Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because a pre-natal developmental toxicity study is available
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
[Specific explanation in addition to field 'Justification for data waiving']
Dipentaerythritol hexaesters with 3,5,5,-trimethylhexanoic and n-heptanoic acids is a substance of low toxicological activity, as other similar fatty esters of dipentaerythritol and pentaerythritol. Negative results for eye irritation, skin irritation and sensitization were obtained with the structural and chemical analogue substance Dipentaerythritol with fatty acids, C5 and C9iso (EC 444-000-2). The LD50 values found for acute toxicity by oral and dermal route (GLP studies OECD 423 and OECD 402 respectively) were both > 2000 mg/kg bw .
Furthermore, the subacute study (28 day, OECD 407, GLP) performed via the oral route did not reveal any adverse effects on reproductive organs and tissues including epididymis, ovaries, prostate, seminal vesicles, testes and uterus. No treatment-related effects on organ weight were noted. Males treated with 500 mg/kg bw/day showed a statistically significant reduction in absolute epididymis weight when compared with control but, in the absence of a convincing dose-response relationship, the intergroup difference was considered to be incidental and of no toxicological importance.
In addition, the prenatal developmental toxicity study (similar to OECD TG 414) with the analogue substance Trimethylolpropane caprylate caprate (CAS 11138-60-6, currently identified as EC 812-652-0 Fatty acids, C8-10-(even numbered), diesters and triesters with trimethylolpropane), via the dermal route did not show any treatment-related or adverse effects on intrauterine development and on reproductive organs and tissues (uterus and ovaries).
On the other side, as discussed in the toxicokinetic assessment, only a low potential for absorption is considered for the test substance while the limited amount of substance that may have become systemically available will hydrolyse and the breakdown cleavage products can be further metabolized.
In conclusion, Dipentaerythritol hexaesters with 3,5,5,-trimethylhexanoic and n-heptanoic acids (EC 945-883-2, CAS 1379424-11-9 ) is considered to exhibit low toxicological activity based on the available studies with structural analogue substances, including a developmental toxicity study showing no adverse effects.
Therefore, according to Regulation (EC) No 1907/2006 and with respect to animal welfare, further reproductive toxicity studies are not considered scientifically necessary.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion