oral toxicity study following a protocol similar to OECD Guideline 401 standard method demonstrated an LD50 of 11'600 mg/kg bw for male and 12'400 for female rats. Further studies, similar to OECD standard method, demonstrated an LD50 value of 4'580 mg/kg bw for female rats and 3'780 mg/kg bw for male rats but different vehicle were used in these studies. Another study with both sexes showed an LD50 of 5'600 mg/kg bw for females and 4'800 mg/kg bw for males. In the last study report the LD50 value for female and male rats was 4'300 mg/kg bw and did not show a higher sensitivity for males in the test. The lowest value of 3'780 mg/kg bw, representing the most sensitive response, was identified to be suitable for classification purposes. Findings of another not OECD Guideline conform range finder study by using different species (LD50 between 1900 - 5000 mg/kg bw.) is not considered to be acceptable for reliability and therefore results are not relevant for classification purposes.

Observation of lethality following methemoglobin formation is not usual, as several animals are more tolerant to it. We have to assume that methemoglobinemia contributes to the mechanism of toxicity to chemicals from this group (see also German MAK-commission). The acute toxicity study in the cat has demonstrated the methemoglobin formation and therefore if lethality is observed in animals or can be predicted (QSAR), methemoglobin generating substances should be classified in the Acute Toxicity Hazard Class.

Justification for classification or non-classification

If lethality is observed in animals or can be predicted (QSAR), methemoglobin generating substances of this group should be classified in the Acute Toxicity Hazard Class.

Therefore, Acetoacet-o-chloranilide will be classified in Toxicity Category 4 according to expert judgement.