[2-(Isopropoxycarbonyloxy)-benzoyl]-benzoylperoxide

Endpoint summary

Description of key information

An additional acute toxicity study is not necessary as there is data available from short-term 14-day repeated dose toxicity studies of CD08467 and CD08479 in minipigs and rats, respectively. Repeated dose-administration studies supersede the need of additional single dose acute toxicity testing.

The acute toxicity potential of CD08467 as well as its analogue CD08479 has been investigated in two sub-acute studies (see IUCLID section 7.5.1: Weiler, 2012 and Maury, 2012). CD08467 was administered daily for 2 weeks via oral gavage to minipigs at 300, 600, or 1 200 mg/kg bw/day (the maximal feasible dose due to the limit of formulability of CD08467). No mortality was observed with all 3 doses and slight treatment-related effects were seen only at the highest dose of 1 200 mg/kg. No toxicity was seen at 300 or 600 mg/kg bw/day. In another study, CD08479, the structurally related analogue of CD08467, was administered daily to rats at 420 mg/kg bw/day for 2 weeks, and no toxicity was observed at this dose. Thus, the sub-acute non-toxic dose levels have been demonstrated to be 600 mg/kg bw/day in minipigs for CD08467 and 420 mg/kg bw/day in rats for CD08479.

Based on the available data showing no mortality of both studies, it can be expected that the LD50 of CD08467 by oral route is higher than the maximum (technically feasible) dose of 1 200 mg/kg bw/day in the minipigs (non-rodent toxicity with CD08467) and higher than 420 mg/kg bw/day in the rat (rodent toxicity with CD08479).

In addition, both CD08467 and CD08479 are rapidly converted into salicylic acid and benzoic acid (1 mol CD08467 or CD08479 yields 1 mol salicylic acid and 1 mol benzoic acid), which are known compounds with available acute toxicity data. According to the ECHA’s C&L inventory, benzoic acid is not classified for acute toxicity. Salicylic acid is classified as Acute Tox. 4 (H302) based on a LD50 of 891 mg/kg bw (see registration dossier of salicylic acid). By extrapolating the LD50 of the metabolite salicylic acid (MW = 122.12 g/mol) to CD08467 (MW = 344.32 g/mol), the LD50 for CD08467 would be 2512 mg/kg bw, and thus, no classification is warranted for CD08467 for acute toxicity based on the criteria under CLP Regulation.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

An acute toxicity study is not necessary as there is data available from short-term 14-day repeated dose toxicity studies of CD08467 and CD08479 in minipigs and rats, respectively. Repeated dose-administration studies supersede the need of additional single dose acute toxicity testing.

The acute toxicity potential of CD08467 as well as its analogue CD08479 has been investigated in a few short-term duration studies (see IUCLID section 7.5.1: Weiler, 2012 and Maury, 2012). CD08467 was administered daily for 2 weeks via oral gavage to Göttingen® minipigs at 300, 600, or 1 200 mg/kg bw/day (the maximal feasible dose due to the limit of formulability of CD08467). No mortality was observed with all 3 doses and slight treatment-related effects were seen only at the highest dose of 1 200 mg/kg. No toxicity was seen at 300 or 600 mg/kg bw/day. In another study, CD08479, the structurally related analogue of CD08467, was administered daily to rats at 420 mg/kg bw/day for 2 weeks, and no toxicity was observed at this dose. Thus, the acute non-toxic dose levels have been demonstrated to be 600 mg/kg bw/day in minipigs for CD08467 and 420 mg/kg bw/day in rats for CD08479.
Based on the available data showing no mortality of both studies, it can be expected that the LD50 of CD08467 by oral route is higher than the maximal feasible dose of 1 200 mg/kg bw/day in the minipigs (non-rodent toxicity with CD08467) or higher than 420 mg/kg bw/day in the rat (rodent toxicity with CD08479).

In addition, both CD08467 and CD08479 are rapidly converted into salicylic acid and benzoic acid (1 mol CD08467 or CD08479 yields 1 mol salicylic acid and 1 mol benzoic acid), which are known compounds with available acute toxicity data. According to the ECHA’s C&L inventory, benzoic acid is not classified for acute toxicity, but salicylic acid is classified as Acute Tox. 4 (H302) based on a LD50 of 891 mg/kg bw (see registration dossier of salicylic acid). By extrapolating the LD50 of salicylic acid (MW = 122.12 g/mol) to CD08467 (MW = 344.32 g/mol), the LD50 for CD08467 would be 2512 mg/kg bw, and thus, no classification is warranted for CD08467 for acute toxicity based on the criteria under CLP Regulation.

For further details see attached justification “CD08467 Acute toxicity waiver 7844907273609635930.pdf”

Reason / purpose for cross-reference:

data waiving: supporting information

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

2-week oral gavage study in Göttingen minipigs

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data, CD08467 does not warrant classification for acute toxicity.