Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 May to 28 July, 2017
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
An in vivo test was done for chemical registration purposes in China in accordance with the Guidelines for the testing of chemicals "Skin Sensitization Study" (406) published by the Ministry of Environmental Protection of People's Republic of China in 2013. The test results are being provided for classification purposes.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
China in accordance with the Guidelines for the testing of chemicals "Skin Sensitization Study" (406) published by the Ministry of Environmental Protection of People's Republic of China in 2013.
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
An in vivo test was done for chemical registration purposes in China in accordance with the Guidelines for the testing of chemicals "Skin Sensitization Study" (406) published by the Ministry of Environmental Protection of People's Republic of China in 2013. The test results are being provided for classification purposes.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
White solid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Remarks:
Albino
Sex:
female
Details on test animals and environmental conditions:
On arrival, the guinea pigs were between 4 to 6 weeks old and in the weight range of 254 to 313 g. Prior to test administration, the guinea pigs were between 5 to 7 weeks old and in the weigh trange of 300.03 to 357.27 g. The guinea pigs were female, nulliparous, and non-pregnant. All animals were acclimatized for 8 days prior to the study.

The animals were fed pellet diet with complete nutrition and were provided with purified water. Food and water were available to the animals ad libitum during the test. They were housed in plastic cages with corn cob bedding and each cage contained no more than 12 animals. The temperature in the animal roooms were between 17 to 23°C and the relative humidity was between 40 to 70%. The animals experienced 12 hours of light and 12 hours of dark.

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
0.4 mL
Day(s)/duration:
Days 0, 7, and 14
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
0.3 mL
Day(s)/duration:
Day 27
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
32 animals total were divided into three groups. One preliminary irritation test group (2 animals), one negative control group (10 animals), and one treated group (20 animals).
Details on study design:
For the treated animal group, the left flanks of the guinea pigs were clipped free of hair. For both treated and control groups animals in the challenging group, right flanks of the guinea pigs were clipped free of hair on the morning prior to testing. The induction treatment group was given 0.255 g of raw test material via a patch. The treated group was given dosing on the left flank on day 0 (first induction day), day 7 and day 14. The negative control group received no treatment. The patches were rmoved after 6 hours of exposure and the test sites were gently cleanse dof any residual test item with water. At approximately 24 hours after the patch was removed, each dosing site was observed for both erythema and edema. The challenging treatment and control groups were given 0.237 g of raw test material via a patch. The challenge treatment and control groups were dosed on their right flanks on day 27. At appxoimately 24 and 48 hours after exposure, the application sites were observed for erythema and edema.

All animals were observed once per day for mortality and moribund states during the test period. Animals were weighed on arrival day, grouping day, and at the end of the study.

At the end of the test all surviving animals were euthanized by carbon dioxide asphyxiation and discarded without necropsy.
Challenge controls:
Challenge controls were dosed with 0.237 g of raw test materialls via a patch.
Positive control substance(s):
yes
Remarks:
DNCB (2,4-Dinitrochlorobenzene)

Results and discussion

Positive control results:
Historical data for the skin sensitization results of positive control 2,4-Dinitrochlorobenzene (DNCB) were referred to. DNCB resulted in a severity index of 0.85, 24 hours following removal of the patch in the treated group. DNCB resulted in a severity indext of 1.45, 48 hours following removal of the patch in the treated group. The incidence for the treated group was 16/20.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: Induction 1: Day 0: 24 hours after removal of test patches
Group:
test group
Dose level:
0.255 g raw test material and 0.4 mL purified water
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No visible changes were observed in all animals of treated group.
Reading:
other: Induction 2: Day 7: 24 hours after removal of test patches
Group:
test group
Dose level:
0.255 g raw test material and 0.4 mL purified water
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No visible changes were observed in all animals of treated group
Reading:
other: Induction: 3: Day 14: 24 hours after removal of test patches
Group:
test group
Dose level:
0.255 g raw test material and 0.4 mL purified water
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No visible changes were observed in all animals of treated group
Reading:
other: Challenge
Hours after challenge:
24
Group:
test group
Dose level:
0.237 g raw test material and 0.3 mL purified water
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No visible changes were observed in all animals of both negative control group and treated group
Remarks on result:
no indication of skin sensitisation
Reading:
other: Challenge
Hours after challenge:
48
Group:
test group
Dose level:
0.237 g raw test material and 0.3 mL purified water
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No visible changes were observed in all animals of both negative control group and treated group
Remarks on result:
no indication of skin sensitisation
Reading:
other: Challenge
Hours after challenge:
24
Group:
negative control
Dose level:
0.237 g raw test material and 0.3 mL purified water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No visible changes were observed in all animals of both negative control group and treated group
Remarks on result:
no indication of skin sensitisation
Reading:
other: Challenge
Hours after challenge:
48
Group:
negative control
Dose level:
0.237 g raw test material and 0.3 mL purified water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No visible changes were observed in all animals of both negative control group and treated group
Remarks on result:
no indication of skin sensitisation
Reading:
other: Challenge
Hours after challenge:
24
Group:
positive control
No. with + reactions:
14
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
other: Challenge
Hours after challenge:
48
Group:
positive control
No. with + reactions:
16
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on above results, Difluorosulfonamide HCl is not a skin sensitizer to guinea pigs.