Registration Dossier

Administrative data

Description of key information

Acute toxicity: via oral route: LD 50 (Female) > 2500 mg/kg bw (OECD 423, GLP, rel.1).
Acute toxicity: via dermal route: LD 50 (Combined) > 2000 mg/kg bw (OECD 402, GLP, rel.1).

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:
From 11 May 2004 to 01 June 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to OECD test guideline No. 423 and in compliance with GLP.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
UK GLP Compliance Programme (Inspected on 2002-12-02)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Female Sprague-Dawley CD (Crl: CD® (SD) IGS BR) strain rats were supplied by Charles River (UK) Ltd, Margate, Kent, UK.
- Age at study initiation: eight to twelve weeks old
- Weight at study initiation: 184-204 g
- Fasting period before study: overnight fast immediately before dosing and for approximately three to four hours after dosing§
- Housing: The animals were housed in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum (Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London, UK)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days


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


IN-LIFE DATES: From: 11 May 2004 To: 01 June 2004
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
In the absence of data suggesting the test material was toxic, 2000 mg/kg bw was chosen as the starting dose (limit test).
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 females (3+3)
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 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: Signs of systemic toxicity noted during the study were hunched posture, lethargy, ataxia, diarrhoea, pilo-erection, increased activity, pallor of the extremities, decreased respiratory rate and laboured respiration. Animals appeared normal two or three days after dosing.
Statistics:
Not applicable (limit test)
Preliminary study:
Not Applicable (In the absence of data suggesting the test material was toxic, 2000 mg/kg bw was chosen as the starting dose (limit test))
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death were recorded during the test
Clinical signs:
Signs of systemic toxicity noted during the study were hunched posture, lethargy, ataxia, diarrhoea, pilo-erection, increased activity, pallor of the extremities, decreased respiratory rate and laboured respiration. Animals appeared normal two or three days after dosing.
Body weight:
All animals showed expected gains in bodyweight over the study period
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
None

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 (Female) > 2500 mg/kg bw (OECD 423 flowchart)
Executive summary:

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of the following method: OECD Guidelines for the Testing of Chemicals No. 423 “Acute Oral Toxicity – Acute Toxic Class Method” (adopted 17 December 2001).

In the absence of data suggesting the test material was toxic, a limit test at one dose level of 2000 mg/kg bw was carried out. A group of three fasted females was treated with the test material at a dose level of 2000 mg/kg bw. This was followed by a further group of three fasted females at the same dose level. The test material was administered orally undiluted. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths. Signs of systemic toxicity noted during the study were hunched posture, lethargy, ataxia, diarrhoea, pilo-erection, and increased activity, pallor of the extremities, decreased respiratory rate and laboured respiration. Animals appeared normal two or three days after dosing. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated from the OECD Guideline 423 flow chart Test Procedure with a Starting Dose of 2000 mg/kg bw as being greater than 2500 mg/kg bw.

The test material does not meet the criteria for classification according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and of the Directive 67/548/EEC.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 500 mg/kg bw
Quality of whole database:
The key study is GLP-compliant and of high quality (Klimisch score = 1)

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:
From 24 June to 08 July 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to OECD test guideline No. 402 and in compliance with GLP.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other 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
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
UK GLP Compliance Programme (Inspected on: 2007-08-21)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Sprague-Dawley CD (CD® (SD) IGS BR) strain rats were supplied by Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: 8-12 weeks of age
- Weight at study initiation: at least 200g
- Fasting period before study: not required
- Housing: solid-floor polypropylene cages furnished with woodflakes. Individually housed during the 24-hour exposure period and in groups of five, by sex, for the reminder of the study.
- Diet (e.g. ad libitum): ad libitum (Certified Rat and Mouse Diet, routinely analysed)
- Water (e.g. ad libitum): ad libitum, routinely analysed
- Acclimation period: at least 5 days


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


IN-LIFE DATES: From: 11 June 2008 To: 03 June 2008
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks (clipped)
- % coverage: 10 %
- Type of wrap if used: surgical gauze semi-occluded with a piece of self-adhesive bandage


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


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.10 mL/kg bw
- Concentration (if solution): 0.954 g/mL
- Constant volume or concentration used: yes

Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, dermal irritation, body weight, necropsy.
Statistics:
None (limit test)
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no death, no signs of systemic toxicity
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no death
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
Other findings:
None

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 (Combined) > 2000 mg/kg bw
Executive summary:

In a limit acute dermal toxicity study performed according to the OECD guideline No. 402 and in compliance with GLP, groups of 8-12 weeks Sprague-Dawley CD rats (5/sex) were semi-occlusively exposed to the undiluted test material for 24 hours at dose of 2000 mg/kg bw. The animals were observed for mortality, clinical signs including dermal reactions and body weight for 14 days and then necropsied for macroscopic observations.

No death, no signs of systemic toxicity, no signs of dermal irritation and expected bodyweight gains were monitored / observed during the study. No abnormalities were noted at necropsy.

Dermal LD50 Combined > 2000 mg/kg bw

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and of the Directive 67/548/EEC.

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The key study is GLP-compliant and of high quality (Klimisch score = 1)

Additional information

Acute oral toxicity:

A key study was identified (Sanders, 2004, rel.1). This limit test was conducted according to the OECD test guideline No. 423 and in compliance with GLP. A group of three fasted Sprague-Dawley CD females was treated with the test material at a dose level of 2000 mg/kg bw. This was followed by a further group of three fasted females at the same dose level. There were no deaths. Signs of systemic toxicity noted during the study were hunched posture, lethargy, ataxia, diarrhoea, pilo-erection, and increased activity, pallor of the extremities, decreased respiratory rate and laboured respiration. Animals appeared normal two or three days after dosing. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy.

Oral LD50 (Female) > 2500 mg/kg bw.

Acute dermal toxicity:

A key study was identified Sanders, 2008, rel.1). In this limit acute dermal toxicity study performed according to the OECD guideline No. 402 and in compliance with GLP, groups of Sprague-Dawley CD rats (5/sex) were semi-occlusively exposed to the undiluted test material for 24 hours at dose of 2000 mg/kg bw. No death, no signs of systemic toxicity, no signs of dermal irritation and expected bodyweight gains were monitored / observed during the study. No abnormalities were noted at necropsy.

Dermal LD50 Combined > 2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
Only one study available

Justification for selection of acute toxicity – inhalation endpoint
This endpoint is not required for substances at the REACH Annex VII tonnage level.

Justification for selection of acute toxicity – dermal endpoint
Only one study available

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 including ATP3.

Self classification:

Acute toxicity (Oral):

Based on the available information, the substance is:

- not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is greater than 2500 mg/kg bw

- not classified according to the Annex VI of the Directive 67/548/EEC as the oral LD50 is greater than 2500 mg/kg bw

Acute toxicity (Dermal):

Based on the available information, the substance is:

- not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the dermal LD50 is higher than 2000 mg/kg bw

- not classified according to the Annex VI of the Directive 67/548/EEC as the dermal LD50 is higher than 2000 mg/kg bw

Acute toxicity (Inhalation):

This information is not available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, oral for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value, oral for a Category 2 classification (2000 mg/kg bwc ≥C > 300 mg/kg bw). No classification required.

Specific target organ toxicity: single exposure (Dermal):

The classification criteria according to the Annex VI of the Regulation (EC) No 1272/2008 as specific target organ toxicant (STOT) – single exposure, dermal are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, dermal for a Category 1 classification (C≤ 1000 mg/kg bw) and at the guidance value, dermal for a Category 2 classification (2000 mg/kg bw ≥C > 1000 mg/kg bw). No classification required.

Specific target organ toxicity: single exposure (Inhalation):

This information is not available.