Ethyl 2-cyclohexylpropionate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 24 October to 8 November 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to the EU Method B.1 and it is GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl 2-cyclohexylpropionate

EC Number:

412-280-5

EC Name:

Ethyl 2-cyclohexylpropionate

Cas Number:

2511-00-4

Molecular formula:

C11H20O2

IUPAC Name:

ethyl 2-cyclohexylpropanoate

Details on test material:

- Physical state: clear liquid
- Storage condition of test material: 4ºC in the dark

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Limited, Margate, Kent, England
- Age at study initiation: 7 weeks
- Weight at study initiation: 123 to 139 g
- Housing: in group of up to five rats of the same sex in metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 days prior to the start of the test

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 61 R.H
- Air changes (per hr): 10 to 15 air
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

other: glass syringe and metal cannula (17g)

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The absorption of the test substance was not determined.

Doses:

5.23 ml/kg

No. of animals per sex per dose:

tes rats ( five males and five females) was treated at g/kg bodyweight

Control animals:

no

Details on study design:

Mortality: Cages of rats were checked at least twice daily for any moratlities
Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 ( a period of five hours). On subsequent days the animals surviving treatment were observed once in the morning and again at the end of the experimental day. This latter observation was at approximately 16.30 hours on week days or 11.30 hours on Saturdays, sundays and public holidays. The nature and severity of the linical signs and time were recorded at each observation.
the animals on the preliminary and main studies were observed for 5 and 14 days respectively after dosing.
Bodyweight: Individual bodyweights were recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes were calculated.
Macroscopic examination: All animals on the main study were killed on Day 15 by cervical dislocation and were subjected to a macroscopic examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of all examined tissues was recorded.

Results and discussion

Preliminary study:

The results of the preliminary study indicated that the acute lethal oral dose to male and female rats of the test substance was greater than 2.5 g/kg bodyweight.

Mortality:

Table 1
There were no deaths following a single oral dose of the test substance at 5.0g/kg bodyweight

Clinical signs:

other: Table 2 Pilo-erection and increased salivation were observed in all rats within five minutes of dosing. Pilo-erection persisted and was accompanied at later intervals on Day 1 by abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy

Gross pathology:

No macroscopic abnormalities were observed for animals killed on Day 15.

Any other information on results incl. tables

TABLE 1
Motality data for groups of rats dosed orally
Study	Dose (g/kg)	Moltality ratio (No.of deaths)/(No.dosed)
		Male	Female	Combined
Preliminary	2,5	0/2	0/2	0/4
Main	5	0/5	0/5	0/10
TABLE 2
Signs of reaction to treatment observed in rats dosed orally
Main Study
Signs	No. of rats in group of 5 showing signs
	Dose (g/kg)
	5
	Male	Female
Pilo-erection	5	5
Abnormal body carriage (hunched posture)	5	5
Abnormal gait (waddling)	5	5
Lethargy	5	5
Decreased respiratory rate	5	5
Ptosis	5	5
Pallor of the extremitis	5	5
Increased salivation	5	5
TABLE 3
Individual bodyweights (g) of rats dosed orally
Sex	Dose (g/kg)	Animal number & ear mark	Bodyweight (g) at
			Day 1	Day 8	Day 15
Male	5	1 RP	134	211	280
		2 LP	139	230	299
		3 RPLP	139	220	291
		4 RIRO	139	223	305
		5 LILO	134	220	289
Female	5	6 RP	128	190	217
		7 LP	132	192	228
		8 RPLP	123	176	208
		9 RIRO	132	184	211
		10 LILO	129	174	215
TABLE 4
Individual bodyweight changes (g) of rats dosed orally
Main Study
Sex	Dose (g/kg)	Animal number & ear mark	Bodyweight gains (g) at
			Week 1	Week 2
Male	5	1 RP	77	69
		2 LP	91	69
		3 RPLP	81	71
		4 RIRO	84	82
		5 LILO	86	69
Female	5	6 RP	62	27
		7 LP	60	36
		8 RPLP	53	32
		9 RIRO	52	27
		10 LILO	45	41

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute lethal oral dose to rats of the test substance was found to be greater than 5.0 g/kg bodyweight

Executive summary:

A study was performed to assess the acute oral toxicity of the test substance to the rat. the method followed was that described in EEC Methods for the determination of toxicity, Directive 84/449/EEC, Part B, Method B.1. Acute toxicity (oral).

A group of ten fasted rats (five males and five females) was given a single dose by gavage of the test substance, as supplied, at a dose level of 5.0 g/kg bodyweight. All animals were killed and examined macroscopically on Day 15, the end of the observation period.

There were no deaths. Clinical signs of reaction to treatment included pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, decreased respiratory rate, ptosis, pallor of the extremities and increased salvation; recovery was comolete by Day 3.

All rats achieved anticipated bodyweight gains throughout the study.

No abnormalities were recorded at the macroscopic examination on Day 15.

The acute lethal oral dose to rats of the test substance was found to be greater than 5.0 g/kg bodyweight.

The test substance does not require labelling with the risk phrase R22 "Harmful if swallowed", in accordance with Council Directive 79/831/EEC Annex VI, Part II (D) as described in Commission Directive 91/325/EEC.