3,5,5-trimethylcyclohex-2-enone

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Restriction: one dose only

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1968

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

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Four groups of male and female albino rats (10 per sex and dose) were exposed to the test substance (as vapour) in filtered room air at a concentration of 0.25 mg/L air for 6h per day, on 5 days per week, for a duration of 4 weeks. The animals were observed at frequent intervals for signs of irritation. At the end of the 4-week study period, hematological dererminations were carried out in 5 animals per sex per group. Terminal body weights were recorded and the animals were necropsied. Lung, liver, kidneys, adrenal and spleen were examined histopathologically in 3 animals per sex per dose.

GLP compliance:

no

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

Molecular formula:

C9H14O

IUPAC Name:

3,5,5-trimethylcyclohex-2-enone

Test animals

Species:

rat

Strain:

other: Charles River Caesarian-derived albino rats

Sex:

male/female

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 1000 L stainless steel and glass exposure chambers
- Method of holding animals in test chamber: not specified
- Source and rate of air: Air flow through the chamber was maintained by a positive pressure rotary pump located at the exhaust side of the chamber.
- Method of conditioning air: not specified
- System of generating particulates/aerosols: The vapours were generated by metering the liquid into a positive pressure spray nozzle with a Harvard infusion pump. The resultant aerosol was introduced into a large, triple necked distilling flask. A heating mantle was used to maintain the flask at a temperature adequate to vaporize the entering aerosol.
- Temperature, humidity, pressure in air chamber: not specified
- Air flow rate: The air flow rate was monitored by a rotameter
- Air change rate: not specified
- Treatment of exhaust air: not specified

TEST ATMOSPHERE
- Brief description of analytical method used: The analytical concentration of the chamber was determined daily by analysis of samples with a Beckman BD spectrometer. Each sample was obtained by drawing a known volume of the chamber atmosphere through a scrubber containing methanol as absorbent. The concentration of test material in each sample was ascertained from a standard curve which was prepared by plotting known concentrations of standard solution against percent transmission of the solutions. The concentration of the experimental atmosphere was calculated from the volume of chamber atmosphere which had been passed through the scrubber and the total liquid volume of the sample.
- Samples taken from breathing zone: not specified

VEHICLE (if applicable)
- filtered room air

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

28 d

Frequency of treatment:

6 hours/day; 5 days/week

Doses / concentrations

Dose / conc.:

0.25 mg/L air (nominal)

No. of animals per sex per dose:

10

Control animals:

yes, concurrent no treatment

Details on study design:

Post-exposure period: none

Examinations

Observations and examinations performed and frequency:

- Clinical signs: at frequent intervals

- Mortality: at frequent intervals

- Body weight: at study initiation and termination

- Haematology: at study initiation and termination, identical 50 % of animals of each group

Sacrifice and pathology:

ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):
- Macroscopic: brain, pituitary, trachea, thyroid, parathyroid, lungs, heart, liver, spleen, stomach, small intestine, large intestine, adrenals, kidneys, urinary bladder, gonads, femur
- organ weights: lungs, liver, kidneys, adrenal, spleen

- Microscopic: lungs, liver, kidneys, adrenal, spleen for three males and three females of each group

Statistics:

performed on body and organ weights

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Slight nasal bleeding on day 3, reddish-brown discoloration of the fur surrounding the nasal regions on days 6 through 8

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Body weight only of male rats was significantly reduced compared to control.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Differential blood count: increase of the percentage of lymphocytes (pre-exposure: 81.6 and 80.2 % among males and females, respectively; post-exposure: 84.6 and 86.0 %, respectively), decrease in the percentage of segmented neutrophiles (pre-exposure: 17.4 and 18.2 % among males and females, respectively; post-exposure: 14.6 and 13.3 %, respectively).

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Absolute and relative liver weight only of male rats were significantly reduced compared to control.

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Effect levels

Dose descriptor:

NOAEL

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Target system / organ toxicity

Critical effects observed:

not specified