Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 - 28 Oct 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 guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Crl:CD(SD), SPF
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 weeks
- Weight at study initiation: 179.4 - 199.9 g
- Fasting period before study: Animals were fasted overnight, approx. 16 h prior and for approx. 4 h after dosing.
- Housing: 1 animal per cage in stainless wire mech cages (260W x 350D x 210H mm)
- Diet: Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C (Harlan Laboratories, Inc., USA), ad libitum
- Water: public tap water filtered and irradiated by ultraviolet light, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.8 - 22.3
- Humidity (%): 48.3 - 54.1
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 30 min and 1, 2, 4 and 6 h after dosing and thereafter once daily for 14 days. Individual body weights were recorded prior to dosing on Day 0 and on Days 1, 3, 7 and on the day of necropsy, Day 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
Abnormal gait was evident in 2 animals at 1 and 2 h after dosing. The sign disappeared 4 h after dosing.
Body weight:
All animals showed expected gains in body weight over the study period
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study in rats a LD50 cut-off value of ≥ 5000 mg/kg bw was found.
Executive summary:

The acute oral toxicity of the test substance was assessed in a study according to OECD Guideline 423 and in compliance with GLP (2015a). In a first step, a total dose of 2000 mg/kg bw of the test substance diluted in corn oil was administered to 3 female rats. Animals were observed 0.5, 1, 2, 4 and 6 hours after dosing and subsequently once daily for 14 days. Individual body weights were recorded prior to dosing on Day 0 and on Days 1, 3, 7 and on the day of necropsy, Day 14. Macroscopic examination was performed at the end of the observation period at terminal sacrifice. In a second step, 3 additional female rats were treated with 2000 mg/kg bw of the test substance diluted in corn oil. No mortalities were observed at 2000 mg/kg bw until the end of the study. Abnormal gait was evident in 2 animals at 1 and 2 hours after dosing. The sign disappeared 4 hours after dosing. All animals showed expected gains in body weight over the study period and no abnormalities were noted at necropsy. Based on the results of this study, the LD50 value was determined to be > 2000 mg/kg bw in rats. In accordance with OECD Guideline 423, Annex 2d, a cut-off value of5000 mg/kg bw was derived, since no mortality occurred at 2000 mg/kg bw.