Tin sulphide

Endpoint summary

Description of key information

Skin: A skin irritation/corrosion study with rabbits according to OECD guideline 404 was performed to  determine the irritant or corrosive effects, if any, of tin sulfide when applied to the skin. There was no 
erythema or edema noted for any animal at any observation period. Test item stained the dose sites  at all observation periods. There were no abnormal physical signs noted during the observation period. 
All body weights were normal. Tin sulfide had no skin irritating/corrosive effects.The supporting in vitro studies, In Vitro Epiderm Skin Irritation Test according to the MatTek protocol 
and In Vitro Skin Corrosion - Human Skin Model Test according to OECD guideline 431, confirm the result of the in vivo study. Respective studies on the read-across substance tin disulfide confirmed these results.
Eyes: The eye irritating/corrosive properties of tin sulfide were determined in a study with rabbits  according to OECD guideline 405. There was no corneal opacity or iritis noted at any observation period. 
Conjunctival irritation, noted in 3/3 eyes, cleared by 48 hours. There were no abnormal physical signs noted  during the observation period. In addition, the mean total score at 24 hours was 0.67, at 48 and 72 hours 0.
The supporting HET-CAM study confirms the result of the in vivo study.Respective studies on the read-across substance tin disulfide confirmed these results.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-04-11 to 2010-04-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline compliant study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

, adopted 24 April 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animals were received from Covance Research Products Inc., Denver, PA on 03/31/10. Following an
acclimation period of at least five days, three healthy New Zealand White rabbits (females) were selected
from a larger group without conscious bias.
The animals were born on 12/12/09. The pretest body weight range was 2.8-2.9 kg.
The animals were identified by cage notation and a uniquely numbered metal eartag and individually
housed in suspended cages. Paper bedding was placed beneath the cages and changed at least three
times/week. Fresh PMI Rabbit Chow (Diet #5321) was provided daily. Water was available ad libitum.
The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12-
hour light/dark cycle, and was kept clean and vermin free.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not required

Amount / concentration applied:

0.5g substance/ site, moistened with 0.2 mL distilled water as a pasty.

Duration of treatment / exposure:

4h

Observation period:

After 60 minutes and 24, 48 and 72 hours

Number of animals:

3

Details on study design:

The day prior to application of the test article, the dorsal area of the trunk of each animal was clipped free
of hair. Each dose site was approximately 3 x 3 cm.
The test article was individually weighed, 0.5 g/site and moistened with 0.2 mL of distilled water to form a
pasty consistency. The test article was applied under a 2.5 x 2.5 cm gauze patch. Gentle pressure was
applied to aid in the distribution of the test article over the prepared site. The patch was secured with nonirritating
tape. The torso was covered with a piece of porous dressing (semi-occlusive) large enough to
cover all dose sites with at least 5 cm square to spare on all sides of the gauze patch. Porous, nonirritating
tape was used to encircle the trunk of the animal. The test article was kept in contact with the skin
for 4 hours at which time the wrappings and patches were removed . Distilled water was used to aid in the
attempted removal of residual test article at the end of the exposure period, prior to scoring for dermal
reactions. However, test material stained all of the dose sites. The test sites were scored for dermal irritation at
60 minutes and at 24, 48 and 72 hours following patch removal. Erythema and edema were scored according to the
numerical Draize technique below. The skin was also evaluated for ulceration and necrosis or any evidence of tissue
destruction. Additional signs were described.

Erythema
0: No erythema
1: Very slight erythema (barely perceptible)
2: Well defined erythema
3: Moderate to severe erythema
4: Severe erythema (beet redness) to slight eschar formation (injuries in depth)

Edema
0: No edema
1: Very slight edema (barely perceptible)
2: Slight edema (edges of area well-defined by definite raising)
3: Moderate edema (raised approximately 1.0 mm)
4: Severe edema (raised more than 1.0 mm, extending beyond the area of exposure)

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1, 24, 48, 72

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1, 24, 48, 72

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

There was no erythema or edema noted for any animal at any observation period.
There were no abnormal physical signs noted during the observation period and
all body weights were normal. Therefore the test item tin sulfide is not a dermal irritant.

Other effects:

No abnormal physical signs were noted during the observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

Tin sulfide had no skin irritating/corrosive effects in an in vivo study according to OECD guideline 404.

Executive summary:

A skin irritation/corrosion study with rabbits according to OECD guideline 404 was performed to determine the irritant or corrosive effects, if any, of tin sulfide when applied to the skin. There was no erythema or edema noted for any animal at any observation period. Test item stained the dose sites at all observation periods. There were no abnormal physical signs noted during the observation period. All body weights were normal.

Reference 2

Endpoint:

skin corrosion: in vitro / ex vivo

Remarks:

in vitro

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-01-18 to 2010-02-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline compliant study

Qualifier:

according to guideline

Guideline:

OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)

Version / remarks:

effective April 2004

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

other: not specified

Source strain:

not specified

Vehicle:

other: Tissue culture water TCH2O (no formulation but to improve the contact between powder and tissue)

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: MatTek EpiDermTM Skin Corrosivity Test
- Tissue batch number(s): Lot 12926 Kits L & BB
- Production date: Not specified
- Shipping date: Not specified
- Delivery date: 02/16/10
- Date of initiation of testing: Start exposure to test substance 01/19/10

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: No temperature data during exposure.
- Temperature of post-treatment incubation (if applicable): No temperature data of post-treatment incubation.
At the end of the exposure period, each EpiDerm TM tissue was rinsed with phosphate buffered saline (PBS) and transferred to a 24-well plate containing 300 µL of MTT solution (1 mg/mL MTT in DMEM). The tissues were then returned to the incubator for a three-hour MTT incubation period. Following the MTT incubation period, each EpiDerm™ tissue was rinsed with PBS and then treated overnight with 2.0 mL of extractant solution (isopropanol) per well. The absorbency of an aliquot of the extracted MTT formazan was measured at 540 nm using a microplate reader.

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: 2 washing steps with PBS, no data on volume used.
At the end of the exposure period, each EpiDerm TM tissue was rinsed with phosphate buffered saline (PBS) and transferred to a 24-well plate containing 300 µL of MTT solution (1 mg/mL MTT in DMEM). The tissues were then returned to the incubator for a three-hour MTT incubation period. Following the MTT incubation period, each EpiDerm™ tissue was rinsed with PBS and then treated overnight with 2.0 mL of extractant solution (isopropanol) per well. The absorbency of an aliquot of the extracted MTT formazan was measured at 540 nm using a microplate reader.
- Observable damage in the tissue due to washing: Not specified
- Modifications to validated SOP: There were no amendments to the protocol. The test article characterization was not conducted according to the Good Laboratory Practices. This is not expected to have any impact on the study.

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL MTT in DMEM
- Incubation time: three-hour MTT incubation period
- Spectrophotometer: a microplate reader
- Wavelength: 540 nm

FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
Not specified

NUMBER OF REPLICATE TISSUES: 2

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
No direct MTT interference was observed. The test article did not reduce MTT and the assay continued as per the protocol.

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 12 tests (2 replicates with each 3 aliquots at 2 time points)

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be corrosive to skin if the viability after 3 minutes exposure is less than 50%, or if the viability after 3 minutes exposure is greater than or equal to 50 % and the viability after 1 hour exposure is less than 15%.
- The test substance is considered to be non-corrosive to skin if the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour exposure is greater than or equal to 15%.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

25 mg of the test article plus 25 µL tissue culture water were applied to the top of each EpiDerm tissue.

Duration of treatment / exposure:

3 and 60 minutes

Number of replicates:

2

Irritation / corrosion parameter:

% tissue viability

Remarks:

mean

Run / experiment:

3 minutes

Value:

101

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Predicted corrosivity of tin sulfide: non-corrosive.

Irritation / corrosion parameter:

% tissue viability

Remarks:

mean

Run / experiment:

60 minutes

Value:

107.8

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Predicted corrosivity of tin sulfide: non-corrosive.

Other effects / acceptance of results:

- OTHER EFFECTS:
- Visible damage on test system: Not specified.
- Direct-MTT reduction: No direct MTT interference was observed. The test article did not reduce MTT.
- Colour interference with MTT: Not specified.

DEMONSTRATION OF TECHNICAL PROFICIENCY:

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes. The mean OD of the two Negative Control tissues is ≥ 0.8 (1.58 at 3 minutes and 1.53 at 60 minutes).
- Acceptance criteria met for positive control: Yes. The mean relative tissue viability of the Positive Control tissues at the 3-minute time point is ≤30% (26.79%).
- Acceptance criteria met for variability between replicate measurements: Yes. The difference between two identically treated tissues is no greater than 30%: Viability differences between the two identically treated tissues in all samples and controls at 3 minutes were 5.0% to 9.2%. Viability differences between the two identically treated tissues at 60 minutes were 0.9% to 15.1%.

Interpretation of results:

GHS criteria not met

Conclusions:

Tin sulfide had no skin corrosive effect in an in vitro skin corrosion test according to OECD guideline 431.

Executive summary:

Objective of this test was to predict dermal corrosion potential of tin sulfide according to OECD guideline 431. The mean viability in MatTek EpiDerm tissue samples was 101.0% (3min.) and 107.8% (60 min.). Therefore, tin sulfide is non-corrosive under the present test conditions.

Reference 3

Endpoint:

skin irritation: in vitro / ex vivo

Remarks:

in vitro

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-01-18 to 2010-01-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline compliant study

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Version / remarks:

Draft from March 2009

Qualifier:

according to guideline

Guideline:

other: MatTek protocol in Vitro Epiderm Skin Irritation Test

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

other: not specified

Source strain:

not specified

Vehicle:

other: PBS was used to improve the contact between powder and tissue

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: MatTek EpiDermTM Skin Irritation Test
- Tissue batch number(s): Lot 12907 Kits DD & NN
- Production date: Not specified
- Shipping date: Not specified
- Delivery date: 01/19/10
- Date of initiation of testing: Start dosing 01/20/10

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: The exposure period for the test item and controls was 60 minutes. The dosed tissues were placed in an incubator at 37°C ± 1°C, 5% ± 1% CO2 for 35 ± 1 minutes, then returned to the sterile hood for the remainder of the 60-minute exposure period.
- Temperature of post-treatment incubation (if applicable): No temperature data of post-treatment incubation available.
After dosing and incubation, the tissues were rinsed with PBS, blotted to remove the test substance and dry the tissue, and transferred to fresh medium. The rinsed EpiDerm TM tissues were returned to the incubator for 42 ± 2 hours. Medium was changed at 24 ± 2 hrs.
At the end of the incubation period, each EpiDerm™ tissue was rinsed with phosphate buffered saline (PBS) and transferred to a 24-well plate containing 300 µL of MTT solution (1 mg/mL MTT, Alfa Aesar Lot# E12T018, in DMEM). The tissues were then returned to the incubator for a three-hour MTT incubation period.
Following the MTT incubation period, each EpiDerm™ tissue was rinsed with PBS and then treated with 2.0 mL of extractant solution (isopropanol, Alfa Aesar Lot# 081 0065) per well for at least 2 hours, with shaking, at room temperature. Two aliquots of the extracted MTT formazan were measured at 540 nm using a plate reader.

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: 3 washing steps with PBS, no data on volume used.
After dosing and incubation, the tissues were rinsed with PBS, blotted to remove the test substance and dry the tissue, and transferred to fresh medium. The rinsed EpiDerm TM tissues were returned to the incubator for 42 ± 2 hours. Medium was changed at 24 ± 2 hrs. At the end of the incubation period, each EpiDerm™ tissue was rinsed with phosphate buffered saline (PBS) and transferred to a 24-well plate containing 300 µL of MTT solution (1 mg/mL MTT, Alfa Aesar Lot# E12T018, in DMEM). The tissues were then returned to the incubator for a three-hour MTT incubation period. Following the MTT incubation period, each EpiDerm™ tissue was rinsed with PBS and then treated with 2.0 mL of extractant solution (isopropanol, Alfa Aesar Lot# 081 0065) per well for at least 2 hours, with shaking, at room temperature. Two aliquots of the extracted MTT formazan were measured at 540 nm using a plate reader.
- Observable damage in the tissue due to washing: Not specified.
- Modifications to validated SOP: There were no amendments to the protocol. The test article characterization was not conducted according to the Good Laboratory Practices. This is not expected to have any impact on the study.

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL MTT, Alfa Aesar Lot# E12T018, in DMEM
- Incubation time: three-hour MTT incubation period
- Spectrophotometer: a plate reader
- Wavelength: 540 nm

FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
Not specified

NUMBER OF REPLICATE TISSUES: 3

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
No direct MTT interference was observed. The test article did not reduce MTT and the assay continued as per the protocol.

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 6 tests (3 replicates with each two aliquots)

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be irritant to skin if the mean tissue viability after 60 minutes exposure is smaller than or equal to 50%,
- The test substance is considered to be non-irritant to skin if the mean tissue viability after 60 minutes exposure is greater than 50%

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 mg of the test article (chopped into fine pieces) was added into the Milllicell atop the tissue

VEHICLE
- Amount(s) applied (volume or weight with unit): The EpiDermTM tissue was moistened with 25 µL PBS before dosing
- Lot/batch no. (if required): Lot#AUF34778

NEGATIVE CONTROL: PBS
- Amount(s) applied (volume or weight): not specified
- Concentration (if solution):

POSITIVE CONTROL: 5% SDS
- Amount(s) applied (volume or weight): not specified
- Concentration (if solution):

Duration of treatment / exposure:

60 minutes

Duration of post-treatment incubation (if applicable):

42 ± 2 hours

Number of replicates:

3

Irritation / corrosion parameter:

% tissue viability

Remarks:

mean

Run / experiment:

60 minutes

Value:

101.5

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other:

Remarks:

The results obtained from the in vitro MatTek Epiderm Skin Irritation Test (SIT) with tin sulfide indicated a mean viability of 101.5 % (SD 5.32) therefore the test item is considered to be a non-irritant.

Other effects / acceptance of results:

- OTHER EFFECTS:
- Visible damage on test system: Not specified.
- Direct-MTT reduction: No direct MTT interference was observed. The test article did not reduce MTT.
- Colour interference with MTT: Not specified.

DEMONSTRATION OF TECHNICAL PROFICIENCY:

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes. The mean OD540 of the Negative Control tissues is ≥ 1.0 and ≤ 2.5 (1.732).
- Acceptance criteria met for positive control: Yes. The mean viability of the Positive Control tissues, expressed as percentage of the negative control tissues is ≤ 20% (9.2%)
- Acceptance criteria met for variability between replicate measurements: Yes. The standard deviation (SD) calculated from individual percent tissue viabilities of the three identically-treated replicates is < 18% (SD 0.15-5.32).

Interpretation of results:

GHS criteria not met

Conclusions:

Tin sulfide had no skin irritating effect in an in vitro skin irritation test.

Executive summary:

Objective of this test was to predict dermal irritation potential of tin sulfide in the context of identification and classification of skin irritation hazard according to the EU and GHS classification. This study was designed based on the MatTek protocol In Vitro Epiderm Skin Irritation Test. The mean tissue viability of test item was 101.5%. Therefore, tin sulfide is not skin irritating.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-04-20 to 2010-04-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline compliant study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

, adopted 24 April 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

New Zealand White rabbits were received from Covance Research Products, Inc., Denver, PA on 03/31/10 and acclimated for at least five days. Only animals in apparent good health were made available for study assignment. Prior to being selected for this study, both eyes of each animal were examined according to the Draize technique for any evidence of irritation or abnormalities of the cornea, iris and/or conjunctiva. A Mini-Maglite® flashlight equipped with a high intensity bulb was used to aid in the examination. Three rabbits (2 males- 1 female), free from evidence of ocular irritation or abnormalities, were assigned to this study without conscious bias. The animals were born on 12/12/09. The pretest body weight range was 2.6- 3.0 kg. The animals were identified by cage notation and a uniquely numbered metal eartag. The animals were housed 1/cage in suspended cages. Paper bedding was placed beneath the cages and changed at least three times/week. Fresh PMI Rabbit Chow (Diet #5321) was provided daily. Water was available ad libitum. The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12-hour light/dark cycle and was kept clean and vermin free.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

The test article (0.1 mL equivalent (87.6 mg)) was used for the study, in a single dose.

Duration of treatment / exposure:

The eyes of the test animals were not washed out after the application of test item.

Observation period (in vivo):

1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

Three healthy New Zealand White rabbits (2 males- 1 female), free from evidence of ocular irritation and corneal abnormalities, were dosed with tin sulfide. The test article (0.1 mL equivalent (87.6 mg)) was placed into the conjunctival sac of one eye of each rabbit. The contralateral eye served as a control. The eyes were examined pretest and scored by the Draize technique at 1, 24, 48 and 72 hours postdose. The control eyes were observed at the same time periods. Sodium fluorescein dye procedures were used at the 24-hour observation interval. Observations for toxicity and pharmacological effects were recorded at each ocular observation period. Body weights were recorded pretest and at termination. The mean total scores for 24, 48 and 72 hours were calculated by adding the total score for each time period and dividing by the number of animals.

Irritation parameter:

other: Mean total score

Basis:

mean

Time point:

other: 24 h

Score:

0.67

Max. score:

110

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: The "Max. score" gives the max. reachable score in the present test system.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

There was no corneal opacity or iritis noted at any observation period. Conjunctival irritation, noted in 3/3 eyes after 1 hour, cleared in two animals by 24 hours and in all animals by 48 hours. The control eyes were normal at all observation periods. There were no abnormal physical signs noted during the observation period. Body weights increased in 2/3 animals and stayed the same in one animal.

Interpretation of results:

GHS criteria not met

Conclusions:

Tin sulfide had no eye irritating/corrosive effect in an in vivo study according to OECD guideline 405.

Executive summary:

The eye irritating/corrosive properties of tin sulfide were determined in a study with rabbits according to OECD guideline 405. There was no corneal opacity or iritis noted at any observation period. Conjunctival irritation, noted in 3/3 eyes after 1 hour, cleared in two animals by 24 hours and in all animals by 48 hours. There were no abnormal physical signs noted during the observation period. In summary, the mean total score at 24 hours was 0.67, at 48 and 72 hours it was 0.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-01-15 to 10-01-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline compliant study

Qualifier:

according to guideline

Guideline:

other: Invittox 1992 Protocol no. 47: HET-CAM Test

Principles of method if other than guideline:

Objective:
To determine the potential irritancy using an alternative to the Draize methodology. The methodology was based on that described in INVITTOX. 1992 Protocol No. 47: Het - CAM; Test

Methos Synopsis:
The chorioallantoic membrane (CAM) of 24 White Lenghorn eggs, incubated for 10 days, were dosed with 0.1 ml of the test subststance. The eggs were observed continously for five minutes immediatly following dosing for the appearance of lysis (sec L), hemorrhage (sec H) and/or coagulation (sec C). In additon, the eggs werescored for severity at 1 and 5 minutes postdose. The irritating potential of the test article was classified based on the irritation score (IS) and the threshold concentration (TH).

GLP compliance:

yes (incl. QA statement)

Species:

other: not applicable; fertile, white Leghorn eggs

Strain:

other: not applicable; fertile, white Leghorn eggs

Details on test animals or tissues and environmental conditions:

Fertile, White Leghorn eggs (twenty four) received from Moyer's Chicks, Quakertown, PA were selected for use from a larger group and incubated on 01/15/10. The eggs were kept in incubators at 99 ± 2°F for 10 days.
Pre-dose Procedures
The eggs were marked on one side with an "X" and on the other side with an "0", and placed horizontally in the incubator trays. The eggs were rotated once daily during the first 9 days of incubation to ensure even atmospheric exposure.
On day 9 of incubation, the eggs were rotated and turned up in the incubator with the large end upwards containing the air sac to facilitate access to the CAM.
On day 10 of development, the eggs were removed from the incubator and candled to determine the viability of the embryo. A rectangular window was removed from the shell directly over the air cell using a rotating Dremel® drill with a diamond wheel bit. The egg membrane was carefully moistened with 2-3 mL 0.9% saline and returned to the incubator. Eggs were examined for any abnormalities. All abnormal eggs were discarded.

Vehicle:

other: corn oil

Controls:

other: not applicable; fertile white Leghorn eggs

Amount / concentration applied:

The eggs were dosed within 30 minutes of opening. The excess saline solution was gently poured off of the egg membrane which was then removed, and the CAM exposed. The eggs were numbered and 0.3 mL of the 10% mixture of the test article, positive controls (0.1 N Sodium Hydroxide [NaOH] and 1% Sodium Dodecylsulfate [SOS]) or vehicle control (Corn oil) was pipetted onto the CAM.

Duration of treatment / exposure:

The eggs were dosed within 30 minutes of opening. The excess saline solution was gently poured off of the egg membrane which was then removed, and the CAM exposed. The eggs were numbered and 0.3 ml of the 10% mixture of the test article, positive controls (0.1 N Sodium Hydroxide [NaOH] and 1% Sodium Dodecylsulfate [SOS]) or vehicle control (Corn oil) was pipetted onto the CAM.

Observation period (in vivo):

The eggs were observed continuously for 5 minutes and the appearance of lysis (sec L), hemorrhage (sec H) and/or coagulation (sec C) was documented. If no reaction was observed, a value of 301 seconds was recorded . In addition, the eggs were scored for severity at 1 and 5 minutes.
The severity of each reaction after 1 and 5 minutes were recorded as follows:
0 = no reaction
1 = slight reaction
2 = moderate reaction
3 = severe reaction

Number of animals or in vitro replicates:

6 eggs per group (test item, corn oil, 0.1N NaOH, 1% SDS)

Details on study design:

The chorioallantoic membrane (CAM) of 24 White Leghorn eggs, incubated for 10 days, were dosed with 0.3 mL of the test substance as listed in study report. The eggs were observed continuously for 5 minutes immediately following dosing for the appearance of lysis (sec L), hemorrhage (sec h) and/or coagulation (sec C). In addition, the eggs were scored for severity at 1 and 5 minutes postdose. The irritating potential of the test article was classified based on the irritation score (IS) and the threshold concentration (TH).

Irritation parameter:

in vitro irritation score

Run / experiment:

1 and 5 minutes

Value:

0

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

Based on the threshold concentration of gretaer than 10 % and the Irritating Score (10 %) of 0, the irritating potential of tin sulfide was determined as none to slight.

Interpretation of results:

GHS criteria not met

Conclusions:

Tin sulfide had no eye irritating/corrosive effect in a HET-CAM Test.

Executive summary:

The eye irritation/corrosion of tin sulfide was determined using the HET-CAM Test described in INVITTOX. 1992, protocoll no 47. Based on the threshold concentration of gretaer than 10% and the IS10% of 0, the irritating potential of tin sulfide was determined as none to slight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
GLP and guideline compliant in vivo study on tin sulfide

Justification for selection of eye irritation endpoint:
GLP and guideline compliant in vivo study on tin sulfide

Justification for classification or non-classification

Based on skin and eye irritation/corrosion data available for tin sulfide no classification and labelling is required according to Regulation No (EC) 1272/2008 (CLP) or Directive 67/548/EEC (DSD) criteria.