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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study performed according to the OECD guideline.
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
yes
Remarks:
during the acclimation phase the relative humidity in the animal room was between 27 and 65% instead of 45-65%. This has no impact on the validity of the study.
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
other: CBA/CaOlaHsd
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan laboratories BV
- Age at study initiation: 8-12 weeks
- Weight at study initiation: between 17.4 and 24.3 g
- Housing: single caging, in Makrolon type II cages, with wire mesh top. Bedding: granulated soft wood.
- Diet: pelleted standard diet, ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 2°C
- Humidity (%): 27-65%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 16-MAR-2010 to 14-APR-2010
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
0.5; 1; 2.5; 5 and 10%
No. of animals per dose:
4
Details on study design:
RANGE FINDING TESTS:
- Compound solubility: pre-test on solubility showed that the highest item concentration was 100%
- Irritation: due to the acute toxicity of the substance the highest concentration tested in the pre-test was 25%. The 2 mice died, so a new pre-test was performed with 10%. Sign of local irritation were not observed, reduced spontaneous activity was observed within 1 hour after treatment, and not seen afterwards.
- Lymph node proliferation response: not determined

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response:
A test item is regarded as a sensitiser in the LLNA if the following criteria are fulfilled:
- First, that exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the stimulation index.
- Second, that the data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression


TREATMENT PREPARATION AND ADMINISTRATION:
The test item was placed into a volumetric flask on a tared balance and acetone:olive oil (4+1) was quantitatively added. The different test item concentrations were prepared serially.
The preparations were made freshly before each dosing occasion.
A correction factor of 1.02 for the purity was used

Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear (left and right) with test item concentrations of 0.5, 1, 2.5, 5, and 10% (w/w) in acetone:olive oil (4+1). The application volume, 25 µl, was spread over the entire dorsal surface (  8 mm) of each ear once daily for three consecutive days. A further group of mice was treated with an equivalent volume of the vehicle (acetone:olive oil (4+1)) alone (control animals).
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
The mean values and standard deviations were calculated in the body weight tables. The ANOVA (Dunnett-test) was conducted on the ear thickness to assess whether the difference is statistically significant between test item groups and negative control (vehicle) group. However, both biological and statistical significance were considered together.
Positive control results:
test performed in Nov 2009.
EC3 value is 12.9%
Parameter:
SI
Remarks on result:
other: see table 1
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: see table 1

Table 1: calculation and results of individual data

Vehicle: acetone:olive oil (4+1)

Test item concentration % (w/w)

Group

Measurement DPM

Calculation

Result

DPM-BGa)

number of lymph nodes

DPM per lymph nodeb)

S.I.

---

BG I

30

---

---

---

---

---

BG II

62

---

---

---

---

---

1

5461

5415

8

676.9

 

0.5

2

5822

5776

8

722.0

1.07

1

3

6324

6278

8

784.8

1.16

2.5

4

6890

6844

8

855.5

1.26

5

5

9263

9217

8

1152.1

1.70

10

6

6063

6017

8

752.1

1.11

BG =  Background (1 ml 5% trichloroacetic acid) in duplicate

1    =  Control Group

2-6=  Test Groups

S.I. =  Stimulation Index

a)   =  The mean value was taken from the figures BG I and BG II

b)    =  Since the lymph nodes of the animals of a dose group were pooled, DPM/node was determined by dividing the measured value by the number of lymph nodes pooled

The EC3 value could not be calculated, since all S.I.´s are below 3.

The measured ear thickness of all animals treated was recorded prior to the 1stapplication and prior to necropsy. A relevant increase in ear thickness was not observed in the animals treated with different test item concentrations in comparison to the control group.

Table 2: ear thickness

Animal No.

Ear thickness before the 1st application (µm)

Ear thickness prior to treatment with3HTdR (µm)

Ear thickness gain (µm)

right

left

mean

Mean dose group±SD

right

left

mean

Mean dose group±SD

Thick-ness gain

Mean dose group

1

250

250

250.0

250.0±3.8

255

250

252.5

253.8±4.3

2.5

3.8±3.2

2

255

240

247.5

255

250

252.5

5.0

3

250

255

252.5

260

260

260.0

7.5

4

250

250

250.0

255

245

250.0

0.0

5

255

260

257.5

250.0±5.4

260

265

262.5

253.1±8.8

5.0

3.1±4.3

6

250

245

247.5

250

250

250.0

2.5

7

245

245

245.0

240

245

242.5

-2.5

8

250

250

250.0

255

260

257.5

7.5

9

250

250

250.0

245.0±3.5

260

255

257.5

253.8±4.8

7.5

8.8±4.3

10

245

245

245.0

250

255

252.5

7.5

11

240

245

242.5

250

245

247.5

5.0

12

245

240

242.5

260

255

257.5

15.0

13

250

255

252.5

252.5±2.0

255

250

252.5

254.4±3.8

0.0

1.9±4.3

14

255

255

255.0

250

255

252.5

-2.5

15

250

255

252.5

260

260

260.0

7.5

16

250

250

250.0

255

250

252.5

2.5

17

245

250

247.5

246.3±4.3

250

255

252.5

251.9±5.2

5.0

5.6±1.3

18

250

245

247.5

255

250

252.5

5.0

19

245

255

250.0

255

260

257.5

7.5

20

240

240

240.0

250

240

245.0

5.0

21

250

245

247.5

249.4±2.4

245

250

247.5

255.0±5.4

0.0

5.6±3.8

22

245

250

247.5

255

255

255.0

7.5

23

250

250

250.0

260

255

257.5

7.5

24

250

255

252.5

255

265

260.0

7.5

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Quinoline is not a skin sensitizer.
Executive summary:

In the study, the test item Quinoline dissolved in acetone:olive oil (4+1) was assessed for its possible contact allergenic potential.

For this purpose a local lymph node assay was performed using test item concentrations of 0.5, 1, 2.5, 5, and 10%.

The animals did not show any clinical signs during the course of the study and no cases of mortality were observed. A statistically significant increase in ear thickness was not observed in the animals treated with different test item concentrations in comparison to the control group.

In this study Stimulation Indices (S.I.) of 1.07, 1.16, 1.26, 1.70, and 1.11 were determined with the test item at concentrations of 0.5, 1, 2.5, 5, and 10% in acetone:olive oil (4+1), respectively.

The test item Quinoline was not a skin sensitiser in this assay.

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

A valid study performed according to the OECD guideline and to GLP is available and is used as a key study.


Migrated from Short description of key information:
Quinoline has no sensitizing properties.

Justification for selection of skin sensitisation endpoint:
This is the only study considered as valid.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No data available to consider that quinoline is a respiratory sensitizer. However as it is a CMR substance, the exposure has to be avoided, so the respiratory sensitisation (if any) should not occur.


Migrated from Short description of key information:
No data available.

Justification for classification or non-classification

No data available, so no classification is proposed.