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Description of key information

Oral: LD50 > 2000 mg/kg bw female rat, OECD TG 420, 2013

Inhalation: LC50 > 5.11 mg/L male/female rat, OECD TG 436, 2013

Dermal: LD50 > 2000 mg/kg bw male/female rat, OECD TG 402, 2014

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:
2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met.
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
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:
inspected: July 2012; signature: November 2012
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Recognised supplier
- Age at study initiation: 8 - 12 weeks.
- Weight at study initiation: 188 g (sighting test; sentinel); 154 - 170 g (main study); The weight variation did not exceed ±20% of the mean weight.
- Fasting period before study: Overnight before dosing and three to four hours after dosing.
- Housing: Group housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): Certified diet from recognised supplier, provided ad libitum (except for fasting period).
- Water (e.g. ad libitum): ad libitum (except for fasting period)
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70%
- Air changes (per hr): > 15 air changes per hour
- Photoperiod: 12 h light / 12 h dark

IN-LIFE DATES: From: To: 2013-01-22 to 2013-02-28
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Remarks:
Arachis oil BP only used in 300 mg/kg bw sighting study; in main study 2000 mg/kg bw undiluted or as supplied
Details on oral exposure:
The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.
For the purpose of the 300 mg/kg dose level, the test item was freshly prepared, as required, as a solution in arachis oil BP. Arachis oil BP was used because the test item did not dissolve/suspend in distilled water.
For the purpose of the 2000 mg/kg dose level, the test item was used as supplied. The 2000 mg/kg bw dose level was treated stepwise. Singuarly and in the absence of mortality or evident toxicity a further group of 4.
Doses:
300 mg/kg bw (sighting study); 2000 mg/kg bw (main study)
No. of animals per sex per dose:
1 (sighting study) and 5 (main 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 hours after dosing and then 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
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
300 mg/kg bw: No mortality.
2000 mg/kg bw: No mortality.
Clinical signs:
300 mg/kg bw: No signs of systemic toxicity were noted during the observation period.
2000 mg/kg bw: Hunched posture was noted in three animals during the day of dosing and persisted in one animal one day after dosing. No signs of systemic toxicity were noted in the remaining animals. Fully reversed by day two.
Body weight:
300 mg/kg bw: All animals showed expected bodyweight gains over the study period.
2000 mg/kg bw: All animals showed expected bodyweight gains over the study period.
Gross pathology:
300 mg/kg bw: No abnormalities were noted at necropsy.
2000 mg/kg bw: No abnormalities were noted at necropsy.
Interpretation of results:
GHS criteria not met
Remarks:
EU criteria not met
Conclusions:
Under the conditions of this study the oral LD50 was established to exceed 2000 mg/kg bw in female Wistar rats.
Executive summary:

The study was performed according to OECD TG 420 and EU Method B.1 bis Acute Toxicity (Oral) and in accordance with GLP to assess the acute oral toxicity of the test material following a single oral administration in the female Wistar strain rat by the fixed dose method. The test substance was administered by oral gavage in an initial sighting study at 300 mg/kg and then in a single 2000 mg/kg dose. Subsequently a further group of four fasted females was given a single oral dose of test item, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study and gross necropsy performed. There was no mortality during the course of the study. Hunched posture was noted in three animals treated at a dose level of 2000 mg/kg. No signs of systemic toxicity were noted in the remaining animals. Animals showed expected gains in bodyweight over the study period and there were no abnormalities were noted at necropsy. Under the conditions of this study the oral LD50 was established to exceed 2000 mg/kg bw in female Wistar rat.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The available information as a whole meets the tonnage driven information requirements of REACH.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
5 110 mg/m³
Quality of whole database:
The available information as a whole meets the tonnage driven information requirements of REACH.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The available information as a whole meets the tonnage driven information requirements of REACH.

Additional information

ORAL: OECD TG 420, 2013 - The study was performed according to OECD TG 420 and EU Method B.1 bis Acute Toxicity (Oral) and in accordance with GLP to assess the acute oral toxicity of the test material following a single oral administration in the female Wistar strain rat by the fixed dose method. The test substance was administered by oral gavage in an initial sighting study at 300 mg/kg and then in a single 2000 mg/kg dose. Subsequently a further group of four fasted females was given a single oral dose of test item, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study and gross necropsy performed. There was no mortality during the course of the study. Hunched posture was noted in three animals treated at a dose level of 2000 mg/kg. No signs of systemic toxicity were noted in the remaining animals. Animals showed expected gains in bodyweight over the study period and there were no abnormalities were noted at necropsy. Under the conditions of this study the oral LD50 was established to exceed 2000 mg/kg bw in female Wistar rat.

 

INHALATION: OECD TG 436, 2013 - The study was performed according to OECD TG 436 and in accordance with GLP to assess the acute inhalation toxicity of the test substance. A group of Wistar rats comprising three males and three females was exposed to an aerosol atmosphere for four hours using a nose only exposure system, followed by a fourteen day observation period. The target concentration was 5.0 mg/L and the mean achieved atmosphere concentration was 5.11 mg/L. The additional characteristics of the atmosphere was Mean Mass Median Diameter (particle size) 3.42 μm ; Inhalable Fraction <4 μm was 57.5% with a geometric standard deviation of 2.30. There was no mortality and no macroscopic abnormalities were detected amongst animals at necropsy. Body weight losses exhibited or no gains were seen on the first day post-exposure. Two female animals exhibited either a body weight loss or showed no body weight gain from days 3 to 7 post-exposure. Reasonable body weight gains were noted in all other animals during the remainder of the recovery period. Under the conditions of this study the acute inhalation LC50 was established to exceed 5.11 mg/L in male/female Wistar rats.

 

DERMAL: OECD TG 402, 2014 - The study was performed according to OECD TG 402 and EU Method B.3 Acute Toxicity (Dermal) and in accordance with GLP to assess the acute dermal toxicity of the test substance in the Wistar strain rat. A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. There were no signs of system toxicity or abnormalities on necropsy. There was no mortality during the study. No signs of dermal irritation were noted. Animals showed expected gains in bodyweight over the study period. Under the conditions of this study the dermal LD50 was established to exceed 2000 mg/kg bw in male/female Wistar rat.

Justification for classification or non-classification

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity: oral.

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity: inhalation

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity: dermal

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