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Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

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:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report date:
1987

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
according to: Gad, S.C. et al. Toxicol. Appl. Pharmacol., 84, 93-114, 1986
GLP compliance:
yes
Type of study:
mouse ear swelling test
Justification for non-LLNA method:
The Mouse Ear Swelling Test (1987) met the previous requirements before the entry into force of REACH. This test is suitable and reliable to cover this endpoint. For this reason and for animal welfare reasons, no further in vivo study (LLNA test) needs to be performed.

Test material

Constituent 1
Chemical structure
Reference substance name:
2-ethylhexylamine
EC Number:
203-233-8
EC Name:
2-ethylhexylamine
Cas Number:
104-75-6
Molecular formula:
C8H19N
IUPAC Name:
2-ethylhexylamine

In vivo test system

Test animals

Species:
mouse
Strain:
CF-1
Sex:
not specified
Details on test animals and environmental conditions:
- Age:6-8 weeks
- Weight at study initiation: 20-24 g

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, open
Vehicle:
other: 70% ethanol
Concentration / amount:
5%
Day(s)/duration:
Day 0, 1, 2, and 3, respectively
Adequacy of induction:
other: a non-corrosive concentration
Route:
intradermal
Concentration / amount:
application of Freund's Complete Adjuvans (FCA)
Day(s)/duration:
Day 0
Challengeopen allclose all
No.:
#1
Route:
epicutaneous, open
Vehicle:
other: 70% ethanol
Concentration / amount:
25%
Day(s)/duration:
Day 10
No.:
#2
Route:
epicutaneous, open
Vehicle:
other: 70% ethanol
Concentration / amount:
25%
Day(s)/duration:
Day 17
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS:
Doses were chosen in a range-finding study.
-Positive control: induction: 0.5% w/v mixture DCNB in 70% ethanol
challenge: 1.0% w/v mixture DCNB in 70% ethanol
-Test substance: induction: 5.0% w/v mixture 2-ethylhexylamine in 70% ethanol (non-corrosive)
challenge: 25% w/v mixture 2-ethylhexylamine in 70% ethanol non-corrosive)
-Adjuvant: 50% v/v Freund's Complete Adjuvant (FCA)in water

EXPOSURE:
On day 0 of induction, 20 µL FCA was administered by i.d. injection on and left and right sides of the abdomen of all animals. On days 0, 1, 2, and 3 of induction, the test (100 µL) or control substance was administered topically to the abdomen and an appropriate vehicle was applied to the irritation control animals. The test (10 µL) and positive control animals were challenged on day 10 on the left ear (dorsal and ventral surfaces) and re-challenged on day 17 on the right ear. An appropriate vehicle was applied to the opposing ear. Five irritation control animals (previously treated with vehicle and FCA) were subjected to the same challenge as the test animals on day 10 and another set of five on Day 17.

EXAMINATIONS:
- Mortality and clinical signs: twice daily
- Presence of irritation (erythema,edema): day 9 and 16
- Evaluation of dermal response (ear thickness under light anesthesia with ether): 24 and 48 hr after challenge or re-challenge
- The sensitization response was considered positive if the test ear was 20% thicker than the control ear.

STATISTICAL METHOD:
- Not applicable

Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene (DCNB)

Results and discussion

Positive control results:
80 and 100% of the animals showed a positive response (at least 20%  increase in ear thickness) after 24 and 48 h, respectively.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
1%
No. with + reactions:
8
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
1%
No. with + reactions:
10
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
rechallenge
Group:
test chemical
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10

Any other information on results incl. tables

TEST GROUP:

Few animals challenged with the TS showed weakly positive reactions at challenge or re-challenge in the test group, but not in the 

irritation control group: The incremental increases in ear thickness ranged from 0 - 11 %.    

 

The test provided no evidence of a sensitising potential of 2-ethylhexylamine. The functionality of the test system was demonstrated by using an appropriate positive control substance which was clearly positive.

 

Despite the limited number of animals used and the test restrictions, the result can be weighed in relation to the positive control, the dose used to provoke an effect and the negative results obtained with four structure-related primary amines (cyclohexylamine, hexylamine, isopropylamine, n-octylamine).

 

Hence, 2-ethylhexylamine is not considered to be a potent sensitiser and unlikely to elicit a skin allergic reaction.

 

The mouse-ear swelling test (MEST) serves as a screen to detect potent sensitisers (moderate and strong ones). Weak sensitisers are unlikely to be detected in this test. According to EPA guideline OPPTS 870.2600, a negative result in the MEST does not indicate that the substance is a non-sensitizer, and should be confirmed in an accepted test using guinea pigs and or LLNA if appropriate.

 

 

 

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met