Reaction mass of [3R-(3α,3aβ,6α,7β,8aα)]-octahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-6-ol and [3R-(3α,3aβ,6α,7β,8aα)]-octahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-5-yl acetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline study performed under GLP. All relevant validity criteria were met.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected June 2015; signature: September 2015

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(1S,2R,5S,7R,8R)-2,6,6,8-tetramethyltricyclo[5.3.1.0^{1,5}]undecan-8-yl acetate

Molecular formula:

C17H28O2

IUPAC Name:

(1S,2R,5S,7R,8R)-2,6,6,8-tetramethyltricyclo[5.3.1.0^{1,5}]undecan-8-yl acetate

Test material form:

liquid

Details on test material:

- Physical state: Liquid.- Storage condition of test material: Approximately 4°C in the dark- Other: Pale yellow

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: Recognised supplier- Age at study initiation: 8 - 12 weeks.- Weight at study initiation: 195 g (sighting test; sentinel); 176 - 198 g (main study); The weight variation did not exceed ±20% of the mean weight.- Fasting period before study: Overnight before dosing and three to four hours after dosing.- Housing: Group housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.- Diet (e.g. ad libitum): Certified diet from recognised supplier, provided ad libitum (except for fasting period).- Water (e.g. ad libitum): ad libitum (except for fasting period)- Acclimation period: At least 5 days.ENVIRONMENTAL CONDITIONS- Temperature (°C): 19 - 25- Humidity (%): 30 - 70%- Air changes (per hr): > 15 air changes per hour - Photoperiod: 12 h light / 12 h darkIN-LIFE DATES: From: To: 2015-10-21 to 2015-11-11

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.The initial starting dose was chosen using available information on toxicity. For the purpose of the 2000 mg/kg dose level, the test item was used as supplied. The 2000 mg/kg bw dose level was treated stepwise. Singuarly and in the absence of mortality or evident toxicity a further group of 4 was tested.

Doses:

2000 mg/kg bw (initial sighting test and main study)

No. of animals per sex per dose:

1 (sighting study) and 4 (main study); total 5 per dose.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days- Frequency of observations and weighing: Clinical observations were made 0.5, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

2000 mg/kg bw: No mortality.

Clinical signs:

2000 mg/kg bw: No signs of systemic toxicity were noted.

Body weight:

2000 mg/kg bw: All animals showed expected bodyweight gains over the study period.

Gross pathology:

2000 mg/kg bw: No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the oral LD50 was established to exceed 2000 mg/kg bw in female Wistar rats. Under the conditions of this study, and according to the OECD TG 420 criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.

Executive summary:

The study was performed according to OECD TG 420 and EU Method B.1 bis Acute Toxicity (Oral) and in accordance with GLP to assess the acute oral toxicity of the test material following a single oral administration in the female Wistar strain rat by the fixed dose method. The test substance was administered by oral gavage in an initial sighting study at 2000 mg/kg. Subsequently a further group of four fasted females was given a single oral dose of test item, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study and gross necropsy performed. There was no mortality during the course of the study. No signs of systemic toxicity were noted in the remaining animals. Animals showed expected gains in bodyweight over the study period and there were no abnormalities noted at necropsy. Under the conditions of this study the oral LD50 was established to exceed 2000 mg/kg bw in female Wistar rat. Under the conditions of this study, and according to the OECD TG 420 criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.