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Administrative data

Description of key information

The objective was the evaluation of the acute toxicity of the test substance, by in vivo test models

In an acute oral toxicity study with Wistar Han rats, performed according to OECD/EC guidelines, the oral LD50 value of the test substance  was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

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:
15 March 2017 - 31 March 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
issue 3 november 2015
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
female
Details on test animals or test system and environmental conditions:
Source: Charles River Deutschland, Sulzfeld, Germany
Age at the Initiation of Dosing: Young adult animals (approximately 8 weeks old)
Weight at the Initiation of Dosing: 144 to 176 g
Fasting period before study: Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item. Water was available
Housing: Group housing up to 5 animals of the same sex and same dosing group together in polycarbonate cages (Makrolon MIV type; height 18 cm)
Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
Water: Free access to municipal tap-water
Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS:
Temperature (°C): 18 - 24
Humidity (%): 40 - 70
Air changes (per hr): 10 or more
Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
Gavage method: Plastic gavage cannula
Frequency: Single dosage, on day 1
Maximum Dose Volume Applied: 2000 mg/kg body weight. A dose volume of 10 mL/kg body weight was used for each dose
Dosage preparation: The dosing formulations were heated for a maximum of 30 minutes at a maximum temperature of 75.1°C in order to obtain a homogenous formulation The dosing formulations were kept at room temperature until dosing. The dosing formulations and vehicle were stirred until and during dosing
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
2 x 3 animals at dose 2000 mg/kg body weight
Control animals:
no
Details on study design:
The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups. The first group was treated at a dose level of 2000 mg/kg. Based on the results, one additional group was dosed at 2000 mg/kg

Duration of observation following administration: 14 days
Frequency of observation of Mortality / Viabillity: Twice daily
Frequency of observation of body weight: Days 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15
Necropsy of survivors performed: All moribund animals and animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded
Other examinations performed: none

Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Clinical signs observed during the study period as follows:
Hunched posture, uncoordinated movements and/or piloerection were noted for all animals on Day 1.


Body weight:
The body weight gain shown by the animals over the study period was considered to be normal (similar to that expected of normal untreated animals of the same age and strain)
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
GHS criteria not met
Remarks:
The test substance does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).
Conclusions:
In an acute oral toxicity study with Wistar rats, performed according to OECD/EC guidelines, the oral LD50 value of the test substance was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Based on these results, the test substance does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).
Executive summary:

The acute oral toxicity of the test substance in rats was assessed by the Acute Toxic Class Method according to OECD guidelines and GLP principles. The test substance was administrated by oral gavage to two groups of three female Wistar rats at 2000 mg/kg body weight, stepwise. No mortality occurred. Hunched posture, uncoordinated movements and/or piloerection were noted for all the animals on Day 1. No changes in body weight gain were noted in exposed animals, and no toxicological significant abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value was established to exceed 2000 mg/kg body weight. According to the OECD 423 guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results, the test substance does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The selected study has a reliability score 1

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study technically not feasible
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Waiver: The study need not be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of teh substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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:
other:
Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Waiving is applied accordingly to REACH Annex VIII 8.5.3 COLUMN 2; SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1

Additional information

Acute Toxicity: oral

The acute oral toxicity of the test substance in rats was assessed by the Acute Toxic Class Method according to OECD guidelines and GLP principles. The test substance was administrated by oral gavage to two groups of three female Wistar Han rats at 2000 mg/kg body weight, stepwise. No mortality occurred. Hunched posture, uncoordinated movements and/or piloerection were noted for all the animals on Day 1. No changes in body weight gain were noted in exposed animals, and no toxicological significant abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value was established to exceed 2000 mg/kg body weight. According to the OECD 423 guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Acute Toxicity: dermal

In accordance with column 2 of REACH Annex VIII, an acute dermal study (required in the section 8.5.3) is not considered necessary as the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route.

Justification for selection of acute toxicity - oral end point.

The study has been performed according to OECD and/or EC guidelines and according to GLP principles and resulted in an LD50 cut-off value suitable for classification

Justification for classification or non-classification

Based on the results from OECD guideline 423, the oral LD50 value was established to exceed 2000 mg/kg body weight. According to the OECD 423 guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results, the test substance does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).