[No public or meaningful name is available]

Endpoint summary

Description of key information

Oral LD50 Females > 2000 mg kg bw (OECD 420, GLP, K, rel.1).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Adopted 17 December 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

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

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.

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

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

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).

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

None

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is GLP compliant and of high quality (Klimisch score = 1)

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute toxicity: oral

A key study was identified (Envigo, 2019). This acute oral toxicity study was performed according to the OECD test guideline No. 420 and in compliance with GLP.

Clinical signs observed were red extremities and elevated gait seen in all females dosed at 2000 mg/kg bw 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 bw in the main study. Also, hindlimbs splayed was observed for one female dosed at 2000 mg/kg bw in the sighting study and unsteady gait was observed for two females dosed at 2000 mg/kg bw in the main study and one female in the sighting study dosed at 2000 mg/kg bw. 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 bw.

All animals were considered to have achieved satisfactory body weight gains throughout the study.

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Oral LD₅₀Females > 2000 mg/kg bw.

Justification for classification or non-classification

Harmonised classification:

The substance has no harmonised classification for health hazards according to the Regulation (EC) No. 1272/2008 (CLP).

Self classification:

Acute toxicity via Oral route:

Based on the available data, the substance is:

- not classified according to the CLP as the LD50 is greater than 2000 mg/kg bw

- classified in Category 5 (May be harmfull if swallowed) according to the GHS as based on the clinical observations at 2000 mg/kg bw.

Acute toxicity via Dermal route:

No data was available.

Acute toxicity via Inhalation:

No data was available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

No data was available.

Specific target organ toxicity: single exposure (Inhalation):

No data was available. However, the registered substance is not a skin or an eye irritant, therefore respiratory tract irritation is not expected.

 

Aspiration hazard:

The substance is not a hydrocarbon and no effects were observed on lungs in oral studies, therefore the criteria for aspiration toxicity according to the CLP and to the GHS are not met.