Reaction mass of (1R)‐1‐[(1S)‐3,3‐dimethylcyclohexyl]ethyl relacetate and (1R,2R)‐2,6,6‐trimethylcycloheptyl rel‐acetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Apr 1981 to May 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Four animals were used instead of five and they were not of the same sex

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(1R)-1-[(1S)-3,3-dimethylcyclohexyl]ethyl rel-acetate

Molecular formula:

C12H22O2

IUPAC Name:

(1R)-1-[(1S)-3,3-dimethylcyclohexyl]ethyl rel-acetate

Constituent 2

Reference substance name:

(1R,2R)‐2,6,6‐trimethylcycloheptyl rel‐acetate

Molecular formula:

C12H22O2

IUPAC Name:

(1R,2R)‐2,6,6‐trimethylcycloheptyl rel‐acetate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

CD strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: males 101 – 134 g and females 100 - 117g
- Fasting period before study: overnight before treatment

IN-LIFE DATES: April/May 1981

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test substance was administered at a range of dosage volumes of 6.88 to 17.2 mL/kg body weight.

Doses:

6.4, 8.0 10.0 and 16.0 g/kg body weight

No. of animals per sex per dose:

2

Control animals:

yes

Remarks:

Rats treated with distilled water (17.2 mL/kg) served as controls.

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes
- Examinations performed: a record was kept of all mortalities and signs of toxicity. All rats that died were examined macroscopically in an attempt to identify the target organs, and those animals surviving termanally were similarly examed to detect posibible residual damage.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 6 400 - < 16 000 mg/kg bw

Based on:

test mat.

Mortality:

Death occurred in rats treated at 8.0 g/kg and above from within one hour to 22 hours of dosing.

Clinical signs:

other: Signs of reaction to treatment observed shortly after dosing amongst treated rates included pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, a decreased respiratory rate, pallor of the extremities, increased sal

Gross pathology:

Autopsy of the rats that died within one hour to 22 hours of dosing revealed congestion in the lungs and pallor of the liver, spleen and kidneys. A haemorrhagic appearance of the glandular region of the stomach and a dark colouration of the kidney medulla was observed in one male at 8.0 g/kg.
Thermal autopsy findings were within normal limits.

Any other information on results incl. tables

Table 1: Mortality ratio and individual body weights (g) of rats dosed orally with the test substance

Sex	Dosage (g/kg)	Body weight (g) at			Mortality ratio: (no. of deaths /no. dosed)	time of death after dosing (hours)
		Dosing	Week 1	Week 2
♂	0	134	204	255	0/2	-
		119	168	227
	6.4	124	148	205	0/2	-
		127	182	232
	8.0	113	DIED	-	2/2	< 15 minutes - < 6 hours
		102	DIED	-
	10.0	124	195	263	1/2	>5 -<22
		123	DIED	-
	16.0	101	DIED	-	2/2	>5 -<22
		119	DIED	-
♀	0	116	158	182	0/2	-
		117	167	190
	6.4	113	144	166	0/2	-
		110	161	192
	8.0	100	148	182	0/2	-
		102	154	185
	10.0	106	147	156	1/2	>5 -<22
		107	DIED	-
	16.0	103	DIED	-	2/2	<1-<22

Table 2: Signs of reaction to treatment ratio of rats dosed orally with the test substance

Sign	Signs of reaction ratio (No. showing signs / No. dosed)
	Dose (g/kg)
	0	6.4	8.0	10.0	16.0
Pilo-erection	4/4	4/4	4/4	4/4	3/4
Abnormal body carriage (hunched posture)	0/4	4/4	3/4	4/4	3/4
Abnormal gait (waddling)	0/4	4/4	3/4	4/4	3/4
Decreased respiratory rate	0/4	4/4	3/4	4/4	3/4
Lethargy	0/4	4/4	3/4	4/4	3/4
Pallor of the extremities	0/4	4/4	4/4	4/4	3/4
Increased salivation	0/4	4/4	4/4	4/4	3/4
Ataxia	0/4	2/4	3/4	3/4	3/4
Ptosis	0/4	2/4	3/4	4/4	3/4
Diarrhoea	0/4	3/4	0/4	1/4	0/4
Râles	0/4	2/4	0/4	2/4	0/4
Diuresis	0/4	1/4	2/4	1/4	0/4
Gasping respiration	0/4	0/4	1/4	4/4	0/4
Comatose-like condition	0/4	0/4	1/4	1/4	1/4
Facial oedema	0/4	0/4	0/4	0/4	2/4

Applicant's summary and conclusion

Interpretation of results:

other: not harmful

Remarks:

In accordance with EU CLP (EC no 1272/2008 and its amendments)

Conclusions:

The acute oral LD50 in rats was determined to be between 6400 and 16000 mg/kg bw in a study performed similar to OECD TG 401.

Executive summary:

A study was performed to assess the acute oral toxicity of the substance to the rat according to a protocol similar to OECD TG 401. A group of four fasted rats (two of each sex) was given a single dose by gavage of the substance, as supplied, at a dose level ranging from 6.4 to 16.0 g/kg bw. All animals were observed for 14 days and necropsied.

Clinical signs observed were ptosis, lethargy, pilo-erection, ataxia, abnormal body carriage, abnormal gait, a decreased respiratory rate, pallor of the extremities and increased salivation. Reduced body weight gains were seen in one male and one female at 6.4 g/kg during the first week of observation and in one female at 10.0 g/kg during the second week of observation, compared to the controls. Body weight gains of the remaining animals were normal throughout the two-week observation period. The acute oral LD50 in rats was determined to be between 6400 and16000  mg/kg bw.