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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989-02-20 to 1989-05-25
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
GLP compliance:
yes (incl. certificate)
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): propylene carbonate (TEXACAR PC)
- Analytical purity: at least 99.9%
- Storage condition of test material: Chemical storage room blanketed with nitrogen
- Lot/batch No.: 9A-502
- Other: Source- Texaco Chemical Company, Austin, Texas

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague-Dawley, Inc., Fredrick, MD
- Age at study initiation: 61 days
- Housing: 1-3 per cage, same sex, during non exposure period, individual during exposure, 15 x 22 x 18 cm wire mesh cages
- Diet: Agway Pro Lab powdered food, ad libitum
- Water: Water ad libitum via automatic watering system
- Acclimation period: 2 -3 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): monitored continuously.
- Humidity (%): monitored continuously.
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hour light/dark photoperiod throughout the study.


Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Remarks on MMAD:
MMAD / GSD: The MMAD for the 100, 500 and 1000 mg/m³ concentrations were 5.32, 4.62, and 4.72 microns, respectively, with a geometric standard deviation of 2.74, 2.52 and 2.32, respectively.
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Inhalation chamber
- Method of holding animals in test chamber: wire mesh cage
- Source and rate of air: Filtered forced air
- System of generating particulates/aerosols: The test substance was metered from a piston pump into an atomizer fitted withe a liquid nozzle and and air nozzle. The atomizer was inserted into the top of the inhalation turret where the liquid aerosols were dispersed by the filtered chamber supply air.
- Air flow rate: 300 L/min
- Air change rate: 13.5 changes/hr
- Method of particle size determination: Cascade impactor. Measurements made twice a week for each concentration.

TEST ATMOSPHERE
- Brief description of analytical method used: A 25 minute sample was taken from each chamber each day isng a vacuum pump dry gas meter or flow meter.
- Samples taken from breathing zone: no


Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
6 hours/day, 5 days/week, 13 weeks (93 days)
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/m³ air (nominal)
Remarks:
control group
Dose / conc.:
100 mg/m³ air (nominal)
Dose / conc.:
500 mg/m³ air (nominal)
Dose / conc.:
1 000 mg/m³ air (nominal)
No. of animals per sex per dose:
15 males, 15 females
Control animals:
yes, sham-exposed
Details on study design:
- Rationale for selecting satellite groups: A satellite group of 10 rats per sex/dose was assigned to each group for acute neurotoxicity testing
Positive control:
None

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No


DETAILED CLINICAL OBSERVATIONS: no


BODY WEIGHT: Yes- prior to test initiation for group assignment

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION: No


OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Prior to exposure and on May 17, 1989.
- Dose groups that were examined:All rats


HAEMATOLOGY: Yes
- Time schedule for collection of blood: Week 5 and 14
- Anaesthetic used for blood collection: Yes (methoxyflurane)
- Animals fasted: Yes
- How many animals: 10/sex/group
-20 blood chemistry analyses performed


CLINICAL CHEMISTRY: Yes -see above


URINALYSIS: Yes
- Time schedule for collection of urine: 15 hours from 10/sex/group prior to sacrifice
- Metabolism cages used for collection of urine: Yes
- Animals fasted: No

NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: 1 and 13 hrs, 6 weeks, 13 weeks
- Dose groups that were examined: Satellite group, 10/sex/dose
- Battery of functions tested: motor activity


Statistics:
Standard analyses were used, including Levene's test for equal variance, ANOVA, and t-tests. Fisher's exact test was used for the microscopy. The limit of 0.05 was used as the critical level of significance in all tests.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
The only clinical sign believed to be exposure related was periocular swelling observed in 13-33% of male animals in the propylene carbonate exposure groups. Female animals were also observed to have periocular swelling, however, this finding was observed at a high frequency in the control group making the significance of the observation in the exposure groups dubious.

At the end of the exposure regimen, there were no exposure related lesions observed in any animal.
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effects on body weight or body weight gain.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
No treatment related effects in females. A statistically significant increase in food consumption was noted in week 2 of exposure in the 500 and 1000 mg/m³ males.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
no effects observed
Description (incidence and severity):
No treatment related effects
Ophthalmological findings:
effects observed, treatment-related
Haematological findings:
no effects observed
Description (incidence and severity):
No treatment related effects.
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
No treatment related effects.
Urinalysis findings:
no effects observed
Description (incidence and severity):
No treatment related effects.
Behaviour (functional findings):
no effects observed
Description (incidence and severity):
No treatment related effects.
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
No test substance related effects.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
The only gross lesion was swollen periocular tissue in one 500 mg/m³ animal and two animals in the 1000 mg/m³ animals.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No microscopic lesions were attributed to propylene carbonate treatment.
Histopathological findings: neoplastic:
not examined
Other effects:
not specified

Effect levels

open allclose all
Dose descriptor:
NOAEC
Remarks:
systemic
Effect level:
1 000 mg/m³ air (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
ophthalmological examination
other: No systemic adverse effects were observed.
Dose descriptor:
NOAEC
Remarks:
local
Effect level:
100 mg/m³ air (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: ophthalmoscopic examination: swollen periocular tissue was observed in 2 animals of the 500 mg/m³ group and four animals of the 1000 mg/m³
Dose descriptor:
LOAEC
Remarks:
local
Effect level:
500 mg/m³ air (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: ophthalmoscopic examination: swollen periocular tissue was observed in 2 animals of the 500 mg/m³ group and four animals of the 1000 mg/m³

Target system / organ toxicity

Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
Repeated exposure to propylene carbonate in rats at concentrations up to 1000 mg/m3 produced only signs of minimal irritation to the eyes in rats. Therefore the NOAEC (systemic effects) is considered to be 1000 mg/m3, the highest dose tested.