1,2,3,4,4a,5,6,7-octahydro-2,5,5-trimethyl-2-naphthol

Endpoint summary

Description of key information

For Ambrinol 95 the LD50 is >2000 mg/kg bw which based on read-across from a multi-constituent containing 56% Ambrinol and a similar analogue tested in an OECD TG 401.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Additional information

For Ambrinol 95, the acute oral toxicity is derived from a multi-constituent containing 56% Ambrinol. The summary of the experimental information is presented first and thereafter the read across rationale.

 

Ambrinol S (Reaction mass of 1,2,3,4,4a,5,6,7-octahydro-2,5,5-trimethyl-2-naphthol and 4-(2,6,6-trimethyl-2-cyclohexen-1-yl)butan-2-one)

The acute oral toxicity has been studied in an OECD TG 401 test following GLP principles. The substance was administered at a dose of 2000 mg/kg bw to 5 male and 5 female SD rats and animals were observed for 14 days. Two females were found to be hypoactive, ataxic and suffering tremors 5.5 hours after dosing and were killed in extremis. In the surviving animals, clinical signs were limited to brown peribuccal staining in 3 animals 30 minutes after dosing and hypoactivity in all animals 4 hours after dosing. Generally recovery had occurred by day 2. There were no adverse effects an bodyweight gain in animals of either sex. There were no treatment related necropsy findings. The acute oral toxicity (LD50) was determined to be >2000 mg/kg.

 

Ambrinol 95 (Cas no. 41199-19-3) and its acute oral toxicity of using read across from Ambrinol S (EC number: 915-610-0)

 

Introduction and hypothesis for the analogue approach

For Ambrinol 95 (2,5,5-trimethyl-1,2,3,4,4a,5,6,7-octahydronaphthalen-2-ol) no acute oral toxicity data are available. In accordance with Article 13 of REACH, lacking information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. For assessing the acute oral toxicity of Ambrinol 95 the constituent approach is selected because acute oral toxicity information is available of a multi-constituent containing 56% Ambrinol and 30% Dihydro-alpha-ionone (CAS 31499-72-6). This information can be used for read across.

Hypothesis: The toxicity of Ambrinol 95 can be derived from Ambrinol S (Reaction mass of 1,2,3,4,4a,5,6,7-octahydro-2,5,5-trimethyl-2-naphthol and 4-(2,6,6-trimethyl-2-cyclohexen-1-yl)butan-2-one) containing 56% Ambrinol.

Available information: Ambrinol S has been tested in a well conducted acute oral toxicity test (OECD TG 401 under GLP) at 2000 mg/kg bw, in which 2/10 animals died. Test result receives a reliability of 1.

Target chemical and source chemical(s)

Chemical structures of the target chemical and the source chemical are shown in the data matrix, including physico-chemical properties and toxicological information, thought relevant for acute oral toxicity and read across.

Purity / Impurities

Ambrinol 95 is a mono-constituent containing >90% 2,5,5-trimethyl-1,2,3,4,4a,5,6,7-octahydronaphthalen-2-ol. The impurities are all below 4%.

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 Ambrinol 95 the constituent approach is selected as Ambrinol S contains 56% Ambrinol. For Ambrinol S acute oral toxicity information is available. The other constituent of Ambrinol S, Dihydro-alpha-ionone is almost a structural isomer of Ambrinol with expected similar toxicological properties. For Dihydro-alpha-ionone no data is available, but for the structural analogue Dihydro-beta-ionone (CAS# 17283-81-7), which has a double bond in the ring at one carbon different from the alpha, there is. (https://echa.europa.eu/nl/registration-dossier/-/registered-dossier/19009/7/3/2).

Structural similarities: Ambrinol and Dihydro-alpha-ionone have the same unsaturated hexylring with 2 methyl groups at the same spot. The difference is the closed hexyl-ring in Ambrinol compared to the open alkyl chain. The other difference is the functional tertiary alcohol versus the ketone group.

Toxicol-kinetics: The very similar structure of both constituents, phys-chem properties would indicate similar bioavailability (see Datamatrix).

Toxico-dynamics: The reactivity of the ketone group of Dihydro-alpha-iononone will be lower compared to the tertiary alcohol of Ambrinol. This is supported with skin and eye irritation properties, as Ambrinol is causing more severe eye damage compared to Ambrinol S, which can be explained as Dihydro-beta-iononone is not a skin or eye irritant.

Uncertainty of the prediction: In the study with Ambrinol S, 2 out of 10 animals had to be killed in extremis within 6 hours after dosing, which is expected for this substance too. For the constituent: Dihydro-alpha-ionone, no acute oral toxicity information is available. However, it is for the structural analogue Dihydro-beta-ionone. This substance shows a LD50 >2000 mg/kg bw without any mortality. Hence, the mortality observed for Ambrinol S could be a result of Ambrinol instead of Dihydro-alpha-ionone. Nonetheless, extrapolating the mortality of 2 out 10 for 56% Ambrinol to >90% Ambrinol would however not cause the LD50 to be below 2000 mg/kg bw . 

Data matrix

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

Conclusions on acute oral toxicity

For Ambrinol 95 no acute oral toxicity information is available. For the Ambrinol S this information is present and will be used for read across. 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. The current document fulfills this documentation. For Ambrinol S a well conducted acute oral toxicity test is available (OECD TG 401, Klimisch 1) with a LD50 of >2000 mg/kg bw. Based on these data, for Ambrinol 95 also a LD50 of >2000 mg/kg bw can be derived.

Final conclusion: Ambrinol 95 has an acute oral LD50 of >2000 mg/kg bw.

 

Data matrix to support the read across on acute oral toxicity

Common names	Ambrinol 95	Ambrinol S	Dihydro-beta-ionone
	Target	Source
Chemical structures		56%   Dihydro-alpha-ionone 30%
CAS no	41199-19-3	41199-19-3 31499-72-6	17283-81-7
EC number	255-256-8	915-610-0	241-318-1
REACH registration		Registered	Registered
Empirical formula	C13H22O	C13H22O	C13H22O
Molecular weight	194.3	194.3	194.3
Physico-chemical data
Physical state	Liquid	Liquid
Vapour pressure (Pa)	0.4 (measured)	2 (measured)	0.42 (measured)
Water solubility (mg/l)	585 (measured)	211 (measured)	43 (measured)
Log Kow	4.6 (measured)	3.96 (measured)	4.5 (measured)
Human health endpoints
Acute oral tox (mg/kg bw)	Read across	> 2000 (OECD TG 401)	> 2000 (OECD TG 423)
Skin irritation	Skin irritant (OECD TG 439)	Skin irritant (OECD TG 404)	Non irritant (OECD TG 404)
Eye irritation	Eye irritant with severe eye damage (OECD TG 438)	Eye irritant (OECD TG 438)	Non irritant Draize method)

 

Justification for classification or non-classification

The substance does not have to be classified for Acute oral toxicity according to EU CLP (EC No. 1272/2008 and its amendments).