Carboxylic acids, C5-9, triesters with 2-ethyl-2-(hydroxymethyl)propane-1,3-diol

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

There is one study available that assesses the possible toxic effect of the test substance after repeated oral dosing. It was performed according to GLP and internationally accepted guidelines. The experimental procedures were based on the OECD guideline 422, in which both female and male rats were treated during 5 weeks. Three doses were tested (100, 300 and 1000 mg/kg bw/day) and compared to a control group that received the vehicle only.

Concerning the parents:

No differences in body weights and food consumption were observed in treated animals compared to the control group.

No clinical signs were observed during the study.No adverse findings were recorded in clinical pathology investigations (haematology, clinical chemistry and urine analysis) apart for lymphocytosis in mid- and high dose groups. No relevant differences were recorded in the absolute and relative organ weights of treated animals. No treatment-related changes were noted at macroscopic and microscopic observations.

Concerning the pups:

Fertility index and copulatory index were unaffected by treatment. Fertility index and copulatory index were unaffected by treatment and litter data parameters and sex ratio did not show differences.

Based on the results of the present study, the NOAEL (No Observed Adverse Effect Level) for reproductive and developmental toxicity was considered to be the highest dose of 1000 mg/kg bw/day.

There are no test reports are available that address the repeated dose toxicity of the test substance when exposure occurs via the inhalation or the dermal pathway. However, based on the outcome of the available study data, it is not deemed necessary to evaluate the other routes in more detail.

Short description of key information:

A NOAEL of 1000 mg/kg bw/d was determined for the test item based on effects observed in a combined repeated dose / reprotox screening test (OECD422).

Justification for selection of Effect on fertility via oral route:

Well documented study according to GLP and internationally accepted guidelines.

Effects on developmental toxicity

Description of key information

There is only one study available describing developmental toxicity effects (Azuka and Daston, 2014) on the read-across substance Trimethylolpropane Caprylate Caprate (CAS11138-60-6). Based on the results of that study there is no indication of any potency to cause developmental effects as the determined NOAEL for developmental effects was > 2000 mg/kg bw.

Qsar evaluation were also carried out using Developmental/Reproductive Toxicity library (PG) (version 1.0.0) and also the DART Scheme (from QsarToolBox).

The results of the Developmental/Reproductive Toxicity library (PG) indicate that all the constituents of the target substance have not potential toxicity and from the DART Scheme it resulted: not known to have DART - Not known precedent reproductive and developmental toxic potential

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

2 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

Read-across justification

 From TMP Pelargonate CAS 127-57 -8

·Carbon number in Fatty Acids: C9     

·Carbon number in Polyol: C6

·Total Carbons in Polyol Ester: C33     

·Molecular Weight:     554

 

AND

From Decanoic acid, ester with 2-ethyl-2(hydroxymethyl)-1,3-propanediol octanoate (CAS 11138-60-6)

·Carbon number in Fatty Acids: C8, 10    

·Carbon number in Polyol: C6

·Total Carbons in Polyol Ester: C24     

·Molecular Weight: 414.63   

 

To Fatty Acids, C5 -9

 ·Carbon number in Fatty Acids: C5-9     

·Carbon number in Polyol: C6

·Total Carbons in Polyol Ester: C26 - C32   

·Molecular Weight: 400 - 540  

All of them belong to the Trimethylolpropane (TMP) Esters as they have the trimethylolpropane group as a common structural part.

 

For all of them, it is valid to assume that when metabolism of these triesters takes place, this firstly leads to the generation of the corresponding fatty acids and of the polyol alcohol.

For substance “TMP Pelargonate" (CAS 127 -57 -8) this relates to trimethylolpropane and three C9 fatty chains.

For substance "Decanoic acid, ester with 2-ethyl-2(hydroxymethyl)-1,3-propanediol octanoate" (CAS 11138-60-6) this relates to trimethylolpropane and

For substance “TMP Fatty Acids, C5 -9” this also relates to trimethylolpropane and 3 C5-9 fatty chains.

As it is not expected that the developmental toxicity is different between C5 - C10 fatty acid chains, read-across is, then, considered justified.

Justification for selection of Effect on developmental toxicity: via dermal route:

There is only one study available (Azuka and Daston, 2014) on the read-across substance Trimethylolpropane Caprylate Caprate.

Toxicity to reproduction: other studies

Description of key information

Qsar evaluations according to IRFMN ( Estrogen Receptor relative binding affinity model (IRFMN) (Version 1.0.0)) and IRFMN/CERAPP ( Estrogen Receptor-mediated effect (IRFMN/CERAPP) (version 1.0.0)) reveal that at an endocrine disruptor screening the target substance results inactive.

Justification for classification or non-classification

Based on the results of the combined reprotox / repeated dose toxicity testing and developmental toxicity tests, the test item should not be classified for reproductive effects according to the criteria described in Directive 67/548/EEC (Dangerous Substances Directive) and the EU Regulation No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures (CLP) respectively.