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Description of key information

An acute oral and dermal toxicity study according to OECD 423 and OECD 402, respectively are available. Both are establishing a LD50 of 2000 mg/kg bw.

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:
2001-04-09 to 2001-04-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
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
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
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:
No clinical signs of toxicity were observed throughout the observation period.
Body weight:
Throughout the 14-days observation period no weight loss was recorded (table 1). The weight gain was within the expected range.
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

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

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
2011-12-28 to 2011-12-14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
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
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
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

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

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

In an acute oral toxicity study according to OECD 423, a limit dose of 2000 mg/kg bw TDI-Urone in 1% Carboxymethylcellulose did not show any signs of toxicity in female and male rats. A LD0 of 2000 mg/kg bw was established.

In an acute dermal toxicity study according to OECD 402 a limit dose of 2000 mg/kg bw TDI-Urone did not show any toxic effects in 5 female and 5 male Wistar rats. 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 practically non-toxic.

Justification for classification or non-classification

According to Regulation (EC) No 1272/2008 LD50-doses of more than 2000 mg/kg are not considered to indicate oral and dermal acute toxicity.