A mixture of: 3,3'-dicyclohexyl-1,1'-methylenebis(4,1-phenylene)diurea; 3-cyclohexyl-1-(4-(4-(3-octadecylureido)benzyl)phenyl)urea; 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 May 1990 - 06 June 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24 February 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

September 1984

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1‐cyclohexyl‐3‐[4‐({4‐[(octadecylcarbamoyl)amino]phenyl}methyl)phenyl]urea

EC Number:

604-940-8

Cas Number:

154099-21-5

Molecular formula:

C39 H62 N4 O2

IUPAC Name:

1‐cyclohexyl‐3‐[4‐({4‐[(octadecylcarbamoyl)amino]phenyl}methyl)phenyl]urea

Constituent 2

Reference substance name:

3,3'-dicyclohexyl-1,1'-methylenebis(4,1-phenylene)diurea

EC Number:

406-370-3

EC Name:

3,3'-dicyclohexyl-1,1'-methylenebis(4,1-phenylene)diurea

Cas Number:

58890-25-8

Molecular formula:

C27 H36 N4 O2

IUPAC Name:

3‐cyclohexyl‐1‐[4‐({4‐[(cyclohexylcarbamoyl)amino]phenyl}methyl)phenyl]urea

Constituent 3

Reference substance name:

3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea

EC Number:

406-690-3

EC Name:

3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea

Cas Number:

43136-14-7

Molecular formula:

C51 H88 N4 O2

IUPAC Name:

3‐octadecyl‐1‐[4‐({4‐[(octadecylcarbamoyl)amino]phenyl}methyl)phenyl]urea

Test material form:

solid

Details on test material:

Appearance: White yellowish solid
Storage conditions: At room temperature in the dark

The data on the individual constituents CHA/MDI/CHA (EC 406-370-3) and ODA/MDI/ODA (EC 406-690-3) for physicochemical, environmental fate, ecotoxicological and mammalian toxicological endpoints are very similar to the data available for the different compositions of the multi-constituent or represent the outer boundaries of the data on the multi-constituent. Hence, they confirm that the different compositions are expected to have similar properties for physicochemical, environmental fate, ecotoxicological and mammalian toxicological endpoints.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL Ltd., Basel, Switzerland
- Age at study initiation: Approx. 9 weeks
- Weight at study initiation: Males 238 - 269 g; Females: 174 - 190 g
- Housing: Individually in polycarbonate cages containing purified sawdust as bedding material.
- Diet: Free access to standard pelleted laboratory animal diet (Kliba 343 from Klingentalmühle AG, Kaiseraugst, Switzerland).
- Water: Free access to tap water.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 -24
- Humidity (%): 40 -64
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23 May 1990 To: 06 June 1990

Administration / exposure

Type of coverage:

occlusive

Vehicle:

corn oil

Remarks:

Specific gravity: 0.92 g/mL

Details on dermal exposure:

Method: Dermal application

TEST MATERIAL
- Amount applied: 10 mL/kg body weight
Adjustment was made for the specific gravity of vehicle.

TEST SITE
- Area of exposure: 5 x 5 cm for males; 3.5 x 5 cm for females
- Type of wrap if used: A gauze patch fixed successively to aluminium foil and 3M Coban flexible bandage with drops of petrolatum.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test item was removed with a tissue moistened with tap-water.
- Time after start of exposure: 24 hours

Frequency: single application, on day 1.

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

One day before treatment an area of approx. 5 x 7 cm on the back of the animal was clipped.

- Duration of observation period following administration: 14 days
- Frequency of observations: At periodic intervals on the day of dosing (day 1) and once daily thereafter for 14 days
- Body weights: Animals were weighed individually on day 1 (pre-administration), 8 and 15.
- Mortality: At periodic intervals on the day of dosing (day 1) and twice daily thereafter for 14 days
- Irritation: Changes of treated skin were described immediately after bandage removal (day 2) and on day 5, 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: none

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 occurred.

Clinical signs:

other: Slight erythema was noted on the treated skin surface of one female following bandage removal. The erythema was fully reversed at observation day 5.

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

Conclusions:

The dermal LD50 value of MDI/CHA/ODA in Wistar rats was determined to exceed 2000 mg/kg body weight. Based on this result, MDI/CHA/ODA is not classified according to GHS and CLP criteria.