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Description of key information

5000 mg/kg bw < Oral LD50 < 10000 mg/kg bw (OECD 401, WoE, Rel.2, limit test in rats)
Dermal LD50 > 5000 mg/kg (U.S.- FHSA, K, Rel. 2, limit test in rabbits)
Inhalation LC50 > 4.96 mg/L (OECD 403, K, Rel.2, limit test in rats)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The three studies were of high quality (Klimisch score = 2). The reliability score was lowered to 2 which is the maximum score for read-across in 2 out of 3 studies.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
4 930 mg/m³ air
Quality of whole database:
The key study is GLP-compliant and of high quality (Klimisch score = 2). The reliability score was lowered to 2 which is the maximum score for read-across.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The key study is GLP-compliant and of high quality (Klimisch score = 2). The reliability score was lowered to 2 which is the maximum score for read-across.

Additional information

No study was available on the substance itself, therefore a read-across approach was used. The supporting substances are considered adequate for read-across purpose as data relates to a mixture of cis- and trans-isomers whereas the registered substance is the pure cis-isomer (see Iuclid section 13 for additional justification).

 

Acute toxicity: Oral:

 

Table 7.2.1/1: Acute Oral Toxicity Tests Performed (limit tests)

 

Test n°

Test Guideline

Test Substance isomer composition

Number of animals tested

Number of deaths

Concentration tested

(mg/kg bw)

LD50

(mg/kg bw)

Recovery of clinical signs after14 days?

1

Life Science Research, 1980

OECD 401

90% trans-

10%cis-

20

3/20

10000

> 10000

Yes*

2

Istituto di Ricerche Biomedichea, 1996a

OECD 401

70 % trans

30 %cis-

10

4/10

10000

~ 10000

Yes

3

Istituto di Ricerche Biomedichea 1996b

OECD 401

30 % trans-

70 %cis-

10

9/10

10000

< 10000

Yes

* Excepted hair loss observed in one female

 

Three limit tests performed with different qualities of the test substance were carried out according to the OECD TG 401 “Acute Oral Toxicity” using a limit test concentration of 10000 mg/kg bw (see table above). Test substance was administrated to rats by gavage. All the tests were selected within a weight of evidence approach as different mixture of cis/trans isomers were tested in these limit tests. High test concentrations were tested in all of these tests in comparison with current test guidelines (i.e. OECD TG 423) which now recommend testing of a concentration of 2000 mg/kg bw in limit tests.

 

Test n°1 (see table) was performed with high trans-isomer quality (~90% trans). Less than 20 % of tested animal died at the limit test concentration of 10000 mg/kg bw and surviving animals totally recovered from clinical signs in less than 7 days. Therefore the LD50 can be estimated to be greater than 10000 mg/kg bx for high trans-isomer quality.

Test n°2 and 3 were performed on qualities having higher cis-isomers content (30 % and 70 % respectively). An LD50 of ~10000 mg/kg bw was determined with a 30 % cis content quality whereas higher cis content quality (70%) indicate than LD50 is lower than 10000 mg/kg bw.

In view of these results made with different qualities of the substance, it can be assumed than the oral LD50 of the substance is greater than 5000 mg/kg bw and smaller than 10000 mg/kg bw.

 

Acute toxicity: dermal

A limit test was carried out on New Zealand White Rabbits according to FHSA test guideline using a test concentration of 5000 mg/kg bw of high trans-isomer quality. The FHSA test guideline used to determine acute dermal toxicity (48 h substance application on abraded skin in occlusive conditions), is more severe than classical guidelines like OECD TG Guideline 402 (4 hours application on shaved skin in semi-occlusive conditions). Animals were observed for 14 days for mortality, clinical signs and bodyweight changes. A necropsy was performed on all animals at the end of the study. No relevant clinical signs were observed, bodyweight changes were normal and no abnormalities were noted during the necropsy.

The dermal LD50 was therefore determined to greater than 5000 g/kg bw.

 

Acute toxicity: inhalation

A limit test study was performed on ten Sprague-Dawley rats to assess the acute inhalation toxicity of the high trans-isomer quality according to the OECD TG (1981) No. 403 "Acute Inhalation Toxicity". The animals were exposed for four hours to a unique nominal dose of 5 mg/L as an aerosol atmosphere using a nose only exposure system, followed by a fourteen day observation period.

Animals recovered steadily to common abnormalities and appeared to be normal from Days 3 - 6. Normal bodyweight development was noted during the study and with the exception of a single instance of dark foci on the lungs, No abnormalities were detected at necropsy. No deaths occurred in a group of ten rats exposed to a mean achieved atmosphere concentration of 4.93 mg/L.The inhalation LC50 was therefore determined to be much greater than 4.93 mg/L as no death occurred as this concentration.



Justification for selection of acute toxicity – oral endpoint
No study was selected since a weight-of-evidence approach using three studies performed on different mixture of cis/trans isomers was used to conclude on acute oral toxicity of the registered substance.

Justification for selection of acute toxicity – inhalation endpoint
No study was available on the substance itself, therefore a read-across approach was used. The supporting substance is considered adequate for read-across purpose as data relates to a mixture of cis- and trans-isomers whereas the registered substance is the pure cis-isomer (see Iuclid section 13 for additional justification).

Justification for selection of acute toxicity – dermal endpoint
No study was available on the substance itself, therefore a read-across approach was used. The supporting substance is considered adequate for read-across purpose as data relates to a mixture of cis- and trans-isomers whereas the registered substance is the pure cis-isomer (see Iuclid section 13 for additional justification).

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 including ATP4.

Self-classification:

Acute toxicity via Oral route:

Based on the available data, the substance is:

- not classified according to the Regulation (EC) No. 1272/2008 as the LD50 is greater than 5000 mg/kg bw

- not classified according to the Directive 67/548/EEC as the LD50 is greater than 5000 mg/kg bw.

Acute toxicity via Dermal route:

Based on the available data, the substance is:

- not classified according to the Regulation (EC) No. 1272/2008 as the LD50 is greater than 5000 mg/kg bw

- not classified according to the Directive 67/548/EEC as the LD50 is greater than 5000 mg/kg bw.

Acute toxicity (Inhalation):

Based on the available data, the substance is:

- not classified according to the Regulation (EC) No. 1272/2008 as the LD50 is greater than 4.93 mg/L

- not classified according to the Directive 67/548/EEC as the LD50 is greater than 4.93 mg/L.

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.

Specific target organ toxicity: single exposure (Dermal):

The classification criteria according to the Annex VI of the Regulation (EC) No 1272/2008 as specific target organ toxicant (STOT) – single exposure, dermal 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 (dermal) for a Category 1 classification (C≤ 1000 mg/kg bw) and at the guidance value (dermal) for a Category 2 classification (2000 mg/kg bw≥C > 1000 mg/kg bw). No classification is required.

Specific target organ toxicity: single exposure (Inhalation):

The classification criteria according to the Annex VI of the Regulation (EC) No 1272/2008 as specific target organ toxicant (STOT) – single exposure, inhalation 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 (inhalation, dust/mist) for a Category 1 classification (C≤ 1 mg/L) and at the guidance value (inhalation, dust/mist) for a Category 2 classification (5 mg/L ≥C > 1 mg/L). No classification is required.

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