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Administrative data

Description of key information

Acute toxicity: oral: LD50 > 10000 mg/kg bw (OECD 401, GLP, rel.1, K)

Acute toxicity: inhalation: LC50 > 0.439 mg/L air and expected to be > 5 mg/L air - see explanation in the "Additional information" section (sim OECD 403, non-GLP, rel.2, K)

Acute toxicity: dermal: LD50 > 2000 mg/kg bw and expected to be > 5000 mg/kg bw - see explanation in the "Additional information" section (OECD 402, GLP, rel.2, K)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
10 000 mg/kg bw
Quality of whole database:
The key study was a GLP study conducted in compliance with OECD Guideline No. 401 without any deviation. This study was considered sufficiently robust to cover this endpoint.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
439 mg/m³
Quality of whole database:
The key study was a Non-GLP study conducted similarly to the OECD Guideline No. 403 with acceptable restrictions. This study was considered sufficiently robust to cover this endpoint.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
The key study was a GLP study conducted in compliance with OECD Guideline No. 402 with minor deviations. This study was considered sufficiently robust to cover this endpoint.

Additional information

Acute toxicity: oral

A key study was identified (Jouffrey, 1996, rel.1). In this acute oral toxicity study performed according to OECD Guideline No. 401 and in compliance with GLP, a single dose of 2000 or 10000 mg/kg bw (in two fractions of 5000 mg/kg bw each) of the test substance was given by oral gavage to groups of Sprague Dawley rats (5/sex/dose). The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations. 

No death occurred at 2000 or 10000 mg/kg bw. Signs of hypoactivity were observed at 2000 mg/kg bw within two hours after treatment in two females only. No clinical signs were noted at 10000 mg/kg bw. The body weight gain of the animals was not affected by treatment with the test substance. No abnormalities were observed at necropsy.

 

Oral LD50(rats) > 10000 mg/kg bw.

 

Acute toxicity: inhalation

A key study was identified (Thyssen, 1983). In an acute inhalation toxicity study performed similarly to the OECD Guideline No. 403, groups of Wistar rats (10/sex/dose) were exposed to the test item aerosol at concentrations of 5 and 10% in a (1:1) mixture of ethanol and Lutrol in a dynamic inhalation system for 4 hours. The theoretical concentrations were 1000 or 2000 mg/m3 air (maximum producible concentration in air); and the corresponding analytical concentrations were 280 or 439 mg/3 air. All animals were observed for mortality, clinical signs and body weight changes for 14 days, and were all sacrificed for macroscopic examinations.

No deaths occurred and the rats tolerated the concentrations without symptoms. No toxicologically relevant or concentration-related effects on the bodyweights were observed. No indications of organic injury were found during necropsy.

 

Inhalation LC50(4h, rats) > 0.439 mg/L (i.e. 439 mg/m3 air).

However, based on the absence of effect in this study and in the acute oral toxicity study up to 10000 mg/kg bw, the inhalation LC50(4h, rats) is expected to be higher than 5 mg/L air.

 

 

Acute toxicity: dermal

A key study was identified (Manciaux, 2002). In an acute dermal toxicity study performed according to the OECD Guideline No. 402 and in compliance with GLP,

a single dose of 2000 mg/kg bw of the test substance was applied to the skin of 5 male and 5 female Sprague-Dawley rats under semi-occlusive dressings for 24 hours. Animals were then observed for mortality, clinical signs and body weight changes for 14 days, and were all sacrificed for macroscopic examinations.

No clinical signs and no deaths were observed during the study. No cutaneous reactions were observed. A reduced weight gain or a slight body weight loss was seen in 3/5 females between Day 1 and Day 8 and in 2/5 females during the second week of the observation period. The body weight gain of the other treated animals was similar to that of historical control animals. No apparent abnormalities were observed at necropsy in any animal.

 

Dermal LD50(rats) > 2000 mg/kg bw.

However, based on the absence of effects in this acute dermal toxicity study up to 2000 mg/kg bw and in the acute oral toxicity up to 10000 mg/kg bw, the dermal LD50(rats) is expected to be higher than 5000 mg/kg bw.

Justification for classification or non-classification

Harmonized classification:

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

Self classification:

Acute toxicity via Oral route:

Under the test conditions, the substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS as the estimated oral LD50 is higher than 10000 mg/kg bw.

Acute toxicity via Dermal route:

Based on the available data, the substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS as the dermal LD50 is expected to be greater than 5000 mg/kg bw.

Acute toxicity (Inhalation):

Based on the available data, the substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS as the inhalation LC50 is expected to be greater than 5 mg/L air.

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) 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. No classification is required.

Specific target organ toxicity: single exposure (Dermal):

Based on available data via the oral, inhalation and dermal route, the classification criteria according to the Annex VI of the Regulation (EC) No 1272/2008 as specific target organ toxicant (STOT) – single dermal exposure Category 1 or 2 are not considered to be met. No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute dermal toxicity study, nor in the acute oral and inhalation toxicity studies.

Specific target organ toxicity: single exposure (Inhalation):

Based on available data via both the oral and inhalation route, the classification criteria according to the Annex VI of the Regulation (EC) No 1272/2008 as specific target organ toxicant (STOT) – single dermal exposure Category 1 or 2 are not considered to be met. No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute inhalation toxicity study, nor in the acute oral toxicity study.