N-methylaniline

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Remarks:

Guideline study reported in Japanese with a summary in English, but no data available concerning the year of performance or reporting.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-methylaniline

EC Number:

202-870-9

EC Name:

N-methylaniline

Cas Number:

100-61-8

Molecular formula:

C7H9N

IUPAC Name:

N-methylaniline

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals: Rats were used in the test at age of 6 weeks, bodyweights at time of administration, males: 143-162 g, females: 110-133 g.
Test conditions: temperature 23 ± 2 ° c, humidity 55 ± 10%, ventilation 20 times / hour, light 150 to 300 lux, lighting hours 12 hours (am 7: lit, pm 7: off), automatic flush type breeding machine (Ltd. Tokyo Motor Service), stainless steel mesh rearing cage housing 5 animals, breeding cage and supercharging feeding machine replaced once a week, solid feed MF (Oriental yeast co., Ltd. ), food and tap water ad libitum.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

A predetermined amount of test substance dissolved in corn oil (Nacalai Tesque Ltd.).
Solution concentrations: 512, 640, 800, 1000 and 1250 mg / kg per rat, each 10.2, 8.0, 16.0, 20.0 and 25.0% w/v in corn oil.
Animals 16 hours fasted before start of the administration.
Administration: test substance solution dosed for 4 hours using an injection pump via a probe in the stomach at 0.5 ml per 100 g bw.

Doses:

Prior to the main study, three rats of each sex were administered doses of 500, 1000 and 2000 mg/kg bw
Main study: 512, 640, 800, 1000, 1250 mg/kg bw.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Observations:
Symptoms of poisoning and death: during exposure, after 1 hour and thereafter twice daily (AM and PM, holidays only at AM) conducted over 14 days.
Body weights: before the start of dosing and 7 and 14 days after exposure or when an animal was found dead.
Gross pathology: performed on rats that died during the observation period and on survivors after ether anesthesia at the end of the observation period. Gross organ abnormalities were observed and recorded.
Histopathology: A part of the organs were stored in 10% neutral buffered formalin solution for selective subjection to histopathological examination.

Statistics:

Calculation of the LD50 value and its 95% confidence limits after 14 days based on the method of Litchfield-Wilcoxon (1949)

Results and discussion

Preliminary study:

For both sexes there were no deaths at 500 mg/kg bw, and 100% mortality at 1000 and 2000 mg/kg bw..

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

782 mg/kg bw

Based on:

test mat.

95% CL:

>= 648 - 945

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

716 mg/kg bw

Based on:

test mat.

95% CL:

>= 638 - 803

Effect levels 3

Sex:

male/female

Dose descriptor:

LD0

Effect level:

512 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Observed LD0

Mortality:

See table 1.

Clinical signs:

other: other: Locomotor activity decreased in many cases; cyanosis and dark urine was observed in dead rats; salivation; prone position; lateral position; decrease of body temperature; muscle spasms.

Gross pathology:

Pleural effusion in cases of death, black dimples on the thymus and the heart, urine retention, red spots on the esophagus, white or red spots on the small intestine and black or red spots on the stomach.

Any other information on results incl. tables

Mortality of rats treated orally with test substance

 

Sex	Dose	No. of	Number of deaths at day:								Relative	Dead
	(mg/kg bw)	animals	1	2	3	4	5	6	7	14	mortality	%
Male	512	5	0	0	0	0	0	0	0	0	0/5	0
	640	5	0	0	1	0	0	0	0	0	1/5	20
	800	5	3	0	0	0	0	0	0	0	3/5	60
	1000	5	2	1	1	0	0	0	0	0	4/5	80
	1250	5	0	5	0	0	0	0	0	0	5/5	100
Female	512	5	0	0	0	0	0	0	0	0	0/5	0
	640	5	1	0	0	0	0	0	0	0	1/5	20
	800	5	2	2	0	0	0	0	0	0	4/5	80
	1000	5	1	4	0	0	0	0	0	0	5/5	100
	1250	5	2	3	0	0	0	0	0	0	5/5	100

 

Applicant's summary and conclusion

Interpretation of results:

other: Category 4 based on CLP criteria

Conclusions:

LD50 males = 782 mg/kg bw
LD50 females = 716 mg/kg bw