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Diss Factsheets

Administrative data

Description of key information

Oral LD50 > 2000 mg/kg bw (OECD 423, K, Rel.2, class method in rats)

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:
25 March to 09 April 2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
GLP study conducted in compliance with OECD Guideline No. 423 without any deviation. However, the isomers ratio is not reported.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17 December 2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
Directive n° 2004/73/EC.
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
Inspected on 2007-01-11 / Signed on 2007-02-21.
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
- Test item was considered at 100% for the study.
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle – France)
- Age at study initiation: 8 weeks
- Weight at study initiation: 195-207 g
- Fasting period before study: Food was removed at Day 1 and then redistributed 4 h after the test item administration.
- Housing: Animals were housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet, ad libitum
- Water: Drinking water (tap-water from public distribution system), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-24 °C
- Humidity: 42-60 %
- Air changes: at least ten changes per hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: 25 March to 09 April 2008
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
TEST SUBSTANCE ADMINISTRATION
- Test substance was administered by gavage under a volume of 2.06 mL/kg bw using a suitable syringe graduated fitted with an oesophageal metal canula.

MAXIMUM DOSE VOLUME APPLIED: 2.06 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 females/dose
Control animals:
yes
Remarks:
control animals received distilled water at 2 mL/kg bw
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions 14 days after administration of the test item. Observations and a mortality report were then carried out every day for 14 days. Animals were weighed on Day 0 (just before administering the test item) then on Days 2, 7 and 14.
- Necropsy of survivors performed: Yes; On Day 14, the animals were anaesthetised with sodium pentobarbital and administration continued to fatal levels, then animals were subjected to macroscopic observations.
Statistics:
None
Preliminary study:
None
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 2 500 mg/kg bw
Based on:
test mat.
Mortality:
It was noted the death of 1 treated rat, 24 hours after the test item administration.
Clinical signs:
A decrease of the spontaneous activity (6/6) associated with a bradypnea (3/6), an absence of Preyer’s reflex (2/6), eyes partly or completely closed (2/6) and an absence or a decrease of righting reflex (4/6) was registered during the 1st day of the test. The animals recovered a normal activity the 2nd day of the test.
Body weight:
The body weight evolution of the animals remained normal throughout the study.
Gross pathology:
The macroscopical examination of the animal which died during the study revealed the presence of red foci on the corpus and the lungs and a thinning of the forestomach.
The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.
Other findings:
None

None

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Under the test conditions, the oral LD50 for test substance is higher than 2000 mg/kg bw and the LD50 cut-off is 2500 mg/kg bw in female rats. Therefore the test substance is not classified according to the criteria of the Regulation (EC) No. 1272/2008 (CLP) and classified in category 5 according to the GHS.
Executive summary:

In an acute oral toxicity study (limit test) performed according to OECD Guideline 423 and in compliance with GLP, 6 female Sprague Dawley rats were given a single oral (gavage) dose of test substance at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

It was noted the death of 1 treated rat, 24 hours after the test item administration. A decrease of the spontaneous activity (6/6) associated with a bradypnea (3/6), an absence of Preyer’s reflex (2/6), eyes partly or completely closed (2/6) and an absence or a decrease of righting reflex (4/6) was registered during the 1st day of the test. The animals recovered a normal activity the 2nd day of the test. The body weight evolution of the animals remained normal throughout the study. The macroscopical examination of the animal which died during the study revealed the presence of red foci on the corpus and the lungs and a thinning of the forestomach. The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes. In this study, the oral LD50 for test substance was considered to be higher than 2000 mg/kg bw in female rats.

 

Under the test conditions, the oral LD50 for test substance is higher than 2000 mg/kg bw and the LD50 cut-off is 2500 mg/kg bw in female rats. Therefore the test substance is not classified according to the Regulation (EC) No. 1272/2008 (CLP) and classified in category 5 (H303) according 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:
2 500 mg/kg bw
Quality of whole database:
The key study is GLP compliant and of high quality. However, the isomers are not adequately characterised and as such the reliability of the study was reduced.

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

A key study was identified (Phycher, 2008, rel. 2). In this acute oral toxic class method study performed according to the OECD guideline No. 423 and in compliance with GLP, six fasted female Sprague Dawley rats received a single oral (gavage) dose of the test substance at a dose level of 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

It was noted the death of 1 treated rat, 24 hours after the test item administration. A decrease of the spontaneous activity (6/6) associated with a bradypnea (3/6), an absence of Preyer’s reflex (2/6), eyes partly or completely closed (2/6) and an absence or a decrease of righting reflex (4/6) was registered during the 1st day of the test. The animals recovered a normal activity the 2nd day of the test. The body weight evolution of the animals remained normal throughout the study. The macroscopical examination of the animal which died during the study revealed the presence of red foci on the corpus and the lungs and a thinning of the forestomach. The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

Oral LD50 > 2000 mg/kg bw and the LD50 cut-off  is 2500 mg/kg bw

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 the available information, the substance is:

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

- classified according to the GHS into Category 5 as the LD50 cut-off  is 2500 mg/kg bw.

Acute toxicity (Dermal):

No information was available. Not required for substances at the REACH Annex VII tonnage level.

Acute toxicity (Inhalation):

No information was available. Not required for substances at the REACH Annex VII tonnage level.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of 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 / Narcotic effects) according to Annex VI of the Regulation (EC) No. 1272/2008 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. Not required for substances at the REACH Annex VII tonnage level.

Specific target organ toxicity: single exposure (Inhalation):

No information was available. Not required for substances at the REACH Annex VII tonnage level.

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.