Pyrrolo[3,4-c]pyrrole-1,4-dione, 2,5-dihydro-3,6-bis(4-methylphenyl)-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994-12-20 to 1995-01-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted February 24, 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

92/69/EEC, 31-Jul-1992

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1100 (Acute Dermal Toxicity)

Version / remarks:

Revised as of July 01, 1991

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Testing Methods for New Chemical Substances according to the Revised Japanese Chemical Substance Law (March 31, 1987).

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, 4414 Füllinsdorf / Switzerland
- Age at study initiation: males: 8 weeks, females: 11 weeks
- Weight at study initiation: males: 223.5 - 239.7 g, females: 197.0 - 219.4 g
- Fasting period before study: no
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with autoclaved standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz). During treatment and observation individually in Makrolon type-3 cages with autoclaved standard softwood bedding.
- Diet: Pelleted standard Kliba 343, Batch no. 82/94 rat maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst) available ad libitum.
- Water: Community tap water from Füllinsdorf, available ad libitum.
- Acclimation period: One week under laboratory conditions, after health examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-20.5
- Humidity (%): 46-62
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1994-12-13 To: 1995-01-03

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: 10 % of the total body surface
- Type of wrap if used: semi-occlusive dressing: The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: Twenty-four hours after the application the dressing was removed and the skin was washed with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 500 mg/mL
- Constant volume or concentration used: yes

VEHICLE
- Amount(s) applied: 4.0 mL/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female animals

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality / Viability: Four times during test day 1 and daily for surviving animals during days 2-15.
Body Weights: On test days 1 (pre-administration), 8 and 15 for surviving animals.
Clinical Signs: Each animal was examined for changes in behaviour and appearance (with special emphasis on the application area, except for the time when the semi-occlusive dressing was in place) four times during day 1, and once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes
At the end of the observation period all animals were anesthetized by intraperitoneal injection of NARCOREN (Rhone Merieux GmbH, D -88471 Laupheim, Germany) at a dose of at least 2.0 mL/kg bw (equivalent to at least 320 mg/kg sodium pentobarbitone/kg bw) and sacrificed by exsanguination. The animals were examined macroscopically and all abnormalities recorded.

Statistics:

No statistical assessment was performed due to lack of mortality.

Results and discussion

Preliminary study:

No preliminary study

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths as a result of treatment with the test article.

Clinical signs:

other: Clinical signs of systemic toxicity were observed in one female and local effects of the test article on the skin at the application site (red skin, back) were observed in all animals during the observation period. Discoloration of the skin at the applica

Gross pathology:

No organ abnormalities were observed at necropsy.

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU