4-methoxy-N-phenyl-o-toluidine

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

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 peer reviewed publication

Data source

Reference

Reference Type:

publication

Title:

Production Of Cataract In Rats By Betatetralol And Other Derivatives Of Naphthalene

Author:

O. Garth Fitzhugh ; Wilhelm H. Buschke

Year:

1949

Bibliographic source:

Arch Ophthalmol. 1949;41(5):572-582

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Repeated dose feeding study was performed to determine the toxic nature of β-naphthyl ethyl ether

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl 2-naphthyl ether

EC Number:

202-226-7

EC Name:

Ethyl 2-naphthyl ether

Cas Number:

93-18-5

Molecular formula:

C12H12O

IUPAC Name:

2-Ethoxynaphthalene

Test material form:

solid

Details on test material:

Name of test material (as cited in study report): 2-Ethoxynaphthalene
Molecular formula :C12H12O
Molecular weight :172.226 g/mol
Smiles notation :c12c(ccc(c1)OCC)cccc2
InChl:1S/C12H12O/c1213128710534611(10)912/h39H,2H2,1H3
Substance Type: Organic
Physical State: Solid

Specific details on test material used for the study:

- Name of test material: β-Naphthyl ethyl ether
- Molecular formula: C12H12O
- Molecular weight: 172.226 g/mol
- Subsatnce type: Organic
- Physical state: Solid
- Purity: No data

Test animals

Species:

rat

Strain:

not specified

Details on species / strain selection:

No data

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data

Administration / exposure

Route of administration:

oral: feed

Details on route of administration:

No data

Vehicle:

not specified

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: 2% (1000 mg/Kg bw/day) chemical was mixed with the diet

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Diet
- Concentration in vehicle: 2000 mg/Kg bw/day
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

2 months (60 days)

Frequency of treatment:

Daily

Doses / concentrations

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

5 wealing rats

Control animals:

not specified

Details on study design:

No data

Positive control:

No data

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. No data

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: No data

BODY WEIGHT: No data
- Time schedule for examinations: No data

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: after 5 days
- Dose groups that were examined: 2000 mg/Kg/day

HAEMATOLOGY: No data
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

CLINICAL CHEMISTRY: Y No data
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data

OTHER: No data

Sacrifice and pathology:

No data

Other examinations:

No data

Statistics:

No data

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

effects observed, treatment-related

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

Clinical signs and mortality: No data
Body weight and weight gain: No data
Food consumption and compound intake: No data
Food efficiency: No data
Water consumption and compound intake: No data
Opthalmoscopic examination: Cataracts were observed in the eyes of treated rats
Haematology: No data
Clinical chemistry: No data
Urinanalysis: No data
Neurobehaviour: No data
Organ weights: No data
Gross pathology: No data
Histopathology: No data

Effect levels

Dose descriptor:

NOAEL

Effect level:

< 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

ophthalmological examination

Remarks on result:

other: No toxic effect were observed

Target system / organ toxicity

Critical effects observed:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

The No Observed Adverse Effect Level (NOAEL) for β-naphthyl ethyl ether is < 1000 mg/Kg/day.

Executive summary:

Repeated dose feeding study was performed to determine the toxic nature of β-naphthyl ethyl ether. 5 weanling rats were dosed at dose level of 2% (approximately 1000 mg/Kg bw) in the diet for 2 months. During the 2 months study period, rats developed cataracts and the chemical was considered to be cataractogenic. Based on the observations made, the No Observed Adverse Effect Level (NOAEL) for β-naphthyl ethyl ether is < 1000 mg/Kg/day.