A mixture (1:2:1) of: bis(N-cyclohexyl-N'-phenyleneureido)methylene; bis(N-octadecyl-N'-phenyleneureido)methylene; bis(N-dicyclohexyl-N'-phenyleneureido)methylene

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 23, 1990 - June 06, 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

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:

(1987)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(1984)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

A mixture (1:2:1) of: bis(N-cyclohexyl-N'-phenyleneureido)methylene; bis(N-octadecyl-N'-phenyleneureido)methylene; bis(N-dicyclohexyl-N'-phenyleneureido)methylene

EC Number:

406-550-1

EC Name:

A mixture (1:2:1) of: bis(N-cyclohexyl-N'-phenyleneureido)methylene; bis(N-octadecyl-N'-phenyleneureido)methylene; bis(N-dicyclohexyl-N'-phenyleneureido)methylene

IUPAC Name:

Reaction mass (1:2:1) of bis(N-cyclohexyl-N'-phenyleneureido)methylene and bis(N-octadecyl-N'-phenyleneureido)methylene and bis(N-dicyclohexyl-N'-phenyleneureido)methylene

Details on test material:

- Name of test material (as cited in study report): MDI/CHA/ODA/DCHA
- Description: 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:

- Source: BRL Ltd., Basel, Switzerland
- Age at study initiation: Approx. 9 weeks
- Weight at study initiation: males: 249-274 g; females: 170-200 g
- Housing: Individually housed in polycarbonate cages
- Diet: Free access to standard pelleted laboratory animal diet (Kliba 343, 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: May 23 to June 6, 1990

Administration / exposure

Type of coverage:

occlusive

Vehicle:

corn oil

Details on dermal exposure:

One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females, using a gauze patch fixed successively to aluminium foil and flexible bandage, with drops of petrolatum.

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance with tissue moistened with tap water.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

VEHICLE
- Justification for choice of vehicle: no data

Dose volume: 10 mL/kg bw

DOSAGE PREPARATION
The formulations were prepared immediately prior to dosing. Adjustment was made for specific gravity of the vehicle (0.92 g/mL). Homogeneity of the test substance in vehicle was obtained by the use of a homogeniser.

Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
Mortality/Viability: At periodic intervals on the day of dosing (day 1) and twice daily thereafter for 14 days
Body weights: Day 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter for 14 days
Skin irritation: Changes of the treated skin were described immediately after bandage removal (day 2) and on day 5, 8 and 15
- Necropsy of survivors performed: Yes (all animals)

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality occurred. No irritation was observed.

Mortality:

No mortality occurred.

Clinical signs:

- Lethargy was noted in 1 male on day 1
- There were no clinical signs of toxicity noted from day 2 that were considered to be an effect of treatment

Body weight:

- During the 1st week of observation 1 male showed 5 gram body weight loss and females slightly gained body weight
- All animals showed body weight gain over the study period

Gross pathology:

No abnormalities were observed.

Other findings:

There was no irritation observed on the treated skin surface of the animals at any observation time.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified according to Regulation (EC) No. 1272/2008.

Conclusions:

In an acute dermal toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined. Based on this, the substance does not need to be classified for acute dermal toxicity in accordance with the CLP Regulation.

Executive summary:

An acute dermal toxicity study was performed with the substance in accordance with OECD 402 (1987) and according to GLP principles. Five male and five female rats were exposed to 2000 mg/kg bw for 24 hours under occlusive conditions. No mortality occurred. Lethargy was noted in 1 male on day 1. Macroscopic examination of the animals did not reveal any abnormalities. The LD50 of MD/CHA/ODA/DCHA was concluded to be >2000 mg/kg bw. There was no skin irritation observed.