Methyl (R)-lactate

Endpoint summary

Description of key information

Inhalation is the only relevant exposure pathway for methyl lactate under REACH.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Dose descriptor:

NOAEC

200 mg/m³

Study duration:

subacute

Species:

rat

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Dose descriptor:

LOAEC

150 mg/m³

Study duration:

subchronic

Species:

rat

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

In a subchronic inhalation toxicity study ethyl lactate was administered to 5 male and 5 female Wistar rats/concentration by whole body exposure at concentrations of 0, 0.025, 0.075 and 0.2 mg/L (0, 25, 75 and 200 mg/m³) for 6 hours per day, 5 days/week for a total of 28 days. Two additional (recovery) groups of 5 male and 5 female Wistar rats exposed to 0 or 0.2 mg/ were kept untreated for 28 post-exposure days. Clinical observations, growth, macroscopical observations at autopsy and microscopical examinations of the nose were used as criteria for disclosing possible harmful effects.

There were no compound related effects in mortality, clinical signs, body weight or gross and histological pathology. Microscopic examination revealed minimal changes (nest-like infolds, slight hypertrophy, and slight hyperplasia) in the nasal respiratory epithelium of animals in all groups, the control group included. Type and incidence of the changes were similar in the various groups, or the changes occurred in a single animal only. These changes were not ascribed to treatment. The NOAEL is 200 mg/m³.

In contrast to a previous study (TNO report V 90.322), in which rats were exposed to 150, 600 or 2500 mg ethyl lactate per m³ for 28 days, the results of the last study show that rats exposed to 25, 75 or 200 mg ethyl lactate per m³ for the same period did not develop compound-related histopatholocial changes in the nose. The histopathological changes observed at an exposure concentration of 150 mg/m³ (TNO report V 90.322), viz. replacement of olfactory epithelium by respiratory epithelium, goblet cell hypertrophy and moderate goblet cell hyperplasia, were considered to be in line with the changes observed at concentration-response relationshop including the response seen at the 150 mg/m³ exposure concentration. The minimal changes observed in the present study consisting of nest-like infolds and slight hypertrophy and hyperplasia are fully comparable to the minimal changes observed at the 150 mg/m³ level of the previous study. However, since in the present study these minimal changes were observed in all groups, controls included, and their incidences in treatment groups were not different from those in the control group, or the changes occurred in a single animal only, these minimal alterations were not ascribed to treatment. Therefore, it is concluded that the no-adverse-effect level of ethyl lactate in the present study is 200 mg/m³, indicating that the level of 150 mg/m³ used in the previous study (TNO report V 90.322), should be considered a no-adverse-effect level as well.

The exposure to ethyl lactate at levels up to 2500 mg/m³ resulted in concentration-related adverse effects in the nose of all test groups and in growth retardation and decreased food consumption in rats exposed to 2500 mg ethyl lactate/ m³ air. Growth retardation might be explained by the impaired ability to smell and taste as a result of severe damage to the olfactory epithelium. The increased blood glucose value in males exposed to 2500 mg/m³ is considered an isolated finding unrelated to treatment. Further all observed effects can be explained from the reduced food intake and subsequent growth retardation.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
Inhalation toxicity information is available for ethyl lactate and ethylhexyl lactate. There is a definitive but not very steep correlation between no-effect levels and alkyl chain length with longer alkyl chain lactates being more toxic. As such methyl lactate will be less toxic than ethyl lactate, and the NOAEC can be set at the NOAEC for ethyl lactate.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
Ethyl lactate is irritating to the lung epithelium; irritation is caused by enzymatic hydrolysis to lactic acid. With a lower molecular weight and faster hydrolysis rate, methyl lactate will also be iriitating to the lung epithelium

Justification for classification or non-classification

No compound related effect in mortality, clinical signs, body weight or gross and histological pathology were observed at concentrations up to 200 mg/m³.

Microscopic examination revealed minimal changes (nest-like infolds, slight hypertrophy, and slight hyperplasia) in the nasal respiratory epithelium of animals in all groups, the control group included. Type and incidence of the changes were similar in the various groups, or the changes occurred in a single animal only. These changes were not ascribed to treatment. The NOAEL is 200 mg/m³.