Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998-02-03 - 1998-04-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted on 24th February 1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
-
EC Number:
426-650-9
EC Name:
-
Cas Number:
191743-75-6
Molecular formula:
Unspecified
IUPAC Name:
2-{[4,6-bis({butyl[1-(cyclohexyloxy)-2,2,6,6-tetramethylpiperidin-4-yl]amino})-1,3,5-triazin-2-yl]amino}ethan-1-ol

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Boyertown, PA (on 1/27/98)
- Age at study initiation: Animals were born in the weeks of 11/16 through 11/30/1997, Experimental Start Date: 02/23/98
- Weight at study initiation: 2.4 – 2.7 kg (males), 2.3 – 2.5 g (females)
- Housing: 1 animal/sex/cage in suspended wire cages, Bedding was changed three times/week
- Diet: Fresh Purina Rabbit Chow, provided daily
- Water: ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Photoperiod: 12 hours dark / 12 hours light
- Animal room was temperature controlled, kept clean and vermin free

IN-LIFE DATES: From: 1998-02-23 To: 1998-03-09

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
physiological saline
Details on dermal exposure:
TEST SITE
- 24 h before: Dorsal area of the trunk of each animal was clipped free of hair
- Area of exposure: approximately 10% of the body surface
- Test item was applied under a 4 layered surgical gauze patch measuring 4 x 6 inches; patch and test item were moistened with saline
- Gentle pressure was applied to the gauze to aid in the distribution of the test item
- Type of wrap: Plastic which was secured with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test item was gently wiped from the dose site prior to dermal observations.

TEST MATERIAL
- Amount applied: 2000 mg/kg bw, based on the dry weight
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Toxicity and pharmacological effects: 1, 2 and 4 hours postdose and once daily for 14 days
- Mortality: twice daily for 14 days
-Test sites were scored for dermal irritation at 30 to 60 minutes post patch removal and again at 24, 48 and 72 hours post patch removal using the numerical Draize scoring code. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. Additional signs were described.
- Frequency of weighing: recorded pretest and on days 3, 7 and 14
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived the 2000 mg/kg bw dermal application.
Clinical signs:
Dermal reactions (including irritation) were absent on days 1, 2, 3 and 4.
Instances of diarrhea, soiling of the anogenital area, few feces and wetness of the anogenital area were noted during the observation period. Five males and three females appeared normal at each observation period.
Body weight:
Body weight changes were normal in 7/10 animals. Three animals lost weight at some time during the observation period.
Gross pathology:
Necropsy results were normal in 9/10 animals. Excess fluid in the peritoneal cavity was noted in one female.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met