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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
Percutaneous absorption of aliphatic compounds.
Author:
Iwata Y, Moriya Y, Kobayashi T
Year:
1987
Bibliographic source:
Cosmet. Toiletries 102(2): 53-68.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
¹⁴C labelled test substances were applied to the dorsal skin using a plaster for a 24 hour period. Immediately following application each animal was placed in a container to measure expiratory excretion. At the end of the exposure period the treated area of skin was excised and dissolved using tissue  solubiliser. The carcass was homogenised in a blender with sodium hydroxide. An aliquot of the homogenate was then dried and combusted for determination of radioactivity. The effect of different solvents and concentration of the solvent was also investigated. The role of skin irritation in absorption of test substance was examined.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Radiolabelling:
yes
Remarks:
14-Carbon

Test animals

Species:
mouse
Strain:
other: HR/De
Sex:
not specified

Administration / exposure

Route of administration:
dermal
Vehicle:
unchanged (no vehicle)
Duration and frequency of treatment / exposure:
24 hour exposure
Doses / concentrationsopen allclose all
Dose / conc.:
0.05 other: %
Dose / conc.:
0.5 other: %
Dose / conc.:
5 other: %
Dose / conc.:
50 other: %
No. of animals per sex per dose:
3 hairless mice/group
Control animals:
no

Results and discussion

Main ADME results
Type:
excretion
Results:
The expiratory excretion rate of lauryl alcohol (dodecanol) was 91%; for the other alcohols including octan-1-ol, at least 65% of the absorbed dose was excreted as CO2 in the expired air.

Any other information on results incl. tables

The publication reported in full the results only for lauryl aclohol (Dodecanol C12) arriving at a value for the expiratory excretion rate which was the ratio of amount of 

compound excreted via expired air to the amount absorbed. It  was 91% for lauryl alcohol. The respiratory excretion rates for all the other alcohols 

investigated were >65% although the actual data is not reported. Following skin application of lauryl alcohol about 2.84 % of  the administered dose  was absorbed. Of this absorbed dose >90% was excreted in expired air (CO2).

Absorption decreased with increasing carbon chain length. The absorption rate was investigated in different solvents (squalene, castor oil, triethyl 

citrate (TEC). The percutaneous absorption rate of undiluted n-octanol was 50%, this was increased in squalene but decreased in castor oil or TEC This was also reported with the other alcohols tested and the tendency was more pronounced at higher concentrations.

The degree of skin irritation reported in the study was proportionally related to the degree of percutaneous absorption.

Applicant's summary and conclusion

Conclusions:
Interpretation of results: no or very low bioaccumulation potential based on study results
Absorption of the alcohols tested decreased with increasing carbon chain length and was affected by solvent and concentration; 50% of undiluted octan-1-ol was absorbed, compared with approximately 15% of a 5% solution. The expiratory excretion rate of lauryl alcohol (dodecan-1-ol) was 91%. For the other alcohols, including octan-1-ol, at least 65% of the absorbed dose was excreted as CO₂ in the expired air.
Executive summary:

The publication reported in full the results only for lauryl aclohol (Dodecanol, C12) arriving at a value for the expiratory excretion rate which was the ratio of amount of 

compound excreted via expired air to the amount absorbed. It  was 91% for lauryl alcohol. The respiratory excretion rates for all the other alcohols 

investigated were >65% although the actual data is not reported. Following skin application of lauryl alcohol about 2.84 % of  the administered dose  was absorbed. Of this absorbed dose >90% was excreted in expired air (CO2).

The absorption rate was investigated in different solvents (squalene, castor oil, triethyl citrate (TEC). The percutaneous absorption rate of undiluted n-octanol was 50%, this was increased in squalene but decreased in castor oil or TEC. This was also reported with the other alcohols tested and the tendency was more pronounced at higher concentrations. Overall the study showed that absorption decreased with increasing carbon chain length