Carvacrol

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from publication.

Data source

Reference

Reference Type:

publication

Title:

Short-Term Inhalation Toxicity study of the given test chemical.

Author:

PINCHING et al.

Year:

1974

Bibliographic source:

Brain Research

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Short-Term Inhalation Toxicity Study was conducted by using the given test chemical in rats.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Carvacrol

EC Number:

207-889-6

EC Name:

Carvacrol

Cas Number:

499-75-2

Molecular formula:

C10H14O

IUPAC Name:

2-methyl-5-(propan-2-yl)phenol

Details on test material:

- Name of test material : 2-methyl-5-(propan-2-yl)phenol
- Common name : Carvacrol
- Molecular formula : C10H14O
- Molecular weight : 150.2196 g/mol
- Smiles notation : CC(C)c1ccc(C)c(O)c1
- InChl : 1S/C10H14O/c1-7(2)9-5-4-8(3)10(11)6-9/h4-7,11H,1-3H3
- Substance type: Organic
- Physical state: Liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: about 2 weeks old
- Weight at study initiation: weighed between 28 and 39 g
- Housing: Rats were raised in cylindrical lucite cages, 20 cm in diameter and 20 cm high, with closed tops.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Vehicle:

other: filtered fresh air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: No data
- Method of holding animals in test chamber: Rats were raised in cylindrical lucite cages, 20 cm in diameter and 20 cm high, with closed tops. The cages were placed on a coarse grid, and the droppings were removed twice a day.
- Source and rate of air: Fresh air was blown through filters of charcoal and molecular sieves. The flow of air was monitored with a venturimeter for each of two sets of 6 cages and kept at about 0.6 litre × sec -1 through each cage.
- Method of conditioning air: No data
- System of generating particulates/aerosols: Test chemical was introduced into the air stream from a glass bottle, the content of which was weighed before and after the experiments to measure the concentration of substance in the stream.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

2 different exposure times were used, i.e. 4 weeks and 8 weeks

Frequency of treatment:

not specified

Doses / concentrations

Remarks:

2.1 ×10−8 M (0.0315 mg/l)

No. of animals per sex per dose:

3 per group

Control animals:

yes, concurrent vehicle

Details on study design:

not specified

Positive control:

not specified

Examinations

Observations and examinations performed and frequency:

OTHER: The study examined the distribution of changes in the mitral cells of the olfactory bulbs following exposure to odor, rather than on the nature and progression of the morphological
alternations.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, the animals were sacrificed at about 1, 2 and 3 months of age. The animals were perfused in buffered saline and fixed with a formaldehyde-glutaraldehyde mixture.

Statistics:

not specified

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

The principal microscopic morphological changes noted were a darkening and shrinkage of the cell bodies (both cytoplasm and nucleus). Moderate to dense selective degeneration was noted in the olfactory bulbs of rats.

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

no effects observed

Description (incidence and severity):

A specific pattern of mitral cell degeneration was observed in the olfactory bulb; the pattern and extent of this 'selective degeneration' did not appear to be correlated with the concentration of the chemical. The pattern of degeneration in coronal sections was maintained through the antero-posterior extent of the bulb. These results suggest a topological representation of test chemical in
the olfactory bulb.

Effect levels

Dose descriptor:

LOAEC

Effect level:

0.032 mg/L air

Based on:

test mat.

Sex:

not specified

Basis for effect level:

gross pathology

other: Moderate to dense selective degeneration was noted in the olfactory bulbs of rats

Remarks on result:

other: Moderate to dense selective degeneration was noted in the olfactory bulbs of rats

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The LOAEC value was considered to be 0.0315 mg/l, when rats were treated with the given test chemical via inhalation route for 4 or 8 weeks of exposure.

Executive summary:

Short-Term Inhalation Toxicity study was conducted by using the given test chemical on 3/group Wistar rats at test concentration of 2.1×10−8 M (0.0315 mg/l) at two different exposure times as, 4 and 8 weeks. Rats were raised in cylindrical Lucite cages, 20 cm in diameter and 20 cm high, with closed tops. The cages were placed on a coarse grid, and the droppings were removed twice a day. Fresh air was blown through filters of charcoal and molecular sieves. The flow of air was monitored with a venturimeter for each of two sets of 6 cages and kept at about 0.6 litre × sec -1 through each cage. Each substance was introduced into the air stream from a glass bottle, the content of which was weighed before and after the experiments to measure the concentration of substance in the stream. Control animals exposed to filtered fresh air only. The animals were sacrificed at about 1, 2 and 3 months of age. The animals were perfused in buffered saline and fixed with a formaldehyde-glutaraldehyde mixture. Animals have been fixed and their olfactory bulbs have been examined and compared with control litter-mates, which have been exposed to filtered room air only. In this study emphasis has been placed upon the distribution of changes in the mitral cells of the olfactory bulbs following exposure to the given test chemical, rather than on the nature and progression of the morphological alterations. The principal microscopic morphological changes noted were a darkening and shrinkage of the cell bodies (both cytoplasm and nucleus). Moderate to dense selective degeneration was noted in the olfactory bulbs of rats. A specific pattern of mitral cell degeneration was observed in the olfactory bulb; the pattern and extent of this 'selective degeneration' did not appear to be correlated with the concentration of the chemical. The pattern of degeneration in coronal sections was maintained through the antero-posterior extent of the bulb. These results suggest a topological representation of test chemical in the olfactory bulb. Under the condition of this, the LOAEC value was considered to be 0.0315 mg/l, when rats were treated with the given test chemical via inhalation route for 4 or 8 weeks of exposure.