Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 January 2017 - 11 April 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17 December 2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
Appearance: colourless or light yellow viscous liquid
Storage conditions: at room temperature, container tightly closed, flushed with nitrogen.

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., Atsugi Breeding Center, Japan
- Age at study initiation: 8 weeks
- Weight at study initiation: first administration group: 197 - 198 g; second administration group: 189-198 g.
- Fasting period before study: yes
- Housing: polycarbonate flat-bottomed cages (W260 x D420 x H180 mm) with pulp bedding, 3 animals per cage during the main study
- Diet (analysed): pellet diet MF, offered ad libitum.
- Water (analysed): municipal tap water filtered through a 5 µm cartridge filter and sterilized with an ultraviolet sterilizer, offered ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.3-24.8
- Humidity (%): 36.8-63.2
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 17 January 2017 To: 2 February 2017

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20-w/v%
- Amount of vehicle (if gavage): 1.998 g (first administration) and 2.001 g (second administration) of test substance was made up to 10 mL with corn oil
- Justification for choice of vehicle: corn oil was used as the vehicle according to the sponsor's instructions.
- Lot/batch No.: U5429

MAXIMUM DOSE VOLUME APPLIED: yes, 10 mL/kg body weight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: according to the guidance document on Acute Oral Toxicity, OECD Guideline No. 423.
Doses:
For the first and for the second administration: 2000 mg/kg body weight (the study was performed in a stepwise manner where the second administration dose depended on the results of the first administration).
No. of animals per sex per dose:
2 groups of 3 females, dosed in a step-wise manner
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations (general condition): at least once within 30 minutes after administration, and subsequently at 1, 2, 3, 4 and 6 hours after administration. On the following days (from day 1), it was performed once daily.
- Frequency of weighing: before administration (on day 0) and 1, 2, 3, 7 and 14 days after administration.
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred in any of the groups.
Clinical signs:
No abnormalities were noted in either of the first or second administration group.
Body weight:
In the first administration group, the weights increased from 1 day after administration, and the mean gain for 14 days was 66.0 g. In the second administration group, the weights incresed from 1 day after administration and the mean gain for 14 days was 66.7 g. Weight gains were satisfactorily compared to normal, untreated animals from the same age and strain.
Gross pathology:
No abnormalities were noted in either of the first administration or second administration group.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of an acute oral toxicity study, performed accordig to OECD guideline 401 and GLP principles, the LD50 of STABiO D-376N exceeded 2000 mg/kg body weight and therefore the substance is not classified under GHS.
Executive summary:

In an acute oral toxicity study, performed according to OECD guideline 401 and GLP principles, STABiO D-376N was tested in 6 female rats. The study was conducted in a stepwise manner, with a starting dose of 2000 mg/kg in 3 rats. After confirming no animal died, the same dose was used for the second administration. The test substance was administered by oral gavage and corn oil was used as a vehicle (20 w/v %). Observations were made for 14 days after exposure. No animal died in either group and no abnormalities were noted during the in-life phase as well as during gross pathology. Body weights increased satisfactory compared to animals of the same age and strain. Based on these results, the LD50 was determined to be >2000 mg/kg body weight and STABiO D-376N is not classified under GHS.