Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 September 2015 - 08 October 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
(2001)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
(2002)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Appearance: White powder
Specific details on test material used for the study:
- pH (1% in water, indicative range): 6.2 - 6.5
- Insoluble in water

Test animals

Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 8-11 weeks old)
- Weight at study initiation: 186-206 g (1st group) and 155-159 g (2nd group)
- Fasting period before study: Animals were deprived of food overnight prior to dosing
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: Free access to tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS (set conditions)
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 22 September 2015 To: 08 October 2015

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
(Elix, Millipore S.A.S., Molsheim, France)
Details on oral exposure:
GAVAGE METHOD: plastic feeding tubes.

Frequency: single dosage, on Day 1.

VEHICLE
- The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw (10 mL/kg bw)

DOSAGE PREPARATION
The preparations (w/w) were dosed within 4 hours after adding the vehicle to the test item. Homogeneity was assessed by visual inspection of the solutions and the formulations were stirred during dosing, which ensures homogeneity sufficient for these kinds of studies. No correction was made for purity of the test item.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
6 (2 groups of three females in a stepwise manner)
Control animals:
no
Details on study design:
Animals were deprived of food until 3-4 hours after administration of the test substance.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: 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: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. 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).

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture, piloerection and/or uncoordinated movements were noted for the animals on Day 1.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Gross pathology:
- No test substance related abnormalities were found.
- Pelvic dilatation of the right kidney was found in one animal. Since this is occasionally seen among rats of this age and strain and it was found in one animal only, this was considered not toxicologically significant.

Applicant's summary and conclusion

Interpretation of results:
other: the substance does not need to be classified for acute toxicity by the oral route according to GHS and CLP
Conclusions:
In an acute oral toxicity study in rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined.
Executive summary:

The acute oral toxicity of the substance was determined in accordance with OECD 423 (2001) and according to GLP principles. The substance was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. No mortality occurred. Hunched posture, piloerection and/or uncoordinated movements were noted for the animals on Day 1. Necropsy did not show any abnormality. The acute oral toxicity (LD50) was determined to be >2000 mg/kg bw. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight. Based on the results of this study, the substance does not need to be classified for acute toxicity by the oral route according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and Regulation (EC) No 1272/2008 (CLP Regulation).