Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From November 20,2009 to December 30,2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well described GLP compliant study conducted to recognized international test guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: 1,2,3,6 tetrahydrophthalic anhydride (THPA)
- Molecular formula : C8H8O3
- Molecular weight : 152.1473
- Smiles notation : O=C1OC(=O)C2C1C/C=C\C2
- InChl : 1/C8H8O3/c9-7-5-3-1-2-4-6(5)8(10)11-7/h1-2,5-6H,3-4H2
- Physical state: solid , white scale
- Analytical purity: 99.92%
- Lot/batch No.: SAT4209215
- Expiration date of the lot/batch: 03/04/2010
- Storage: Room temperature in a desiccator

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Italy S.r.l., 33049 San Pietro al Natisone (UD), Italy
- Choice of the species: The Sprague Dawley SD rat was used, being the species and strain of choice because is accepted by many regulatory authorit ies and there is ample experience and background data on this species and strain.
- Age at study initiation: 6 to 8 weeks old
- Weight at study initiation: 176 to 200 grams:
- Housing: Harlan Italy S.r.l., 33049 San Pietro al Natisone (UD), Italy
- Caging: Polycarbonate cages measuring 42.5x26.6x18 cm with stainless steel mesh lid and floor.
- Cage tray control: Daily inspected and changed as necessary (at least 3 times/week)
- Diet : 4 RF 18 ; ad libitum throughout the study
- Water : drinking water supplied to each cage via a water bottle , ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22°C ± 2°C
- Humidity (%): 55% ± 15%
- Air changes: Approximately 15 to 25 air changes per hour
- Photoperiod : Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours

- Selection/Allocation: Random at arrival/The body weight of each individual was within 20% of the mean and within the range of 200-300 grams.
- Animal Identification: Permanent, following arrival, by a combination of ear notch (units) and tattoo on the hind feet. Males and females were identifi ed by even and odd numbers, respectively.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
corn oil
Details on dermal exposure:
TEST SITE
- Area of exposure and % coverage: An aliquot of the supplied test item was spread evenly over an area of approximately 10% of the body surface area.
- Type of wrap : A patch of surgical gauze covered by a strip of synthetic film was placed over the treated site and the whole assembly held in place by encircling the trunk of the animal with a length of elastic adhesive bandage, this forming a semi-occlusive barrier.

REMOVAL OF TEST SUBSTANCE
- Washing After exposure, the adhesive bandage and gauze patch were removed. The treatment area was cleaned by gentle swabbing of the skin with cotton wool soaked with corn oil.:

Duration of exposure:
24 hours
Doses:
single dose of 2000 mg/kg bw
No. of animals per sex per dose:
A single group of 5 male and 5 female animals was dosed at a level of 2000 mg/kg.

Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality observed
Clinical signs:
no clinical signs were observed in male or female animals during the observation period.
Body weight:
Changes in body weight were within the expected range for this species and age of animals at the end of the study.
Gross pathology:
No abnormalities were found at necropsy examination performed on all animals at termination of the study.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
These results indicate that tetrahydrophthalic Anhydride (THPA), has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.
Executive summary:

Acute dermal toxicity has been investigated in accordance with OECD/EU test methods. A single dose of 2000 mg/kg was administered to a group of 5 male and 5 female animals for 24 hours. No toxicity occurred and the lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.