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Administrative data

Description of key information

Acute oral toxicity using read across from Cedarwood Texas oil distilled: (similar to OECD TG 401): LD50 >5000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
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
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Interpretation of results:
other: not acute toxic
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 not acute toxic via the oral route.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Aug 1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Well conducted study with limited detailed information
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
pre-GLP
Test type:
fixed dose procedure
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: obtained from sponsor, Material number 74-172
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 5000 mg/kg bw
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10 (Sex unspecified)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Daily
- Necropsy of survivors performed: Not specified
- Other examinations performed: Clinical signs
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
None
Body weight:
Not reported
Gross pathology:
Not reported
Interpretation of results:
other: Not acute toxic
Remarks:
in accordance with EU CLP (EC 1272/2008 and its updates)
Conclusions:
The oral LD50 value of Cedrenol in rats was established to be higher than 5000 mg/kg bw, under the conditions of this study.
Executive summary:

The acute toxic potential of Cedrenol was assessed in an acute oral toxicity limit test performed similar to OECD TG 401. Ten rats were exposed to 5000mg/kg bw Cedrenol 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 occured in the test animals. Based on these results the LD50 for acute oral toxicity was set at > 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Well conducted study with limited detailed information

Additional information

The acute oral toxicity of Cedarwood oil Himalayan was assessed by using read across from Cedarwood Texas oil distilled. First the experimental acute toxicity 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.

Acute oral toxicity:

The acute toxic potential of Cedrenol was assessed in an acute oral toxicity limit test performed in 10 rats. The rats were exposed to 5000 mg/kg bw Cedrenol 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 occured in the test animals. The LD50 for acute oral toxicity was therefore set at >5000 mg/kg bw.

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 in Cedarwood 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 acute oral toxicity in accordance with the criteria outlined in EU CLP (EC no 1272/2008 and its amendments).