reaction product of diphenylmethanediisocyanate, toluenediisocyanate ( reaction mass of isomers: 65 % 2,4- and 35 % 2,6-diisocyanate), octylamine, oleylamine and 4-ethoxyaniline (molar ratio 3.88:1:6.38:0.47:2.91)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999-01-18 to 1999-02-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 1987-02-24

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Directive 92/69 EEC

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

EPA 712-C-96-192, June 1996

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

other:

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

430-970-4

EC Name:

-

Cas Number:

1266545-66-7

Molecular formula:

Not applicable (UVCB substance)

IUPAC Name:

Reaction product of (C8 – C18) aliphatic primary amines (partly unsaturated) and p-phenetidine with a mixture of aromatic isocyanates comprising of primarily 4,4’-methylenediphenyl diisocyanate and 4-methyl-m-phenylene

Details on test material:

NA

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Source: Harlan Winkelmann GmbH, D-33178 Borchen
- Weight at study initiation: 202-235 g
- Housing: Macrolon cages on Altromin saw fibre bedding
- Diet: ad libitum, Altromin 1324, totally-pathogen-free totally-pathogen-free-TPF
- Water : tap water (drinking water, municipal residue microbiol. controlled periodically)
- Acclimatisation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C
- Humidity: 55 ± 10%
- Air changes: 10 x per hour
- Photoperiod: 12/12 hrs dark / hrs light (light 6.00 - 18.00)

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1 % in aqua bidest

Details on dermal exposure:

TEST SITE
- % coverage: approx. 10 % of the total body surface.
- Type of wrap if used: gauze-dressing and non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing : with vehicle - Carboxymethylcellulose (1% in aqua bidest.)
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw
- For solids, paste formed: yes

VEHICLE
- Amount applied: test material was moistened with Carboxymethylcellulose (1 % in aqua bidest.)

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw applied to a skin area of approx. 10 % of the body surface.

No. of animals per sex per dose:

5 male, 5 female

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: careful clinical examination was made once a day; animals were weighed prior to first application and once a week thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality

Clinical signs:

other: Signs of toxicity related to dose levels: All animals showed reduced spontaneous activity throughout the contact period. Activity rose immediately after removal of the dressing. No clinical signs of toxicity were observed throughout the observation perio

Gross pathology:

No compound related macroscopic findings were recorded in necropsy.

Other findings:

No clinical signs of toxicity were observed.

Applicant's summary and conclusion

Interpretation of results:

not classified

Conclusions:

LD50 value of > 2000 mg/kg bw was determined.

Executive summary:

The test substance was tested for its acute dermal toxicity according to EU Method B.3, OECD Guideline 402 and EPA OPPTS 870.1200. The test item was applied to clipped backs (appr. 10 % of the body surface) of 5 male and 5 female Wistar rats in limit dose of 2000 mg/kg bw (limit dose). The application site was covered with a semi-occlusive dressing for a 24 hours contact time. Observations were recorded daily for a period of 14 days. No mortality was observed. The LD50 value was determined greater 2000 mg/kg bw. In two out of five females a weight loss was recorded. Furthermore, no irritant effects on the intact skin or other clinical signs were observed. No compound related macroscopic findings were recorded in necropsy.