Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP repeated dose guideline study with appropriate sattelite group to determine bioavailability via dermal route.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: OECD 411
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
425-950-7
EC Name:
-
Cas Number:
187393-00-6
Molecular formula:
C38-H49-N3-O5
IUPAC Name:
5-[(2-ethylhexyl)oxy]-2-(4-{4-[(2-ethylhexyl)oxy]-2-hydroxyphenyl}-6-(4-methoxyphenyl)-1,3,5-triazin-2-yl)phenol
Details on test material:
- Name of test material (as cited in study report): FAT 70’884/C
- Other names (as cisted in study report): TINOSORB S, CGF-C-1607
- Physical state: yellowish powder
- Analytical purity: >=97.6%
- Purity test date: 27 Feb 2003
- Lot/batch No.: 02464CL3
- Expiration date of the lot/batch: 26 February 2008
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories France (l’Arbresle, France)
- Age at study initiation: approximately 7 weeks
- Weight at study initiation: 221 g (range: 201 to 240 g) for the males and 166 g (range: 145 to 178 g) for the females
- Fasting period before study: None reported
- Housing: individually in suspended wire-mesh cages (43.0 x 21.5 x 18.0 cm); autoclaved sawdust
- Diet (e.g. ad libitum): A04 C pelleted maintenance diet [SAFE, Villemoisson, Epinay-sur-Orge, France], ad libitum
- Water (e.g. ad libitum): tap (filtered with a 0.22 µm filter), ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50 ± 20
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12h/12h (7:00 - 19:00)

IN-LIFE DATES: From: 6 May 2003; To: 14 Aug 2003

Administration / exposure

Type of coverage:
open
Vehicle:
polyethylene glycol
Duration of exposure:
13 weeks
Doses:
Daily: 0, 250, 500, 1000 (without collar), 1000 (with collar) mg/kg-bw
Control animals:
yes
Details on study design:
Satellite animals (1000 mg/kg-bw; with collars) were allocated for the determination of the test item plasma levels and were sampled prior to dosing, on day 8 and weeks 6 and 13.
Details on in vitro test system (if applicable):
10 (principal), plus 3 satellite animals per sex per dose group.

Results and discussion

Signs and symptoms of toxicity:
no effects
Dermal irritation:
yes
Remarks:
Scabs at site of administration
Absorption in different matrices:
Not determined
Total recovery:
Not determined
Percutaneous absorption
Dose:
1000 mg/kg-bw
Parameter:
percentage
Absorption:
ca. 0.01 - 0.06 %
Remarks on result:
other: Days 8, 37, & 91
Remarks:
Based on estimated total blood volume of 22 ml for a 350g male rat.

Applicant's summary and conclusion

Conclusions:
The plasma levels of the test item measured in animals given 1000 mg/kg/day with or without collar were very low and indicated that the test item was not bioavailable by cutaneaous route. Because of the very low levels in the high-dose groups, the samples for lower dose groups were not analyzed.