N-methylnaphthalene-1-methylamine

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:

N-methylnaphthalene-1-methylamine

EC Number:

238-497-3

EC Name:

N-methylnaphthalene-1-methylamine

Cas Number:

14489-75-9

Molecular formula:

C12H13N

IUPAC Name:

methyl[(naphthalen-1-yl)methyl]amine

Test material form:

liquid: viscous

Details on test material:

Test item: SECONDARY AMINE
CAS No.: 14489-75-9
Batch No.: L35009N
Physical state: Colourless oil
Colour: Colourless

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
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): 155 - 161 g
Body weight range at starting (second step): 153 - 171 g
Body weight range at starting (third step): 155 - 170 g
Body weight range at starting (fourth step): 184 - 187 g
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.
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 all female animals died the test was continued at 300 mg/kg bw dose level on further three female rats. Two animals died in the second step at 300 mg/kg bw dose level, the test was continued at 50 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 (50 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, 30 and 5 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. Food was given back 3 hours after the treatment.

Doses:

2000, 300, 50 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 days. Animals were observed individually after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 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 survivor rats were sacrificed and necropsy were perfomed.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

50 - 300 mg/kg bw

Based on:

test mat.

Mortality:

All rats dosed at 2000 mg/kg ”Secondary amine” died. All females of group 1 died on the treatment day, 15 min. after the treatment. Besides, two rats treated with 300 mg/kg dose died during the study. One animal died on the treatment day 1 hour after the treatment and one animal died on Day 1. All deaths seemed to be consequences of systemic toxic effect of the test item. No death occurred at 50 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 dose: Clinical sign of reaction comprised of tonic convulsion, clonic convulsion and dyspnoea. These symptoms occurred in all animals. These symptoms (score +4) were detected on the treatment day 15 min. after the tre

Gross pathology:

All rats treated with 2000 mg/kg bw dose of the test item spontaneously died during the study and two rats treated with 300 mg/kg bw dose spontaneously died, too. Slight hydrometra was detected in two animals and moderate hydrometra was observed in one female of the group 1 (2000 mg/kg bw), as well as slight hydrometra was detected in one animal of group 2 (300 mg/kg bw). The hydrometra is physiological finding and connected to the cycle of the animal.
All animals treated with 50 mg/kg bw dose survived until the scheduled necropsy on Day 15. Slight hydrometra was observed in two females of the group 3. The hydrometra is physiological finding and connected to the cycle of the animal. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.

Any other information on results incl. tables

Groups	Treatment		Lethality
	Test item	Dose (mg/kgbw)	Females
1	“secondary amine” Step1	2000	3/3
2	“secondary amine” Step2	300	2/3
3	“secondary amine” Step3	50	0/3
4	“secondary amine” Step4	50	0/3

 

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The method used, was not intended for the precise 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. 3

Executive summary:

Dose (mg/kg bw)	Mortality (dead/treated)	LD50 (mg/kg bw)	GHS category
50	0/6	between 50 and 300	3