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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
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

Constituent 1
Chemical structure
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
Constituent 2
Chemical structure
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 1
Chemical structure
Reference substance name:
Water
EC Number:
231-791-2
EC Name:
Water
Cas Number:
7732-18-5
Molecular formula:
H2O
IUPAC Name:
Water
impurity 2
Reference substance name:
unknown
IUPAC Name:
unknown
Test material form:
solid

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 levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
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:
There were no signs of systemic toxicity.
Body weight:
All animals showed expected gains in bodyweight over the study period.
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.