Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met.

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)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
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 (incl. certificate)
Remarks:
inspected March 2013; signature: May 2013
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: Liquid.
- Storage condition of test material: At room temperature protected from light.
- Other: Colourless

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: Approximately 11 weeks (young adults)
- Weight at study initiation: 194 - 204 g; Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: Overnight and until 3-4 hours after administration of the test substance.
- Housing: Group housing of 3 animals per cage containing sterilized sawdust as bedding material and paper as cage-enrichment.
- Water: ad libitum
- Acclimation period: Five (5) days under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 24 (controlled)
- Humidity (%): 40 -70 (controlled)
- Air changes (per hr): 10/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark

IN-LIFE DATES: From: 20 January 2015 To: 06 February 2015

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of data suggesting the test material was toxic, 2000 mg/kg was chosen as the
starting dose. The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. 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.
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: 15 days
- Frequency of observations and weighing: Mortality/Viability: Twice daily; Bodyweights: 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. The signs were graded according to fixed scales and the time of onset, degree and duration were recorded: Maximum grade 4: grading slight (1) to very severe (4); Maximum grade 3: grading slight (1) to severe (3) an Maximum grade 1: presence is scored (1).
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality.
Clinical signs:
Hunched posture and piloerection were noted for all animals on Days 1 and 2. (Max grade = 1).
Body weight:
All animals showed bodyweight gains over the study period. 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 abnormalities were found at macroscopic post mortem examination.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the oral LD50 established to exceed 2000 mg/kg bw in female Wistar rats. According to OECD TG 423 the LD50 cut-off value was considered to exceed 5000 mg/kg bw.
Executive summary:

The study was performed according to OECD TG 423 and EU Method B1 tris Acute Toxicity, US EPA OPPTS 870.1100 and Japanese JMAFF guidelines and in accordance with GLP to assess the acute oral toxicity of the test material following a single oral administration in the female Wistar strain rat by the acute class method. The test substance was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. Hunched posture and piloerection were noted for all animals on Days 1 and 2. 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. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of the test substance in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD TG 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.