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Toxicological information

Repeated dose toxicity: oral

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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

Constituent 1
Chemical structure
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.