Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study reliable without restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
- Animals were not observed during the exposure. - Measure of variablity for air flow, actual concentration, nominal concentration, temperature and humidity was missing.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Potassium thiosulfate
- Physical state: Clear pale yellow liquid
- Analytical purity: 49.13 % K2S2O3
- Lot No.: 0828-00
- Expiration date of the lot: 1997-12-31
- Storage condition of test material: At room temperature
- Specific gravity: 1.475 (at 21.1 °C)
- pH (full-strength): 7.30
No further information on the test material was stated.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Portage, Michigan
- Weight at study initiation: Mean body weight males (on day 0): 268 +/- 11.4 g; mean body weight females (on day 0): 249 +/- 11.6 g
- Housing: The animals were housed individually in suspended stainless steel cages. All housing and care were based on the standards recommedned by the Guide for the Care and Use of Laboratory Animals ((Guide for the Care and Use of Laboratory Animals, DHHS Publication No. (NIH) 86-23, 1995.).
- Diet (ad libitum, except during the time that the animals were maintained in the inhalation room forthe exposure procedure): PMI Certified Rodent Chow #5002 (Purina Mills, Inc.)
- Water (ad libitum, except during the time that the animals were maintained in the inhalation room for the exposure procedure): Municipal tap water treated by reverse osmosis
- Acclimation period: A minimum of five days; All animals received a detailed pretest observation prior to dosing. Only healthy animals were chosen for study use.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.2 - 21.1 °C
- Relative humidity: 49 - 65 %
- Air changes: 10 -15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
TEST ARTICLE VOLATILIY DETERMNIATION:
The volatility of the test article relative to a distilled water standard was determined prior to experimental initiation. This procedure was performed in order to determine if the test article had sufficiently low volatility to allow for an accurate gravimetric determination of the aerosol concentration. A kown quantiy of the test article was placed on the preweighed filter disk and was allowed to evaporate for a total of ten minutes. The test article weight was determined each minute and the amount of evaporation of the test article was then determined. The results of this volaility trial indicated that the test article evaporation rate (0.41 mg/minute) was comparable to the SLS determined distilled water evaporation rate (0.55 mg/minute). therefore, standard gravimetric sampling techniques would be acceptable for this test article-

PRELIMINARY AEROSOL GENERATION TRIALS.
Prior to experimental initiation, preliminary aerosol generation trials were conducted. These trials were performed in order to determine the most efficient means of generating an aerosol of the appropriate concentration while utilizing equipment that would reduce the aerodynamic particle size.

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: RHS-100L whole body inhalation chamber
- Exposure chamber volume: 100 L

- System of generating particulates/aerosols: The test aerosol was generated with a TSI Model 9306 6-Jet Atomizer. Conditioned high pressure external air was used in generating the test atmosphere. The aerosol was blown through the RHS- 100L whole-body inhalation chamber and then vented from the chamber to an air treatment system which consisted of a prefilter, a HEPA filter, a charcoal bed and a water scrubbing tower.
The aerosol expsoure consisted of an 8 minute equilibration period, a 240 minute exposure period and an 8 minute de-equilibration period.

- Method of particle size determination: The aerosol aerosynamic paricle size distribution was determined twice during the aerosol exposure using the ITP 7 L/min. cascade impactor.Each stage of the impactor was fitted with a preweighed glass fiber filter. Seven liters per minute of the chamber air was drwan through the impactor and the change in weight of each filter was then determined and recorded. The mean particle size distribution was subsequently plotted on log probability paper. The mass median aerodynamic diameter, geometric standard deviation and percentage of particles ≤10.0 µ were then determined. At least one hour passed between the first and second aerosol paricle size analysis.

- Temperature, humidity, chamber air flow, and chamber oxygen: Air flow readings were recorded at the initiation of the equilibrium period, at approximate 30-miunute intervals during the aerosol exposure and at the conclusion of the de-equilibrium period (calibrated Magnehelic gauge). The inhalation chamber was maintained at a slightly negative pressure at all times during operation.
The chamber temperature and humidity were measured electronically and recorded at approximate 30-minute intervals during the aerosol exposure.
Chamber oxygen content was measured and recorded at approximate 30.minute intervals during the aerosol exposure.
- Mean air flow rate: 60.7 L/min
- Mean air changes per hour: 36.42
- Temperature: 23.2 - 25.7 °C
- Humidity range: 58.8 -69.9 %
- Oxygen content: 21 %

TEST ATMOSPHERE
- Brief description of analytical method used: The aerosol concentration was measured at the beginning of the aerosol exposure (after equilibration), at approximate 30-minute intervals during the aerosol exposure and at the conclusion of the aerosol exposure (before de-equilibrium). The concentration of the test article aerosol was measured in the inhalation chamber by gravimetric technique. A sample of the aerosol was drawn from the breathing zone of the chamber through a preweighed glass fiber filter. The change in weight of the filter (mg) was then determined and this value was divided by the volume of chamber atmosphere sampled (L) to yield the gravimetric concentration (mg/L). The average time-weighted gravimetric concentration of the test atmosphere was then calculated for the exposure.
- Samples taken from breathing zone: Yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD: 2.1 µ (GSD: 1.9)
- Percentage of particles ≤10.0: 99.1 %
No further information on the inhalation exposure was stated.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
see above "Details on inhalation exposure"
Duration of exposure:
4 h
Concentrations:
2.60 mg/L (time -weighted mean gravimetric concentration)
10.28 mg/L (nominal concentration)
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Limit test animals were observed for clinical abnormalities two times on study day 0 (postexposure) and daily thereafter (days 1-14). An attempt was made to observed the animals during the aerosol exposure period; however, due to the density of the test article aerosol, the animals could not be seen. A general health/mortality check was performed twice daily (in the morning and in the afternoon).
Individual body weights were obtained for the limit test animals prior to dosing on day 0 and on days 7 and 14.
- Necropsy of survivors performed: Yes, all limit test animals were euthanized by carbon dioxide inhalation at study termination (day 14) and necropsied. Body cavities (cranial, thoracic, abdominal and pelvic) were opened and examined. No tissues were retained.
No further information on the study design was stated.
Statistics:
Data from the limit test were analyzed and an LC50 value estimated as follows:
< 50 % Mortality: LC50 was estimated as greater than the administered dose
= 50 % Mortality: LC50 was estimated as equal to the administered dose
> 50 % Mortality: LC50 was estimated as less than the administered dose.
Body weight means and standard deviations were calculated separately for males and females for each limit level administered. The aerodynamic particle size distribution of the test atricle aerosol was plotted using three cycle log/log probability paper as per the ITP Cascade Impactor instruction manual.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
> 2.6 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
> 2.6 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.6 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred during the four-hour limit test.
Clinical signs:
The most notable clinical abnormalities observed during the study included rales, salivation, urine stain, rough haircoat and dark material around the facial area. Also, scab(s) and hairloss were observed.
Body weight:
Body weight gain or maintenance was noted for all animals during the test period.
Gross pathology:
No gross internal findings were observed at necropsy on study day 14.
Other findings:
No data

Applicant's summary and conclusion

Conclusions:
Under the conditions of this test, the four-hour acute inhalation LC50 of potassium thiosulfate was estimated to be greater than 2.60 mg/L in the rat.
No concentration values greater than this given value have been examined.
Thus, classification according to the criteria specified by Directive 67/548/EEC and subsequent regulations, and according to the EC Regulation No. 1272/2008 and subsequent regulations, is not possible.