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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Only secondary literature available. Data are derived from the structural methyl ionone analog alpha-iso-methylionone, for more information please refer to the read-across justification.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1980
Reference Type:
publication
Title:
A toxicologic and dermatologic assessment of ionones when used as fragrance ingredients
Author:
D. Belsito, D. Bickers, M. Bruze, P. Calow, H. Greim, J.M. Hanifin, A.E. Rogers, J.H. Saurat, I.G. Sipes, H. Tagami
Year:
2007
Bibliographic source:
Food and Chemical Toxicology 45: S130–S167

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
subchroic dermal toxicity study
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
3-methyl-4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3-buten-2-one
EC Number:
204-846-3
EC Name:
3-methyl-4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3-buten-2-one
Cas Number:
127-51-5
Molecular formula:
C14H22O
IUPAC Name:
3-methyl-4-(2,6,6-trimethylcyclohex-2-en-1-yl)but-3-en-2-one
Constituent 2
Reference substance name:
Reference substance 001

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Type of coverage:
open
Vehicle:
not specified
Details on exposure:
Route of Administration: dermal
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 day
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
50, 170, 580, and 2000 mg/kg bw/day
Basis:
nominal per unit body weight
No. of animals per sex per dose:
15
Control animals:
yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS/CHECK FOR MORTALITY: Yes
- Time schedule: twice daily


DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule:


DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: scoring for erythema and eschar formation on a daily basis


BODY WEIGHT: Yes

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes


OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: pre test and at termination of study


HAEMATOLOGY: Yes
- Time schedule for collection of blood: on 7th and 13th week of study


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on 7th and 13th week of study


URINALYSIS: Yes
- Time schedule for collection of urine: on 7th and 13th week of study
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
Other examinations:
- Determination of wet organ weight

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
effects observed, treatment-related
Haematological findings:
effects observed, treatment-related
Urinalysis findings:
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Details on results:
50 mg/kg bw/day:
- liver, dose related increase in liver weight and changes in urinalysis parameters at this dose.

170 mg/kg bw/day:
- blood effects, kidney, liver, Changes in hematology parameters in both sexes.
- BUN levels increased with dose in males.
- Urine albumin levels were significantly increased in male groups at termination.
- Increases in the absolute and relative weights in the liver and kidneys in both sexes.

580 mg/kg bw/day:
- body weight changes, blood effects, efficiency food utility, kidney, liver, Reduced body weight gain in males.
- Food consumption elevations in females, lower efficiency food utilization in both male and females.
- Changes in hematology parameters of both sexes.
- Serum glucose levels were depressed in males at week 7 and in both sexes at termination.
- BUN levels increased with dose in males.
- Urine albumin levels were significantly increased in male groups at termination.
- Increases in the absolute and relative weights in the liver and kidneys in both sexes.

2000 mg/kg day:
- body weight changes, blood effects, bone marrow effects, efficiency food utility, kidney, liver, musculo-skeletal, microscopic examination revealed an unequivocal effect on the kidneys of males and a slight effect on bone marrow at this dose.
- Reduced body weight gain in females and in males.
- Food consumption elevations in females, lower efficiency food utilization in both male and females.
- Serum glucose levels were depressed in males at week 7 and in both sexes at termination.
- BUN levels increased with dose in males. Urine albumin levels were significantly increased in male groups at termination.
- Increases in the absolute and relative weights in the liver and kidneys in both sexes.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day
Sex:
male/female
Dose descriptor:
LOEL
Effect level:
170 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: haematology; histopathology

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion