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)

Endpoint summary

Description of key information

The test substance was tested for acute toxicity via the oral and the dermal routes in two limit tests in rats according to OECD Guideline 423 and OECD Guideline 402 respectively. No mortality was noted following administration of single oral and dermal doses of 2000 mg/kg bw (limit dose). The LD50 values determined for the oral and the dermal route were > 2000 mg/kg bw. Additionally, no skin irritation findings were observed during the acute dermal study, no clinical signs were observed and no macroscopic findings were recorded in autopsy following oral and dermal exposures. The test for acute inhalation toxicity was waived according to REACH Regulation No. 1907/2006, Annex VIII, 8.5.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999-01-18 to 1999-02-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 22. March, 1996

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

EPA 712-C-96-190, June 1996

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan, Winkelmann GmbH, D-33178 Borchen
- Weight at study initiation: female 127-138 g; male 145-153 g
- Fasting period before study: over night
- Housing: Macrolon cages on Altromin saw fibre bedding
- Diet: ad libitum, Altromin 1324 totally-pathogen-free-TPF
- Water : tap water: drinking water, municipal residue control, microbiol. controlled periodically
- Acclimatisation period: 1 week

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

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1 % in aqua bidest.

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: The vehicle was chosen due to its non-toxic characteristics
- Lot/batch no.: 36H0738

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 animals per sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: careful clinical examination twice a day on the day of dosing and once a day thereafter; animals weighed prior to first application and once a week thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: changes in the skin, fur, eyes and mucous membranes. Changes in 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.

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: No compound related toxicity/signs. No weight loss was recorded. The weight gain for the male animals was within the expected range. The female rats showed a slightly diminished weight gain.

Gross pathology:

No compound related macroscopic necropsy findings were recorded.

Interpretation of results:

not classified

Conclusions:

LD50 > 2000 mg/kg bw

Executive summary:

The test substance was tested for its acute oral toxicity in a limit test according to EU Method B.1, OECD Guideline 423 and EPA OPPTS 870.1100. The test substance was administered in a dose of 2000 mg/kg bw (limit dose) to groups of 3 male and 3 female Wistar rats in a single exposure via gavage. No mortality and no clinical signs of toxicity were observed within the 14 days observation period. Additionally, no gross pathological changes were recorded at necropsy. The LD50 value was determined greater 2000 mg/kg bw based on the available data.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Reliable study according to OECD Guideline and in compliance with GLP.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 1987-02-24

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Directive 92/69 EEC

Deviations:

no

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

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)

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Reliable study according to OECD Guideline and in compliance with GLP.

Additional information

Acute oral toxicity:

The test substance was tested for its acute oral toxicity in a limit test according to EU Method B.1, OECD Guideline 423 and EPA OPPTS 870.1100. The test substance was administered in a dose of 2000 mg/kg bw (limit dose) to groups of 3 male and 3 female Wistar rats in a single exposure via gavage. No mortality and no clinical signs of toxicity were observed within the 14 days observation period. Additionally, no gross pathological changes were recorded at necropsy. The LD50 value was determined greater 2000 mg/kg bw based on the available data.

Acute dermal toxicity:

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.

Acute inhalation toxicity:

The test for acute inhalation toxicity was waived. According to REACH Regulation No. 1907/2006/EEC, Annex VIII, 8.5 data for maximum two routes of exposure are to be provided. As data on acute oral and acute dermal toxicity were available, acute toxicity via the inhalation route was not determined.

Justification for classification or non-classification

Based on the results obtained, the test substance was not classified and labelled for acute toxicity according to Regulation No (EC) 1272/2008 (CLP).