Reaction mass of 3-[(3aS,7aR)-octahydro-1H-4,7-methanoinden-1-yl]propanal and 3-[(2s,3aR,7aS)-octahydro-1H-4,7-methanoinden-2-yl]propanal and 3-[(2r,3aR,7aS)-octahydro-1H-4,7-methanoinden-2-yl]propanal

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 November, 2014 - 18 December, 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliability 1 is assigned because the study conducted according to OECD TG 423 in compliance with GLP, without deviations that influence the quality of the results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

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:

(2001)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2008)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

(2002)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 3-[(3aS,7aR)-octahydro-1H-4,7-methanoinden-1-yl]propanal and 3-[(2s,3aR,7aS)-octahydro-1H-4,7-methanoinden-2-yl]propanal and 3-[(2r,3aR,7aS)-octahydro-1H-4,7-methanoinden-2-yl]propanal

EC Number:

942-467-1

Molecular formula:

C13H20O

IUPAC Name:

Reaction mass of 3-[(3aS,7aR)-octahydro-1H-4,7-methanoinden-1-yl]propanal and 3-[(2s,3aR,7aS)-octahydro-1H-4,7-methanoinden-2-yl]propanal and 3-[(2r,3aR,7aS)-octahydro-1H-4,7-methanoinden-2-yl]propanal

Test material form:

other: liquid

Details on test material:

- Name of test material in report: FRET 09-0536
- Physical state: Clear liquid
- Storage condition of test material: At room temperature protected from light

Test animals

Species:

rat

Strain:

other: Wistar strain Crl:WI (Han) (outbred, SPF-Quality)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 11-12 weeks old).
- Weight at study initiation: 178 - 214 g
- Fasting period before study: overnight prior to dosing and until 3-4 hours after administration of the test substance.
- Housing: Group housing of 3 animals per cage in labeled Makrolon cages.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 24
- Humidity (%): 40 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2 mL/kg body weight. Dose volume calculated as dose level (g/kg) / density (g/mL)

Frequency Single dosage on Day 1.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 (2x3)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations:
Mortality/Viability: Twice daily.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes, at the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Body weights: Days 1 (pre-administration), 8 and 15.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture and piloerection were noted for all animals between Days 1 and 4. Additionally, uncoordinated movements were noted for one animal on Day 1.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral toxicity test showed an LD50 of >2000 mg/kg bw.

Executive summary:

Acute oral toxicity according to OECD 423 guideline and GLP principles: In this study, 6 female rats were administered to the substance at the dose level of 2000 mg/kg bw. No mortality occurred. Hunched posture and piloerection were noted for all animals between Days 1 and 4. Additionally, uncoordinated movements were noted for one animal on Day 1. The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. The acute oral LD50 for FRET 09 -0536 in female rats was determined to be >2000 mg/kg bw, the substance does not have to be classified as acute toxic by the oral route.