Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 21 - August 19, 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to current OECD test guidelines and GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): E-Y110
- Physical state: Orange powder (Solid)
- Lot/batch No.: MB-1
- Expiration date of the lot/batch: July 6, 2015
- Storage condition of test material: Room temperature, dark place

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc. (Hino breeding center)
- Age at study initiation: 9 weeks
- Weight at study initiation: 189.2-199.7 g
- Fasting period before study: From the evening on the day before the administration (approx 18 hours predose) to about 3 hours postdose.
- Housing: Stainless steel cages (W226xD346xH198 mm), stainless steel racks and feeders, one animal per cage
- Diet (ad libitum): Pellet diet (CRF-1, Oriental Yeast Co., Ltd.) (each lot analysed: contaminants confirmed to be within acceptable limits established by the testing facility)
- Water (ad libitum): Well water admixed with NaClO (about 2 ppm) (analysed every 6 months: contaminants confirmed to be within acceptable limits in compliance with waterworks law, Japan)
- Acclimation period: 6 days for experiment 1 and 8 days for experiment 2

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.6-24.6
- Humidity (%): 44.9-61.3
- Air changes (per hr): 10 to 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: test substance solved to make a dosing solution at a concentration of 100 mg/ml

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg bw

DOSAGE PREPARATION: The dosing volumes for individual animals were calculated on the basis of the body weight measured just before administration.

CLASS METHOD
- Rationale for the selection of the starting dose: The lethal dose of a similar substance was reported to be 2000 mg/kg or above. Therefore, the dose level for the first administration was set at 2000 mg/kg, which is the maximum dose recommended in the guideline applied to this study. As a result, as no death or moribundity was observed on the day after the first administration the dose level for the second administration was also set at 2000 mg/kg.
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 females in each of 2 experiments
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and clinical signs were observed before the dosing (Day 1, day of initial administration), 30 min, 1, 3, and 5 hours postdose on Day 1 and once daily for 14 days thereafter. Body weight was measured just before the administration (Day 1) and on Days 4, 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: none
Statistics:
not applicable

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths were noted in any animal in experiment 1 and 2.
Clinical signs:
Test substance mixed feces was observed in 1 or 2 animals at 3 hours, all animals at 5 hours on Day 1 and Day 2, and chromaturia (thick yellowish) was observed in all animals on Day 2 in experiment 1 and 2. These changes were attributed to the test substance as this is an orange powder.
Body weight:
No abnormalities were noted in body weight gain in any animal in experiment 1 or 2.
Gross pathology:
No abnormalities were noted in any animal in experiment 1 or 2.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of E-Y110 in rats was determined to be above 2000 mg/kg bw under the conditions of this study (OECD 423).
Executive summary:

A single oral administration of E-Y110 (dissolved in water) by gavage was conducted to female SD (Crl:CD(SD)) rats aged 9 weeks to evaluate its acute oral toxicity in accordance with the OECD test guideline 423. A dose of 2000 mg/kg bw was employed for the first and second administration to each of three rats. As a result, there was no mortality, body weight gain effects, or necropsy findings. Clinical signs were restricted to test substance mixed feces and chromaturia (thick yellowish). In conclusion, the LD50 of E-Y110 was determined to be above 2000 mg/kg bw under the conditions of this study.