2,5-dihydroxy-3,6-dimethyl-3,6-bis(dihydroxyphosphinyl)-1,4,2,5-dioxadiphosphorane-2,5-dioxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

2015

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2010

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSARs R.6, May/July 2008

Principles of method if other than guideline:

ACD labs/Percepta (Release 2014) - Acute Toxicity Prediction Module The ACD/Labs Acute Toxicity predictor (LD50 module) provides predictions of LD50 values for rats and mice according to various routes of administration Advanced Chemistry Development, Inc. (ACD/Labs).

Test type:

other: QSARs prediction

Test material

Test material information

Constituent 1

Reference substance name:

2,5-Dihydroxy-3,6-dimethyl-3,6-bis(dihydroxyphosphinyl)- 1,4,2,5-dioxadiphosphorinane-2,5-dioxide

EC Number:

921-798-5

Cas Number:

32421-74-2

Molecular formula:

C4H12O12P4

IUPAC Name:

2,5-Dihydroxy-3,6-dimethyl-3,6-bis(dihydroxyphosphinyl)- 1,4,2,5-dioxadiphosphorinane-2,5-dioxide

Constituent 2

Reference substance name:

O=P1(O)OC(C)(P(=O)(O)O)P(=O)(O)OC1(C)P(=O)(O)O

IUPAC Name:

O=P1(O)OC(C)(P(=O)(O)O)P(=O)(O)OC1(C)P(=O)(O)O

Details on test material:

- Chemical name: ADPA
- Structural formula: C4H12O12P4
- SMILES: O=P1(O)OC(C)(P(=O)(O)O)P(=O)(O)OC1(C)P(=O)(O)O
- InChI: InChI=1S/C4H12O12P4/c1-3(17(5,6)7)15-20(13,14)4(2,18(8,9)10)16-19(3,11)12/h1-2H3,(H,11,12)(H,13,14)(H2,5,6,7)(H2,8,9,10)

Results and discussion

Effect levels

Sex:

not specified

Dose descriptor:

LD50

Effect level:

1 000 mg/kg bw

Based on:

other: QSARs prediction

Any other information on results incl. tables

- Applicability domain (OECD principle 3):

Domains: ACD/Percepta provides an estimation of the reliability of the prediction, by a reliability index (RI). This index provides values in a range from 0 to 1 and gives an evaluation of whether a submitted compound falls within the model applicability domain. In particular: RI < 0.3 (Not Reliable), RI in range 0.3-0.5 (Borderline Reliability), RI in range 0.5-0.75 (Moderate Reliability), RI >= 0.75

(High Reliability). Estimation of the RI takes into account the following two aspects: similarity of the tested compound to the training set and the consistency of experimental values for similar compounds. In this case the prediction is considered as moderately reliable since RI is equal to 0.66.

i. descriptor domain: not applicable.

ii. structural fragment domain: not applicable.

iii. mechanism domain: not applicable.

iv. metabolic domain, if relevant: not applicable.

 

- Structural analogues:

Five training set compounds found to be mostly similar to ADPA:

Alendronate LD50 = 970 mg/kg (Similarity: 0.85)

Etidronic acid LD50 = 1800 mg/kg (Similarity: 0.85)

Ethephon LD50 = 2900 mg/kg (Similarity: 0.66)

Phosphonic acid, tetradecyl LD50 = 2100 mg/kg (Similarity: 0.65)

IMPA LD50 = 5600 mg/kg (Similarity: 0.75)

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

ACD/Percepta predicted for ADPA an acute oral LD50 to mouse equal to 1000 mg/kg. The prediction is considered of moderate reliability. Based on these results, ADPA is considered as harmful if swallowed and classified into category. 4 (H302).

Executive summary:

The acute oral toxicity on mouse was estimated by using ACD/Percepta predictor. The reliability of ACD/Percepta prediction is estimated with the reliability index (RI), which takes into account the similarity of the tested compound with the training set compounds and the consistency of experimental values for similar compounds. It ranges from 0 to 1, in particular: RI in range 0.3-0.5 (Borderline Reliability), RI in range 0.5-0.75 (Moderate Reliability), RI >= 0.75 (High Reliability).

For ADPA, ACD/Percepta provided a prediction of LD50 equal to 1000 mg/kg. The prediction is of

moderate reliability being the reliability index equal to 0.63. Together with the prediction, ACD/Percepta displays up to 5 most structurally similar structures from the training set along with experimental results. The information on the structurally similar compounds in the training set is used to further assess the reliability of the prediction, since it illustrates how the test compound, i.e. ADPA, is represented in the training set. The five mostly similar compounds from the training set exhibit moderate to high similarity with respect to ADPA (similarity index ranging from 0.65 to 0.85), and experimental LD50 (mouse oral) values ranging from 970 to 5600 mg/kg.

 

Based on ACD/Percepta acute oral toxicity on mouse, moderately reliable LD50 predictions were obtained for ADPA (LD50 equal to 1000 mg/kg).