Fatty acids, C8-18 and C18-unsatd., reaction products with diethanolamine and propylene oxide

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes (incl. QA statement)

Remarks:

testing lab.

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, C8-18 and C18-unsatd., reaction products with diethanolamine and propylene oxide

EC Number:

600-026-8

Cas Number:

1000817-22-0

Molecular formula:

Unspecified

IUPAC Name:

Fatty acids, C8-18 and C18-unsatd., reaction products with diethanolamine and propylene oxide

Details on test material:

Identity: Kerocom FM 38
Batch No.: 2008250
Purity: mixture of reaction products
Aggregate State at Room Temperature: liquid
Colour: yellow to brownish, clear
Stability in solvent: stable for at least 4 h at room temperature in corn oil
Storage: at room temperature

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male

Details on test animals or test system and environmental conditions:

Acclimation: 7 days
Initial age at start of experiment: 8 - 12 weeks
Initial body weight at start of treatment: mean value 39.6 g (SD ± 3.0g)
The animals were under acclimation in the animal house of Harlan CCR for a minimum of five days after their arrival. During this period the animals did not show any signs of illness or altered behaviour.
The animals were distributed into the test groups at random and identified by cage number.
Housing: single
Cage Type: Makrolon Type II/III, with wire mesh top (EHRET GmbH, 79302 Emmendingen, Germany)
Bedding: granulated soft wood bedding (Rettenmaier & Söhne GmbH + Co. KG, 73494 Rosenberg, Germany)
Feed: pelleted standard diet, ad libitum (Harlan Laboratories GmbH, 33178 Borchen, Germany)
Water: tap water, ad libitum, (Gemeindewerke, 64380 Rossdorf, Germany)
Environment: temperature 22 + 2 °C; relative humidity 45 - 65 %; artificial light 6.00 a.m. - 6.00 p.m.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Duration of treatment / exposure:

once orally

Frequency of treatment:

once orally

Doses / concentrations

Remarks:

Doses / Concentrations:
24 h preparation interval: 500, 1000, and 2000 mg/kg b.w. 48 h preparation interval: 2000 mg/kg b.w.
Basis:

No. of animals per sex per dose:

Seven males per test group

Control animals:

yes

Positive control(s):

Cyclophosphamide

Examinations

Tissues and cell types examined:

bone marrow cells

Details of tissue and slide preparation:

It is generally recommended to use the maximum tolerated dose or the highest dose that can be formulated and administered reproducibly or 2000 mg/kg as the upper limit for non-toxic test items.
The maximum tolerated dose level is determined to be the dose that causes toxic reactions without having major effects on survival within 48 hours.
Since no gender specific differences concerning signs of toxicity in the pre-experiment were observed, the main study was performed using males only.
The administered volume was 10 ml/kg b.w.
Three adequately spaced dose levels spaced by a factor of 2 were administered, and samples were collected at the central sampling interval 24 h after treatment. For the highest dose level an additional sample was taken at 48 h after treatment.
Sampling of the bone marrow was done 24 and 48 hours after treatment, respectively.

Evaluation criteria:

A test item is classified as mutagenic if it induces either a dose-related increase or a clear increase in the number of micronucleated polychromatic erythrocytes in a single dose group. Statistical methods (nonparametric Mann-Whitney test [8] are used as an aid in evaluating the results, if necessary. However, the primary point of consideration is the biological relevance of the results. A test item that fails to produce a biological relevant increase in the number of micronucleated polychromatic erythrocytes is considered non-mutagenic in this system.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

After treatment with the test item the number of PCEs was not substantially decreased as compared to the mean value of PCEs of the vehicle control thus indicating that Kerocom FM 38 did not exert any cytotoxic effects in the bone marrow.
In comparison to the corresponding vehicle controls there was no biologically relevant or statistically significant enhancement in the frequency of the detected micronuclei at any preparation interval after administration of the test item and with any dose level used.
40 mg/kg b.w. cyclophosphamide administered orally was used as positive control which showed a substantial increase of induced micronucleus frequency.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative