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EC number: 215-252-9
CAS number: 1315-01-1
Validation Report: Validation of the analytical method for quantitation of tin disulphide in lung samples by XRF spectroscopy – CRL Hungary Study code: 19/106-994ANA (non-GLP):
The purpose of this study was to validate the analytical method developed for quantitative determination of tin disulphide in lung samples by XRF spectroscopy to support a repeat dose inhalation study in rats. This validation established all the significant factors influencing the quali1ty of the method, allowing a much more efficient/rapid GLP cross validation to be made, fully meeting the GLP requirements for Charles River Laboratories.
Summary Table: Results of the Method Validation
The Sn Kα1 X-ray line is in the expected position and the calculated concentration of the blank sample is below 20% of the LOQ. Passed
RSD 3.03% Passed
R2 = 0.9952; all values <15% of nominal. Passed.
Calibrated linear range
0.025 – 0.375 mg/mL of the test item Passed
Limit of Quantification
The LOQ is established as the lowest calibration point (0.025 mg/mL)
Recovery of the test item from filters
107.09%, RSD 5.44% Passed.
Final Study Report: Cross-validation of the analytical method for quantitation of tin disulphide in lung samples– Study code: FPBSTUDY-220-XVAL3; CRL-VES Study code: 19/106-994AN (GLP):
The purpose of this study was to cross-validate the developed and validated (study title: Validation of the analytical method for quantitation of tin disulphide in Lung Samples by XRF spectroscopy) analytical method for the quantitative determination of Tin Disulphide. The procedure was found to be suitable for the analysis of the test item in Lung Samples. The cross-validation parameters met the requirements. Summary of the cross-validated method parameters is presented in Table 1.
Table 1. Results of cross-validation
CV% of the found concentrations not more than 10%
4.34% CV for the concentration of the Test item
Linearity (Detector response)
In 0.025 – 0.375 mg/mL concentration range
Acceptable, if a correlation coefficient of 0.99 or above is obtained
R² >= 0.9931
Deviation of the re-calculated values from the nominal concentration > 20.0% for the LOQ level
94.1 – 112.7%
Deviation of the re-calculated values from the nominal concentrations > 15.0%
90.1 – 104.3%
Re-calculated concentration values at LOQ level are in 80.0 – 120.0% of the nominal concentrations
0.05 mg/mL calibration sample
99.4 – 110.5%
CV% < 20.0%
Accuracy and precision
c TI (mg/g)
The mean value should be within 15% of the nominal value.
The precision determined at each concentration level should not exceed 15% of the coefficient of variation (CV).
Validation Report: Validation of the analytical method for quantitation of tin disulphide on inhalation filter by XRF spectroscopy - CRL Hungary Study code: 19/106-901AN (non-GLP):
The purpose of this study was to validate the analytical method developed for quantitative determination of tin disulphide captured on inhalation filters by XRF spectroscopy to support a repeat dose inhalation study in rats. This validation established all the significant factors influencing the quality of the method, allowing a much more efficient/rapid GLP cross validation to be made, fully meeting the GLP requirements for Charles River Laboratories.
The Sn Kα1 X-ray line is specific. Passed
RSD 2.28% Passed
R2 = 0.9901 and 0.9923. Passed.
0.1 – 0.4 mg/mL of the test item Passed
The LOQ is established as the lowest calibration point (0.1 mg/mL)
98.2%, RSD 2.6% Passed.
RSD 2.3% Passed
Stability of the test item on filter
> 6 months Passed
PLS data analysis verified by Leave-one-out cross validation
Final Study Report: Cross-validation of the analytical method for quantitation of tin disulphide on inhalation filter – Study code: FPBSTUDY-220-XVAL2; CRL-VES Study code: 19/106-901ANA (GLP):
The purpose of this study was to cross-validate the developed and validated (study title: Validation of the analytical method for quantitation of tin disulphide on inhalation filter by XRF spectroscopy) analytical method for the quantitative determination of Tin Disulphide. The procedure was found to be suitable for the analysis of the test item on Inhalation Filters. The cross-validation parameters met the requirements. Summary of the cross-validated method parameters is presented in Table 1.
The found concentration of the calibration sample should be RSD < 5.0%
3.96% CV for the concentration of the Test item
Correlation coefficient is above of 0.99
R² >= 0.9985
Re-calculated concentration values at LOQ level are in the 80.0 – 120.0% of the nominal concentrations
89.3% - 95.2%
Re-calculated concentration values above LOQ level are in 85.0 – 115.0% of the nominal concentrations
94.0 – 105.3%
0.025 mg/mL calibration sample
84.3 – 104.8%
m captured (mg)
4.32 – 5.89
90.0 – 110.0%
Equivalence of variances (F-test)
P > 0.05
P = 0.487 (the variances were equal)
Equivalence of mean values (T-test)
P = 0.024*
* This is a common case when the standard deviations of the two measurement series fall into narrow ranges and the number of observations is low. It does not necessarily mean that any of the two measurements provide false or incomparable results. Although the criteria set in the validation plan is not met, it is important to highlight that the accuracy acceptance range is ±10% and the difference between the two averages is less than 5% (but with small standard deviations). It can be concluded that the results of the measurements carried out in Fumoprep match the results obtained at the Science Port within a reasonable acceptance range (both were 100 ± 3%). Therefore, the method is considered valid.
The objective of this 90-day study was to obtain information on the toxicity of the test item when administered to Wistar (Han) rats via inhalation route for at least 90 days with the aim of inducing toxic effects but no death or suffering or excessive lung overload at the highest concentration, and little or no evidence of toxicity at the lowest concentration level. The methods used aims to follow OECD 413, with the procedures that are for a test item which does not accumulate in the lungs. According to this, additional subgroups were used to evaluate the recovery of the animals and to investigate the clearance rate of the Test Item from the lung.
The animals were exposed to the test atmosphere at target concentrations of 0.02, 0.2 and 1.0 mg/L, as the Low, Mid and High Dose Concentration, respectively, using a nose-only exposure system over 90 days. The concentration levels, based on a preliminary dose range study, were approved by the Study Monitor and Sponsor; it was considered that higher atmosphere concentrations would have caused a lung dust overload within the 90-day study period.
Ten male and 10 female Wistar Hannover rats Crl:WI(Han) in each main group were treated by a 6 hour nose-only exposure to filtered air or three fixed aerosol concentrations for 5 days/week. The main animals were sacrificed on the day following the last exposure on Day 91 (histopathology evaluation and BALF† analysis were performed). Additionally, 5 females per group were treated and allowed to recover for 6 weeks and sacrificed on Day 132 (histopathology evaluation and BALF analysis were performed) and 15 males per group were treated and allowed to recover and sacrificed on Day 91, Day 132 (6-week recovery) and Day 174 (approximately 3-month recovery) for histopathology and/or lung burden evaluation.
Male and female Crl:WI(Han) rats were treated as follows:
Target Test Atmosphere Concentration (mg/L)
PEO-1 (end of dosing)
(Satellite Group 2)
(recovery for 6 weeks)
(Satellite Group 3)
Main Study Animals
Satellite Group 1
*: Actual concentration was very slightly above the target concentrations to ensure the classification cut-off was met. † BALF: Bronchoalveolar lavage fluid
Examinations in the study were performed as follows:
recovery for 6 weeks
*: Actual concentration was very slightly above the target concentrations to ensure the classification cut-off was met.
Start of the exposure for all 4 groups was Day 1. For practical reasons, the start of treatment of males and females was staggered on different days.
An Air Control Group was exposed to filtered air.
The treatment was performed in 4 parallel inhalation towers, one tower for each treatment or control group.
PEO-1 animals including control were terminated on the day following the last exposure on Day 91. The PEO-2 (Satellite Group 2) animals were terminated on Day 132, the PEO-3 (Satellite Group 3) animals were terminated on Day 174.
The actual atmospheric concentrations were:
Low Dose (mg/L)
Mid Dose (mg/L)
High Dose (mg/L)
The achieved concentrations for all groups were considered to be fully acceptable for Concentration and Stability of the exposures.
Analysis of control samples for concentration showed that no test item was detected.
No mortality occurred during the study.
The exposure to the test item Tin disulphide to Hannover Wistar rats for 90 days at dose levels was measured at 0.020 mg/L (Low Dose), 0.21 mg/L (Mid Dose) and 1.03 mg/L (High Dose).
The exposure did not cause any test item-related adverse clinical signs or change in body weight/weight gain or food consumption.
The functional observation battery (FOB) and neuromuscular observations showed no changes in animal behaviour, general physical condition, grip strength, motor activity, or in the reactions to different type of stimuli in the control or test groups.
No treatment-related changes were noted on ophthalmoscopy examination.
No test-item related changes in haematology, clinical chemistry or urine parameters were noted.
There were no test item-related observations in the oestrus cycle.
All treated groups showed respiratory related changes due to test item. But there were no significant test item-related macroscopic or microscopic changes in any organs or tissues outside the respiratory system.
Results of lung burden determination showed ~2.5, ~14 and ~30 mg test item per gram of lung at 91 days. A continuous clearance was observed from the lung over time in all dose groups, however clearance at the High dose was slow and limited.
At the 91 day necropsy, yellow discoloration (test item) and enlargement of the lungs and mediastinal lymph node were seen with a dose relationship in all dosed groups, as were lung weights. In the BAL, a dose-dependent increase of LDH and albumin values, and live and dead cell numbers were seen in both males and females after 91 days. At histology, there was a massive, dose-related presence of brown pigment (test item) in the alveolar/bronchiolar lumen, bronchio-alveolar macrophages and in the regional lymphoid tissues. Despite the amount of test item present, there were no evident toxic effects (no degenerative or inflammatory changes). Pigmented macrophages were also seen in nasal mucosa and trachea subserosa, without degenerative or inflammatory changes. An exacerbation of eosinophil droplets in the respiratory epithelium of the nasal cavity was correlated with treatment (dust), but is not considered to be a degenerative change or a specific toxic effect of the test item. All changes seen in the respiratory tract and related tissues were considered to be a response to inhaled dust. Test concentrations higher than 1 mg/L would be above the maximum tolerated dose.
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