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Administrative data

Description of key information

Skin corrosion: Not corrosive based on read-across from alpha-Terpineol: OECD TG 404


Skin irritation: Skin irritant Cat 2 based on read-across from alpha-Terpineol: OECD TG 404


Eye irritation: Eye irritation Cat 2 based on read-across from Terpineol multi: OECD TG 405


Respiratory inhalation: Not a respiratory irritant in absence of human data for Terpene hydrocarbon alcohols and Terpineols and absence of corrosion of Terpineol (alpha and multi)

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Terpene hydrocarbon alcohols skin and eye irritation is based on read-across from alpha-Terpineol and Terpineol multi. The executive summaries of the source information are presented below followed by the read-across rationale.


 


Alpha-Terpineol and its skin irritation


For alpha-Terpineol, an in vivo skin irritation study is available. In three primary dermal irritation studies performed according to OECD guideline 404 and in compliance with GLP, 3 or 4 albino rabbits were dermally exposed to 0.5 mL of undiluted alpha-Terpineol under a semi-occlusive patch for 4 hours to intact skin of the flank. Animals were then observed for 7 days. Irritation was scored by the method of Draize at 1, 24, 48 and 72 hours and 7 days after exposure.  Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals of the first test were 1.67, 2 and 2.33 for erythema score and 2, 2.33 and 3 for oedema score. For the second test the mean individual scores were 2, 2.67, 2 and 2 for erythema score and 3, 3, 2.67 and 1.67 for oedema score. For the third test the mean individual scores were 2, 2, 1.67 and 2 for erythema score and 2.67, 2, 0.67 and 3 for oedema score. Under the test conditions the substance is considered to be irritating to the skin because the average oedema score exceeded 2 (DSD C&L) or 2.5 (CLP) and the effects were not fully reversible within the observation period of 7 days. These data indicate that alpha-Terpineol has irritating properties to the skin (Cat. 2).


 


Terpineol multi and its eye irritation


For Terpineol Multi, an in vivo eye irritation study according to OECD TG 405 and in compliance with GLP criteria is available. In this study, 3 healthy adult female rabbits of the New Zealand White strain were exposed to 0.1 mL of undiluted Terpineol multi in one eye while the other eye corresponded to the control. The eyes were examined unwashed and the changes were observed at 1, 24, 48 and 72 hours after dosing and graded (scale of lesion scores according to Directive n° 2004/73/EC and OECD guideline 405). The ocular reactions observed during the study have been moderate. The individual mean scores for conjunctival chemosis were 1.0, 1.0 and 1.7, conjunctival redness scores were 2.0, 1.7 and 1.3, cornea opacity scores were 2.0, 2.0 and 0.7 and iris lesion scores were 0.0 for all animals. At the conjunctivae level, a moderate redness, noted 24 h after the test item installation and totally reversible between the 6th and 7th day of the test, was associated with a moderate chemosis, noted 1h after the test item instillation and totally reversible between the 5th and 6th day of the test. At corneal level, moderate opacity was observed 24 h after the test substance administration and totally reversible between the 3rd and 6th day. Under these test conditions, Terpineol multi is considered as irritating to eyes (Cat.2).


 


Terpene hydrocarbon alcohols respiratory irritation


For respiratory irritation mostly human data are used for the assessment because no suitable in vitro or in vivo tests are available that can identify respiratory irritation. There are no human data such as indicated in R7.2.3 of the ECHA guidance that indicate respiratory reactions of the substance e.g. from consumer experience or occupational exposure. In addition, the substance is not corrosive or severely irritating which further minimizes the respiratory irritation hazard (REACH guidance: 7.2.1.2).


The skin and eye irritation of Terpene hydrocarbon alcohols using read across from alpha-Terpineol (CAS# 98-55-5) and Terpineol Multi (CAS# 8000-41-7).


Introduction and hypothesis for the analogue approach


Terpene hydrocarbon alcohols have the following constituent types of substances: Solely hydrocarbons-terpene type, Alcohol-type, Ketone-type and Ether-type all having a saturated or unsaturated cyclic hydrocarbon backbone. For this substance no skin and eye irritation information is available. In accordance with Article 13 of REACH, lacking information can be generated by other means than experimental testing, i.e. applying alternative methods such as QSARs, grouping and read-across. For assessing the skin and eye irritation potential the information from the constituent Terpineol is used, which can represent the Terpene hydrocarbon alcohols.


Hypothesis: Terpene hydrocarbon alcohols have the same skin and eye irritation potential as alpha-Terpineol and Terpineol multi.


Available information, Skin irritation: Alpha-Terpineol is tested in a rabbit skin irritation test (OECD TG 404, Rel. 1). The substance is considered to be irritating to the skin (Cat 2) because the average oedema score exceeded Draize score 2.5 and the effects were not fully reversible within the observation period of 7 days.


Eye irritation: Terpineol multi is tested in an in vivo eye irritation test (OECD TG 405, Rel. 1). Based on moderate ocular reactions, especially cornea opacity, though reversible within 7 days, result in eye irritation (Cat 2).


Target chemical and source chemical(s)


Constituent types of the target substance and chemical structure of the source substances are shown in the data matrix, including physico-chemical properties and toxicological information, thought relevant for skin and eye irritation.


Purity / Impurities


Constituent types of the target substance are covered by the presented constituent types, there are no other constituent that impacts the skin and eye irritation.


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.


Analogue selection: For Terpene hydrocarbon alcohols their key constituents alpha-Terpineol and Terpineol Multi (with alpha-Terpineol as its main constituent) being representative for at least 40% of the substance, were selected as source because for these skin and eye information is available, which can be used for read across.


Structural similarities and differences: The Terpene hydrocarbon alcohol constituent types have alpha-Terpineol/Terpineol as key constituents and therefor the same structures. The differences with the other constituent types can be presented as follows. Alcohol-type has a saturated or unsaturated cyclohexyl ring with a secondary or tertiary alcohol. The ones with the saturated bonds are expected to be less electrophilic compared to the ones with the unsaturated bones. The unsaturated ones can also represent the Solely hydrocarbon-terpene type. The latter type has a very similar backbone but often have an additional unsaturated bond in the ring instead of an alcohol group. Also the Ketones have similar rings but the functional group is a ketone instead of an alcohol. These groups, alcohol, double bond, ketone have similar electrophilicity. The Ether in the aromatic Ether is not very electrophilic either. Its double bond adjacent to the aromatic ring is more electrophilic. In view of its presence in the Terpene hydrocarbon alcohols < 4%, this reactivity is covered in the overall skin and eye irritation potential.


Skin and eye tissue absorption: All Terpene hydrocarbon alcohol constituents have molecular weights, are liquids and physico-chemical properties, log Kow, that present potential absorption.


Skin and eye irritation reactivity: The Terpene hydrocarbon constituents have similar electrophilicity and therefore similar reactivity. The saturated Alcohol and Ketones types are slightly less and cis-Anethole slightly more reactive all have lower presence in the Terpene hydrocarbon alcohols and there the reactivity of this substance can be presented with alpha-Terpineol and Terpineol multi.


Uncertainty of the prediction: There are no uncertainties other than those already addressed above.


Data matrix


The relevant information on physico-chemical properties and toxicological characteristics are presented in the Data Matrix.


Conclusions on skin and eye irritation for hazard and risk assessment


For Terpene hydrocarbon alcohols no skin and eye irritation information is available but for its key constituents alpha-Terpineol and Terpineol multi such information is available, which can be used for read across and fill the data gap. When using read across the result derived should be applicable for C&L and/or risk assessment and be presented with adequate and reliable documentation. This documentation is presented in the current text. For the source chemicals alpha-Terpineol and Terpineol Multi, reliable in vivo skin and eye irritation data is available (OECD TG 404 and 405, respectively, Rel. 1) resulting in skin irritation Cat 2 and eye irritation Cat 2. These data can be used directly for read-across to the Terpene hydrocarbon alcohols.


Final conclusionThe Terpene hydrocarbon alcohols have skin irritation (Cat 2) and eye irritation (Cat 2) properties.


Data matrix presenting the skin and eye information relevant for read across to the Terpene hydrocarbon alcohols from alpha-Terpineol and Terpineol multi.

























































































































Terpene hydrocarbon alcohols



Terpineol hydrocarbon alcohols



Terpineol alpha and multi



 



Target



Source



Structure



Not applicable



 


(α-Terpineol and γ-Terpineol)



CAS



Not applicable



98-55-5 and 8000-41-7



EC No.



945-149-0



202-680-6 /232-268-1



Reach registration



2018



Registered



Molecular weight



136-154



154



Phys-chem properties



 



 



Appearance



Liquid



Liquid



Log Kow



3.3-5.5; IFF



2.6



Identity, Constituent type (%)



100%



 



Solely hydrocarbons



 



 



Terpinolene or Limonene type



0-15



 



Alcohol type



 



>80



Tertiary alcohols



40-90



 



Secondary alcohols



7-40



 



Ketone type



-



 



Camphor-Type



0-17.5%



 



Ether type



 



 



Aromatic ether type



<4%



 



Human health



 



 



Skin irritation



Skin irritant Cat 2


(Read across)



Skin irritant Cat 2


(OECD TG 404)



Eye irritation



Eye irritant Cat 2


(Read across)



Eye irritant Cat 2


(OECD TG 405)



 

Justification for classification or non-classification

The substance needs to be classified as Skin irritant Category 2 and shall be labelled with 'H315: Causes skin irritation', according to EU CLP (EC No. 1272/2008 and its amendments).

The substance needs to be classified as Eye irritant Category 2 and shall be labelled with 'H319: Causes serious eye irritation', according to EU CLP (EC No. 1272/2008 and its amendments).

The substance does not need to be classified for respiratory irritation according to EU CLP (EC No. 1272/2008 and its amendments).

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