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

Endpoint summary

Description of key information

HAT ISO was tested for acute toxicity by oral and dermal application in fixed dose studies in the rat. These studies showed a LD50 > 2000 mg/kg bw in both application routes. A study for investigating the toxicity by inhalation was waived, as the risk of exposure to HAT ISO by the inhalation route is not likely. For more details on exposure assessment see risk assessment report in section 13.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

EC 92/69

Deviations:

no

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

Specific details on test material used for the study:

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

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

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

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

  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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

EC92/69

Deviations:

no

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

Specific details on test material used for the study:

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

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;

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

Preliminary study:

No preliminary study was performed

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

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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

HAT ISO was tested for acute oral toxicity in a fixed dose study in the rat according to EU Method B.1 / OECD Guideline 401.

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.

HAT ISO was tested for acute dermal toxicity in a fixed dose study in the rat according to EU Method B.3 / OECD Guideline 402.

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.

The testing of acute toxicity by inhalation was waived. Due to the risk assessment report of HAT ISO, exposure by the inhalation route is not likely.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute toxicity, the test item does not require classification according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.