Diphenyl methylphosphonate

Endpoint summary

Description of key information

Predicted NOAEL of 318 mg/kg bw.

 

A 28 Day Oral Gavage Toxicity Study in the Rat (without recovery; according to OECD 407 / OPPTS 870.3050 / EC B.7 / GLP) has been ordered in a CRO to improve the dataset for this endpoint and have a more robust point-of-departure for the DNEL derivation. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

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

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

Species:

other: rat;mouse

Strain:

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

Sex:

not specified

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

Critical effects observed:

not specified

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

318 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

4 of 5 category members are phosphates while DPP is a phosphonate. An additional assessment factor of 5 is proposed to cover uncertainties due to the read-across.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are no repeated dose toxicity studies available for Diphenyl methylphosphonate. The studies are waived due to the fact that no relevant exposure to humans exists (please refer to waiver). Therefore, 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 in order to have a NOAEL/LOAEL for the derivation of DNELs. 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 possess other chemical elements was performed. 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). For hazardous risk assessment (derivation of DNEL), an assessment factor of 5 has to be applied to the predicted LOAEL.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Acceptable, recommended by ECHA software for grouping chemicals into categories and read-across.

Justification for classification or non-classification

The registered substance is not subject for classification and labelling for STOT-RE according to Regulation (EC) No 1272/2008 since the read-across chemicals are not classified for this endpoint.