2-methoxy-N,N,β-trimethyl-10H-phenothiazine-10-propylamine

Skin sensitisation

Administrative data

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

2-methoxy-N,N,β-trimethyl-10H-phenothiazine-10-propylamine

EC Number:

212-706-8

EC Name:

2-methoxy-N,N,β-trimethyl-10H-phenothiazine-10-propylamine

Cas Number:

851-68-3

Molecular formula:

C19H24N2OS

IUPAC Name:

2-methoxy-N,N,β-trimethyl-10H-phenothiazine-10-propylamine

Test material form:

solid: crystalline

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source:
- Females (if applicable) nulliparous and non-pregnant: [yes/no/not specified]
- Microbiological status of animals, when known:
- Age at study initiation:
- Weight at study initiation:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:
- Indication of any skin lesions:

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):
- IN-LIFE DATES: From: To:TEST ANIMALS
- Source: TOXI-COOP ZRT. H-1103, Budapest Cserkesz utca 90.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 11 weeks
- Weight at study initiation: 18.1-21.8 g
- Housing: grouped caging in small groups
- Diet (e.g. ad libitum): ssniff Rat/Souris-Elevage E complete, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+-3 °C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light):12-12

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

0,25%, 0,5%, 1%

No. of animals per dose:

4

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

No mortality, cutaneous reactions or signs of toxicity were observed in the positive control group.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

>= 0.7 - <= 1.2

Test group / Remarks:

0.25%, 0.5%, 1%

Results 2

Parameter:

SI

Value:

5

Test group / Remarks:

2.5%

Cellular proliferation data / Observations:

Body Weight Measurement:
Significant, treatment related effect on body weights was observed in the 2.5 % (w/v) dose group: body weight decrease by > 5% was observed for 3 of the 4 animals (7%, 9% or 8% decrease) together with decrease of the mean value by 6%. Although body weight decrease by 5% was observed also in the 1% and 0.5% (w/v) dose groups (1 of the 4 animals, 7% decrease in each) the effect was considered not significant as the mean values did not decrease significantly and similar effect was observed also in the vehicle (AOO) control group (1 of the 4 animals, 6% decrease).

Clinical Observations and Signs of Irritation:
No mortality was observed during the test. As a sign of systemic toxic effect decreased activity was observed on Day 3 (prior to and after the treatment) and on Day 4 for all 4 animals in the 2.5% (w6v) dose group. No symptom of systemic toxicity was observed in the other treatment group. No sign of irritation (indicated by a significant erythema) or any other local effect was observed at the treatment site (ears) in any treatment group.

Proliferation Assay:
Visually larger lymph nodes compared to the vehicle control (AOO) were observed in the positive control group only. Appearance of the lymph nodes was normal in the negative control group (AOO) and in the test item treated groups.
Significant lymphoproliferative response (SI>=3) compared to the control (AOO) was noted for Racem Tisercin base at 2.5% (w/v) test concentration with an SI value of 5.0.
No significant lymphoproliferative response (SI>=3) compared to the control (AOO) was observed at the other test concentrations (1%, 0.5% or 0.25%, w/v). The stimulation index values were 1.2, 1.1 and 0.7 at test item concentrations of 1%, 0.5% and 0.25% (w/v), respectively. No dose-related response was considered up to 1% (w/v) concentration of the test item.

Reliability of the Test:
The positive control group animals were treated with 25% (w/v) HCA solution (dissolved in AOO) concurrent to the test treated groups. No mortality, cutaneous reactions or signs of toxicity were observed in the positve control group.
Significant lymphoproliferative response (SI>=3) was noted for HCA (SI=6.6). The results of the positive control item demonstrated appropriate performance of the test in accordance with the relevant guidelines and confirmed validity of the assay.

Applicant's summary and conclusion

Interpretation of results:

other: no skin sensitization potencial

Conclusions:

Under the conditions of the present assay, Racem Tisercin base tested as formualtions in a suitable vehicle (AOO) at 1% (w/v) as the maximum non-toxic, non-irritant concentration and also at concentrations of 0,5 % and 0,25 % (w/v) was shown to have no skin sensitization potental in the Local Lymph Node Assay.

According to the effective regulations concerning to the classification, labelling and packaging odf substances and mixtures no specific label elements regarding to skin sensitization potential of the test item should be used for Racem Tisercin base.