Dapsone

Biodegradation in water and sediment: simulation tests

Link to relevant study record(s)

Reference

Endpoint:

biodegradation in water: simulation testing on ultimate degradation in surface water

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

In order to identify the relevant degradation products of the substance as a standard information requirement according to Column 1, Section 9.2.3 of Annex IX to REACH and for assessment of potential PBT/vPvB properties, degradation products were predicted using the EAWAG-BBD Pathway Prediction System.

1. SOFTWARE
EAWAG-BBD Pathway Prediction System (http://eawag-bbd.ethz.ch/predict/)

2. MODEL (incl. version number)
EAWAG-BBD Pathway Prediction System: Last updated January 18, 2016.

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See attached QPRF

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
The EAWAG-BBD Pathway Prediction System predicts (EAWAG-BBD PPS) microbial catabolic reactions using substructure searching, a rule-base, and atom-to-atom mapping. The system is able to recognize organic functional groups found in a compound and predict transformations based on biotransformation rules. The biotransformation rules are based on reactions found in the EAWAG-BBD database or in the scientific literature. The EAWAG-BBD database contains information on microbial biocatalytic reactions and biodegradation pathways for primarily xenobiotic, chemical compounds. Individual reactions and metabolic pathways are presented with information on the starting and intermediate chemical compounds, the organisms that transform the compounds, the enzymes, and the genes. The EAWAG-BBD (Biocatalysis/Biodegradation Database) is a manually curated database containing information on over 1350 microbial catabolic reactions and about 200 biodegradation pathways. The EAWAG-PPS (Pathway Prediction System) predicts biodegradation pathways using 250 biotransformation rules based on data in the BBD (Biocatalysis/Biodegradation Database) and the scientific literature. Further details can be found in the attached QMRF.

5. APPLICABILITY DOMAIN
Although there is no specifically identified applicability domain for EAWAG-BBD PPS, there are certain chemicals whose biodegradation profile should not be predicted with the system. There are a number of chemical classes that should not be investigated using the current version of the Pathway Prediction System (PPS). Compounds modelled with the EAWAG-BBD PPS can be structurally compared to the compounds present in the EAWAG-BBD database, which presently contains 1400 compounds. The experimental biotransformation data on which the biotransformation rules within the model are based, originate from data on these 1400 substances. More information on the model's applicability domain can be found in the attached QMRF and QPRF.

6. ADEQUACY OF THE RESULT
The results are considered appropriate to fulfill the REACH requirements for identification of degradation products (Annex IX, Section 9.2.3.). The compounds meet the criteria for applicability of the EAWAG-BBD model. None of the constituents fall within the categories of chemicals that should not be investigated with the model. More information on this can be found in the attached QPRF.

Principles of method if other than guideline:

- Software tool(s) used including version: EAWAG-BBD (last update: January 2016)
- Model(s) used: EAWAG-BBD Pathway Prediction System
- Model description: see attached QMRF
- Justification of QSAR prediction: see attached QPRF

GLP compliance:

no

Specific details on test material used for the study:

SMILES codes for calculation: see attached QPRF.

Oxygen conditions:

aerobic

Inoculum or test system:

other: model calculation

Details on source and properties of surface water:

The model makes predictions for chemicals exposed to air, moist soil or water at moderate temperature and pH

Parameter followed for biodegradation estimation:

other:

Details on study design:

For the purpose of this QSAR analysis, only products formed through "Very likely" and "Likely" and "Neutral" reactions were included.

Key result

Remarks on result:

other: Formation of 4 transformation products via aerobic degradation was predicted (1 transformation product was predicted to be not readily biodegradable, 3 were predicted to be readily biodegradable)

Transformation products:

not specified

The EAWAG-BBD PPS system predicted that the metabolites in the table below would be likely or very likely formed by aerobic microbial degradation.

#	Name	CAS number (EC number)	Smiles
1	4-(4-aminophenyl)sulfonylbenzene-1,2-diol	/	Nc1ccc(cc1)S(=O)(=O)c1ccc(O)c(O)c1
2	3-(4-aminophenyl)sulfonylhexa-2,4-dienedioate	/	Nc1ccc(cc1)S(=O)(=O)C(C=C/C([O-])=O)=CC([O-])=O
3	3-(3,4-dihydroxyphenyl)sulfonylhexa-2,4-dienedioate	/	Oc1ccc(cc1O)S(=O)(=O)C(C=C/C([O-])=O)=CC([O-])=O
4	3-[3-carboxylato-1-(carboxylatomethylene)allyl]sulfonylhexa-2,4-dienedioate	/	[O-]C(=O)C=C/C(=CC([O-])=O)/S(=O)(=O)C(C=C/C([O-])=O)=CC([O-])=O

Conclusions:

Degradation products of the substance were identified by use of QSAR. The EAWAG-BBD Pathway Prediction System identified four transformation products for the substance 4,4'-sulfonyldianiline to be formed by neutral or likely pathways by microbial degradation under aerobic conditions.

Executive summary:

In order to identify the relevant degradation products of the substance as a standard information requirement accordign to Column 1, Section 9.2.3 of Annex IX to REACH and for the assessment of potential PBT/vPvB properties, degradation products were predicted using the EAWAG-BBD Pathway Prediction System. The PBT/vPvB assessments of the predicted degradation products are included in the report "PBT assessment_degradation products_Dapsone.pdf" which can be found under the PBT assessment in Section 2.3. QMRF and QPRF documentation has also been included to support the QSAR modelling results.

Description of key information

A QSAR exercise was completed for endpoint coverage. The relevant degradation products of the substance were identified by means of EAWAG-BBD Pathway Prediction system model. Four degradation products were identified, and these were subsequentely assessed for their P (B and T) properties in view of the PBT/vPvB assessment.

The biodegradability of each of the degradation products was predicted using the QSAR model BIOWIN available in the EPI Suite software. Of the four degradation products, one was predicted to be not readily biodegradable. The remaining three degradation products were predicted to be readily biodegradable.