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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
reproductive toxicity, other
Remarks:
Subchronic Toxicity Test
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 peer-reviewed journal

Data source

Reference
Reference Type:
publication
Title:
Toxicological tests on flavouring matters
Author:
Oser, B.L., et.al
Year:
1965
Bibliographic source:
Food and Cosmetic Toxicology,1965

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: as below
Principles of method if other than guideline:
Subchronic Toxicity Test of Beta-Naphthyl ethyl ether in rats
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name of test material: 2-Ethoxynaphthalene
- Molecular formula: C12H12O
- Molecular weight: 172.226 g/mole
- Smiles notation: c12c(ccc(c1)OCC)cccc2
- InChl: 1S/C12H12O/c1-2-13-12-8-7-10-5-3-4-6-11(10)9-12/h3-9H,2H2,1H3
- Substance type: Organic
- Physical state: Solid

Test animals

Species:
rat
Strain:
other: FDRL
Sex:
male/female
Details on test animals 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 wire mesh cages.
- Diet (e.g. ad libitum): nutritionally adequate basal ration
- 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
Type of inhalation exposure (if applicable):
not specified
Vehicle:
cotton seed oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Each test substance 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.
Details on mating procedure:
not specified
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Frequency of treatment:
Dailly
Details on study schedule:
not specified
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
5.1 mg/kg bw/day
Remarks:
for male
Dose / conc.:
5.7 mg/kg bw/day
Remarks:
for female
No. of animals per sex per dose:
Total: 60
0 mg/kg bw: 15 male, 15 female
5.1 mg/kg bw: 15 male
5.7 mg/kg: 15 female
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.
Positive control:
not specified

Examinations

Parental animals: Observations and examinations:
BODY WEIGHT: Yes
Time schedule for examinations
8 rats of each sex at 8 weeks period and in all rats at 12 weeks.

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: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes

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: Yes

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: 8 rats of each sex at a 6-wk period, and in all rats at 12 week.

OTHER:
Organ weight: liver and kidney weight were weighted.
Oestrous cyclicity (parental animals):
not specified
Sperm parameters (parental animals):
not specified
Litter observations:
not specified
Postmortem examinations (parental animals):
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.
Postmortem examinations (offspring):
not specified
Statistics:
not specified
Reproductive indices:
not specified
Offspring viability indices:
not specified

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effect on body weight were observed in treated rats.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No effect on food consumption were observed in treated amle and femlae rats as compared to control.
Food efficiency:
no effects observed
Description (incidence and severity):
No effect on food efficiency were observed in treated amle and femlae rats as compared to control.
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
When treated with 5.1 mg/kg for males and 5.7 mg/kg for females, no change in Haematocrit, haemoglobin, Red blood cell, White blood cell, Neutrophills, Lymphocytes and Blood urea Nitrogen was observed as compared to control.
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:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No histopathological changes were observed in treated male and female rats in 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 as compared to control.
Histopathological findings: neoplastic:
no effects observed
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Effect levels (P0)

open allclose all
Dose descriptor:
NOAEL
Effect level:
5.1 mg/kg bw/day
Based on:
test mat.
Sex:
male
Basis for effect level:
body weight and weight gain
food consumption and compound intake
food efficiency
haematology
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic
other: No effect on histopathology of reproductive oragns
Remarks on result:
other: No toxic effects on reproductive organ
Dose descriptor:
NOAEL
Effect level:
5.7 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
body weight and weight gain
food consumption and compound intake
food efficiency
haematology
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic
other: No effect on histopathology of reproductive oragns
Remarks on result:
other: No effects on reproductive organ

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
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:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Dose descriptor:
other: not specified
Generation:
other: not specified
Based on:
not specified
Sex:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified

Target system / organ toxicity (F1)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
No adverse effect level (NOAEL) was considered to be 5.1 mg/kg for males and 5.7 mg/kg for females when FDRL male and female rats were treated with Beta-Naphthyl ethyl ether orally in feed for 90 days.
Executive summary:

In a Subchronic Toxicity Test,  FDRL male and female rats were treated with Beta-Naphthyl ethyl ether in the concentration of 5.1 mg/kg for males and 5.7 mg/kg for females orally by feed for 90 days. No adverse effects on body weight and food consumption or food efficiency throughout the administration period were observed in treated rats as compared to control. Similarly, No effect on Hematological parameters and organ weight of treated male and female rats were observed as compared to control. In addition, No gross pathological and histopathological changes were observed in treated male and female rats in 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 as compared to control. Therefore, No adverse effect level (NOAEL) was considered to be 5.1 mg/kg for males and 5.7 mg/kg for females when FDRL male and female rats were treated with Beta-Naphthyl ethyl ether orally in feed for 90 days.