Isotridecyl 3,5,5-trimethylhexanoate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

The OECD 421 study is not required to be conducted as a reliable OECD 414 study is available.

Link to relevant study records

Reference

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

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Effects on developmental toxicity

Description of key information

Study conducted to recognised testing guideline with GLP conditions.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Read-across to similar substance.

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
Full information on the read-across approach is provided in the attached justification document.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source and target substances are composed of the same chemical groups and are bonded together in functionally the same way. The source substance and target substances have low water solubility, high partition coefficient, and are in the physical form of a liquid with a neutral pH. Available toxicity information on the source and target substances indicates that they behave in substantially similar ways in the body. The potential for reproductive toxicity is therefore the same in all substances.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The substances are hydrophobic oils at room temperature, with no hydrophilic groups and poor water solubility (all < 0.1 mg/l). The only chemical group present in each substance is the ester group. The boiling points are > 160°C, typically with decomposition >300 °C. The substances are also lipophilic, all with partition coefficients >7.2. The relative densities are all closely related, all being approximately 0.85
All are UVCB substances – with only one part of each substance being from a UVCB source (the stearic acid component of the 2-ethylhexyl stearate, and the alcohol components of the target substances. All the carbon-carbon bonds are saturated, giving a constant ratio of one carbon to two hydrogens across all the substances.
Each substance also has a branched component, which is present from the ester due to the mono-constituent substance used to synthesise it. In the case of the 2-ethylhexyl stearate, this is the alcohol part of the substance. In the case of the target substances Isodecyl 3,5,5-trimethylhexanoate and Isotridecyl 3,5,5-trimethylhexanoate, both the acid part and the alcohol part are branched (although the alcohol is varied due to the UVCB alcohols used as an ingredient for both). The C12-15 Alkyl Ethylhexanoate has the same branched aliphatic chain that the 2-ethylhexyl stearate does, but it is from the acid component rather than the alcohol component.
A difference is that the variation for the 2-ethyl hexyl stearate is along the acid but only in increments of two carbons, which are all linear. The target substances show variation in the alcohol part of the ester, and this variation involves both linear and branched aliphatics – with the C12-15 Alkyl Ethylhexanoate showing additional variation here due to the number of carbons being between twelve and fifteen, whereas they are constant for Isodecyl 3,5,5-trimethylhexanoate (ten carbons) and Isotridecyl 3,5,5-trimethylhexanoate (thirteen carbons). The three target substances also all have a branched acid component which the source substance does not share.
The source substance also only has an even numbered amount of carbons in the acid component, whereas this is only shared in the C12-15 Alkyl Ethylhexanoate, with the Isodecyl 3,5,5-trimethylhexanoate and Isotridecyl 3,5,5-trimethylhexanoate having an odd numbered amount of carbons in the acid component.
The alcohol component of the 2-ethylhexyl stearate is both branched, which it shares with C12-15 Alkyl Ethylhexanoate, Isodecyl 3,5,5-trimethylhexanoate, and Isotridecyl 3,5,5-trimethylhexanoate. The alcohol component is also even numbered, which it only shares with C12-15 Alkyl Ethylhexanoate and Isodecyl 3,5,5-trimethylhexanoate, and not Isotridecyl 3,5,5-trimethylhexanoate. It should also be noted that due to the nature of the alcohol component of C12-15 Alkyl Ethylhexanoate, both even numbered and odd numbered amounts of carbons are present in the alcohol chain in the substance.
The substances have also been tested for toxicity (oral) and the conclusions were that neither the source substance nor target substances were classified for toxicity (LD50 > 2000 mg/kg bw). In addition, skin and irritation tests also concluded no classification under CLP 1278/2008.
These common phys-chem properties, and the similar results for toxicity and skin/eye irritation/corrosion, indicate that the substances will share similar bioavailability and toxicity.

3. ANALOGUE APPROACH JUSTIFICATION
Due to the similarities of the source and target substances with regards to branching, odd and even numbered alkyl and acid chains, the target substances are expected to behave in a substantially similar manner in vivo.
The target substances are therefore predicted to fail to induce effects of developmental toxicity in the OECD 414 study when conducted in the rat. By extension, the target substances are considered not to fulfil the criteria for reproductive toxicity under the Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

4. DATA MATRIX
Full information on the read-across approach is provided in the attached justification document.

Reason / purpose for cross-reference:

read-across source

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

test mat. (total fraction)

Basis for effect level:

body weight and weight gain

mortality

Abnormalities:

no effects observed

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

test mat. (total fraction)

Sex:

male/female

Basis for effect level:

reduction in number of live offspring

changes in sex ratio

fetal/pup body weight changes

changes in litter size and weights

external malformations

skeletal malformations

visceral malformations

Abnormalities:

no effects observed

Developmental effects observed:

no

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

1

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based upon the result of the key study the registered substance does not meet the criteria for classification as a reproductive toxic substance under the EU classification, Labelling, and Packaging (CLP) regulation (1272/2008).