[No public or meaningful name is available]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From January 14, to February 12, 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study performed according to OECD test guideline No. 420 and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

30 May 2008

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

Adopted 17 December 2001

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nousan No 8147, Agricultural Production Bureau

Version / remarks:

24 November 2000

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP Compliance Monitoring Programme (inspected on 2018-01-16 / signed on 2018-06-05)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(±)-1-[(1RS,2SR,4SR)-BICYCLO[2.2.1]HEPT-2-YL]-5-HEXEN-2-ONE

Cas Number:

1352216-65-9

Molecular formula:

C13H20O1

IUPAC Name:

(±)-1-[(1RS,2SR,4SR)-BICYCLO[2.2.1]HEPT-2-YL]-5-HEXEN-2-ONE

Constituent 2

Reference substance name:

(±)-1-[(1RS,2RS,4SR)-BICYCLO[2.2.1]HEPT-2-YL]-5-HEXEN-2-ONE

Cas Number:

1352216-63-7

Molecular formula:

C13H20O1

IUPAC Name:

(±)-1-[(1RS,2RS,4SR)-BICYCLO[2.2.1]HEPT-2-YL]-5-HEXEN-2-ONE

Test material form:

liquid

Details on test material:

Appearance: Colourless liquid

Specific details on test material used for the study:

Storage conditions: Dry area, protected from light, in a refrigerator (temp 2-8°C), store under nitrogen in a closed container after first opening.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS (RccHanTM:WIST)
- Source: Envigo RMS (UK) Ltd
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 153-176 g
- Fasting period before study: overnight prior to and approximately four hours after dosing.
- Housing: grouped in group of one or four rats in polypropylene cages with stainless steel mesh lids and furnished with softwood based bark-free fiber bedding.
- Diet (e.g. ad libitum): Rodent 2014C Teklad Global Certified Diet ad libitum. Not contaminated.
- Water (e.g. ad libitum): Tap water ad libitum. Not contaminated.
- Acclimation period: at least 5 days before treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 40-70
- Air changes (per hr): TBC
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14 January 2019 To: 12 February 2019

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: Corn oil was used because the test item did not dissolve/suspend in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test item formulations were prepared on the day of dosing.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

300 mg/kg bw: 1 female
2000 mg/kg bw: 5 females

Control animals:

no

Details on study design:

SIGHTING TEST
- a single animal per dose, 300 and 2000 mg/kg bw

MAIN TEST
- 5 animals per dose level (made up of one animal from the sighting test dosed at the selected dose level together with an additional 4 animals)
- Duration of observation period following administration: 14 days
- Frequency of mortality / morbidity inspection: twice daily.
- Frequency of clinical observations: at least two occasions during the first hour following dosing (ca. thirty minutes apart) and thereafter at approximately hourly intervals for the remainder of Day 1 (for at least 4 hours). On subsequent days, the animals were observed at least once in the morning and once towards the end of the experimental day. On the day the study terminated there was only one observation (morning only).
- Weighing: recorded on Days -1, 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: yes, on Day 15 by carbon dioxide asphyxiation. All animals were subject to a macroscopic examination.

Statistics:

None

Results and discussion

Preliminary study:

In the absence of mortality at a dose levels of 300 and 2000 mg/kg bw, an additional group of animals was treated at the highest dose level (i.e 2000 mg/kg bw).

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 was observed.

Mortality:

There were no deaths.

Clinical signs:

other: Clinical signs observed were red extremities and elevated gait seen in all females dosed at 2000 mg/kg in the main and sighting studies and underactivity, piloerection, hunched posture and yellow staining in the ventral surface were seen in four females d

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Oral LD50 Females > 2000 mg kg bw.

Executive summary:

In an acute oral toxicity study performed according to the OECD test guideline No. 420 and in compliance with GLP, groups of fasted, eight to twelve weeks of age Wistar (RccHan^TM:WIST) female rats were given a single oral dose of ST 03 C 18 as a suspension in corn oil. Following a sighting test using two single animals at dose levels of 300 and 2000 mg/kg bw. As no mortality or toxicity was observed at 2000 mg/kg bw, an additional four fasted female animals were given a single oral dose of test item, at the highest dose level (i.e 2000 mg/kg bw). Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Oral LD₅₀ Females > 2000 mg/kg bw

There were no deaths during the study.

Clinical signs observed were red extremities and elevated gait seen in all females dosed at 2000 mg/kg in the main and sighting studies and underactivity, piloerection, hunched posture and yellow staining in the ventral surface were seen in four females dosed at 2000 mg/kg in the main study. Also, hindlimbs splayed was observed for one female dosed at 2000 mg/kg in the sighting study and unsteady gait was observed for two females dosed at 2000 mg/kg in the main study and one female in the sighting study dosed at 2000 mg/kg. These signs were first noted approximately one hour after dosing. Recovery of animals, as judged by external appearance and behavior, was complete by Day 3. No clinical signs were seen in any animal dosed at 300 mg/kg.

All animals showed expected gains in bodyweight.

No abnormalities were noted at necropsy.

Under the test conditions, ST 03 C 18 is not classified as toxic if swallowed according to the Regulation (EC) No. 1272/2008 (CLP) but is included in Category 5 according to the Global Harmonised System (GHS), based on the clinical observations.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.