Registration Dossier

Administrative data

Description of key information

A guinea pig maximisation study is available for the submission substance.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions- incomplete characterization of the test substance (no data on test substance purity available)- no GLP
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted in 1986. The OECD test guideline for the local lymph node assay was first issued in 2002.
Specific details on test material used for the study:
Report title states test material is N,N,N'-Trimethylaminoethylethanolamine
Appearance: Clear light yellow liquid
Storage conditions: Room temperature
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
Further characterization: Pirbright White, HOE DHPK (SPF - LAC ) Boe
Source: Lippische Versuchstierzucht, Hagemann GmbH & Co. KG, 0-4923 Extertal 1, FRG
Weight at study initiation: 244 - 311 g
Housing: 5 per Makrolon cage (type IV)
Diet: Kliba 341.4 mm (Kaninchen-Meerschweinchen-Haltungsdiaet), Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland; available ad libitum
Water: Tap water; supplemented with ca. 2 g of ascorbic acid per 10 L water twice a week
Acclimation period: at least 7 days
Other: Feed and water were analysed frequently for contaminantion. Levels detected were not expected to influence the outcome of this study.
ENVIRONMENTAL CONDITIONS-
Temperature (°C): 20 24
Humidity (%): 30 - 70
Air changes (per hr): 12
Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Induction: 2 % (intradermal), 40 % (topical)
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
10%
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
10%
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Control: 20 (2 control groups containing 10 animals each)
Test group: 20
Details on study design:
JUSTIFICATION FOR CHOICE OF CONCENTRATIONS
Based on results of range finding test (see below)
RANGE FINDING TESTS (RFT):
Epicutaneous application
Frequency of treatment: 2 times for 24 hours within a period of 96 hours
No. of animals per concentration: 4
Site: flanks
Type of coverage: occlusive
Concentrations: no data
Application volume: 0.15 g of substance formulation applied on 2 cm x 2 cm filter paper
Vehicle: water
Evaluation (hr after challenge): 24 and 48 hours after removal of patch (Draize scoring)

MAIN STUDY
A. INDUCTION EXPOSURE
A1. Intradermal injection
Site of injection: shoulder
Formulations: 1). mixture of Freund's adjuvant and water (1:1), 2). test compound vehicle (test group) or vehicle only (control group), 3). mixture of Freund's adjuvant and water (1:1) with test compound (test group) or mixture of Freund's adjuvant and water (1:1) without test compound (control)
Concentration of test substance in formulation: 2 %
Number of injections per formulation: 2
Volume per injection: 0.1 mL/ formulation
Number of injections per animal: 6
Evaluation (hr after injection): 24

A2. Epicutaneous induction exposure
Time schedule: one week after intradermal injections
Site: same as intradermal injection (shoulder)
Method of test substance application: on 2 cm x 4 cm test patches
Type of coverage: occlusive
Concentrations: 40 % (test group); control animals were not treated since the distilled water used as formulating agent was not expected to influence the result of the study.
Vehicle: water
Amount applied: ca. 0.3 g of test substance formulation
Duration: 48 hours
Evaluation (hr after challenge): 48 hours

B. CHALLENGE EXPOSURE
Number of challenges: 2
Time schedule: first challenge was performed 14 days after termination of induction exposure and the second challenge followed 1 week later
1st challenge: treatment of the test group and of control group 1 (10 animals) with the test substance formulation (control group 2 (10 animals) remained untreated)
2nd challenge: treatment of the test group and of control groups 1 and 2 with the test substance formulation
Site: right flank (test substance), in the rechallenge, the test substance was applied on the left flank
Area of application: 2 cm x 2 cm
Concentrations: 10 %
Vehicle: water
Amount applied: ca. 0.15 g of test substance formulation
Duration: 24 hours
Evaluation (hr after challenge): 24, 48 and 72 hours after start of challenge
Positive control substance(s):
no
Remarks:
Not concurrent; A reliability check of the test with a positive control substance is performed at BASF laboratories regularly (at least once in 6 months)
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10 %
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
other: 3rd Reading
Hours after challenge:
72
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10 %
No. with + reactions:
3
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
other: 3 rd Reading
Hours after challenge:
72
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
other: negative control (group 1 + 2)
Dose level:
10 %
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
other: negative control (group 1 + 2)
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
72
Group:
other: negative control (group 1 + 2)
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
10 %
No. with + reactions:
6
Total no. in group:
20
Remarks on result:
other:
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
72
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation

The findings obtained 48 hours after application are taken into account for the determination of the sensitization rate. At this time point, none of the 20 animals tested (0%) with the test substance at the concentration of 10 % elicited positive skin reactions. This was true after the challenge and the rechallenge treatments. This is below the threshold of 30% positive animals required for the categorisation of a compound as sensitising according to CLP

First challenge (two weeks following percutaneous induction)

 

Number of positive reactions

 

24 hours

48 hours

72 hours

 

E

O

E

O

E

O

Control group 1

1/10

0/10

0/10

0/10

0/10

0/10

Control group 2

N/A

N/A

N/A

N/A

N/A

N/A

Test group

3/20

0/20

0/20

0/20

0/20

0/20

E            Erythema
O           Oedema

Second challenge (one week following first challenge)

 

Number of positive reactions

 

24 hours

48 hours

72 hours

 

E

O

E

O

E

O

Control group 1

0/10

0/10

0/10

0/10

0/10

0/10

Control group 2

1/10

0/10

0/10

0/10

0/10

0/10

Test group

6/20

0/20

0/20

0/20

0/20

0/20

E            Erythema
O           Oedema

Interpretation of results:
GHS criteria not met
Conclusions:
No animals showed a positive reaction 48 or 72 hours following the first or second challenge after an intradermal indution with a 2% formulation. The test material is not classified for skin sensitisation.
Executive summary:

A guinea pig maximisation test (GPMT) was conducted with N,N,N'-Trimethylaminoethylethanolamine according to OECD 406. Twenty female guinea pigs assigned to the test group were induced by intradermal injections with a 2% formulation. In addition, these guinea pigs were topically induced 1 week later with a 40% formulation. The test group were challenged twice (14 days after percutaneous challenge and again one week later). Two groups of 10 negative control female guinea pigs, previously not induced with the test material, were challenged topically for 24 hours with a 40% formulation. Control group 1 was challenged twice (14 days after percutaneous challenge and again one week later), and control group two was challenged once only (21 days after percutaneous challenge). Skin examinations were performed at 24, 48 and 72 hours after the completion of the challenge exposures. The 48 and 72 hour observations indicated as the time points in the OECD guideline showed no positive sensitisation reactions in the test or negative control groups.

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

A guinea pig maximisation test (GPMT) was conducted with N,N,N'-Trimethylaminoethylethanolamine according to OECD 406. Twenty female guinea pigs assigned to the test group were induced by intradermal injections with a 2% formulation. In addition, these guinea pigs were topically induced 1 week later with a 40% formulation. The test group were challenged twice (14 days after percutaneous challenge and again one week later). Two groups of 10 negative control female guinea pigs, previously not induced with the test material, were challenged topically for 24 hours with a 40% formulation. Control group 1 was challenged twice (14 days after percutaneous challenge and again one week later), and control group two was challenged once only (21 days after percutaneous challenge). Skin examinations were performed at 24, 48 and 72 hours after the completion of the challenge exposures. The 48 and 72 hour observations indicated as the time points in the OECD guideline showed no positive sensitisation reactions in the test or negative control groups.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification for skin sensitisation under CLP is not required for N,N,N'-Trimethylaminoethylethanolamin, based on the results of a guinea pig maximisation test.