Dodecan-1-ol

Basic toxicokinetics

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

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

Test material information

Constituent 1

Reference substance name:

Dodecan-1-ol

EC Number:

203-982-0

EC Name:

Dodecan-1-ol

Cas Number:

112-53-8

Molecular formula:

C12H26O

IUPAC Name:

dodecan-1-ol

Test material form:

other: Liquid

Radiolabelling:

yes

Remarks:

14-Carbon

Test animals

Species:

mouse

Strain:

other: HR/De

Sex:

not specified

Administration / exposure

Route of administration:

dermal

Vehicle:

other: unchanged (no vehicle), and solutions in squalene, castor oil and triethyl citrate (TEC)

Duration and frequency of treatment / exposure:

24 hour exposure

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.05 other: %

Doses / concentrations 2

Dose / conc.:

0.5 other: %

Doses / concentrations 3

Dose / conc.:

5 other: %

Doses / concentrations 4

Dose / conc.:

50 other: %

Doses / concentrations 5

Dose / conc.:

100 other: %

No. of animals per sex per dose / concentration:

3 hairless mice/group

Control animals:

no

Details on study design:

Groups of 3 hairless mice were used to investigate percutaneous absorption of various n-alkanols including dodecan-1-ol. The 1-C14 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 wwith 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 in some of the compounds tested.

Results and discussion

Main ADME results

Type:

excretion

Results:

The expiratory excretion rate of lauryl alcohol (dodecanol) was 91%; for the other alcohols, at least 65% of the absorbed dose was excreted as CO₂ in the expired air.

Any other information on results incl. tables

Distribution results were reported for lauryl alcohol (98% pure). 95% of the dose adminstered was recovered from the application site at 24 hours after 

dosing. 0.13% remained in the body while 0.10% was excreted in the urine and faeces. 2.61% was excreted in expired air as CO₂. The ratio of the 

amount of compound excreted via expired air to the amount absorbed is the expiratory excretion rate. It was 91% for lauryl alcohol. The respiratory 

excretion rates for all the other alcohols investigated were >65% although all the actual data is not reported. 

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 dodecan-1-ol was 3%, this was increased in squalene but largely unchanged 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 was proportionally related to the degree of percutaneous absorption.

The publication reported in full the results only for lauryl aclohol (dodecan-1-ol 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 are 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 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 bioaccumulation potential based on study results
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). A similar trend was observed with the other alcohols tested. Absorption decreased with increasing carbon chain length and was affected by solvent and concentration.

Executive summary:

The publication reported in full the results only for lauryl aclohol (dodecan-1-ol 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). For the other alcohols, at least 65% of the absorbed dose was excreted as CO₂ in the expired air for the other alcohols.

The absorption rate was investigated in different solvents (squalene, castor oil, triethyl citrate (TEC)). The percutaneous absorption rate of undiluted dodecan-1-ol was 2.84%, 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.