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

Endpoint summary

Description of key information

Cyclacet ready biodegradability (OECD TG 301F): not readily biodegradable

Cyclacet DT50 in water-sediment using ready biodegradability tests, analogue information and QSARs: 17 days (12oC)

Additional information

Cyclacet's biodegradation profile is presented using read across from Cyclabute together with Cyclacet's DT50 derivation. This is presented here because both the biodegradation profile and the metabolic identification is used to derive the DT50.

Cyclacet and its estimated DT50 in water using biodegradation information from Cyclacet and read across information from Cyclabute

Introduction and hypothesis for the analogue approach

Cyclacet has a tricyclodecenyl fused ring backbone to which an acetic ester is attached. For this substance, data on biodegradation are available but no DT50 value from a water-simulation system.

In accordance with Article 13 of REACH,lacking information can be generated by means of applying alternative methods such QSARs, grouping and read-across. For assessing the half-life of Cyclacet in water the analogue approach is selected because for one closely related analogue estimated but sufficiently reliable DT50 value, similar towater-simulation-system information, can be derived.

Hypothesis: Cyclacet has the same DT50 value in a water-simulation-system as Cyclabute.

Available experimental information: Cyclacet and Cyclabutehave ready biodegradability information from a water – screenings –system, with a Klimisch 1 score. From the ready biodegradability study with Cyclabute a DT50 can be derived for the water compartment (water-simulation-system) because the parent substance and the key degradation products were determined on which basis a DT50 value can be estimated.

Target chemical and source chemical(s)

Chemical structures of the target chemical and the source chemical are shown in the data matrix. Also, physico-chemical properties thought relevant for biodegradation are listed in there.

Purity / Impurities

The purity, the constituents and impurities of Cyclacet indicate a similar biodegradation potential. The impurities are all below < 1%.

Analogue approach justification

According to Annex XI 1.5 read across can be used to replace testing when the similarity can be based on a common backbone and a common functional group. When using read across the result derived should be applicable for C&L and/or risk assessment and it should be presented with adequate and reliable documentation, which is presented below.

Structural similarities and differences:Cyclacet and Cyclabute have the same hydrocarbon backbone, a tricyclodecenyl fused ring structure with an unsaturated bond in the outside ring. On the other side of the ring an ester bond is attached with a short alkyl chain. The alkyl chain of Cyclacet (target) is an ethyl chain while the source Cyclabute has an isobutyl chain. Cyclabute will show somewhat higher biodegradation because the isobutyl will present a higher part of the substance compared to the ethyl chain of Cyclacet.

Degradation pathways of Cyclacet (read across) and Cyclabute based on experimental information:

 

Fig. 1    The degradation pathway of Cyclacet and Cyclabute into Cyclacet’s and Cyclabute’s alcohol (Cycla-alcohol: Cas no 3385-61-3) and to Cyclacet’s and Cyclabute’s ketone (Cycla-ketone: Cas no 14888-58-5). In addition to these degradation products acetic acid and isobutyl acid, respectively, will be formed but these will be consumed by bacteria and therefore these are not identified in the test solutions.

 

Defined endpoint DT50 for water – simulation-system: For the source substance, Cyclabute, a DT50 can be derived from its prolonged ready biodegradability test. In this ready biodegradability test 22% biodegradation in 28-days is seen, indicating that most of the alkyl part of Cyclabute is biodegraded but not the tricyclodecenyl backbone of the ester (Cycla-alcohol and its isobutyl part has a MW of 150 and 72, respectively, the isobutyl part making up ca. 30% of the molecule). The formation of Cycla-alcohol his is confirmed by determining the degradation products in this ready test.

Degradation products: The main biodegradation product is Cyclabute alcohol (82% of the relative peak area) and the minor is Cyclabute ketone (18% of the relative peak area). Also, the log Kow of these were determined being 2.4 and 3.3, respectively. The alkyl part of this Cycla-ester has not been found because an iso-butyl acid will biodegrade fast.

Degradation rate at 25oC: The percentage degradation after 28 and 61 days shows that after 28 days no additional biodegradation took place. Therefore, it can be assumed that the degradation products after 28 days are the same as after 61 days. This means that the DT50 of < 61 days is actually a DT50 of < 28 days. In view of the structural analogy between Cyclabute and Cyclacet also for Cyclacet a DT50 of < 28 days can be derived. The half-life of < 28 day is however conservative as can be seen from the biodegradation curves. Within 6 days the maximum biodegradation is achieved both for Cyclacet and Cyclabute. Therefore the primary degradation half-life is considered to be 6days.

Degradation rate at 12oC: The ready tests are generally performed at 20-25oC, while currently in the ECHA guidance the 12oC DT50 value is preferred. The DT50 of 6d at 25oC can be converted to a half-life of 17d at 12oC, which value will be used for Cyclacet. This can be done with the equation presented in Fig. 2 as presented in EUSES.

Fig. 2 Equation to convert DT50s from one temperature to another

 

Uncertainty of the prediction considering structural differences: The uncertainty on the primary degradation in the water compartment is minor between Cyclacet and Cyclabutein view of the minor structural differences and anticipated degradation pathways. In addition, the ester degradation is likely in all compartments as e.g. shown by Wheelock et al. (2008). Therefore, there is limited uncertainty on the biodegradation of the ester.

Uncertainty of the prediction considering test systems (ready tests versus water simulation tests ):

In general, the percentage biodegradation in biodegradability tests is not used to derive DT50s when the parent substance is not readily biodegradable.

The BIOWIN models support the biodegradation of the ester as an example the prediction is shown in which the acetic ester, Frag. 1, is the key fragment that has the highest degradable value.

Firstly it is shown in Figure 3 that BIOWIN 5 and BIOWIN 3 models support the biodegradation of the ester part of Cyclacet, which is Frag 1. This ester functionality has the highest degradation value.

 

Fig. 3    Biowin 5 and 3 predictions for Cyclacet showing that fragment 1 is the key fragment for degradation, which is the acetic ester.

 

Secondly a half-life in water can be estimated with Arnot et al. (2005):

Arnot et al. (2005) have presented half- lives based on BIOWIN results and experimental testing. They have predicted half-lives for ready biodegradability (BIOWIN 5) and for ultimate biodegradation (BIOWIN 3).

 

The equation of the half-life derived from the Ready biodegradability BIOWIN 5 model is:

DT50 in days: 10^(-1.86*BIOWIN 5 value + 2.23)

The equation of the half-life derived from the Ultimate biodegradability BIOWIN 3 model is:

DT50 in days: 10^(-1.07*BIOWIN 3 value + 4.12)

 

For Cyclacet the BIOWIN 5 and 3 values are 0.61 and 2.9, respectively, resulting in DT50’s of 12.4 and 10-days, respectively, which is in line with the primary degradation expected based on ester degradation as was seen in the ready biodegradability test of Cyclacet.

 

In addition, Arnot et al. (2005) have presented half- lives based on BIOWIN results and experimental testing. They have predicted half-lives for ready biodegradability (BIOWIN 5) and for ultimate biodegradation (BIOWIN 3). The ready biodegradability equation is: o DT50 in days: 10^(-1.86*BIOWIN 5 value + 2.23); For Ultimate biodegradability the equation is: o DT50 in days: 10^(-1.07*BIOWIN 3 value + 4.12). For Cyclacet the BIOWIN 5 and 3 values are 2.9 and 0.61, resulting in DT50’s of 10.4 and 12-days,respectively, which is in line with the primary degradation expected based on ester degradation.

Data matrix

The relevant information on physico-chemical properties and biodegradation characteristics are presented in the data matrix below.

Conclusions on the half-life of Cyclacet

For Cyclacet no DT50 is available for the water compartment. For a closely related analogue, Cyclabute, a DT50 can be estimated, which was tested in a similar ready biodegradability test but with additional identification of the parent and its metabolites. When using read across the result should be applicable for risk assessment and accompanied with adequate and reliable documentation. This documentation is presented in the current document. For Cyclabute a DT50 of 17 days in water was derived, which can be directly applied to Cyclacet because the primary degradation products will be the same.

Final conclusion on DT50 of Cyclacet: Cyclacet has a DT50 in water of 17 days.

 

Data matrix of Cyclacet using read across from Cyclabute

Common names	Cyclacet Target	Cyclabute Key source
Chemical structures
Cas no 5-yl Cas no of the generic	- 54830-99-8	67634-20-2 93941-73-2
Empirical formula	C12H16O2	C14H20O2
Molecular weight	192	`220
Physico-chemical data
Physical state	liquid	liquid
Melting point °C	< -20	< -20
Boiling point °C	247	273
Vapour pressure Pa (measured)	2.1	0.61
Water solubility mg/l (measured)	186	16
Log Kow (measured)	3.9 (HPLC, OECD TG 117)	5.1 (HPLC, OECD TG 117))
Biodegradation %	10	22
DT50 in water estimated at 25oC in days	RA from Cyclabute	6d (OECD TG 301F)
DT50 in water estimated at 12oC in days	RA from Cyclabute	17 d

 

References

Arnot J, Gouin T and Mackay D, 2005. Practical Methods for Estimating Environmental Biodegradation Rates, Report to Environment Canada. CEMN Report No 200503. Canadian Environmental Modelling Network, Trent, University, Peterborough, ON, Canada,https://www.trentu.ca/academic/aminss/envmodel/CEMNReport200503.pdf, site visited, October 2018.

 

Lijzen, J.P.A. and Rikken, M.G.J., 2004, EUSES, European System for the Evaluation of Susbstances,

https://www.rivm.nl/bibliotheek/rapporten/601900005.pdf

 

Wheelock, C.E., Philips, B.M., Anderson, B.S., Miller, J.L., Miller, M.J., and Hammock, B.D., 2008, Application of carboxylesterase activity in environmental monitoring and toxicity identification evaluations, (TIEs), in Reviews of Environmental Contamination an Toxicology, ed. Whitacre, 117-178, D.M., Springer.