Reaction mass of 1-hydroxydecan-3-one and 3-(hydroxymethyl)nonan-2-one and nonan-2-one

Endpoint summary

Description of key information

LD50 is 3436 mg/kg bw which is derived from the acute oral LD50 of two of the constituents.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 436 mg/kg bw

Additional information

For Methyl Lavender Ketone, the acute oral toxicity is derived from the constituents Nonan-2-one and 1-Hydroxydecan-3-one (constituent 2 and 3). Based on the available data the LD50 for Methyl Lavender Ketone can be calculated to be (0.63*2980+0.21*5000+0.09*2980)/0.93 = 3436 mg/kg bw. The summary of the experimental information is presented first and thereafter the read across rationale.

Nonan-2-one

The acute oral toxicity to male rats has been studied similar to OECD TG 401. The substance was administered at a dose of 5000 mg/kg bw to 10 male rats and animals were observed for 14 days. One animal died on day 7. Toxic signs included lethargy, ataxia, prostration, flaccid muscle tone, ptosis, and tachypnea. One animal had swollen back feet and difficulties in walking, probably due to an infection. The internal organs appeared normal except of congested and hemorrhagic lungs, dilated heart, distended stomach and intestines and reddish intestines noted in the animal found dead. The acute oral toxicity (LD50) was determined to be >5000 mg/kg.

1-Hydroxydecan-3-one

The acute oral toxicity to rats has been studied similar to OECD TG 401. The substance was administered at a dose of 5000 mg/kg bw to 10 rats per dose. Dose levels were 1730, 2470, 3510, and 5000 mg/kg bw. Mortality was observed at 2470, 3510, and 5000 mg/kg bw: 5, 5, and 9 out of 10 animals, respectively. The LD50 was determined to be 2980 mg/kg bw. Toxic signs included lethargy, ataxia, diarrhea, piloerection, flaccid muscle tone, ptosis, and comatose. The internal organs appeared normal of the animals exposed to 1730 mg/kg bw. With increasing dose levels, the number of affected organs and number of affected animals increased. Organs affected included lungs, liver, kidney, stomach, spleen and intestines.

Methyl Lavender Ketone(EC no. 909-017-6) and its acute oral toxicity of using read across from nonan-2-one (Cas no. 821-55-6) and 1-hydroxydecan-3-one (Cas no. 67633-95-8), which are two of the three constituents

Introduction and hypothesis for the analogue approach

Methyl Lavender Ketone is a reaction mass of 3-(hydroxymethyl)nonan-2-one (63%), nonan-2-one (21%), and 1-hydroxydecan-3-one (9%). For this substance 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 of Methyl Lavender Ketone the constituent and analogue approach is selected because for two of the three constituents (nonan-2-one and 1-hydroxydecan-3-one), acute oral toxicity information is available and this data can be used for read across to the third constituent (3-(hydroxymethyl)nonan-2-one).

Hypothesis: The acute oral toxicity of Methyl Lavender Ketone can be based on the data of two constituents and that the acute oral toxicity of the third constituents is comparable to the others.

Available information: Nonan-2-one has been tested in a well conducted acute oral toxicity test performed similar to OECD TG 401 at 5000 mg/kg bw and the test result receives a reliability of 2. 1-Hydroxydecan-3-one has been tested in a well conducted acute oral toxicity test performed similar to OECD TG 401 up to 5000 mg/kg bw and the test result receives a reliability of 2.

Target chemical and source chemical(s)

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

Purity / Impurities

Methyl Lavender Ketoneis a reaction mass containing three main constituents:3-(hydroxymethyl)nonan-2-one(63%), nonan-2-one (21%), and 1-hydroxydecan-3-one (9%) with a combined purity of 93%. The impurities are all below 2.5%.

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 Methyl Lavender Ketone both the constituent as the analogue approach is selected. Nonan-2-one and 1-hydroxydecan-3-one have been selected being keyconstituents of Methyl Lavender Ketone and data is available. In addition,1-hydroxydecan-3-one is selected based on thesimilarity in chemical structure to the other key constituent: 3-(hydroxymethyl)nonan-2-one.

Constituent approach: Nonan-2-one, and1-hydroxydecan-3-oneare present in Methyl Lavender Ketone for 21 and 9%, respectively. Hence, they cover 30% of Methyl Lavender Ketone. The 1-hydroxydecan-3-one is used for read across to the first constituent: 3-(hydroxymethyl)nonan-2-one.

Structural similarities and differences: 1-hydroxydecan-3-one and 3-(hydroxymethyl)nonan-2-onehave a similar backbone and the same functional primary alcohol and ketone group. The backbone contains the same amount of carbon atoms. The difference in the backbone is that 3-(hydroxymethyl)nonan-2-one has a nonanone backbone with a hydroxymethyl-group attached, while 1-hydroxydecan-3-one has a decanone backbone with a hydroxyl group attached.

Toxico-kinetic, absorption: 3-(hydroxymethyl)nonan-2-one (target) and 1-hydroxydecan-3-one andhave a similar absorption and distribution behavior based on the similarity in chemical structure and physico-chemical properties. They have the same molecular weight, the vapour pressure lies in the 0.05 to 0.20 range for both substance and the water solubility lie for both substance within the 6.3 to 7.4-gram range. The log Kow for3-(hydroxymethyl)nonan-2-one is a little lower compared to 1-hydroxydecan-3-one, but still less than log 0.5 difference. Metabolism: the primary alcohol can be oxidized to an acid in both substances. The straight alkyl chain can be beta-oxidised in the mitochondrion as well as the functional primary alcohol or acid. The OECD Toolbox presents a similar oxidized metabolic profile for both substances as presented in Annex 1. The slight differences are due to the branched chain versus the straight chain but all are oxidized product resulting in additional primary alcohols and acids. Therefore, these are not expected to result in difference in toxicity. Therefore, thetoxico-kinetic behavior is comparable between the two substances.

Toxico-dynamic features: Both Constituent 1 (target) and Constituent 3 (source) have the same toxicological profile as presented by the OECD Toolbox in Annex 1, showing the likelihood that both substances are expected to have similar acute oral toxicity. 

Uncertainty of the prediction: There or no remaining 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 below.

Conclusions on acute oral toxicity

For Methyl Lavender Ketone no acute oral toxicity information is available. For the constituent nonan-2-one and 1-hydroxydecan-3-one this information is present, and the latter will be used for read across to the main constituent and the calculation of the LD50. 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 nonan-2-one and 1-hydroxydecan-3-one well conducted acute oral toxicity tests are available (Similar to OECD TG 401, Klimisch 2) with a LD50 of >5000 and 2980 mg/kg bw, respectively. Based on the study with 1-hydroxydecan-3-one, the LD50 of 3-(hydroxymethyl)nonan-2-one is also determined to be 2980 mg/kg bw. Based on this information the LD50 of Methyl Lavender Ketone can be determined to be (0.63*2980+0.21*5000+0.09*2980)/0.93 = 3436 mg/kg bw.

Final conclusion: Methyl Lavender Ketonehas an acute oral LD50 of 3436 mg/kg bw.

Data matrix to support the read across on acute oral toxicity

Common names	3-(hydroxymethyl)nonan-2-one	nonan-2-one	1-hydroxydecan-3-one
	Constituent 1	Constituent 2	Constituent 3
Chemical structures
Constituent concentration range	63% (55 – 70%)	21% (15 – 25%)	9% (5 – 15%)
CAS no	67801-33-6	821-55-6	67633-95-8
REACH registration	No	Registered	No
Empirical formula	C10H20O2	C9H18O	C10H20O2
Molecular weight	172	142	172
Physico-chemical
Vapour pressure (Pa)	0.17 (EpiSuite)	83.2 (Measured) (ECHA) 86.2 (EpiSuite)	0.07 (EpiSuite)
Water solubility (mg/l)	7357 (EpiSuite)	371 (Measured) (ECHA) 171 (EpiSuite)	6367 (EpiSuite)
Log Kow	2.8 (Measured) 1.66 (EpiSuite)	4.0 (Measured) 2.71 (EpiSuite)	3.1 (Measured) 1.74 (EpiSuite)
Human health
Acute oral tox (mg/kg bw)	2980 (Read across from Constituent 3)	>5000 (Moreno 1980)	2980 (Moreno 1978)
Acute dermal tox (mg/kg bw)	5000 (Read across from Constituent 3)	>5000 (Moreno 1980)	>5000 (Moreno 1978)
Acute oral toxicity of Methyl Lavender ketone =3436 mg/kg bw

 

Annex 1: QSAR Toolbox to support read across to3-(hydroxymethyl)nonan-2-one from 1-hydroxydecan-3-one

 

Rat S9 metabolism predicted

The repeated dose (HESS) toxicity is not considered for acute toxicity.

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).