Reaction mass of 3,6-Bis(3-chlorophenyl)-2,5-dihydro-pyrrolo[3,4-c]pyrrole-1,4-dione, 3-(3-Chlorophenyl)-6-(4-chlorophenyl)-2,5-dihydro- pyrrolo[3,4-c]pyrrole-1,4-dione and 3,6-Bis(4-chlorophenyl)-2,5-dihydro-pyrrolo[3,4-c]pyrrole-1,4-dione

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Description: Orange-red powder
- Test substance storage: At room temperature in the dark
- Stability under storage conditions: Stable
- Expiry date: 15 August 2007

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charies River Deutschland, Sulzfeld, Germany.
- Age at study initiation: approx. 8 weeks old
- Weight at study initiation: mean: males 263 ± 6 g, females 188 ± 4 g
- Housing: Individually housed in labeled Macrolon cages (MIll type, height 18 cm.) containing sterilized sawdust as bedding material (Woody-Clean type 3/4; Tecnilab-BMI BV, Someren, The Netherlands) and paper as cage-enrichment (Enviro-dri, Tecnilab-BMI BV, Someren, The Netherlands).
- Diet: Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany).
- Water: Free access to tap water.
- Acclimation period: at least 5 days before start of treatment under laboratory conditions. During the acclimatization period the animals were group housed in Macrolon cages (MIV type).

ENVIRONMENTAL CONDITIONS
- Temperature (°C): actual range 20.1-22.8
- Humidity (%): actual range 36-67
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: 20% Ethylacetate in propylene glycol (Merck, Darmstadt, Germany) (specific gravity 1.009)

Details on dermal exposure:

TEST SITE
- Area of exposure: approx. 25 cm² for males and 18 cm² for females.
- % coverage: approx. 10% of the total body surface
- Type of wrap if used: The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy ID)(Laboratoires Stella s.a., Liege, Belgium), successively covered with aluminum foil and Coban elastic bandage (3M, St. Paul, Minnesota, U.SA.). A piece of Micropore tape (3M, St. Paul, Minnesota, U.SA.) was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing: tap water
- Time after start of exposure: 24 hours

VEHICLE
- Amount(s) applied (volume or weight with unit): 20 mL/kg body weight.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability: twice daily; Body weights: Days 1 (pre-administration), 8 and 15; Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No signs of systemic toxicity were noted in the animals. Red staining of skin on several body parts, scales and/or scabs were seen on the treated skin of the animals during the observation period.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met