Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996-04-29 to 1996-06-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to the good clinical practices regulation 21CFR part 50, 56.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Test guideline
Qualifier:
according to
Guideline:
other: Good clinical practices guidelines 21CFR part 50, 56
Deviations:
yes
Remarks:
Clinical history of the subjects is not given
Principles of method if other than guideline:
According to the good clinical practices guidelines in 1973. Informed consent was given to subjects. Institutional review board reviewed the general protocol and materials tested in this study.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Maleic acid
- Molecular formula (if other than submission substance): C4-H4-O4
- Molecular weight (if other than submission substance): 116.072
- Substance type: Pure active substance
- Physical state: Clear liquid
- Analytical purity: See below
- Impurities (identity and concentrations): See below
- Composition of test material, percentage of components: See below
- Isomers composition: Not available
- Purity test date: See below
- Lot/batch No.: Not available
- Expiration date of the lot/batch: See below
- Stability under test conditions: Not available
- Storage condition of test material: Room temperature
- Other: None

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
- Number of subjects exposed: 105 subjects commenced and 101 completed the study
- Sex: Males and Females
- Age: Females (18 - 65+) and Males (25 - 65+)
- Race: Predominately Caucasian
- Demographic information: Loch Centre, Tranent, East Lothian
- Other: None
Clinical history:
- History of allergy or casuistics for study subject or populations: Not available
- Symptoms, onset and progress of the disease: Not available
- Exposure history: Not available
- Aggravating factors both in home and workplace: Not available
- Family history: Not available
- Medical history (for respiratory hypersensitivity): Not available
- Any other allergic or airway disorders: Not available
- Smoking history: Not available
- Other: None
Controls:
None
Route of administration:
dermal
Details on study design:
TYPE OF TEST(S) USED: patch test (epicutaneous test)


ADMINISTRATION
- Type of application: occlusive
- Description of patch: Not available
- Vehicle / solvent: Distilled water
- Concentrations: 0.3% v/v maleic acid in diatilled water
- Volume applied: 0.5ml
- Testing/scoring schedule: 48 hours after each of the 9 induction patches and at 48 & 96 hours after the challenge patch application.
- Removal of test substance: 24 hours after each of the 9 induction patch and 24 hours after the challenge patch.
- Other:None


EXAMINATIONS
- Grading/Scoring system: 0=no visible reaction, 1= mild erythema, 1E = mild erythema with papules and/or edema, 2=Definite pink to red erythema, 2E= moderate erythema with edema and/or papules, 3= strong erythema, 3E= strong erythema with marked edema, and/or papules, 4= severe reaction with erythema, edema, papules and vesicles, 5= bullous reaction, 6= reaction spread beyond webril pad area.
- Statistical analysis: Not applicable
- Other: None

Results and discussion

Results of examinations:
SYMPTOMS
- Frequency, level, duration of symptoms observed: Treatment sites were observed 48 hours after patching on a Monday, Wednesday, Friday regimen for 3 weeks for 9 induction exposures. A total of 21/101 subjects completing the study had mild erythema (grade 1). After two weeks, treatment sites were challenged and observed at 48 & 96 hours after patch. A total of 1/101 subjects completing the study had mild erythema (grade 1)


NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 0/101
- Number of subjects with negative reactions: 101/101
- Number of subjects with equivocal reactions: 0/101
- Number of subjects with irritating reactions: 1/101 exhibited mild skin irritation (grade 1) during challenge


OTHER RESULTS: None

Applicant's summary and conclusion

Conclusions:
Maleic Acid did not produce skin sensitization in humans.
Executive summary:

The skin sensitization potential of Maleic Acid was assessed in a human repeat insult patch study. A total of 105 subjects participated in the study. Subjects were exposed to 9 induction patches containing 0.5 ml of 0.3 % v/v Maleic Acid in distilled water under occlusion on a Monday, Wednesday and Friday schedule for a period of 3 weeks. Patches were removed 24 hours after each application and patch sites were graded at 48 hours after patch application prior to the next patch application. After a two week rest period subjects were challenged with 0.5 ml of 0.3 % v/v Maleic Acid in distilled water (24 hour patch exposure). Challenge patch sites were graded at 48 and 96 hours after patch application.

In this study, 101/105 subjects completed the study. A total of four (4) subjects discontinued participation because of reasons listed below:

 Subject number  Reasons
 T762

Unable to attend due to illness not skin related

 T225

 Unable to attend due to employment circumstances

 T850, T1116  Unable to meet attendance requiremnts

No positive responses indicative of skin sensitization was observed. Maleic Acid did not produce skin sensitization in humans.