Registration Dossier

Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
other: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Justification for Read Across is given in Section 13 of IUCLID

Data source

Reference
Reference Type:
publication
Title:
Fate of n-Butanol in rats after oral administration and its uptake by dogs after inhalation or skin application
Author:
Di Vincenzo GD, Hamilton ML
Year:
1979
Bibliographic source:
Toxicology and applied Pharmacology 48: 317-325

Materials and methods

Principles of method if other than guideline:
Dogs were exposed to radioactively labelled test item dermally for 60 minutes. Breath and urine were collected for 8 hours. The dermal absorption and the excretion of the substance were determined.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Radiolabelling:
yes

Test animals

Species:
dog
Strain:
Beagle
Sex:
male

Administration / exposure

Type of coverage:
not specified
Vehicle:
not specified
Duration of exposure:
60 min
Doses:
20 µCi n-[1-14C]butanol in carrier
No. of animals per group:
2 males
Details on study design:
TEST SITE
- Area of exposure: dog skin
- % coverage: ca. 55.6 cm2
- Time intervals for shavings or clippings: 24 hours before application

TEST MATERIAL
- Amount(s) applied: ca. 15 mL
- Concentration: 20 µCi n-[1-14C]butanol in 15 mL carrier

USE OF RESTRAINERS FOR PREVENTING INGESTION: yes, animals were anaesthetised

Results and discussion

Percutaneous absorption
Time point:
60 min
Parameter:
rate
Absorption:
ca. 8.8 other: µg/min/cm^2

Any other information on results incl. tables

After 60 min, 29 mg of n-butanol was absorbed through the skin of each dog. The absorption rate was 8.8 µg/min/cm2. For comparison the 8-hr elimination of radioactivity in the breath and urine of dogs dosed intravenously with n-[1-14C]butanol was examined. The results are expressed as a percentage of the administered dose. About 15 % of the dose was eliminated in the breath as 14CO2 and 2.7 % was excreted in the urine. There was no unchanged n-butanol detected in the breath. The 8-hr elimination of radioactivity in the breath and urine averaged about 17 % of the administered dose.

Applicant's summary and conclusion

Conclusions:
Absorption: 8.8 µg/min/cm2 (29 mg of test item in 60 minutes)
Excretion: 15 % via breath as radioactively-labelled CO2; 2.7 % via urine; 0 % of unchanged test item via breath
Executive summary:
The elimination of radioactivity after the application of radioactively-labelled test item to the skin of two male Beagle dogs was examined. The hypothesis was that the metabolic fate and disposition of the test item is identical following either iv or dermal administrations. After 60 min, 29 mg of test item was absorbed dermally. The absorption rate was 8.8 µg/min/cm2. By comparison, the 8-hr elimination of radioactivity in the breath and urine of dogs dosed intravenously with the test item was examined. The results are expressed as a percentage of the administered dose. About 15 % of the dose was eliminated in the breath as 14CO2 and 2.7 % was excreted in the urine. There was no unchanged test item detected in the breath. The 8-hr elimination of radioactivity in the breath and urine averaged about 17 % of the administered dose.