p-anisylamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from authoritative database

Data source

Reference

Reference Type:

other: authoritative database

Title:

Acute oral toxicity study of test chemical was performed in rats.

Author:

Ministry of Health, Labour and Welfare, Ministry of the Environment and National Institute of Technology and Evaluation.

Year:

2010

Bibliographic source:

J-CHECK Japan Chemicals Collaborative Knowledge database

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Acute Oral toxicity test was carried out to study the effects of test chemical on rats.

GLP compliance:

not specified

Test type:

other: no data available

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

m-anisidine

EC Number:

208-651-4

EC Name:

m-anisidine

Cas Number:

536-90-3

Molecular formula:

C7H9NO

IUPAC Name:

3-Methoxyaniline

Details on test material:

- Name of test material (IUPAC name): 3-Methoxyaniline
- Common name: m-Anisidine
- Molecular formula: C7H9NO
- Molecular weight: 123.1541 g/mol
- Smiles notation: COc1cccc(N)c1
- InChl: 1S/C7H9NO/c1-9-7-4-2-3-6(8)5-7/h2-5H,8H2,1H3
- Substance type: Organic
- Physical state:yellow-brown liquid
- Purity :98%
- Impurities (identity and concentrations):2%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

[Crj: CD (SD)]

Sex:

male/female

Details on test animals or test system and environmental conditions:

Details on test animal
TEST ANIMALS
- Source: Charles River Japan Co., Ltd.
- Age at study initiation: 4 weeks
- Weight at study initiation: The body weight range on the 2nd day after acquisition was 84 to 106 g for males and 78 to 95 g for females.
- Fasting period before study:19 hours
- Housing: stainless steel suspended cage (W: 240 × D: 380 × H: 200 mm) to keep up to 5 animals per cage, They were bred individually using a continuous cage (W: 755 × D: 210 × H: 170 mm). Replacement of the cage dish and water bottle was done more than twice a week, and the cage and feeder was changed more than once every 2 weeks.
- Diet (e.g. ad libitum): solid feed
- Water (e.g. ad libitum): Drinking water freely consumed tap water using a water supply bottle.
- Acclimation period:2-day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24 °C.
- Humidity (%):40 to 70 %
- Air changes (per hr): 12 times / hour.
- Photoperiod (hrs dark / hrs light): 12 hours

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

Details on exposure:
VEHICLE
- Concentration in vehicle: 200 and 300 mg / kg in distilled water
- Amount of vehicle (if gavage): distilled water:20 ml/kg

MAXIMUM DOSE VOLUME APPLIED:300 mg/kg bw

Doses:

0,200, 300 mg / kg bw

No. of animals per sex per dose:

Groups of 5 male and 5 females (per sex/dose) were used

Control animals:

yes

Details on study design:

Details on study design
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
General condition:
The general condition and the presence or absence of death were observed once a day until the administration day and 6 hours after administration (30 minutes after administration, 2, 4 and 6 hours after administration) before administration and during the observation period from the day after administration .

Weight measurement:
Measurement was made on the administration day (immediately before administration) and 1, 3, 7, 10 and 14 days after administration in the morning.

Autopsy:
The dead animals were necropsied promptly after discovery. At the end of the observation period, the surviving animals were sacrificed by exsanguination from the abdominal aorta under ether anesthesia and then necropsied, and findings were recorded. A control group of lung abnormalities is accepted lung and its comparison with autopsy, after taking a picture for a representative example, and fixed and stored in 10% neutral buffered formalin.

Histopathological examination:
Of the animals that survived for more than 24 hours after administration, the lungs of the representative examples of the male example and control group 500 mg / kg group abnormalities of the lung were observed at necropsy, Hematoxylin-Eosin staining after paraffin embedding according to a conventional method Samples were prepared and histopathologically examined.

- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

(1)LD 50 value:
The LD50 value and its 95% confidence limit value were calculated by the Behrens- Ker method.

(2) Body weight:
For each group, the average value and the standard deviation were calculated. Significant difference test was carried out using a multiple
comparison test between the control group and the test substance administered each group, and a significant risk rate of less than 5%, less than 5% and (p <0.05) less than 1% and (p <0.01) Respectively.
That performs equal variances assay by Bartlett method, in the case of equal variance was dispersed analysis by one-way layout method, Dunnett
method between groups compared with the control group if significant (if the number of cases is equal to) or Scheff Method (when the number of cases are not equal). On the other hand, when the observed and equal variance was analyzed by one-way method using rank (Kruskal-Wallis tests),Dunnett method or Scheff between groups compared with the control group if significant using a ranking method .

Results and discussion

Preliminary study:

As a result of preliminary test,groups of 300 and 200 mg / kg were set using distilled water as a medium. As a control, a group to administer the same liquid volume of each medium was provided.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 300 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality was observed

Mortality:

No death occurred in the highest dose group in both males and females, and the LD50 value was 300 mg / kg or more

Clinical signs:

other: No abnormal symptoms were observed in any of the control groups. In the 200 mg / kg group, a staggering walking, salivation, lacrimation and the like were observed from about 15 minutes after the administration,but in 2 hours after the administration, the

Gross pathology:

In the surviving cases, there was no remarkable change.

Other findings:

No data available

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The lethal concentration (LD50) value for acute oral toxicity test was considered to be >300 mg/kg bw,when male and female Sprague Dawley rats[Crj: CD (SD)] were treated with test chemical orally via gavage.

Executive summary:

Acute oral toxicity study was performed in male and female Sprague Dawley rats[Crj: CD (SD) ]

using test material test chemical.Distilled water was used as vehicle.Preliminary test was also done.No mortality was observed at dose 300 mg/kg bw.Animals were examined for clinical signs,histopathology, changes in body weight and organ weights.In clinical signs observation,No abnormal symptoms were observed in any of the control groups.In the 200 mg / kg group, a staggering walking, salivation, lacrimation and the like were observed from about 15 minutes after the administration, but in 2 hours after the administration, there was only a decrease in locomotor activity in one males, and other symptoms It disappeared. On the first day after the administration, contamination of the lower abdomen was observed in 2 females, but no abnormal symptoms were observed in any of the males and females after 2 days from the administration.In the 300 mg / kg group, immediately after administration, prone and breathing slowed, salivation from about 5 to 20 minutes after the administration, staggering walking and the like were observed, but disappeared at 2 hours after administration. Spontaneous exercise reduction and epidermal decline were observed after 2 hours from the administration, and the locomotor activity reduction continued even 6 hours after the administration. On the first day after administration, females showed dirt on the lower abdomen and brown urine, but no abnormal symptoms were observed in any of the males and females after 2 days from the administration.In body weight examination,each group of male and female rats showed almost the same trend as the control group, and no significant difference was observed. In the surviving cases, there was no remarkable change in gross pathological examination.Hence, Thelethal concentration (LD50) valuefor acute oral toxicity testwas considered to be>300mg/kg bw,when male and female Sprague Dawley rats were treated with test chemical orally via gavage.Thelethal concentration (LD50) valuefor acute oral toxicity testwas considered to be>300mg/kg bw,when male and female Sprague Dawley rats [Crj: CD (SD)]were treated with test chemical orally via gavage.