3,5,5-trimethylcyclohex-3-en-1-one

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Accepted study design. Restriction: Insufficient documentation, one dose only.

Data source

Reference

Reference 1

Reference Type:

other: thesis

Title:

Contribution a l'etude analytique toxicologique et biochimique de l'isophorone.

Author:

Dutertre-Catella H

Year:

1976

Bibliographic source:

Universite Rene Descartes, Paris

Reference 2

Reference Type:

other: OECD SIDS

Title:

3,5,5-Trimethylcyclohex-2-enone (Isophorone), CAS No. 78-59-1

Author:

OECD SIDS

Year:

2003

Bibliographic source:

SIDS Initial Assessment Report for SIAM 16

Materials and methods

Principles of method if other than guideline:

The method followed is not described in the OECD SIDS Initial Assessment Report

GLP compliance:

not specified

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3,5,5-trimethylcyclohex-2-enone

EC Number:

201-126-0

EC Name:

3,5,5-trimethylcyclohex-2-enone

Cas Number:

78-59-1

IUPAC Name:

3,5,5-trimethylcyclohex-2-en-1-one

Details on test material:

- Analytical purity: not reported
- Origin: Elf Atochem S.A.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: approximately 200 g

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

air

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

18 months

Frequency of treatment:

6 hours/day; 5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
1.436 mg/L (250 ppm)
Basis:
no data

No. of animals per sex per dose:

10
The report suggests that two identical groups of males and two groups of females were exposed in addition to the unexposed control groups, corresponding to a total of six groups. As the presentation of results does not refer to absolute numbers of animals but only to percentages of total animals, their misinterpretation can be excluded.

Control animals:

yes, concurrent vehicle

Details on study design:

Post-exposure period: none

Examinations

Observations and examinations performed and frequency:

CLINICAL OBSERVATIONS AND FREQUENCY:
Mortality and signs of irritation: daily.

Body weight: weekly.

Hematology: monthly during first 10 months.

Urinanalysis: weekly.

Sacrifice and pathology:

Macroscopic and microscopic examination.

Results and discussion

Results of examinations

Details on results:

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL
Mortality and time to death: 40 % each of males and females, controls as well as exposed, died; time not reported.

Signs of irritation: Slight irritation of conjunctiva, no opacity of cornea, by end of third week bloody exsudate from nose indicating irritation of mucosa.
Body weight gain: No differences between exposed and control.

Hematology: No differences between exposed and control.

Urinalysis: No differences between exposed and control; pH approximately 9 in all groups.

Gross pathology: More or less pronounced hemorrhages of the lungs were observed in exposed and control animals likewise. Discoloration of the livers was also observed in the control group independent on exposure. The other organs inspected appeared normal.

Histopathology: Lesions in lungs were found in both exposed and control animals. Microvacuolisation in livers was more pronounced in exposed animals than in controls. The other organs were normal, or changes were considered to be insignificant.

Effect levels

Dose descriptor:

NOAEL

Basis for effect level:

other: See 'Details on results'

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Target system / organ toxicity

Critical effects observed:

not specified