N-cyclohexyl-N-methylcyclohexylamine

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:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: no guideline study but a very thoroughly reported test.

Data source

Reference

Reference Type:

publication

Title:

Tier II mutagenic screening of 13 NIOSH priority compounds; individual compound report: N-methyl-dicyclohexylamine, Report No. 1190

Author:

McGregor DB

Year:

1981

Bibliographic source:

Project No. 409959, Inveresk Research International Ltd., at the request of the National Institute for Occupational Safety and Health (NIOSH) Cincinnati/OH, PB83-126607

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

GLP compliance:

not specified

Type of assay:

mammalian germ cell cytogenetic assay

Test material

Test material information

Constituent 1

Reference substance name:

N-methyl dicyclohexylamine

IUPAC Name:

N-methyl dicyclohexylamine

Constituent 2

Reference substance name:

N-cyclohexyl-N-methylcyclohexylamine

EC Number:

231-453-4

EC Name:

N-cyclohexyl-N-methylcyclohexylamine

Cas Number:

7560-83-0

Molecular formula:

C13H25N

IUPAC Name:

N-cyclohexyl-N-methylcyclohexanamine

Test material form:

not specified

Details on test material:

purity 98%

Test animals

Species:

rat

Strain:

other: CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

ANIMAL MAINTAINANCE
test(1) 30 rats /sex/concentration
test(2) 10 rats/sex/concentration
housed individually in cages
room light intensity: 200 lux
12 hour light-dark cycle,
temperature ca. 22°C,
relative humidity: 50 %,
food and water freely available
Each animal was examined for any signs of ill health before being transferred into the exposure chamber.

ATMOSPHERE GENERATION and EXPOSURE
The test atmosphere was produced by bubbling dry, oxygen-free nitrogen (BOC Limited) through a liquid reservoir of N-methyl dicyclohexylamine contained in a 500 ml glass flask contained within a temperature controlled heating mantle. The nitrogen/N-methyl dicyclohexylamine vapor mixture was ducted through 7/8" stainless steel piping to a glass mixing vessel and diluted with filtered, compressed air; the resulting mixture was ducted to the top of the exposure chamber. The atmospheres in the exposure chamber were dynamic in that they were continuously generated for a single pass through the animal holding zone, before being extracted from the bottom and ducted away.
The required atmospheric concentration within the exposure chamber were maintained finely regulating the flow of nitrogen and diluting air into the mixing vessels by means of adjustable flow meteres.
Animals were whole-body exposed.

CONTROLS
Negative control animals were exposed to air.
Animals serving as positive controls received ethylmethane sulphonate orally:
test (1): 250 mg/kg bw
test (2): 100 mg/kg bw/day for 5 consecutive days

Administration / exposure

Route of administration:

inhalation

Duration of treatment / exposure:

(1) once, 7 hours (2) 7 hrs/day, 5 consecutive days

Frequency of treatment:

6,24, 48h

No. of animals per sex per dose:

test(1) 30 rats /sex/concentration
test(2) 10 rats/sex/concentration

Examinations

Details of tissue and slide preparation:

CYTOGENETIC ANALYSES
Cytogenetic analysis was made of rat bone marrow cells from femur after 6 hours, 24 hours and 48 hours (single exposure experiment: 10 rats sacrificed at each sampling time) or 6 hours after the last exposure(repeat exposure experiment: all 10 rats sacrificed). Two hours before sacrifice animals were injected i.p. with colchicine dissolved in Hank's balanced Salt solution.

Evaluation criteria:

For each animal 50 cells with a minimum of 41 well spread chromosomes were examined and scored.
The number of abnormalities was recorded including gaps, breaks, fragments, dicentrics, translocations and pulverisation.

Statistics:

STATISTICAL EVALUATION
Freeman-Tukey transformation
one-sided Student's t-test

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

valid

Any other information on results incl. tables

N-methyl dicyclohexylamine did not increase the frequency of aberrant cells in rat bone marrow. The positive control was functional..

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
N-methyl dicyclohexylamine did not increase the frequency of aberrant cells in rat bone marrow.

Executive summary:

N-methyl dicyclohexylamine did not increase the frequency of aberrant cells in rat bone marrow.