Registration Dossier

Administrative data

Description of key information

Oral (OECD 420), rat: LD50 > 2000 mg/kg bw (limit test)
Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw (limit test)

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:
27 Jan - 19 Feb 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
No analytical purity is given.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM
Test type:
fixed dose procedure
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Remarks:
HsdRccHan®™:WIST®™
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: 174 - 192 g
- Fasting period before study: Overnight fast immediately before dosing
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: 2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK; ad libitum
- Water: drinking water; ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.68 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Using available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose.
Doses:
Starting dose: 2000 mg/kg
Additional group: 2000 mg/kg
No. of animals per sex per dose:
Starting dose: 1 female
Additional group: 4 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made ½, 1, 2, and 4 hours after dosing and subsequently once daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths noted.
Clinical signs:
There were no signs of systemic toxicity noted.
Body weight:
Animals showed expected gains in body weight except for one animal which showed body weight loss during the first week with expected gain in body weight during the second week (see table 1).
Gross pathology:
No abnormalities were noted at necropsy.

Table 1.  Individual Body weights and Body weight Changes

Dose Level mg/kg

Animal Number and Sex

Body weight (g) at Day

Body weight Gain (g) During Week

0

7

14

1

2

2000

1-0 Female

192

211

221

19

10

2-0 Female

192

199

209

7

10

2-1 Female

188

194

205

6

11

2-2 Female

174

189

204

15

15

2-3 Female

189

185

197

-4

12

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study a LD50 value > 2000 mg/kg bw in female rats was found.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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:
04 - 18 Feb 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
No analytical purity is given.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM.
Test type:
fixed dose procedure
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Remarks:
HsdRccHan®™:WIST®™
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: at least 200 g
- Housing: during the exposure period: individually housing in suspended soli-floor polypropylene cages furnished with woodflakes; group housing for the remainder of the study period (groups of 5, by sex)
- Diet: 2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK; ad libitum
- Water: drinking water; ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Back and flanks
- % coverage: 10% of the total body surface area
- Type of wrap if used: Self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Cotton wool moistened with distilled water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.68 mL/kg
Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 h after dosing and subsequently once daily for fourteen days.
- Necropsy of survivors performed: yes
- Other examinations performed: body weight was recorded prior to application of the test substance on Day 0, and on Day 7 and 14; test sites were examined for evidence of primary irritation and scored according to the Draize system
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths noted.
Clinical signs:
There were no signs of systemic toxicity noted.
Body weight:
All animals showed expected gains in body weight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
There were no signs of dermal irritation (all scores = 0).
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute dermal toxicity study a LD50 value > 2000 mg/kg bw in male and female rats was found.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch Score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Acute toxicity: oral

The test substance was tested for acute oral toxicity in the fixed dose procedure according to OECD 420 (Pooles, 2009). A sighting test at a dose level of 2000 mg/kg bw was performed in one female rat. Since no toxicity was observed in the sighting test, a dose level of 2000 mg/kg bw was selected for the main study. In the main test, 4 female rats received the test substance in a single dose by gavage. No deaths and no signs of toxicity were noted during the study period. Macroscopic examinations at necropsy did not reveal any abnormalities. The LD50 of the test substance is > 2000 mg/kg bw.

Acute toxicity: dermal

In accordance with OECD 402, the undiluted test substance was applied to the intact skin of 5 female and 5 male rats at a dose level of 2000 mg/kg bw (Pooles, 2009). Under semi-occlusive conditions, the test substance was held in contact with the skin with a self-adhesive bandage for 24 h. Thereafter, the dressing was removed and the treated skin site was cleaned with distilled water. There were no deaths and no signs of toxicity during the study period. No abnormal findings were noted at necropsy. The LD50 of the test substance is > 2000 mg/kg bw.

Justification for classification or non-classification

The available data on acute toxicity via the oral and dermal route do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

No data on acute inhalation toxicity are available. Therefore, no classification is given for this endpoint due to lacking data.