3,3'-dicyclohexyl-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:

17 May 1990 - 31 May 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:

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:

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

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report): MDI/CHA
- Physical state: white yellowish solid
- Storage condition of test material: at room temperature in the dark

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. 8 weeks
- Weight at study initiation: Males 197 - 224 g; Females: 164 - 183 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 -62
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 17 May 1990 To: 31 May 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 the
reafter 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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: The treated skin surface of the animals showed spots with crusts in 2 females on day 8 and 1 female on day 15.

Body weight:

other body weight observations

Remarks:

All animals showed body weight gain over the study period.

Gross pathology:

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

Applicant's summary and conclusion

Interpretation of results:

other: not classified according to Regulation (EC) No 1272/2008 and its amendments.

Conclusions:

In an acute dermal toxicity study with rats, performed according to OECD 402 (1987) and EC B.3 (1984) test guidelines and GLP, an LD50 >2000 mg/kg bw was determined.

Executive summary:

MDI/CHA was administered by dermal application, to five rats of each sex, at 2000 mg/kg body weight. No animals died during the study.

The treated skin surface of the animals showed spots with crusts in 2 females on day 8 and 1 female on day 15. All animals showed body weight gain over the study period. No abnormalities were found at macroscopic post mortem examination of the animals.

Based on these results, MDI/CHA does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to Regulation (EC) No 1272/2008 and its amendments.