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Diss Factsheets

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:
18 Jul - 1 Aug 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
GLP compliance unknown, deviations from guideline (3 instead of 4 animals / group, no information on positive control, no clinical observations performed; only 2 concentrations tested)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
adopted 22 Jul 2010
Deviations:
yes
Remarks:
- 3 instead of 4 animals/group - no information on positive control - no statistical analysis performed - no clinical observations performed - only 2 concentrations + control tested
GLP compliance:
not specified
Remarks:
in-house safety study
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(2,2,4-trimethyl-3,4-dihydroquinolin-l (2H)-yl)ethanone
EC Number:
855-228-0
Cas Number:
4497-59-0
Molecular formula:
C14 H19 N O
IUPAC Name:
1-(2,2,4-trimethyl-3,4-dihydroquinolin-l (2H)-yl)ethanone

In vivo test system

Test animals

Species:
mouse
Strain:
other: CBA/JCrlj
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 weeks (preliminary study); 9 weeks (main study)
- Weight at study initiation: preliminary study: 18.69 - 23.04 g; main study: 19.21 - 23.41 g
- Housing: 3 animals per cage in suspended cages with aluminum/stainless steel walls and stainless steel netting floor and front opening (W176 × D302 × H130 mm, Yamato Scientific Co., Ltd.); cages were exchanged for clean sterile cages once a week
- Diet: solid mouse chow (CRF-1, Oriental Yeast Co., Ltd.); ad libitum
- Water: tap water; ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 25
- Humidity (%): 40 - 70
- Air changes (per hr): ≥ 10
- Photoperiod: 12 / 12

IN-LIFE DATES:
Preliminary study: 18 - 23 Jul 2012
Main study: 25 Jul - 01 Aug 2012

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
preliminary study: 2%, 10% and 50%
main study: 10% and 50%
No. of animals per dose:
preliminary study: 3 animals (one per dose group)
main study: 9 animals (3 per dose group and negative control)
Details on study design:
PRE-SCREEN TESTS
- Compound solubility: The test substance dissolved at 50% (v/v) in acetone/olive oil (4:1 v/v). Therefore, acetone/olive oil (4:1 v/v) was selected as the vehicle.
- Irritation: No irritation was observed after applying the test substance at any concentration.
- Lymph node weights: 0.0046 g, 0.0042 g and 0.0044 g in the 2%, 10% and 50% application groups, respectively.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: 3H-methyl thymidine incorporation
- Criteria used to consider a positive response: The ratios [radioactivity in the groups with the test substance applied (dpm) / radioactivity in the control group (dpm)] were calculated, and a ratio of ≥3 was assessed as positive.

TREATMENT PREPARATION AND ADMINISTRATION
For the preliminary study, acetone/olive oil (4:1 v/v) solutions with the test substance at 2%, 10% and 50% were applied open to both ears of the mice at 0.025 mL/site for 3 consecutive days (1 mouse / concentration). The day that application was started was calculated as day 1 of the study, and the presence or absence of irritation (erythema) was confirmed on day 2, 3 and 6 of the study. In addition, on day 6 of the study the auricular lymph nodes were collected, and the weight was measured.
For the main study, concentrations of the test substance were set to on the basis of the results of the preliminary study (10%, 50% acetone/olive oil (4:1 v/v) solutions) and were applied open to both ears of the mice at 0.025 mL/site for 3 consecutive days (3 mice / concentration). In addition, there was a group to which acetone/olive oil (4:1 v/v) only was applied, as a control group. The day that application was started was calculated as day 1 of the study, and the presence or absence of irritation (erythema) was confirmed on days 2 and 3 of the study. On day 6 of the study, [methyl-3H]thymidine prepared to a concentration of 2.96 MBq (80 µCi)/mL by using PBS was administered intravenously at 0.25 mL/animal, and 5 hours after administration cells were recovered from auricular lymph nodes, and radiation (dpm) was measured by liquid scintillation counting.
Positive control substance(s):
not specified
Statistics:
not performed

Results and discussion

Positive control results:
No data

In vivo (LLNA)

Resultsopen allclose all
Key result
Parameter:
SI
Value:
1.8
Test group / Remarks:
50%
Key result
Parameter:
SI
Value:
2.4
Test group / Remarks:
10%
Parameter:
SI
Remarks on result:
other: not measured/tested (only two concentrations assessed)
Cellular proliferation data / Observations:
DETAILS ON STIMULATION INDEX CALCULATION:
The SI of the 10 and 50% treatment group was 2.4 and 1.8, respectively.

EC3 CALCULATION:
The EC3 value could not be calculated, since all S.I. are below the threshold value of 3.

CLINICAL OBSERVATIONS:
Not performed.

BODY WEIGHTS:
Body weight gain after application of the test substance averaged 0.81 g, 1.19 g, and 0.69 g in the control group and the 10% and 50% application groups, respectively.

SIGNS OF TOXICITY:
No irritation was noted at any concentration.

LYMPH NODE WEIGHTS:
Lymph node weight in the control group and the 10% and 50% application groups, averaged 0.0045 g, 0.0057 g and 0.0052 g, respectively.

Any other information on results incl. tables

Table 1: Results of the skin sensitisation study (main study)











































































































Dose (%)*



Body weight (g)



Irritation



Lymph node weight



Radioactivity



Study day 1



Study day 6



Weight gain



Average weight gain



Study day 2



Study day 3



Indivi-dual



Group total



Group average



dpm



ratio



0



21.50



22.62



1.12



0.81



No irritation



0.0040



0.0134



0.0045



1146



-



20.39



20.63



0.24



No irritation



0.0045



22.54



23.60



1.06



No irritation



0.0049



10



21.69



22.51



0.82



1.19



No irritation



0.0058



0.0172



0.0057



2694



2.4



19.95



21.39



1.44



No irritation



0.0063



22.07



23.39



1.32



No irritation



0.0051



50



23.41



24.59



1.18



0.69



No irritation



0.0054



0.0156



0.0052



2081



1.8



21.63



21.28



-0.35



No irritation



0.0055



19.21



20.44



1.23



No irritation



0.0047



*in acetone/olive oil (4/1); vehicle

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
The test substance did not exhibit skin sensitising potential and does therefore not meet the criteria for classification as skin sensitising.