2(1H)-Naphthalenone, 3,4-dihydro-5-methoxy-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Februari 2012 - March 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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 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:

May 2008, including most recent amendments

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 Nohsan, Notification No 8147

Version / remarks:

April 2011, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

457-080-9

EC Name:

-

Cas Number:

32940-15-1

Molecular formula:

C11H12O2

IUPAC Name:

5-methoxy-1,2,3,4-tetrahydronaphthalen-2-one

Test material form:

solid

Details on test material:

- Appearance: Ochre-yellow solid
- Storage condition of test material: In refrigerator (2-8°C) in the dark

Test animals

Species:

rat

Strain:

other: Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult female animals (approx. 8 weeks old)
- Weight at study initiation: 146 - 163 gram. Body weight variation was within +/- 20% of the sex mean.
- Fasting period before study: Animals were deprived of food 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 Macrolon cages containing sterilized sawdust as bedding material and paper as cage-enrichment.
- 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
set to maintain:
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

Variations to these conditions occurred (i.e. minimum relative humidity of 26, 36 and 39% on a single day, respectively). Based on the laboratory’s extensive experience with variations in these parameters and absence of any clinical signs among the animals that could be associated to these variations, these were considered to have no effect on the outcome of the study.

IN-LIFE DATES: From: 20 March 2012 to 06 April 2012

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Remarks:

s.g. 1.036

Details on oral exposure:

GAVAGE METHOD: plastic feeding tubes.

Frequency: single dosage, on Day 1.

VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (10 mL/kg) body weight.

DOSAGE PREPARATION: The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle. No correction was made for purity of the test substance. In order to obtain homogeneity, the test substance (formulations) were slightly heated in a water bath with a maximum temperature of 34.5ºC for a maximum of 18 minutes.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 (2 groups of three females in a stepwise manner)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.
- Necropsy of survivors performed: The animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.
- Other examinations performed: none.

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One female was found dead on day 1 approximately one and a half hours after dosing. No macroscopic findings were noted for this animal. No further mortality occurred.

Clinical signs:

other: Lethargy, hunched posture, uncoordinated movements, piloerection, rales and/or ptosis were noted in all animals on day 1. One animal showed hunched posture on days 6 and 7 and brown staining of the nose on day 6.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.
In one animal pelvic dilation in the kidney (only left side) was noted. This finding is occasionally seen among rats of this age and strain and was therefore considered not toxicologically significant.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Remarks:

according to Regulation (EC) No 1272/2008

Conclusions:

In an acute oral toxicity study with rats, performed according to OECD 423 test guideline and in accordance GLP principles, an LD50 >2000 mg/kg bw was determined.

Executive summary:

An acute oral toxicity study in rats was performed with the substance according to OECD 423 guideline and in accordance with GLP principles. The test item was formulated in propylene glycol and administired by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg bw. One female was found dead on day 1, no macroscopic findings were noted for this animal. No further mortality occured. Lethargy, hunched posture, uncoordinated movements, piloerection, rales and/or ptosis were noted in all animals on day 1. One animal showed hunched posture on days 6 and 7 and brown staining on the nose on day 6. The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of the substance in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 5000 mg/kg body weight.

Based on these results:

- according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011), the substance should be classified as: may be harmful if swallowed (Category 5) for acute toxicity by the oral route.

- according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures, the substance does not have to be classified and has no obligatory labelling requirement for oral toxicity.