1,1'-(methylenedi-4,1-phenylene)bis(3-butylurea)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993-07-09 to 1993-10-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

EC92/69

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

416-600-4

EC Name:

-

Cas Number:

77703-56-1

Molecular formula:

C23H32N4O2

IUPAC Name:

3-butyl-1-[4-({4-[(butylcarbamoyl)amino]phenyl}methyl)phenyl]urea

Specific details on test material used for the study:

Analytical purity: >= 99.65 %
Lot/batch No.: 93.166;

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa-Crédo, B.P. 0109; 69592 L'Arbresle Cedex - France;
- Age at study initiation: adult 5 to 7 weeks old;
- Weight at study initiation: 200 to 300 g;
- Fasting period before study: no
- Housing: individually in polycarbonate cages type FI;
- Diet: ad libitum; pelleted complete rat-mouse diet, reference AO4 C10; Usine d'Alimentation Rationelle, Villemoisson s/Orge, France;
- Water: ad libitum, filtered (0.2 µm) drinking water;
- Acclimation period: 5 days minimum between animal arrival and start of treatment;


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25;
- Humidity (%): 30 to 70 R.H.
- Air changes (per hr): min. 8;
- Photoperiod (hrs dark / hrs light): 12 / 12;

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: Aqueous dispersion of 1 % carboxymethylcellulose

Details on dermal exposure:

Preparation of animals:
The day before the application of the test article, the back and the flanks of each animal will be carefully clipped, to expose an area of the skin which should not be less than 10 % of the total body surface. At the time of the application, only those animals showing a perfectly healthy skin and no sign of macroscopic irritation will be kept for the test.

Application of the test article:
The test article was applied, once only as a 58.47 % (W/V) paste in a 1 % aqueous dispersion of carboxymethylcellulose and at the dose level of 2000 mg/kg by the cutaneous route.

Duration of exposure:

24 h

Doses:

males: 2000 mg/kg bw;
females. 2000 mg/kg bw;

No. of animals per sex per dose:

5 males; 5 females;

Control animals:

no

Details on study design:

The test article was applied, once only as a 58.47 % (w/v) paste in a 1 % aqueous dispersion of carboxymethylcellulose and at the dose level of 2000 mg/kg, by the cutaneous route in the Sprague Dawley rat (5 males and 5 females).
Examinations for mortality and abnormal clinical signs were performed 15 minutes after application, then at 1, 2 and 4 hours, and then daily for the 14 day study period.
Cutaneous examinations were performed from day 2 to 15.
All animals were weighed, immediately before application of the test article (Day 1), on Day 8 and 15.
A necropsy was performed for all the animals after the final in vivo observation on Day 15.

Statistics:

LD50 deviation

Results and discussion

Preliminary study:

No preliminary study was performed

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: There were no changes in behaviour or clinical signs in any of the treated animals during the observation period.

Gross pathology:

There were no macroscopic findings that could be associated with treatment.

Other findings:

Cutaneous examinations:
The local tolerance of the test article was good: no cutaneous lesion (erythema or oedema) was noted to the application site of the test article during the observation period

Any other information on results incl. tables

MORTALITY:

 

Dose Level Mg/	Sex	Cumulative Mortality																		TOTAL MORTALITY %
		DAY 1				DAY
		1/4	1	2	4	2	3	4	5	6	7	8	9	10	11	12	13	14	15
		Hours
2000	M	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	F	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

HAT ISO was tested for acute dermal toxicity in a fixed dose study in the rat. The LD50 for male and female rats was found to be > 2000 mg/kg bw. No classification and labelling is necessary according to Regulation 1272/2008/EC (CLP).

Executive summary:

HAT ISO was tested for acute dermal toxicity in a fixed dose study in the rat. The LD50 for male and female rats was found to be > 2000 mg/kg bw.

Under the conditions of the applied test, HAT ISO can be regarded as practically non-toxic.