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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-01-18 to 2010-02-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and Guideline compliant study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
, published in O.J. L142, 2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
, adopted 24. April 2002
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Chemical structure
Reference substance name:
Tin sulphide
EC Number:
215-248-7
EC Name:
Tin sulphide
Cas Number:
1314-95-0
Molecular formula:
SSn
IUPAC Name:
tin sulphide
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

In vivo test system

Test animals

Species:
mouse
Strain:
Balb/c
Sex:
female
Details on test animals and environmental conditions:
Animals species and strain: Young adult female mice (nulliparous and non-pregnant), strain
BALB/CBYJICO
Source: Breeding farm VELAZ s.r.o., Kolec u Kladna, Czech Republic,
RCH CZ 21760118
Age: 8 to 1 0 weeks (at start of dosing)
Body weight range at starting: 19.0 to 21.9 g (at start of dosing)
Health examination: All animals were examined during the acclimatisation period
Acclimatisation: At least 5 days
Animal rooms: Monitored conditions, microbiologically defined background,
according to SOP No.40
Microclimatic conditions: Room temperature 22.5 -- 23.3°C, permanently monitored
Relative humidity 44 - 49 %, permanently monitored
Light: 12 hours light/dark cycle: 6am-6pm/6pm-6am
Animal caging: Animals in groups: maximum six in macrolon cages (35x20xl5
cm) with sterilized softwood shavings
Water: Drinking tap water ad libitum. Water quality corresponded to
Regulation No. 252/2004 Czech Coll. of Law, Health Ministry
Diet: Pelleted standard diet for experimental animals ad libitum (ST 1
BERGMAN, manufacturer: Ing. Miroslav Mrkvicka- Vyroba
krmnych smesi, Mlyn Kocanda No. 19, 252 42 Jesenice u
Prahy). Microbiological control and content of nutrients is
performed according SOP No. 72.

Study design: in vivo (LLNA)

Vehicle:
other: DAE 433
Remarks:
mixture of 40% dimethylacetamide, 30% acetone and 30% ethanol
Concentration:
0.3%, 3% and 30 % (1,5 g; 0,15 g; 0,015g tin sulfide)
No. of animals per dose:
5
Details on study design:
The volume of the application form was constant at all groups of animals - 25 µL of the
appropriate dilution to the dorsum of each ear once a day morning for 3 consecutive days. The
application was performed very slowly by micropipette. Losses caused by draining from the
ear must be minimized.
This route of administration is listed in the guideline and it is similar to expected exposure
conditions at the workplace. The application form of test substance was prepared immediately
before administration.
Day 1:
Open application of 25µL (in the morning, by pipette) of appropriate suspensions of the test
substance, the vehicle alone or the positive control to the dorsum of each ear.
Days 2 and 3:
The application procedure repeated as carried out on day 1.
Days 4 and 5:
No treatment.
Day 6:
Injection 250 µL of phosphate-buffered saline (PBS) containing 7.87 x10E5 Bq of ³H-methyl
thymidine into all test and control mice via the tail vein.
Five hours later, the animals were killed.
Positive control substance(s):
other: Dinitrochlorobenzene (DNCB)
Statistics:
For statistical calculations the software Statgraphic ® Centurion (version XV, USA) was
used. Statistical evaluation of measured parameters was performed at first by applying the
non-parametric Kruskal-Wallis test for the comparison ofthe measured effect in all treatment
groups with the vehicle control group, as global test, and then the non-parametric two-group
Mann-Whitney rank test (probability level 0.05) for all two-group comparisons.

Results and discussion

Positive control results:
Dinitrochlorobenzene provided a positive result in LLNA test.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
other: clinical observations
Remarks:
72h after challenge
Value:
0
Test group / Remarks:
30% in DAE
Remarks on result:
other: No observations
Parameter:
SI
Remarks:
mean per treatment group
Value:
1.35
Test group / Remarks:
30% in DAE 433
Parameter:
SI
Remarks:
mean per treatment group
Value:
1.91
Test group / Remarks:
3% in DAE 433
Parameter:
SI
Remarks:
mean per treatment group
Value:
1.86
Test group / Remarks:
0.3% in DAE 433
Parameter:
SI
Remarks:
mean per treatment group
Value:
1
Test group / Remarks:
negative control
Parameter:
SI
Remarks:
mean per treatment group
Value:
16.94
Test group / Remarks:
positive control 0.5% DNCB
Parameter:
other: DPM: desintegrations per minute
Remarks:
mean per treatment group
Value:
319.4
Test group / Remarks:
30% in DAE 433
Parameter:
other: DPM: desintegrations per minute
Remarks:
mean per treatment group
Value:
452.9
Test group / Remarks:
3% in DAE 433
Parameter:
other: DPM: desintegrations per minute
Remarks:
mean per treatment group
Value:
441.5
Test group / Remarks:
0.3% in DAE 433
Parameter:
other: DPM: desintegrations per minute
Remarks:
mean per treatment group
Value:
237.3
Test group / Remarks:
negative control
Parameter:
other: DPM: desintegrations per minute
Remarks:
mean per treatment group
Value:
4 018.4
Test group / Remarks:
positive control 0.5% DNCB

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Tin sulfide had no sensitising effect in the murine local lymph node assay according to OECD guideline 429.
Executive summary:

Tin sulfide was assessed for skin sensitisation potential with the murine local lymph node assay (LLNA). The LLNA with radionuclides was performed according to OECD guideline 429.

The animals exposed to the test substance at all concentrations (30 %, 3 %, 0.3 % in DAE 433) showed no pathological skin reactions and no other negative clinical symptoms of intoxication throughout the experiment. There was no significant difference in body weight increment of all groups in comparison to the vehicle control. The positive control substance DNCB elicited a reaction pattern with statistically significant increase in ear weight and Stimulation Index of cell proliferation 16.9, which was in congruence with his expected mode of action as a contact allergen. The test substance tin sulfide did not show a tendency to increased ear weight in any of concentrations tested. The result of skin irritation effect was considered as negative - it means the test substance did not cause irritation of skin. Comparison of Stimulation Indexes between all treated groups and control vehicle group revealed that the test substance tin sulfide did not cause increase in radioisotope incorporation into the DNA of dividing lymphocytes. In conclusion, at the given experimental conditions the test substance tin sulfide provided a negative result in LLNA test.

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