Methyl 3-oxo-2-pentylcyclopentaneacetate

Endpoint summary

Description of key information

Oral LD50 > 5 g/kg (US-FHSA),  limit test in rats
Oral LD50 ~ 10 g/kg (OECD 401),  limit test in rats
Oral LD50 < 10 g/kg, (OECD 401),  limit test in rats
Dermal LD50 > 5 mg/kg (U.S.- FHSA),  limit test in rabbits 
Inhalation LC50 >  4.96 mg/l (OECD 403),  limit test in rats

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

4 930 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Additional information

 

Table1: Acute Toxicity Tests Performed (limit tests)

Test n°	Test Guideline	Test Substance isomer composition	Number of animals tested	Number of deaths	Concentration tested	LD(C)50	Recovery of clinicalsigns after14 days?
Acute Oral Toxicity
1	US-FHSA	90% trans- 10%cis-	10	0	5g/kg	> 5g/kg	N.A. (no clinical signs observed)
2	OECD 401	90% trans- 10%cis-	20	3/20	10g/kg	> 10g/kg	Yes*
3	OECD 401	70 % trans 30 %cis-	10	4/10	10g/kg	~ 10g/kg	Yes
4	OECD 401	30 % trans- 70 %cis-	10	9/10	10g/kg	< 10g/kg	Yes
* Excepted hair loss observed in one female
Acute Dermal Toxicity
5	US-FHSA	90% trans- 10%cis-	10	0	5g/kg	> 5g/kg	N.A. (no clinical signs observed)
Acute Inhalation Toxicity
6	OECD 403	90% trans- 10%cis-	10	0	5mg/l/4h	>4.93 mg/l/4h	Yes

 

Acute Oral Toxicity

Four 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 10 g/kg or according to US-FHSA test guideline using a limit test concentration of 5 g/kg (see table above). Test substance was administrated to rats by gavage. All the tests were selected as key studies as different test qualities and concentrations 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 2 g/kg in limit tests.

 

Test n°1 and 2 (see table) were performed with high trans isomers qualities (~90% trans). Less than 20 % of tested animal died at the limit test concentration of 10 g/kg and surviving animals totally recovered from clinical signs in less than 7 days. No death occurred at the limit test concentration of 5.0 g/kg and no relevant clinical signs were observed. Therefore the LD50 can be estimated to be greater than 10 g/kg for high trans isomers qualities.

Test n°3 and 4 were performed on qualities having higher cis isomers content (30 % and 70 % respectively). An LD50 of ~10 g/kg was determined with a 30 % cis content quality whereas higher cis content quality (70%) indicate than LD50 is lower than 10 g/kg.

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 5 g/kg and smaller than 10 g/kg. The substance is therefore not classified according to both DSD and CLP as the test substance LD50 is well above the minimal concentration to be classified (≤ 2000 mg/l).

 

Acute dermal toxicity. A limit test was performed was carried out on New Zealand White Rabbits according to FHSA test guideline using a test concentration of 5 mg/kg. 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 5 g/kg and the test material is classified as non toxic according to FHSA and would also not be classified according to DSD and CLP.

 

Acute inhalation toxicity. A limit test study was performed on ten Sprague-Dawleyrats to assess the acute inhalation toxicity of the test material according to the OECD TG (1981) No. 403 "Acute Inhalation Toxicity". The animals were exposed for four hours to a unique 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 thelungs,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 dermal LC50 was therefore determined to be much greater than 4.93 mg/l as no death occurred as this concentration. We can therefore conclude that it is therefore not classified according to DSD and CLP.

Justification for classification or non-classification

Oral LD50 of the substance is greater than 5 g/kg and smaller than 10 g/kg is therefore not classified according to both FHSA and CLP.

 

Dermal LD50 was determined to greater than 5 g/kg; the test material is not classified according to both FHSA and CLP.

 

Inhalation LC50 was determined to be much greater than 4.93 mg/l as no death occurred as this concentration. It is therefore not classified according to CLP.