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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
one-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Contribution a l'etude analytique toxicologique et biochimique de l'isophorone.
Author:
Dutertre-Catella H
Year:
1976
Bibliographic source:
Thesis, Universite Rene Descartes, Paris.

Materials and methods

Principles of method if other than guideline:
Method: Limited one generation study
GLP compliance:
not specified
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Elf Atochem S.A.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ORGANISMS
- Weight at study initiation: approximately 140 g
- Number of animals: 10 males, 10 females

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure (if applicable):
whole body
Vehicle:
other: air
Details on exposure:
ADMINISTRATION / EXPOSURE
- Type of exposure: inhalation
- Vehicle: air
- Control group: 10 males, 10 females
Details on mating procedure:
MATING PROCEDURES: 
- after three months of exposure overnight mating of   
5 exposed males with 5 exposed females   
5 exposed males with 5 control females   
5 control males with 5 exposed females   
5 control males with 5 control females
- next morning exposure continued for exposed animals (females until  littering)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Exposure period: 6 hours/day
Premating exposure period (males): 3 months
Premating exposure period (females): 3 months
Duration of test: females: 4 months; males: 6 months
Frequency of treatment:
5 days/week
Details on study schedule:
PARAMETERS ASSESSED DURING STUDY P AND F1: 
- Clinical observations:    behaviour, body weight development, mortality of P,  number and vitality of F1
Limitations of the study: Only one dose tested
                          Small group size
                           No information on mating success
Doses / concentrations
Remarks:
Doses / Concentrations:
500 ppm = 2873 mg/m3 (saturation)
Basis:
analytical conc.
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Positive control:
not applicable

Examinations

Parental animals: Observations and examinations:
Clinical observations: behaviour, body weight development, mortality
Oestrous cyclicity (parental animals):
no data
Sperm parameters (parental animals):
no data
Litter observations:
Litter size and weights
Postmortem examinations (parental animals):
gross pathology, histopathology
Postmortem examinations (offspring):
gross pathology, histopathology
Statistics:
no data
Reproductive indices:
no data
Offspring viability indices:
no data

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
effects observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
not examined

Details on results (P0)

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: 
- Parental data and F1: 
- Body weight: no difference between exposed and control
- Description, severity, time of onset and duration of clinical signs:    
irritation of eyes and nose (exposed)
- Mortality:    
no mortalities in control groups   
1/10 of exposed females and 2/10 of exposed males died
- Gross pathology incidence and severity: traces of bleeding in lungs of  both exposed and control animals
- Histopathology incidence and severity:    
slight to medium congestion in lungs with similar intensity in exposed  and control;   
granular state and clarification of liver cytoplasma with similar  intensity in exposed and control

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
< 2 873 mg/m³ air
Sex:
male/female
Basis for effect level:
other: irritation of eyes and nose

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
not examined
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed

Details on results (F1)

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: 
- Offspring toxicity F1 and F2: 
- Litter size and weights: 7-10 per female, normal behaviour, none dead
- Post natal survival until weaning: no difference between exposed and  control
- Effects on offspring: no difference between exposed and control  observed at necropsy

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
> 2 873 mg/m³ air
Sex:
male/female
Basis for effect level:
other: Treatment with isophorone did not influence pregnancy rates and litter sizes nor were there any abnormalities observed in the pups.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

no remarks

Applicant's summary and conclusion

Conclusions:
Under the conditions of this study, it can be concluded that isophorone has no adverse effect on reproduction of Wistar rats.
Executive summary:

In a limited one generation study, 10 male and 10 female Wistar rats were exposed to 2873 mg/m3 (500 ppm) isophorone in air. After three months of exposure, 5 exposed males each were mated with 5 control and 5 exposed females, 5 control males each were mated with 5 control and 5 exposed females. Exposure of females continued throughout gestation and they were allowed to deliver. All females were reported to have delivered 7 to 10 pups.

Treatment with isophorone did not influence pregnancy rates and litter sizes nor were there any abnormalities in the pups. However only one isophorone concentration was used, the group size was small, and no information was provided on reproductive success and maternal survival.

Under the conditions on this study, it can be concluded that isophorone has no adverse effect on reproduction of rats.