Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study report with minor details (characterisation of test item) lacking

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
see principles
Principles of method if other than guideline:
Five young. adult, male and female albino rats (approximately 8 weeks of age) of the Sprague-Dawley derived strain were used in this study. The rats were chosen by ran-dom selection from the acclimated animals. Animals selected for the study weighed be-tween 206 and 217 grams. The animals were exposed to the test article for 4 hours. Six minutes were added to the 240 minute exposure period in order to allow the test system to reach 99 percent of the desired concentration (point of equilibration). Food and water were not made available during the exposure period. During the exposure period, the animals were individually housed in wire-mesh cages. Following exposure, the animals remained in the chamber for a minimum. of six minutes. The chamber was maintained during these six minutes at the designated airflow rate of 100 L/minute using clean am-bient air only.. After the exposure, animals were again individually housed. Animals were observed twice daily and body weights were recorded periodically throughout the 14-day study period. All animals were subjected to a gross necropsy and examined for lesions and/or abnormalities.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
not reported

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
1. Species/Strain: Sprague-Dawley Rats
2. Source: Charles River Breeding Laboratories. Inc.
3. Age at Initiation: Young adult
4. Number/Sex: 5/sex.
5. Identification: Color coded cage tag.
6. Housing: Individually housed in stainless steel wire
mesh bottom cages.
8. Water: Tap water, ad libitum. except during the exposure period. Water is monitored for contaminants at periodic intervals according to the FDRL Standard Operating Pro-cedures
9: Environment: All animals will be housed in environment controlled rooms with tem-perature and relative humidity regulated as per “Guide for the Care and Use of Labora-tory Animals”. A 12-hour light-dark cycle will be maintained.
10. Quarantine: Minimum of 5 days. During this conditioning period, the rats will be ob-served for any clinical signs of disease. All rats with any evidence of disease or physical abnormalities will be discarded.
Animals selected for the study weighed between 206 and 217 grams.

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
The exposure was performed in a 128 L acrylic (plexiglass), portable chamber designed by the FDRL scientific staff. Total airflow through the chamber was maintained at a rate of 100 L/minute using a transvector jet and monitored using a pre-standardized pressure gauge attached to the transvector jet. The test atmosphere was vented via an air treatment system constructed of a glass fiber pre-filter, Micretain HEPA filter and an activated charcoal bank. The test article was delivered into the exposure chamber by means of a NBS-II dust generator using an air inlet port, which allows the test article and incoming air to mix evenly within the chamber at the top before being drawn down over the animals.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetry
Duration of exposure:
4 h
Remarks on duration:
6 additional minutes were chosen in order to allow the test system to reach 99 percent of the desired concentration (point of equilibration)
Concentrations:
Nominal Concentration: The nominal concentration of Beta Cyclodextrin was 15.4 mg/L, Which was calculated by dividing the total amount of test article utilized in milli-grams by the total volume of air in liter that passed through the chamber.
Actual Concentration: The actual chamber concentration of Beta Cyclodextrin was 4.9 mg/L of air which was determined by gravimetric analysis.
Chamber air was drawn through a pre-weighed glass fiber filter (Gelman Type A/E, 99.7% efficient at 0.3 µm) held in an open-faced holder. The change in weight of the filter was then determined (mg) and divided by the volume of chamber air sampled through the filter (L). Four samples per hour were taken and the average actual concen-tration calculated.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Five young. adult, male and female albino rats (approximately 8 weeks of age) of the Sprague-Dawley derived strain were used in this study. The rats were chosen by ran-dom selection from the acclimated animals. Animals selected for the study weighed be-tween 206 and 217 grams. The animals were exposed to the test article for 4 hours. Six minutes were added to the 240 minute exposure period in order to allow the test system to reach 99 percent of the desired concentration (point of equilibration). Food and water were not made available during the exposure period. During the exposure period, the animals were individually housed in wire-mesh cages. Following exposure, the animals remained in the chamber for a minimum. of six minutes. The chamber was maintained during these six minutes at the designated airflow rate of 100 L/minute using clean am-bient air only. After the exposure, animals were again individually housed. Animals were observed twice daily and body weights were recorded periodically throughout the 14-day study period. All animals were subjected to a gross necropsy and examined for le-sions and/or abnormalities.
Statistics:
not reported

Results and discussion

Preliminary study:
not applicable
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC0
Effect level:
> 4.9 mg/L air
Exp. duration:
4 h
Remarks on result:
other: no mortality observed at limit concentration
Sex:
male/female
Dose descriptor:
LC50
Effect level:
>= 4.9 mg/L air
Exp. duration:
4 h
Remarks on result:
other: none
Mortality:
none obserbed
Clinical signs:
other: No mortality occurred. Nasal discharge was noted in all animals immediately following exposure. This effect generally cleared by day 2 of the study. .
Body weight:
Body weight data were just slightly affected. The test article exposure did not exhibit an adverse effect upon body weight gain in males. Weight loss was recorded in one female at days 8 and 15.
Gross pathology:
No lesions or abnormalities were noted during gross necropsy examination.

Other findings:
none observed

Any other information on results incl. tables

Particle SizeAnalysis: Particle size analyseswereperformed once perhourusing a multijet cascade impactor (Model 02-200, In-ToxProductsAlbuquerque, NM). Stages one to seven of the impactorwerefittedwith preweighedstainless steel impaction substrates. Stage eight (final filter stage)wasfitted with a preweighed cellulose filter membrane (Gelman TypeA/Et47mm,Triacetate,99.7%efficient at 0.3µm).Chamber airwas drawn throughthe impactor at a rate of 20 L/minute and the change in weight of each collection substrate (including the filter) was subsequently determined. The mean cumulative percent of aerosol collected at each stage was determined and a lognormal distribution curve plotted. Themeanparticle size of the aerosolgenerated ,geometric standard deviation and percent of the sample (by weight) comprised of particles < 12µmin size were determined. 

 

Chamber Specifications

Chamber volume (L): 128 L

Airflow exchange rate: 100 L/minute

Equilibrium time (99%): 6 minutes

Exposure duration at equilibrium: 240 minutes

Total exposure duration: 246 minutes '

Equilibrium/total exposure duration: 2%

Total volume of air: 24600 L

Test article utilized: 379.6 g

 

Mass median aerodynamic diameter (MMAD): 3.8 µm

Geometric standard deviation (ag): 2.2

Estimated percent of collected particles < 12 µm: 92%

 

Test Atmosphere Temperature and Relative Humidity:

Initial temperature (OC): 22

Final temperature (OC): 23

Average temperature (OC): 23

Range (QC): 22-23

Initial relative humidity (%): 41

Final relative humidity (%): 44

Average relative humidity (%): 43

Range (%): 40-46

Applicant's summary and conclusion

Interpretation of results:
relatively harmless
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Substanec reveals a low degree of toxicity.
Executive summary:

Five young. adult, male and female albino rats (approximately 8 weeks of age) of the Sprague-Dawley derived strain were used to evaluate the inahaltion toxicity of .beta.-cyclodextrin. The study was a limit whole body inhalation study at a nominal concentration of 15.4 mg/l and a gravimetrically measured concentration of 4.9 mg/l. It was performed to a guideline equivalent to OECD 403. The average actual concentration of Beta Cyclodextrin was 32% of the nominal concentration. Adsorption of the test article to chamber surfaces, dermal exposure to the animals and the generation of particle aggregates which do not remain suspended in the test atmosphere, contributed to this difference.. The animals were exposed to the test article for 4 hours. Six minutes were added to the 240 minute exposure period in order to allow the test system to reach 99 percent of the desired concentration (point of equilibration). Food and water were not made available during the exposure period. During the exposure period, the animals were individually housed in wire-mesh cages. Animals were observed twice daily and body weights were recorded periodically throughout the 14-day study period. All animals were subjected to a gross necropsy and examined for lesions and/or abnormalities. No mortality occurred. Nasal discharge was noted in all animals immediately following exposure. Body weight data were just slightly affected. The test article exposure did not exhibit an adverse effect upon body weight gain in males. Weight loss was recorded in one female at days 8 and 15. No lesions or abnormalities were noted during gross necropsy examination. Four-hour whole-body exposure to a dust generated from Beta Cyclodextrin at an average actual concentration of 4.9 mg/L failed to produce mortality in five male and five female Sprague-Dawley rats. The LC0 is >= 4.9 mg/l and it can be assumed that the LC50 is also > 5.0 mg/l due to lack of mortality and only slight signs of toxicity in this test.