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Description of key information

Acute toxicity: oral: LD50 = ca. 3800 mg/kg bw (similar to OECD 401 in rats; K2) _ Read-across from alpha-santalol.

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
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included as attachment to Section 13

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar Physico-Chemical, and Toxicological properties because of their structural similarity.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The target substance is a multi-constituent substance, defined as a reaction mass of two isomers. The source substance is a mono-constituent substance, defined as the major isomer of the target substance.

3. ANALOGUE APPROACH JUSTIFICATION
Alpha- and beta-santalols are classified under Cramer class I, i.e. substance with simple chemical structures and for which efficient modes of metabolism exist, suggesting a low order of oral toxicity.
The LD50 value of apha-santalol in rats is 3800 mg/kg bw. Although no data is available on beta-santalol itself, data on the natural Sandalwood oil was available. Natural Sandalwood oil contains ca. 50 % of alpha-santalol, ca. 20 of beta-santalol and similar impurities than the target substance. The LD50 in rat of the oil was determined to be 5580 mg/kg bw. As the LD50 of the oil is greater than the LD50 of the alpha-santalol, it is considered that the presence of beta-santalol has no adverse outcome on the toxicity of the oil. As a worst case, it is assumed that the LD50 value of the source substance alpha-santalol can be applied to the target substance.
It is therefore considered appropriate and scientifically justified to read-across the data from the source to the target substance.
Although not performed according to GLP, the study design (eq. to OECD TG 401) is considered to be sufficiently adequate and reliable for the purpose of the prediction based on read-across. The test material used represents the source substance as described in the hypothesis in terms of purity and impurities. The results of the studies are adequate for the purpose of classification and labelling.
Therefore, based on the considerations above, it can be concluded that the result of the acute oral test conducted with the source substance is highly likely to predict the properties of the target substance and is considered as adequate to fulfil the information requirement of Annex VII, 8.5.1.

4. DATA MATRIX
Cf. document attached to Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Reason / purpose for cross-reference:
read-across source
Preliminary study:
Not applicable
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
ca. 3 800 mg/kg bw
Based on:
test mat.
95% CL:
>= 3 060 - <= 4 710
Mortality:
1/10 at 2000 mg/kg bw; 2/10 at 2500 mg/kg bw; 5/10 at 3200 mg/kg bw; 5/10 at 4000 mg/kg bw; 7/10 at 5000 mg/kg bw.
Clinical signs:
Immediate stimulation followed by ataxia.
Body weight:
No data
Gross pathology:
No data
Other findings:
None

None

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Under the test conditions, the oral LD50 is ca. 3800 mg/kg bw in rats [3060-4710 mg/kg bw] therefore alpha-santalol (source substance) is classified in Category 5 according to the Regulation EC No. 1272/2008 (CLP) and to the GHS. The same conclusion applies to the target sustance.
Executive summary:

In an acute oral toxicity study (limit test), performed similarly to OECD Guideline No. 401, groups of rats (10/dose) were administered a single oral dose of alpha-santalol (source substance) at 2000, 2500, 3200, 4000 or 5000 mg/kg bw. Animals were then observed for mortality and clinical signs daily for 14 days.


 


Mortality was observed at all dose levels: 1/10 at 2000 mg/kg bw; 2/10 at 2500 mg/kg bw; 5/10 at 3200 mg/kg bw; 5/10 at 4000 mg/kg bw; 7/10 at 5000 mg/kg bw. Clinical signs included immediate stimulation followed by ataxia.


Rat Oral LD50 = 3800 mg/kg bw [3060 -4710 mg/kg bw]


 


Under the test conditions, alpha santalol (source substance) is classified in Category 5 according to the Regulation EC No. 1272/2008 (CLP) and to the GHS. The same conclusion applies to the target substance.


 


Although poorly detailed, this study is considered to be acceptable to fulfill the acute oral toxicity endpoint.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
No details on study protocol
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
No data
Route of administration:
oral: unspecified
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
No data
Doses:
2000, 2500, 3200, 4000 and 5000 mg/kg bw
No. of animals per sex per dose:
10 animals/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no data
Statistics:
No data
Preliminary study:
Not applicable
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
ca. 3 800 mg/kg bw
Based on:
test mat.
95% CL:
>= 3 060 - <= 4 710
Mortality:
1/10 at 2000 mg/kg bw; 2/10 at 2500 mg/kg bw; 5/10 at 3200 mg/kg bw; 5/10 at 4000 mg/kg bw; 7/10 at 5000 mg/kg bw.
Clinical signs:
Immediate stimulation followed by ataxia.
Body weight:
No data
Gross pathology:
No data
Other findings:
None

None

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Under the test conditions, the oral LD50 is ca. 3800 mg/kg bw in rats [3060-4710 mg/kg bw] therefore alpah-santalol is classified in Category 5 according to the Regulation EC No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute oral toxicity study (limit test), performed similarly to OECD Guideline No. 401, groups of rats (10/dose) were administered a single oral dose of alpha-santalol at 2000, 2500, 3200, 4000 or 5000 mg/kg bw. Animals were then observed for mortality and clinical signs daily for 14 days.


 


Mortality was observed at all dose levels: 1/10 at 2000 mg/kg bw; 2/10 at 2500 mg/kg bw; 5/10 at 3200 mg/kg bw; 5/10 at 4000 mg/kg bw; 7/10 at 5000 mg/kg bw. Clinical signs included immediate stimulation followed by ataxia.


Rat Oral LD50 = 3800 mg/kg bw [3060 -4710 mg/kg bw]


 


Under the test conditions, alpha santalol is classified in Category 5 according to the Regulation EC No. 1272/2008 (CLP) and to the GHS. 


Although poorly detailed, this study is considered to be acceptable to fulfill the acute oral toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 800 mg/kg bw
Quality of whole database:
The available study was non-GLP but was considered to be reliable enough to cover this endpoint (Klimish score= 2)

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Not required for substances at the REACH Annex VII tonnage level.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute toxicity: oral


A key study was identified on the source substance, i.e. on the major constituent of the registered substance, alpha-santalol (Snell, 1972, rel.2). Read-across justification is attached to Iuclid Section 13.



In this acute oral toxicity study, performed similarly to OECD Guideline No. 401, rats were given a single oral dose of test material at 2000, 2500, 3200, 4000 or 5000 mg/kg bw. Animals were then observed for mortality and clinical signs for 14 days and at the end of the study the surviving animals were sacrificed for necropsy.


Mortality was observed at all dose levels: 1/10 at 2000 mg/kg bw; 2/10 at 2500 mg/kg bw; 5/10 at 3200 mg/kg bw; 5/10 at 4000 mg/kg bw; 7/10 at 5000 mg/kg bw. Clinical signs included immediate stimulation followed by ataxia.


Rat Oral LD50 = 3800 mg/kg bw [3060 -4710 mg/kg bw].


 


No data was available on the second constituent of the target substance, beta-santalol. However, both alpha- and beta-santalols are classifed under Cramer class I, i.e. substances with simple chemical structures and for which efficient modes of metabolism exist, suggesting a low order of oral toxicity. In addition, the acute oral toxicity (LD50) of natural sandalwood oil in rats, which contains both alpha- and beta-santalols, was reported to be 5580 mg/kg bw (Burdock and Carabin, 2007). It was therefore considered that the presence of beta-isomer has no adverse outcome on the toxicity of the target substance.


As a worst case, it was assumed that the LD50 value of the source substance alpha-santalol can be applied to the target substance.


 


Reference:


Burdock GA, Carabin IG. Safety assessment of sandalwood oil (Santalum album L.). Food Chem Toxicol. 2008 Feb;46(2):421-32. doi: 10.1016/j.fct.2007.09.092. Epub 2007 Sep 21. PMID: 17980948.

Justification for classification or non-classification

Harmonised classification:


The substance has no harmonised classification according to the Regulation (EC) No. 1272/2008 (CLP).


 


Self classification:


Acute toxicity via Oral route:


Based on the available information, the registered substance is:


- not classified according to the CLP as the oral LD50 is expected to be higher than 2000 mg/kg bw based on constituent data (alpha-santalol).


- classified in Category 5 according to the GHS as the oral LD50 is expected to be between 2000 and 5000 mg/kg bw based on constituent data (alpha-santalol).



Acute toxicity via Dermal route:


No data was available.Not required for substances at the REACH Annex VII tonnage level.



Acute toxicity (Inhalation):


No data was available. Not required for substances at the REACH Annex VII tonnage level.



Specific target organ toxicity: single exposure (Oral):


The classification criteria according to the CLP and the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C ≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.


The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and the GHS No. 1272/2008 are not met since narcotic effects were not observed in the acute oral toxicity study.



Specific target organ toxicity: single exposure (Dermal):


No data was available. Not required for substances at the REACH Annex VII tonnage level.



Specific target organ toxicity: single exposure (Inhalation):


No data was available. Not required for substances at the REACH Annex VII tonnage level.


 


Aspiration hazard:


The substance is not a hydrocarbon and no effects were observed on lungs in oral study, therefore the criteria for aspiration toxicity according to the CLP and to the GHS are not met.