Sodium hydroxyquinoline propanesulfonate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Aug 2015 -Jan 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Sodium rac-1-hydroxy-3-(quinolin-6-yl)propanesulfonate

Cas Number:

1609934-65-7

Molecular formula:

C12H12NO4SNa

IUPAC Name:

Sodium rac-1-hydroxy-3-(quinolin-6-yl)propanesulfonate

Test material form:

solid: particulate/powder

In vivo test system

Test animals

Species:

mouse

Strain:

Balb/c

Sex:

female

Details on test animals and environmental conditions:

Animal species and strain: Mouse, Balb/c strain, inbred, SPF-Quality.
Number of animals 30 females (nulliparous and non-pregnant), six females per group.
Age: Approximately 8 weeks (at initiation of treatment).
Body weight range: 18.1 to 22.1 gram (at initiation of treatment).

Location: Specific Pathogen Free area: animal rooms A0.18.
Conditions: Environmental controls for the animal room were set to
maintain 18 to 24°C, a relative humidity of 40 to 70%, at least
10 air changes/hour, and a 12-hour light/12-hour dark cycle.
Any variations to these conditions were maintained in the raw
data and had no effect on the outcome of the study.
Animal caging:
Group housing in Makrolon cages (MIII type; height 18 cm)
containing sterilized sawdust as bedding material (Lignocel S
8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG,
Rosenberg, Germany).
The acclimatization period was at least 5 days before the start
of treatment under laboratory conditions.
Cage enrichment: Paper (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd),
Surrey, United Kingdom) and shelters (disposable paper corner
home, MCORN 404, Datesand Ltd, USA) were supplied as
cage-enrichment.
Food: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF®
Spezialdiäten GmbH, Soest, Germany).
Water: Free access to tap-water.
Analysis of food, sawdust,
paper, shelters and water:
Results of analysis for diet (nutrients and contaminants),
sawdust, paper, shelters and water were assessed and did not
reveal any findings that were considered to have affected the
study integrity. All certificates and results of analysis are
retained in the WIL Research Europe archives.

Study design: in vivo (LLNA)

Vehicle:

other: Ethanol: Elix Water (7:3, v:v)

Concentration:

Pre-screen test: 25% and 40%
Main study: 0.5%, 5% and 40%

No. of animals per dose:

Pre-screen test: Four young adult animals were selected and two test item concentrations were tested, each on two animals. Concentrations of 25% and 40% were tested and the highest concentration was the maximum that could be prepared homogeneously.
Main study: Three groups of six animals were treated with one test item concentration per group. The
highest test item concentration was selected from the pre-screen test. One group of six animals
was treated with vehicle and one group with the positive control item.

Details on study design:

A pre-screen test was conducted in order to select the highest test item concentration to be
used in the main study. In principle, this concentration should cause no systemic toxicity and
may give well-defined irritation (maximally grade 2.
Four young adult animals were selected and two test item concentrations were tested, each on
two animals. Concentrations of 25% and 40% were tested and the highest concentration was
the maximum that could be prepared homogeneously.
The test system, procedures and techniques were the same to those used in the main study,
with the exceptions that Makrolon MII type cages (height 14 cm) were used for group
housing, the animals were 9 weeks old, no examinations were performed after the animals
were sacrificed on Day 4 and scoring for irritation included scoring for oedema.
Main study:
Three groups of six animals were treated with one test item concentration per group. The
highest test item concentration was selected from the pre-screen test. One group of six animals
was treated with vehicle and one group with the positive control item.

Positive control substance(s):

other: 0.5% 1-Chloro-2,4-Dinitrobenzene (DNCB)

Statistics:

Calculations were performed in MS EXCEL and statistical analysis was performed with
GraphPad Prism 4 (Kruskal-Wallis test, followed by the Mann Whitney test).

Results and discussion

Positive control results:

The positive control item DNCB elicited a reaction pattern with increased LN hyperplasia,
which was in congruence with the expected mode of action of a contact allergen.

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Test group / Remarks:

0.5% solution

Remarks on result:

not measured/tested

Results 2

Key result

Parameter:

SI

Test group / Remarks:

5% solution

Remarks on result:

not measured/tested

Results 3

Key result

Parameter:

SI

Test group / Remarks:

40% solution

Remarks on result:

not measured/tested

Results 4

Key result

Parameter:

other: Ear weight index

Value:

0.99

Test group / Remarks:

0.5% solution

Results 5

Key result

Parameter:

other: Ear weight index

Value:

1

Test group / Remarks:

5% solution

Results 6

Key result

Parameter:

other: Ear weight index

Value:

0.99

Test group / Remarks:

40% solution

Results 7

Key result

Parameter:

other: LN weight index

Value:

0.99

Test group / Remarks:

0.5% solution

Results 8

Key result

Parameter:

other: LN weight index

Value:

1.17

Test group / Remarks:

5% solution

Results 9

Key result

Parameter:

other: LN weight index

Value:

1.14

Test group / Remarks:

40% solution

Results 10

Key result

Parameter:

other: Cell count index

Value:

0.94

Test group / Remarks:

0.5% solution

Results 11

Key result

Parameter:

other: Cell count index

Value:

1.24

Test group / Remarks:

5% solution

Results 12

Key result

Parameter:

other: Cell count index

Value:

1.22

Test group / Remarks:

40% solution

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In conclusion, no sensitizing or irritating potential was ascribed to INC280-C1 in the murine LLNA TIER I.
Based on these results INC280-C1 would not be regarded as a skin sensitizer according to the recommendations made in the test guidelines. It does not have to be classified and has no obligatory labelling requirement for sensitization by skin contact according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United
Nations (2007) (including all amendments).