Betaines, C12-16 (even numbered) -alkyldimethyl

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100

Additional information

Absorption

The physicochemical data suggest that the substance, betaines, C12-16 (even numbered) -alkyldimethyl, would be expected to be absorbed after oral exposure and therefore be systemically available. This was corroborated by the acute oral, sub-chronic studies and developmental toxicity study where some toxicity was evident. However, the data overall suggest that the substances tested were of relatively low to moderate toxicity despite their systemic availability after oral exposure.

Absorption by the dermal route might be expected to be low as reflected in the LD50 result from the acute toxicity study. However, in a study on two Zwitterionic surfactants (Buckset al, 1993) there was significant adsorption into the upper layers of the stratum corneum. It was suggested that such adsorption might not make the test substance readily available for absorption. In another study, using excised hairless mouse skin, cetyl betaine was partitioned into the skin but was only slowly transferred to the receptor phase - approximately 1.3% of the applied dose absorbed within 24 hours (study reviewed in CIR, 2018). In the same CIR publication, another study using human skin in vivo also suggested that the test substance (lauryl betaine) was adsorbed mostly into the stratum corneum. Overall, the evidence suggests that dermal penetration of betaine, cetyl betaine and lauryl betaine was exceptionally low (CIR,2018). As a conservative estimate it is likely that less than 10% dermal absorption (i.e. dose available systemically) would be considered as appropriate for use in risk assessments.

Information on the absorption and elimination of betaine has been described from a double-blind crossover study in humans (reviewed in CIR, 2018). Each subject ingested betaine in doses of 1, 3, and 6 g mixed with 150 mL orange juice. The doses were ingested 7 days apart following a 12-hour overnight fast. Blood samples for serum betaine concentration measurement were drawn just before receiving the betaine dose, at 20-minute intervals during the first 3 hours and then at 4, 7, and 24 hours post-dosing. Urine samples were collected before dosing and during the 24-hour follow-up period. Within 2 hours, a dose-dependent increase in serum betaine concentration was observed. Absorption and elimination of betaine were dose dependent, with urinary excretion of betaine increasing with betaine dose. Only a small proportion of the ingested betaine was excreted in urine with only 3.2%, 4.3%, and 7.4% of the 1, 3, and 6 g doses accounted for, respectively.

The physicochemical data for the substance suggest that it is unlikely that acute inhalation exposure (not expected to present an exposure risk) would result in adverse toxicity considering the relatively low toxicity evident in the acute or repeat dose studies presented.

Distribution

No data were found that specifically dealt with body, organ, or tissue distribution of the substance or associated read-across substances. However, the evidence suggests that there was some absorption after oral exposure which would indicate a moderate degree of oral absorption. It is likely, given the physicochemical nature of the substance, that there would be significant distribution in the GI tract and the liver and kidneys (as the main organs of metabolism and systemic excretion). There was no evidence to suggest bioaccumulation.

Metabolism

It is expected, from both the physicochemical and toxicity data, that metabolism (of the absorbed dose) would be mostly via the liver and secondarily the kidneys (e.g. effects on the kidneys were seen after sub-chronic exposure). It is also likely that significant metabolism/degradation would occur within the GI tract.

Excretion

Given the physicochemical properties of the substance, the nature of the effects seen in the repeat dose toxicity studies and probable limited bioaccumulation, it is predicted that excretion, (of parent and metabolites) would mostly be via the urine and faeces.

References

CIR (2018)	Safety Assessment of Alkyl Betaines as Used in Cosmetics. International Journal of Toxicology, Vol. 37(Supplement 1) 28S-46S.
Bucks DA, Hostynek JJ, Hinz RS and Guy RH (1993)	Uptake of two Zwitterionic surfactants into human skin in vivo. Toxicology and Applied Pharmacology, 120, 224-227.
US EPA (2010)	U.S. Environmental Protection Agency: Hazard Characterization Document; Screening level hazard characterization, Fatty Nitrogen-Derived Amphoterics Category, Subcategory I: Acyl amino propanaminium amphoterics.