rac-(1R,4S,4aR,8R,8aS)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 Mar 2014 to 08 Apr 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

rac-(1R,4S,4aR,8R,8aS)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one

EC Number:

941-628-3

Cas Number:

1263184-87-7

Molecular formula:

C12H14Cl2O2

IUPAC Name:

rac-(1R,4S,4aR,8R,8aS)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHan

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 160-179 g
- Fasting period before study: Overnight prior to treatment
- Housing: Individually in Type II polypropylene/polycarbonate cages. Rodents were housed with deep wood sawdust bedding to allow digging and other normal rodent activities Lignocel bedding for laboratory animals was available to animals during the study
- Diet: Autoclavable complete diet for rats and mice – breeding and maintenance ad libitum (except for pre-dose overnight fast).
- Water: Tap water ad libitum
- Acclimation period: At least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
11 Mar 2014 to 08 Apr 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled

Details on oral exposure:

VEHICLE
- Amount of vehicle: 10 mL/kg bw

DOSAGE PREPARATION
Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations after 30 mins, 1, 2, 3, 4 and 6 hours after dosing, then once daily thereafter for 14 days. Body weights recorded on days -1 and 0 (prior to dosing), 7 and 14.
- Necropsy of survivors performed: Yes. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. All gross pathological changes were recorded for each animal on the post mortem record sheets.

Statistics:

Data was evaluated using the Acute Oral Toxicity (OECD Test Guidelines 425) Statistical Programme (AOT 425 Stat Pgm).

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality

Clinical signs:

other: Hunched back (2/5) and piloerection (1/5). All animals were symptom free from Day 2 until at the end of the observation period.

Gross pathology:

No treatment-related effects.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute oral median lethal dose LD50 of the test item was greater than 2000 mg/kg bw in RccHan:WIST female rats.

Executive summary:

In this GLP compliant, OECD 425 study, the acute toxicity of the test substance was evaluated in a limit test conducted with 5 female rats (RccHan:WIST). Animals were treated with a single oral (gavage) dose of the test substance at a dose level of 2000 mg/kg bw followed by a 14 day observation period. The animals were fasted overnight prior to treatment and food was returned 3 hours after dosing. All animals were observed individually after dosing at 30 minutes, 1, 2, 3, 4 and 6 hours post treatment and once each day for 14 days thereafter. Body weight was measured on Day -1 (prior to removal of food), Day 0 (prior to administration) and weekly thereafter. All animals were examined macroscopically at the end of the study.

There were no deaths and treatment at a dose level of 2000 mg/kg bw caused hunched back (2/5) and piloerection (1/5). All animals were symptom free from Day 2. There were no treatment related changes in the body weights. There was no evidence of the macroscopic observations in animals terminated on Day 14.

Under the conditions of this study, the acute oral median lethal dose LD50 of the test item was greater than 2000 mg/kg bw in RccHan:WIST female rats.