Registration Dossier

Administrative data

Description of key information

Acute toxicity, oral in rats: LD50 > 2000 mg/kg bw (OECD 423, GLP, K, Rel. 1)

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:
04-25 April 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study performed according to OECD Guideline 423 with minor deviations: temperature and humidity were occasionally lower than the minimum optimum values
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
dated 17 December, 2001
Deviations:
yes
Remarks:
temperature and humidity were occasionally lower than the minimum optimum values
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
temperature and humidity were occasionally lower than the minimum optimum values
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
23 October 2015
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage JANVIER LABS, France
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8 or 9 weeks
- Weight at study initiation: 187-205 g
- Fasting period before study: Food was removed on Day 1 and then redistributed 4 hours after the test item administration.
- Housing: Animals were housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet (e.g. ad libitum): Foodstuff (ENVIGO - 2016), ad libitum
- Water (e.g. ad libitum): Drinking water (tap-water from public distribution system), ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18-25°C
- Humidity: 17-70%
- Air changes: At least 10/hour
- Photoperiod: 12 hours dark / 12 hours light
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.47 mL/kg bw

DOSAGE PREPARATION: In the first and the second step of the study, the test item was administered by gavage under a volume of 2.47 mL/kg bw (corresponding to 2000 mg/kg bw, according to the density of 0.809 g/mL supplied by the Sponsor) using a suitable graduated syringe fitted with an oesophageal metal canula.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 female rats
Control animals:
other: historical control
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and mortality were recorded at 30 minutes, 1 hour, 3 hours, 4 hours, and then once daily for 14 days. Animals were weighed on Day D0 (just before administering the test item) and then on Day 2, Day 7, and Day 14.
- Necropsy of survivors performed: Yes; animals were euthanized with sodium pentobarbital on Day 14 and macroscopic observations were noted.
Statistics:
No data
Preliminary study:
Not applicable
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study.
Clinical signs:
A decrease or an absence in spontaneous activity (3/6), Preyer’s reflex (3/6), muscle tone (3/6), righting reflex (2/6), associated with an increase in salivation (2/6), a hypothermia (1/6), myosis (1/6), eyes partly closed (3/6), dyspnea (3/6) and piloerection (3/6) were observed. The animal recovered a normal activity on Day 7.
Body weight:
The body weight evolution of the animals revealed an absence of body weight gain on Day 2 versus Day 0. The body weight evolution was as expected from Day 7.
Gross pathology:
The macroscopic examination of the animals at the end of the study revealed a thickening and yellow coloration of the forestomach.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of the test substance is >2000 mg/kg bw in rats. Therefore it is not classified according to Regulation (EC) No 1272/2008 and GHS regulation. No signal word or hazard statement is required.
Executive summary:

In an acute oral toxicity study performed according to Guideline OECD 423 and in compliance with GLP, a single dose of 2000 mg/kg bw of the test substance was given by oral gavage to a group of 6 female Wistar rats. Animals were then observed for mortality and clinical signs of toxicity for 14 days.

No mortality occurred during the study. A decrease or an absence in spontaneous activity (3/6), Preyer’s reflex (3/6), muscle tone (3/6), righting reflex (2/6), associated with an increase in salivation (2/6), a hypothermia (1/6), myosis (1/6), eyes partly closed (3/6), dyspnea (3/6) and piloerection (3/6) were observed. The animal recovered a normal activity on Day 7. The body weight evolution of the animals revealed an absence of body weight gain on Day 2 versus Day 0. The body weight evolution was as expected from Day 7. The macroscopic examination of the animals at the end of the study revealed a thickening and yellow coloration of the forestomach.

Therefore, the oral LD50 of the test substance is >2000 mg/kg bw in rats. Therefore it is not classified according to Regulation (EC) No 1272/2008 and GHS regulation. No signal word or hazard statement is required.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
GLP study conducted according to OECD TG 423

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity:

In an acute oral toxicity study performed according to the Guideline OECD 423 and in compliance with GLP, a single dose of 2000 mg/kg bw of the test substance was given by oral gavage to a group of 6 female Wistar rats. Animals were then observed for mortality and clinical signs of toxicity for 14 days. No mortality occurred during the study. A decrease or an absence in spontaneous activity (3/6), Preyer’s reflex (3/6), muscle tone (3/6), righting reflex (2/6), associated with an increase in salivation (2/6), a hypothermia (1/6), myosis (1/6), eyes partly closed (3/6), dyspnea (3/6) and piloerection (3/6) were observed. The animal recovered a normal activity on Day 7. The body weight evolution of the animals revealed an absence of body weight gain on Day 2 versus Day 0. The body weight evolution was as expected from Day 7. The macroscopic examination of the animals at the end of the study revealed a thickening and yellow coloration of the forestomach. Rat Oral LD50 >2000 mg/kg bw.

Justification for classification or non-classification

Acute oral toxicity:

The oral LD50 of the registered substance is >2000 mg/kg bw in rats. Therefore it is not classified according to Regulation (EC) No 1272/2008 and GHS regulation. No signal word or hazard statement is required.