Allyl 3-cyclohexylpropionate

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Remarks:

Pre-GLP, pre-OECD TG study with sufficient detail in documentation

Data source

Reference

Reference Type:

publication

Title:

Food flavorings and compounds of related structure. II. Subacute and chronic toxicity

Author:

Hagan EC, Hansen WH, Fitzhugh OG, Jenner PM, Jones WI, Taylor JM, Long EL, Nelson AM, Brouwer JB

Year:

1967

Bibliographic source:

Food and Cosmetics Toxicology 5(2), 141-157

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 452 (Chronic Toxicity Studies)

Deviations:

not specified

Principles of method if other than guideline:

The study was conducted prior to the publication of OECD TGs. The compound was fed in the diet. Fresh diets were made and distributed weekly for a period of 1 year.

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Allyl 3-cyclohexylpropionate

EC Number:

220-292-5

EC Name:

Allyl 3-cyclohexylpropionate

Cas Number:

2705-87-5

Molecular formula:

C12H20O2

IUPAC Name:

prop-2-en-1-yl 3-cyclohexylpropanoate

Test animals

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: not reported
- Age at study initiation: weaning
- Weight at study initiation: not reported
- Fasting period before study: not reported
- Housing: individually in wire cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- not reported

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Mixing appropriate amounts with (Type of food): not reported
- Storage temperature of food: not reported

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

1 year

Frequency of treatment:

continuous

Doses / concentrations

Dose / conc.:

2 000 ppm

Remarks:

Basis:
nominal in diet

No. of animals per sex per dose:

5

Control animals:

yes, plain diet

Details on study design:

- Dose selection rationale: not reported

Positive control:

No

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

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

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: No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at 3, 6, 12 and 22 months
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- The following parameters were examined: white cell counts, red cell counts, haemoglobins and haematocrits

CLINICAL CHEMISTRY: No data

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Statistics:

No data

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

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:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Details on results:

CLINICAL SIGNS AND MORTALITY: no effects

BODY WEIGHT AND WEIGHT GAIN: no effects

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): no effects

FOOD EFFICIENCY: no data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): no data

OPHTHALMOSCOPIC EXAMINATION: no data

HAEMATOLOGY: no effects

CLINICAL CHEMISTRY: no data

URINALYSIS: no data

NEUROBEHAVIOUR: no data

ORGAN WEIGHTS: no effects

GROSS PATHOLOGY: no effects

HISTOPATHOLOGY: NON-NEOPLASTIC: no effects

Effect levels

1

Dose descriptor:

NOEL

Effect level:

> 2 500 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: based on 30 g/day food consumption and 350 g/rat body weight

2

Key result

Dose descriptor:

NOEL

Effect level:

> 214 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: based on 30 g/day food consumption and 350 g/rat body weight

Target system / organ toxicity

Key result

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

In 1-year feeding study no effects on the test item was observed up to 2500 ppm (mg/kg diet) or > 214 mg/kg bw/day.

Executive summary:

Groups of 5 weanling Osborne-Mendel rats per sex were housed individually in wire cages, and were allowed food and water ad libitum. The animals were administered the test material at 2500 ppm in the diet for 1 year, and the diet was prepared weekly. Weight, food intake and general condition were recorded weekly. Hematological examinations included white cell counts, red cell counts, hemoglobin and hematocrits and these were conducted at the termination of the study. On completion of the study, all surviving animals were sacrificed and examined macroscopically. Organ weights were recorded and tissues were preserved for histopathologic examination. Detailed microscopic examinations were done on 6 or 8 animals evenly divided by sex. No effects on the test item were observed up to 2500 ppm (mg/kg diet) or > 214 mg/kg bw/day.