Lorenox™

Endpoint summary

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:

17 February to 04 March 2009

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. The substance is adequately identified, but some data on composition is missing. Therefore validation applies with restrictions.

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)

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2008-04-14&15 /Signed on 2008-07-16.

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

- Date received: 10 February 2009 (Flask 1); 18 February 2009 (Flask 2)

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: 7-8 weeks
- Weight at study initiation: 180-196 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: 19-25 °C
- Humidity: 30-70 %
- Air changes: at least ten changes per hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: 17 February to 04 March 2009

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: Animals of the treated group during the first step, received the test item (Flask 1) under the dose volume of 2.22 mL/kg bw; animals of the treated group during the 2nd step, received the test item under the dose volume of 2.18 mL/kg bw.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females/dose

Control animals:

yes

Remarks:

3 animals received distilled water at 10 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:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No clinical signs related to the administration of the test item were observed.

Gross pathology:

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:

GHS criteria not met

Conclusions:

Under the test conditions, the oral LD50 of test item is higher than 2000 mg/kg bw in female rats therefore it must not be classified according to the CLP Regulation (EC) No. 1272/2008 and Globally Harmonized System (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 item 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.

 

No mortality occurred during the study. No clinical signs related to the administration of the test item were observed. The body weight evolution of the animals remained normal throughout the study. The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

 

Under the test conditions, the oral LD50 of test item is higher than 2000 mg/kg bw in female rats therefore it must not be classified according to the CLP Regulation (EC) No. 1272/2008 and Globally Harmonized System (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 was lowered to 2 because of missing information regarding the identification of the substance)

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, 2009, rel. 2). In this acute oral toxic class method study performed according to the OECD guideline No. 423 and in compliance with GLP, six 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.

No mortality occurred during the study. No clinical signs related to the administration of the test item were observed. The body weight evolution of the animals remained normal throughout the study. The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

Oral LD50 > 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 (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.

- 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 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 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 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. 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.