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

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment. Restriction: No organ weight determination, no clinical biochemistry.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Toxicology and carcinogenesis studies of isophorone in F344 rats and B6C3F1 mice.

Author:

Bucher JR, Huff J, Kluwe WM

Year:

1986

Bibliographic source:

Toxicology 39: 207-219

Reference 2

Reference Type:

review article or handbook

Title:

Toxicology and Carcinogenesis Studies of Isophorone in F344/N Rats and B6C3F1 Mice.

Author:

NTP (U.S. National Toxicology Program)

Year:

1986

Bibliographic source:

Techn Rep Ser No. 291, U.S. Department of Health and Human Services

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Repeated Dose Toxicity, U.S. NTP

GLP compliance:

not specified

Limit test:

no

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: 97% , 0.3% water
- Origin: Leidy Chemical Corporation

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8 weeks

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

- Total volume applied: 1 mL

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

13 weeks (91 days)

Frequency of treatment:

5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
62.5; 125; 250; 500; or 1000 mg/kg bw d
Basis:
actual ingested

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Details on study design:

Post-exposure period: none

Examinations

Observations and examinations performed and frequency:

CLINICAL OBSERVATIONS AND FREQUENCY
Clinical signs: twice daily.

Mortality: twice daily.

Body weight: weekly.

Hematology: no.

Urinalysis: no.

Biochemistry: no.

Sacrifice and pathology:

ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC)
Organ weight: no.

Macroscopic: no details reported.

Microscopic: Skin, mammary gland, sciatic nerve, salivary gland, mandibular lymph node, thymus, heart, lungs, trachea, thyroid gland, parathyroids, esophagus, stomach, duodenum, jejunum, ileum, colon, rectum, mesenteric lymph node, pancreas, spleen, liver, kidneys, adrenal glands, urinary bladder, seminal vesicles, prostate/testes or ovaries/uterus, brain, pituitary gland, bone marrow, spinal cord, and nasal cavity.

Statistics:

Survival, body weight, dose-related effects were statistically evaluated.

Results and discussion

Results of examinations

Details on results:

Mortality and time to death: 1 female (1000 mg/kg, week 5).

Clinical signs: Rats that received 1000 mg/kg were sluggish and lethargic after dosing.

Body weight: 1000 mg/kg bw, males: slightly reduced body weight gain. (No information given on significance)

Gross pathology: No compound-related pathologic effects were observed.

Histopathology: No compound-related pathologic effects were observed.

Other: Toxic changes in the kidneys were not found, even by recuts and special stains.

Effect levels

Dose descriptor:

NOAEL

Effect level:

500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: reduced body weight gain (males) mortality (females)

Target system / organ toxicity

Critical effects observed:

not specified