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Administrative data

Description of key information

Acute toxicity: oral: LD50 > 2000 mg/kg bw (read-across, OECD 401, GLP, K, rel. 1).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included as attachment to section 13.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar physico-chemical, (eco)toxicological and environmental fate properties because of their structural similarity.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The target substance is one of the constituents of the source substance, together with isomers: the target substance is a mono-constituent, individual optical isomer, while the source substance is defined as a multi-constituent, with three pairs of racemate.

3. ANALOGUE APPROACH JUSTIFICATION
The source substance and the target substance are isomers. Based on structural and physico-chemical similarities, it is considered appropriate to read-across data from the source substance.
No toxicity was observed in the Acute Oral Toxicity test performed on the source substance.
The study design (OECD 401, GLP) is adequate and reliable for the purpose of the prediction based on read-across. The test material used represents the source substance as described in the hypothesis in terms of purity and impurities. The results of the studies are adequate for the purpose of classification and labelling.
Therefore, based on the considerations above, it can be concluded that the result of the Acute Oral Toxicity test conducted with the source substance is highly likely to predict the properties of the target substance and is considered as adequate to fulfil the information requirement of Annex VII, 8.5.1.

4. DATA MATRIX
Cf. attachment to section 13.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across: supporting information
Preliminary study:
not applicable
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred throughout the study
Clinical signs:
No clinical signs were observed throughout the study
Body weight:
There was no adverse effect on bodyweight gain
Gross pathology:
The necropsy findings were consistent with the background macroscopic pathology of this strain of rats:
- Urinary bladder: contained white waxy plug in 1M
- Left eye: appeared small, palpebral fissure reduced in size in 1M
- Uterus: minimally distended with fluid in 1F
Other findings:
None

No other information

Interpretation of results:
GHS criteria not met
Conclusions:
Oral LD50Combined > 2000 mg/kg bw
Executive summary:

In a limit acute oral toxicity study performed according to the OECD test guideline No. 401 and in compliance with GLP, groups of fasted, 5-7 weeks old, Crl:CD(SD) rats (5/sex) were administered a single oral dose of the source substance at 2000 mg/kg bw by gavage. The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.

 

No mortality and no clinical signs were observed throughout the study. There was no adverse effect on bodyweight gain. No abnormality was revealed at autopsy.

 

Oral LD50Combined > 2000 mg/kg bw

 

Under the test conditions, the source substance, is not classified according to the Regulation EC No. 1272/2008 (CLP) and to the GHS. The same conclusion applies to the target substance.

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

Read-across justification is attached to Iuclid section 13.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 1991-07-11 to 1991-07-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 401 and in compliance with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
During the acclimation period the temperature rose above the range 19-25°C on several occasions, a maximum temperature of 33°C being recorded on one occasion.
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
UK GLP (inspection date: 1990-06-19 / signature date: 1990-10-05)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD(SD)BR strain (VAF plus)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate Kent
- Age at study initiation: 5-7 weeks
- Weight at study initiation: M: 110 to 129 g; F: 119 to 127
- Fasting period before study: overnight before dosing
- Housing: in groups of 5, by sex, in grid bottomed cages suspended over cardboard lined excreta trays
- Diet: pelleted diet ad libitum (SQC rat and mouse maintenance No. 1 expanded, produced by Special Diets Services, Witham, Essex).
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C/ During the acclimatisation period the temperature rose above this range on several occasions, a maximum temperature of 33°C being recorded on one occasion.
- Humidity (%): 42-62 %
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: no data
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: not justified
- Lot/batch no. (if required): no data
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Assess to food was permitted immediately after dosing
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs: approximately 30 minutes, 1, 2 and 4 hours afters dosing and thereafter for 14 consecutive days.
Weighing: on the day of dosing, on days 8 and 15.
- Necropsy of survivors performed: yes, including opening of the thoracic and visceral cavities, opening and examination of the stomach and representative sections of the gastro-intestinal tract and examination of the major organs. Abnormal tissues and organs were preserved in buffered formol saline.
Statistics:
not done
Preliminary study:
not applicable
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred throughout the study
Clinical signs:
No clinical signs were observed throughout the study
Body weight:
There was no adverse effect on bodyweight gain
Gross pathology:
The necropsy findings were consistent with the background macroscopic pathology of this strain of rats:
- Urinary bladder: contained white waxy plug in 1M
- Left eye: appeared small, palpebral fissure reduced in size in 1M
- Uterus: minimally distended with fluid in 1F
Other findings:
None

No other information

Interpretation of results:
GHS criteria not met
Conclusions:
Oral LD50Combined > 2000 mg/kg bw
Executive summary:

In a limit acute oral toxicity study performed according to the OECD test guideline No. 401 and in compliance with GLP, groups of fasted, 5-7 weeks old, Crl:CD(SD) rats (5/sex) were administered a single oral dose of 2000 mg test material/kg bw by gavage. The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.

 

No mortality and no clinical signs were observed throughout the study. There was no adverse effect on bodyweight gain. No abnormality was revealed at autopsy.

 

Oral LD50Combined > 2000 mg/kg bw

 

Under the test conditions, the test material is not classified according to the Regulation EC No. 1272/2008 (CLP) and to the GHS.

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 on a source substance (Safepharm, 1992, Klim.1). In this limit acute oral toxicity study performed according to the OECD test guideline No. 401 and in compliance with GLP, rats were administered a single oral dose of 2000 mg/kg bw by gavage. 

No mortality and no clinical signs were observed throughout the study. There was no adverse effect on bodyweight gain. No abnormality was revealed at autopsy. 

Oral LD50 Combined > 2000 mg/kg bw

(see Iuclid section 13 for read-across justification).

Justification for classification or non-classification

Harmonised classification:

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

Self classification:

Acute toxicity (Oral):

Based on read-across data, the substance is:

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

- not classified according to the GHS as the LD50 is higher than 2000 mg/kg bw and the substance does not meet the specific criteria for the Category 5 defined in the GHS.

Acute toxicity (Dermal):

No information was available.

Acute toxicity (Inhalation):

No information 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 information was available.

Specific target organ toxicity: single exposure (Inhalation):

No information was available.

Aspiration hazard:

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