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 and its terrestrial toxicity

Test species	Method	Result EC10 / NOEC Mg/kg soil dw	Remarks
Eisenia fetida	Read across	57 (EC10)	The value is converted from Verdox (tested in an OECD TG 222), for which an EC10 of 45 mg/kg soil dw is derived.
Plants (6 species)	Read across	56 (EC10)	The value is converted from Verdox (tested in an OECD TG 208), for which an EC10 of 44 mg/kg soil dw is derived.
Soil micro-organisms	Read across	110 (NOEC)	The value is converted from Verdox (tested in an OECD TG 216), for which a NOEC of 100 mg/kg soil dw is derived.

Additional information

The PNEC soil for Cyclacet derived based on Equilibrium Partitioning from aquatic toxicity result in a value of 1.53 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 5.6 mg/kg soil dw. Cyclacet's terrestrial toxicity is derived from Verdox. The read across justification is presented below.

Cyclacet (EC no 911-369-0) and its terrestrial toxicity using read across from Verdox (Cas no 20298-69-5)

Introduction and hypothesis for the analogue approach

Cyclacet is an acetic 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 Cyclacet the analogue approach is selected because for one closely related analogue reliable soil toxicity information is available.

Hypothesis: Cyclacet’s terrestrial EC10/NOEC values can be derived from Verdox after conversion using molecular weight and log Kow.

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

Cyclacet 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:Cyclacet and Verdox have a similar hydrocarbon backbone to which the same acetic ester functionality is attached. These backbones have the same number of carbons. The difference is that Cyclacet 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.

Bioavailability:Cyclacet (target) and Verdox (source) have somewhat similar bioavailability based on the similarity in chemical structure and molecular weight Cyclacet, the lower log Kow of Cyclacet compared to Verdox is not too different to present a difference in bioavailability.

Mode of action (MoA): Cyclacet and Verdox have both the same acetic ester as a functional group and therefore the MoA is the same based on the same acetic ester as the functional group. The difference in log Kow between Cyclacet and Verdox 3.9 and 4.75 are accounted for when deriving the terrestrial toxicity values for Cyclacet as presented in Table 1 using the following equation: (Log NOEC/EC10 target (mmol) = Log NOEC/EC10 source (mmol) x log Kow source/Log Kow target).

Uncertainty of the prediction: The lower log Kow of Cyclacet compared to Verdox will result in higher EC10/NOECs for terrestrial organisms. This is supported with information from aquatic toxicity where, after conversion for molecular weight and log Kow, these two substances have very similar aquatic toxicity (See Table 2). 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 Cyclacet 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 45.1, 44 and 100 mg/kg dw soil for earthworm, plants and micro-organisms. For Cyclacet these EC10/NOECs are converted using molecular weight and log Kow differences. Final conclusion: Cyclacet has EC10/NOEC values of 56, 57 and 110 mg/kg dw for earthworms, plants and micro-organisms.

 

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

Common names	Cyclacet	Verdox
	Target	Source
Chemical structures
Cas no of the main isomer Cas no of the generic	2500-83-6 (5-yl) 54830-99-8	20298-69-5
EINECS no	911-369-0	243-718-1
REACH registration	Registered	Registered
Empirical formula	C12H16O2	C12H22O2
Molecular weight	192	198
Physico-chemical data
Physical state	liquid	Liquid
Melting point (°C)	< -20	29.8
Boiling point (°C)	247	232
Vapour pressure (Pa at 23°C)	2.12	9.72
Log Kow	3.9	4.75
Fate
Log Koc	2.62	3.12
Aquatic toxicity
Acute fish LC50 mg/L	15.8 (OECD TG 203) 10.3 (RA from Verdox after conversion)	5.6 (OECD TG 203)
Acute invertebrates EC50) mg/L	25 (OECD TG 202) 25 (RA from Verdox after conversion_	17 (OECD TG 202)
Acute algae 72h-EC50 mg/L	3.7 (OECD TG 201) 8.11 (RA from Verdox after conversion)	4.2 (OECD TG 201)
Chronic algae EC10 72-h in mg/l	1.2 (OECD TG 201)	0.57 (OECD TG 201)
Chronic algae EC10 in mg/l	1.6 (RA from Verdox after conversion)
Terrestrial toxicity
Earthworm (EC10) mg/kg soil dw	57 (RA from Verdox after conversion*)	45.1 (OECD TG 222)
Terrestrial plants (EC10, average of 6 species) mg/kg soil dw	56 (RA from Verdox after conversion*)	44 ((OECD TG 208)
Micro-organisms (NOEC) mg/kg soil dw	110 (RA from Verdox after conversion*	100 (OECD TG 216)

*Conversion is necessary in view of the difference in log Kow exceeding 0.5 (3.9 and 4.75, for Cyclacet and Verdox, respectively).

 

Table 1 Terrestrial toxicity conversion table to Cyclacet from Verdox

Substance	Species	Effect in mg/l source	MW Source	Mmol/L Source	Log mMol/l Source	Log Kow source	Log Kow target	Convert to Log Mmol/l target	Convert to 10^	MW Target	EC50 value in mg/l Cyclacet
Cyclacet	Earthworm	45.1	198	0.2278	-0.64249	4.75	3,9	-0.52752	0.2968	192	56.988
	Plant	44	198	0.2222	-0.65321	4.75	3,9	-0.53632	0.2909	192	55.844
	Micro-org	100	198	0.5051	-0.29667	4.75	3,9	-0.24358	0.5707	192	109.58

 

 

Table 2 Aquatic toxicity conversion table to Cyclacet from Verdox

Substance	Species	Effect in mg/l source	MW Source	Mmol/L Source	Log mMol/l Source	Log Kow source	Log Kow target	Convert to Log Mmol/l target	Convert to 10^	MW Target	EC50 value in mg/l Cyclacet
Cyclacet	Algae EC50	4,2	198	0.0212	-1.,67342	4.75	3.9	-1.37396	0.0423	192	8.1159
	Daphnia	17	198	0.0859	-1.06622	4.75	3.9	-0.87542	0.1332	192	25.579
	Fish	5,6	198	0.0283	-1.54848	4.75	3.9	-1.27138	0.0535	192	10.278
	Algae EC10	0,57	198	0.0029	-2.54079	4.75	3.9	-2.08612	0.0082	192	1.5746