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Description of key information

No evidence of skin sensitisation was observed in a Buehler Test conducted in guinea pigs according to OECD Test Guideline 406.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
6th November - 12th November 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
A Buehler study was conducted for research and development purposes. However, in the interest of promotong the 3R principle it would be unethical to run another in vivo study to the LLNA method.
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
Prior to use, all animals were acclimated for at least five days. Animals were individually housed
in wire mesh suspension cages. The animals were maintained on a 12-hour cycle light controlled
room, at a temperature of 64° - 79°F and a relative humidity of 30-70%.
Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.4 mL at a 20% concentration
Day(s)/duration:
six hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
5%
Day(s)/duration:
14
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 animals in test group,
6 control animals
Details on study design:
0.4 ml of the test substance at a 20% concentration diluted in mineral oil directly into Hilltop Chambers® and applying
them to the clipped left shoulder of twenty albino guinea pigs in the following manner: The
animals were held gently, and the chambers were applied as quickly as possible to the clipped left
shoulder. The chambers were secured with Micropore tape and further secured with Kendall
adhesive tape. Approximately six hours later, the tape and chambers were removed. Two
additional induction doses were conducted following the same procedure, at weekly intervals.
Two weeks after the final application the animals received a topical primary challenge dose (6
hour contact) of X-16151, Batch #: R17-2934 at 5% concentration diluted in mineral oil, on a naive
site located on the right shoulder. Animals were scored for irritation at 24 and 48 hours after
initiation of the primary challenge application.
Ten guinea pigs served as a naive control group, and remained untreated through the induction
phase. Six naive control animals received only the primary challenge dose, at a 5% concentration
diluted in mineral oil. The four remaining guinea pigs were designated for a re-challenge, if
necessary.
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
not measured/tested
Interpretation of results:
GHS criteria not met
Conclusions:
The test susbtance did not induce skin sensitization
Executive summary:

The test substance was evaluated for sensitization potential by applying 0.4 ml at a 20% concentration diluted in mineral oil directly into Hilltop Chambers® and applying them to the clipped left shoulder of twenty albino guinea pigs in the following manner: The animals were held gently, and the chambers were applied as quickly as possible to the clipped left

shoulder. The chambers were secured with Micropore tape and further secured with Kendall adhesive tape. Approximately six hours later, the tape and chambers were removed. Two additional induction doses were conducted following the same procedure, at weekly intervals.

Two weeks after the final application the animals received a topical primary challenge dose (6 hour contact) of the test substance at 5% concentration diluted in mineral oil, on a naive site located on the right shoulder. Animals were scored for irritation at 24 and 48 hours after initiation of the primary challenge application.

Ten guinea pigs served as a naive control group, and remained untreated through the induction phase. Six naive control animals received only the primary challenge dose, at a 5% concentration diluted in mineral oil. The four remaining guinea pigs were designated for a re-challenge, if necessary.

Following primary challenge of test substance at 5% concentration, the incidence of grade 1 response or greater in the test group (0 of 20) was compared to that of the naive control group (0 of 6). The incidence and severity of these responses were not significantly greater than those produced by the naive control group indicating that sensitization had not been induced.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The test substance was evaluated for sensitization potential by applying 0.4 ml at a 20% concentration diluted in mineral oil directly into Hilltop Chambers® and applying them to the clipped left shoulder of twenty albino guinea pigs in the following manner: The animals were held gently, and the chambers were applied as quickly as possible to the clipped left

shoulder. The chambers were secured with Micropore tape and further secured with Kendall adhesive tape. Approximately six hours later, the tape and chambers were removed. Two additional induction doses were conducted following the same procedure, at weekly intervals.

Two weeks after the final application the animals received a topical primary challenge dose (6 hour contact) of the test substance at 5% concentration diluted in mineral oil, on a naive site located on the right shoulder. Animals were scored for irritation at 24 and 48 hours after initiation of the primary challenge application.

Ten guinea pigs served as a naive control group, and remained untreated through the induction phase. Six naive control animals received only the primary challenge dose, at a 5% concentration diluted in mineral oil. The four remaining guinea pigs were designated for a re-challenge, if necessary.

Following primary challenge of test substance at 5% concentration, the incidence of grade 1 response or greater in the test group (0 of 20) was compared to that of the naive control group (0 of 6). The incidence and severity of these responses were not significantly greater than those produced by the naive control group indicating that sensitization had not been induced.

The study was assessed as Klimisch 1, as it is compliant with GLP and OECD Test Guidelines. It is therefore considered to be sufficiently reliable for classification purposes. In vitro skin sensitisation studies are not available; these do not need to be conducted since adequate data are already available from an in vivo skin sensitisation study.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No data are available on respiratory sensitisation. However, exposure of humans via inhalation is considered unlikely.

Justification for classification or non-classification

Based on the available data, the substance is not classified for skin sensitisation in accordance with Regulation (EC) No. 1272/2008. No data are available on respiratory sensitisation.