Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral: measured LD50 > 2000 mg/kg bw and applicant assessment indicates LD50 -cut off > 5000 mg/kg bw, female rat, OECD TG 423, 2004

Dermal: estimated LD50 > 2000 mg/kg bw based upon absence of systemic toxicity in oral and other relevant studies, applicant assessment 2019

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:
27-11-2004 to 15-12-2004
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 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
inspected: December 2002 ; signature: February 2003
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl: CD (SD) IGS BR
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 207 - 242 g
- Fasting period before study: Overnight
- Housing: The animals were housed in 3 per cage suspended solid-floor polypropylene cages furnished with woodflakes
- Water: ad libitum
- Acclimation period: Five (5) days

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

IN-LIFE DATES: From: 27-11-2003 To: 02-12-2003
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Not applicable.
- Amount of vehicle (if gavage): Not applicable.
- Justification for choice of vehicle: Not applicable.
- Lot/batch no. (if required): Not applicable.
- Purity: Not applicable.

MAXIMUM DOSE VOLUME APPLIED: 2.22 mL/kg

DOSAGE PREPARATION (if unusual): Not applicable.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of data suggesting the test item was toxic, 2000 mg/kg was chosen as the starting dose.
Doses:
2000 mg/kg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: prior to and then 0.5, 1, 2, 4 hours after dosing; once daily. Individual bodyweights prior to and at 7 and 14 days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities.
Clinical signs:
other: Hunched posture, lethargy and ataxia were noted in three of six females during the day of dosing and up to 24 hours after dosing. All signs ceased by 48 hours. Three of six animals appeared normal throughout the study period.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the test item oral median LD50 was estimated to be greater than 2500 mg/kg bw in female Sprague-Dawley CD strain rats.
Executive summary:

The study was performed according to OECD 423 and EU Method B1 tris Acute Toxicity and according to GLP to assess the acute oral toxicity of the test item following a single oral administration in the Sprague-Dawley CD strain rat by the acute class method. A group of three fasted females was treated with the test item 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 item was administered orally undiluted. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. There were no mortalities. Hunched posture, lethargy and ataxia were noted in three of six females during the day of dosing and up to 24 hours after dosing. All signs ceased by 48 hours. Three of six animals appeared normal throughout the study period. All females 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 item in the female Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bw. Applicant assessment indicates: under the conditions of this study the acute toxicity estimate could be considered to be > 5000 mg/kg bw.

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 study available
Quality of whole database:
The available information as a whole meets the tonnage driven information requirements of REACH.

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 does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
In accordance with REACH Regulation (EC) No. 1907/2006 Annex VII, column 2 section 8.5 (as amended by Commission Regulation (EU) 2016/863) the acute dermal toxicity (OECD TG 402) study does not need to be conducted based on available information. The data via the oral route indicates that the acute oral toxicity LD50 > 2000 mg/kg bw. There is an absence of systemic toxicity in available Skin Sensitisation tests and in acute dermal irritation tests (eq. or similar to OECD TG 404). This indicates a clear weight of evidence that the EU criteria (Acute Toxicity and STOT-SE) will not been met. Toxicity via the dermal route is not envisaged. Further testing is not scientifically justified. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.4, July 2017) the study does not need to be conducted.
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 : Key Study : OECD TG 423, 2004 : The study was performed according to OECD 423 and EU Method B1 tris Acute Toxicity and according to GLP to assess the acute oral toxicity of the test item following a single oral administration in the Sprague-Dawley CD strain rat by the acute class method. A group of three fasted females was treated with the test item 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 item was administered orally undiluted. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. There were no mortalities. Hunched posture, lethargy and ataxia were noted in three of six females during the day of dosing and up to 24 hours after dosing. All signs ceased by 48 hours. Three of six animals appeared normal throughout the study period. All females 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 item in the female Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bw. Applicant assessment indicates: under the conditions of this study the acute toxicity estimate could be considered to be > 5000 mg/kg bw.

 

DERMAL: No data.

In accordance with REACH Regulation (EC) No. 1907/2006 Annex VII, column 2 section 8.5 (as amended by Commission Regulation (EU) 2016/863) the acute dermal toxicity (OECD TG 402) study does not need to be conducted based on available information. The data via the oral route indicates that the acute oral toxicity LD50 > 2000 mg/kg bw. There is an absence of reported systemic toxicity in available Skin Sensitisation tests and in acute dermal irritation tests (eq. or similar to OECD TG 404). This indicates a clear weight of evidence that the EU criteria (Acute Toxicity and STOT-SE) will not been met. Toxicity via the dermal route is not envisaged. Further testing is not scientifically justified. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.4, July 2017) the study does not need to be conducted.

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: dermal

 

The substance meets classification criteria under Regulation (EC) No 1272/2008 for Specific Target Organ Toxicity: Single Exposure – Category 3 : narcotic effects: H336

 

Ataxia, and lethargy was observed at Acute Oral : GHS Category 4 dose levels. All effects were transient in nature.