Registration Dossier

Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Remarks:
based on test type (migrated information)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Secondary source from OECD SIDS
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Combined Repeated Dose/Reproductive Protocol (one generation)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Propionaldehyde
- Molecular formula (if other than submission substance): Not documented
- Molecular weight (if other than submission substance): Not documented
- Smiles notation (if other than submission substance): Not documented
- InChl (if other than submission substance): Not documented
- Structural formula attached as image file (if other than submission substance): see Fig. Not documented
- Substance type: Not documented
- Physical state: Not documented
- Analytical purity: Not documented
- Impurities (identity and concentrations): Not documented
- Composition of test material, percentage of components: Not documented
- Isomers composition: Not documented
- Purity test date: Not documented
- Lot/batch No.: Not documented
- Expiration date of the lot/batch: Not documented
- Radiochemical purity (if radiolabelling): Not documented
- Specific activity (if radiolabelling): Not documented
- Locations of the label (if radiolabelling): Not documented
- Expiration date of radiochemical substance (if radiolabelling): Not documented
- Stability under test conditions: Not documented
- Storage condition of test material: Not documented
- Other: Not documented

Test animals

Species:
rat
Strain:
other: CD
Sex:
male/female
Details on test animals and environmental conditions:
No information provided

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Details on exposure:
Whole-body exposure
Details on mating procedure:
No information provided
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
0, 150, 750 or 1500 ppm
Duration of treatment / exposure:
6 hours exposure per day
Frequency of treatment:
7 days per week
Males received 52 consecutive daily exposures, while females were exposed for 2 weeks prior to mating, during a 14-day (Maximum) mating period and through day 20 of gestation.
Details on study schedule:
No information provided
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 150, 750 and 1500 ppm
Basis:
no data
No. of animals per sex per dose:
15 male and female rats per exposure group
Control animals:
not specified
Details on study design:
Females were allowed to litter and the offspring body weight, visibility, disposition were monitored from birth until postnatal day 4. On day 4 of lactation, necropsies were performed on the adult females and the offspring were examined externally and sacrificed without pathologic evaluation.
Positive control:
No information provided

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: No data
- Time schedule: Not documented
- Cage side observations checked in table [No.?] were included. Not documented

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: Not documented

BODY WEIGHT: No data
- Time schedule for examinations: Not documented

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: Not documented

OTHER:
Repeated whole-body inhalation exposure to propionaldehyde vapor at concentrations of 0, 150, 750, or 1500 ppm was associated with minimal toxicity at the two highest concentrations in females; males showed no apparent toxicity. Microscopic examination of the nasal epithelium revealed treatment-related effects at all concentrations in both parental sexes. No significant effects of exposure were noted on any reproductive parameter assessed.
Oestrous cyclicity (parental animals):
Not documented
Sperm parameters (parental animals):
Not documented
Litter observations:
STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: [yes]
- If yes, maximum of [...] pups/litter ([...]/sex/litter as nearly as possible); excess pups were killed and discarded. Not documented

PARAMETERS EXAMINED
The following parameters were examined in [F1 / F2 / F3] offspring:
[number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities, other:] litter size and viability

GROSS EXAMINATION OF DEAD PUPS:
no
Postmortem examinations (parental animals):
No information provided
Postmortem examinations (offspring):
No information provided
Statistics:
Not documented
Reproductive indices:
No information provided
Offspring viability indices:
No information provided

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
no effects observed
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 specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Microscopic examination of the nasal epithelium revealed treatment-related effects at all concentrations in both parental sexes.
Other effects:
not specified

Reproductive function / performance (P0)

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

Details on results (P0)

No additional information

Effect levels (P0)

open allclose all
Dose descriptor:
LOAEC
Effect level:
150 ppm
Based on:
not specified
Sex:
male/female
Dose descriptor:
NOAEC
Effect level:
1 500 ppm
Based on:
not specified
Sex:
male/female

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
a slight decrease in body weight gain was observed in the 1500 ppm offspring
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified

Details on results (F1)

No additional information

Effect levels (F1)

Dose descriptor:
NOAEC
Generation:
F1
Effect level:
750 ppm
Based on:
not specified
Sex:
male/female

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

No further information

Applicant's summary and conclusion

Conclusions:
The LOAEC for parental toxicity is 150 ppm, based on the presence of nasal lesions at 150 ppm, the lowest concentration tested.
The NOAEC for reproductive toxicity is 1500 ppm
The NOAEC for pup toxicity, based on a slight decrease in body weight gain in pups at day 4, is 750 ppm.
Executive summary:

In the study conducted by Driscoll (1993), 15 male and female CD rats were exposed to the test substance, Propionaldehyde, by whole-body exposure at air concentrations of 0, 150, 750 and 1500ppm. Exposures were conducted 6‑hours per day, 7‑days per week. Males received 52 consecutive daily exposures, while females were exposed for 2 weeks prior to mating, during a 14-day (Maximum) mating period and through day 20 of gestation. On day 4 of lactation, necropsies were performed on the adult females and the offspring were examined externally and sacrificed without pathologic evaluation.

Following repeated whole-body exposure to the test substance at the aforementioned concentrations, there was minimal toxicity at the two highest concentrations in females; males showed no apparent toxicity. Microscopic examination of the nasal epithelium revealed treatment-related effects at all concentrations in both parental sexes. No significant effects of exposure were noted on any reproductive parameter assessed. Litter size and viability were similar among exposed and control groups. Pup body weights on postnatal day 0 and 4 were not affected by exposure, however, a slight decrease in body weight gain was observed in the 1500 ppm offspring.  The LOAEC for parental toxicity is 150 ppm, based on the presence of nasal lesions at 150 ppm, the lowest concentration tested. The NOAEC for reproductive toxicity is 1500 ppm and the NOAEC for pup toxicity, based on a slight decrease in body weight gain in pups at day 4, is 750 ppm.