Registration Dossier

Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study predated GLP but followed accepted scientific standards at the time of performance.

Data source

Reference
Reference Type:
publication
Title:
Metabolism of cutaneously applied surfactants
Author:
Drotman RB
Year:
1977
Bibliographic source:
Cutan. toxic., 3, 95-109

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The labeled material was applied to the skin of experimental animals. Urine, feces and carbon dioxide were collected at intervals for a predetermined period of time and finally the excess of substance was washed from the application site and the experimental animals were sacrificed. The excreta, skin washings, various organs and especially the skin at the application site were then assayed for radioactivity. When it was appropriate, biotransformation products were isolated and identified.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):Dioctadecyl dimethyl[1- 14C] ammonium chloride
- Specific activity (if radiolabelling): 30 µCi
- Locations of the label (if radiolabelling): First carbon of one alkyl group

No other data available
Radiolabelling:
yes

Test animals

Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no data available

Administration / exposure

Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Duration of exposure:
72 h (collection period)
Doses:
- Nominal doses: 10 mg (corresponding to 30 µCi) over a 5 - 8 cm area on the back of the rabbits
No. of animals per group:
one group of 4 rabbits
Control animals:
no
Details on study design:
TEST SITE
- Area of exposure: back of the animal
- % coverage: 5- 8 cm2
- The rabbits were restrained for 72 hours so they could not lick the material from thair backs or rub against their cages.

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Absorption in different matrices:
Administered radioactivity detected over a 72 hour-period expressed as mean +/- SEM (n=4)

- Skin test site: 88 ± 2.3%
- Skin, untreated site: 0.2% ± 0.1
- Urine: 0.15% ± 0.0
- Faeces: 0.16% ± 0.0
- Expired air: 0.27% ± 0.0
- Cage wash + cage wipe: 0.29% ± 0.0
Total recovery:
- Total recovery: 89 ± 2.4 expressed as mean +/- SEM (n=4)
Percutaneous absorption
Dose:
10 mg
Parameter:
percentage
Absorption:
< 1 %
Remarks on result:
other: 72 hours
Remarks:
Only traces of administered radioactivity detected over a 72 h period. Dermal absorption of DODMAC considered to be very low.

Applicant's summary and conclusion

Conclusions:
The dermal absorption of the Dioctadecyldimethylammonium chloride was very low.
Executive summary:

After dermal administration of 10 mg (≈ 30μCi) 14C-labelled test substance to the back of each of four rabbits over a 5 . 8 cm area most of the radioactivity remained at the site of application (88 ± 2.3%). Only traces of administered radioactivity were detected over a 72 h-period in urine (0.15 %), faeces (0.16 %), exhaled carbon dioxide (0.27 %), other skin (0.2%) and cage wash (0.3%).

Based hereupon, the dermal absorption and the concentration of Dioctadecyldimethylammonium chloride in the skin can be assumed to be very low.