Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991-09-16 to 1991-10-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This guideline-comparable proprietary study was carried out according to GLP (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 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
The methods were broadly comparable to OECD 402 with the following exceptions: The test substance was not applied moistened, instead the shaved application site was moistened immediately prior to test article application. There was no information on the purity of the test article. There was no evidence that cage-side observations were carried out.
GLP compliance:
yes
Remarks:
self-certified including GLP compliance statement
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): Trimellitic anhydride (TMA)
- Physical state: White flake solid
- Lot/batch No.: ATTA 91-35 (TA 1281)
- Stability under test conditions: Stable
- Storage condition of test material: Room temperature (approximately 22C)

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
The animals were male and female New Zealand White rabbits, 2-4 months of age, purchased from Johnson Rabbit Ranch. The rabbits weighed 1.97-2.65 kg on arrival, and were held in quarantine for approximately 12 weeks, during which time they were 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 Lab Rabbit Chow HF #5326. Reverse-osmosis purified water was supplied ad libitum.
The rabbits were housed individually in stainless steel cages with Polyzorb cage liners underneath the grid floor. The animal room was maintained at an average temperature and relative humidity of 23°C and 39%, respectively. Fluorescent lighting was provided on a 12 hour light/dark cycle.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test material was applied undiluted. Individual doses were dispensed onto aluminium foil prior to application.
Approximately 24 hours prior to treatment initiation the fur was clipped from an area of approximately 240 cm² on the back of each rabbit and the skin was examined for abnormalities. The shaved application site was moistened immediately prior to test article application, and the test article covered with a 12.8x11.5 cm surgical dressing. The dressing was then covered by plastic film and secured by lint-free cloth and an Elastoplast bandage.
The dressings were removed after 24 hours and the skin was wiped gently with a paper towel and light mineral oil, to remove residual test material.
Duration of exposure:
24 hours
Doses:
Single dose of 2000 mg/kg bw
No. of animals per sex per dose:
One group of five rabbits/sex
Control animals:
no
Details on study design:
Rabbits used in the study were selected at random. Clinical signs were recorded over a 14 day post exposure period. Body weights were recorded immediately prior to dosing (and used for dosing calculations), then at 7 and 14 days post-application.
A limited gross necropsy was performed at the end of the observation period.
Statistics:
Statistical analysis was not performed.

Results and discussion

Preliminary study:
No preliminary results.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality at the limit dose
Mortality:
There were no mortalities.
Clinical signs:
All animals showed signs of irritation (erythema and oedema immediately following removal of the dressing). On day 2, none of the rabbits showed signs of oedema. Superficial flaking was noted in two animals during the course of the study. By day 10 -14, four males had recovered and by day 10 -11, four females had recovered. At study completion complete recovery from all signs of dermal irritation was observed in all rabbits.
Body weight:
The initial mean body weights of the male and female rabbits were 3.57 kg and 3.44 kg, respectively. Mean female body weights increased during the study, however one male rabbit lost 0.07 kg and another male rabbit lost 0.15 kg during the 14 day observation period, resulting in no change in group mean body weight for the males.
Gross pathology:
No abnormalities were detected at necropsy.
Other findings:
No other findings reported.

Any other information on results incl. tables

Summary of mortality data

Dose levels (mg/kg bw)

Number of deaths/group

 

Male

Female

Total

2000

0/5

0/5

0/10

LD50

>2000 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 is greater than 2000 mg/kg bw in both sexes. On this basis, trimellitic anhydride does not warrant any classification according to Directive 67/548/EEC and Regulation (EC) No. 1272/2008.
Executive summary:

Trimellitic anhydride was administered to one group of 5 animals/sex at 2000 mg/kg bw. Clinical signs and body weights were recorded over a 14 day post exposure period. All animals survived during the course of the study. Clinical signs reported included signs of dermal irritation such as erythema and oedema immediately after removal of the dressing. All surviving animals had recovered at the end of the 14-day post exposure period. No adverse treatment-related effects were reported in any rabbit during the course of the study. All females gained weight during the study while two out five males lost weight. No lesions were noted at necropsy. Under the conditions of this test, the dermal LD50 of trimellitic anhydride was greater than 2000 mg/kg bw. On this basis, trimellitic anhydride does not warrant any classification according to Directive 67/548/EEC and Regulation (EC) No. 1272/2008.