3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-indenyl propionate

Endpoint summary

Description of key information

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

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

Additional information

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

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

Introduction and hypothesis for the analogue approach

Cyclaprop has a tricyclodecenyl fused ring backbone to which a propionic 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 Cyclaprop in water the analogue approach is selected because for one closely related analogue estimated but sufficiently reliable DT50 value, similar to water-simulation-system information, can be derived.

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

Available experimental information: Cyclaprop and Cyclabute have 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 Cyclaprop 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: Cyclaprop 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 Cyclaprop (target) is a propyl 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 propyl chain of Cyclaprop.

Degradation pathways of Cyclaprop and Cyclabute based on experimental information:

Fig. 1   The degradation pathway of Cyclaprop and Cyclabute into Cyclaprop’s and Cyclabute’s alcohol (Cycla-alcohol: Cas no 3385-61-3) and to Cyclaprop’s and Cyclabute’s ketone (Cycla-ketone: Cas no 14888-58-5). In addition to these degradation products propionic 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 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 (readily biodegradable as presented on the ECHA dissemination site).

Degradation rate at 25°C: 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 Cyclaprop and Cyclabute also for Cyclaprop 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 about 6 days the maximum biodegradation is achieved both for Cyclaprop and Cyclabute. Therefore, the primary degradation half-life is considered to be 6 days.

Degradation rate at 12°C: The ready tests are generally performed at 20-25°C, while currently in the ECHA guidance the 12°C DT50 value is preferred. The DT50 of 6 days at 25°C can be converted to a half-life of 17 days at 12°C, which value will be used for Cyclaprop. 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 Cyclaprop and Cyclabute in 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 propionic 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 Cyclaprop, which is Frag 1. This ester functionality has the highest degradation value.

Fig. 3    Biowin 5 and 3 predictions for Cyclaprop showing that fragment 1 is the key fragment for degradation, which is the propionic 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 Cyclaprop the BIOWIN 5 and 3 values are 0.63 and 2.9, respectively, resulting in DT50’s of 12.3 and 10.8 days, respectively, which is in line with the primary degradation expected based on ester degradation as was seen in the ready biodegradability test of Cyclaprop.

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 Cyclaprop

For Cyclaprop 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 Cyclaprop because the degradation pathway and the primary degradation product (Cycla-alcohol) will be the same.

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

 

Data matrix of Cyclaprop using read across from Cyclabute

Common names	Cyclaprop Target	Cyclabute Key source
Chemical structures
Cas no	68912-13-0	93941-73-2
Empirical formula	C13H18O2	C14H20O2
Molecular weight	206	220
Physico-chemical data
Physical state	liquid	liquid
Melting point °C	< -20	< -20
Boiling point °C	263	273
Vapour pressure Pa (measured)	0.67	0.61
Water solubility mg/l (measured)	57	16
Log Kow (measured)	4.4 (HPLC, OECD TG 117)	5.1 (HPLC, OECD TG 117))
Biodegradation %	15	22
DT50 in water estimated at 25°C in days	RA from Cyclabute	6 (OECD TG 301F)
DT50 in water estimated at 12°C in days	RA from Cyclabute	17

 

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 Substances,

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 and Toxicology, ed. Whitacre, 117-178, D.M., Springer.