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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: Chronic repeated dose toxicity
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:
Reproductive toxicity study of the test chemical
Author:
Oser et al
Year:
1965
Bibliographic source:
Food and Chemical Toxicology

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD 408
Principles of method if other than guideline:
Chronic repeated dose toxicity study of test material orally in rats.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: alpha -Ionone
- Molecular formula: C13H20O
- Molecular weight: 192.3 g/mol
- Substance type:organic
- Physical state:liquid

Test animals

Species:
rat
Strain:
other: FDRL
Sex:
male/female
Details on test animals and environmental conditions:
- Source: No data available
- Age at study initiation: (P) x wks; (F1) x wks No data available
- Weight at study initiation: (P) Males: x-x g; Females: x-x g; (F1) Males: x-x g; Females: x-x g
P : Males: 59.5 ±1.5 g, Females: 58.0 ± 1.6 g
- Fasting period before study: No data available
- Housing: Animals were housed individually in wire mesh cages
- Diet (e.g. ad libitum): Purina Laboratory Chow, ad libitum
- Water (e.g. ad libitum): Fresh water, ad libitum
- Acclimation period: No data available

Administration / exposure

Route of administration:
oral: feed
Vehicle:
cotton seed oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: The 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 (Purina Laboratory Chow).

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

VEHICLE
- Justification for use and choice of vehicle (if other than water): Purina Laboratory Chow
- Concentration in vehicle: 0 or 10.6 mg/kg body weight/day (expected dose) (0 or 11.8 (males) and 11.1 (females) mg/Kg bw/day)
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available
Details on mating procedure:
- Any other deviations from standard protocol: Reproductive organ weight were observed
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Frequency of treatment:
Daily
Details on study schedule:
No data available
Doses / concentrations
Remarks:
Doses / Concentrations:
Males: 11.8 mg/Kg bw/ day Females: 11.1 mg/Kg bw/ day (0 or 10.6 mg/kg body weight/day (expected dose))
Basis:
actual ingested
No. of animals per sex per dose:
Total: 30 males and 30 females
0 mg/kg bw/day: 15 male, 15 female
10.6 mg/kg bw/day: 15 male, 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.
- Rationale for animal assignment (if not random): No data available
- Rationale for selecting satellite groups: No data available
- Post-exposure recovery period in satellite groups: No data available
- Section schedule rationale (if not random): No data available
Positive control:
No data available

Examinations

Parental animals: Observations and examinations:
Body weight, Food consumption, haematology and clinical chemistry were examined.
Oestrous cyclicity (parental animals):
No data available
Sperm parameters (parental animals):
No data available
Litter observations:
No data available
Postmortem examinations (parental animals):
Organ weight, Gross pathological and histopathology were examined.
Postmortem examinations (offspring):
No data available
Statistics:
Statistical analysis were performed by the average values for those individual groups of either males or females which deviated by more than two standard errors from those of the controls.
Reproductive indices:
No data available
Offspring viability indices:
No data available

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 effects were observed on body weight and body weight gain of treated male and female rats as compared to control.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No effects were observed on food consumption of treated male and female rats as compared to control.
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:
no effects observed
Description (incidence and severity):
No effect was observed on clinical chemistry of treated rats as compared to control.
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):
Slight degree foci of myeloid metaplasia were observed in one male and control rats and no histopathologial changes were observed in reproductive gonads of male and female rats as compared to control.
Histopathological findings: neoplastic:
not specified
Other effects:
no effects observed

Reproductive function / performance (P0)

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

Details on results (P0)

Body weight:
No effects were observed on body weight and body weight gain of treated male and female rats as compared to control.

Food consumption: No effects were observed on food consumption of treated male and female rats as compared to control.

Test substance intake: 11.8 mg/Kg bw/day for male and 11.1 mg/Kg bw/day for female estimated compound intake

Organ weights: No effect was observed on liver and kidney weights of treated and reproductive gonads of male and female rats as compared to control.

Gross pathology: No significant gross pathological changes were observed in treated rats except occasional pulmonary alterations associated with a respiratory infection.
No gross pathological changes were observed in reproductive gonads of male and female rats as compared to control.

Histopathology: Slight degree foci of myeloid metaplasia were observed in one male and control rats and no histopathologial changes were observed in reproductive gonads of male and female rats as compared to control.

other findings:
Haematology: In female rat, slightly increased Haematocrit level was observed as compared to control.
The observed effect were considered to be non significant.

Clinical chemistry: No effect was observed on clinical chemistry of treated rats as compared to control.

Effect levels (P0)

open allclose all
Dose descriptor:
NOAEL
Effect level:
11.8 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: No adverse effect on body weight, food consumption, food efficiency, haematology, clinical chemistry, reproductive organ weight, reproductive gross pathology and histopathology
Remarks on result:
other: No effects observed reproductive organ
Dose descriptor:
NOAEL
Effect level:
11.1 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: No adverse effect on body weight, food consumption, food efficiency, haematology, clinical chemistry, reproductive organ weight, reproductive gross pathology and histopathology
Remarks on result:
other: No effetcs observed on reproductive organ

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: not specified
Organ:
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:
not measured/tested

Target system / organ toxicity (F1)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified

Applicant's summary and conclusion

Conclusions:
The no observed adverse effect level (NOAEL) was considered to be 11.8 mg/Kg bw/ day for male and 11.1 mg/Kg bw/ day for female when FDRL male and female rats were treated with test chemical orally by feed for 90 days.
Executive summary:

In a Chronic repeated dose toxicity study, FDRL male and female rats treated with test material orally by feed. The 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 (Purina Laboratory Chow). No effects were observed on body weight and body weight gain, food consumption and efficiency of food utilization of male and female rats as compared to control. Estimated compound intake for male were 11.8 mg/Kg bw/day and for female were 11.1 mg/Kg bw/day. Slightly increased in haematocrit level was observed in female rat as compared to control. The observed effects were considered to be non significant. Similarly, no effect was observed on liver and kidney weight of treated rats as compared to control. In addition, No significant gross pathological and histopathological changes were observed on reproductive gonads in treated male and female rats as compared to control. Therefore, the no observed adverse effect level (NOAEL) was considered to be 11.8 mg/Kg bw/ day for males and 11.1 mg/Kg bw/ day for females when FDRL male and female rats were treated with test chemical orally by feed for 90 days.