Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: OECD TG 401: LD50 >5000 mg/kg bw based on read-across from Patchouli oil.

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
Study period:
2017
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: read-across information
Justification for type of information:
The read across rationale for this substance is presented in the Acute Toxicity Endpoint summary, the documents 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 harmful.
Remarks:
According to EU CLP Regulation (EC) No. 1272/2008 and its amendments.
Conclusions:
The substance has an LD50 >5000 mg/kg bw.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Reliability has been presented as 2 because similar to OECD Guideline protocol has been followed but not GLP.
Justification for type of information:
Information is used for read across to Patchouli Alcohol
Reason / purpose:
read-across: supporting information
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
no details on test animals and environmental conditions
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
No details.

ENVIRONMENTAL CONDITIONS
No details.
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
gavage
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
Total 10 (no sex specified)
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
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred.
Clinical signs:
No clinical signs were observed.
Interpretation of results:
other: Not acute harmful.
Remarks:
According to EU CLP Regulation (EC) No. 1272/2008 and its amendments.
Conclusions:
An LD50 of >5000 mg/kg bw was obtained in the acute oral toxicity study with rats similar to OECDTG 401.
Executive summary:

In an acute oral toxicity study one groups of 10 rats were orally exposed to 5000 mg/kg bw of the substance in as study similar to OECD TG 401, pre-guideline and pre-GLP. The rats were observed for signs of toxicity and clinical signs for a period of 14 days. No deaths occurred and no clinical signs were observed. Based on the results, an LD50 of >5000 mg/kg bw was obtained in the acute oral toxicity study with rats and is not considered harmful.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The acute oral toxicity result is of sufficient quality and adequate for this dossier.

Additional information

The executive summary of the source substance Patchouli oil is presented first. Thereafter the read across justification for Patchouli alcohol from Patchouli oil is presented. The accompanying files are also attached in the present section.

Patchouli oil and its acute oral toxicity

In an acute oral toxicity study one groups of 10 rats were orally exposed to 5000 mg/kg bw of the substance in as study similar to OECD TG 401, pre-guideline and pre-GLP. The rats were observed for signs of toxicity and clinical signs for a period of 14 days. No deaths occurred and no clinical signs were observed. Based on the results, an LD50 of >5000 mg/kg bw was obtained in the acute oral toxicity study with rats and is not considered harmful.

The acute oral toxicity of Patchouli alcohol using read across from Patchouli oil

Introduction and hypothesis for the analogue approach

Patchouli alcohol is a mono-constituent and its chemical structure has two rings, these two rings are bridged with a C-atom. Four methyl groups are attached to the rings or to the bridge. The one hydroxyl ring is attached to one of the rings. For this substance no acute oral toxicity data are available.

In accordance with Article 13 of REACH, lacking information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. For assessing the acute oral toxicity of Patchouli alcohol the analogue approach is selected because for one closely related analogue acute oral toxicity information is available which can be used for read across.

Hypothesis: Patchouli alcohol has similar acute oral toxicity compared to Patchouli oil resulting in a similar LD50 because the Patchouli alcohol is the key component of Patchouli oil.

Available information: The source chemical Patchouli oil has been tested in an acute oral toxicity test up to 5000 mg/kg bw with a 2-week observation period similar to OECD 401 and the test result, LD50 > 5000 mg/kg bw, receives a reliability of 2 (non-GLP).

Target chemical and source chemical(s)

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

Purity / Impurities

Patchouli alcohol is a mono-constituent and therefore the acute oral toxicity will be due to this main component. All impurities are < 10% and are expected to have a similar acute oral toxicity because these have similar structures.

Analogue approach justification

According to Annex XI 1.5 read across can be used to replace testing when the similarity can be based on a common backbone and a common functional group. When using read across the result derived should be applicable for C&L and/or risk assessment and it should be presented with adequate and reliable documentation.

Analogue selection:The first selected analogue is Patchouli oil because Patchouli alcohol is the key component of this oil (which was also found when running the OECD Toolbox). Other similar alcohols areΒ-Caryophyllene alcohol (CAS 472-97-9) and Cedrol (CAS 77-53-2) but no acute oral toxicity was available for these two substances. Other analogues in the OECD Toolbox were without data (CAS no.:73049-85-1, 98167-54-5).

Structural similarities and differences:Patchouli oil’s key component is Patchouli alcohol (ca. 32%) and therefore these two are anticipated to have the same acute oral toxicity. Patchouli oil has other hydrocarbon components, which are similar to the alcohol type but with no alcohol group and with one or two non-conjugated bonds. These double bonds may result in a slightly more flat and less flexible structure compared to absence of double bonds.

Toxico-kinetic:Absorption: Patchouli alcohol and Patchouli oil have similar toxico-kinetic characteristics based on the similarity in chemical structure and physico-chemical properties. Patchouli alcohol and Patchouli oil have both molecular weights favourable for uptake; the measured log Kows are within the range for favourable uptake (Log Kow between 2 and 7). The non-alcohol constituents of Patchouli oil are somewhat more flat and less flexible and therefore may pass the cell membranes more easily resulting in a faster exposure. From this perspective the acute oral toxicity of Patchouli oil would be conservative.

Metabolism: The metabolism of the non-alcohol constituents will result in oxygenated methyl groups. Alcohols and/or acids may be formed during Phase 1 metabolism and thereafter these will be conjugated. The double bonds to which a methyl group is attached may be oxidized to epoxides and further react into alcohols and subsequently be conjugated.

Toxico-dynamics: The reactivity of Patchouli alcohol and Patchouli oil are similar because the key constituents are very similar.

Uncertainty of the prediction:Patchouli alcohol is the key component of Patchouli oil and therefore the acute oral toxicity can be predicted from this oil.

Data matrix

The relevant information on physico-chemical properties and toxicological characteristics are presented in the Data Matrix.

Conclusions for acute oral toxicity

When using read across the result derived should be applicable for C&L and/or risk assessment and be presented with adequate and reliable documentation. For Patchouli oil an acute oral toxicity test with 2-week observation period is available (Reliability 2) with a LD50 of >5000 mg/kg bw. In view of the structural similarity and/or metabolites as presented above these results can be used for Patchouli alcohol.

Final conclusion on hazard: Patchouli alcohol has an LD50 of >5000 mg/kg bw.

Data matrix: Data to support the assessment of the acute oral toxicity of Patchouli alcohol using read across from Patchouli oil

Common names

Patchouli alcohol

Patchouli oil

 

Target

Source

Chemical structures

CAS no

5986-55-0

8014-09-3

REACH registration

Registered before 2018 deadline

Registered*

EC no

227-807-2

939-227-3

Empirical formula

C15H26O

NA

Physico-chemical data

 

Data are from the ECHA dissemination site

Molecular weight

222.37

NA

Physical state

Solid

Liquid

Melting point,oC

75.52 (c)^
50.2 (m)#

<-50

 

Boiling point,oC

280.20 (c)
321.7 (m)

320

Vapour pressure, Pa

0.033 (c)
0.14 (m)

0.94 at 20°C

Water solubility, mg/l

8-40 (c)
41.8 (m)

12.3

Log Kow

3.98 (c)
5.5 (m)

1.8-5.7

Human health endpoints

 

 

Acute oral tox in mg/kg bw

Read-across to patchouli oil

>5,000

^(c) means calculated using EpiSuite; #(m) is measured by IFF

*https://echa.europa.eu/nl/registration-dossier/-/registered-dossier/14973

Justification for classification or non-classification

The substance does not need to be classified for acute oral toxicity according to EU CLP Regulation (EC) No. 1272/2008 and its amendments.