Calcium (S)-2-hydroxypropionate

Endpoint summary

Description of key information

There are no reliable studies available for the assessment of the repeated dose toxicity endpoint with the target substance Calcium (S)-lactate itself, but available data from an oral repeated dose toxicity study conducted with the pentahydrate of calcium lactate was used to assess the specific target organ toxicity of the target substance. Based on the results, no classification for specific target organ toxicity is warranted for Calcium (S)-lactate.

For details and justification of read-across please refer to the report attached in section 13 of IUCLID.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Details on results:

All observed effects could be attributed to calcium overload/imbalance. No lactate toxicity was observed.

Dose descriptor:

NOAEL

Effect level:

50 000 mg/L drinking water

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

Critical effects observed:

no

Conclusions:

In conclusion, 5% calcium lactate in drinking water or diet does not result in adverse effects attributable to lactate.

Executive summary:

In a subchronic toxicity study (similar to OECD 408), Calcium lactate was administered to Fischer 344/DuCrj rats.

In Experiment I, Calcium lactate was mixed at 5, 2.5, 1.25, 0.6, and 0.3 % in the drinking water and the rats were given this solution ad libitum for 13 weeks. As a result, the inhibition of body weight gain in the 5 % group fell within 10 % of that in the control group. Some examination values showed variations in the hematological and hematobiochemical studies, but no controversial findings were obtained in the pathohistological search. Since the highest solubility of Calcium lactate is 5%, experiments II and III were carried out by giving blended diet in order to study the toxicity at higher doses. In experiment II, Calcium lactate was mixed at concentrations of 30, 20, 10, and 5 % in the B-blend powder diet and then the rats were given this diet ad libitum for 20 weeks. In experiment III, the rats were given the CRF-1 or the B-blend powder diet ad libitum for 8 weeks. As a result, in experiment II, nephrocalcinosis was observed in all the groups including the control group. The degree of the lesion was in reverse correlation with the administered concentrations of calcium and the lesion was seen more intensely in female rats. In experiment III, nephrocalcinosis resulting from the administration of the B-blend diet was already observed in the 4th week. Nephrocalcinosis as observed in experiments II and III was attributable to the small Ca/P value in the B-blend diet.

From the above results, the optimal dose for a long-term toxicity/carcinogenicity study has been determined to be 5 and 2.5 % based on the values obtained from experiment I.

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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

There are no reliable studies available for the assessment of the repeated dose toxicity endpoint with the target substance Calcium (S)-lactate itself, but available data from oral repeated dose toxicity studies conducted with the pentahydrate of calcium lactate were used to assess the specific target organ toxicity of the target substance.

In a 13-week sub-chronic oral toxicity study conducted similar to OECD TG 408, calcium lactate in drinking water was administered to Fischer 344/DuCrj rats. In this study, 5% calcium lactate in drinking water does not result in adverse effects.

By using the default values of water intake and body weights of Fischer 344 rats established by US EPA, 1988: Recommendations for and Documentation of Biological Values for Use in Risk Assessment, EPA/600/6-87/008 the 5% dose can be estimated to be equivalent to 7777 mg/kg bw/day for males and 8468 mg/kg bw for females. 

In addition, the long-term toxicity, carcinogenicity of calcium lactate was examined in F344 rats. Calcium lactate was given ad libitum in the drinking-water at levels of 0, 2.5 or 5% to groups of 50 male and 50 female rats for two years. No clear toxic lesion was specifically caused by long-term administration of calcium lactate. No significant dose-related increase was found in the incidences of tumors in any organ or tissue. The results indicated that calcium lactate had neither toxic nor carcinogenic activity in F344 rats (see IUCLID section 7.7).

Justification for classification or non-classification

Based on the available data, classification of Calcium (S)-lactate is not warranted according to CLP Regulation 1272/2008.