Registration Dossier

Toxicological information

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:
1989-02-14 to 1989-03-10
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions: No positive control (not required by 1981 version of Test Guideline)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A skin sensitization test according to OECD 406 has already excisted since 1989 and is sufficient for evaluation of the skin sensitisation potential of the test substance.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Dodecanedioic acid of Hüls AG. Purity ca. 99 %;
main impurities: Homologous dicarboxylic acids

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Fa Winkelmann, 4799 Borchem, Germany
- Age at study initiation:
- Weight at study initiation:324 g (mean test); 322 g (mean control)
- Housing: 1-5 animals per cage
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5-8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1°C
- Humidity (%): 60 +/- 5%
- Air changes (per hr):15 per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14.2.1989 To: 10.03.1989

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
petrolatum
Concentration / amount:
1st application: Induction 0.5 % intracutaneous
2nd application: Induction 50 % occlusive epicutaneous
3rd application: Challenge 25 % occlusive epicutaneous
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
1st application: Induction 0.5 % intracutaneous
2nd application: Induction 50 % occlusive epicutaneous
3rd application: Challenge 25 % occlusive epicutaneous
No. of animals per dose:
20
Details on study design:
ADMINISTRATION/EXPOSURE 
- Induction schedule:   
day 0 injection,   
day 6 induction of slight inflammation (10 % sodium lauryl sulfate in  petrolatum)   
days 7-9 patch treatment (48 hours)
- Injection details: 0.1 ml each at 6 positions on shoulders:  
2 x Freund's Complete Adjuvant / deionized water (50:50)   
2 x test substance 0.5 % in corn oil   
2 x test substance 0.5 % in Freund's Complete Adjuvant / corn oil  (50:50)   
simultaneous and symmetrical application of each solution   
controls: corn oil instead of test substance
- Challenge schedule: 2 weeks after end of induction, patch treatment for  24 hours
- Concentrations used for challenge:   
25 % in vehicle with filter paper on left side; petrolatum on opposite  side   readings 24 and 48 hours after removal of patch
- Rechallenge: no
- Positive control: no
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1st application: Induction 0.5 % intracutaneous; 2nd application: Induction 50 % occlusive epicutaneous; 3rd application: Challenge 25 % occlusive epicutaneous
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1st application: Induction 0.5 % intracutaneous; 2nd application: Induction 50 % occlusive epicutaneous; 3rd application: Challenge 25 % occlusive epicutaneous. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1st application: Induction 0.5 % intracutaneous; 2nd application: Induction 50 % occlusive epicutaneous; 3rd application: Challenge 25 % occlusive epicutaneous
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1st application: Induction 0.5 % intracutaneous; 2nd application: Induction 50 % occlusive epicutaneous; 3rd application: Challenge 25 % occlusive epicutaneous. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

RESULTS OF PILOT STUDY: no skin irritation at 50 %
RESULTS OF TEST
- Sensitization reaction: 
  0/20 animals positive at 24 and 48 hours = no sensitization
  no animals positive in control group
- Clinical signs: 
  1st induction, FCA application sites: severe erythema and edema,  necroses
  1st induction, test substance + vehicle application sites: slight  erythema and edema
  1st induction, vehicle application sites: slight erythema
  2nd induction, test and control group: severe erythema of the whole  shoulder region; inflammation of the FCA injection sites, 

in part with  pus discharge and/or bleeding from scratching; eschar formation within 24  hours
- Other: Mean body weight gain 121 g in test group, 122 g in control  group = expected range

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions of the study dodecanedioic acid is not a skin sensitizer.
Executive summary:

In the Guinea pig maximization test performed within this study, after intradermal and epicutaneous inductions with the test substance dodecanedioic acid none of the 20 guinea pigs showed positive response 24 hours (48 hours) after epicutaneous challenge. Under the conditions of the study dodecanedioic acid is not a skin sensitizer.