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Toxicological information

Toxicity to reproduction: other studies

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Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1979-05-07 to 1979-08-03
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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Principles of method if other than guideline:
Method: Sub-chronic Repeated Dose Toxicity, U.S. NTP
GLP compliance:
not specified
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Leidy Chemical Corporation, 97 % pure, 0.3 % water
- purity and identity analyses were conducted at Midwest Research Institute (Kansas City, MO)
- isophorone test material was stored at 4°C

Test animals

Species:
rat
Strain:
other: Fischer 344/N
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Industries, Indianapolis
- Age at study initiation: 8 weeks
- Diet: ad libitum. Purina Lab Chow
- Water: ad libitum
- Acclimation period: 18 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 - 24 °C
- Humidity (%): not monitored
- Air changes (per hr): 18-20 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours/day

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
ADMINISTRATION / EXPOSURE 
- Duration of test/exposure: 5days/week, 13 weeks
- Vehicle: corn oil
- Total volume applied: 1 ml
- Isophorone was added to corn oil in a graduated cylinder. Dose mixtures were prepared by further diluting this stock solution with corn oil to the
appropriate concentrations.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
All chemical/vehicle analyses were performed by gas chromatography.
Isophorone in corn-oil was found to be stable for 7 days at room temperature.
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
5 days/week
Duration of test:
13 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
62.5, 125, 250, 500, or 1000 mg/kg bw d
Basis:
other: nominal (gavage)
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Details on study design:
- Details of this study are described in chapter 7.5.1.
- Histopathological examinations in reproductive organs were performed:  mammary gland, seminal vesicles, prostate/testes or ovaries/uterus.
- Post-exposure period: none
Statistics:
STATISTICAL METHODS:
Survival, body weight, dose-related effects are statistically evaluated.

Results and discussion

Effect levels

Dose descriptor:
other: NOAEL (reproduction)
Effect level:
>= 1 000 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: no changes in reproductive organs

Observed effects

No compound-related changes in reproductive organs are reported.

Any other information on results incl. tables

no remarks

Applicant's summary and conclusion

Conclusions:
In this subchronic oral gavage study male and female Fischer rats were administered 0, 62.5, 125, 250, 500 and 1000 mg isophorone/kg bw/day in a 13 week investigation. No changes were observed in histopathological examinations of the reproduction organs.
Executive summary:

The histological examinations of the reproductive organs of male and female Fischer 344 rats (mammary gland, seminal vesicle, prostate/testis or ovary/uterus) treated orally with up to 1000 mg isophorone/kg bw for 13 weeks did not reveal any adverse effects after macroscopic and microscopic examination.

Under the conditions of this study, the No-Observed-Adverse-Effect-Level (NOAEL, reproduction) is considered to be >= 1000 mg isophorone/kg bw/day for male and female rats.