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Description of key information

Acute oral toxicity: LD50 > 2000 mg/kg bw (OECD 420, GLP compliant, female rats)
Acute inhalation toxicity: data waiving
Acute dermal toxicity: LD50 > 2000 mg/kg bw (OECD 402, GLP compliant, male and female rats)

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:
2008-04-07 to 2008-04-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study reliable without restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
, adopted 2001-12-17
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2007-10-15
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Crj: CD(SD)
Sex:
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: eight to twelve weeks of age
- Weight at study initiation: 212 - 242 g
- Fasting period before study: an overnight fast immediately before dosing and for approximately three to four hours after dosing.
- Housing: the animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (ad libitum, exception see "Fasting period before study" above): Certified Rat and Mouse diet
- Water (ad libitum): mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25 °C
- Relative humidity: 30 to 70 %
- Air exchanges: at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
SIGHTING STUDY / MAIN STUDY
Using available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose. A single animal was treated as follows: dose level: 2000 mg/kg; specific gravity: 0.892; dose volume: 2.25 mL/kg. In the absence of mortality at a dose level of 2000 mg/kg, an additional group of four animals was treated as follows: dose level: 2000 mg/kg; specific gravity: 0.892; dose volume: 2.25 mL/kg. A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.
The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

MAXIMUM DOSE VOLUME APPLIED: 2.25 mL/kg

DOSAGE PREPARATION: the test material was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.
Doses:
2000 mg/kg bw. (sighting study / main study)
No. of animals per sex per dose:
5 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations were made 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
not applicable
Preliminary study:
2000 mg/kg bw:
- no deaths were recorded.
- animal had diarrhoea during the day of dosing. No other signs of systemic toxicity were noted during the study.
- animal gained the expected gains in body weight over the observation period.
- no abnormalities were noted at necropsy
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
other: Two animals had diarrhoea during the day of dosing. No other signs of systemic toxicity were noted during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bw.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the oral route, as well.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
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:
2008-10-15 to 2008-10-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study reliable without restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
, adopted 1987-02-24
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
, 1992
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2007-10-15
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Limited, Bicester, Oxon, UK
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: males: 222 - 249 g; females: 200 - 223 g
- Housing: animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (ad libitum): 2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK
- Water (ad libitum): mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25 °C
- Relative humidity: 30 to 70 %
- Air exchanges: at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure and type of wrap used: back and flanks of each animal were clipped free of hair.
- % coverage: approximately 10 % of the total body surface area
- Type of wrap if used: piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material.
- Time after start of exposure: after the 24-hour contact period

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): dose volume: 2.27 mL/kg; the specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males / 5 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 deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of irritation and scored according to the Draize scale. Any other skin reactions were also recorded. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
other: There were no signs of systemic toxicity.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Dermal reactions: there were no signs of dermal irritation.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
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.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the dermal route.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Acute oral toxicity

One reliable animal study described in Bradshaw (2008) (OECD 420, GLP compliant, female rats) is considered to be reliable without restrictions. The LD50 was determined to be greater than 2000 mg/kg bw.

Acute inhalation toxicity

The study does not need to be conducted since exposure of humans via the inhalation route is not likely taking into account the vapour pressure of 0.22 Pa at 22.5°C (Annex VII section 8.5.2 Column 2 of regulation 1907/2006). Furthermore, the substance is a liquid at 20°C with a melting point of -32.5°C at atmospheric pressure and not a powder with an inhalable size.

Acute dermal toxicity

One reliable animal study described in Bradshaw (2008) (OECD 402, GLP compliant, male and female rats) is considered to be reliable without restrictions. The LD50 was determined to be greater than 2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
GLP guideline study conducted with the test item

Justification for selection of acute toxicity – inhalation endpoint
The study does not need to be conducted since exposure of humans via the inhalation route is not likely taking into account the vapour pressure of 0.22 Pa at 22.5°C (Annex VII section 8.5.2 Column 2 of regulation 1907/2006). Furthermore, the substance is a liquid at 20°C with a melting point of -32.5°C at atmospheric pressure and not a powder with an inhalable size.

Justification for selection of acute toxicity – dermal endpoint
GLP guideline study conducted with the test item

Justification for classification or non-classification

Acute oral toxicity

Reference Bradshaw (2008) is considered as the key study for acute oral toxicity and will be used for classification. The LD50 was determined to be greater than 2000 mg/kg bw. Thus, according to regulation (EC) 1272/2008 and subsequent amendments the substance is not classified.

Specific target organ toxicant (STOT) - single exposure: oral

The classification criteria according to regulation (EC) 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 required.

Acute dermal toxicity

Reference Bradshaw (2008) (OECD 402, GLP complaint, male and female rats) is considered as the key study for acute dermal toxicity and will be used for classification. The LD50 was determined greater than 2000 mg/kg bw. Thus, according to regulation (EC) 1272/2008 and subsequent amendments the substance is not classified.

Specific target organ toxicant (STOT) - single exposure: dermal

The classification criteria according to regulation (EC) 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 bwC > 1000 mg/kg bw). No classification required.