Benzene-1,2,4-tricarboxylic acid 1,2-anhydride

Skin irritation / corrosion

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

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

Test material information

Constituent 1

Reference substance name:

Benzene-1,2,4-tricarboxylic acid 1,2-anhydride

EC Number:

209-008-0

EC Name:

Benzene-1,2,4-tricarboxylic acid 1,2-anhydride

Cas Number:

552-30-7

Molecular formula:

C9H4O5

IUPAC Name:

1,3-dioxo-1,3-dihydro-2-benzofuran-5-carboxylic acid

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 or test system 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

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 hours

Score:

1

Reversibility:

fully reversible

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48 hours

Score:

0.33

Reversibility:

fully reversible

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72 hours

Score:

0.33

Reversibility:

fully reversible

Results 4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 hours

Score:

1.17

Reversibility:

fully reversible

Results 5

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 48 hours

Score:

1

Reversibility:

fully reversible

Results 6

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72 hours

Score:

0.83

Reversibility:

fully reversible

Results 7

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24-72 hours

Score:

0.39

Reversibility:

fully reversible

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24-72 hours

Score:

1

Reversibility:

fully reversible

Results 9

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.