2-methylpropyl-(R)-2-hydroxypropanoate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Publication. Meets national standard methods. Lactic acid used as read-across partner.

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

not specified

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7-12 weeks

Vehicle:

dimethyl sulphoxide

Concentration:

5.0, 10.0 and 25 %

No. of animals per dose:

No data

Details on study design:

Groups of CBA female mice were exposed topically on the dorsum of both ears to 25 µL of test material or to an equal volume of the relevant vehicle. Treatment was performed daily for 3 consecutive days. Five days after the initiation of exposure, all mice were injected via the tail vein with 250 µL of phosphate-buffered saline containing 20 µCi of tritated thymidine. The mice were sacrificed 5 hours later, and the draining auricular lymph nodes were excised and pooled for each experimental group or each individual animal. The incorporation of tritiated thymidine measured by beta scintillation counting was reported in disintegrations per minute. A stimulation index (SI) was calculated for each chemical-treated group as the ratio of the disintegrations per minute in the treated group (or mean disintegrations per minute when individual animals were assessed) to the disintegrations per minute or mean disintegrations per minute of the concurrent vehicle control group.

Positive control substance(s):

not specified

Statistics:

No data

Positive control results:

No data

Parameter:

SI

Remarks on result:

other: Dose group 5 %: 1.0 Dose group 10 %: 1.4 Dose group 25 %: 2.2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: No data

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a local lymph node assay in mice, lactic acid was tested negative for skin sensitisation.

Executive summary:

In a dermal sensitisation test according to OECD 429 female CBA mice were treated with concentrations of 5, 10 and 25 % lactic acid in DMSO. Stimulation indices of 1.0 (test group 5 %), 1.4 (test group 10 %) and 2.2 (test group 25 %) were measured. As the maximum stimulation index was < 3, lactic acid can be considered as not skin sensitising. This result is used in a read-across approach for the assessment of isobutyl-R-lactate.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No data is available for isobutyl-R-lactate (target substance). Due to the rapid enzymatically driven hydrolysis of isobutyl-R-lactate into isobutanol and lactic acid, the toxicology of isobutyl-R-lactate can be understood in terms of the toxicology of isobutanol and lactic acid. Thus, available data on the degradation product lactic acid (source substance) is considered to be suitable for read-across. No data is available for the second degradation product isobutanol, but 1-propanol and 1-butanol (structural isomer of isobutanol) were used as read-across substances due to their structural similarity, representing alcohols of similar alkyl chain length as the degradation product of interest, isobutanol. Details on the read-across rational are provided in the corresponding read-across report.

The source substance lactic acid was tested negative for skin sensitization in two studies. In the first study lactic acid was tested negative in a mouse LLNA according to OECD test guideline 429. In a second test conducted under GLP, lactic acid was tested negative in a modified Buehler closed patch test using guinea pigs of the Hartley strain. The source substance 1-propanol was tested as not sensitising in a study equivalent to OECD test guideline 406 using the method of Magnusson and Kligman. Finally, 1-butanol, considered to be a structural equivalent to isobutanol, was tested negative in a mouse LLNA according to OECD test guideline 429. Furthermore, ethyl lactate (ethyl ester of lactic acid, structurally similar to isobutyl-R-lactate) was tested negative for skin sensitisation in 25 human volunteers (see IULCID chapter 7.10.4), which supports the hypothesis that lactate esters are not sensitising to skin.

Migrated from Short description of key information:
The source substance lactic acid was tested negative for skin sensitisation in two studies (mouse LLNA according to OECD 429 and modified Buehler closed patch test using guinea pigs). The source substance 1-propanol was tested as non-sensitiser in a study equivalent to OECD test guideline 406 using the method of Magnusson and Kligman. Finally, the structural isomer of isobutanol, 1-butanol, was tested negative in a mouse LLNA (OECD 429). In conclusion, by read-across from lactic acid and source substances that are structurall similar to the second metabolic breakdown product, isobutanol, isobtuyl-R-lactate is considered not to be a skin sensitiser.

Justification for selection of skin sensitisation endpoint:
Guideline study according to OECD 429 conducted with lactic acid.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the negative results for the read-across partners, no classification of isobutyl-R-lactate for is warranted.