4-tert-pentylcyclohexanone

Endpoint summary

Description of key information

For Orivone the following results were derived:

Guideline	Test species	Endpoint	Result	Remark
OECD TG 203	Danio rerio	96-h LC50	4.0 mg/L	Data derived from read-across to p-tert.-Butylcyclohexanone (CAS # 98-53-3). Semi-static conditions and measured concentrations were used. Key study, rel. 1.
OECD TG 202	Daphnia magna	48-h LC50	43.2 mg/L	Data derived from read-across to   p-tert.-Butyl-trans-cyclohexanol (CAS # 21862-63-5). Semi-static conditions and nominal concentrations were used. Key study, rel. 1.
OECD TG 201	Desmodesmus subspicatus	72-h ErC50 72-h ErC10	60 mg/L 26 mg/L	Data derived from read-across to   p-tert.-Butylcyclohexanone (CAS # 98-53-3). Static conditions and measured concentrations were used. Key study, rel. 1.
OECD TG 209	Activated sludge, domestic	3-h EC50 3 -h EC10	517 mg/L 103 mg/L	Data derived from read-across to   p-tert.-Butylcyclohexanone (CAS # 98-53-3). Static conditions and nominal concentrations were used. Key study, rel. 1.

Additional information

The aquatic toxicity of Orivone is based on read-across from p-tert-butylcyclohexanone and p-tert butyl-trans-cyclohexanol. The read-across documentation is for fish, Daphnia, algae and microorganisms and is included in the study records of the respective endpoints. The read-across justification is also presented below:

Aquatic toxicity ofOrivone (CAS #16587-71-6) based on read-across from data available for p-tert-butylcyclohexanone (CAS #98-53-3) and p-tert butyl-trans-cyclohexanol (CAS #21862-63-5)

Introduction and hypothesis for the analogue approach

Orivone has a cyclohexanone backbone substituted with a(1,1)dimethyl-propyl moietyon theparaposition. For this substance no aquatic toxicity data are available. In accordance with Article 13 of REACH,lacking information can be generated by means of applying alternative methods such asin vitrotests, QSARs, grouping and read-across. For assessing the aquatic toxicity of Orivone the analogue approach is selected because for two closely related analogues, p-tert-butylcyclohexanoneandp-tert butyl-trans-cyclohexanolreliable aquatic toxicity data are available.

Hypothesis: Orivone has similar aquatic toxicity potential asp-tert-butylcyclohexanone and p-tert butyl-trans-cyclohexanol as these substances are similar in structures and related properties.

Available experimental information:For the source chemicalp-tert-butylcyclohexanone data are available from GLP guideline studies with fish, algae and activated sludge. For the source chemical p-tert butyl-trans-cyclohexanol data are available from a GLP guideline study with aquatic invertebrates.

The L(E)C50 values for fish, Daphnia, algae and microorganisms are 4.0, 43.2, 60 and 517 mg/L, respectively. The E(r)C10 for algae and microorganisms were 26 and 103 mg/L. The data are reliable without restriction (Klimisch 1).

Target chemical and source chemicals

Chemical structures of the target chemical and the source chemicals are shown in the data matrix, including physicochemical properties and available ecotoxicological information.

Purity / Impurities

Orivone containscis‐4‐(2‐methylbutan‐2‐yl)cyclohexanol (1.6%) as impurity.All purities of the source chemicals in the respective studies were ≥ 97%.There are no indicationsto expect a different aquatic toxic potential for Orivone compared to the source chemicals as a result of impurities.

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.

Analogue selection:Possible analogues were identified in the OECD QSAR toolbox by using structural similarity with a Tanimoto coefficient of 80%. Also, analogues from the RIFM database were identified and expert judgement was used for selection of the most appropriate read-across candidates.

Structural similarities and differences:The target and the source chemicals have an alkyl tail and either a ketone or alcohol as functional group attached to the cyclohexane ring. The source chemicalp-tert-butylcyclohexanonehas one methyl group less in the tail of the structure compared to Orivone and is thereforeexpected to have the same ecotoxicological effects. The source chemical p-tert butyl-trans-cyclohexanol also has one methyl group less in the tail of the structure compared to Orivone. Additionally, it has an alcohol group instead of a ketone. This chemical is a stereoisomer because of the chiral orientation of the hydroxyl and tert-butyl group. The trans-isomer is used as source chemical in this read-across and isexpected to have the same ecotoxicological effects.

Bioavailability:The source chemicals and the target chemical have similar bioavailability based on the similarity in chemical structure and physicochemical properties. The molecular weight of the target substance (Orivone) is 168.28 g/mol, which is in the same range as the sources p-tert-butylcyclohexanone and p-tert butyl-trans-cyclohexanol (154.25 g/mol and 156.27 g/mol, respectively). The log Kow values (3.4, 2.91 and 3.21 (calculated, ECOSAR), respectively) are comparable, as are the vapour pressures of the target and source chemicals (4.5, 23.1 and 1.04 at 25 °C). The water solubility of the target and source chemicals is above 100 mg/L (a relevant cut-off value for CLP classification).

Reactivity:Both the target and source substances are cyclohexanes and are substituted by either a ketone or alcohol and have an alkyl tail on theparaposition. These functional groups are not presenting reactivity beyond the neutral organic mode of action. This is supported by ECOSAR calculations provided in the data matrix.

Uncertainty of the prediction:There is no remaining uncertainty. There is no need to convert the toxicity levels of the source chemicals data towards Orivone, because of the comparable properties of the substances. Also, using the non-converted data is a worst-case approach (Orivone has a higher molecular weight) and as such will not lead to an underestimation of the effects.

Data matrix

The relevant information on physicochemical properties and toxicological characteristics are presented in the data matrix below.

Conclusions for hazard assessment and environmental classification

For Orivone no aquatic toxicity information is available. Read-across is performed from the structural analoguesp-tert-butylcyclohexanoneandp-tert butyl-trans-cyclohexanol. The lowest acute effect value is the LC50 for fish of p-tert-butylcyclohexanone: 4.0 mg/L; the one available ErC10 for algae is 26 mg/L, of structural analogue p-tert butyl-trans-cyclohexanol. Orivone has a higher molecular weight and therefore the same values will be used for Orivone.

Final conclusion on hazard and C&L:The lowest L(E)C50 for Orivone is the LC50 for fish being 4.0 mg/L and the one long-term for algae is 26 mg/L. These values will be forwarded for classification and labelling and the risk assessment.

Data matrix presenting physicochemical and ecotoxicological information on read-across for Orivone fromp-tert-butylcyclohexanone and p-tert butyl-trans-cyclohexanol

Source/target	Target	Source	Source
Common names	Orivone	p-tert-butylcyclohexanone	p-tert butyl-trans-cyclohexanol
Chemical structures
CAS No. generic	16587-71-6	98-53-3	21862-63-5 ( 98-52-2 generic)
EINECS	240-642-0	202-678-5	700-127-8
Tanimoto	1	0.83	0.77
Empirical formula	C11H20O	C10H20O	C10H20O
Molecular weight	168.28	154.251	156.267
Physical state	Liquid	Solid	Solid
Melting point °C	< -20 (IFF measured)	48 (measured) (EPISuite database match)	78 (measured) (ECHA dissemination site)
Boiling point °C	246.8 (IFF measured)	210.92 (estimated)	216.91 (estimated)
Vapour pressure Pa	4.2 (IFF measured at 24 °C)	23.1 (estimated)	0.74 (measured at 20 °C) (ECHA dissemination site)
Water solubility mg/L (measured)	370.8 (IFF measured at 24 °C)	590 (measured at 20 °C) (ECHA dissemination site)	106.1 (measured at 20 °C) (ECHA dissemination site)
Log Kow (measured)	3.9 (IFF measured at 25 °C)	-	3.09 (EPISuite database match)
Log Kow (calculated - ECOSAR)	3.4	2.91	3.21
Acute Aquatic toxicity
Fish 96-h LC50 in mg/L (experimental)	Read-across to CAS 98-53-3	4.0#	-
ECOSAR neutral organics; Fish 96-h LC50 in mg/L	7.7	19.5	6.9
Daphnia 48-h EC50 in mg/L (experimental)	Read-across to CAS 21862-63-5	-	43
ECOSAR neutral organics; Daphnia 48-h EC50 in mg/L	5.0	12.0	4.4
Algae 72-h ErC50 in mg/L (experimental)	Read-across to CAS 98-53-3	60	16 mg/L (ECHA dissemination site)
ECOSAR neutral organics; Algae 72-h ErC50 in mg/L	6.3	12.7	5.7
Microorganisms 3-h EC50 in mg/L (experimental)	Read-across to CAS 98-53-3	517	-
Long-term Aquatic toxicity
Algae 72-h ErC10 in mg/L (experimental)	Read-across to CAS 98-53-3	26	2.19 (ECHA dissemination site)
ECOSAR neutral organics; Algae 72-h NOErC in mg/L	2.2	4.0	2.0
Microorganisms 3-h EC10 in mg/L (experimental)	Read-across to CAS 98-53-3	103	-

#Calculated as the geometric mean of the LC0 and LC100