2-cyclohexylethyl acetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

2-cyclohexylethyl acetate

EC Number:

244-543-3

EC Name:

2-cyclohexylethyl acetate

Cas Number:

21722-83-8

Molecular formula:

C10H18O2

IUPAC Name:

2-cyclohexylethyl acetate

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

The animals were maintained in groups of 3 animals per treatment in polypropylene cage closed with a metallic grid, papered with shavings of Pinnus. Housing hygienic conditions and sanitation cares were in accordance with the patterns advised by SOP-M 0825.

The animals’ rooms were maintained in controlled and monitored environmental conditions during the entire study conduct for: temperature, humidity and room ventilation. Temperature and humidity data were noted in book of records.
Temperature
Min: 19.8 ºC
Max: 23.9 ºC
Humidity
Min: 48 %
Max: 70%
Light cycles
12 hours light / 12 hours dark
Room Ventilation
10 to 15 air changes per hour

Pelleted and commercial diet for rats was provided ad libitum throughout the acclimation and observation periods. Samples of food are regularly assayed for nutritional components and environmental contaminants. Water was provided ad libitum throughout the study, in bottles with metal spouts. For water microbiological analyzes were also performed, and the same quality for human consumption. The results of analyzes of feed and water are kept in the laboratory.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Doses:

The test was initially conducted with the dose of 300 mg kg-1 of body weight, following the flowchart shown in Appendix 1. This starting dose was based on historical information from studies carried out with the same active ingredient and data from literature. The time interval between treatment groups was determined according to the duration and severity of signs of toxicity.

No. of animals per sex per dose:

Twelve rats female (Rattus Norvegicus) young adult lineage Wistar, nulliparous and non-pregnant were used after inspection and acclimation to the laboratory conditions for 5 days.

Control animals:

yes

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

Under the test conditions, the test substance Cyclohexyl Ethyl Acetate, when administered by oral route in female rats, did not cause deaths, for every step taken at the dose levels of 300 and 2000 mg kg-1 of body weight.

Clinical signs:

other: All the animals exposed to the test substance by the oral route at the doses of 300 and 2000 mg kg-1 of body weight presented no systemic signs of toxicity (Table 2).

Gross pathology:

The results of the animals necropsied at study are presented in Table 3.

Any other information on results incl. tables

 

Table 1 –Individual body weight and quantity of the substance data.

Step	Dose (mg kg^-1)	Animal #	Body weight (g)				Administered quantity (mL)	Date and hour of application
			Initial (Day 0)	Day 7	Day 14 (Final)	Difference between final and initial weight
1^st	300	1	200.73	217.66	218.53	17.80	0.07	19/Dec/2017 08:50 a.m.
		2	193.65	212.55	223.65	30.00	0.07
		3	205.83	224.52	227.27	21.44	0.07
2^nd	300	1	178.93	190.76	201.36	22.43	0.05	21/Dec/2017 08:20 a.m.
		2	185.98	203.86	213.86	27.88	0.05
		3	200.72	226.93	236.18	35.46	0.06
3^rd	2000	1	227.50	229.80	237.34	9.84	0.49	26/Dec/2017 10:00 a.m.
		2	191.64	209.98	214.37	22.73	0.41
		3	189.59	197.00	206.22	16.63	0.41
4^th	2000	1	192.76	207.31	216.03	23.27	0.41	28/Dec/2017 10:00 a.m.
		2	204.08	210.65	220.34	16.26	0.44
		3	204.26	224.95	233.60	29.34	0.44

 

1 mL of sample = 0.8816 g (M_i) (1^sttreatment); 1 mL of sample = 1.0314 g (M_i) (2^ndtreatment); 1 mL of sample = 0.9320 g (M_i) (3^rdtreatment) 1 mL of sample = 0.9299 g (M_i) (4^thtreatment)

Equations: (1) V_id= P_rx K         (2) K = Dose / 10⁶x M_i

Legend: M_i= mass in g of test item            V_id: volumen of quantity of test item 

P_r: initial animal weight             K: constant of multiplication

Table 2 –Behavioral and clinical alterations observed during the experimental period.

Treatment	Step	Sex	Animal #					observation day
				0				1	2	3	4	5	6	7	8	9	10	11	12	13	14
				0:30h*	10:00h	11:08h	12:05h
300	1	♀	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
			2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
			3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Treatment	Step	Sex	Animal #					observation day
				0				1	2	3	4	5	6	7	8	9	10	11	12	13	14
				0:30h*	09:50h	10:31h	14:04h
300	2	♀	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
			2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
			3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Treatment	Step	Sex	Animal #					observation day
				0				1	2	3	4	5	6	7	8	9	10	11	12	13	14
				0:30h*	11:00h	12:30h	14:05h
2000	3	♀	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
			2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
			3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Treatment	Step	Sex	Animal #					observation day
				0				1	2	3	4	5	6	7	8	9	10	11	12	13	14
				0:30h*	11:40h	12:30h	14:00h
2000	4	♀	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
			2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
			3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Legend:

0.            none visual alterations observed;

1.            Skin, pile and eyes alterations;

2.            Mucous membranes alterations;

3.            Respiratory system alteration;

4.            System circulation alteration;

5.            Nervous system alteration;

6.            Behavior pattern alteration;

7.            Convulsions;

8.            Salivation;

9.            Diarrhea;

10.          Lethargy;

11.          Tremble.

 

Table 3 –Pathological findings in animals at doses of 300 and 2000 mg kg^-1of body weight.

Step	Dose (mg kg^-1)	Animal #	Macroscopic Alterations
			Skin	Brain	Eyes	Lungs	Heart	Liver	Spleen	Urinary system	G.I.T	R.T	Carcass
1^st	300	1	0	0	0	0	0	0	0	0	0	0	0
		2	0	0	0	0	0	0	0	0	0	0	0
		3	0	0	0	0	0	0	0	0	0	0	0
2^nd	300	1	0	0	0	0	0	0	0	0	0	0	0
		2	0	0	0	0	0	0	0	0	0	0	0
		3	0	0	0	0	0	0	0	0	0	0	0
3^rd	2000	1	0	0	0	0	0	0	0	0	0	0	0
		2	0	0	0	0	0	0	0	0	0	0	0
		3	0	0	0	0	0	0	0	0	0	0	0
4^th	2000	1	0	0	0	0	0	0	0	0	0	0	0
		2	0	0	0	0	0	0	0	0	0	0	0
		3	0	0	0	0	0	0	0	0	0	0	0

Legend:

G.I.T – Gastrointestinal tract

R.T – Reproductive tract

0 – Not observed alteration

A – Observed alteration

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test substance Cyclohexyl Ethyl Acetate, when administered by oral route in female rats, did not cause deaths, for every step taken at the dose levels of 300 and 2000 mg kg-1 of body weight. In clinical examinations, the tested animals did not show systemic signs of toxicity. In macroscopic evaluations no alterations were observed during the necropsies. Based on the flow chart with the starting dose of 300 mg kg-1 of body weight, the test substance was classified as category 5, according to the GHS (Globally Harmonized Classification System for Chemical Substances and Mixtures). The oral LD50 value of test substance Cyclohexyl Ethyl Acetate, for female rats, was estimated to be greater than > 5000 mg kg-1 of body weight.