Registration Dossier

Administrative data

Description of key information

Acute toxicity: oral: LD50 > 2000 mg/kg bw (OECD 420, 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 16 October 2012 to 15 November 2012
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.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Monitoring Programme (inspection date: 10 July 2012/ signed on 30 November 2012)
Test type:
fixed dose procedure
Limit test:
yes
Specific details on test material used for the study:
Storage conditions: room temperature in the dark
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS (RccHanTM:WISTAR)
- Source: Harlan Laboratories UK Ltd, Oxon UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 154-170 g
- Fasting period before study: overnight. Food will be returned approximately 3 to 4 hours after dosing.
- Housing: grouped in group of up to four in suspended solid-floor polypropylene cages furnished with wood flakes.
- 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

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Sighting test: 1 female
Main test: 4 additional females
Control animals:
no
Details on study design:
SIGHTING TEST
- a single animal, 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, early and late, during normal working days, once daily at weekends and public holidays.
- Frequency of clinical observations: 30 min, 1, 2 and 4 hours after dosing, then at least once daily.
- Weighing: recorded on Day 0 (prior to dosing), Day 7 and 14, or at death.
- Necropsy of survivors performed: yes, gross necropsy on all animals
Statistics:
None
Preliminary study:
In the absence of mortality at a dose level of 2000 mg/kg bw, an additional group of animals was treated at the same dose level.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity noted in the initial treated animal. Hunched posture and ataxia were noted up to one day after dosing in the four additional treated animals.
Body weight:
All animals showed expected gains in bodyweight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, the test item is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS since the Rat Oral LD50 (females) > 2000 mg/kg bw and no
mortality or any adverse effects were observed.
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 (RccHanTM:WIST) female rats were given a single oral dose of ST 15 C 12.

Following a sighting test using one animal at a dose level of 2000 mg/kg bw, an additional four fasted female animals were given a single oral dose of test item, at the same dose level. 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. Hunched posture and ataxia were noted in four animals. There were no signs of systemic toxicity noted in the initial treated animal

All animals showed expected gains in bodyweight. No abnormalities were noted at necropsy.

Under the experimental conditions of this study, the test item is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS since the Rat Oral LD50 (females) > 2000 mg/kg bw and no mortality or any adverse effects were observed.

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
Quality of whole database:
Not required for substances at the REACH Annex VII tonnage level.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Not required for substances at the REACH Annex VII tonnage level.

Additional information

Acute toxicity: oral:

A key study was identified (Harlan, 2012). This acute oral toxicity study was according to the OECD test guideline No. 420 and in compliance with GLP. Following a sighting test using one animal at a dose level of 2000 mg/kg bw, an additional four fasted female animals were given a single oral dose of test item, at the same dose level.

There were no deaths during the study. Hunched posture and ataxia were noted in four animals. There were no signs of systemic toxicity noted in the initial treated animal. All animals showed expected gains in bodyweight. No abnormalities were noted at necropsy.

Oral LD50 Females > 2000 mg/kg bw.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self-classification:

Acute toxicity (Oral):

Based on the available data, the substance is:

- not classified according to the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw

- not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met).

Acute toxicity (Dermal):

No data was available

Acute toxicity (Inhalation):

No data was available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Regulation (EC) No. 1272/2008 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 Regulation (EC) No. 1272/2008 are not met since only hunched posture and ataxia were observed at a high dose level (2000 mg/kg bw) and animals fully recovered within one day.

Specific target organ toxicity: single exposure (Dermal):

No information was available

Specific target organ toxicity: single exposure (Inhalation):

No information was available.