Octylphosphonic acid

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

no

Test guideline 2

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

Test material information

Constituent 1

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

Controls

Controls 1

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

Controls 2

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: human

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

True negative controls validity:

not applicable

Positive controls validity:

valid

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:

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.