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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study to GLP
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
Deviations:
not specified
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Constituent 1
Chemical structure
Reference substance name:
Octylphosphonic acid
EC Number:
225-218-5
EC Name:
Octylphosphonic acid
Cas Number:
4724-48-5
Molecular formula:
C8H19O3P
IUPAC Name:
octylphosphonic acid
Test material form:
other: liquid
Details on test material:
Name in study report: Octylphosphonic Acid

Method

Target gene:
Not applicable.
Species / strain
Species / strain / cell type:
lymphocytes: human
Metabolic activation:
with and without
Metabolic activation system:
Rat S9 mix
Test concentrations with justification for top dose:
100 to 750 µg/mL
Vehicle / solvent:
DMSO
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
without activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
with activation
Details on test system and experimental conditions:
No data
Evaluation criteria:
The data are interpreted as follows:
a) No statistically significant increase in the percentage of aberrant cells (at any concentration) above concurrent solvent control values - NEGATIVE.
b) A statistically significant increase in the percentage of aberrant cells above concurrent solvent control values, which falls within the laboratory solvent control range - NEGATIVE
c) An increase in the percentage of aberrant cells, at least at one concentration, which is substantially greater than the laboratory historical solvent control values - POSITIVE.
d) A statistically significant increase in the percentage of aberrant cells which is above concurrent solvent values and which is above the historical solvent control range upper value but below that described in (c) may require further evaluation.
Statistics:
The Fisher Exact Probability Test (one-sided) was used to evaluate statistically the percentage of metaphases showing aberrations (excluding cells with only gap-type aberrations).

Results and discussion

Test results
Species / strain:
lymphocytes:
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
above 750 ug/mL
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Mean Chromosomal Aberrations and mitotic Indices without metabolic activation

(68 hour sampling time):

Treatment

 

Mean % aberrant cells excluding gaps

Aberations/cell excluding gaps

Mean % Mitotic Index

Donor 1

 

 

 

 

Solvent control

10 µL/mL

2.50

0.025

14.7

Mitomycin C

0.2 µg/mL

24.00**

0.400

9.3

OPA

500 µg/mL

2.00

0.020

9.4

 

250 µg/mL

2.50

0.025

12.1

 

100 µg/mL

2.00

0.020

13.4

Donor 2

 

 

 

 

Solvent control

10 µL/mL

1.00

0.010

7.3

Mitomycin C

0.2 µg/mL

32.00**

0.480

4.2

OPA

500 µg/mL

4.00

0.040

5.6

 

250 µg/mL

2.00

0.020

8.2

 

100 µg/mL

0.50

0.005

8.7

** p<0.01

 

Mean Chromosomal Aberrations and mitotic Indices with metabolic activation

(68 hour sampling time):

Treatment

 

Mean % aberrant cells excluding gaps

Aberations/cell excluding gaps

Mean % Mitotic Index

Donor 1

 

 

 

 

Solvent control

10 µL/mL

1.00

0.010

15.8

Mitomycin C

0.2 µg/mL

20.00**

0.360

12.6

OPA

500 µg/mL

2.00

0.020

15.3

 

250 µg/mL

0.00

0.000

12.7

 

100 µg/mL

1.00

0.010

11.9

Donor 2

 

 

 

 

Solvent control

10 µL/mL

3.00

0.030

8.2

Mitomycin C

0.2 µg/mL

36.00**

0.480

3.0

OPA

500 µg/mL

2.00

0.020

8.3

 

250 µg/mL

3.50

0.035

8.2

 

100 µg/mL

0.50

0.005

8.9

** p<0.01

 

Mean Chromosomal Aberrations and mitotic Indices with and without metabolic activation

(92 hour sampling time):

Treatment

 

Mean % aberrant cells excluding gaps

Aberations/cell excluding gaps

Mean % Mitotic Index

Donor 2 (+S9)

 

 

 

 

Solvent control

10 µL/mL

0.00

0.000

13.9

OPA

750 µg/mL

0.00

0.000

15.7

Donor 2 (-S9)

 

 

 

 

Solvent control

10 µL/mL

3.00

0.030

14.7

OPA

750 µg/mL

3.50

0.045

14.4

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Under the conditions of this assay, OPA was not clastogenic to cultured human lymphocytes treated in vitro in either the presence or absence of S9-mix.
Executive summary:

Octylphosphonic acid was evaluated for its clastogenic potential in an in vitro cytogenetic assay using human lymphocytes from two donors treated in the presence and absence of a rat liver-derived metabolic activation system (S9-mix). Cultures from both donors were harvested at the standard time of 68 hours after culture initiation and additional cultures from Donor 2 were harvested at the later time of 92 hours after culture initiation. Cultures treated with octylphosphonic acid at concentrations from 100 to 750 µg/mL were selected for chromosomal aberration analysis along with the appropriate solvent and positive control cultures. The highest concentration selected for chromosomal aberration analysis was based on a reduction in mitotic activity or was the lowest precipitating concentration.

At the 68 hour sampling time, no statistically or biologically significant increases in the percentage of aberrant cells, compared to the solvent control values, were recorded in cultures from either donor treated in either the presence or absence of S9-mix. No statistically or biologically significant increases in the percentage of aberrant cells, compared to the solvent control values, were recorded at the 92 hour sampling time in cultures from Donor 2 treated in either the presence or absence of S9-mix. The sensitivity of the test system, and the metabolic activity of the S9-mix employed, were clearly demonstrated by the increases in the percentage of aberrant cells induced by the positive control agents, mitomycin C and cyclophosphamide.

It is concluded that, under the conditions of this assay, octylphosphonic acid is not clastogenic to cultured human lymphocytes treated in vitro in either the presence or absence of S9-mix.