Diphenyl methylphosphonate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OECD Toolbox 2.2, is a harmonized system for OSAR application and grouping chemicals into categories, whose OECD principles are met

Data source

Reference

Reference Type:

other: prediction by the OECD QSAR Toolbox

Title:

Unnamed

Year:

2011

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: CSCL; CSCL, OECD TG409; CSCL, OECD TG 407; CSCL, OECD TG408; CSCL, OECD TG410; OECD TG 422

Principles of method if other than guideline:

Prediction by the OECD QSAR Toolbox (read-across approach)

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tris(2-butoxyethyl) phosphate

EC Number:

201-122-9

EC Name:

Tris(2-butoxyethyl) phosphate

Cas Number:

78-51-3

Molecular formula:

C18H39O7P

IUPAC Name:

tris(2-butoxyethyl) phosphate

Constituent 2

Reference substance name:

Triisobutyl phosphate

EC Number:

204-798-3

EC Name:

Triisobutyl phosphate

Cas Number:

126-71-6

Molecular formula:

C12H27O4P

IUPAC Name:

triisobutyl phosphate

Constituent 3

Reference substance name:

Tributyl phosphate

EC Number:

204-800-2

EC Name:

Tributyl phosphate

Cas Number:

126-73-8

Molecular formula:

C12H27O4P

IUPAC Name:

tributyl phosphate

Constituent 4

Reference substance name:

Diphenyl tolyl phosphate

EC Number:

247-693-8

EC Name:

Diphenyl tolyl phosphate

Cas Number:

26444-49-5

Molecular formula:

C19H17O4P

IUPAC Name:

4-methylphenyl diphenyl phosphate

Constituent 5

Reference substance name:

Diethyl phosphonate

EC Number:

212-091-6

EC Name:

Diethyl phosphonate

Cas Number:

762-04-9

Molecular formula:

C4H11O3P

IUPAC Name:

diethyl phosphonate

Details on test material:

Target substance:
- Name of test material (as cited in study report): diphenyl methylphosphonate;
- SMILES:c1(OP(C)(=O)Oc2ccccc2)ccccc1;
- CAS: 7526-26-3

Analogues:
- Name: 2-butoxyethanol, phosphate (3:1)
- CAS: 78-51-3

- Name: tris(2-methylpropyl) phosphate
- CAS: 126-71-6

- Name: tributyl phosphate
- CAS: 126-73-8

- Name: cresyl diphenyl phosphate
- CAS: 26444-49-5

- Name: diethyl phosphonate
- CAS: 762-04-9

Test animals

Species:

other: rat;mouse

Strain:

other: Wistar; Crj:CD(SD); Sprague-Dawley; no data; CD-1;F344; B6C3F1

Sex:

not specified

Results and discussion

Effect levels

Dose descriptor:

other: "Effect LOEL", LOEL, NOEC, NOEL, "Study LOEL", "Study NOEL"

Effect level:

318 mg/kg bw/day (nominal)

Basis for effect level:

other: taking the average from the nearest 5 neighbours, based on 5 data points from 5 neighbour chemicals

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The prediction was based on dataset comprised from the following descriptors: "effect LOEL","study NOEL","study LOEL",NOEL,LOEL
Estimation method: Taking average value from the 5 nearest neighbours
Domain logical expression: Result: In Domain

((("a" and ("b" and ( not "c") ) ) and "d" ) and ("e" and "f" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Esters AND Esters (phosphate) by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Phosphorus P AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N OR Group 16 - Sulfur S OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "d"

Similarity boundary:Target: c1(OP(C)(=O)Oc2ccccc2)ccccc1
Threshold=50%,
Dice(Atom pairs)

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.156

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.25

Applicant's summary and conclusion

Conclusions:

A NOAEL for the target chemical is considered to be 318 mg/kg bw. An assessment factor of 5 has to be applied due to uncertainties arisen from data base quality (4 of 5 category members are phosphates).

Executive summary:

The chemical diphenyl methylphosphonate (CAS 7526 -26 -3) was evaluated by the OECD QSAR Toolbox software for its level of toxicity by the prolonged exposure. The prediction was based on the measured values of chemicals assigned into the category.

The target chemical was classified as "Esters, Esters (phosphates)" by the profiling method "Aquatic toxicity classification by ECOSAR". Therefore, primarily a search for chemicals with the same classification was performed. Thereafter, a refinement to eliminate the chemicals which do have other chemical elements was perfomed. Finally, the chemicals were subcategorized according to their structural similarity. Four chemicals used for read-across were phosphates while only one chemical is phosphonate.

A LOAEL of 318 mg/kg bw was calculated for the target chemical (as average of the experimentally obtained LOEL, effect LOEL, LOEL etc. of the analogues). An assessment factor of 5 has to be applied to the calculated value to obtain a NOAEL which can cover uncertainties arisen from a data base quality.