Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable publication which meets basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Subchronic inhalation studies of complex fragrance mixtures in rats and hamsters.
Author:
Fukayama MY, Easterday OD, Serafino PA, Renskers KJ, North-Root H and Schrankel KR
Year:
1999
Bibliographic source:
Toxicology Letters 111(1-2): 175-187

Materials and methods

Principles of method if other than guideline:
6 and 13 week inhalation study with fragrance mixtures

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Fragrance mixtures (FM) B, E, F
- Composition of test material, percentage of components:

Test animals

Species:
rat
Strain:
other: CD and Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Wilmington (CD rats), Taconic Farms, Germantown, NY (SD rats)
- Age at study initiation: young
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 weeks

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
other: ethanol
Remarks on MMAD:
MMAD / GSD: 0.5 µm in FM E
4.3 µm in FM F
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Method of holding animals in test chamber: individually and placed in custom-made stainless steel inhalation chambers fitted with Plexiglas doors in the front and back.
- Source and rate of air: Compressed air, 6 to 34 cubic feet per minute
- Method of conditioning air: oil free and dried to 2°C
- System of generating particulates/aerosols: Laskin-type nebulizer
- Temperature, humidity, pressure in air chamber:
- Air flow rate: 1.6 - 4 l/min
- Method of particle size determination: Andersen Cascade Impactor
- Treatment of exhaust air: filtered through a comination of pre- and absulute filters, followed by a charcoal filter


TEST ATMOSPHERE
- Brief description of analytical method used: exposure concentration was established gravimetrically


Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
6 or 13 weeks, 4 h a day, 5 days a week
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
5.7 µg/m^3 in FM B
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
37.8 µg/m^3 in FM F
Basis:

No. of animals per sex per dose:
20 for FM B
12 for FM E
24 for Fm F
Control animals:
yes, concurrent no treatment
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

HAEMATOLOGY: Yes
- Time schedule for collection of blood: on the day or two following the last exposure
- Anaesthetic used for blood collection: Yes (sodium pentobarbital)
- Animals fasted: Yes, 16 h
- How many animals: all
- Parameters examined: red blood cell count, total and differential white blood cell counts, mean corpuscular volume, hemoglobin concentration and hematocrit.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on the day or two following the last exposure
- Animals fasted: Yes, 16 h
- How many animals: all
- Parameters examined: fasting glucose, urea nitrogen, glutamicoxalacetic transaminase, glutamic-pyruvic transaminase and alkaline phosphatase
Sacrifice and pathology:
GROSS PATHOLOGY: Yes: adrenal glands (both),brain, esophagus, eye, heart, muscle with sciatic nerve, kidneys, colon, trachea, lungs, hilar lymph
node, liver, pancreas, spleen, stomach, skin, duodenum, spinal cord, sternum, thyroid, urinary bladder, uterus, ovaries or testes, and any lesions or tissue masses and their regional lymph nodes



HISTOPATHOLOGY: Yes: trachea, lungs, adrenals, brain, esophagus, heart, kidneys, liver, panereas, spleen, sternum and uterus.
Statistics:
Student's t-test

Results and discussion

Results of examinations

Details on results:
No abnormalities in any parameter due to fragrance mixtures including geraniol compared to control group was observed

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion