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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The objective of the study was to determine levels of D4 in blood and expired air after dermal application.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes
Remarks:
13C

Test animals

Species:
human
Strain:
other: NA
Sex:
male/female

Administration / exposure

Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 hours
Doses:
Males: 1.4 g; Females: 1.0 g
No. of animals per group:
Three males and three females
Control animals:
no

Results and discussion

Conversion factor human vs. animal skin:
NA

Any other information on results incl. tables

D4 levels were significantly elevated above baseline in blood and plasma at 1, 2, 4 and 6 hours and in exhaled air at all time points after application. The peak levels were observed at one hour (0.57 -5.67 ng/g blood and 0.85 -7.02 ng/g plasma) and dropped rapidly at subsequent time points. The three female subjects had a significantly higher blood and plasma levels of D4 compared with the three males subjects. The mean blood peak level of D4 was 4.45 ng/gm (SD. 1.10) for women and 1.30 ng/gm (S.D. 0.77) for men. There were considerably higher levels of D4 in exhaled air (at one hour the mean peak D4 level in exhaled air was 111 ng/L (S.D. 113) for women and 30 ng/L (S.D. 37) for men) than would have been expected from the blood levels. This could not be explained. Dermal absorption rate was not included in the report.

D4 blood levels in blood and plasma for women and men were significantly different at 1, 2, and 4 hrs. post-application.

The correlation between blood and plasma levels of D4 at all time points was excellent. In contrast, these was a
relatively poor correlation between blood levels and exhaled air levels of D4 especially at one hour post application,
i.e. considerably higher levels were found in exhaled air than would have been expected based on the blood levels. The
authors do not have an explanation for this phenomenon. Additional blood and exhaled air D4 levels at earlier time
points (0-2 hrs) would provide a more detailed evaluation of this phenomenon and help to clarify this discrepancy.

Applicant's summary and conclusion

Conclusions:
In a non-GLP, non-guideline dermal absorption study using human volunteers (Dow Corning Corporation, 2000), D4 was absorbed into the blood, and found to be exhaled, with peak blood/plasma levels at one hour after exposure. Levels decreased rapidly after this. Female absorbed more D4 than males.