1,3-dihydroxyacetone

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - dermal (%):

37.2

Additional information

ADME:

Data on the ADME of dihdroxyacetone are not available. However, considering the close structural relationship of DHA to glycerol, data for glycerol are presented in the following as a read across:

The publications were used in the OECD evaluation of glycerol (SIDS). OECD concluded as follows:

Data from studies in humans and animals indicate glycerol is rapidly absorbed in the intestine and the stomach, distributed over the extracellular space (Lin 1977, Tourtelotte 1970) and excreted. Glycerol is phosphorylated to alpha-glycerophosphate by glycerol kinase predominantly in the liver (80-90%) and kidneys (10-20%) and incorporated in the standard metabolic pathways to form glucose and glycogen (Tao 1983, Lin 1977).

Considering the close structural relationship of glycerol and DHA it can be concluded that DHA is absorbed and excreted in a similar manner than glycerol, i.e. DHA is also rapidly and completely absorbed.

Dermal absorption:

The in vitro percutaneous absorption of [¹⁴C]-DHA was determined in human dermatomed skin. This evaluation was performed in two separate experiments using typical self-tanning formulations containing DHA at a concentration of 2.5% , 5%, 7% or 10%.

About two (2) mg.cm^-2 of each self-tanning formulation was applied to the skin surface. After 24 hours of exposure, the skin surface was rinsed off, and the percutaneous absorption of DHA was determined by measuring radioactivity in various skin compartments (Liquid Scintillation Counting). The amounts of DHA penetrated into the receptor fluid and considered as absorbed (sum of amounts contained in living epidermis/dermis and receptor fluid) were estimated as follows:

- 2.5% DHA : 1.09% (0.77 µg.cm^-2), and 27.5% (18.0 µg.cm^-2), respectively

- 5%   DHA :     0.89% (1.07 µg.cm^-2), and 27.7% (34.0 µg.cm^-2), respectively

- 7%   DHA :     1.46% (2.22 µg.cm^-2), and 31.0% (49.5 µg.cm^-2), respectively

- 10% DHA : 1.33% (2.99 µg.cm^-2), and 37.2% (84.4 µg.cm^-2), respectively. A study in human volunteers was conducted under in-use conditions (cosmetic use). Approximately 1 g of a gel containing 50 mg of [¹⁴C]-DHA (5%, w/w), was applied on a skin area of 333 cm² on the upper arm of each volunteer, i.e. skin application rate was 3 mg.cm^-2. The treated area was protected with a non-occlusive cover, the latter not being in contact with the gel layer. Six hours after the application, the whole application area was washed and the remaining gel and SC removed by ten successive skin strips with adhesive films. The skin stripping procedure was repeated on the day of discharge (72 hours after start of the exposure period). All plasma DHA concentrations were below 0.005 µg-eq/ml, with plasma radioactivity always lower than two times the radioactivity background value. Consequently, standard pharmacokinetic parameters could not be calculated. At the end of the study, mean total excretion rate in urine and faeces was 0.074 % of the radioactivity applied (min-max: 0.025%-0.133%). The total recovery rate was low in that study, i.e. in the range 42%-51% of the applied dose. This may have been due to the use of a gel formulation which dried during the exposure period (under non-occlusive conditions) and eventually cracked and fell off, thus leading to test substance loss and low recovery. Additionally, it is well known that DHA binds to lysine residues of proteins within the skin, to produce the intended brown colouration of the skin [23]. Consequently, it can reasonably be assumed that a significant proportion of the DHA/radioactivity applied remained bound to skin proteins, as indicated by the brown discolouration of the skin still present after tape stripping on the day of discharge. This observation also reveals that the tape stripping procedure used, i.e. ten subsequent tape strips taken, could not remove the entire SC. The results of human volunteer study showed that the findings obtained in the in vitro study might be considered as an overestimation of the bioavailability.