reaction mass of 3-methyl-4-(2,6,6-trimethylcyclohex-2-en-1-yl)but-3-en-2-one and 1-(2,6,6-trimethylcyclohex-2-en-1-yl)pent-1-en-3-one

Repeated dose toxicity: dermal

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

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1980

Reference 2

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

Test material information

Constituent 1

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

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

1

Dose descriptor:

NOAEL

Effect level:

50 mg/kg bw/day

Sex:

male/female

2

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