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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
Toxicological Tests on Flavouring Matters
Author:
B. L. OSER
Year:
1965
Bibliographic source:
Fd Chem. Toxicology:

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
A repeated dose study investigating theeffect of alpha-ionone in rats for 90 days when administered orally.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
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-en-1-yl)but-3-en-2-one
Test material form:
other: liquid
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
- Impurities (identity and concentrations): Not available

Test animals

Species:
rat
Strain:
other: FDRL
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source:Not available
- Age at study initiation: Not available
- Weight at study initiation: 59.5±1.5 g(males) and 58.0±1.6 g (females)
- Fasting period before study: Not available
- Housing: Animals were housed individually in wiremesh cages.
- Diet (e.g. ad libitum): Purina Laboratory Chow, ad libitum
- Water (e.g. ad libitum): Fresh water, ad libitum
- Acclimatization period: No data available

ENVIRONMENTAL CONDITIONS
Not available

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: Purina Laboratory Chow
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS:
alpha-Iononewas 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 basal ration.

DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): 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)
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Not available
Duration of treatment / exposure:
90 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0 or 10.6 mg/kg/day (expected dose)
Basis:
nominal in diet
No. of animals per sex per dose:
Control: 15 males, 15 females
10.6 mg/kg/day: 15 males, 15 females
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: Single dosage levels for each substance were derived from total estimated daily intake, calculated on a mg/kg body weight basis assuming 50kg as the average body weight, and multiplying by 100.

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data available
BODY WEIGHT: Yes
- Time schedule for examinations: No data available
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
- Time schedule for examinations: No data available
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: 6 and 12 week period
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals:8 rats of each sex at a 6-week period andall rats at 12 weeks.
- Parameters checked:Haematocrit,haemoglobin, red blood cells, white blood cells, neutrophils, lymphocytes and blood urea nitrogen.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: 6 and 12 week period
- Animals fasted: No data available
- How many animals: 8 rats of each sex at a 6-week period andall rats at 12 weeks.
- Parameters checked:Endpoints not specified.
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
OTHER:No other observations described.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
At autopsy, liver and kidney weights were recorded.

HISTOPATHOLOGY: Yes
Organs from half of the animals in each group were taken for histological examination. The following organs and tissues were investigated: liver, kidneys, stomach, small and large intestines, spleen, pancreas, heart, lungs, bonemarrow, muscle, brain, spinal cord, bladder, adrenals, thyroid, pituitary, gonads, salivaryglands and lymph nodes.
Other examinations:
No other examinations.
Statistics:
Not available

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effect on body weight and weight gain were observed.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No effect in food consumption and compound intake were observed.
Food efficiency:
no effects observed
Description (incidence and severity):
No effect in food efficiency was observed.
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
No effect in any the examined heamotological parameters was noted.
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
No effect in clinical chemistry was observed.
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
Liver and kidney weights were normal.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No significant gross pathological changes were observed, with the exception of occasional pulmonary alterations associated with a respiratory infection.
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No dose related effect was observed.
Histopathological findings: neoplastic:
not specified
Details on results:
Body weight and weight gain: No effects observed on rat weight or weight gain.
FOOD CONSUMPTION AND COMPOUND INTAKE:No effects observed at intake of 11.8 mg/kg/day(males) and 11.1 mg/kg/day(females).
FOOD EFFICIENCY: No effects observed.
HAEMATOLOGY: No other effects observed in any of the parameters examined.
CLINICAL CHEMISTRY: No effects observed in the blood parameters examined.
GROSS PATHOLOGY: No significant gross pathological change was observed at autopsy in any of the rats in
this study.
Histopathology: slight lymphatic hyperplasia.No other effects observed.

Effect levels

open allclose all
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 effects were observed based on evaluations of body weight, food and water intake, hematology, bloodchemistry,liver and kidney weights and histopathology.
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 effects were observed based on evaluations of body weight, food and water intake, hematology, bloodchemistry,liver and kidney weights and histopathology.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be the measured dose 11.8 mg/kg/day in male and 11.1 mg/kg/day in female FDRL rats. The expected dose of -ionone was 10.6 mg/kg/day.
Executive summary:

In a toxicological study, male and female FDRL rats were fed diet containing 0 or 10.6 mg/kg/daya-ionone, a concentration that was reported by conducted measurement to provide an average intake of 11.8 mg/kg/day for males and 11.1 mg/kg/day for females for 90 days. No exposure-related effects were observed based on evaluations of body weight, food intake, hematology, blood chemistry (endpoints not specified), liver and kidney weights and histopathology. Therefore, NOAEL for male FDRL rats was considered to be 11.8 mg/kg/day while NOAEL for female FDRL rats was considered to be 11.1 mg/kg/day when exposed toalpha -ionone.