Registration Dossier

Administrative data

Description of key information

Skin sensitisation using read across from Cedarwood Texas oil distilled (OECD TG 429): sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 Mar 2017 - 30 May 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 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
2010
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Version / remarks:
2003
Qualifier:
according to
Guideline:
other: EC, No 440/2008, part B "Skin Sensitization: Local Lymph Node Assay"
Version / remarks:
2008
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymphnode assay (LLNA)
Test material information:
Composition 1
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and Batch No.of test material: Provided by sponsor, B-64530
- Expiration date of the lot/batch: 25 January 2019
- Purity test date: 26 January 2017
- Test Facility test item number: 207804/A

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

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
-Test item was equilibrated to 100C for several minutes until completely liquefied to obtain a homogeneous sample. Test item dosing formulations (w/w) were homogenized to visually acceptable levels at appropriate concentrations to meet dose level requirements. The dosing formulations were prepared daily and dosed within 4 hours after adding the vehicle to the test item. The dosing formulations were kept at room temperature until dosing. The dosing formulations were stirred until and during dosing.
Species:
mouse
Strain:
CBA
Remarks:
J
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Females (if applicable) nulliparous and non-pregnant: yes
- Microbiological status of animals: SPF-quality
- Age at study initiation: approx. 10 weeks old
- Weight at study initiation: 18.7 to 23.6 g
- Housing: animals were group housed (up to 5 animals of the same sex and same dosing group together) in polycarbonate cages (Makrolon MIII type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles.
- Diet: ad libitum, pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: ad libitum, municipal tap-water (periodically analysed)
- Acclimation period: at least 5 days
- Indication of any skin lesions: before the initiation of dosing, a health inspection was performed and any assigned animal considered unsuitable for use in the study were replaced by alternate animals obtained from the same shipment and maintained under the same environmental conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24
- Humidity (%): 42 to 66%
- Air changes (per hr): >10 (no recirculation)
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES:
-Experimental study start date 09 March 2017 - 30 May 2017 (completion of In-life)
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
Pre-screen: 10, 25, 50, 100 % w/w
Main study: 0, 5, 10, 25 % w/w
No. of animals per dose:
5
Details on study design:
PRE-SCREEN TESTS:
- Irritation: erythema and eschar formation observations were performed once daily on Days 1-6 (on Days 1-3 within 1 hour after dosing)
- Systemic toxicity: observations were performed once daily on Days 1-6 (on Days 1-3 between 3 and 4 hours after dosing).
- Ear thickness measurements: ear thickness measurements were conducted using a digital thickness gauge (Kroeplin C110T-K) prior to dosing on Days 1 and 3, and on Day 6
- Erythema scores:
0 No erythema
1 Very slight erythema (barely perceptible)
2 Well-defined erythema
3 Moderate to severe erythema (beet redness) to slight eschar formation (injuries in depth)
4 Severe erythema (beet redness) to eschar formation preventing grading of erythema

MAIN STUDY
In the main study, three experimental groups of five female CBA/J mice were treated with test item concentrations on three consecutive days, by open application on the ears. Five vehicle control animals were similarly treated, but with the vehicle alone (Aceton/Olive Oil (4:1 v/v)). Three days after the last exposure, all animals were injected with 3H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised and pooled for each animal. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed. The activity was expressed as the number of disintegrations per minute (DPM) and a stimulation index (SI) was subsequently calculated for each group.

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA

EVALUATION CRITERIA
DPM values are presented for each animal and for each dose group. A Stimulation Index (SI) is calculated for each group using the individual SI values. The individual SI is the ratio of the DPM/animal compared to the DPM/vehicle control group mean. If the results indicate a SI ≥ 3, the test item may be regarded as a skin sensitizer. Consideration was given to the EC3 value (the estimated test item concentration that will give a SI =3), EC3 value ≤ 2%: sub-category 1A, EC3 value > 2%: sub-category 1B.

TREATMENT PREPARATION AND ADMINISTRATION:
Test item dosing formulations (w/w) were homogenized in the vehicle (acetone/olive oil (4:1 v/v)) to visually acceptable levels at appropriate concentrations to meet dose level requirements. The dosing formulations were prepared daily and dosed within 4 hours after adding the vehicle to the test item. The dosing formulations were kept at room temperature until dosing. The dorsal surface of both ears was topically treated (25 μL/ear) with the test item, at approximately the same time on each day. The concentrations were stirred with a magnetic stirrer immediately prior to dosing. The control animals were treated in the same way as the experimental animals, except that the vehicle was administered instead of the test item.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
- DPM values are presented for each animal and for each dose group.
- A Stimulation Index (SI) is calculated for each group using the individual SI values. The individual SI is the ratio of the DPM/animal compared to the DPM/vehicle control group mean.
- Consideration was given to the EC3 value (the estimated test item concentration that will give a SI =3)
Positive control results:
The SI values calculated for the item concentrations 5, 10 and 25% were 1.4, 2.4 and 4.3 respectively. An EC3 value of 14.7% was calculated using linear interpolation. The calculated EC3 value was found to be in the acceptable range of 4.8 and 19.5%. The results of the 6 monthly HCA reliability checks of the recent years were 13.4, 14.1, 17.3, 9.8, 17.8% and 18.0%. The six-month reliability check with Alpha-hexylcinnamaldehyde indicates that the Local Lymph Node Assay as performed at Charles River Den Bosch was found a appropriate model for testing for contact hypersensitivity.
Parameter:
SI
Value:
1
Variability:
0.3
Test group / Remarks:
0% dose
Parameter:
SI
Value:
2
Variability:
0.6
Test group / Remarks:
5% dose
Parameter:
SI
Value:
2.3
Variability:
0.6
Test group / Remarks:
10% dose
Key result
Parameter:
SI
Value:
5.4
Variability:
1.3
Test group / Remarks:
25% dose
Key result
Parameter:
EC3
Value:
13.4
Cellular proliferation data / Observations:
CELLULAR PROLIFERATION DATA
-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.

DETAILS ON STIMULATION INDEX CALCULATION
-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.

EC3 CALCULATION
-The EC3 value (the estimated item concentration that will give a SI=3) was determined based on the dose response relationship or calculated using linear interpolation. The test item elicits a SI ≥ 3 when tested at 25%. The data showed a dose response and an EC3 value of 13.4% was calculated.

CLINICAL OBSERVATIONS:
-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.

BODY WEIGHTS
-Body weights and body weight gain of experimental animals remained in the same range as controls over the main study period.
Interpretation of results:
other: skin sensitiser
Remarks:
in accordance with EU CLP (EC 1272/2008 and its updates)
Conclusions:
Based on the results of this LLNA, the calculated EC3 value is 13.4%. Therefore, Cedrol, Cedarwood Texas oil distilled is considered to be a skin sensitiser.
Executive summary:

The skin sensitisation potential of Cedrol, Cedarwood Texas oil distilled was tested according to OECD, Section 4, Health Effects, No.429 (2010). 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, Cedrol, Cedarwood Texas oil distilled is considered to be a skin sensitiser.

Endpoint:
skin sensitisation: in vivo (LLNA)
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
Parameter:
SI
Value:
1
Variability:
0.3
Test group / Remarks:
0% dose
Parameter:
SI
Value:
2
Variability:
0.6
Test group / Remarks:
5% dose
Parameter:
SI
Value:
2.3
Variability:
0.6
Test group / Remarks:
10% dose
Key result
Parameter:
SI
Value:
5.4
Variability:
1.3
Test group / Remarks:
25% dose
Key result
Parameter:
EC3
Value:
13.4
Interpretation of results:
other: skin sensitiser
Remarks:
in accordance with EU CLP (EC 1272/2008 and its updates)
Conclusions:
Based on the results of the study for read-across substance Cedarwood Texas oil distilled, Cedarwood oil Himalayan is considered to be a skin sensitiser.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

The skin sensitisation potential of Cedarwood oil Himalayan was assessed by using read across from Cedarwood Texas oil distilled. First the experimental skin sensitisation 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.

Skin sensitisation

The skin sensitisation potential of Cedrol, Cedarwood Texas oil distilled was tested according to OECD, Section 4, Health Effects, No.429 (2010). 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, Cedrol, Cedarwood Texas oil distilled is considered to be a skin sensitiser.

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 information, the substance should be classified as sensitising to the skin in accordance with the criteria outlined in the EU CLP Regulation (1272/2008/EC and its amendments) resulting in Skin Sens. 1B, H317