1,1,3,3-Tetraoctyl-1-3-bis((2,2,3,5-oxotetramethylhexyl)oxy)distannoxane, dimer

Endpoint summary

Description of key information

one Guideline study on skin corrosion in vitro testing available. The results indicate no effects on the RHE test system at all. This information is concluded to be sufficient for the endpoint skin irritation in vitro testing as well.

one Guideline study on eye irritation available

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June - September 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
16JSVA015
- Expiration date of the lot/batch:
14. September 2018
- Purity test date:
not state

RADIOLABELLING INFORMATION (if applicable)
not applicable

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
Room Temperature: (20 ± 5°C), keep container tightly closed, store under inert gas
- Stability under test conditions:
assumed stable


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
none

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

other: not specified

Source strain:

other: Keratinocyte Strain: 00267

Justification for test system used:

according to Guideline

Vehicle:

unchanged (no vehicle)

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
EpiDermTM tissues were procured from MatTek In Vitro Life Science Laboratories, Bratislava.
Designation of the kit: EPI-200-SCT
Day of delivery: 20. Jun. 2017
Batch: 25822

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: Room temperature (3 min) and 37 °C (1 h)
- Temperature of post-treatment incubation (if applicable): 37 °C

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: 1 washing step by thoroughly rinsing
- Observable damage in the tissue due to washing: none noted
- Modifications to validated SOP:

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL
- Incubation time: e h
- Spectrophotometer: 96-well-plate photometer, Anthos Reader
- Wavelength: 570 nm.
- Filter:
- Filter bandwidth:
- Linear OD range of spectrophotometer:

FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
see additional information incl. tables section

NUMBER OF REPLICATE TISSUES: 2

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
not applicable, no direct MTT interference observed

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION:

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
according to GL
- Justification for the selection of the cut-off point(s) if different than recommended in TG 431 and 439:

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

50 μL

Duration of treatment / exposure:

3 min and 1 h

Duration of post-treatment incubation (if applicable):

3 h

Number of replicates:

2

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

3 min exposure

Value:

95.5

Negative controls validity:

valid

Positive controls validity:

valid

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

1 hour exposure

Value:

102.5

Negative controls validity:

valid

Positive controls validity:

valid

Interpretation of results:

GHS criteria not met

Conclusions:

Therefore, Bis(neodecanoyloxy)dioctylstannane is considered
non-corrosive to skin in the Reconstructed Human Epidermis (RHE) Test Method.

Executive summary:

One valid experiment was performed.

Two tissues of the human skin model EpiDermTM were treated with the test item

Bis(neodecanoyloxy)dioctylstannane for 3 minutes and 1 hour, respectively. The test item

was applied to each tissue and spread to match the tissue size.

Demineralised water was used as negative control, 8 M KOH was used as positive control.

After treatment, the respective substance was rinsed from the tissues. Then, cell viability of

the tissues was evaluated by addition of MTT, which can be reduced to a blue formazan.

Formazan production was evaluated by measuring the optical density (OD) at 570 nm of the

resulting solution.

After treatment with the negative control, the absorbance values were within the required

acceptability criterion of mean OD ≥ 0.8 and ≤ 2.8 for both treatment intervals thus showing

the quality of the tissues. The OD was 1.8 (3 minutes experiment) and 1.6 (1 hour experiment).

The positive control showed clear corrosive effects for both treatment intervals. The

mean relative tissue viability value was reduced to 7.8 % after the 1 hour treatment (and

reduced to 19.5 % after the 3 min treatment).

After 3 minutes treatment with the test item, the mean value of relative tissue viability was

reduced to 95.5 %. This value is above the threshold for corrosion potential (50%). After 1

hour treatment, the mean value of relative tissue viability was increased to 102.5 %. This

value, too, is above the threshold for corrosion potential (15%).

Therefore, Bis(neodecanoyloxy)dioctylstannane is considered

non-corrosive to skin in the Reconstructed Human Epidermis (RHE) Test Method.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May - August 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)

Qualifier:

according to guideline

Guideline:

EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
16JSVA015
- Expiration date of the lot/batch:
14. September 2018
- Purity test date:
not state

RADIOLABELLING INFORMATION (if applicable)
not applicable

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
Room Temperature: (20 ± 5°C), keep container tightly closed, store under inert gas
- Stability under test conditions:
assumed stable


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
none

Species:

cattle

Strain:

not specified

Details on test animals or tissues and environmental conditions:

Specification
Species Bos primigenius Taurus (fresh bovine corneas)
Origin
Fresh bovine eyes were obtained from the slaughterhouse Müller Fleisch GmbH, Enzstr.
2-4, 75217 Birkenfeld, Germany, on the day of the test. The cattle were between 12 and
60 months old. The eyes were transported to the test facility in Hanks’ Balanced Salt Solution
with 1% Penicillin-Streptomycin solution (Penicillin 100 U/mL, Streptomycin 100
μg/mL) in a suitable cooled container. Then, the corneas were dissected and incubated in
medium at 32 ± 1 °C in an incubation chamber for 1 hour.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

750 µL

Duration of treatment / exposure:

10 min

Duration of post- treatment incubation (in vitro):

2 h post incubation, 90 min incubation with sodium fluorescein.

Number of animals or in vitro replicates:

3

Details on study design:

SELECTION AND PREPARATION OF CORNEAS
QUALITY CHECK OF THE ISOLATED CORNEAS
After the arrival of the corneas, they were examined and only corneas which were free
from damages were used. The corneas were excised with a scalpel and cut from the globe
with a 2-3 mm ring of sclera around the outside. Each cornea was transferred to a cornea
holder in which pre-warmed cMEM (32 ± 1 °C) without phenol red was filled. The holders
were then incubated for 1 hour in the incubation chamber at 32 ± 1 °C.


NUMBER OF REPLICATES
3
NEGATIVE CONTROL USED
HBSS: Hank’s Balanced Salt Solution (HBSS) 10-fold concentrated, diluted in demin. water
(1:10)
SOLVENT CONTROL USED (if applicable)
not applicable
POSITIVE CONTROL USED
Dimethylformamide, DMF, CAS-No. 68-12-2, undiluted,
APPLICATION DOSE AND EXPOSURE TIME
750 µL, 10 min
TREATMENT METHOD: closed chamber

POST-INCUBATION PERIOD: yes, 2 h

REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: 1
- POST-EXPOSURE INCUBATION: 2h

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: The change of opacity value of each treated cornea with test item, positive control and
negative control was calculated by subtracting the initial basal opacity from the post treatment
opacity reading for each cornea.
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of microtiter plate reader (OD490)

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)

DECISION CRITERIA: please specify if the decision criteria as indicated in the TG was used. yes

Irritation parameter:

in vitro irritation score

Run / experiment:

Mean of three replicates

Value:

ca. 2.13

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

According to the guideline, the test is considered as valid if the positive control causes an
IVIS that falls within two standard deviations of the current historical mean.
The negative control has to show an IVIS ≤ 3.
The validity criteria and findings are given in the following table:

Parameter Criterion Found Assessment
IVIS of negative control HBSS ≤ 3 -0.64 ok
IVIS of positive control DMF undiluted 45.08 – 153.86 74.09 ok

Values for negative and positive controls were within the range of historical data of the test
facility. Therefore, the test was acceptable.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the test item Bis(neodecanoyloxy)dioctylstannane showed no effects on the cornea of the bovine eye.

Executive summary:

One valid experiment was performed.

Bovine corneas were used. They were collected from slaughtered cattle which were between

12 and 60 months old.

The test item Bis(neodecanoyloxy)dioctylstannane was brought onto the cornea of a bovine

eye which had been incubated with cMEM without phenol red at 32 ± 1 °C for 1 hour

and whose opacity had been measured.

The test item was incubated on the cornea for 10 minutes at 32 ± 1 °C. After removal of

the test item and 2 hours post-incubation, opacity and permeability values were measured.

HBSS-solution was used as negative control. The negative control showed no irritating

effect on the cornea and the calculated IVIS (in vitro irritancy score) is -0.64.

Dimethylformamide (DMF) undiluted was used as positive control. The positive control induced

serious eye damage on the cornea and falls within two standard deviations of the

current historical mean. The calculated IVIS (in vitro irritancy score) is 74.09.

Under the conditions of this study, the test item Bis(neodecanoyloxy)dioctylstannane

showed no effects on the cornea of the bovine eye. The calculated IVIS (in vitro irritancy

score) is 2.13.

According to OECD Guideline no. 437 (Jul. 2013), a substance with an IVIS ≤ 3 requires

no classification for eye irritation or serious eye damage.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available information is conclusive but not sufficient for classification.