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Toxicological information

Respiratory sensitisation

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Administrative data

Endpoint:
respiratory sensitisation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
July-August 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
no guideline available
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Colour: colourless
- Odour: odourless
- CAS-Number: 89-32-7
- Molecular formula: C10 H2 O6
- Molecular weight: 218.12
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: identification no. 10820-33-D
- Expiration date of the lot/batch: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature (approximately 20°C)
- Stability under test conditions: stable

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories. Inc., Portage. MI, USA
- Age at study initiation: 6 weeks
- Weight at study initiation: ca. 270-430 g
- Housing: gang housing
- Diet (e.g. ad libitum): Purina Rodent Chow 5001, Ralston Purina Co., St. Louis. MO, USA
- Water (e.g. ad libitum): supplied from a reverse-osmosis (RO) purifier by an automatic watering system
- Acclimation period: 2-week quarantine period
- Fasting period: 18 hours
- Indication of any skin lesions: no

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 40%
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent lighting, 12 hours darkness

Test system

Route of induction exposure:
inhalation
Route of challenge exposure:
inhalation
Vehicle:
unchanged (no vehicle)
Concentration:
Induction and challenege exposure: 50 microgr/m3 of test article aerosol in air
No. of animals per dose:
10 rats/sex/group
Details on study design:
Following a 2-week quarantine period. three groups of rats (10 rats/sex/group = 60 total rats) were randomly selected from a pool of rats whose body weigllts did not deviate more than three standard deviation units from the population mean. One group was exposed to 50 ug/m3 of the test article aerosol in air and two groups were exposed in a cbamber to clean filtered air only. The duration of the exposures was 6 hours per day for 5 days.
Following a 3-week rest, the test article-exposed rats along with one filtered air control (F AC) group were cbal1eDged with 50 ug/m3 of test item for 6 hours. The third group of rats was designated as nonchallenged filtered air controL All rats were euthanized and necropsied approximately 18 hours after the final exposure.
Challenge controls:
None
Positive control substance(s):
none
Negative control substance(s):
none

Results and discussion

Results:
The time-weighted average concentrations of the test item for the five exposures and one challenge were 56.5 and 48.6 ug/m3, respectively. No significant clinical signs were observed in any rat during the study. There were no statistically significant effects of treatment on body weight. lung foci or absolute and relative lung weight and volume. Serum IgG antibody levels_were significantly elevated in the PMDA-exposed male rats only. When antibody values for the males and females were combined, these values were also statistically significant from controls. The three test item exposed males which had the highest number of lung foci (i.e. 14, 20 and 24) also had the highest levels of serum IgG antibody. However, this observation did not hold true for other animals (Le. rats exhibiting low numbers of foci, or no foci at all. had higher levels of antibody than rats exhibiting more lung foci).
In conclusion, and based on the results of this study, it is believed that the test item could cause respiratory sensitization if the exposure concentration was higher and/or of a longer duration.
Positive control results:
Not tested
Negative control results:
Not tested

Applicant's summary and conclusion

Interpretation of results:
Category 1 (respiratory sensitising) based on GHS criteria
Conclusions:
Based on the results of this study, it is believed that PMDA could cause respiratory sensitization if the exposure concentration was higher and/or of a longer duration.
Executive summary:

The purpose of this study was to determine the pulmonary sensitization potential of of the test item in male and female rats following multiple inhalation exposures. The time-weighted average concentrations of the test item for the five exposures and one challenge were 56.5 and 48.6 ug/m3, respectively. No significant clinical signs were observed in any rat during the study. There were no statistically significant effects of treatment on body weight. lung foci or absolute and relative lung weight and volume. Serum IgG antibody levels_were significantly elevated in the PMDA-exposed male rats only. When antibody values for the males and females were combined, these values were also statistically significant from controls. The three test item exposed males which had the highest number of lung foci (i.e. 14, 20 and 24) also had the highest levels of serum IgG antibody. However, this observation did not hold true for other animals (Le. rats exhibiting low numbers of foci, or no foci at all. had higher levels of antibody than rats exhibiting more lung foci).

In conclusion, and based on the results of this study, it is believed that the test item could cause respiratory sensitization if the exposure concentration was higher and/or of a longer duration.