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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-12-28 to 2011-12-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

standard acute 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:

- Name of test material (as cited in study report): TDI urone
- Substance type: organic
- Physical state: solid, white powder
- Analytical purity: 97.5 %
- Lot/batch No.: 126815
- Expiration date of the lot/batch: 2013-06-01
- Storage condition of test material: room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: at least 200 g +/-20 %
- Fasting period before study: no
- Housing: housed individually during the 24-Hour exposure period and in groups of five, by sex, for the remainder of the study
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 15 changes per hours
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 10% of the total body surface
- % coverage: approximately 10% of the total body surface
- Type of wrap if used: surgical gauze; piece of self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): treated skin and surrounding hair was wiped with cotton wool moistened with distilled water to remove any residual test item
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): see below
- Dose applied: 2000 mg/kg bw.
- For solids, paste formed: For the purpose of the study the test item was weighed out according to each animal's individual bodyweight and moistened with distilled water prior to application.

VEHICLE
- Amount(s) applied (volume or weight with unit): not specified
- Concentration (if solution): n.a.
- Lot/batch no. (if required): not reported
- Purity: distilled water

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 females and five males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual bodyweights were recorded prior to application of the test item on Day 0 and on Days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,dermal reations

Statistics:

none

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

no other findings

Any other information on results incl. tables

Table 1: Individual Bodyweights and Weekly Bodyweight Changes

Dose Level mg/kg	Animal number and sex	Body weight (g) at day			Body weight change (g) during week
2000		0	7	14	1	2
	1-0 male	390	402	419	12	17
	1-1 male	365	379	400	14	21
	1-2 male	329	351	390	22	39
	1-3 male	357	369	381	12	12
	1-4 male	330	357	383	27	26
	2-0 female	216	220	232	4	12
	2-1 female	209	215	217	6	2
	2-2 female	200	204	217	4	13
	2-3 female	208	213	219	5	6
	2-4 female	218	222	228	4	6

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

TDI-Urone is considered to be practically nontoxic when dermally applied in a single dose. The LD50 was determined to be > 2000 mg/kg bw. As none of the animals died the LD0 is > 2000 mg/kg bw.

Executive summary:

In an acute dermal toxicity study groups of 8-12 week old Wistar rats (5 males and 5 females) were dermally exposed to TDI-Urone (97.5%) moistened with water for 24 hours to 10% of the body surface area at a dose of 2000 mg/kg bw. Animals then were observed for 14 days.

The dermal LD50 (combined) was determined to be > 2000 mg/kg bw. As none of the animals died the LD0 is > 2000 mg/kg bw.

Therefore, TDI-Urone is considered as practically non-toxic when applied dermally in a single dose of 2000 mg/kg bw.