Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 January 2010 to 3 February 2010 (in-life phase)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study undertaken according to current OECD and EU Test Guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute dermal toxicity (2-1-2), 12 Nohsan No 8147, Agricultural Production Bureau, November 24, 2000.
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tetrabutane
- Substance type: technical material
- Physical state: liquid
- Impurities (identity and concentrations): no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: 16.06.2008 0649/82535
- Expiration date of the lot/batch: 8 June 2010
- Stability under test conditions: no data
- Storage condition of test material: refrigerated, in the dark

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd.
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 228 to 334 g
- Fasting period before study: none
- Housing: idividually in solid bottomed polycarbonate cages with a stainless steel mesh lid
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23°C
- Humidity (%): 40-70 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

IN-LIFE DATES: From: 14 January 2010 (animal allocation) To: 3 February 2010 (terminal necropsy)

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorso-lumbar region (approximately 50 mm x 50 mm)
- % coverage: 10% of total body surface area
- Type of wrap if used: porous gauze held in place with a non-irritating dressing, and further covered by a waterproof dressing encircled firmly around the trunk of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water (30 - 40°C)
- Time after start of exposure: 24 hrs.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.532 ml/kg bodyweight
- Constant volume or concentration used: test material used as supplied (SG 0.79 g/ml)

Duration of exposure:
24 hours
Doses:
2000 mg/kg bodyweight
No. of animals per sex per dose:
5 male and 5 female animals
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). Local dermal irritation at the treatment site was assessed daily. The weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
Not undertaken

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
0/5 males and 0/5 females
Clinical signs:
There were no clinical signs considered to be related to treatment.
Very slight erythema was observed in one male and three females from Day 2, this sign had resolved in all animals by Day 4. In addition, desquamation (exfoliation) was observed in three males and three females from Day 4 to 6, resolving completely in all animals by Day 8.
Scabbing was also observed in two males from Day 7 or 8, resolving in one animal by Day
12 and persisted in the other until Day 15.
Body weight:
One female (Animal No. B7) was considered to have a low bodyweight gain Days 8 to 15.
All other animals were considered to have achieved satisfactory bodyweight gains throughout
the study.
Gross pathology:
No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute median lethal dermal dose (LD50) to rats of Tetrabutane was demonstrated to be greater than 2000 mg/kg bodyweight. Thus, the LD50 is above 2000 mg/kg/bw, and according to Regulation (EC) 1272/2008 the data are conclusive but not sufficient for classification.
Executive summary:

A study was performed at the Laboratories of Huntingdon Life Sciences, Alconbury, on behalf of Evonik Oxeno GmbH. , to assess the acute dermal toxicity of the test substance Tetrabutane. The study was conducted to GLP and in accordance with OECD Guideline 402 and EU Method B.3. The test substance was administered to the clipped dorsal skin of 5 male and 5 female rats at a dosage of 2000 mg/kg bodyweight under occlusive dressings for 24 hours (Limit test). Systemic and local signs of reaction to treatment were recorded at least once daily for 14 days following removal of the dressings.  There were no deaths and no systemic signs of reaction to treatment. Transient very slight erythema was observed at the application sites of one male and three females from Day 2 to 4 and desquamation (exfoliation) in three males and three females from Day 4 to 7, followed by scabbing in two of the males up to Days 12 or 15. One female rat was considered to have low bodyweight gain from Day 8 to 14.

The acute dermal median lethal dosage (LD50) to rats of Tetrabutane was demonstrated to be greater than 2000 mg/kg bodyweight.