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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 Apr - 29 Apr 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
no information on test substance formulation

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 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
Annex V to Directive 92/69/EEC (OJ No. L383A, 29,12,92) , Part B , Methods for the determination
of Toxicity , B.3
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2,5-bis(1,1,3,3-tetramethylbutyl)hydroquinone
EC Number:
212-990-3
EC Name:
2,5-bis(1,1,3,3-tetramethylbutyl)hydroquinone
Cas Number:
903-19-5
Molecular formula:
C22H38O2
IUPAC Name:
2,5-bis(1,1,3,3-tetramethylbutyl)hydroquinone
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Expiration date of the lot/batch: 03 July 1999

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature in the dark


Test animals

Species:
rat
Strain:
Wistar
Remarks:
Wistar strain Crl : (WI) BR (outbred, SPF-Quality)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: Young adult animals (approx. 9 weeks old)
- Weight at study initiation: Males: 328 +/- 22 g (mean +/- SD); Females: 222 +/- 12 g (mean +/- SD). Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: No
- Housing: Individually housed in labelled poycarbonate cages containing purified sawdust as bedding material (Woody SPF, supplied by B.M.I., Helmond, The Netherlands)
- Diet: Standard pelleted laboratory animal diet (from Carfil Quality BVBA, Oud-Turnhout, Belgium), ad libitum
- Water: Free access to tap water , ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): Approximately 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: Back (one day before exposure an area of approx. 5 x 7 cm was clipped)
- % coverage: Approx. 10% of the total body surface, i. e. approx. 25 square cm for males and 18 square cm for females
- Type of wrap if used: Nonwoven swab ( Dispomed® L) covered with aluminium foil and Coban flexible bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only. Suppliers: Lohmann, Neuwied, Germany (Dispomed) and 3M, St. Paul, USA (Coban & Micropore).

REMOVAL OF TEST SUBSTANCE
- Washing: Yes, with a tissue moistened with tap water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 10 mL/kg bw

Duration of exposure:
24 h
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
- Frequency of observations and weighing: Mortality / Viability: twice daily, body weight: Day 1 (pre-administration), 8 and 15, clinical signs: at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15
- Necropsy of survivors performed: Yes
Statistics:
No

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality
Mortality:
No mortality occurred.
Clinical signs:
Red staining of the head, neck and / or periorbital region was noted in three animals on Day 2. Erythema (Grade 1), scales and scabs were seen in the treated skin-area among some animals between Days 3 and 6. Brown staining of the skin on the back by the test substance was noted in two females on Day 2.
Body weight:
The changes noted in mean body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
Pelvic dilatation in the right kidney, found in one female at macroscopic post mortem examination, is commonly noted among rats of this age and strain and was therefore not considered to be toxicologically significant. No further abnormalities were noted among the animals.

Any other information on results incl. tables

Table 1. Mortality and clinical signs in the acute dermal toxicity study.

Dose

[mg/kg bw]

Mortality

Clinical signs

N*

N*

Males

2000

0/5

3/5

Females

2000

0/5

4/5

*N= Number of animals / number of animals used

Clinical signs: Red staining of the head, neck and / or periorbital region was noted in three animals (2 males and 1 female) on Day 2. Erythema (Grade 1), scales and scabs were seen in the treated skin-area among some animals (2 males and 3 females) between Days 3 and 6. Brown staining of the skin on the back by the test substance was noted in two females on Day 2.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
The acute lethal dermal dose (LD50) of AF-317 to rats was found to be greater than 2000 mg/kg bw.