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Description of key information

A 28-day oral toxicity study with the methyl ester of 3-mercaptopropionic acid (MMP) in rats showed only minor effects on organ weights as well as forestomach hyperplasia at the highest dose level (100 mg/kg/day). These effects are not adverse or relevant for human risk assessment. The NOAEL of MMP is equivalent to a NOAEL of 88.3 mg/kg/d for 3-mercaptopropionic acid (3-MPA).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
88.3 mg/kg bw/day

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The corrosivity of 3-MPA forbids the testing of doses that are sufficiently high to elicit systemic toxicity. The methyl ester of 3-MPA (methyl 3-mercaptopropionate, MMP) is not corrosive but is systemically cleaved to yield 3-MPA and methanol.

The NOAELs for MMP can be converted into NOAELs for 3-MPA by considering the relative molecular weight (120.2 vs. 106.1 g/mol). The MMP NOAEL of 100 mg/kg/day is equivalent to a NOAEL of 88.3 mg/kg/day for 3-MPA.

Study results from the combined repeated-dose / reproductive toxicity screening study with MMP (OECD422) can be used as a read across study for other esters of 3-mercaptopropionic acid (3-MPA) and for 3-MPA itself. This is because 3-MPA is a foreseeable metabolite of all 3-MPA esters. Carboxyesterases are expressed in many tissues, including skin, liver, lung and gastrointestinal tract. Their enzymatic activity leads to the formation of 3-MPA and the respective alcohol after systemic uptake.

The oral LD50 of 3-MPA in the rat is 63-126 mg/kg. 3-MPA is an inhibitor of GABA synthesis and causes neurotoxic effects. In contrast, the alcohol component of MMP, methanol, has a negligible acute toxicity in the rat, with an oral LD50 of >6000 mg/kg (IPCS, EHC No. 196).

Furthermore, methanol is not a reproductive toxicant in the rat so that any reproductive or developmental effect potentially seen in a study with MMP is attributable to 3-MPA rather than methanol.

Thus, 3-MPA and not methanol is the critical metabolite of MMP in rats. Because of the very small alcohol component in MMP, it can be assumed that ester cleavage and thus MPA formation is more rapid from MMP than for any other alkyl ester of 3-MPA. MMP thus represents a worst-case analogue substance for other 3-MPA esters.

Justification for classification or non-classification

No specific organ toxicity was noted in this study. A STOT or R48 classification is not warranted.