(3S-cis)-3,6-dimethyl-1,4-dioxane-2,5-dione

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Review

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Metabolic acidosis.

Author:

Connor, H. and Woods, H.F.

Year:

1982

Bibliographic source:

Pitman|Books Ltd London (Ciba Foundation symposium 87) p. 214-234

Reference 2

Reference Type:

publication

Title:

Lactate and glucose interactions during rest and exercise in men: effect of exogenous lactate infusion.

Author:

Miller, B.F., Fattor, J.A., Jacobs, K.A., Horning, M.A., Navazio, F., Lindinger, M., I., and Brooks, G.A.

Year:

2002

Bibliographic source:

Journal of Physiology, Vol.544, Nr.3, p.963-975

Reference 3

Reference Type:

publication

Title:

Lactate - a signal coordinating cell and systemic function.

Author:

Philp, A., Macdonald, A.L., Watt, P.W.

Year:

2005

Bibliographic source:

The Journal of Experimental Biology, Vol.208, p.4561-4575

Materials and methods

Objective of study:

other: Evaluation of the native biology of lactic acid in mammals, including humans, including metabolism.

Principles of method if other than guideline:

Lactic acid is a ubiquitous and essential molecule for life. The metabolism and kinetics of lactic acid in organisms is well understood and extensively treated in handbooks and numerous research articles..

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

L-(+)-lactic acid

EC Number:

201-196-2

EC Name:

L-(+)-lactic acid

Cas Number:

79-33-4

IUPAC Name:

2-hydroxypropanoic acid

Test animals

Species:

other: mammal

Details on test animals or test system and environmental conditions:

Information on endogenous lactic acid.

Administration / exposure

Details on exposure:

Information on endogenous lactic acid.

Duration and frequency of treatment / exposure:

Information on endogenous lactic acid.

Doses / concentrations

Remarks:

Doses / Concentrations:
Information on endogenous lactic acid.

Details on study design:

Information on endogenous lactic acid.

Details on dosing and sampling:

Information on endogenous lactic acid.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: Lactic acid is an essential part of basic metabolism
he metabolism of lactic acid is well understood.

In the evaluation of the use of lactic acid as the active substance in biocidal products, the natural occurrence of lactic acid in human food and the human body, as well as the role of the compound in human metabolism and physiology should be taken into account. This means that, when the risk for its use in biocidal products is assessed, the natural exposure to lactic acid in food and via endogenous sources, as well as exposure via the use of lactic acid as a food additive should be considered.
In the present report it is concluded that lactic acid can no longer be considered as a “dead-end” waste product of human metabolism, but should instead be seen to play an important role in cellular, regional, and whole body metabolism. Lactic acid has been detected in blood, several other body fluids and tissues. Concentrations of lactic acid increase significantly during intense exercise. At rest, blood concentrations have been reported of 1-1.5 mMol/L (90.1-135.12 mg/L), which can increase up to 10 mMol/L (900.8 mg/L) during exercise.
External human exposure to lactic acid can occur via its natural presence in food, for example in fruit, vegetables, sour milk products, and fermented products such as sauerkraut, yogurt and beer. Based on the available information on concentrations of lactic acid in some of these products, an estimate of the daily consumption of lactic acid due to its natural presence in food was made using the ‘FAO/WHO standard European diet’. A (minimum) daily intake of 1.175 g/person/day was calculated using the available information.
Another source of external exposure is its use as food additive; as such it is authorized in Europe (E270) and the United States (generally recognized as safe = GRAS). A daily intake of 1.65-2.76 g/person/day was estimated using the “Per Capita times 10” method, based on the amount of lactic acid put onto the market (EU and USA) as a food additive by Purac.
Based on the high levels of lactic acid in the human body and in human food, and its use as food additive, the evaluation of the human health effects of lactic acid should first and for all be based on a comparison of this background exposure and the potential contribution of lactic acid in biocidal products to these levels. Therefore, a risk assessment should not be based on the comparison with effects of exposure, but on the comparison with the total daily intake of lactic acid via food, both naturally and as food additive, which was estimated to be 2.8 g/person/day. When the application of Purac’s products will not result in a systemic exposure that contributes substantially to the total systemic exposure, many of the standard human toxicological studies dealing with systemic effects are deemed superfluous.

Executive summary:

The natural occurrence of lactic acid in human food and the human body, as well as the role of the compound in human metabolism and physiology is of primary importance in the understanding of the metabolism and toxicology of lactic acid. This means that, in risk assessment, the natural exposure to lactic acid in food and via endogenous sources, as well as exposure via the use of lactic acid as a food additive should be considered.

In the present report it is concluded that lactic acid, in contrast to previously held belief, can no longer be considered as a “dead-end” waste product of human metabolism, but should instead be seen to play an important role in cellular, regional, and whole body metabolism. Lactic acid has been detected in blood, several other body fluids and tissues. Concentrations of lactic acid increase significantly during intense exercise. At rest, blood concentrations have been reported of 1-1.5 mMol/L (90.1-135.12 mg/L), which can increase up to 10 mMol/L (900.8 mg/L) during exercise.

External human exposure to lactic acid can occur via its natural presence in food, for example in fruit, vegetables, sour milk products, and fermented products such as sauerkraut, yogurt and beer. Based on the available information on concentrations of lactic acid in some of these products, an estimate of the daily consumption of lactic acid due to its natural presence in food was made using the ‘FAO/WHO standard European diet’. A (minimum) daily intake of 1.175 g/person/day was calculated using the available information.

Another source of external exposure is its use as food additive; as such it is authorized in Europe (E270) and the United States (generally recognized as safe = GRAS). A daily intake of 1.65-2.76 g/person/day was estimated using the “Per Capita times 10” method, based on the amount of lactic acid put onto the market (EU and USA) as a food additive by Purac.

Based on the high levels of lactic acid in the human body and in human food, and its use as food additive, the evaluation of the human health effects of lactic acid should first and for all be based on a comparison of this background exposure and the potential contribution of lactic acid in biocidal products to these levels. Therefore, a risk assessment should not be based on the comparison with effects of exposure, but on the comparison with the total daily intake of lactic acid via food, both naturally and as food additive, which was estimated to be 2.8 g/person/day. When the application of Purac’s products will not result in a systemic exposure that contributes substantially to the total systemic exposure, many of the standard human toxicological studies dealing with systemic effects are deemed superfluous.