(3R)-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-amine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 - 16 Oct 2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

GLP compliance unknown, minor deviations from guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2014

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

Version / remarks:

adopted 17 Dec 2001

Deviations:

no

Remarks:

- Animals should be 8-12 weeks old, but were 7 weeks old - No information on sighting study - In case of at least 2 mortalities amongst test animals, the dose 300 mg/kg bw should have been tested

GLP compliance:

no

Remarks:

in-house safety study

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(3R-)1,1,3-trimethylindan-4-amine

EC Number:

836-285-0

Cas Number:

125349-37-3

Molecular formula:

C12H17N

IUPAC Name:

(3R-)1,1,3-trimethylindan-4-amine

Test animals

Species:

rat

Strain:

other: Crl:CD (SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan
- Age at study initiation: 7 weeks
- Weight at study initiation: 159 - 174 g
- Fasting period before study: Animals were fasted 20 h prior to administration and 4 h after.
- Housing: 2 - 3 animals per cage in aluminium cages equipped with 5 shelves and 5 ladders
- Diet: solid feed for mice/rats (CRF-1, Oriental Yeast Co., Ltd.); ad libitum (besides fasting period)
- Water: filter-treated Osaka municipal tap water automatic water drinking device; ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 26
- Humidity (%): 40 - 70
- Air changes (per hr): ≥ 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Remarks:

stock solution administered

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.06 mL/kg (2000 mg/kg bw); forced oral administration

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: Animals were observed 10 and 30 min and 1, 2 and 4 h after administration and once daily thereafter, for 14 days. Individual body weights were determined immediately before administration, 7 and 14 days after administration, and in the event of being discovered dead.
- Necropsy: performed upon completion of the observation period, and in the event of being discovered dead

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000

Based on:

test mat.

Remarks on result:

other: 2/5 animals died at 2000 mg/kg bw. No higher concentrations were tested and no statistics were applied to determine the precise LD50.

Mortality:

In the 2000 mg/kg bw group, 2 animals were found dead 1 day after administration (cumulative number of deaths: 2/5).

Clinical signs:

irregular respiration

other:

Gross pathology:

The surviving animals in the 2000 mg/kg bw group exhibited no effects attributable to test substance administration. In the animals that were found dead, scattered brown foci on the gastric mucosa were observed in 1 animal, and scattered red foci on the gastric mucosa were observed in 1 animal.

Applicant's summary and conclusion

Interpretation of results:

other: Acute Oral 4 (H302) according to Regulation (EC) No 1272/2008

Conclusions:

In this acute oral toxicity study in 5 female rats receiving one dose of 200 mg/kg bw, the test substance (3R-)2,3-dihydro-1,1,3-trimethyl-1H-inden-4amine induced mortality in 2/5 animals, and the LD50 was > 2000 mg/kg bw. According to the OECD 420 testing of an additional dose (300 mg/kg bw) is required in case of 2 or more dead animals at a starting dose of 2000 mg/kg bw associated with a classification for Acute oral 4 (H302) according to Regulation (EC) No. 1272/2008. This step is missing in the available Japanese acute oral toxicity study with (3R-)2,3-dihydro-1,1,3-trimethyl-1H-inden-4amine. In addition, the substance 1,1,3-trimethylindan-4-amine (CAS 94568-76-0), which consists to 50% of (3R-)2,3-dihydro-1,1,3-trimethyl-1H-inden-4amine (CAS 125349-37-3) is classified for Acute Oral 4 (H302). Therefore, a worst-case approach was applied for (3R-)2,3-dihydro-1,1,3-trimethyl-1H-inden-4amine, which resulted in the decision that (3R-)2,3-dihydro-1,1,3-trimethyl-1H-inden-4amine is also classified for Acute Oral 4 (H302).