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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Principles of method if other than guideline:
Intradermal skin sensitising study. Guinea pigs injected into dermis with test substance or positive/negative control substance every 48 hours for 10 applications. Challenged at 2 weeks after final injection with injectionof test material at a virgin site. Scores for erythema and edema at 24 and 48 hours post challenge to assess sensitising response.
GLP compliance:
not specified
Type of study:
intracutaneous test
Justification for non-LLNA method:
Existing study conducted in 1982.

Test material

Constituent 1
Chemical structure
Reference substance name:
2-amino-2-ethylpropanediol
EC Number:
204-101-2
EC Name:
2-amino-2-ethylpropanediol
Cas Number:
115-70-8
Molecular formula:
C5H13NO2
IUPAC Name:
2-amino-2-ethylpropanediol
Constituent 2
Reference substance name:
2-Amino-2-ethyl-1,3-propanediol
IUPAC Name:
2-Amino-2-ethyl-1,3-propanediol
Specific details on test material used for the study:
- AEPD Lot No.: NPP-41344
- 2-Amino-2-ethyl-1,3-propanediol: 85.34 wt%
- Methanol: 1.48 wt%
- Monomethyl amino butanol: 10.92 wt%
- Water: 1.89 wt%
- pH at 100%: 11.78
- pH 1% solution: 11.18

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
water
Concentration / amount:
first 5 induction injections with a 1% aqueous solutionof AEPD, remaining 5 injections with a 0.05% aqueous solution of AEPD.
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
intradermal
Vehicle:
water
Concentration / amount:
Challenge injection with 0.05 and 0.01% injections (at different virgin sites)
Adequacy of challenge:
not specified
No. of animals per dose:
10
Details on study design:
The intradermal sensitisation study with AEPD (P-1050) was conducted in male guinea pigs according to Landsteiner and Jacobs procedure (Landsteiner, K., and J. Jacobs. "Studies on Sensitization of Animals with Simple Chemical Compounds." J. Exp. Med. -61: 643-656, 1935). Forty male guinea pigs weighing 250 to 300 g were divided into four groups of 10 each. The animals' backs and flanks were shaved free of hair. Group XIV was intradermally injected with 0.05 ml of 1% solution of P-1050 in saline. Group V (positive control) was similarly injected with 0.05 ml of 0.3% dinitrochlorobenzene (DNCB) solution (solubilized in minimum volume of alcohol and made to volume with saline). Groups XVI and XVII (negative controls) were injected with 0.05 ml of saline. After 24 hours and 48 hours the injected sites scored for erythema edema, according to Draize. At 48 hours, the intradermal injection procedure was repeated for each group with 0.1 ml of each solution two or three times a week until a total of 10 injections have been made. After the last injection, the animals were allowed to rest for two weeks. On the first day of the third week (or the 35th day after the first injection), the animals in each group were challenged intradennally with 0.1 m l of solution at a virgin site. Group XIV and Group XVII animals were challenged with P-1050 solution (0.05 and 0.01%). Groups V and XVI animals were challenged with 0.03% DNCB solution. At the end of 24 h, the injected sites were depilated. Three hours after the removal of the hair , the injected sites were scored for inflammatory skin reactions (erythema and edema). The sites were re-scored at 48 hours (24 hours after the first scoring).
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene (DNCB) 0.3%

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction with saline; challenge with 0.01% solution of test substance
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction with 0.9% saline; challenge with 0.05% solution of test substance
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: necrosis
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction with 0.9% saline; challenge with 0.03% solution of DNCB
No. with + reactions:
2
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction with 0.9% saline; challenge with 0.03% solution of DNCB
No. with + reactions:
2
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Induction with test substance; challenge with 0.01% solution of test substance
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Induction with test substance; challenge with 0.01% solution of test substance
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Induction with test substance; challenge with 0.05% solution of test substance
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: necrosis
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Induction with test substance; challenge with 0.05% solution of test substance
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: necrosis
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Induction with 0.3% DNCB; challenge with 0.3% DNCB
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Induction with 0.3% DNCB: challenge with 0.3% DNCB
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

During the induction phase the guinea pigs in the test group showed some skin reactions with AEPD (P-1050). The first five injections were made with 1% solution and the last five injections were made with 0.05% solution. None of the negative control animals showed any skin reactions. The positive control animals showed mild to necrotic skin reactions during the entire induction period. At challenge with 0.05% of AEPD, all the animals in the treatment group and the negative control group showed skin reactions, but none of the animals in either group showed any skin reactions with 0.01% solution. The DNCB (0.03%) eluted positive skin reactions in the positive control group and in some animals in the negative control group.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Conclusions:
Undiluted AEPD was found to be a non-sensitizer when tested in the guinea pig (intradermal application).
Executive summary:

An intradermal sensitization test was conducted by injecting an AEPD solution (P-1050) intradermally in male guinea pigs according to Landsteiner and Jacobs procedure (Landsteiner, K., and J. Jacobs. "Studies on Sensitization of Animals with Simple Chemical Compounds." J. Exp. Med. -61: 643-656, 1935). Forty male guinea pigs weighing 250 to 300 g were divided into four groups of 10 each. The animals' backs and flanks were shaved free of hair. Group XIV was intradermally injected with 0.05 ml of 1% solution of P-1050 in saline. Group V (positive control) was similarly injected with 0.05 ml of 0.3% dinitrochlorobenzene (DNCB) solution (solubilized in minimum volume of alcohol and made to volume with saline). Groups XVI and XVII (negative controls) were injected with 0.05 ml of saline. After 24 hours and 48 hours the injected sites scored for erythema edema, according to Draize. At 48 hours, the intradermal injection procedure was repeated for each group with 0.1 ml of each solution two or three times a week until a total of 10 injections have been made. After the last injectio n , the animals were allowed to rest for two weeks. On the first day of the third week (or the 35th day after the first injection), the animals in each group were challenged intradennally with 0.1 m l of solution at a virgin site. Group XIV and Group XVII animals were challenged with P-1050 solution (0.05 and 0.01%). Groups V and XVI animals were challenged with 0.03% DNCB solution. At the end of 24 h, the injected sites were depilated. Three hours after the removal of the hair , the injected sites were scored for inflammatory skin reactions (erythema and edema). The sites were re-scored at 48 hours (24 hours after the first scoring).

During the induction phase the guinea pigs i n Group XIV showed some skin reactions with P-1050. The first five injections were made w i t h 1% solution and the last five injections were made with 0.05% solution. None of the animals in Groups XVI and XVII (negative controls) showed any skin reactions. The animals in Group V (positive control ) showed mild to necrotic skin reactions during the entire induction period. At challenge with 0.05% of P-1050, all the animals i n Group IV (treatment) and Group XVII (negative control) showed skin reactions, but none of the animals in either group showed any skin reactions with 0.01% solution. The DNCB (0.03%) eluted positive skin reactions in Group V (positive control group) and in some animals in Group XVI (negative control group).