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Toxicological information

Repeated dose toxicity: oral

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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

Reference
Name:
Unnamed
Type:
Constituent
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 / concentrationsopen allclose all
Dose / conc.:
250 other: mg/kg bw Salvia oil containing 7-50% camphor
Dose / conc.:
500 other: mg/kg bw Salvia oil containing 7-50% camphor
Dose / conc.:
1 000 other: mg/kg bw Salvia oil containing 7-50% camphor
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

open allclose all
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
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.