Ocimum basilicum, ext.

Endpoint summary

Description of key information

Acute oral toxicity using read across from Linalool (tested in a study similar to OECD TG 401): LD50 = 2790 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1964

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Pre-GLP, pre-guideline study which seems to be performed under standardized conditions.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: young adults
- Weight at study initiation: no data
- Fasting period before study: 18 hours
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
No data

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Not specified

Doses:

Not specified

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: The usual observation period was 2 weeks; in a few cases, where no acute toxic signs were seen, the animals were observed for only one week.
- Frequency of observations and weighing: Frequency not known, all animals were maintained under close observation for recording toxic signs and time of death. Such observation was continued until animals appeared normal or showed weight gain.

Statistics:

LD50's were computed by the method of Litchfield & Wilcoxon (1949).

Preliminary study:

Not relevant

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 790 mg/kg bw

95% CL:

> 2 440 - < 3 180

Remarks on result:

other: Slope function 1.3 (95% CI 1.2-1.4)

Mortality:

Time of death between 4 and 18 hours after exposure

Clinical signs:

other: Ataxia was observed soon after treatment

Gross pathology:

Not specified

Interpretation of results:

other: Not acute toxic

Remarks:

in accordance with EU CLP (EC 1272/2008 and its updates)

Conclusions:

The acute oral toxicity test showed a LD50 of 2790 mg/kg bw. Based on this result, the test substance is considered to have a relatively low acute toxicity hazard via the oral route. In accordance with the criteria outlined in the UN-GHS legislation, the substance should be classified for acute oral toxicity (Acute Tox. 5 / H303).

Executive summary:

The acute oral toxicity of Linalool to rats was investigated, in a study performed similar to OECD TG 401. Ten Osborne-Mendel rats per concentration were used, the substance was administered orally via gavage, in a fasted state. Clinical signs and mortality were recorded over a 2 week period. The rats showed ataxia soon after treatment and mortality was observed after 4 -18 hrs. The LD50 was determined to be 2790 mg/kg body weight (confidence interval 2440 -3180).

Reference 2

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:

Remarks:

Information is derived from read across

Justification for type of information:

The read across justification is presented in the acute toxicity endpoint summary and the accompanying files are also attached there.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 790 mg/kg bw

95% CL:

> 2 440 - < 3 180

Remarks on result:

other: Slope function 1.3 (95% CI 1.2-1.4)

Interpretation of results:

other: Not acute toxic

Remarks:

in accordance with EU CLP (EC 1272/2008 and its updates)

Conclusions:

The acute oral toxicity test showed a LD50 of 2790 mg/kg bw. Based on this result, the test substance is considered to have a relatively low acute toxicity hazard via the oral route. In accordance with the criteria outlined in the UN-GHS legislation, the substance should be classified for acute oral toxicity (Acute Tox. 5 / H303).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

The acute oral and dermal toxicity of Basil oil was assessed by using read across from Linalool (CAS No.: 78-70-6). First the experimental acute toxicity information of Linalool will be summarised. Thereafter the read across justification is presented. The accompanying files are attached in the present endpoint summary.

Acute oral toxicity (Linalool)

The acute oral toxicity of Linalool to rats was investigated, in a study performed similar to OECD TG 401. Ten Osborne-Mendel rats per concentration were used, the substance was administered orally via gavage, in a fasted state. Clinical signs and mortality were recorded over a 2 week period. The rats showed ataxia soon after treatment and mortality was observed after 4 -18 hrs. The LD50 was determined to be 2790 mg/kg body weight (confidence interval 2440 -3180).

Read across justification

The acute oral toxicity of Basil oil obtained from the stems and leaves of Ocimum basilicum by steam distillation (Basil oil - Linalool type) CAS no: 84775-71-3 (target) using read across from Linalool, CAS no: 78-70-6 (source)

Introduction and hypothesis for the analogue approach

Basil oil - Linalool type is a UVCB which consists of hydrocarbon constituents some of which include oxygen. Its major constituents are Linalool(contains a tertiary OH group and two C=C bonds)and Eucalyptol(contains a cyclic ether group. The full composition is given at the end of the document in the data matrix. For Basil oil - Linalool type (target) no acute oral toxicity data are available. 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 acute oral toxicity of Basil oil - Linalool type, the acute oral toxicity effects of Linalool is used, which is the main constituent of Basil oil - Linalool type.

Hypothesis:Basil oil-Linalool type (target)is expected to have the same acute oral toxicity asLinalool (source).

Available information:The acute oral toxicity of Linalool to rats was investigated in a study performed similar to OECD TG 401 pre-GLP (Reliability 2). Ten Osborne-Mendel rats per concentration were used, they were administered the substance orally via gavage, in a fasted state. Clinical signs and mortality were recorded over a 2 week period. The rats showed ataxia soon after treatment and mortality was observed after 4 -18 hrs. The LD50 was determined to be 2790 mg/kg body weight (confidence interval 2440 -3180).

Target and Source chemical(s): The information onBasil oil - Linalool type(target)and the information from Linalool (source) are presented in the data matrix 1 of this document. This includes chemical structure of source, physico-chemical properties and toxicological information, relevant for acute oral toxicity.

Purity / Impurities:

The impurities are not relevant forBasil oil - Linalool type(target) as it is a UVCB (Naturally Complex Substance).

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:

Linaloolwas selected as analogue source because Basil oil – Linalool type consist of at least 45% Linalool.

Basil oil-Linalool type (target), beside Linalool, consists of various constituents that are present in variable ranges, as shown in data matrix 2. For only a two constituents acute oral toxicity information is available: Eugenol and Estragole)

Structural similarities and differences:Basil oil linalool type (target) contains mostly Linalool. Linalool has a tertiary alcohol, a terminal double bond and a terminal isopropene group. Such (functional) groups are also apparent in the other constituents: Alpha-bergamotene(contains two C=C double bonds), Germacrene D (contains three C=C double bonds), Gamma-cadinene (contains two C=C double bonds), Alpha-cadinol (contains a C=C bond and a tertiary OH group), Beta-elemene (contains three C=C double bonds), Alpha-bulnesene (contains two C=C double bonds), Myrcene (contains three C=C double bonds) and Gamma elemene (contains three C=C double bonds). Two constituents have other functional groups: Eugenol (contains C=C double bonds (aromatic and aliphatic), an alcohol and ether group) and Estragole (contains C=C double bonds (aromatic and aliphatic), and an ether group).

Toxicokinetics:All constituents of Basis oil will have a high oral absorption pattern based on the fairly low molecular weights ca <=200 and all log Kows are in the range of good absorption. The non-Linalool constituents will be prone to oxidation into primary, secondary and tertiary alcohols. The primary alcohols can turn into acids and will be excreted as such or when remain alcohols they can be glucuronated and/or conjugated to alpha-2u globulins, which all will be excreted via kidneys.Toxicodynamics:According to the ECHA Chapter R.7a: endpoint specific guidance R7.4.1.1, acute toxicity can be related to three main types of toxic effect, i.e. (i) general basal cytotoxicity, (ii) selective cytotoxicity and (iii) cell function specific toxicity. Acute toxicity may also result from substances interfering with extracellular processes (Seibert, 1965). Toxicity to the whole organism also depends on the degree of dependence of the organism on the specific function affected. For Linalool a general basal cytotoxicity can be anticipated, though some reactivity cannot be excluded because of the oxidation of some groups. The other constituents in Basil oil – Linalool type are expected to have similar basal cytotoxicity and reactivity in view of the similarities in oxidation patterns.

Remaining uncertainties:Linalool is the key constituent, and the other constituents are expected to have a similar reactivity mechanism and therefore the LD50 of Linalool represents the Basil oil – Linalool type. For Eucalyptol and Eugenol likely similar LD50s are anticipated being > 2000 mg/kg bw and some mortality is seen at 2000 mg/kg bw and higher. Estragole is more toxic with an LD50 of 1230 mg/kg bw. In view of its presence < 3% this will not significantly change the LD50 of Basil oil – Linalool type.

 

Conclusions on the acute oral toxicity endpoint

For Basil oil – Linalool type no acute oral toxicity data are available. Basil oil mainly contains Linalool and therefore the acute oral toxicity is derived from Linalool. The other constituents are expected to have a similar reactivity profile and the LD50 will be in the same order of magnitude. Linalool has an LD50 of 2790 mg/kg bw and therefore Basil oil – Linalool type will have an LD50 of 2790 mg/kg bw.

Final hazard conclusion: Basil – Linalool type has an LD50 of 2790 mg/kg bw.

 

Data matrix 1. Basil oil – Linalool type (target) and Linalool (source) information to support the read across for skin and eye irritation

CHEMICAL NAME	Basil oil - Linalool type	Linalool*
Molecular structure	N/A
	Target	Source
CAS	84775-71-3	78-70-6
REACH registration	To be registered (Annex VII)	Yes
Einecs	283-900-8	201-134-4
Molecular formula	N/A	C10H18O
Molecular weight	N/A	154.253
Physico-chemical properties
Appearances	Clear liquid (IFF, 2017)	Clear liquid
Melting point (˚C)	<-20(IFF, 2017)	>-74
Vapour pressure (Pa)	29.1 (IFF, 2017)	27
Exp. Water solubility	940.5 (IFF, 2017)	1560
Exp. Log Kow	2.4-5.6 (IFF, 2017)	2.9
Human health
Acute toxicity (oral)	Read across	LD50 2790 mg/kg bw  (OECD TG 401)
Genetic toxicity (Ames)	Negative (OECD TG 471)	Negative (OECD TG 471)

* Hazard properties from ECHA disseminated dossier (accessed March 2018)

 Data matrix 2. Key constituents of Basis oil and available information on acute oral toxicity ordered according to functional group starting with the linolool the key constituent

NAME#	CAS	Min conc	Max conc	Functional group and metabolic pathway	Acute oral toxicity
Linalool	126-91-0	45.00%	62.00%	Tertiary alcohol Glucuronation of alcohol	LD50 = 2790 mg/kg bw (Jenner et al., 1964* and ECHA dissemination site)
Alpha-cadinol	481-34-5	0.50%	5.00%	Tertiary alcohol Glucuronation of alcohol	Not available
Myrcene	123-35-3	< 0.01%	2.00%	Oxidation of (final) double bond	Not available
Germacrene D	37839-63-7	1.00%	5.00%	Oxidation of double bonds	Not available
Gamma-cadinene	39029-41-9	1.00%	5.00%	Oxidation of double bonds	Not available
Beta-elemene	33880-83-0	0.50%	5.00%	Oxidation of double bonds	Not available
Gamma elemene	3242-08-8	< 0.01%	2.00%	No addition	Not available
Alpha-bergamotene	17699-05-7	0.01%	8.00%	No addition	Not available
Eucalyptol	470-82-6	3.00%	12.00%	Ether in ring May oxidise	LD50 2480 mg/kg bw (Jenner et al., 1964*)
Estragole	140-67-0	< 0.01%	3.00%	Ether Demethylation and oxidation of final double bond, being more reactive compared to Linalool	1230 mg/kg bw (Moreno, 1972, RIFM database)
Eugenol	97-53-0	0.01%	8.00%	Ether Demethylation; Oxidation of final double bond	LD50 >2,000 mg/kg body weight (NTP, 1983; 1/10 rat died). LD50 >1,500 <3,000 mg/kg body weight. (NTP, 1983; 1/5 male mid dose mice and 2/5 male + 5/5 female high dose mice died).
Alpha-bulnesene	3691-11-0	0.10%	3.00%	No addition	Not available
Other minor and unknown constituents	N/A	5.00%	20.00%		Not available

# Chemical structures are present in the attached document

*Jenner, P.M., Hagan, E.C., Taylor, J.M., Cook, E.L., Fitzhugh, O.G., 1964, Food Flavorings and Compounds of Related Structure I. Acute Oral Toxicity, Food and Cosmetics Toxicology, 2, 327-343.

Justification for classification or non-classification

Based on the available data, the substance needs to be classified for acute oral toxicity in accordance with UN-GHS (Acute Tox. 5 / H303), but does not need to be classified according to the criteria outlined in EU CLP (EC no 1272/2008 and its amendments).