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Diss Factsheets

Administrative data

Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well-documented study conducted according to CPA Good Laboratory Practice Regulations

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Haskell Laboratory Protocol
Principles of method if other than guideline:
1. 10 animals were used as test group animals, 10 as vehicle control and 10 as positive control
2. The induction phase was initiated two days after the primary irritation phase using the same animals.
3. No data about exposure period (test material in contact with skin) during challenge exposure.
4. Challenge exposure was conducted on 43-d day after the first application in induction phase
GLP compliance:
yes
Remarks:
CPA Good Laboratory Practice Regulations
Type of study:
other: Haskell Laboratory Protocol

Test material

Constituent 1
Chemical structure
Reference substance name:
Octamethylenediamine
EC Number:
206-764-3
EC Name:
Octamethylenediamine
Cas Number:
373-44-4
Molecular formula:
C8H20N2
IUPAC Name:
octane-1,8-diamine
Details on test material:
- Name of test material (as cited in study report): 1,8-Octanediamine
- Medical Research No.: 7952-001
- Haskell No.: 16,531
- Other Code: N.B. 43454-35
- Physical state: white solid
- Stability under test conditions: The test material was assumed to be stable under the conditions of administration.
- Analytical purity: greater than 99 %
- Impurities: Dioctamethylenetriamine

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Stone Ridge, New York
- Age at study initiation: young adult
- Weight at study initiation: 443 - 634 g
- Housing: singly in suspended, stainless steel, wire-mesh cages
- Diet (ad libitum): Purina Certified Guinea Pig Chow(R)
- Water (ad libitum): water
- Acclimation period: approximately one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 2
- Humidity (%): 50 +/- 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: physiol. saline at induction phase and distilled water at challenge phase
Concentration / amount:
Irritation phase: 4 % and 0.4 % (w/v) suspensions of test material in distilled water;
Induction phase: 1% (w/v) suspension in physiological saline;
Challenge phase: 4 % and 0.4 % (w/v) suspensions of test material in distilled water.
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
other: physiol. saline at induction phase and distilled water at challenge phase
Concentration / amount:
Irritation phase: 4 % and 0.4 % (w/v) suspensions of test material in distilled water;
Induction phase: 1% (w/v) suspension in physiological saline;
Challenge phase: 4 % and 0.4 % (w/v) suspensions of test material in distilled water.
No. of animals per dose:
10 animals (two doses were tested on one animal each on one site)
Details on study design:
RANGE FINDING TESTS:
A preliminary range finding test was conducted to estimate the primary irritation potential of the test material. The results of the range finding study were used to select the exposure concentrations for the main study. This test was conducted with 3 male guinea pigs ranging in weight from 426 to 461 grams. Aliquots (approximately 0.05 mL) of 40 %, 20 %, 10 % and 4 % ( w/v) suspensions of the test material in distilled water were applied and lightly rubbed onto separate test sites on the shaved, intact skin of each animal's back. Irritation responses were scored approximately 24 and 48 hours after treatment .

MAIN STUDY
A. PRIMARY IRRITATION PHASE
The primary irritation phase (dermal application) was conducted in 10 unexposed guinea pigs, weighing from 443 to 634 grams, by applying and lightly rubbing in 1 drop ( approximately 0 .05 mL) of 4 % and 0.4 % (w/v) suspensions of the test material in distilled water onto separate sites of shaved, intact shoulder skin of each animal.
At the same time, 10 unexposed vehicle control guinea pigs, weighing from 430 to 574 grams, were also treated by applying and lightly rubbing in 1 drop (approximately 0.05 mL) of distilled water onto separate sites of shaved, intact skin of each animal. In addition, 10 unexposed positive control guinea pigs, weighing from 411 to 541 grams, were treated by applying and lightly rubbing in 1 drop of 30 % and 3 % (w/v) suspensions of p-phenylenediamine in acetone :dimethyl phthalate (1:9 ratio) onto separate sites of shaved, intact shoulder skin of each animal. Dermal responses were scored approximately 24 and 48 hours after application of the test material.

B. INDUCTION EXPOSURE
Two days after the primary dermal application, the induction phase of the study was initiated using the same 10 test guinea pigs in which primary irritation had been evaluated .
- No. of exposures: 4
- Exposure period: 4 weeks
- Test groups: 10 animals
- Control group: 10 animals
- Site: back
- Frequency of applications: 1xeach week
- Duration: single injection
- Concentrations: 0.1 mL of a 1% (w/v) suspension of test material in physiological saline

C. CHALLENGE EXPOSURE
Two weeks following the last intradermal injection, the test guinea pigs were challenged for sensitization by applying and lightly rubbing in 1 drop of 4 % and 0.4 % (w/v) suspensions of the test material in distilled water onto separate sites of shaved, intact shoulder skin. At the same time, the 10 vehicle control guinea pigs received identical topical applications of 1,8-octanediamine. The positive control animals were challenged for sensitization by applying and lightly rubbing in 1 drop of 30 % and 3 % (w/v) suspensions of p-phenylenediamine in acetone:dimethylphthalate (1:9) onto separate sites of shaved, intact shoulder skin.Responses were scored approximately 24 and 48 hours after application of the test material. Ouring the study, body weights were recorded weekly.

- No. of exposures: 1
- Day(s) of challenge: 43 (without account of irritation phase)
- Exposure period: no data
- Test groups: 10 animals
- Control group: 10 animals
- Site: shoulder
- Concentrations: 4 % and 0.4 % (w/v) suspensions of test material in distilled water
- Evaluation (hr after challenge): 24 and 48

OTHER:
Challenge controls:
Vehicle control animals served as challenge controls
Positive control substance(s):
yes
Remarks:
p-phenylenediamine

Results and discussion

Positive control results:
All positive control guinea pigs showed significant sensitisation score increases during the challenge phase (10 of 10 animals). A significant score increase was defined as a 2-or-more step increase (e.g. , from 0 to 2, from 1 to 3, etc.).

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.4%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no erythema or edema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.4%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no erythema or edema.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.4%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no erythema or edema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.4%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no erythema or edema.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
4%
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
mild erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 4%. No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: mild erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
4%
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
mild erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 4%. No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: mild erythema.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.4 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no erythema or edema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.4 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no erythema or edema.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.4 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no erythema or edema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.4 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no erythema or edema.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
4 %
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
6 with moderate erythema, 2 with mild erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 4 %. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: 6 with moderate erythema, 2 with mild erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
4 %
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
1 with erythema and edema, 6 with moderate erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 4 %. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: 1 with erythema and edema, 6 with moderate erythema.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
3 %
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
2 with strong erythema, 6 with moderate erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 3 %. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: 2 with strong erythema, 6 with moderate erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
3 %
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
1 with strong erythema, 3 with moderate erythema, 3 with mild erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 3 %. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: 1 with strong erythema, 3 with moderate erythema, 3 with mild erythema.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
30 %
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
1 with erythema and edema, 5 with strong erythema, 4 with moderate erythema
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 30 %. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: 1 with erythema and edema, 5 with strong erythema, 4 with moderate erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
30 %
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
2 with strong erythema, 5 with moderate erythema, 3 with mild erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 30 %. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: 2 with strong erythema, 5 with moderate erythema, 3 with mild erythema.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Skin Sensitiser, Category 1, H317 Criteria used for interpretation of results: other: EU GHS
Conclusions:
The study report is well-documented and the experiment conducted according to CPA Good Laboratory Practice Regulations according to the procedure of Haskell Laboratory to identify compounds as skin sensitsers. The test substance was found to be a skin sensitiser in guinea pigs under these experimental conditions and has to be classified according to EU GHS (CLP VO 1272/2008 EG)as Skin Sensitiser, Category 1, H317.
Executive summary:

The test substance Octamethylenediamine was investigated upon its skin sensitising potential on young Dunkan-Hartley albino guinea pigs according to the procedure of the Haskell Laboratory, Newark, Delaware (Henry, 1987). The study was conducted according to CPA Good Laboratory Practice Regulations on shaved, intact skin of 10 male animals. p-Phenylenediamine was used as positive control. The test substance concentrations in the challenge phase were 0.4 % and 4 % (w/v) as suspensions in distilled water. The primary irritation phase was conducted by applying and lightly rubbing of the test suspensions and scoring was done 24 and 48 h after this dermal application. Two days later the induction phase was initiated with the same animals and consisted of a series of 4 sacral intradermal injections (1 time per week) of 0.1 mL of a 1.0 % (w/v) test suspension. After about 24 h skin responses were evaluated. The challenge started two weeks later by applying and lightly rubbing 4 % and 0.4 % of the test material suspension onto separate sites of shaved, intact shoulder skin. In 6 of 10 animals moderate erythema was recorded and 2 of 10 guinea pigs had mild erythema at the 4 % concentration site by 24 hours. After 48 hours, 1 guinea pig exhibited erythema and edema and 6 guinea pigs had moderate erythema. Positive control substance produced a significant response in 10 of 10 animals which is evident for valid test system. As overall result, at challenge, the test substance produced a significant score increase in 7 animals over the reponse observed during the induction phase; therefore, the test item was classified as skin sensitiser according to EU GHS (Category 1, H317).