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Description of key information

A read-across from the 90-days repeated dose subchronic toxicity study on the structural analogue sodium salt undecylenic acid is being proposed. 
This read-across is based on the following justification.
Referring to ECHA's "Guidance on information requirements and chemical safety assessment - Chapter R.6: QSARs and grouping of chemicals", endpoint information is read-across from a structural analogue. A structural analogue is a source chemical whose physico-chemical and toxicological properties are likely to be similar to the target chemical as a result of structural similarity. The similarity may be based on a common precursor and/or breakdown product, that results via physical or biological processes (metabolic pathway similarity). This is used to examine related chemicals, such as acid/ester/salt.
Since the target chemical methyl-10-undecenoate is the methyl ester of the source chemical undecylenic acid, read-across between the two substances based on structural analogy therefore technically is possible. The scientific justification for the read-across of the study on oral repeat dose toxicity from undecylenic acid to methyl-10 –undecenoate is based on the similiar behaviour of the two substances observed during the six in-vivo studies on acute effects :
 
- Acute oral toxicity: methyl-10 -undecenoate is classified as category 4, which is the lowest toxicity category. Since the LD50 of methyl-10 -undecenoate (1563 mg/kg) still is in the same order of magnitude compared to the LD50 of undecylenic acid (> 2000 mg/kg), the observed slight differences of the acute oral toxic effect should be insignificant in a repeated dose toxicity study.
- Acute dermal toxicity, and skin sensitization: both substances with the same results "not classified".
- Acute inhalative toxicity: methyl-10 –undecenoate is classified as category 4, which is the lowest toxicity category ...

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
60 mg/kg bw/day

Additional information

The 13 week oral repeated dose toxicity study perfomed with sodium salt undecylenic acid was used for evaluation of Methyl-10 -undecenoate. Read accross of the in vivo data should be justified based on the comparable chemical structure of both substances and because it was demonstrated that Methyl-10 -undecenoate undergo rapid hydrolysis to undecylneic acid under gastric pH conditions.

In the GLP 13 weeks oral toxicity study performed according to OECD 408, treatment with the undecylenic acid at 20, 60 and 180/360 mg/kg/day did not result in mortality. The observed signs included ptyalism, loud breathing/respiratory difficulties and poor clinical condition. Body weight gain and food consumption were reduced in males of the high dose group, especially after dose increase starting day 50 of the study. Reduced glucose plasma levels and reduced triglyceride-levels were found in females of the high dose group, the first being reversible and the latter not reversible in the treatment-free period. Histopathology revealed cardiomyopathy in some animals of the highest dose group (myocardial degeneration/monocellular aggregation) which was reversible during treatment free period. Forestomach oedema/inflammatory cell infiltration was observed in the high dose group. There were no treatment related effects in the low and intermediate dose-groups.

Under the experimental conditions, the 13 week oral toxicity study derived LOAEL for the source chemical sodium salt of undecylenic acid was 180 mg/kg BW.


Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: heart

Justification for classification or non-classification

With a LOAEL of > 180 mg/kg bw / day in the 90-days repeated dose subchronic oral study toguether with reversible observed target effects (cardiomyopathy), the substance is not classified as to its chronic toxic properties according to EU regulation (EC) No. 1272/2008 (CLP).

According to EU 67/548/ECC classification system, the substance is not classified. No serious damage was observed in the repeated oral study.

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