ε-caprolactam

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Evaluation of chromosomal aberrations in bone marrow of 1C3F1 mice.

Author:

Adler, I.D. & Ingwersen, I.

Year:

1989

Bibliographic source:

Mutat. Res. 224, 343-345

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Principles of method if other than guideline:

The present experiment was conducted according to the test procedure described in Annex V of EEC Directive 79-831, Part B (1984).

GLP compliance:

not specified

Type of assay:

mammalian bone marrow chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

ε-caprolactam

EC Number:

203-313-2

EC Name:

ε-caprolactam

Cas Number:

105-60-2

Molecular formula:

C6H11NO

IUPAC Name:

azepan-2-one

Test animals

Species:

mouse

Strain:

other: 1C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 10-14 weeks
- Weight at study initiation: 25-28 g


ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: water for test substance, corn oil for positive control

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: Caprolactam (CAP) was dissolved in distilled water and orally applied by stomach intubation in a volume of 0.1 ml/10 g body weight.

Duration of treatment / exposure:

single administration

Frequency of treatment:

1

Post exposure period:

24-48 h

Doses / concentrations

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

benzo(a)pyrene
- Route of administration: gavage
- Doses / concentrations: 63 mg/kg bw

Examinations

Tissues and cell types examined:

bone marrow cells

Details of tissue and slide preparation:

TREATMENT AND SAMPLING TIMES:
Bone marrow of CAP-treated animals was sampled after 24, 30 and 48 h.
The sampling time for benzo(a)pyrene (BP)-treated animals was 30 h after treatment.
Each experimental group consisted of 5 treated males and 5 treated females plus 2 animals of each sex given distilled water. BP was tested with 5 males only. A total of 100 cells at mitotic metaphase per animal were scored microscopically. Mitotic indices were determined by counting the number of mitoses among 500 cells in a given field on each slide, i.e., a total of 1000 cells per animal.


METHOD OF ANALYSIS: The aberrations scored were of the chromatid or isochromatid type, i.e., gaps, breaks and fragments.

Evaluation criteria:

not reported

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

 Tab. 1:

Treatment	Interval (h)	Numbers of cells scored	Number of cells with			Aberrant cells (%±SE)^a	Mitotic index^b
			Gaps	Breaks	Exchanges
Water	-	1000	16	5	0	0.5±0.2	3.1
CAP	24	1000	20	3	0	0.3±0.2	2.4
	30	1000	4	0	0	0.0±0.0	2.1*
	48	1000	4	3	0	0.3±0.2	2.1*
BP	30	500	20	10	4	2.4±0.9**	2.8

^aExcluding cells with only gaps

^bPercent cells at mitosis (based on 1000 cells counted per animal)

* p<0.05, ** p<0.01

Applicant's summary and conclusion

Conclusions:

Based on the results, the test substance is negative for induction of chromosomal aberrations in bone marrow of mice.

Executive summary:

A study compareable to OECD testguideline 475 was performed. The test substance did not induce chromosomal aberrations in mouse bone marrow under the present experimental conditions. The frequencies of cells with breaks and gaps remained at the control level in all 3 sampling groups. The mitotic indices were reduced at the 30- and 48-h intervals indicating a cytotoxic effect. The positive control data with 63 mg/kg BP show a significant increase of chromosomal aberrations over the control. Based on the results, the test substance is negative for induction of chromosomal aberrations in bone marrow of mice.