(E,Z)-2,6-dimethylocta-2,4,6-triene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04-25 April 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study performed according to OECD Guideline 423 with minor deviations: temperature and humidity were occasionally lower than the minimum optimum values

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

dated 17 December, 2001

Deviations:

yes

Remarks:

temperature and humidity were occasionally lower than the minimum optimum values

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

temperature and humidity were occasionally lower than the minimum optimum values

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

23 October 2015

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(E,Z)-2,6-dimethylocta-2,4,6-triene

EC Number:

230-603-6

EC Name:

(E,Z)-2,6-dimethylocta-2,4,6-triene

Cas Number:

7216-56-0

Molecular formula:

C10H16

IUPAC Name:

(E,Z)-2,6-dimethylocta-2,4,6-triene

impurity 1

Reference substance name:

(E,E)-2,6-dimethylocta-2,4,6-triene

EC Number:

221-153-1

EC Name:

(E,E)-2,6-dimethylocta-2,4,6-triene

Cas Number:

3016-19-1

Molecular formula:

C10H16

IUPAC Name:

2,6-dimethylocta-2,4,6-triene

impurity 2

Reference substance name:

(R)-p-mentha-1,8-diene

EC Number:

227-813-5

EC Name:

(R)-p-mentha-1,8-diene

Cas Number:

5989-27-5

Molecular formula:

C10H16

IUPAC Name:

(4R)-isopropenyl-1-methylcyclohexene

impurity 3

Reference substance name:

(S)-p-mentha-1,8-diene

EC Number:

227-815-6

EC Name:

(S)-p-mentha-1,8-diene

Cas Number:

5989-54-8

Molecular formula:

C10H16

IUPAC Name:

(4S)-isopropenyl-1-methylcyclohexene

impurity 4

Reference substance name:

Non identified impurities

Molecular formula:

Not applicable

IUPAC Name:

Non identified impurities

Test material form:

liquid

Details on test material:

Batch No.: 189119
Purity: 88.1%
Name of test material (as cited in study report): (E,Z)-2,6-DIMETHYLOCTA-2,4,6-TRIENE
Physical state: colourless liquid
Storage conditions: +2°C to +8°C, under nitrogen and protected from light
Expiry date: 12 July 2017

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER LABS, France
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8 or 9 weeks
- Weight at study initiation: 187-205 g
- Fasting period before study: Food was removed on Day 1 and then redistributed 4 hours after the test item administration.
- Housing: Animals were housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet (e.g. ad libitum): Foodstuff (ENVIGO - 2016), ad libitum
- Water (e.g. ad libitum): Drinking water (tap-water from public distribution system), ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18-25°C
- Humidity: 17-70%
- Air changes: At least 10/hour
- Photoperiod: 12 hours dark / 12 hours light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.47 mL/kg bw

DOSAGE PREPARATION: In the first and the second step of the study, the test item was administered by gavage under a volume of 2.47 mL/kg bw (corresponding to 2000 mg/kg bw, according to the density of 0.809 g/mL supplied by the Sponsor) using a suitable graduated syringe fitted with an oesophageal metal canula.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 female rats

Control animals:

other: historical control

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and mortality were recorded at 30 minutes, 1 hour, 3 hours, 4 hours, and then once daily for 14 days. Animals were weighed on Day D0 (just before administering the test item) and then on Day 2, Day 7, and Day 14.
- Necropsy of survivors performed: Yes; animals were euthanized with sodium pentobarbital on Day 14 and macroscopic observations were noted.

Statistics:

No data

Results and discussion

Preliminary study:

Not applicable

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: A decrease or an absence in spontaneous activity (3/6), Preyer’s reflex (3/6), muscle tone (3/6), righting reflex (2/6), associated with an increase in salivation (2/6), a hypothermia (1/6), myosis (1/6), eyes partly closed (3/6), dyspnea (3/6) and piloer

Gross pathology:

The macroscopic examination of the animals at the end of the study revealed a thickening and yellow coloration of the forestomach.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of the test substance is >2000 mg/kg bw in rats. Therefore it is not classified according to Regulation (EC) No 1272/2008 and GHS regulation. No signal word or hazard statement is required.

Executive summary:

In an acute oral toxicity study performed according to Guideline OECD 423 and in compliance with GLP, a single dose of 2000 mg/kg bw of the test substance was given by oral gavage to a group of 6 female Wistar rats. Animals were then observed for mortality and clinical signs of toxicity for 14 days.

No mortality occurred during the study. A decrease or an absence in spontaneous activity (3/6), Preyer’s reflex (3/6), muscle tone (3/6), righting reflex (2/6), associated with an increase in salivation (2/6), a hypothermia (1/6), myosis (1/6), eyes partly closed (3/6), dyspnea (3/6) and piloerection (3/6) were observed. The animal recovered a normal activity on Day 7. The body weight evolution of the animals revealed an absence of body weight gain on Day 2 versus Day 0. The body weight evolution was as expected from Day 7. The macroscopic examination of the animals at the end of the study revealed a thickening and yellow coloration of the forestomach.

Therefore, the oral LD50 of the test substance is >2000 mg/kg bw in rats. Therefore it is not classified according to Regulation (EC) No 1272/2008 and GHS regulation. No signal word or hazard statement is required.