4-(2,6,6-trimethylcyclohex-2-ene-1-yl)-but-3-ene-2-one

Toxicity to reproduction

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

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

Test material information

Constituent 1

Reference substance name:

4-(2,6,6-trimethylcyclohex-2-ene-1-yl)-but-3-ene-2-one

EC Number:

204-841-6

EC Name:

4-(2,6,6-trimethylcyclohex-2-ene-1-yl)-but-3-ene-2-one

Cas Number:

127-41-3

Molecular formula:

C13H20O

IUPAC Name:

4-(2,6,6-trimethylcyclohex-2-ene-1-yl)-but-3-ene-2-one

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 or test system 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)

1

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

2

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.