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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000
Reference Type:
secondary source
Title:
OECD SIDS Hydroxypropyl acrylate, CAS No. 25584-83-2.
Author:
OECD SIDS
Year:
2006
Bibliographic source:
OECD SIDS for SIAM 20, UNEP Publications, October 2006.

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes (incl. certificate)
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-Hydroxypropylacrylate
- Analytical purity: 97.8 %
- Batch No. 790201167; Lot No. 32114707

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelman, D-33178 Borchen
- Assigned to test groups randomly: yes
- Housing: 5 animals of identical sex/cage
- Diet (ad libitum): pelleted standard diet (Altromin, D-32791 Lage/Lippe)
- Water (ad libitum): tap water
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 55±10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent used: CMC (carboxymethyl cellulose)
- Amount of vehicle (if gavage): 33 mL/kg bw
Duration of treatment / exposure:
single doses
Frequency of treatment:
once
Post exposure period:
not applicable
Doses / concentrations
Remarks:
Doses / Concentrations:
100, 300 and 600 mg/kg body weight
Basis:
actual ingested
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide

- Route of administration: single i.p. injection of 10 mL/kg bw cyclophosphamide in 0.9 % NaCl.
- Doses / concentrations: 30 mg/kg b.w

Examinations

Tissues and cell types examined:
One bone marrow smear was prepared per animal from the tissue cleared from each femur.
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION:
An initial experiment to determine the toxicity of the test substance was conducted. Three male and three female mice were administered the test
substance orally at 1000 mg/kg b.w. This dose resulted in only slight toxicity and was therefore chosen as the top dose. In the main experiment,
two animals died within the first 6 hours of dosing at 1000 mg/kg b.w. so a dose of 600 mg/kg b.w. was chosen as the highest dose that could be used for analysis of micronuclei. All 10 mice at 1000 mg/kg b.w. died within 24 hours of dosing.


TREATMENT AND SAMPLING TIMES:
Five males and five females from each group were sacrificed 24 hours after dosing. Forty eight hours after dosing five animals per sex from the 600 mg/kg dose level were killed.

DETAILS OF SLIDE PREPARATION:
Stained smears were examined by light microscopy for incidence of micronucleated cells per 2000 polychromatic erythrocytes per animal. To describe a cytotoxic effect, the ratio of polychromatic to normochromatic erythrocytes was assessed by the examination of at least 1000 erythrocytes.

Evaluation criteria:
Evaluation of Results:
Cells were evaluated for large (aneugenic effects) and small (clastogenic effects) micronuclei. The test substance was classified as mutagenic if it induced either a statistically significant (Mann-Whitney test), dose-related increase in the number of micronucleated polychromatic erythrocytes or a reproducible, statistically significant positive response for at least one of the test points.
Statistics:
Mann-Whitney test

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
600 mg/kg bw
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid

Any other information on results incl. tables

The ratio of normochromatic to polychromatic erythrocytes was slightly affected by the treatment with 2-hydroxypropyl acrylate at a dose of 600 mg/kg bw (at 24 and 48 hours in male mice and at 48 hours in female mice). At this dose level, only slight toxic effects, as evidenced by reduced spontaneous reactivity, were obtained up to 6 hours after dosing. There was no increase in the frequency of micronuclei at any dose level at either 24- or 48-hours after dosing compared to the negative control group.

The positive control compound, cyclophosphamide, produced significantly increased frequencies of micronucleated polychromatic and normochromatic erythrocytes.

 

Following are the results:

 

Males sacrificed at 24 hours:

 

 

Mean Micronuclei/2000 PCE

 

Dose group

All (%)

Small (%)

Mean PCE/NCE

Negative control

3.2 (0.16)

2.8 (0.14)

1000/873.6

600 mg/kg bw

4.4 (0.22)

3.8 (0.19)

1000/1056.8

300 mg/kg bw

5.4 (0.27)

5.4 (0.27)

1000/1177.6

100 mg/kg bw

4.8 (0.24)

3.8 (0.19)

1000/974.6

Positive control

20.2 (1.01)

18.8 (0.94)

1000/739.6

 

 

 

Females sacrificed at 24 hours:

 

 

Mean Micronuclei/2000 PCE

 

Dose group

All (%)

Small (%)

Mean PCE/NCE

Negative control

3.2 (0.16)

2.8 (0.14)

1000/737.4

600 mg/kg bw

2.8 (0.14)

2.0 (0.10)

1000/854.6

300 mg/kg bw

5.2 (0.26)

4.8 (0.24)

1000/773.8

100 mg/kg bw

3.2 (0.16)

2.8 (0.14)

1000/918.8

Positive control

19.6 (0.98)

18.4 (0.92)

1000/688.6

 

 

 

Males and Females sacrificed at 48 hours:

 

 

Mean Micronuclei/2000 PCE

 

Dose group

All (%)

Small (%)

Mean PCE/NCE

600 mg/kg bw males

2.2 (0.11)

2.0 (0.10)

1000/986.2

600 mg/kg bw females

2.2 (0.11)

1.8 (0.09)

1000/1065.4

 

 

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results: negative