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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
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable deficiencies (only 1 sampling time performed instead of 2; test material specification not indicated.)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
(Only 1 sampling time performed after 2nd test substance administration)
GLP compliance:
no
Remarks:
(study conducted prior to implementation of GLP)
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
other: CF1/W 68
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Winkelmann, Germany
- Age: ca. 8 weeks
- Weight at study initiation: 25-30 g

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Water
Details on exposure:
- Number of applications: 2, separated by 24 hours
- Post-exposure period: 6 hours after 2nd application
- Total volume applied: 2 x 10 mL
- Dose applied: 2 x 200, 2 x 400, 2 x 800 mg P3 Oxonia active/kg bw, , separated by an interval of 24 hours.
- Sampling times: 6 hours after the last administration (= 30 hours after the first administration)
Duration of treatment / exposure:
30 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
400, 800 and 1600 mg P3 Oxonia Active/kg bw|(= 18; 36 and 72 mg peracetic acid/kg bw)
Basis:

No. of animals per sex per dose:
7 male and 7 female mice
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide (20 mg/kg)

Examinations

Tissues and cell types examined:
The femoral bone marrow was removed and examined for the incidence of micronuclei in polychromatic erythrocytes, the proportion of polychromatic erythrocytes in the erythrocyte population and the incidence of micronuclei in normochromatic erythrocytes.
Number of cells examined: 1000 per animal
Statistics:
The data were analysed using the tables of Kastenbaum and Bowman.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
(distict clinical signs at highest dose group; no mortalities)
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
- Clinical signs:
No mortalities.
2 x 200 mg/kg bw group: slightly decreased activity, slight piloerection. 3 males showed signs of bites at the tail
2 x 400 mg/kg bw group: slightly decreased activity after first application, increased breathing rate and marked piloerection after second application. 2 males showed severe bites at testes and in rectal area.
2 x 800 mg/kg bw group: strongly reduced activity, marked piloerection, increased breathing rate after first application. Additionally, prone position, decreased body temperature, severe cyanosis, apathy, tremor/convulsion after second dose, more distinct in male animals. 2 males had white eyes after 26 hours.

- Genotoxicity:
Incidence of micronuclei in polychromatic erythrocytes not statistically different from controls. Therefore, evaluation of lowest dose group obsolete. For details on the incidences of micronucleated polychromatic erythrocytes and the ratio of PCE/NCE, please refer to Tables 1 and 2.

Any other information on results incl. tables

Table 1: Results of the micronucleus test, males

Dose

Micronuclei / 1000 PCE

Normochromatic erythrocytes / polychromatic erythrocytes

Mean

Range

Mean

Range

Negative control (water)

20 mL/kg bw

1

0-2

1.20

1.11-1.35

Positive control (cyclo­phosphamide)

20 mg/kg bw

6.57

3-14

1.56

1.02-2.02

Test material

400 mg/kg bw

*

*

*

*

800 mg/kg bw

0.33

0-2

1.58

1.03-2.21

1600 mg/kg bw

1.00

0-2

2.19

1.16-3.94

* Not evaluated

Table 2: Results of the micronucleus test, females

Dose

Micronuclei / 1000 PCE

Normochromatic erythrocytes / polychromatic erythrocytes

Mean

Range

Mean

Range

Negative control (water)

20 mL/kg bw

1.14

0-2

0.95

0.79-1.24

Positive control (cyclo­phosphamide)

20 mg/kg bw

5.86

4-9

1.05

0.86-1.17

Test material

400 mg/kg bw

*

*

*

*

800 mg/kg bw

0.67

0-1

1.14

0.70-1.42

1600 mg/kg bw

0.43

0-1

1.81

1.11-2.86

* Not evaluated

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
It was concluded that the test substance does not possess a mutagenic potential after oral administration in the described in vivo test system.
Executive summary:

In an in vivo micronucleus test 3 concentrations of P3 oxonia aktiv (2 x 200, 2 x 400 and 2 x 800 mg/kg bw = 18; 36 and 72 mg peracetic acid/kg bw) were orally administered to 7 mice per group with an interval of 24 hours between the two equal doses and a total volume of 2 x 10 mL/kg. 6 hours after the second application animals were sacrificed and bone marrow smears from both femurs of each animal were prepared. The number of micro nuclei and the polychromatic/normochromatic erythrocytes ratio were determined by light microscopy in 1000 cells per animal.

There were no differences in the number of micronuclei between test groups and negative control animals. In the highest dose group the normochromatic/polychromatic erythrocytes ratio was elevated. A preliminary toxicity test showed already moderate to severe clinical signs at this dose. The elevated normochromatic/polychromatic erythrocytes ratio is therefore not considered to be the result of a direct genotoxic effect of P3 oxonia aktiv but rather considered to be secondary to irritating effects and tissue damage at the site of first contact resulting in alterations in haematology. This effect on haematology was already demonstrated in other studies performed with peracetic acid.