Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 03/08/2018 to 08/11/2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Purity: 98%
- Batch: MM212_S4
- Fabrication date: 18/07/2018
- Stabilizers:
7 ppm Methanesulfonic acid;
2000-3000 ppm 2,3,5-trimetilhidroquinona / Hydroquinone;
15 ppm Sulphuric acid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source (supplier): Envigo RMS Spain S.L.
- Age at study initiation: 8 weeks old
- Weight at study initiation: Mean: 221.6g
- Fasting period: Overnight before administration and approx. 3-4h afterwards
- Diet (food): Teklad global 14% protein rodent maintenance diets 2914C (irradiated).
- Food availability: Ad libitum except for an overnight fast prior to dosing and approx. 3-4h afterwards.
- Water: Tap water
- Water availability: Ad libitum.
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 3ºC
- Humidity (%): 30-70%
- Light cycle: 12:12

IN-LIFE DATES: At the end of the 15-day observation period, all surviving animals were euthanized in a CO2 atmosphere.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
300 (starting dose) and 2000 mg/kg
No. of animals per sex per dose:
6 animals per dose 300 mg/kg (in two dose steps: Group A (3 animals) and Group B (3 animals))
6 animals per dose 2000 mg/kg (in two dose steps: Group C (3 animals) and Group D (3 animals))
Therefore:
Total number of animals: 12 animals to perform 4 dose steps (A, B, C and D)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observahhtions: 30min, 2h and 4h post-administration and once daily thereafter during the 15-day observation period.
- Frequency of weighing: once during the acclimatisation period, immediately before administration for dosing purposes (from 3-4h fasted animals), weekly thereafter and prior to sacrifice.
- Necropsy of survivors performed: yes
Any visible clinical signs, discomfort and mortality were recorded.
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Group A - (Step 1) 300 mg/kg: No mortality ocurred.
Group B - (Step 2) 300 mg/kg: No mortality ocurred.
Group C - (Step 3) 2000 mg/kg: No mortality ocurred.
Group D - (Step 4) 2000 mg/kg: No mortality ocurred.
Clinical signs:
Group A - (Step 1) 300 mg/kg: No abnormalities detected.
Group B - (Step 2) 300 mg/kg: No abnormalities detected.
Group C - (Step 3) 2000 mg/kg: No abnormalities detected.
Group D - (Step 4) 2000 mg/kg: No abnormalities detected.
Body weight:
Body weight gain:
Group A - (Step 1) 300 mg/kg: From day 1 to 8: Mean: 24.187g (S.D. 5.606) and from day 8 to 15: Mean: 7.320g (S.D. 5.227).
Group B - (Step 2) 300 mg/kg: From day 1 to 8: Mean: 19.713g (S.D. 2.975) and from day 8 to 15: Mean: -2.527g (S.D. 6.029).
Group C - (Step 3) 2000 mg/kg: From day 1 to 8: Mean: 16.410g (S.D. 7.692) and from day 8 to 15: Mean 7.027g (S.D. 5.845).
Group D - (Step 4) 2000 mg/kg: From day 1 to 8: Mean: 18.590g (S.D. 4.769) and from day 8 to 15: Mean -5.960g (S.D. 4.055).
Gross pathology:
All animals killed at the end of the 15-day observation period.
Gross pathology observations: none

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
At 2000mg/kg no mortality ocurred. Therefore, the oral median lethal dose (LD50) will be >2000 mg/kg (female rats).
Based on these results and according to the EU classification criteria outlined in Regulation 1272/2008 (CLP) the compound does not need to be classified.
Executive summary:

The objective of this study is to evaluate the acute oral toxicity of the test item in female Sprague-Dawley rats by the Acute Toxic Class Method (OECD guideline Nº 423).

6 female Sprague-Dawley rats were treated with test item by oral gavage administration at 300 mg/kg bw (starting dose) and other 6 at 2000 mg/kg bw. The rats were observed for 15 days.

At 300 and 2000 mg/kg bw, no mortality ocurred and no abnormalities were detected. Therefore, the oral median lethal dose (LD50) will be >2000 mg/kg (female rats).

Based on these results and according to the EU classification criteria outlined in Regulation 1272/2008 (CLP) the compound does not need to be classified.