Reaction mass of (R*,R*)-7-methoxy-3,7-dimethyl-2-octanol and (R*,S*)-7-methoxy-3,7-dimethyl-2-octanol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 May - 01 June 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study performed according to OECD Guideline 423 without any deviation

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:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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:

(R*,R*)-7-methoxy-3,7-dimethyl-2-octanol

Cas Number:

87605-57-0

Molecular formula:

C11H24O2

IUPAC Name:

(R*,R*)-7-methoxy-3,7-dimethyl-2-octanol

Constituent 2

Reference substance name:

(R*,S*)-7-methoxy-3,7-dimethyl-2-octanol

Cas Number:

87605-61-6

Molecular formula:

C11H24O2

IUPAC Name:

(R*,S*)-7-methoxy-3,7-dimethyl-2-octanol

impurity 1

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.: 171894
Purity: 99.7% (sum of the two main constituents)
Name of test material (as cited in study report): 7-METHOXY-3,7-DIMETHYLOCTAN-2-OL MULTICONSTITUENT
Physical state: colourless - slightly yellow liquid
Storage conditions: +2°C to +8°C, under nitrogen and protected from light
Expiry date: 14 December 2017

Test animals

Species:

rat

Strain:

Sprague-Dawley

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 weeks
- Weight at study initiation: 200-212 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 (A04, SAFE), 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: 19-25°C
- Humidity: 30-70%
- 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: 2.22 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 2.22 mL/kg bw (corresponding to 2000 mg/kg bw, according to the density of 0.899 g/mL at 20°C 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 (6/6), muscle tones (5/6), righting reflex (6/6), Preyer's reflex (5/6), associated with piloerection (2/6), an increase of salivation (6/6), partial or total ptosis (6/6), an hypothermia (2/6), tremors (2/

Gross pathology:

The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

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. 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 Sprague Dawley rats. Animals were then observed for mortality, body weight changes and clinical signs of toxicity for 14 days.

No mortality occurred during the study. A decrease or an absence in spontaneous activity (6/6), muscle tones (5/6), righting reflex (6/6), Preyer's reflex (5/6), associated with piloerection (2/6), an increase of salivation (6/6), partial or total ptosis (6/6), an hypothermia (2/6), tremors (2/6), and myosis (4/6) were noted during the first hours of the test. The animals recovered a normal activity at 24-hour post dose. The body weight evolution of the animals remained normal throughout the study. The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

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