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

Endpoint summary

Description of key information

In the decision letter from ECHA of 21 October 2021 (CCH-D-2114569822-39-01/F) Long-term toxicity testing on terrestrial invertebrates (OECD TG 222 or 220 or 232) or a Long-term toxicity test to terrestrial plants (OECD TG 208 with at least six species or ISO 22030) with Cyclaprop was requested. Based on the substance properties, it was decided by the lead registrant to conduct an OECD TG 222. In addition, an Effects on soil micro-organisms test (EU C.21./OECD TG 216) with Cyclaprop was requested. The deadline for submission is January 26th 2023, but unfortunately, the test report will not be available before that date. Quotations from several labs were requested, but due to non-availability of some labs, it took some time to find the right lab to perform the study on the shortest notice. The OECD 216 study was initiated on 16 November 2022 and the final results are expected to be available by the end of February 2023. The OECD 222 study will be initiated on 23 February 2023 and the final results are expected to be available by the end of June 2023. The dossier will be updated as soon as possible after receiving the final reports.

 

Cyclaprop and its terrestrial toxicity

Test species	Method	Result EC10 / NOEC (mg/kg soil dw)
Eisenia fetida	Read across from Verdox tested in OECD TG 222	45 (EC10)
Plants (6 species)	Read across from Verdox tested in OECD TG 208	44 (EC10)
Soil micro-organisms	Read across from Verdox tested in OECD TG 216	100 (NOEC)

Additional information

The PNEC soil for Cyclaprop derived based on Equilibrium Partitioning from aquatic toxicity result in a value of 2.24 mg/kg dw soil, showing similar results as when the PNEC is derived from long-term terrestrial toxicity based on read across from Verdox, which results in a PNEC of 4.4 mg/kg soil dw. Cyclaprop's terrestrial toxicity is derived from Verdox. The read across justification is presented below.

Cyclaprop (Cas no 68912-13-0) and its terrestrial toxicity using read across from Verdox (Cas no 20298-69-5)

Introduction and hypothesis for the analogue approach

Cyclaprop is a propionic ester attached to a tricyclodecenyl fused ring backbone. For this substance no experimental terrestrial toxicity information is available. In accordance with Article 13 of REACH, lacking information can be generated by means of applying alternative methods such as QSARs, grouping and read-across. For assessing the terrestrial toxicity of Cyclaprop the analogue approach is selected because for one closely related analogue reliable soil toxicity information is available.

Hypothesis: Cyclaprop’s terrestrial EC10/NOEC values can be derived from Verdox based on structural similarity and similarity in environmental fate and aquatic toxicity.

Available experimental information: For Verdox, long-term terrestrial toxicity information is available for earthworms (OECD TG 222), plants (OECD TG 208, 6 species) and on soil micro-organisms (OECD TG 216) performed according to current guidelines, which all receive Klimisch 1. The EC10/NOEC values are presented in the Data matrix.

Target chemical and source chemical(s)

Chemical structures of the target chemical and the source chemicals are shown in the data matrix below. Physico-chemical properties thought relevant for aquatic and terrestrial toxicity are listed in the Data matrix.

Purity and impurities

Cyclaprop is a reaction mass and is a mixture of two very similar isomers which differ in the position of the double bond at a 5yl or 6yl-position. 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 Verdox have a hydrocarbon backbone to which the same ester functionality is attached. These backbones have the same number of carbons. The difference is that Cyclaprop has an additional hydrocarbon ring structure in which an unreactive double bond is present, while Verdox has a hydrocarbon tert-butyl group attached to its cyclohexyl ring. In addition, Verdox is an acetic ester while Cyclaprop is a propionic ester.

Bioavailability: Cyclaprop (target) and Verdox (source) have similar bioavailability based on the similarity in chemical structure, molecular weight and log Kow values.

Environmental fate: Cyclaprop and Verdox are both not readily biodegradable and have the same adsorption potential: Log Koc is 3.1.

Mode of action (MoA): Cyclaprop and Verdox have both a hydrocarbon backbone and an ester as functional group and therefore the MoA is the considered the same. As the difference in log Kow between Cyclaprop and Verdox is below 0.5 (4.4 and 4.75, respectively) and log Koc values are 3.1 no conversion of effect levels is needed. This is supported with the aquatic effect levels, which are similar between Cyclaprop and Verdox (see data matrix).

Uncertainty of the prediction: There are no other uncertainties than those already accounted for.

Data matrix

The relevant information on physico-chemical properties and toxicological characteristics are presented.

Conclusions for terrestrial toxicity

For Cyclaprop no terrestrial toxicity information is available, but for the related analogue Verdox long-term terrestrial toxicity is available and read across can be applied. When using read across information, the result derived should be applicable for risk assessment and it should be presented with adequate and reliable documentation, which is presented in the current document. For Verdox long-term terrestrial toxicity is available resulting in EC10/NOECs of 45, 44 and 100 mg/kg dw soil for earthworm, plants and micro-organisms, respectively. This effect levels can be used for Cyclaprop without conversion because the log Kow values are sufficiently similar.

Final conclusion: Cyclaprop has EC10/NOEC values of 45, 44 and 100 mg/kg dw for earthworms, plants and micro-organisms, respectively.

 

Data matrix supporting the Cyclaprop terrestrial toxicity information using read across from Verdox

Common names	Cyclaprop	Verdox
	Target	Source
Chemical structures
Cas no generic	68912-13-0	20298-69-5
EINECS no	272-805-7	243-718-1
REACH registration	Registered	Registered
Empirical formula	C13H18O2	C12H22O2
Molecular weight	206	198
Physico-chemical data
Physical state	liquid	Liquid
Melting point (°C)	< -20	29.8
Boiling point (°C)	263	232
Water solubility	57	10
Log Kow	4.4	4.75
Fate
Log Koc	3.11	3.12
Aquatic toxicity
Acute fish LC50 mg/L	6.7 (OECD TG 203)	5.6 (OECD TG 203)
Acute invertebrates EC50 in mg/L	>14 (OECD TG 202)	17 (OECD TG 202)
Acute algae EC50 in mg/L	2.5 (OECD TG 201)	4.2 (OECD TG 201)
Chronic fish EC10 in mg/L	0.86 (OECD TG 210)	No data
Chronic invertebrates EC10 in mg/L	1.0 (OECD TG 211)	0.99 (OECD TG 211)
Chronic algae EC10 in mg/L	1.9 (OECD TG 201)	0.57 (OECD TG 201)
Terrestrial toxicity
Earthworm (EC10) mg/kg soil dw	RA Verdox	45 (OECD TG 222)
Terrestrial plants (EC10, average of 6 species) mg/kg soil dw	RA Verdox	44 (OECD TG 208)
Micro-organisms (NOEC) mg/kg soil dw	RA Verdox	100 (OECD TG 216)
EPM method mg/kg bw	2.24	In absence of experimental long-term fish toxicity this is not calculated.