Reaction mass of 3a,4,5,6,7,7a-hexahydro-4,7-methanoinden-5-yl acetate and 3a,4,5,6,7,7a-hexahydro-4,7-methanoinden-6-yl acetate

Biodegradation in water and sediment: simulation tests

Description of key information

The DT50 of Cyclacet is 17 days at 12oC, which is based on a compilation of data that resembles the outcome of the OECD TG 309 test sufficiently. This DT50 is derived from ready biodegradability curve (OECD TG 301F), showing maximum primary degradation after 6 days at 25oC, the identification of the degradation products in this test, correction to 12oC (using EUSES) and supporting QSAR model results from Arnot et al. (2005). The primary biodegradation product are Cycla-alcohol and Cycla-ketone (measured log Kow values are 2.4 and 3.3, respectively).

Key value for chemical safety assessment

Half-life in freshwater:

17 d

at the temperature of:

12 °C

Additional information

In this section it is outlined that Cyclacet fulfils the Annex IX requirements. The derivation of the DT50 for the water compartment is presented in the Overall Endpoint summary because information from screening study in combination with other information is used.

Cyclacet’s Annex IX requirements on derivation of half-lives in water without experimental testing (OECD TG 309) in these compartments.

 

Summary: Further biodegradation in water-simulation-systems for Cyclacet is not needed because the substance is not hazardous (absence of classification) on which bases only a hazard assessment is needed (REACH regulation, Annex 1 on CSA). The substance is not PBT or vPvB, based on absence of bioaccumulation in fish and in air-breathing organisms, the substance is not T because it is not hazardous for human health and aquatic organisms. In addition, a half-life of the parent substance can be estimated using information from its structure and acetic ester functionality, the ready biodegradability tests and the analysis and identification of the remaining parent substance and the metabolites, which is outlined in the DT50 derivation for water.

 

Introduction

The present document outlines the available information showing the absence of need for further simulation testing based on

1) Regulatory requirements as presented in the Regulation

2) ECHA guidance

3) A DT50 for Cyclacet that can sufficient accurately be predicted, because Cyclacet is an acetic ester

4) The outcome of the OECD TG 309 versus the results obtained with other than experimental methods.

5) QSAR estimates support the primary biodegradation of Cyclacet into its alcohol and acid.

 

Annex IX requirements

According to Annex IX further biotic degradation shall be proposed by the registrant if the chemical safety assessment according to Annex I indicates, the need to investigate further the degradation of the substance and its degradation products. In the LRs view the CSA does not indicate the need for further testing based on the following:

 

1) The Regulation presents the following

1a) According to Annex I (0.6.1) the Lead registrant needs to present a CSA including Human health hazard assessment, Human health hazard assessment of physico-chemical properties, Environmental hazard assessment and a PBT/vPvB assessment.

1b) According to 0.6.3 an Exposure assessment and a Risk characterisation only needs to be performed when the substance is classified for any of the above hazards (0.6.1)

Applying this to Cyclacet

1a) Cyclacet does not need to be classified for human health (including physico-chemical properties) or the environment according to EU CLP (1272/2008 and its amendments) based on the available information for Annex IX, therefore the CSA can be limited to the human health and environmental hazard assessment. This is supported with ECHA guidance (R7b., page 247-248, 2017) in which it is presented that further biodegradation testing can be needed to refine the PEC as is indicated in the title of the Table: ‘Table R.7.9-4 Selection of appropriate biodegradation studies for PEC assessments’, For Cyclacet only a hazard assessment is needed but not a risk characterisation and therefore no PEC derivation.

1b) Cyclacet is also not a PBT or vPvB substance because the substance is not B for fish and air-breathing organisms and not T, despite the screening criteria showing P. This follows from the PBT /vPvB strategy in ECHA guidance R.11.4.1.1.1, Figure R.11-3 (4) at page 41.

For air-breathing organism the exposure will be to the degradation product Cycla-alcohol which has a measured log Kow of 2.4. This alcohol will be glucuronated and because Glucuronic acid has a log Kow of -2.57) the log Kow of the Cycla-alcohol-glucuronic acid drops below the cut off value of 2 (see also toxico-kinetic section).

 

2) ECHA’s further guidance: In one of ECHAs tip and tricks webinars (2014) on degradation it is presented that degradation is an important endpoint to fulfil the following regulatory needs:

2a) Persistency assessment, to identify whether a chemical has PBT or vPvB properties;

2b) Hazard assessment: To determine the potential to cause long-term adverse effects in environmental hazard classification;

2c) Risk assessment: To determine the Predicted Environment Concentration (PEC) of a chemical in environmental exposure assessment for use in risk characterisation.

Applying this to Cyclacet

2a) In Cyclacet’s PBT assessment the substance is not considered PBT. The substance is potentially P based on its non-ready biodegradability. It is not T because the substance is not classified for the environment or for human health. The substance is not B for aquatic organisms, because its BCF in fish is 156 l/kg. The substance is not B for air-breathing organisms because Cyclacet is fully metabolised in Cycla-alcohol (measured log Kow 2.4) and Acetic acid. Cycla-alcohol will be glucuronated and removed from the body. The log Kow of Cycla-alcohol-glucuronic acid will be much below < 2 based on the log Kow of glucuronic acid (-2.57). Acetic acid is a normal constituent of the body. This means that Cyclacet is not PBT in absence of B and T. The overall PBT/vPvB conclusion will not change and therefore further testing is not required.

2b) The substance does not need to be classified for the environment because all long-term aquatic organisms (fish, Daphnia and algae) have EC10/NOEC value > 1 mg/l.

2c) In absence of hazard there is no need to do an exposure assessment and derive a PEC. Therefore further biodegradation studies do not fulfil a regulatory need.

 

3) Cyclacet, its half-life and its metabolites (see section 4)

The Cyclacet’s half-life can be sufficient accurately be derived for fulfilling Annex IX, using existing biodegradation pattern in screening studies, measuring the metabolites therein.

 

4) Cyclacet’s ready biodegradability tests versus expected outcomes of OECD TG 309: Relation between the half-lives and degradation products presented:

4a)Firstly, all the ready biodegradation tests are considered very stringent tests but the OECD TG 309 test is more stringent. In the latter test lower substance concentrations, lower bacteria concentrations and a lower temperature at which the test should be performed (12o versus 20-25oC) have to be used. As a result the pseudo half-life found in the ready test will need to be converted to 12oC.

It has been experimentally shown that the tricyclodecanyl backbone is more stable in the ready biodegradation tests and that these are still present after 60 days in prolonged tests (Cyclabute information). From these data and the expectation that the OECD 309 test is more stringent than the biodegradation ready test the same degradation products can be found.

4b)Secondly, from the OECD TG 309 test, more information can be retrieved compared to a ready biodegradation tests but this additional information will have limited influence on the final results.

4c)Thirdly, difference in experimental procedures will have limited influence on the results. There is no mass balance but considering volatility, the evaporation loss is limited based on the Henry law’s constant of 1.1 Pa.m3/mol at 12oC. Considering adsorption, Cyclacet’s adsorption to suspended solids will also be limited due to a low log Koc of 2.62. This value indicates that Cyclacet will mainly remain in the water phase (93% as is estimated in the Simple Treat model). There is no lag phase seen in the degradation studies and because Cyclacet has an acetic group this group will be biodegraded first, which will also occur in the OECD TG 309 test.

In summaryon Cyclacet’s ready tests versus the OECD TG 309: the key elements of the OECD TG 309 can be deduced from the ready biodegradability tests based on the pattern of degradation, and the experimental determination of the parent and the key metabolites.

5) QSAR modelsas included in the discussion on simulation testing show that the predicted half-lives are 10-12 days which is in line with the derived values. The QSAR model predictions are included in the derivation of the DT50.