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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-11-17 - 1998-12-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 402) performed under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted on 24th February 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1100 (Acute Dermal Toxicity)

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:

not specified

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

416-250-2

EC Name:

-

Cas Number:

84632-59-7

Molecular formula:

C26 H28 N2 O2

IUPAC Name:

3,6-bis(4-tert-butylphenyl)-1H,2H,4H,5H-pyrrolo[3,4-c]pyrrole-1,4-dione

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, Füllinsdorf, Switzerland
- Age at study initiation: Males 10 weeks, Females 11 weeks
- Body weight at study initiation: 283.9 – 292.7 g (males), 200.1 – 213.6 g (females)
- Housing:
- 5 animals/sex/cage in Makrolon type-4 cages, standardized softwood bedding (acclimatization)
- individually in Makrolon type-3 cages (treatment and observation period)
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet (Provimi Kliba AG, Kaiseraugst, Switzerland), ad libitum
- Water: Community tap-water from Füllinsdorf, ad libitum
- Acclimation period: at least 7 days (only animals without any visible signs of illness were used for the study)

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Humidity: 40 – 70 %
- Air changes: 10-15 air changes/hour
- Photoperiod: 12-hour fluorescent light/12-hours dark cycle, music during the light period

IN-LIFE DATES:
From: 1993-11-24 To: 1993-12-08

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: Backs of the animals
- Coverage: Approximately 10 % of the total body surface
- On test day 1, the test item was applied evenly on the intact skin with a syringe and covered with a semi-occlusive dressing
- Type of wrap: Dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: The skin was flushed with lukewarm tap water and dried.

TEST MATERIAL
- Amount applied: 500 mg/mL
- Constant volume or concentration used: Yes, 4 mL/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Mortality/Viability: Four times during test day 1 (according to the raw data the last check was conducted 5 hours after application), and once daily during days 2 - 15
- Frequency of observations (clinical signs): Each animal was examined for changes in behaviour and appearance (with special emphasis on the application area, except for time interval of semi-occlusive dressing) four times during day 1, and once daily during days 2-15. All abnormalities were recorded.
- Frequency of weighing: On test days 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: yes, the animals were examined macroscopically and all abnormalities recorded
- Dose formulation: The test item was placed into a glass beaker on a balance and the vehicle (corn oil) was added. A weight by volume dilution was prepared using a homogenizer. Homogeneity of the test item in the vehicle was maintained during treatment using a magnetic stirrer. The preparation was made shortly prior to dosing.
- Rationale for route of exposure: Dermal administration was used as this is one possible route of human exposure during manufacture, handling and use of the test item.

Statistics:

No statistical analysis was used. The LOGIT-Model could not be applied, since no deaths occurred.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study period.

Clinical signs:

other: No clinical signs of systemic toxicity were observed in any animals during the observation period.

Gross pathology:

The macroscopic examination at study termination revealed no organ abnormalities.