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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented study according to international accepted guidelines and GLP compliant.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

214-078-0

EC Name:

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

Cas Number:

1078-19-9

Molecular formula:

C11H12O2

IUPAC Name:

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

Test material form:

solid: crystalline

Details on test material:

Test item: Methoxy-Tetralone
CAS No.: 1078-19-9
Batch No.: T-5433
Physical state: solid, crystalline powder
Colour: light-yellow
Active Ingredient Content (GC): 99.6 %
Storage: on cool and dry place, protected from light

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species and strain: Crl:(WI)Br rats
Source: TOXI COOP ZRT.
Hygienic level at arrival: SPF
Hygienic level during the study: Good conventional
Number of animals: 3 animals/group
Sex: Female, nulliparous and non pregnant animals
Age of animals: Young adult rat, 8 weeks old in first, second, third and fourth step
Body weight range at starting (first step): 160 - 162 g
Body weight range at starting (second step): 161 - 166 g
Body weight range at starting (third step): 161 - 166 g
Body weight range at starting (fourth step): 162 - 167 g
Acclimatization time: 5 days in first step, 6 days in second step, 7 days in third step and 8 days in fourth step
Animal health: Only healthy animals were used for the study.

Housing: Group caging (3 animals/cage)
Light: Artificial light, from 6 a.m. to 6 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 - 70 %
Ventilation: 10-15 air exchanges/hour by central air-condition system

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Helianthi annui oleum raffinatum

Details on oral exposure:

A single oral administration - followed by a fourteen-day observation period - was performed by gavage.
Starting dose was selected on the basis of the available information about the test item. The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. Since no animal died on the treatment day and day 1 and the symptoms observed was not severe the test was continued at 2000 mg/kg bw dose level on further three female rats. Since two animals of group 1 died on Day 2 and one-one animal of group 2 died on Day 2 and on Day 3, respectively, the test was continued at 300 mg/kg bw dose level on further three female rats. There was no death in third step, so three further female rats were treated with the same (300 mg/kg bw) dose. No animal died in the fourth step, too, so the test was finished.

All doses were formulated in the vehicle. Concentration of formulations was adjusted to maintain a treatment volume of 10 mL/kg bw. The test item was applied in a concentration of 200 and 30 mg/mL. Formulations were prepared just before the administration and stirred continuously during the treatment.

The day before treatment the animals were fasted. The food but not water was withheld overnight. The food was given back 3 hours after the treatment.

Doses:

2000, 300 mg/kg bw

No. of animals per sex per dose:

3 female/dose

Control animals:

no

Details on study design:

The observation period was 14 day. Animals were observed individually after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h, 5 h and 6 h after the treatment and twice each day for 14 days thereafter.
The body weights were recorded on day 0 (just before the treatment), on day 7 and on day 15 with a precision of 1 g.
At the end of the observation period the surviver rats were sacrificed and necropsy were performed.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

300 - 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Altogether four rats dosed at 2000 mg/kg METHOXY-TETRALONE (CAS 1078-19-9) died during the study. Two females of group 1 died on Day 2. One animal died on Day 2 and one animal died on Day 3 from group 2.
All deaths seemed to be consequences of systemic toxic effect of the test item.
No death occurred at 300 mg/kg single oral dose of the test item. All female rats in step 3 and step 4 survived until the end of the 14-day observation period.

Clinical signs:

other: In group 1 treated with 2000 mg/kg bw: Decreased activity (score -1; -2), abnormal gait (score +1; +2), incoordination (score +1; +2; +3), blood around the nose (score +1; +2), decreased righting reflex (score -1), decreased grip- and limb tone (score -1;

Gross pathology:

Four rats out of 6 animals treated with 2000 mg/kg bw dose of the test item spontaneously died during the study. External necropsy findings as anus contaminated with feces and dark urine was detected in one animal of group 1, as well as external necropsy findings as imperfectly developing and undernourishing were recorded in one animal of group 2. An internal necropsy finding as autolysis was observed in two animals of group 1 and in one animal of group 2, but it is normal physiological process after death.
Moderate hydrometra was observed in one female of the group 2 is physiological finding and connected to the cycle of the animal.
All animals treated with 300 mg/kg bw dose survived until the scheduled necropsy on Day 15. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals treated with 300 mg/kg bw dose (group 3 and 4).

Any other information on results incl. tables

Groups	Treatment		Lethality
	Test item	Dose (mg/kgbw)	Females
1	“methoxy-tetralone” Step 1	2000	2/3
2	“methoxy-tetralone” Step 2	2000	2/3
3	“methoxy-tetralone” Step 3	300	0/3
4	“methoxy-tetralone” Step 4	300	0/3

 

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The method used is not intended to allow the calculation of a precise LD50 value.
The test item was ranked into classes of Globally Harmonized Classification System (GHS) described in the OECD Guideline No. 423.
Hazard Category: Acute Tox. 4

Executive summary:

Dose (mg/kg bw)	Mortality (dead/treated)	LD50 (mg/kg bw)	GHS category
300	0/6	between 300 and 2000	4