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Administrative data

Endpoint:
additional toxicological information
Type of information:
other: expert statement
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
This is a custom literature review on the biology and (non)toxicity of D-(-)-lactic acid.
Justification for type of information:
Statement explaining why no further toxicity testing with lactic acid is required. This statement supports the submission of the available toxicity information for Lactic acid for classification and labelling of D-(-)-lactic acid, and consequently general lactic acid.

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
2010

Materials and methods

Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Literature review
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
(R)-lactic acid
EC Number:
233-713-2
EC Name:
(R)-lactic acid
Cas Number:
10326-41-7
Molecular formula:
C3H6O3
IUPAC Name:
2-hydroxypropanoic acid

Results and discussion

Any other information on results incl. tables

D-(-)-lactic acid is a common biological molecule, with low acute and no chronic toxicity, to which humans are continuoualy exposed, from diet, from bacterial generation in the gut, and from intramitochondrial (innate) processes.

Background exposure to D-(-)-lactic acid:

Lactic acid is normally present in human urine. A rough estimate suggests that the daily excretion reaches about 10 mg, which amounts to about 25% of the total amount of lactic acid. Excretion increases upon physical excercise, although the excretion of LL increases much more in absolute terms.

Small amounts of lactic acid are normally present in human blood. One study pointed to a 1.1-3.4 fold increase in the blood concentration of lactic acid due to eating or exercise. A rough indication of the range of the total amount is 3 – 25 mg per person. This range underlines the constant systemic exposure of the non-diseased population.

One study shows that in faeces from non-diseased persons lactic acid concentrations are very low (0 – 0.1 mmol/L). However the studies by Hove consistently point to higher concentrations (1.9 mmol/L).

Presence in the diet:

Dietary exposure of humans to lactic acid can occur when food products and beverages that have undergone lactic acid fermentation are consumed. Notable examples are regular yoghurt, sauerkraut, and wine. A 100 mL serving (small beaker) of regular yoghurt may contain up to 600 mg of lactic acid. Additional dairy sources are cheeses and kefir. A glass of wine may contain up to 160 mg of lactic acid. A moderate consumption of both yoghurt and wine may already result in a daily intake of 1 g lactic acid. 

Metabolism:

Lactic acid is formed in the human body by:

· Fermentation of carbohydrates by anaerobic bacteria in the colon. Although lactic acid is largely converted further into short chain fatty acid, a low but significant steady state concentration results.

· The detoxification of methylglyoxal by the glyoxalase system in the cytosol and in the mitochondria. The omnipresence of this system in living organisms as well as the adverse effects associated with its inhibition or lack of capacity, strongly suggests that lactic acid is formed throughout the body in the healthy individual.

Biokinetics:

The biokinetics of lactic acid is characterized by rapid and complete absorption and rapid elimination, largely by oxidation to pyruvate in the mitochondra, and to a lesser extent by urinary excretion. The importance of urinary excretion increases upon higher dose levels. D-(-)-lactic acid biokinetics thus resembles L-(+)-lactic acid to the extent that it is not expected to result in a difference in toxicity between the two enantiomers. The old idea that humans could not metabolize/utilize D-(-)-lactic acid and that the compound is not ‘physiological’ has been superseded by the notion of efficient utilization and the recognition that the compound should be regarded as fully ‘physiological’.

Overall conclusions:

- Natural exposure of humans and occurrence in humans of D-(-)-lactic acid make repeated-dose toxicity testing with this substance in the context of REACH redundant.

- Biokinetics indicates that the fact that D-(-)-lactic acid is a stereoisomer of L(+)-lactic acid does not preclude the use of toxicity data obtained with L(+)-lactic acid.

- D-(-)-lactic acid acidosis bears no relevance to the context of REACH.

Please refer to the attachment for the entire expert statement.

 

Applicant's summary and conclusion

Conclusions:
D-(-)-lactic acid is a common biological molecule, with low acute and no chronic toxicity, to which humans are continuously exposed, from diet, from bacterial generation in the gut, and from intramitochondrial (innate) processes.
Executive summary:

D-(-)-lactic acid is a common biological molecule, with low acute and no chronic toxicity, to which humans are continuously exposed, from diet, from bacterial generation in the gut, and from intramitochondrial (innate) processes.