Methyl trans-3-oxo-2-pentylcyclopentanecarboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 November - 15 December 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted by GLP accredited laboratory. Method according to OECD guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: JMAFF guidelines (2000) including revisions

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

methyl trans-3-oxo-2-pentylcyclopentanecarboxylate

EC Number:

700-527-2

Cas Number:

1271488-66-4

Molecular formula:

C12H20O3

IUPAC Name:

methyl trans-3-oxo-2-pentylcyclopentanecarboxylate

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Wistar rats strain Crl:WI (Han) (outbred, SPF quality) from Charles River Deutschland, Sulzfeld, Germany. Animals 9-10 weeks old were selected having body weights +/-20% of the sex mean.
A controlled environment was maintained in the room with optimal conditions of approximately 15/h air changes, a temperature of 19.5-23.6ºC, a relative humidity of 32-60% and a 12 hour artificial fluorescent light/12 hour dark cycle per day.
3 animals were present per cage in labeled Macrolon cages containing sterilised sawdust as bedding material and paper as cage-enrichment. Animals were acclimitised for a period of 5 days prior to exposure. The animals had free access to tap water and pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest , Germany.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Animals were orally exposed to a single dose using plastic feeding tubes. The OECD guideline prescribes that the test substance should be administered in a single dose by gavage using a single dose. Therefore no vehicle was necessary.

Doses:

The dose level was 2000 mg/kg (1.98 ml.kg) body weight on day 1. This dose level was selected based on the acute oral toxicity of the closely structure-related dihydro isojasmonate, which is also > 2000 mg/kg.

No. of animals per sex per dose:

3 female rates per group. Two groups of rats.

Control animals:

yes

Details on study design:

The toxicity of the test substance was assessed by stepwise treating the two groups of animals (group 1: 18 November 2010; group 2: 1 December 2010) at a dose level of 2000 mg/kg. The absence or presence of mortality deteremined the dose of the next step.

Statistics:

The method used is not intended to calculate a precise LD50, hence no statistical analysis was performed. The oral LD50 was ranked and an LD50 cut-off value determined based on the OECD 423 guideline.

Results and discussion

Preliminary study:

The structure-related compound dihydro isojasmonate (CAS 37172-53-5) is non-toxic. The test substance and dihydro isojasmonate both belong to the aliphatic ketones and differ by only on carbon in the alkyl group. The LD50 of the dihydro isojasmonate in 10 male Wistar rats exceeds 5000 mg/kg.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

All animals showed hunched posture on day 1. In addition, four out of 6 animals showed piloerection and/or abnormal gait on day 1 and hunched posture on day 2 (Table 1).

Body weight:

The body weight gain during the study period was similar to the group of untreated animals (Table 2).

Gross pathology:

No abnormalities were found at the macroscopic post mortem examinations of the animals. The scheduled necropsy was on day 15 after treatment.

Any other information on results incl. tables

Table 1 Clinical signs of the female Wistar rats treated with 2000mg/kg test substance.

Test Day			1	1	1	2	3-15
hours after treatment			0	2	4
Animal 1
	Hunched posture		-	1	1	1	-
	Abnormal gait		-	1	1	-	-
	Piloerection		-	1	1	-	-
Animal 2			-	1	1	-	-
	Hunched posture		-	1	1	1	-
	Abnormal gait		-	1	1	-	-
	Piloerection		-	1	1	-	-
Animal 3			-	1	1	-	-
	Hunched posture		-	1	1	1	-
	Abnormal gait		-	1	1	-	-
	Piloerection		-	1	1	-	-
Animal 4			-	1	1	-	-
	Hunched posture		1	1	1	1	-
	Piloerection		-	-	1	-	-
Animal 5						-	-
	Hunched posture		1	1	1	-	-
Animal 6			-	1	1	-	-
	Hunched posture		1	1	1	-	-

- : sign not observed; Hunched posture and piloerection: 1 is present; Abnormal gait grading slight (1) to severe (3);

Table 2 Body weight in grams of the female Wistar rats treated with 2000 mg/kg test substance

	Day 1	Day 8	Day 15			Day 1	Day 8	Day 15
Animal					Animal
1	179	198	205		4	175	207	219
2	176	201	211		5	174	205	219
3	175	202	209		6	164	190	202
mean	177	200	208		mean	171	201	213
std	2	2	3		std	6	9	10
n	3	3	3		n	3	3	3

std: standard deviation; n: number of animals

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information: based on GHS (2007) and Regulation (EC) 1272/2008.

Conclusions:

The oral LD50 of the test substance in Wistar rats exceeds 2000 mg/kg body weight. The LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Executive summary:

The acute toxicity class method (OECD 423 (2001)) was used to assess the acute toxicity of test substance in 6 female Wistar rats.

The test substance was administered by oral gavage to two subsequent groups of rats at a dose level of 2000 mg/kg body weight. Animals were observed daily and their body weights were weekly recorded. Macroscopic examination was performed after sacrifice.

No mortality occurred. All animal showed hunched posture on day 1 and four out of six animals showed piloerection and/or abnormal gait on day 1 and hunched posture on day 2.

The body weight gain was normal.

No abnormalities were found at post mortem examinations of the animals.

The LD50 of the test substance exceeds 2000 mg/kg body weight and the LD50 cut-off value exceeds 5000 mg/kg body weight.

Consequently, the test substance does not need to be classified according to the GHS and Regulation (EC) 1272/2008.