dichloromethane; methylene chloride

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Reference 2

Reference Type:

publication

Title:

Inactivity of methylene chloride in the mouse bone marrow micronucleus assay

Author:

Sheldon T, Richardson CR, Elliott BM

Year:

1987

Bibliographic source:

Mutagenesis, 2(1): 57-59

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

no

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Dichloromethane

EC Number:

200-838-9

EC Name:

Dichloromethane

Cas Number:

75-09-2

Molecular formula:

CH2Cl2

IUPAC Name:

dichloromethane

Details on test material:

Purity 99.9%
CTL Y00287/010/001
Supplied by BDH Chemicals, Poole, Dorset, UK

Test animals

Species:

mouse

Strain:

C57BL

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Duration of treatment / exposure:

single application

Frequency of treatment:

once

Post exposure period:

24, 36, 48 or 72 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
1250, 2500, 4000 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Examinations

Statistics:

One-sided Student's t test

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

death (females at 2500 and 4000 mg/kg bw); decreased number of PCE's (males, 2500 and 4000 mg/kg bw)

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Any other information on results incl. tables

Table: mean incidence of PCE

 

Compound	Dose (mg/kg)	Sex	Incidence of MPCEs / 1000 PCEs
			24 h	36 h	48 h	72 h
Corn oil (control)	10 mL/kg	M	1.6±1.7	1.6±0.5	3.6±3.1	2.4±1.7
		F	0.6±0.9	0.8±0.4	0.8±1.3	0.6±0.9
Cyclophosphamide	65	M	16.2±8.6**	18.6±4.3**	17.0±5.7**	6.0±4.6*
		F	10.0±3.5**	14.2±2.2**	7.0±1.4**	3.0±2.3*
Methylene chloride	1250	M	1.4±1.7	2.2±1.3	2.6±3.6	2.0±1.0
		F	0.2±0.4	1.0±1.0	1.2±0.8	1.0±1.0
Methylene chloride	2500	M	1.2±1.3	1.2±0.8	1.8±2.5	1.6±1.5
		F	0.8±1.8	0.8±1.3	1.3±1.3 (4)	1.5±1.3 (4)
Methylene chloride	4000	M	2.2±1.9	2.0±1.7	2.0±0.8 (4)	2.2±1.9
		F	1.0±0.8 (4)	1.3±1.3 (4)	2.0±2.8 (4)	0.5±0.6 (4)

N=5, unless where indicated in parentheses; *p<0.05; **p<0.01

 

 

Table: mean percentage PCE (500 cells counted PCEs + NCSs)

 

Compound	Dose (mg/kg)	Sex	% PCE
			24 h	36 h	48 h	72 h
Corn oil (control)	10 mL/kg	M	35.8±15.1	35.2±9.1	32.3±8.5	28.7±9.6
		F	40.0±8.5	33.1±6.3	35.5±10.3	32.7±7.4
Cyclophosphamide	65	M	21.4±8.3*	35.4±6.3	27.1±9.3	24.4±8.2
		F	23.3±13.2*	28.0±5.7	21.4±10.7*	32.1±10.8
Methylene chloride	1250	M	35.0±9.2	43.1±4.9	31.7±14.7	27.6±13.0
		F	43.6±11.9	34.2±6.1	40.7±18.0	31.6±8.7
Methylene chloride	2500	M	19.1±8.1*	38.2±10.3	25.2±5.5	27.9±6.8
		F	35.2±16.2	32.5±16.4	29.8±11.5 (4)	31.6±5.4(4)
Methylene chloride	4000	M	24.9±11.3	38.9±10.5	38.1±17.0 (4)	37.7±10.6
		F	33.5±11.5 (4)	32.5±7.4(4)	33.2±2.9 (4)	40.0±14.5 (4)

N=5, unless where indicated in parentheses; *p<0.05

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results of MN test in vivo: negative