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Toxicological information

Sensitisation data (human)

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Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

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:
ICH guideline (Good Clinical Practice)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
Test substance: Dehy: A cationic softener (fully saturated TEA-Esterquat)
very pale clear yellow liquid
- Lot/batch No.: SC -3516op-1605d-18.02.98
- storage in sealed container at room temperature
- ph value: 5.32 - 5.95 (daily monitored)

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
- Number of subjects exposed: 105 volunteers
(7 volunteers dropped out, 5 due to personal reason and 2 volunteers due to a serious adverse event (broken wrist and whiplash injury)
- 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)
Current use or history of repeated use of street drugs
A 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
Organ transplant that requires the use of immunosuppressive drugs (cornea or lens transplants are not included).
Immune deficiency disease
History of malignant disease
Insulin dependent diabetes
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
Known sensitivity to the test articles or their constituents including patch materials
Recent immunisation (less than 10 days prior to test patch application)
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

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
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:
None; however 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 on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 to one upper arm. Subjects were instructed to keep the patches in place for 24 hours
then to remove and discard them. 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 moved to the right of the original one.
Where a second move was required this was to the left of the original site. If a third move had been necessary the disc would have been moved back tothe original site if this had been clear of the previous reaction, otherwise the disc would not have been re-applied.

Challenge
Challenge patches, constructed as before, were applied to both upper 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.

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 webril pad 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:
53 % of the subjects showed no visible response to the test substance at any time during induction. Mild irritancy was seen in 46 % of subjects on at least one day during induction. Only one subject (no. 7), showed a moderate erythematous response. This occurred on Day 12 but had resolved by Day 15 following patch relocation.

Minor additional observations accompanied the grading assessments. Two subjects asked not to be repatched (nos. 50 and 57) but it is considered that this was a general request and not specifically related to the test substance. One reported a burning sensation (no.53). This was attributed to a reaction to the adhesive patch itself rather than to the test article.

There was no evidence of sensitisation to test article in any subject at induction or challenge.

There were two serious adverse events (broken wrist and whiplash injury) during study. Neither serious adverse event was considered to be an
adverse reaction to treatment.
One non-serious adverse event was recorded, (abscess on the gum) which was not considered to an adverse reaction to treatment.

Applicant's summary and conclusion