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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:
key 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:
Toxicological Tests on Flavouring Matters
Author:
B. L. Oser,
Year:
1965
Bibliographic source:
Fd Cosmet. Toxicol.

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Refer below principle
Principles of method if other than guideline:
Subchronic toxicity study was performed to determine the toxic nature of test substance
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
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:
other: FDRL
Details on species / strain selection:
No data
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation:
59.54±1.5gm(Males) 58.0±1.6gm(females)
- Fasting period before study:No data
- Housing:Animals were housed individually in wiremesh cages.
- Diet (e.g. ad libitum): nutritionally adequate basal ration (Purina Laboratory Chow) ad libitum
- Water (e.g. ad libitum): fresh water ad lib
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From: To: No data

Administration / exposure

Route of administration:
oral: feed
Details on route of administration:
No data
Vehicle:
other: Cotton seed oil
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: β-Naphthyl ethyl ether was diluted in cotton-seed oil in a concentration sufficient to provide the predetermined dosage in 2% of the diet. The oil solutions were incorporated into a nutritionally adequate basal ration at dose levels of 5.1 mg/kg bw/day in males and 5.7 mg/Kg bw/day in females.

DIET PREPARATION-No data
- Rate of preparation of diet (frequency): Biweekly
- Mixing appropriate amounts with (Type of food): Nutritionally adequate basal ration (Purina Laboratory Chow)
- Storage temperature of food: No data

VEHICLE-No data
- Justification for use and choice of vehicle (if other than water): Cotton seed oil
- Concentration in vehicle: 5.1 mg/kg for males and 5.7 mg/kg for females
- 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:
90 days
Frequency of treatment:
Once daily
Doses / concentrationsopen allclose all
Dose / conc.:
5 mg/kg bw/day (nominal)
Remarks:
Expected dose (Male/female)
Dose / conc.:
5.1 mg/kg bw/day (actual dose received)
Remarks:
Males
Dose / conc.:
5.7 mg/kg bw/day (actual dose received)
Remarks:
Females
No. of animals per sex per dose:
Total: 60 (15 males and 15 females)
0 mg/Kg bw: 15 males and 15 females
5.1 mg/Kg: 15 males
5.7 mg/Kg: 15 females
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: Single dosage levels for each substance were derived from the total estimated daily intake, calculated on a mg/kg body weight basis assuming 50 kg as the average body weight, and multiplying by 100.
- Rationale for animal assignment (if not random):No data
- Rationale for selecting satellite groups: No data
- Post-exposure recovery period in satellite groups: No data
- Section schedule rationale (if not random): No data
Positive control:
No data

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Not specified
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. No data

DETAILED CLINICAL OBSERVATIONS: Not specified
- Time schedule: Not specified

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

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Not specified
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified

FOOD EFFICIENCY: Not specified
- 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: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study):Not specified
- Time schedule for examinations: Not specified

OPHTHALMOSCOPIC EXAMINATION: Not specified
- Time schedule for examinations: Not specified
- Dose groups that were examined: Not specified

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at 6 week and 12 week
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals: 8 rats of each sex at a 6-wk period, and in all rats at 12 wk
- Parameters checked in table [No.?] were examined. Hematocrit, hemoglobin, RBCs, WBCs, Neutrophils, Lymphocytes

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at 6 week and 12 week
- Animals fasted: Not specified
- How many animals: 8 rats of each sex at a 6-wk period, and in all rats at 12 wk
- Parameters checked in table [No.?] were examined. Blood urea nitrogen

URINALYSIS: Not specified
- Time schedule for collection of urine: Not specified
- Metabolism cages used for collection of urine: Not specified
- Animals fasted: Not specified
- Parameters checked in table [No.?] were examined. Not specified

NEUROBEHAVIOURAL EXAMINATION: Not specified
- Time schedule for examinations: Not specified
- Dose groups that were examined: Not specified
- Battery of functions tested: sensory activity / grip strength / motor activity / other: Not specified

IMMUNOLOGY: Not specified
- Time schedule for examinations: Not specified
- How many animals: Not specified
- Dose groups that were examined: Not specified
- Parameters checked in table [No.?] were examined. Not specified

OTHER: Not specified
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, at autopsy, liver and kidney weights were recorded
HISTOPATHOLOGY: Yes, half the animals in each group were taken for histological examination: liver, kidneys, stomach, small and large intestines, spleen, pancreas, heart, lungs, bone marrow, muscle, brain, spinal cord, bladder, adrenals, thyroid, pituitary, gonads, salivary glands, and lymph nodes.
Other examinations:
No data
Statistics:
No data

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
not specified
Body weight and weight changes:
no effects observed
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:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
5.1 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: No significant alterations were noted in the treated and control animals
Remarks on result:
other: No toxic effect were observed
Dose descriptor:
NOAEL
Effect level:
5.7 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: No significant alterations were noted in the treated and control animals
Remarks on result:
other: No toxic effect were observed

Target system / organ toxicity

Critical effects observed:
no
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 test substance is considered to be 5.1 mg/Kg in males and 5.7 mg/Kg in females respectivley.
Executive summary:

Repeated dose subchronic toxicity study was performed to determine the toxic nature of test substance.The chemical was dosed to FDRL strain rats at dose levels of 5.1 mg/Kg in males and 5.7 mg/Kg in females for 90 days. Concurrent solvent control was also incorporated in the study. The animals were noted for usual observations (i.e. body weight and food consumption), haematologieal and blood chemical determinations, gross pathology and histopathology respectively. Administration of test substance for 90 days at a level in excess of at least 100 times the maximum estimated daily dietary intake in man evoked no adverse effect on growth, food consumption, haematology, blood chemistry, liver and kidney weights or on gross and microscopic appearance of major organs at autopsy. Hence, the No Observed Adverse Effect Level (NOAEL) for test substance is considered to be 5.1 mg/Kg in males and 5.7 mg/Kg in females.