Nonan-4-olide

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity

Remarks:

subcutaneous

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1964-1968

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Study performed via subcutaneous route using 16 female mice; individual animal data not reported; no data on body weight, food/water consumption, clinical observations and non-neoplastic histopathological findings

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1970

Materials and methods

Principles of method if other than guideline:

Carcinogenic study: γ-Nonalactone was administered via subcutaneous injections to a group of mice at a dose level of 15 mg/injection; 3 times a week for 4 weeks and the appearance of suspected neoplasms was recorded for 18-24 months.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Nonan-4-olide

EC Number:

203-219-1

EC Name:

Nonan-4-olide

Cas Number:

104-61-0

Molecular formula:

C9H16O2

IUPAC Name:

5-pentyloxolan-2-one

Details on test material:

- Name of test material (as cited in study report): γ-Nonalactone
- Source: Givaudan-Delawanna, Inc., New York, USA
- Analytical purity: > 98 %
- Analytical method: Received test material was purified by fractional distillation under vacuum and/or column chromatography. Purity was determined by functional group analysis and microanalysis coupled with thin-layer, column, and gas-liquid chromatography (if applicable) and nuclear magnetic resonance spectroscopy.

Test animals

Species:

mouse

Strain:

Swiss Webster

Sex:

female

Administration / exposure

Route of administration:

subcutaneous

Vehicle:

other: tricaprylin

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

4 weeks

Frequency of treatment:

3 times a week for 4 weeks

Post exposure period:

18-24 months

Doses / concentrations

Remarks:

Doses / Concentrations:
15 mg/injection
Basis:
other: injected

No. of animals per sex per dose:

- Treatment group: 16 female mice
- Vehicle control: 100 female mice
- Blank control (no treatment): 203 female mice

Control animals:

yes, concurrent no treatment

yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Based on:

test mat.

Sex:

female

Basis for effect level:

other: no evidence of carcinogenic activity

Remarks on result:

not determinable

Remarks:

no NOAEL identified. Effect type:carcinogenicity (migrated information)

Any other information on results incl. tables

- Body weight: No excessive weight losses or gains were found as compared with untreated control groups

- Mortality: See table 7.7/1

- Neoplastic data: See table 7.7/1

Table 7.7/1: Summary of tests for carcinogenic activity in Swiss-Webster mice

 

Compound	Alive/total mice*	Subcutaneous sarcomas	Pulmonary tumors	Breast cancers	Lymphomas	Other tumors
Tricaprylin	97/100	0	4	2	0	4
No treatment	171/203	1	10	14	0	2
γ-Nonalactone	15/16	1	0	0	0	0

*No. of Swiss-Webster mice alive at 6 months/Total no. of mice at the beginning of the test

Applicant's summary and conclusion

Conclusions:

Under the test conditions, there was no evidence of carcinogenic activity of γ-nonalactone for female Swiss-Webster mice.

Executive summary:

In a carcinogenic study, γ-nonalactone was administered via subcutaneous injections to a group of 16 female Swiss-Webster mice at a dose level of 15 mg/injection; 3 times a week for 4 weeks. Untreated and vehicle (tricaprylin) controls were also included in the study. All mice were weighed at the start of the experiments and at regular intervals throughout the ensuing period of observation of 18 to 24 months. Mice were observed twice weekly for the appearance of subcutaneous tumors. Animals with tumors or those in poor condition were killed and autopsied. Suspected neoplasms and other grossly abnormal tissues were removed and fixed in buffered 10 % formalin. All diagnoses were based on histological examination of sections stained with hematoxylin and eosin.

Total alive mice at 6 months were recorded to be 97/100, 171/203 and 15/16 in vehicle control, untreated and treatment groups, respectively. No excessive weight losses or gains were found as compared with untreated control groups. Subcutaneous sarcomas, breast cancers pulmonary and other tumors were identified in control groups. In treatment group, subcutaneous sarcoma was identified in only one mouse.

Under the test conditions, there was no evidence of carcinogenic activity of γ-nonalactone for female Swiss-Webster mice.