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Toxicological information

Genetic toxicity: in vivo

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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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986
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:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
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