3-mercaptopropionic acid

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

No effects on fertility were noted in a screening study conducted according to OECD TG 422 with the methyl ester of 3-mercaptopropionic acid.

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

This scenario covers the category approach for which the read-across hypothesis is based on biotransformation to common compounds. For the REACH information requirement under consideration, the property investigated in studies conducted with different source substances is used to predict the property that would be observed in a study with the target substance if it were to be conducted. Similar properties are observed for the different source substances; this may include absence of effects for every member of the category.
There are differences in strength of the effect(s) forming a regular pattern. The prediction is based either on this regular pattern within the category, when the members are ordered by a variable related to the structural differences in the category or is based on a worst-case approach.
The read-across is a category approach based on the hypothesis that the substances in this category are transformed to a common compound. This approach serves to use existing data on acute toxicity, repeated-dose toxicity, and reproductive toxicity endpoints for substances in this category.
There are differences in strength of the effects forming a regular pattern. This corresponds to Scenario 3 of the RAAF. The substances MMP, BuMP, EHMP, iOMP, iC13MP, and ODMP are esters of a common acid, 3-mercaptopropionic acid (3-MPA). They are likely to be rapidly hydrolysed to 3-mercaptopropionic acid and the respective alcohol (i.e. methanol, butanol, ethylhexanol, iso-octanol, iso-tridecanol, and octadecanol). In vitro studies on hydrolysis/metabolism are planned to strengthen the hypothesis.
The observed differences in effect levels (higher effect levels with increasing carbon chain length were observed in the available acute oral toxicity studies) are assumed to be mainly due to differences in molecular weight (corrections will be made for these differences) and decreasing bioavailability with increasing carbon chain length (no corrections are made for this effect; a worst-case approach is applied here, since based on the available data no exact quantification for bioavailability differences is possible at the moment).
It can be predicted with high confidence that the substances within this category will lead to the same type of effects. The main driver for toxicity is the common compound 3-mercaptopropionic acid, whereas the alcohols do not contribute to a relevant extent to overall toxicity.
For details, please refer to the category document attached to Iuclid section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Species:

rat

Route of administration:

oral: gavage

Key result

Dose descriptor:

NOAEL

Effect level:

>= 88 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects (reproductive parameters))

Remarks on result:

other: correction for difference in molecular weight

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

>= 88 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects (reproductive parameters)

Remarks on result:

other: correction for difference in molecular weight

Key result

Reproductive effects observed:

no

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

88.3 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

No experimental data are available for the target substance 3-MPA. A Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test was conducted with MMP. A justification for read-across is attached to Iuclid section 13.

The test item was administered in corn oil as vehicle at dosages of 25, 50, and 100 mg/kg body weight/day, and controls received the vehicle only. The test item was administered to male rats for at least 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. Administration of 50 and 100 mg/kg/day resulted in dose-dependently increased liver weights relative to body weights and brain weights in males. In the absence of a histopathological correlation these higher weights were considered to be of no adverse character. Furthermore at 100 mg/kg/day, a minimal to slight hyperplasia of the forestomach squamous epithelium was noted in males and females. Based on these results a general NOAEL (No Observed Adverse Effect Level) was established at 50 mg/kg body weight/day. The NOEL (No Observed Effect Level) for reproduction/developmental toxicity was considered to be 100 mg/kg/day.

After correcting for differences in molecular weight, the NOAEL for 3-MPA was calculated as 88 mg/kg bw/d.

 

 

 

Effects on developmental toxicity

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 study available

Additional information

A prenatal developmental toxicity study (OECD TG 414) is required for 3-MPA. However, due to the corrosive properties of 3-MPA, testing on the substance itself is likely to produce prominent local effects to the gastrointestinal tract which may interfere with interpretation of the study. Therefore, based on the predicted ester hydrolysis (in vitro study planned), data obtained with MMP can be used to predict the toxicological properties of 3-MPA. The proposed prenatal developmental toxicity study may be conducted with the source substance MMP. A justification for read-across is attached to Iuclid section 13.

Justification for classification or non-classification

Based on the available data no classification for toxicity to reproduction is required according to regulation (EC) 1272/2008. Hazard assessment will be re-evaluated after the proposed prenatal developmental toxicity study is finished.