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Environmental fate & pathways

Biodegradation in water: screening tests

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Reference
Endpoint:
biodegradation in water: ready biodegradability
Remarks:
prediction
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
1. SOFTWARE: EPI Suite

2. MODEL: v4.11

3. BIODEGRADATION MODELS
Linear model (Biowin1)
The fast biodegradation probability for any  compound is calculated by summing, for all the fragments present in that compound, the fragment coefficient multiplied by the number of instances of the fragment in the compound (for MW, the value of that parameter is multiplied by its coefficient), and then adding this summation to the equation constant which is 0.7475.  

Non-linear model (Biowin2)
Calculation of the fast biodegradation probability for any compound begins by summing, for all the fragments present in that compound, the fragment coefficient multiplied by the number of instances of the fragment in the compound (for MW, the value of that parameter is multiplied by its coefficient), then adding this summation to the equation constant which is 3.0087.  The non-linear fast biodegradation probability is then calculated from the logistic equation, where total = 3.0087 + the summation as described above:
non-linear probability  =  exp(total) / (1 + exp(total) )

Ultimate and primary survey model (Biowin3 and Biowin4)
These two models estimate the time required for "complete" ultimate and primary biodegradation.  Primary biodegradation is the transformation of a parent compound to an initial metabolite.  Ultimate biodegradation is the transformation of a parent compound to carbon dioxide and water, mineral oxides of any other elements present in the test compound, and new cell material.  The models are based upon a survey of 17 biodegradation experts conducted by EPA, in which the experts were asked to evaluate 200 compounds in terms of the time required to achieve ultimate and primary biodegradation in a typical or "evaluative" aquatic environment (Boethling et al. 1994).  Each expert rated the ultimate and primary biodegradation of each compound on a scale of 1 to 5. The ratings correspond to the following time units:   5 - hours;  4 - days;  3 - weeks;  2 - months;  1 - longer.   It should be noted that the ratings are only semi-quantitative and are not half-lives.  
The ultimate or primary rating of a compound is calculated by summing, for all the fragments present in that compound, the fragment coefficient multiplied by the number of instances of the fragment in the compound (for MW, the value of that parameter is multiplied by its coefficient), and then adding this summation to the equation constant which is 3.1992 for Biowin3 and 3.8477 for Biowin4. 

Calculated rating                        Words assigned, representing expected total
(numerical value from model)       degradation time
>4.75 - 5                                 hours
>4.25 - 4.75                                 hours to days
>3.75 - 4.25                                 days
>3.25 - 3.75                                 days to weeks
>2.75 - 3.25                                weeks
>2.25 - 2.75                               weeks to months        
>1.75 - 2.25                                 months
<1.75                                         recalcitrant


Linear and Non-Linear MITI Biodegradation Model (Biowin 5 and Biowin 6)
Under its Chemical Substances Control Law (CSCL), the Japanese have tested approximately 900 discrete substances in the Ministry of International Trade and Industry (MITI)-1 test.  This protocol for determining ready biodegradability is among six officially approved as ready biodegradability test guidelines of the OECD (Organization for Economic Cooperation and Development).  A total dataset of 884 chemicals was compiled to derive the fragment probability values that are applied in this MITI Biodegradability method.  The dataset consists of 385 chemical that were critically evaluated as "readily degradable" and 499 chemicals that were critically evaluated as "not readily biodegradable".
The 884 compound dataset was divided into a training dataset (589 compounds) and a validation dataset (295 compounds).  The critical biodegradation evaluations (results of the MITI tests) were either "readily degradable" or "not readily degradable"; "readily degradable" was assigned a numeric value of 1 and "not readily degradable" was assigned a numeric value of 0 (0 to 1 is the full probability range). The basic approach for deriving the fragment values is very similar to the approach used for the original linear/non-linear model described above.
Although the majority of fragments in the new MITI models are identical to fragments in the models described above, the new MITI models incorporate various changes.  For example, to provide fuller characterization of alkyl chain length and branching, the original C4 terminal alkyl group fragment was replaced with a fragment set consisting of -CH3, -CH2 (both linear and ring types), -CH (both linear and ring types), and -C=CH (alkenyl hydrogen). The final MITI models contain 42 fragments and molecular weight as independent variables.

Anaerobic Biodegradation Model (Biowin 7)
Biowin7 estimates the probability of fast biodegradation under methanogenic anaerobic conditions; specifically, under the conditions of the "serum bottle" anaerobic biodegradation screening test (Meylan et al. 2007).  A total of 169 compounds with serum bottle test data were identified for use in model development.  This data set was not separated into separate training and validation sets: all available compounds were used for the regression. Each compound was scored "pass" or "fail" using 60% of theoretical gas production in 56 days (i.e. normal test duration) as the pass criterion; for model regression, Pass=1 and Fail=0.A set of 37 fragments was developed using existing fragments from the other BIOWIN models. Molecular weight is not used as a predictive variable. The probability of fast biodegradation for any compound is calculated by summing, for all the fragments present in that compound, the fragment coefficient multiplied by the number of instances of the fragment in the compound, and then adding this summation to the equation constant which is 0.8361.  
Guideline:
other: REACH Guidance on QSARs R.6
Parameter:
probability of ready biodegradability (QSAR/QSPR)
Remarks on result:
not readily biodegradable based on QSAR/QSPR prediction
Details on results:
Probability of Rapid Biodegradation (BIOWIN v4.10)
Biowin1 (Linear Model): 0.4552
Biowin2 (Non-Linear Model): 0.0716

Expert Survey Biodegradation Results:
Biowin3 (Ultimate Survey Model): 1.6743 (recalcitrant)
Biowin4 (Primary Survey Model): 2.7042 (weeks-months)

MITI Biodegradation Probability:
Biowin5 (MITI Linear Model): -0.3775
Biowin6 (MITI Non-Linear Model): 0.0003

Anaerobic Biodegradation Probability:
Biowin7 (Anaerobic Linear Model): -2.1875

Ready Biodegradability Prediction: NO

Ready Biodegradability Prediction: YES or NO

 

The criteria for the YES or NO prediction are as follows:  if the Biowin3 (ultimate survey model) result is "weeks" or faster (i.e. days, days to weeks, or weeks) AND the Biowin5 (MITI linear model) probability is >= 0.5, then the prediction is YES (readily biodegradable).  If this condition is not satisfied, the prediction is NO (not readily biodegradable).

 

This method is based on the application of Bayesian analysis to ready biodegradation data for US Premanufacture Notification (PMN) chemicals, derived collectively from all six OECD301 test methods plus OECD310.  The approach is fully described in Boethling et al. (2004).

 

The linear and nonlinear MITI models (Biowin5 and 6) also predict ready biodegradability, but for degradation in the OECD301C test only, and based exclusively on data from the Chemicals Evaluation and Research Institute Japan (CERIJ) database (http://www.cerij.or.jp/ceri_en/otoiawase/otoiawase_menu.html).

Validity criteria fulfilled:
not applicable
Remarks:
estimation by EPI Suite
Interpretation of results:
not readily biodegradable
Conclusions:
Based on prediction carried out with EPI Suite, the substance resulted as non ready biodegradable.
Executive summary:

Method

Estimate of probability of rapid biodegradation relying on BIOWIN v4.10 in EPI Suite prediction tool. The overall assessment is based on the responses given by different predictive models for biodegradability under various conditions: linear and non-linear models, ultimate and primary survey models, MITI linear and non-linear models, anaerobic linear model.

Results

The substance was predicted to be not ready biodegradable.

Description of key information

Not rapidly degradable based on:

- prediction of non ready biodegradability by EPI Suite v4.11

- biodegradation below 20 % in a inherent biodegradability test

Key value for chemical safety assessment

Additional information

The assessment over the biodegradability potential of the substance relied on both predicted data and experimental data.

To be more precise, an experimental study on inherent biodegradability was used as supporting evidence to the prediction of not ready biodegradability made by the EPI Suite tool (v4.11).

The substance resulted as non inherently biodegradable (biodegradation below 20 %) in a Zahn-Wellens test according to OECD guideline 302B.

On these bases, a potential of rapid biodegradation was excluded.