N,N'-methanetetraylbis(1-methylethylamine)

Genetic toxicity: in vivo

Administrative data

Endpoint:

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

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The detailed protocols are described by Witt et al. (1999). Bone marrow tests were initially performed using the standard three-exposure protocol described in detail by Shelby et al. (1993).

GLP compliance:

not specified

Type of assay:

other: bone marrow micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

N,N'-methanetetraylbis(1-methylethylamine)

EC Number:

211-743-7

EC Name:

N,N'-methanetetraylbis(1-methylethylamine)

Cas Number:

693-13-0

Molecular formula:

C7H14N2

IUPAC Name:

(propan-2-yl)({[(propan-2-yl)imino]methylidene})amine

Test material form:

liquid

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

corn oil

Details on exposure:

Single injection bone marrow micronucleus tests were conducted with diisopropylcarbodiimide in B6C3F1 male mice. These studies were designed to permit the testing of higher doses than could be administered in the multiple treatment protocol described above. The positive control was again cyclophosphamide. Two different posttreatment samples were collected; peripheral blood smears were prepared 48 hours after injection and bone marrow slides were prepared 24 and 48 hours after injection.

Duration of treatment / exposure:

single injection

Examinations

Tissues and cell types examined:

Air-dried smears from all the bone marrow micronucleus tests were fixed in absolute methanol and stained with acridine orange (Tice et al., 1990); 2,000 PCEs were scored per animal for frequency of micronucleated cells in blood, bone marrow, or both from up to five animals per group. In addition, the percentage of PCEs among the total erythrocyte population in the bone marrow was scored for each dose group as a measure of toxicity.

Results and discussion

Test results

Key result

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

Diisopropylcarbodiimide was then tested for induction of micronucleated PCEs in male B6C3F1 mice, the same strain employed in the 3-month dermal study, and the results of this test, assaying the frequency of micronucleated PCEs in bone marrow, were negative (Table E3).

Applicant's summary and conclusion

Conclusions:

Diisopropylcarbodiimide was then tested for induction of micronucleated PCEs in male B6C3F1 mice, the same strain employed in the 3-month dermal study, and the results of this test, assaying the frequency of micronucleated PCEs in bone marrow, were negative (Table E3).

Executive summary:

Diisopropylcarbodiimide was then tested for induction of micronucleated PCEs in male B6C3F1 mice, the same strain employed in the 3-month dermal study, and the results of this test, assaying the frequency of micronucleated PCEs in bone marrow, were negative (Table E3). The values of PCE percentages in this mouse study were unchanged with increasing dose, even though chemical-related toxicity was noted at the two highest doses tested. To permit the administration of a higher dose of diisopropylcarbodiimide in mice and to allow scoring of both blood and bone marrow erythrocytes in the same animals, single injection micronucleus studies were conducted with sampling at 24 and 48 hours posttreatment.