Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998-02-23 - 1998-04-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD TG 402) performed under GLP

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted on 24th February 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OTS 798.1100 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
429-460-4
EC Name:
-
Cas Number:
7078-98-0
Molecular formula:
C21 H26 O
IUPAC Name:
2,6-di-tert-butyl-4-(phenylmethylidene)cyclohexa-2,5-dien-1-one

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, U.S.A. (on 2/17/98)
- Age at study initiation: bom the weeks of 11/30 through 12/14/97
- Weight at study initiation: 2.1 – 2.7 kg (males), 2.0 – 2.4 kg (females)
- Housing: 1/cage in suspended wire cages
- Diet: Fresh Purina Rabbit Chow, provided daily
- Water: ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: temperature-controlled
- Humidity: Not indicated
- Photoperiod: 12 hours dark / 12 hours light
- Other: Room was kept clean and vermin free

IN-LIFE DATES: From: 1998-03-02 To: 1998-03-15

Administration / exposure

Type of coverage:
occlusive
Vehicle:
physiological saline
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal area of the trunk of the animals
- Coverage: Approximately 10 % of the total body surface
- On test day 1, the test item was applied under a 4 layered surgical gauze patch approximately 10x15 cm. The patch and test item were moistened with 1.5 mL of saline. Gentle pressure was applied to the gauze.
- Type of wrap: The torso was wrapped with plastic which was secured with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test item was gently wiped from the treated site before observation

TEST MATERIAL
- Amount applied: 2000 mg/kg bw (based on 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 rabbits
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Observation of test sites: 30 to 60 minutes post patch removal and again at 24, 48 and 72 hours post patch removal and on days 5, 7,10 and 14 (using numerical Draize scoring code)
- Frequency of further observations and weighing:
Toxicity and pharmacological effects: 1, 2 and 4 hours postdose and once daily for 14 days
Mortality: Twice daily for 14 days
Body weights: Pretest and on days 3, 7 and 14 or at death.
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was used.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
All animals survived the 2000 mg/kg bw dermal application.
Clinical signs:
There were no abnormal systemic signs noted during the observation period.
Body weight:
Body weight changes were normal in 8/10 animals. One male and one female lost weight at some time during the observation period.
Gross pathology:
Necropsy results were normal in 7/10 animals. Kidney abnormalities were noted in two males and treated skin abnormalities in one female.
Other findings:
- Other observations: Dermal reactions were absent to well defined on day 1, absent to slight on day 2, absent to well defined on day 3, absent to moderate on days 4 and 5, and absent to well defined on day 7. By days 10 and 14, dermal reactions were absent to slight.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU