Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ames test using read across from Cedarwood Texas oil distilled (OECD TG 471): negative

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 Apr 2017 - 26 Apr 2017.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose:
reference to same study
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
21 July 1997
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Version / remarks:
31 May 2008
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay
Test material information:
Composition 1
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Obtained from Sponsor, B-64530
- Expiration date of the lot/batch: 25 January 2019
- Purity test date: 26 January 2016

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
-A solubility test was performed based on visual assessment. The stock was heated to 100˚C in a waterbath and homogenous samples were aliquoted and stored at room temperature. One of these aliquots was used to perform the test. The test item was dissolved in dimethyl sulfoxide. The stock solution was treated with ultrasonic waves until the test item had completely dissolved. Test item concentrations were used within 2 hours after preparation.

OTHER SPECIFICS: UVCB
Target gene:
- S. typhimurium: Histidine gene
- Escherichia coli: Tryptophan gene
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain characteristics:
other: rfa : deep rough (defective lipopolysaccharide cellcoat) gal : mutation in the galactose metabolism chl : mutation in nitrate reductase bio : defective biotin synthesis uvrB : loss of the excision repair system (deletion of the ultraviolet-repair B gene)
Metabolic activation:
with and without
Metabolic activation system:
S9
Species / strain:
E. coli WP2 uvr A
Additional strain characteristics:
other: The strain lacks an excision repair system and is sensitive to agents such as UV
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
Dose range-finder: 1.7, 5.4, 17, 52, 164, 512, 1600 and 5000 μg/plate
First and Second Mutation Experiment: 5.4, 17, 52, 164, 512, 1600 and 5000 μg/plate
Vehicle:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: Suitable solvent, compatible with the used bacterial strains
Negative controls:
no
Solvent controls:
yes
Remarks:
DSMO and Saline
True negative controls:
no
Positive controls:
yes
Positive control substance:
4-nitroquinoline-N-oxide
2-nitrofluorene
sodium azide
methylmethanesulfonate
other: 2-aminoanthracene (all strains with S9), ICR-191 (TA1537, sithout S9)
Details on test system and conditions:
METHOD OF APPLICATION: in medium, in agar: plate incorporation.
- Cell density: 1.0 ± 0.1 at 700 nm (10^9 cells/ml), 0.1 ml added to top agar.

DURATION
- Exposure duration:48 ± 4 h

DETERMINATION OF CYTOTOXICITY
- Method: decrease in the number of revertants, reduction of the bacterial background lawn and/or the presence of microcolonies.

OTHER:
- The revertant colonies were counted automatically with the Sorcerer Colony Counter. Plates with sufficient test item precipitate to interfere with automated colony counting were counted manually. Evidence of test item precipitate on the plates and the condition of the bacterial background lawn were evaluated when considered necessary, macroscopically and/or microscopically by using a dissecting microscope.
- Exposure temperature 37.0 ± 1.0°C (actual range 34.3 – 39.5°C).
Rationale for test conditions:
The study is designed to comply with the experimental methods indicated in the guidelines
Evaluation criteria:
EVALUATION CRITERIA
-A test item is considered negative (not mutagenic) in the test if:
a) The total number of revertants in the tester strain TA100 or WP2uvrA is not greater than two (2) times the concurrent vehicle control, and the total number of revertants in tester strains TA1535, TA1537 or TA98 is not greater than three (3) times the concurrent vehicle control.
b) The negative response should be reproducible in at least one follow-up experiment.
- A test item is considered positive (mutagenic) in the test if:
a) The total number of revertants in the tester strain TA100 or WP2uvrA is greater than two(2) times the concurrent vehicle control, or the total number of revertants in tester strains TA1535, TA1537, TA98 is greater than three (3) times the concurrent vehicle control.
b) In case a follow up experiment is performed when a positive response is observed in one of the tester strains, the positive response should be reproducible in at least one follow up experiment.
-Any increase in the total number of revertants should be evaluated for its biological relevance including a comparison of the results with the historical control data range.
Key result
Species / strain:
other: TA1535, TA1537, TA98, TA100
Remarks:
Main experiment I and II
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
yes
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Key result
Species / strain:
E. coli WP2 uvr A
Remarks:
Main experiment I and II
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
no
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation:
First experiment: at the start of the incubation period at concentrations of 512 μg/plate and upwards and at 5000 μg/plate at the end of the incubation period.
Second experiment: at the start of the incubation period at the concentration of 512 μg/plate and upwards. At the end of the incubation period the test item precipitated at 1600 and 5000 μg/plate in the absence of S9-mix and at 5000 μg/plate in the presence of S9-mix. Except in tester strain TA100 in the absence of S9-mix, where precipitation was already observed at 512 μg/plate.

RANGE-FINDING/SCREENING STUDIES:
In the dose-range finding test, the test item was tested up to concentrations of 5000 μg/plate in the absence and presence of S9-mix in the strains TA100 and WP2uvrA. The test item precipitated on the plates at the dose level of 5000 μg/plate. Cytotoxicity, as evidenced by a decrease in the number of revertants, reduction of the bacterial background lawn and/or the presence of microcolonies, was observed in tester strain TA100 at dose levels of 512 μg/plate and upwards in the absence and presence of S9-mix. In tester strain WP2uvrA, no toxicity was observed at any of the dose levels tested.

HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: available in study report.
- Negative (solvent/vehicle) historical control data: available in study report.
Conclusions:
Based on the results of this study it is concluded that Cedrol, Cedarwood Texas oil distilled is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.
Executive summary:

The mutagenic potential of Cedrol, Cedarwood Texas oil distilled was evaluated according to OECDTG 471. In the dose-range finding test, the test item was tested up to concentrations of 5000 μg/plate in the absence and presence of S9-mix in the strains TA100 and WP2uvrA. The test item precipitated on the plates at the dose level of 5000 μg/plate. Cytotoxicity was observed in tester strain TA100 at dose levels of 512 μg/plate and upwards in the absence and presence of S9-mix. In tester strain WP2uvrA, no toxicity was observed at any of the dose levels tested.  Based on the results of the dose-range finding test, the test item was tested in the first mutation assay at a concentration range of 5.4 to 5000 μg/plate in the absence and presence of 5% (v/v) S9-mix in the tester strains TA1535, TA1537 and TA98. The test item precipitated on the plates at the dose level of 5000 μg/plate. Cytotoxicity was observed in all three tester strains in the absence and presence of S9-mix. In a follow-up experiment of the assay with additional parameters, the test item was tested at a concentration range of 5.4 to 5000 μg/plate in the absence and presence of 10% (v/v) S9-mix in the tester strains TA1535, TA1537, TA98, TA100 and WP2uvrA. The test item was tested up to or beyond a precipitating dose level. Cytotoxicity was observed in all tester strains in the absence and presence of S9 -mix, except in tester strain WP2uvrA in the presence of S9-mix. Cedrol, Cedarwood Texas oil distilled did not induce a significant dose-related increase in the number of revertant (His+) colonies in each of the four tester strains (TA1535, TA1537, TA98 and TA100) and in the number of revertant (Trp+) colonies in the tester strain WP2uvrA both in the absence and presence of S9-metabolic activation. These results were confirmed in a follow-up experiment. In this study, acceptable responses were obtained for the negative and strain-specific positive control items indicating that the test conditions were adequate and that the metabolic activation system functioned properly. In conclusion, based on the results of this study it is concluded that Cedrol, Cedarwood Texas oil distilled is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: read across
Justification for type of information:
The read across justification is presented in the endpoint summary and the accompanying files are also attached there.
Reason / purpose:
read-across source
Related information:
Composition 1
Test material information:
Composition 1
Key result
Species / strain:
other: TA1535, TA1537, TA98, TA100
Remarks:
Main experiment I and II
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
yes
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Key result
Species / strain:
E. coli WP2 uvr A
Remarks:
Main experiment I and II
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
no
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Conclusions:
Based on the results of the study for read-across substance Cedarwood Texas oil distilled, Cedarwood oil Himalayan is considered not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

The mutagenicity of Cedarwood oil Himalayan was assessed by using read across from Cedarwood Texas oil distilled. First the experimental information of Cedarwood Texas oil distilled will be summarised. Thereafter the read across justification is presented. The accompanying files are attached in the present endpoint summary.

Gene mutation study in bacterial cells

The mutagenic potential of Cedrol, Cedarwood Texas oil distilled and/or its  was evaluated according to OECDTG 471. In the dose-range finding test, the test item was tested up to concentrations of 5000 μg/plate in the absence and presence of S9-mix in the strains TA100 and WP2uvrA. The test item precipitated on the plates at the dose level of 5000 μg/plate. Cytotoxicity was observed in tester strain TA100 at dose levels of 512 μg/plate and upwards in the absence and presence of S9-mix. In tester strain WP2uvrA, no toxicity was observed at any of the dose levels tested.  Based on the results of the dose-range finding test, the test item was tested in the first mutation assay at a concentration range of 5.4 to 5000 μg/plate in the absence and presence of 5% (v/v) S9-mix in the tester strains TA1535, TA1537 and TA98. The test item precipitated on the plates at the dose level of 5000 μg/plate. Cytotoxicity was observed in all three tester strains in the absence and presence of S9-mix. In a follow-up experiment of the assay with additional parameters, the test item was tested at a concentration range of 5.4 to 5000 μg/plate in the absence and presence of 10% (v/v) S9-mix in the tester strains TA1535, TA1537, TA98, TA100 and WP2uvrA. The test item was tested up to or  beyond a precipitating dose level. Cytotoxicity was observed in all tester strains in the absence and presence of S9-mix, except in tester strain WP2uvrA in the presence of S9-mix. Cedrol, Cedarwood Texas oil distilled did not induce a significant dose-related increase in the number of revertant (His+) colonies in each of the four tester strains (TA1535, TA1537, TA98 and TA100) and in the number of revertant (Trp+) colonies in the tester strain WP2uvrA both in the absence and presence of S9-metabolic activation. These results were confirmed in a follow-up experiment. In this study, acceptable responses were obtained for the negative and strain-specific positive control items indicating that the test conditions were adequate and that the metabolic activation system functioned properly. In conclusion, based on the results of this study it is concluded that Cedrol, Cedarwood Texas oil distilled is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.

Read across justification

Mammalian toxicity and auto-ignition temperature of Essential oil of Cedarwood Himalayan obtained from the root of Cedrus deodara by distillation (CAS 91771-47-0; target) using read across from Cedarwood Texas oil distilled – Cedrol (CAS 91722-61-6; source)

Introduction and hypothesis for the analogue approach

Cedarwood Himalayan oil is a UVCB which consists of hydrocarbon constituents. Its major constituent is Cedrol. The full composition of Cedarwood Himalayan is presented in data matrix 1. For Cedarwood Himalayan oil no data are available for mammalian toxicity and auto flammability (see data matrix 2). Therefore additional information is used in accordance with Article 13 of REACH where it is said that lacking information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, SARs, grouping and read-across. For assessing the mammalian toxicity and the auto flammability of Cedarwood Himalayan oil, the mammalian toxicity data and auto flammability data of Cedarwood Texas oil distilled - Cedrol were used.The analogue substance-based read-across approach is selected because both the source and target cedarwood oils contain one major constituent, Cedrol. Sufficient reliable information is available for Cedarwood Texas oil distilled - Cedrol which can be used for read across.

 

Hypothesis:

Cedarwood Himalayan oil (target) is expected to have the same auto flammability as Cedarwood Texas oil distilled - Cedrol (source).

Cedarwood Himalayan oil (target) is expected to have the same mammalian toxicity as Cedarwood Texas oil distilled - Cedrol (source).

 

Available information:

 

Auto flammability:

The auto flammability of Texas Cedarwood oil, distilled was tested according to EU Method A.15 and DIN 51794. The test item Texas Cedarwood oil, distilled - Cedrol has an Auto flammability temperature of 260°C at 1016.6 hPa.

 

Acute oral toxicity:

The acute toxic potential of Cedarwood Texas oil distilled - Cedrol was assessed in an acute oral toxicity limit test performed similar to OECD TG 401. Ten rats were exposed to 5000 mg/kg bw Cedarwood Texas oil distilled - Cedrol via the oral route, and observed for clinical signs and mortality over an examination period of 14 days. Daily observations were performed. At the end of the study period no mortality was observed in any of the animals. Furthermore no symptoms occurred in the test animals.Based on these results the LD50 for acute oral toxicity was set at > 5000 mg/kg bw.

 

Skin irritation/corrosion:

Cedarwood Texas oil distilled - Cedrol was evaluated for its ability to induce skin corrosion on a human three dimensional epidermal model according to OECD TG 431.  Cedarwood Texas oil distilled - Cedrol was applied topically for 3 minutes and 1 hour. The test substance was equilibrated to 100°C for several minutes until completely liquefied to obtain a homogeneous liquid sample.  Cedarwood Texas oil distilled - Cedrol (50 µl) was applied directly on top of the skin tissue.  

The positive control had a mean relative tissue viability of 10% after the 1-hour exposure.  The absolute mean OD570 (optical density at 570 nm) of the negative control tissues was within the acceptance limits of OECD 431 (lower acceptance limit ≥ 0.8 and upper acceptance limit ≤ 2.8) and the laboratory historical control data range.  In the range of 20 - 100% viability the Coefficient of Variation between tissue replicates was ≤ 8.0%, indicating that the test system functioned properly.

The relative mean tissue viability obtained after 3-minute and 1-hour treatments with the test substance compared to the negative control tissues was 104% and 116%, respectively.  Because the mean relative tissue viability for Cedarwood Texas oil distilled - Cedrol was above 50% after the 3-minute treatment and above 15% after the 1-hour treatment –the test substance is considered to be not corrosive.

In conclusion, Cedarwood Texas oil distilled - Cedrol is not corrosive in the in vitro skin corrosion test under the experimental conditions described.

 

The skin irritation potential of Cedarwood Texas oil distilled - Cedrol was tested in accordance to OECDTG439. Undiluted Cedarwood Texas oil distilled - Cedrol was topically applied to EPISKIN-SMTM for 15 minutes. After a 42 hour post-incubation period, determination of the cytotoxic (irritancy) effect was performed using MTT conversion measurements.

The relative mean tissue viability obtained after 15 ± 0.5 minutes treatment with – the test substance compared to the negative control tissues was 17%. Since the mean relative tissue viability was below 50% after 15 ± 0.5 minutes treatment it is considered to be an irritant. Both the positive and the negative control were within the historical control data range and therefore considered valid. Furthermore, the standard deviation value of the percentage viability of three tissues treated identically was less than 14%, indicating that the test system functioned properly.

 In conclusion, Cedarwood Texas oil distilled - Cedrol was determined to be an irritant in the in vitro skin irritation test under the experimental conditions described in this report.

 

Eye irritation:

The eye hazard potential of Cedarwood Texas oil distilled - Cedrol was evaluated according to OECD Guideline 437 (BCOP test). The eye damage was assessed through topical application of 750 µl of the undiluted substance for 10 minutes on top of the corneas. Both the negative control and the positive control (Ethanol) were considered valid. It was therefore concluded that the test conditions were adequate and that the test system functioned properly. Cedarwood Texas oil distilled - Cedrol did not induce ocular irritation (no opacity and no permeability), resulting in a mean in vitro irritancy score of 0.7 after 10 minutes of treatment. In conclusion, since Cedarwood Texas oil distilled - Cedrol induced an IVIS ≤ 3, and the test substance is not considered to be an eye irritant.

 

Skinsensitisation:

The skin sensitisation potential of Cedarwood Texas oil distilled - Cedrol was tested according to OECD TG 429 (LLNA). Three experimental groups of five female CBA/J mice were treated with test item concentrations of 5, 10 or 25% w/w on three consecutive days, by open application on the ears. Test item concentrations selected for the main study were based on the results of a pre-screen test. Five vehicle control animals were similarly treated, but with the vehicle alone (AcOO).  No erythema was noted for any of the animals, Scaliness was noted on the ears of four animals treated at 25% between days 3 and 6. No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size. No macroscopic abnormalities of the surrounding area were noted for any of the animals. Body weights and body weight gain of experimental animals remained in the same range as controls over the main study period. Mean DPM/animal values for the experimental groups treated with test item concentrations 5, 10 and 25% were 561, 647 and 1524 DPM, respectively. The mean DPM/animal value for the vehicle control group was 285 DPM. The SI values calculated for the test item concentrations 5, 10 and 25% were 2.0, 2.3 and 5.4, respectively. The data showed a dose-response and an EC3 value (the estimated test item concentration that will give a SI =3) of 13.4% was calculated. Based on the results of this LLNA, Cedarwood Texas oil distilled - Cedrol is considered to be a skin sensitiser.

 

Mutagenicity:

The mutagenic potential of Cedarwood Texas oil distilled - Cedrol was evaluated according to OECD TG 471. In the dose-range finding test, the test item was tested up to concentrations of 5000 μg/plate in the absence and presence of S9-mix in the strains TA100 and WP2uvrA. The test item precipitated on the plates at the dose level of 5000 μg/plate. Cytotoxicity was observed in tester strain TA100 at dose levels of 512 μg/plate and upwards in the absence and presence of S9-mix. In tester strain WP2uvrA, no toxicity was observed at any of the dose levels tested.  Based on the results of the dose-range finding test, the test item was tested in the first mutation assay at a concentration range of 5.4 to 5000 μg/plate in the absence and presence of 5% (v/v) S9-mix in the tester strains TA1535, TA1537 and TA98. The test item precipitated on the plates at the dose level of 5000 μg/plate. Cytotoxicity was observed in all three tester strains in the absence and presence of S9-mix. In a follow-up experiment of the assay with additional parameters, the test item was tested at a concentration range of 5.4 to 5000 μg/plate in the absence and presence of 10% (v/v) S9-mix in the tester strains TA1535, TA1537, TA98, TA100 and WP2uvrA. The test item was tested up to or beyond a precipitating dose level. Cytotoxicity was observed in all tester strains in the absence and presence of S9 -mix, except in tester strain WP2uvrA in the presence of S9-mix. Cedarwood Texas oil distilled - Cedrol did not induce a significant dose-related increase in the number of revertant (His+) colonies in each of the four tester strains (TA1535, TA1537, TA98 and TA100) and in the number of revertant (Trp+) colonies in the tester strain WP2uvrA both in the absence and presence of S9-metabolic activation. These results were confirmed in a follow-up experiment. In this study, acceptable responses were obtained for the negative and strain-specific positive control items indicating that the test conditions were adequate and that the metabolic activation system functioned properly. In conclusion, based on the results of this study it is concluded that Cedarwood Texas oil distilled - Cedrol is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.

Target and Source chemical(s):The information on for Cedarwood Himalayan oil (target) and the information from Cedarwood Texas oil distilled - Cedrol (source) are presented in the data matrix 2 of this document. This includes physico-chemical properties and toxicological information, relevant for auto-flammability and mammalian toxicity.

 

Purity / Impurities:

The impurities are not relevant forCedarwood Himalayan oil(target) andCedarwood Texas oil distilled - Cedrol (source)as both substances are UVCBs (Natural Complex Substances).

Analogue approach justification

According to REACH Annex XI an analogue approach and structural alert information can be used to replace testing when information from different sources provides sufficient evidence to conclude that this substance has or does not have a particular dangerous property. The result derived should be applicable for C&L and/or risk assessment and be presented with adequate and reliable documentation.

Analogue selection:

Cedarwood Texas oil distilled - Cedrolwas selected as analogue source becauseit contains55% - 75% Cedrol.

Cedarwood Himalayan oil(target) contains besides Cedrol, various other constituents in low concentrations that are present in variable ranges, as shown in data matrix 1. None of the other constituents are registered under REACH and no reliable toxicity information is available.

 

Structural similarities and differences:

Cedarwood Himalayan oil(target) as well asCedarwood Texas oil distilled - Cedrol (source)contain mostly Cedrol. Cedrol is a cyclic terpenoid and containsa tertiary alcohol group. The remaining constituents ofCedarwood Himalayan oil(target) andCedarwood Texas oil distilled - Cedrol (source) differ. The remaining constituents in both source and target substance are varying in structure however all constituents are hydrocarbon compounds and some contain tertiary alcohol groups.

 

Absorption:

All constituents of the source and target substance are expected to be absorbed via the oral route based on their physico-chemical properties and molecular weights. The log kow values are comparable, ranges from 4.3 to 5.49 (KOWWIN 1.68) for the source, and was measured to be 5.5 for the target. Due to the LogKow values >4 Absorption though micellular solubilisation is expected to be an important mechanism of absorption.

 

Toxicodynamics

Both target and source contain Cedrol as main constituent, therefore the toxicodynamics for both UVCBs are expected to be comparable. No toxicokinetic information is available for the remaining, minor constituents inCedarwood Himalayan oil(target).

Conclusions on the toxicity endpoints and auto flammability:

Final hazard conclusion:

ForCedarwood Himalayan oil, a UVCB, the potential for mammalian toxicity hazards was derived fromCedarwood Texas oil distilled – Cedrol.Cedarwood Texas oil distilled – Cedrolis classified as a skin irritant (Skin Irrit. 2, H315) and a skin sensitiser (Skin Sens. 1B, H317)

The final conclusion on the classification ofCedarwood Himalayan oil is thereforeskin irritating (Skin Irrit. 2, H315) and a skin sensitiser (Skin Sens. 1B, H317).

 

Data matrix 1 for the comparison of the constituents inCedarwood Himalayan oil(target) andCedarwood Texas oil distilled - Cedrol(source)

NAME

CAS

Target

Target

Source

Source

 

 

Min.

Max.

Min.

Max.

Cedrol

77-53-2

50.00%

70.00%

>=55.00%

<=75.00%

 

 

 

 

 

 

rel-(1R,4S,4aR,8aR)-1,6-dimethyl-4-(propan-2-yl)-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-ol (Hydrolized Cadinene 1)

65700-78-9

1.00%

8.00%

-

-

rel-(1R,4S,4aR,8aS)-4,7-dimethyl-1-(propan-2-yl)-1,3,4,5,6,8a-hexahydronaphthalen-4a(2H)-ol

(Hydrolized Cadinene 2)

86023-67-8

1.00%

5.00%

-

-

rel-(1R,4R,4aR,8aS)-4,7-dimethyl-1-(propan-2-yl)-1,3,4,5,6,8a-hexahydronaphthalen-4a(2H)-ol

(Hydrolized Cadinene 3)

159990-04-2

0.50%

4.00%

-

-

2,5-dimethyl-8-(propan-2-yl)-1,2,3,4,6,7,8,8aoctahydronaphthalen-2-ol

(Hydrolized Cadinene 4)

57440-66-1

0.00%

3.00%

-

-

rel-(3R,3aR,5S,6R,7aR)-3,6,7,7-tetramethyloctahydro-3a,6-ethanoinden-5-ol

159517-24-5

1.00%

8.00%

-

-

(4beta)-cedr-8(15)-en-4-ol

114674-10-1

1.00%

7.00%

-

-

rel-(1R,2R,4aS,8aR)-4a-methyl-8-methylidene-2-(propan-2-yl)decahydronaphthalen-1-ol

38108-86-0

1.00%

5.00%

-

-

rel-(4aR,9S,9aS)-3,5,5,9-tetramethyl-2,4a,5,6,7,8,9,9a-octahydro-1H-benzo[7]annulen-9-ol

126999-77-7

1.00%

7.00%

-

-

rel-2-[(1R,4R,5R)-4,8-dimethylspiro[4.5]dec-7-en-1-yl]propan-2-ol

955007-43-9

1.00%

10.00%

-

-

beta-eudesmol

3287-59-0

0.50%

4.00%

-

-

(7S,9aS)-4,4,7,9a-tetramethyl-1,2,3,6,8,9-hexahydrobenzo[7]annulen-7-ol (Widdrol)

6892-80-4

-

-

>=2.00%

<8.00%

(1R, 5S, 7R)-2,6,6,8-tetramethyltricycle[5.3.1.0 1,5]undec-8-ene (Diepi-alpha-cedrene (Alpha-funebrene))

50894-66-1

-

-

>= 0.01%

<=2.00%

(6R)-1,5,5,9-tetramethylspiro[5.5]undeca-1,8-diene (Chamigrene alpha)

11912-83-5

-

-

>=0.01%

<=2.00%

(4aS,9aR)-3,5,5,9-tetramethyl-2,4a,5,6,7,9a-hexahydro-1H-benzo[7]annulene (Himachalene Gamma)

53111-25-4

-

-

>=0.01%

<=2.00%

3,5,5,9-tetramethyl-1,2,4a,6,7,8-hexahydrobenzo[7]annulene (Beta-himachalene)

1461-03-6

-

-

>=0.01%

<=2.00%

3,5,5-trimethyl-9-methylidene-2,4a,5,6,7,8,9,9a-octahydro-1H-benzo[7]annulene (Himachalene alpha)

3853-83-6

-

-

>=0.01%

<=2.00%

[1aS-(1aα,4aβ,8aR*)]-1,1a,4,4a,5,6,7,8-octahydro-2,4a,8,8-tetramethylcyclopropa[d]naphthalene (Thujopsene)

470-40-6

-

-

>=1.00%

<=5.00%

(R)-(+)-p-(1,2,2-trimethylcyclopentyl)toluene (Cuparene)

16982-00-6

-

-

>=0.01%

<=4.00%

(1S,2R,5S,7R)-2,6,6-trimethyl-8-methylidenetricyclo[5.3.1.0(1,5)]undecane (Beta-cedrene)

546-28-1

-

-

>=1.00%

<=5.00%

[3R-(3a,3ab,7b,8aa)]-2,3,4,7,8,8a-hexahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulene (Cedrene alpha)

469-61-4

-

-

>=1.00%

<=5.00%

(2,6-dimethyl-6-(4-methyl-3-pentenyl)bicyclo[3.1.1]hept-2-ene)(

17699-05-7

-

-

>=0.01%

<=1.00%

Minor and unknown constituents

-

4.00%

15.00%

>=8.00%

<18.00%

 

Data matrix 2. Cedarwood Himalayan oil (target) and Cedarwood Texas oil distilled - Cedrol (source) information to support the read across.

CHEMICAL NAME

Cedarwood Himalayan oil

Cedarwood Texas oil distilled - Cedrol

Molecular structure

N/A

N/A

Target

Source

CAS

91771-47-0

91722-61-6

REACH registration

To be registered (Annex VII)

Yes

Einecs

294-939-5

294-461-7

Molecular formula

N/A

N/A

Molecular weight

N/A

N/A

Physico-chemical properties

 

Appearances

Brown, viscous liquid (IFF, 2017)

Light yellow solid mass

Melting point (˚C)

75.4(IFF, 2017)

- 42.5 (glass transition temperature)

Boiling point (˚C)

305.8 (IFF, 2017)

292.4

Vapour pressure (Pa)

2.81 (IFF, 2017)

0.67 (QSAR)

Water solubility (mg/L)

12.3 (IFF, 2017)

>= 0.03 -< = 29.25 (QSAR)

Log Kow

5.5 (IFF, 2017)

>= 4.33 -<=6.94(QSAR)

Autoflammability (˚C)

Read across

260

Human health

 

Acute toxicity (oral)

Read across

LD50 >5000 mg/kg bw (similar to OECD TG 401)(RIFM, 1974)

Skin irritation/corrosion

Read across

Skin irritating (OECD TG 439)

Not skin corrosive (OECD TG 431)

(NCS Sesquiterpenes HC/Alc consortium, 2017)

Eye irritation/corrosion

Read across

Not eye irritating (OECD TG 438) (NCS Sesquiterpenes HC/Alc consortium, 2017)

Skin sensitisation

Read across

Skin Sensitising (OECD TG 429) (NCS Sesquiterpenes HC/Alc consortium, 2017)

Genetic toxicity (Ames)

Read across

Negative (OECD TG 471)(NCS Sesquiterpenes HC/Alc consortium, 2017)

 

Justification for classification or non-classification

Based on the available data, the substance does not need to be classified for genotoxicity in accordance with the criteria outlined in EU CLP (EC no 1272/2008 and its amendments).