Urea,N'-[3-[[[(dimethylamino)carbonyl]amino]methyl]-3,5,5-trimethylcyclohexyl]-N,N-dimethyl-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001-04-09 to 2001-04-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N,N''-(4-methyl-m-phenylene)bis[N',N'-dimethylurea]

EC Number:

241-523-6

EC Name:

N,N''-(4-methyl-m-phenylene)bis[N',N'-dimethylurea]

Cas Number:

17526-94-2

Molecular formula:

C13H20N4O2

IUPAC Name:

3-[3-(dimethylcarbamoylamino)-4-methylphenyl]-1,1-dimethylurea

impurity 1

Reference substance name:

3-[3-(dimethylcarbamoylamino)-2-methylphenyl]-1,1-dimethylurea

Cas Number:

17607-23-7

Molecular formula:

C13H20N4O2

IUPAC Name:

3-[3-(dimethylcarbamoylamino)-2-methylphenyl]-1,1-dimethylurea

impurity 2

Reference substance name:

unknown

IUPAC Name:

unknown

impurity 3

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

water

Test material form:

solid

Specific details on test material used for the study:

- Substance type: organic
- Physical state: colourless solid
- Analytical purity: 100%
- Purity test date: 01 March 2000
- Lot/batch No.: 0232 07
- Expiration date of the lot/batch: March 2003
- Storage condition of test material: store dry in closed containers
- Other: stable at dry storage conditions for at least 2 years

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, D-33178 Borchen
- Age at study initiation: no data
- Weight at study initiation: Body weight at the commencement of the study: male 150- 168 g and female 142- 160 g. 3 male and 3 female animals were used.
- Fasting period before study: Prior to administration of the test item animals were fasted by withholding food overnight. Following the period of fasting the animals were weighed and the test item was administered. Then the food was withheld for a further 3-4hours.
- Housing: The animals were barrier maintained (semi-barrier) in air conditioned rooms
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: adequate

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3°C
- Humidity (%): 55+/-10%
- Air changes (per hr): 10x per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1%

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2000 mg TDI-Urone in 1 % Carboxymethylcellulose (CMC, Sigma, Lot-No. 36H0738) ad 10 ml
- Amount of vehicle (if gavage): 10 ml/kg body weight
- Justification for choice of vehicle:The vehicle was chosen due to its non-toxic characteristics.
- Lot/batch no. (if required): 36H0738
- Purity: no data

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for 14 days after dosing. The animals were weighed prior to first application and once a week thereafter. A careful clinical examination was made twice a day on the day of dosing and once a day thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

none

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

As none of the animals died the LD0 is >2000 mg/kg body weight.

Clinical signs:

other: No clinical signs of toxicity were observed throughout the observation period.

Gross pathology:

Necropsy revealed an acute injection of blood vessels in all animals in fue abdominal region. This finding is due to euthanasia with an overdose of pentobarbital injected intraperitoneally.

Other findings:

no other findings

Any other information on results incl. tables

Table1: Bodyweight gain

Animal No.		Day 0	Day 7	Day 14
male	1	150	188	229
	2	168	215	256
	3	160	210	240
female	1	142	158	170
	2	146	159	180
	3	160	169	184

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of TDI-Urone was established to be > 2000 mg/kg body weight. As none of the animals died the corresponding LD0 is > 2000 mg/kg bw. Thus, TDI-Urone is practically nontoxic.

Executive summary:

In an acute oral toxicity study according to OECD 423, groups of 3 male and 3 female rats (Wistar) were given a single oral dose of 2000 mg/kg body weight TDI-Urone in 1% Carboxymethylcellulose and were observed for 14 days.

Considering the reported data of this toxicity test it can be stated that the test item TDI-Urone has no acute toxic characteristics.

According to the results obtained the LD50 was determined to be > 2000 mg/kg bw.