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Toxicological information

Sensitisation data (human)

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Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1988-02-15 to 1988-04-15
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted according to Good Clinical Practices guideline 21 CFR parts 50 and 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:
1988
Report Date:
1988

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Test guideline
Qualifier:
according to
Guideline:
other: Good clinical practices guideline 21 CFR parts 50 and 56
Deviations:
yes
Remarks:
- Allergy history of subjects is not given
Principles of method if other than guideline:
According to proposed good clinical practice (GCP) guidelines. Informed consent were given to subjects. Institutional review board reviewed the general protocol and substance 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): Synprolam 35 MX 1QC; C13-15 dimethyl hydroxyethylammonium chloride
- Molecular formula (if other than submission substance): Not available
- Molecular weight (if other than submission substance): Not available
- Substance type: Pure active substance
- Physical state: Liquid
- Analytical purity: See below
- Impurities (identity and concentrations): None
- Composition of test material, percentage of components: See below
- Isomers composition: Not available
- Purity test date: See below
- Lot/batch No.: See below
- Expiration date of the lot/batch: See below
- Stability under test conditions: Not available
- Storage condition of test material: Ambient
- Other: None

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
- Number of subjects exposed: 87 subjects (21-preliminary study, 66-main study) were enrolled and 80 completed the study
- Sex: 82 Females and 5 Male
- Age: Females - (18 to 65+), Males - (18 to 64)
- Race: Predominantly caucasian
- Demographic information: Corn exchange, Haddington, East Lothian; Corn exchange, Dunbar, 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: Human Repeat Insult Patch Test (epicutaneous test)

- Type of application: Occlusive
- Description of patch: 2 cm square webril pad located down the centre line of a piece of Blenderm tape which contained three other such pads for simultaneous application of other substances
- Vehicle / solvent: Distilled water
- Concentrations: 0.2% w/v solution in distilled water ( reduced from 0.5% w/v after five applications to the preliminary panel)
- Volume applied: 0.5 ml
- Testing/scoring schedule: 48 hours after each of the 9 induction patches and at 48 and 96 hours after the challenge patch
- Removal of test substance: 24 hour after each of the 9 induction patch and 24 hours after the challenge patch

Results and discussion

Results of examinations:
There was no evidence of skin sensitization observed on the 80 subjects (21 of preliminary study plus 59 of main study) who completed the test.

Any other information on results incl. tables

RESULTS HRIP-Test:

There was no evidence of skin sensitization observed on the 80 subjects (21 of preliminary study plus 59 of main study) who completed the test . A dose finding pilot study on 8 subjects was organised for four levels (1%, 0.6%, 0.2% and 0.05% w/v aqueous) of test substance. 0.5% w/v was chosen as the initial concentration for preliminary panel which was then reduced to 0.2% w/v after five applications.

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 nine induction exposures. In the preliminary panel a total of 21/21 subjects completing the study had mild erythema (grade 1),

10/21 subjects had moderate erythema (grade 2) and 2/21 subjects had strong erythema (grade 3). In the main panel a total of 54/59 subjects completing the study had mild erythema (grade 1) and 11/59 subjects had moderate erythema (grade 2). 14 days after final insult patch, treatment sites were challenged and observed at 48 and 96 hours after patch. In the preliminary panel a total of 4/21 subjects completing the study had mild erythema (grade 1). In the main panel a total of 7/59 subjects completing the study had mild erythema (grade 1).

No responses indicative of skin sensitization were observed.

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION

- Number of subjects with positive reactions: 0/80

- Number of subjects with negative reactions: 80/80

- Number of subjects with equivocal reactions: 0/80

- Number of subjects with irritating reactions: 11/80 exhibited mild erythema (grade 1)

Applicant's summary and conclusion

Conclusions:
Synprolam 35 MX/ Quaternary ammonium compounds, C12-18-alkyl(hydroxyethyl)dimethyl, chloride did not produce skin sensitization in humans in an Human Repeat Insult Patch Test .
Executive summary:

The skin sensitization potential of C13-15 dimethyl hydroxyethylammonium chloride was assessed in a human repeat insult patch study. A total of 87 subjects commenced the study. Subjects were exposed to 9 induction patches containing 0.2 % (w/v) of test substance in distilled water 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. Fourteen days after the final insult patch (9th patch), subjects were challenged with 0.2% w/v of test substance in distilled water (24 hour patch exposure). Challenge patch sites were graded at 48 and 96 hours after patch application.

A total of 80 subjects completed the study. 7 subjects were dropped during the study.

0.5% w/v was chosen as the intial conecentration for preliminary panel which was then reduced to 0.2% w/v after five applications due to irritation.At challenge there was no evidence of skin sensitization observed on the 80 subjects who completed the test.

Thus, C13-15 dimethyl hydroxyethylammonium chloride (CAS No. 85736 -63 -6) did not produce skin sensitization in humans.