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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
from 1993-08-04 to 1993-08-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline study
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1981
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
84/449/EEC
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): P0314 (Methyltertrahydrophtalic anhydride/NT)
- Physical state: colourless slightly viscous liquid
- Analytical purity: 99.9 %
- Lot/batch No.: 93/307
- Storage condition of test material: room temperature in clear glass jar

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Five male and five female Sprague-Dawley strain rats were supplied by Charles River (UK) Ltd., Manston, Kent, U.K. At the start of the study the males weighed 234-255 g and the females 207-237 g, and were ten to fourteen weeks of age. After a minimal acclimatisation period of at least five days the animals were selected at random and given a unique number within the study by indelible ink marking on the tail and a number written on a cage card.
The animals were housed in suspended polypropylene cages furnished with softwood sawdust. The animals were housed individually during the 24-hour exposure period and in groups of up to five, by sex, for the remainder of the study. Free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.) was allowed throughout the study. The animal room was maintained at a temperature of 19-22°C and relative humidity of 50-56 %. The rate of air exchange was approximately 15 changes per hour and the lightening was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
On the day before treatment the back and flanks of each animal were clipped free of hair using veterinary clippers to expose a skin area of approximately 5 cm x 4 cm. The calculated volume (1.68 mL/kg) of the undiluted test material, as received, was applied uniformly to an area of shorn skin (approximately to 10 % of the total body surface area) using a graduated syringe. A piece of surgical gauze measuring 7 cm x 4 cm was placed over the treatment area and semioccluded with a piece of self-adhesive bandage (HYPERTIE). The bandage was further secured with a piece of BLENDERM wrapped around each end. The animals were caged individually for the 24-hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place. After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw (1.68 mL/kg bw)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. The animals were also observed for any dermal reactions after removal of the dressings and subsequently once daily for the remainder of the study. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
Data evaluations included the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.

Results and discussion

Preliminary study:
no preliminary study
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Sex:
male/female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the study.

Dermal Reactions:
Very slight to well-defined erythema was noted at the treatment sites of all animals one day after dosing with very slight erythema in all females two days after dosing. Haemorrhage of the dermal capillaries was noted in all animals one day after dosing and persisted in all females two days after dosing. Crust formation was noted at the treatment sites of two females three and four days after dosing. Treatment sites appeared normal two to five days after dosing.
Body weight:
All animals showed expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
none

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test material, tetrahydromethylphthalic anhydride, in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bw.
Executive summary:

The study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 402 "Acute Dermal Toxicity" referenced as Method B.3 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

A group of ten animals (five males and five females) was given a single 24-hour, semi-occluded dermal application to intact skin at a dose level of 2000 mg/kg bw. The animals were observed for fourteen days after the day of treatment and were then killed for gross pathological examination.

There were no deaths. No signs of systemic toxicity were noted during the study. Very slight to well-defined erythema was noted at the

treatment sites of all animals. Other skin reactions noted were haemorrhage of the dermal capillaries and crust formation. Treatment sites appeared normal two to five days after dosing. All animals showed expected gain in bodyweight during the study. No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight.