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Diss Factsheets

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
other: Eu Risk Assessment report
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Although the EU risk assessment report is secondary literature, all data and risk assessment for the human, health and the environment have been evaluated and reviewed by Finland prior to publication. The risk assessment report has been submitted to final approval and published in the Official Journal of the European Union C157/10 dated on 21.06.2008. Thus, it is considered the information reported are reliable with the restrictions that reliability of the data presented has not been assessed again.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
European Union Risk Assessment 2,3-epoxypropyltrimethylammonium chloride CAS RN 3033-77-0 Einecs No: 221-221-0
Author:
EC
Year:
2008
Bibliographic source:
Risk Assessment. Final approved version. Rapporteur: Finland (FIN). European communities. Printed in Italy. 147pp

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
Cytotoxicity not evaluated (report not available)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
2,3-epoxypropyltrimethylammonium chloride
EC Number:
221-221-0
EC Name:
2,3-epoxypropyltrimethylammonium chloride
Cas Number:
3033-77-0
Molecular formula:
C6H14NO.Cl
IUPAC Name:
N,N,N-trimethyl(oxiran-2-yl)methanaminium chloride

Test animals

Species:
mouse
Strain:
other: BOR:NMRI
Sex:
male/female

Administration / exposure

Route of administration:
intraperitoneal
Details on exposure:
Three groups of 18 five-weeks old mice each were administered a single 10 ml/kg intraperitoneal injection of either EPTAC, physiological saline or
cyclophosphamide. The test material dose corresponded to 82.4 mg/kg and the positive control was 51.1 mg/kg.
Duration of treatment / exposure:
6 mice per sex and per control group and 7 mice of the treated group were killed 24, 48 and 72 hours after injection.
Doses / concentrations
Remarks:
Doses / Concentrations:
82.4 mg/kg
Basis:
nominal conc.
No. of animals per sex per dose:
6 mice/sex/control group and 7 mice/treated group
Control animals:
yes
Positive control(s):
Cyclophosphamide

- Route of administration: intraperitoneal
- Doses / concentrations: 51.1 mg/kg

Examinations

Tissues and cell types examined:
Bone marrow from mice of the treated and control groups was removed for erythrocyte analysis. For each sampling, five mice per sex and per group were used and 1000 polychromatic erythrocytes (PCE) were counted per animal.
Evaluation criteria:
The ratio of polychromatic to normochromatic (PCE/NCE) was used to assess the toxicity of the substance.
Statistics:
The PCE indices with micronuclei were statistically analysed by using a Poisson test on each treatment group, sex and both sexes combined.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
positive
Toxicity:
yes
Remarks:
slight to moderate clonic convulsions
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
In clinical examination, toxic symptoms, manifested as slight to moderate clonic convulsions, were observed in the EPTAC treated animals. At 72 h
there is a significant increase in the PCE/NCE in males. However, the authors of the report stated that the control values were exceptionally low based on intralaboratory and literature reported historical control incidences. The positive result of the males also caused a significant increase when both sexes were combined. On the other hand, at 24 h, there was a clear, statistically significant increase of micronucleated PCE in females. In males of
this sampling time, the number of PCEs was double the size than in respective negative controls with p-value of 0.076. The increase remained
significant even when both sexes were evaluated as one group.

Any other information on results incl. tables

Table 7.6.2 a PCEs with micronuclei scored in 1000 PCEs with PCE/NCE in control animals

PCE and PCE/NCE / animal

Control group

24h

48h

72h

PCE

(M)

PCE/

NCE

(M)

PCE

(F)

PCE/

NCE

(F)

PCE

(M)

PCE/

NCE

(M)

PCE

(F)

PCE/

NCE

(F)

PCE

(M)

PCE/

NCE

(M)

PCE

(F)

PCE/

NCE

(F)

1

3

2.05

1

1.77

1

1.40

1

2.13

0

2.55

0

2.41

2

0

1.71

1

1.97

2

2.04

2

1.86

1

4.05

0

3.33

3

1

1.93

2

1.67

0

2.09

1

1.72

1

2.70

1

2.70

4

2

2.45

2

1.67

0

1.20

2

1.57

0

2.80

1

2.80

5

2

1.89

1

1.96

0

1.75

2

1.42

0

3.41

1

3.41

Mean

1.6

1.4

0.6

1.6

0.4

0.6

Table 7.6.2 b PCEs with micronuclei scored in 1000 PCEs with PCE/NCE in EPTAC treated animals

PCE and PCE/NCE / animal

82.5 mg/kg EPTAC (i.p.)

24h

48h

72h

PCE

(M)

PCE/

NCE

(M)

PCE

(F)

PCE/

NCE

(F)

PCE

(M)

PCE/

NCE

(M)

PCE

(F)

PCE/

NCE

(F)

PCE

(M)

PCE/

NCE

(M)

PCE

(F)

PCE/

NCE

(F)

1

2

1.99

8

2.10

2

1.08

1

1.71

2

1.70

0

1.81

2

1

0.98

4

1.17

3

0.96

1

2.01

2

1.22

0

2.58

3

1

2.40

10

1.08

3

1.08

1

1.40

3

2.97

2

1.78

4

9

2.40

8

1.21

0

1.82

2

1.06

4

1.55

0

2.89

5

3

2.29

6

1.11

0

1.17

2

1.34

0

1.98

0

2.91

Mean

3.2

7.2

1.6

1.6

2.2

0.4

Table 7.6.2 c Statistical evaluation of mouse micronucleus test

PCE with micronuclei/Group

24h

48h

72h

M

F

M

F

M

F

EPTAC

16

36

8

8

11

2

Negative control

8

7

3

8

2

3

F

1.7778

4.5000

2.000

0.8889

3.6667

0.5000

p-value

0.076

0.000

0.113

0.589

0.011

0.812

Positive control

154

138

94

29

35

19

Negative control

 

8

7

3

8

2

3

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): positive
Under the test conditions, EPTAC is considered as clastogenic in vivo (mouse).
Executive summary:
In an in vivo chromosome aberration test performed according to OECD guideline No 474 and in compliance with GLP, mice (BOR:NMRI) were exposed by intraperitoneal injection to EPTAC at a concentration of 82.5 mg/kg. Positive controls induced the appropriate response.

There was a clear statistically significant increase of micronucleated PCE in males and females.

Under the test conditions, EPATC was clastogenic in mouse in vivo.