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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across from a test procedure according to standard publication

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
According to the publication of Stotts 1980
GLP compliance:
yes
Remarks:
(Good Clinical Practice)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
- Number of subjects exposed: 103 volunteers
- Sex: either sex
- Age: 18 - 65 years
- Race: no data
- Demographic information: no data

Inclusion criteria:
Healthy volunteers of either sex aged 18 to 65 years.
Provision of written informed consent.

Clinical history:
Exclusion criteria
Pregnancy or lactation.
Inadequate or non-existent contraception (women of child bearing potential only)
A current skin disease of any type apart from mild acne
History of skin tumours
Heavy alcohol consumption (i.e. more than 35 units per week or 12 units per day for men; more than 24 units per week or 8 units per day for women)
Febrile illness lasting more than 24 hours in the six days prior to the first patch application
Significant past medical history of hepatic, renal, cardiac, pulmonary, digestive, haematological, neurological, locomotor or psychiatric disease
Current use of history of repeated use of steet drugs
A history of asthma requiring regular medication
A history of multiple drug hypersensitivity
Concurrent medication likely to affect the response to the test articles or confuse the results of the study (eg steroids and anti-histamines)
Known sensitivity to the test articles or their constituents
Sensitisation or questionable sensitisation in a repeat insult patch test (RIPT)
Participation in a repeat insult patch test (RIPT) in the three months before test patch application
Recent immunisation (less than 10 days prior to test patch application)

Prohibitions and restrictions - for the duration of the study
No use of aspirin, or non-steroidal anti-inflammatory drugs, for the duration of the study.
No use of sunbeds or sunlamps and no deliberate exposure of the test sites to natural sunlight or to other sources of UV light during the study
No immunisations from ten days prior to first patching until study completion
Controls:
To one disc purified water was applied as negative control; the use of positive control substances in human sensitization tests is not indicated due to ethical considerations.
Route of administration:
dermal
Details on study design:
Patches consisted of a 5 cm wide strip of occlusive Blenderm® tape (3M Co.) to which four Webril (Kendall Corporation) discs (approximately 2.4 cm
indiameter) were fixed along the midline. If necessary, the tape was trimmed in cases where tape irritation developed.
If reinforcement of the patch was necessary, strips of porous tape (Micropore (3M Co.) were applied.

The test article (0.4 mL) was applied to the centre of the Webril discs.

Induction
Patches were applied to one upper arm and subjects were instructed to keep the patch in place for 24 hours then to remove and discard it. Patches
were applied on Days 1, 3, 5, 8, 10, 12, IS, 17 and 19. If a subject was absent once during this three week period a make-up (MU) patch was applied on Day 22.
Patches were applied to the same site each day unless a reaction stronger than mild erythema was present in which case the patch strip was cut and
the relevant disc/s moved to a site adjacent to the original one. If a second move was indicated this was to the other side of the original one and if a
third move was indicated the disc/s was moved back to the original site if this was clear of the previous reaction otherwise the disc/s were not
re-applied.

Used test concentrations:
Destilled water
0.5 % actives of the test substance
1 % actives of the test substance
2 % actives of the test substance

Challenge
Challenge patches, constructed as before, were applied to both arms of each subject on Day 36. Subjects were required to remain at the test
centre for one hour following application of the patches. The patches were worn for 24 hours and were then removed and discarded by the subject.
If residual reactions from the induction application remained, the patch strip was applied to visually normal skin.

Challenge concentation was 1 % actives of the test substance

Assessment
Assessment of the induction patch sites were made immediately before application of the next patch on Days 3, 5, 8, 10, 12, 15, 17, 19 and on Day 22 (and on Day 24 for MU patches). They were also made 48 hours and 96 hours after application of the challenge patches.

Sensitisation if it occurred would be recognised by rapid response to challenge and would be characterised by severe erythema and oedema, usually with papules and/or vesicles.


Grading/Scoring system:

0 No visible reaction. The score would include superficial skin responses such as glazing, peeling, cracking.
1 Mild erythematous reaction. Faint pink to definite pink.
1E Mild erythematous reaction with papules and/or oedema.
2 Moderate erythematous reaction. Definite pink to red erythema (similar to sunburn).
2E Moderate erythematous reaction with oedema and/or papules.
3 Strong erythematous reaction. Beet red.
3E Strong erythematous reaction with marked oedema, papules and/or few vesicles.
4 Severe reaction with erythema, edema, papules and vesicles (may be evidence of weeping).
5 Bullous reaction.
S reaction spread beyond chamber area.

Note: Erythema, papules, oedema and vesicles are judged to be present if they involve 25 % or more of the patch site. If papules are present
then add P i.e. 1EP. If vesicles then add V i.e. 1EV.

Any grade greater than 1 (which includes 1E and 1S) during induction necessitates relocation of the patch.


- Statistical analysis: Not applicable

Results and discussion

Results of examinations:
At 2 % w/v active substance, minimal irritation was observed. Based on this, the subjects were challenged at 1% w/v active substance and distilled
water and the results indicate that no questionable reactions were observed to the 1 % w/v active substance cationic softener. It can be concluded that this test article would be unlikely to sensitize humans.

No adverse reactions to the test articles were reported. Fourteen non-serious adverse events were reported, none of which were treatment related.
A total of fifteen subjects did not complete the study, six subjects due to non-serious adverse events, one subject due to a protocol violation (use of Metanamic acid and Noresthisterone between induction and challenge) and eight subjects due to personal reasons which were unrelated to the test
articles.

Applicant's summary and conclusion

Conclusions:
There was no evidence of sensitisation to the test substance in any panelist during induction or challenge.
Executive summary:

In a dermal sensitisation study, according to the publication of Stotts 1980, (Current Concepts in Cutaneous Toxicity Academic Press pp. 41-53) with the fully saturated TEA-Esterquat ( 0.5, 1, and 2 % aqueous dilution), a total of 103 healthy volunteers were tested using the Human Repeated Patch Test method (HRIPT).

 

103 volunteers took part in the study and were exposed to 9 induction patches containing 0.4 mL of the aqueous dilutions (water, 0.5, 1 and 2 % test substance) under occlusive dressing during a three week period. On study day 36 challenge patches (1 % test article concentration) were applied to both arms of each subject. 15 volunteers dropped out, two forgot to attend; one due to work. commitments; five due to personal reasons; five due to personal illness and one due to an adverse event (Chicken pox) which was not product related and one due to protocol violation.

 

At 2 % w/v active substance, minimal irritation was observed. Based on this, the subjects were challenged at 1 % w/v active substance and distilled water and the results indicate that no questionable reactions were observed to the 1 % w/v active substance.

There was no evidence of sensitisation to the test substance in any panelist during induction or challenge.