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Administrative data

Description of key information

Acute toxicity: oral: Rat LD50 (female) > 2000 mg/kg bw (OECD 420, GLP, K, rel. 1)
Acute toxicity: dermal: waiver (the substance is corrosive to the skin)
Acute toxicity: inhalation: waiver (the substance is corrosive to the skin)

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 February 20 to March 11, 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
adopted 17 December 2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
UK GLP Compliance Programme (inspected on August 30, 2005/ signed on November 21, 2005)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
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: 8-12 weeks
- Weight at study initiation: 204-219 g
- Fasting period before study: Animals were fasted for overnight period before administration of test material and for approximately 3-4 h after dosing.
- Housing: Animals were housed in groups of up to 4 in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: Food (Certified Rat and Mouse Diet), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: 15 changes/h
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: February 20, 2008 To: March 11, 2008
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: Arachis oil BP was used as vehicle because the test material did not dissolve/suspend in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: Test material was freshly prepared, as required, as a solution in arachis oil BP.

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 bw was chosen as the starting dose.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
- Sighting study: 1 female/dose
- Main study: 5 females/dose (1 animal included from sighting study)
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 h after dosing and then daily for up to 14 days. Morbidity and mortality checks were made twice daily. Body weight of each animal was recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: Yes; on completion of the observation period, animals were killed by cervical dislocation and subjected to gross necropsy.
Statistics:
None
Preliminary study:
- No mortality was observed at 2000 mg/kg bw.
- Ataxia and hunched posture were observed.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
- No mortality was observed at 2000 mg/kg bw.
Clinical signs:
- Signs of systemic toxicity observed up to one day after dosing were hunched posture, ataxia, decreased respiratory rate, lethargy, laboured respiration, ptosis, loss of righting reflex and splayed gait.
- Animals appeared normal one or two days after dosing.
Body weight:
- All animals showed expected gains in bodyweight over the observation period.
Gross pathology:
- No abnormalities were noted at necropsy.
Other findings:
None

None

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Under the test conditions, the substance is::
- not classified according to the Annex VI of the Regulation EC No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw.
- classified as 'category 5' according to the GHS based on narcotic effects observed at 2000 mg/kg bw.
Based on narcotic effects observed at the dose level of 2000 mg/kg bw, the test material is classified as a specific target organ toxicant after single exposure, H336: May cause drowsiness or dizziness according to the Regulation (EC) No. 1272/2008 (CLP)
and to the GHS.
Executive summary:

In an acute oral toxicity study (limit test) performed according to OECD Guideline No. 420 and in compliance with GLP, female Sprague-Dawley CD (Crl: CD® (SD) IGS BR) strain rats were administered a single oral dose of test material by gavage.

Following a sighting study using one animal at a dose level of 2000 mg/kg bw, additional 4 animals were administered a single oral dose of test item at 2000 mg/kg bw (main study). Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

No mortality was observed. Signs of systemic toxicity observed up to one day after dosing were hunched posture, ataxia, decreased respiratory rate, lethargy, laboured respiration, ptosis, loss of righting reflex and splayed gait. Animals appeared normal one or two days after dosing. All animals showed expected gains in body weight over the 14 day study period. No abnormalities were noted at necropsy.

Rat Oral LD50 (females) > 2000 mg/kg bw

Under the test conditions, the oral LD50 for the registered substance is higher than 2000 mg/kg bw in rats therefore:

- it is not classified according to the Annex VI of the Regulation EC No. 1272/2008 (CLP).

- it is classified as 'category 5' according to the GHS base on narcotic effects.

Based on narcotic effects observed at the dose level of 2000 mg/kg bw, the test material is classified as a specific target organ toxicant after single exposure, H336: May cause drowsiness or dizziness 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:
2 000 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

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is classified as corrosive to the skin
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
The substance is a powder with inhalable fraction (27% < 105µm, 4.2% < 11µm, 1.8% < 4.5µm) so human exposure by inhalation could occur. In accordance with REACH Regulation (EC) 1907/2006 as amended: Annex VII, section 8.1.1: an acute inhalation toxicity study should be avoided, in particular in relation with animal welfare considerations, because the substance was shown to be corrosive to the skin in a new in vitro skin corrosion EpiDerm test (Envigo, 2017, Rel.1). Due to its corrosive properties, the substance is presumed to cause toxicity by inhalation exposure. When administered by the oral route, the substance induced narcotic effects (Safepharm, 2008, OECD 420, GLP, Rel 1.). Those effects can be anticipated with an exposure via the inhalation route, therefore, the substance is also classified as STOT SE3 (H336) by the inhalation route.
Reason / purpose for cross-reference:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is classified as corrosive to the skin
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
In accordance with REACH Regulation (EC) 1907/2006 as amended: Annex VII, section 8.1.1: an acute dermal toxicity study should be avoided, in particular in relation with animal welfare considerations, because the substance was shown to be corrosive to the skin in a new in vitro skin corrosion EpiDerm test (Envigo, 2017, Rel.1). Due to its corrosive properties, the substance is presumed to cause toxicity by dermal exposure. When administered by the oral route, the substance induced narcotic effects (Safepharm, 2008, OECD 420, GLP, Rel 1.). Those effects can be anticipated with an exposure via the dermal route, therefore, the substance is also classified as STOT SE3 (H336) by the dermal route.
Reason / purpose for cross-reference:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute toxicity: oral:

A key study was identified (Safepharm, 2008). This acute oral toxicity study was performed according to the OECD test guideline No. 420 and in compliance with GLP.

Following a sighting study using one animal at a dose level of 2000 mg/kg bw, additional four animals were administered a single oral dose of test item at 2000 mg/kg bw (main study).

No mortality was observed. Signs of systemic toxicity observed up to one day after dosing were hunched posture, ataxia, decreased respiratory rate, lethargy, laboured respiration, ptosis, loss of righting reflex and splayed gait. Animals appeared normal one or two days after dosing. All animals showed expected gains in body weight over the 14 day study period. No abnormalities were noted at necropsy.

Rat Oral LD50 (females) > 2000 mg/kg bw

Acute toxicity: dermal:

No data was available. In accordance with REACH Regulation (EC) 1907/2006 as amended: Annex VII, section 8.1.1: an acute dermal toxicity study should be avoided, in particular in relation with animal welfare considerations, because the substance was shown to be corrosive to the skin in a new in vitro skin corrosion EpiDerm test (Envigo, 2017, Rel.1) (Chapter R.7a: Endpoint Specific Guidance, R.7.4.4, December 2016). Due to its corrosive properties, the substance is presumed to cause toxicity by dermal exposure. When administered by the oral route, the substance induced narcotic effects (Safepharm, 2008, OECD 420, GLP, Rel 1.). Those effects can be anticipated with an exposure via the dermal route, therefore, the substance is also classified as STOT SE3 (H336) by the dermal route.

Acute toxicity: Inhalation:

No data was available. In accordance with REACH Regulation (EC) 1907/2006 as amended: Annex VII, section 8.1.1: an acute inhalation toxicity study should be avoided, in particular in relation with animal welfare considerations, because the substance was shown to be corrosive to the skin in a new in vitro skin corrosion EpiDerm test (Envigo, 2017, Rel.1) (Chapter R.7a: Endpoint Specific Guidance, R.7.4.4, December 2016). Due to its corrosive properties, the substance is presumed to cause toxicity by inhalation exposure. When administered by the oral route, the substance induced narcotic effects (Safepharm, 2008, OECD 420, GLP, Rel 1.). Those effects can be anticipated with an exposure via the inhalation route, therefore, the substance is also classified as STOT SE3 (H336) by the inhalation route.

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 (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 higher than 2000 mg/kg bw.

- classified as 'category 5' according to the GHS based on narcotic effects observed at 2000 mg/kg bw.

Acute toxicity (Dermal):

No data was available and since the substance was corrosive to the skin, no further in vivo study has been performed.

Acute toxicity (Inhalation):

No data was available and since the substance was corrosive to the skin, no further in vivo study has been performed.

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 Category 3 (H336: May cause drowsiness or dizziness) are met since narcotic effects, such as lethargy and loss of righting reflex were observed following dosing at 2000 mg/kg bw.

No non-lethal significant and/or severe toxic 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).

Specific target organ toxicity: single exposure (Dermal):

No data was available and since the substance was corrosive to the skin, no further in vivo study has been performed. The registered substance is classified as specific target organ toxicant (STOT) – single exposure, oral Category 3 (H336:May cause drowsiness or dizziness) according to the Annex VI of the Regulation (EC) No. 1272/2008. Thus in the absence of specific data for the dermal route, the registered substance must be classified by default as specific target organ toxicant (STOT) – single exposure, dermal Category 3 according to the Annex VI of the Regulation (EC) No. 1272/2008.

Specific target organ toxicity: single exposure (Inhalation):

No data was available and since the substance was corrosive to the skin, no further in vivo study has been performed. The registered substance is classified as as specific target organ toxicant (STOT) – single exposure, oral Category 3 (H336: May cause drowsiness or dizziness) according to the Annex VI of the Regulation (EC) No. 1272/2008. Thus in the absence of specific data for the inhalation route, the registered substance must be classified by default as specific target organ toxicant (STOT) – single exposure, inhalation Category 3 according to the Annex VI of the Regulation (EC) No. 1272/2008.

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