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Description of key information

- Acute oral toxicity: LD50 > 5000 mg/kg bw  (limit test according to OECD 423, GLP, rel.1, K).

- Acute dermal toxicity: LD50 > 2000 mg/kg bw (limit test according to OECD 402, GLP, rel. 1, K).

- Acute toxicity: inhalation: no data

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 03 June 2004 to 23 June 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 423 and in compliance with GLP
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
Specific details on test material used for the study:
- Storage condition of test material: ca. 4°C in the dark under nitrogen
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 of age old nulliparous and non-pregnant
- Weight at study initiation: 201-242 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), excepted overnight fasting immediately before dosing and 3-4 hours after dosing
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days

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

IN-LIFE DATES: 11 May to 13 June 2004
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.20 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 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:
3+3 (all females)
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 death 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 (Gross pathological examination: this consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained).
Statistics:
Not applicable/Not required by OECD Guideline
Preliminary study:
Not applicable
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: according to OECD Guideline 423 flowchart (Annex 2d)
Mortality:
No death were recorded during the test
Clinical signs:
other: None
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
None

none

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated as being greater than 5000 mg/kg bodyweight according to OECD Guideline 423 flowchart (Annex 2d). Under the test conditions, the test material is not classified according to the Regulation EC No. 1272/2008 (CLP) and to the GHS.
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 OECD Guidelines for the Testing of Chemicals No. 423 “Acute Oral Toxicity – Acute Toxic Class Method” (adopted 17 December 2001), and was conducted in compliance with GLP.

A group of three fasted females was treated with the test material at a dose level of 2000 mg/kg bodyweight. 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.

During the study, there were no deaths, no signs of systemic toxicity and no abnormalities at necropsy. All animals showed expected gains in bodyweight over the study period.

 

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated from the flow chart from OECD Guideline 423 (Appendix 2d) as being greater than 5000 mg/kg bodyweight.

Under the test conditions, the test material is not classified according to the Regulation EC No. 1272/2008 (CLP) and to the GHS.

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:
5 000 mg/kg bw
Quality of whole database:
Only one study available, GLP-compliant and of high quality (Klimisch score = 1).

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Justification for type of information:
In accordance with Column 2 of REACH Annex VIII, in addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 (acute toxicity by inhalation) and 8.5.3 (acute toxicity by the dermal route) shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. In the present case, inhalation exposure will be lower than dermal exposure because the registered substance has a low vapour pressure (7.5 x 10-6 Pa at 25°C) which indicate an absence of volatility and therefore the potential to generate vapor is negligible. Nonetheless, considering the use of the substance, exposure to mist can occur. However, based on the absence of acute toxicity by oral route, no mortality is anticipated during the exposure to mist. Moreover, no respiratory irritation is expected that could increase the absorption of the substance by inhalation. Hence, dermal exposure is the most likely route of exposure during the manufacture and the use of the substance although skin absorption is expected to be limited (Log Kow = 9.5).
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 06 October 2005 to 20 October 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 402 and in compliance with GLP
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 2002-12-02)
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Storage condition of test material: Room temperature in the dark under nitrogen
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: 8-12 weeks of age, female were nulliparous and non-pregnant
- 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 remainder 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
- % 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): 2.19 mL/kg bw
- Concentration (if solution): 0.915 mg/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 (clinical sign and dermal irritation): 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
- Frequency of weighing: day 0, 7 & 14.
- Necropsy of survivors performed: yes
Statistics:
None (limit test at one dose level of at least 2000 mg/kg bw)
Preliminary study:
not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no death
Clinical signs:
other: There were no signs of systemic toxicity
Gross pathology:
No abnormalities were noted
Other findings:
There were no sign of dermal irritations

none

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. Under the test conditions, the test material does not meet the criteria for classification according to the Regulation EC No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In a limit acute dermal toxicity study performed according to the OECD guideline No. 402 and in compliance with GLP, groups of young adult Sprague-Dawley rats (5/sex) were semi-occlusively exposed to 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.

There were no death, no signs of systemic toxicity and no signs of dermal irritation. All animals showed expected bodyweight gains during the study. No abnormalities were noted at necropsy.

Dermal LD50 Combined > 2000 mg/kg bw

Under the test conditions, the test material does not meet the criteria for classification according to the Regulation EC No. 1272/2008 (CLP) and to the GHS.

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:
Only one study available, GLP-compliant and of high quality (Klimisch score = 1).

Additional information

Acute toxicity: oral

A key study was identified (Safepharm, 2004, rel. 1). This limit study was performed according to the OECD test guideline No. 423, with the starting dose of 2000 mg/kg bw, and in compliance with GLP. During the study, there were no deaths, no signs of systemic toxicity and no abnormalities at necropsy. All animals showed expected gains in bodyweight over the study period. The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated from the flow chart from OECD Guideline 423 (Appendix 2d) as being greater than 5000 mg/kg bodyweight.

Acute toxicity: dermal

A key study was identified (Safepharm, 2005, rel. 1). In this limit acute dermal toxicity study performed according to the OECD guideline No. 402 and in compliance with GLP, rats (5/sex) were semi-occlusively exposed to undiluted test material for 24 hours at dose of 2000 mg/kg bw. There were no death, no signs of systemic toxicity and no signs of dermal irritation. All animals showed expected bodyweight gains during the study. No abnormalities were noted at necropsy. Dermal LD50 Combined > 2000 mg/kg bw.

Acute toxicity: inhalation

In accordance with Column 2 of REACH Annex VIII, in addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 (acute toxicity by inhalation) and 8.5.3 (acute toxicity by the dermal route) shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. In the present case, inhalation exposure will be lower than dermal exposure because the registered substance has a low vapour pressure (7.5 x 10-6 Pa at 25°C) which indicate an absence of volatility and therefore the potential to generate vapor is negligible. Nonetheless, considering the use of the substance, exposure to mist can occur. However, based on the absence of acute toxicity by oral route, no mortality is anticipated during the exposure to mist. Hence, dermal exposure is the more likely route of exposure during the manufacture and the use of the substance although skin absorption is expected to be limited (Log Kow = 9.5).

Justification for classification or non-classification

Harmonized classification:

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

Self-classification:

Acute toxicity via Oral route:

Based on the available information, the substance is:

- not classified according to the Regulation (EC) No. 1272/2008 as the LD50 is greater than 5000 mg/kg bw

- not classified according to the GHS as the LD50 is greater than 5000 mg/kg bw.

Acute toxicity via Dermal route:

Based on the available information, the substance is:

- not classified according to the Regulation (EC) No. 1272/2008 as the LD50 is greater than 2000 mg/kg bw

- not classified according to the GHS as the LD50 is greater than 2000 mg/kg bw.

Acute toxicity via Inhalation:

No data was available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to 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 bw ≥ C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

The classification criteria according to 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 is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to he Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute dermal toxicity study.

Specific target organ toxicity: single exposure (Inhalation):

No data was available.