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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993-07-09 to 1993-11-17

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.1 (Acute Toxicity (Oral))

Version / remarks:

EC 92/69

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

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: males: 130 to 230 g; females: 120 to 180 g;
- Fasting period before study: over night (15 to 20 hours) before treatment;
- Housing: in groups of 5 (2 for preliminary study) of same sex and dosing group in polycarbonate cages type FI (preliminary study) or type MI (main study)
- Diet: ad libitum; pelleted complete diet; rat-mouse diet reference AO4 C10; supplier: Usine d'Alimentation Rationelle, Villemoisson s/Orge, France;
- Water: ad libitum; filtered (0.2 µm) mains drinking water;
- Acclimation period: 5 days minimum between arrival of animals 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

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

The test article was administered once only as a 10 % (w/v) suspension in a 1 % aqueous dispersion of carboxymethylcellulose and at the dose levels of 2000 mg/kg; by the oral route (gavage) in the Sprague-Dawley rat (5 males + 5 females);

Doses:

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

No. of animals per sex per dose:

5 males;
5 females;

Details on study design:

The test article was administered once only as a 10 % (w/v) suspension in a 1 % aqueous dispersion of carboxymethylcellulose and at the dose levels of 2000 mg/kg; by the oral route (gavage) in the Sprague-Dawley rat (5 males + 5 females).
Examinations for mortality and abnormal clinical signs were performed 15 minutes after intubation, then at 1, 2 and 4 hours, and then daily for the 14 day study period.
All the animals were weighed the day before treatment (Day-1), immediately before administration of the test article (Day 1), on Days 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

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: Signs of toxicity related to dose levels: None visible.

Gross pathology:

Effects on organs: No macroscopically detectable abnormality was noted.

Other findings:

None

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 oral 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 oral 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.