Terpene hydrocarbon alcohols, terpene processing by-products

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1959

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

This information is used for read-across to Terpene hydrocarbon alcohols

Data source

Reference

Reference Type:

publication

Title:

Camphor in flavourings and other food ingredients with flavouring properties; opinion of hte Scientific panel on food additives, flavourings, processing aids and materials in contact with food on a request from the commission

Author:

EFSA

Year:

2008

Bibliographic source:

The EFSA Journal, 729, 1-15

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Groups of 5 rats were exposed daily for 8 weeks by gavage.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Bornan-2-one

EC Number:

200-945-0

EC Name:

Bornan-2-one

Cas Number:

76-22-2

Molecular formula:

C10H16O

IUPAC Name:

1,7,7-trimethylbicyclo[2.2.1]heptan-2-one

Test material form:

liquid: viscous

Test animals

Species:

other: white rat

Administration / exposure

Route of administration:

oral: gavage

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

8 weeks

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

250 other: mg/kg bw Salvia oil containing 7-50% camphor

Doses / concentrations 2

Dose / conc.:

500 other: mg/kg bw Salvia oil containing 7-50% camphor

Doses / concentrations 3

Dose / conc.:

1 000 other: mg/kg bw Salvia oil containing 7-50% camphor

Doses / concentrations 4

Dose / conc.:

1 250 other: mg/kg bw Salvia oil containing 7-50% camphor

No. of animals per sex per dose:

5

Control animals:

not specified

Examinations

Sacrifice and pathology:

Clinical signs and mortality

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

a daily dose of 250 mg/kg bw Salvia oil was well tolerated. When the dose was increased to 500 mg/kg bw/d, some convulsing was observed.

Mortality:

mortality observed, treatment-related

Description (incidence):

Upon increase to 1000 mg/kg bw/d, most animals died and all animals died when the level was increased to 1250 mg/kg bw/d.

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

18 mg/kg bw/day (nominal)

Based on:

other: camphor

Remarks:

(7% present in Salvia oil).

Sex:

not specified

Basis for effect level:

clinical signs

Target system / organ toxicity

1

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

36 other: mg/kg bw/d based on Camphor (7% present in Salvia oil).

System:

other: convulsions

Organ:

not specified

Treatment related:

yes

Dose response relationship:

not specified

Relevant for humans:

not specified

2

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

72 other: mg/kg bw/d based on Camphor (7% present in Salvia oil).

System:

other: mortality

Organ:

not specified

Treatment related:

yes

Dose response relationship:

yes

Relevant for humans:

not specified

Any other information on results incl. tables

The effect value above presented is based on a reported NOAEL of 250 mg/kg bw Salvia oil containing 7-50% Camphor. In calculation of the NOAEL for Camphor, the lower limit of 7% was used as a conservative approach.

Applicant's summary and conclusion

Conclusions:

For the test substance Savia oil, the NOAEL was determined to be 250 mg/kg bw/d based on convulsions oberved at a test concentration of 500 mg/kg bw/d. Salvia oil containins 7-50% Camphor. In calculation of the NOAEL based on Camphor, the lower limit of 7% was used as a conservative approach.

Executive summary:

In an 8 -week toxicity study with groups of 5 white rats were given an oral daily dose of 250 mg/kg bw Salvia oil (sage oil) which was well tolerated. When the dose was increased to 500 mg/kg bw/d, some convulsing was observed. Further increase of the dose level resulted in mortality of most (1000 mg/kg bw/d), or all animals (1250 mg/kg bw/d). The observed No Observed Adverse Effect Level (NOAEL) is 250 mg/kg bw/d based on sage oil, corresponding to a NOAEL of 18 to 125 mg/kg bw/d, based on Camphor.