Registration Dossier

Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991-07-17 to 1991-07-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study methods are similar to the OECD guideline 404 and the study was conducted in accordance with the GLP principles (self-certified).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
: there is no information on the purity of the test material; the test material was not moistened however it was applied onto the pre-moistened test sites of the animals
GLP compliance:
yes
Remarks:
self-certified including GLP compliance statement

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: White flake solid
- Lot/batch No.: ATTA 91-29 (TA 128H)
- Stability under test conditions: Stable under storage conditions
- Storage condition of test material: approximately 22°C

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
The animals were New Zealand White rabbits, 2-4 months of age, purchased from Johnson Rabbit Ranch. The rabbits arrived in three shipments with overall body weight ranges of 1.84-2.81 kg. The rabbits were held in quarantine for 3-6 weeks and examined to ensure their health and suitability as test subjects. Individuals were identified by metal ear tags and cage cards.
Each rabbit was provided with approximately 150 g of Purina Rabbit Chow HF #5326 daily. Reverse osmosis-purified water was supplied ad libitum. The rabbits were housed individually in stainless steel cages with Polyzorb cage liners placed below the mesh floor. The animal room average temperature and relative humidity were 22°C and 62%, respectively. Fluorescent lighting was provided on a 12 hour light/dark cycle.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
The test article was administered undiluted, individual doses were weighed onto aluminium foil to facilitate dosing. 0.5 g was applied uniformly to the pre-shaved moistened backs of the rabbits.
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
Three males and three females
Details on study design:
Rabbits were selected at random for the study.
The test site was prepared by clipping the fur from an area of approximately 240 cm². Each rabbit's back was moistened with reverse-osmosis-purified water immediately prior to dosing. The test material was covered with a 2.5x2.5 cm adhesive dressing. The mid section of each rabbit was wrapped in a lint-free cloth towel and Elastoplast bandage. The dressings were removed four hours after application of the test material and the test sites were rinsed with light mineral oil and wiped with a paper towel to remove residual test material.
The rabbits were weighed immediately prior to dosing for calculation of doses. All animals were observed daily for signs of mortality and morbidity. Observations for signs of dermal irritation were made at 30-60 minutes after dressing removal, then at 24, 48 and 72 hours, 7 and 24 days later. The descriptive criteria and scores of Draize were used.
Rabbits were euthanised at study termination on day 15, necropsies were not performed.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hours
Score:
0.33
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours
Score:
0.33
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
1.17
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hours
Score:
1
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
0.83
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 hours
Score:
0.39
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 hours
Score:
1
Reversibility:
fully reversible
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
1.7
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
One animal displayed severe erythema 30-60 minutes after removal of dressing. At 24, 48 and 72 hour timepoint, pinpoint areas of eschar formation and scabbing were noted with a localised erythema score of 2. Superficial flaking was noted. No evidence of corrosivity was noted in any animal.
Other effects:
No deaths occurred during the course of the study. The weight of the rabbits on the day of dosing ranged from 2.84 to 3.19 kg.

Any other information on results incl. tables

Summary of dermal irritation scores in rabbits for TMA

Time

Oedema

Erythema

 

952

953

954

955

956

957

952

953

954

955

956

957

1 hour

2

1

2

2

2

2

2

2

4

2

2

3

24 hour

1

1

1

1

0

2

1

1

1

1

1

2

48 hours

0

0

1

0

0

1

1

1

1

0

1

2

72 hours

0

0

1

0

0

1

1

0

1

0

1

2

Mean

0.33

0.33

1

0.33

0

1.33

1

0.67

1

0.33

1

2

 Mean 24 -72 hours

 0.39

1

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Trimellitic anhydride is not considered to be an irritant to the skin according to Directive 67/548/EEC and Regulation (EC) No 1272/2008.
Executive summary:

The skin irritation potential of trimellitic anhydride was evaluated in 3 male and 3 female New Zealand White rabbits. 0.5 g of the test material was applied to the shaved and pre-moistened backs of the rabbits, and covered with a semi-occlusive dressing for 4 hours. The dressings were removed at the end of the exposure period and the test sites rinsed with light mineral oil. Each application site was examined for dermal irritation and corrosivity 30 -60 minutes, 24, 48 and 72 hours and 7 and 14 days following removal of the wrappings. No deaths occurred during the course of the study. The test material was slightly irritating. All animals had recovered by the end of the observation period. No signs of dermal corrosivity were seen in any rabbit. Trimellitic anhydride is not considered as a skin irritant. On this basis, trimellitic anhydride does not warrant any classification according to Directive 67/548/EEC and Regulation (EC) No 1272/2008.