Nonanoic acid

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

2010

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

no

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Nonanoic acid

EC Number:

203-931-2

EC Name:

Nonanoic acid

Cas Number:

112-05-0

Molecular formula:

C9H18O2

IUPAC Name:

nonanoic acid

Details on test material:

- Name of test material (as cited in study report): pelargonic acid
- Substance type: organic acid
- Physical state: clear, clorless liquid
- Analytical purity: 102% (by gas chhromatography)

Test animals

Species:

mouse

Strain:

ICR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc., Frederick, MD, USA
- Age at study initiation: 8 weeks
- Weight at study initiation: males 21.5-37.6 g; females 21.4-31.0 g

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle/solvent used:corn oil
- Justification for choice of solvent/vehicle: low water solubility of the test substance
- Concentration of test material in vehicle: approx. 12.5, 25, and 50%
- Amount of vehicle: dose volume was 10 mL/kg bw

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:

Pelargonic acid was suspended in corn oil.

Duration of treatment / exposure:

single dose

Frequency of treatment:

single dose

Post exposure period:

sampling at 24, 48, and 72 hours post dosing

Doses / concentrations

Remarks:

Doses / Concentrations:
1250, 2500, and 5000 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

15

Control animals:

yes, concurrent no treatment

Positive control(s):

- Positive control substance: cyclophosphamide
- Route of administration: oral gavage
- Doses / concentrations: 80 mg/kg bw

Examinations

Tissues and cell types examined:

Erythrocytes

Details of tissue and slide preparation:

TREATMENT AND SAMPLING TIMES: sampling at 24, 48, and 72 hours after single treatment


DETAILS OF SLIDE PREPARATION: At 24, 48, and 72 hours after administration of the test material or the vehicle, the appropriate groups of animals were sacrificed by CO2 asphyxiation. Sacrifice time for the vehicle and positive control groups was 24 hours. Bone marrow cells were flushed from both femurs of each animal with fetal calf serum and centrifuged. Supernatants were discarded; pellets were resuspended in residual supernatant, spread onto slides and air dried. The slides were fixed in methanol. stained with May-Grunwald and Giemsa solutions. cover slipped, coded and scored.


METHOD OF ANALYSIS: 1000 cells per animal were examined for the occurrence of micronuclei.

Evaluation criteria:

The test material was considered positive for micronuclei induction if a significant increase (p ≤ 0.05) in micronucleated polychromatic erythrocytes at any test dose compared to the vehicle control was seen.

Statistics:

The results were evaluated for statistical significance using an analysis of variance on the square root arcsine transformation, performed on the proportion of cells with micronuclei/animal. Tukey's Studentized range test with adjustment for multiple comparisons was used at each harvest time to determine which dose groups, if any, were significantly different (p ≤ 0.05) from the vehicle control. Analyses were performed separately for each harvest time and sex, and also at each harvest time for the sexes combined.

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): no
- Ratio of PCE/NCE (for Micronucleus assay): unchanged

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative
Pelargonic acid was negative in a mouse micronucleus test.

Executive summary:

Pelargonic acid (in corn oil) was examined in a mouse micronucleus test equivalent to OECD test guideline No. 475 for its genotoxicity in vivo. 15 male and female mice were used per dose level (0, 1250, 2500, 5000 mg/kg bw; single oral gavage). At 24, 48, and 72 hours after administration of the test material or the vehicle, bone marrow cells were harvested from both femurs, washed and stained. 1000 cells per animal were examined for chromosomal changes.

There was no statistically significant increase (p > 0.05) in micronucleated polychromatic erythrocytes at any test dose or any time after dosing compared to the vehicle control. The vehicle control and the positive control (cyclophosphamide, harvest at 24 hours) performed as expected.

 

The study is not yet available. The findings are available in a second source publication (reliability 4) and are used as a Weight of Evidence approach (EPA OPPT, 1995). In conclusion, pelargonic was negative in this adequately conducted in vivo micronucleus test.