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Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
key study
Study period:
7 - 14 April 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Type of study / information:
Cutaneous patch test for skin irritation in healthy human volunteers
Endpoint addressed:
skin irritation / corrosion
Principles of method if other than guideline:
- Principle of test: Determination of the human skin irritation potential of diglycerol fatty acid esters following 3 cutaneous patch applications
- Short description of test conditions: The test was a single-blind within subject comparison study conducted in 30 healthy volunteers of either sex following 3 cutaneous patch applications. Patches were applied for three 24 h periods with assessments 24 h after removal of the first and second patches and 48 h after removal of the third patch. Individual scores, mean scores and standard deviations for each study day have been determined for the 30 subjects who completed the study.
- Parameters analysed / observed: Individual and mean scores determined according to a pre-defined irritancy grading scale
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Isooctadecanoic acid, mixed esters with oxybis[propanediol]
Molecular formula:
not applicable, substance is UVCB
IUPAC Name:
Isooctadecanoic acid, mixed esters with oxybis[propanediol]

Method

Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
STUDY DESIGN:
The study was conducted single-blind. A total of 30 subjects received three 24 hour occlusive patch applications. Reading time points were 24 h after removal of the first and second patch and 48 h after removal of the third patch.

SELECTION OF SUBJECTS:
Only healthy volunteers of either sex aged 18 to 65 who gave wittnessed, written informed consent and who accepted the prohibitions and restrictions were recruited into the study.

Prohibitions and restrictions:
- No use of aspirin, or other non-steroidal anti-inflammatory drugs.
- No use of sunbeds or sunlamps for the duration of the study

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 21 units per week or 8 units per day for men; more than 14 units per week or 4 units per day for women)
- A febrile illness lasting more than 24 h in the six days prior to the first patch application
- A significant past medical history of hepatic, renal, cardiac, pulmonary, digestive, haematological, neurological, locomotor or psychiatric disease
- Immune deficiency disease
- Organ transplant that required the use of irnmunosuppressive drugs (cornea or lens transplants were not included)
- History of malignant disease
- Insulin dependent diabetes
- A history of asthma requiring regular medication or hayfever that required prescription treatment in two or more of the previous three years
- A history of multiple drug hypersensitivity
- Concurrent medication likely to have affected 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
- Current treatment by a physician for allergy unless physician consulted by Investigator and participation approved
- Participation in a repeat insult patch test (RIPT) or follow-up work within the last month
- Sensitization or questionable sensitization in a repeat insult patch test (RIPT)
- Recent immunisation (less than ten days prior to test patch application)

IRRITANCY GRADING SCALE:
0.0: No apparent cutaneous involvement.
0.5: Faint, barely perceptible erythema or slight dryness (glazed appearance).
1.0: Faint but definite erythema, no eruptions or broken skin or no erythema but definite dryness; may have epidermal fissuring.
1.5: Well-defined erythema or faint erythema with definite dryness, may have epidermal fissuring.
2.0: Moderate erythema, may have a very few papules or deep fissures, moderate-to-severe erythema in the cracks.
2.5: Moderate erythema with barely perceptible oedema or severe erythema not involving a significant portion of the patch (halo effect around the edges), may have a few papules or moderate-to-severe erythema.
3.0: Severe erythema (beef redness), may have generalised papules or moderate-to-severe erythema with slight oedema (edges well defined by raising).
3.5: Moderate-to-severe erythema with moderate oedema (confined to patch area) or moderate-to-severe erythema with isolated eschar formations or vesicles.
4.0: Generalised vesicles or eschar formations or moderate-to-severe erythema and/or oedema extending beyond the area of the patch.

If a score greater than 1.5 is recorded, the site is not repatched and the score recorded is the residual score.
Details on exposure:
TYPE OF TEST USED: patch test (epicutaneous test)

ADMINISTRATION
- Type of application: occlusive
- Description of patch: 5 cm wide strip of occlusive Blenderm tape to which Webril squares (approx. 1 cm x 1 cm) were fixed.
- Vehicle / solvent: isopropyl myristate
- Volume applied: 0.4 mL
- Dose: 7 and 25% (w/w)
- Test sites: Patches were fixed along the midline; two patches were applied to the upper left arm. Each test article was applied to each square of each patch. Dots of crystal violet were applied on either side of the top square and below the bottom square of each patch to mark the skin to enable exact location of subsequent patches. Each subject was asked to avoid the dye marks during washing and to keep the patches dry. Where reinforcement of patch adhesion became necessary, strips of porous tape were applied.
- Dose regime: Subjects were instructed to keep the patches dry and in place for 24 h then to remove and discard them. Patches were applied on Days 1, 3 and 5. Patches were applied to the same site each day unless a reaction stronger than a mild erythema (i.e. greater than a score of 1.5) was present in which case the patch strip would have been cut and the relevant square/s not re-applied. Assessment of patch sites was immediately before application of the next patch on Days 3 and 5 and on Day 8.

REFERENCE SUBSTANCES
- Positive control substance: 0.3% sodium layryl sulfate (SLS)
- Negative control substance: distilled water
- Vehicle: isopropyl myristate

Results and discussion

Results:
30 subjects of both sexes were recruited into and completed the study. No adverse events or reactions were reported and the study was completed by all subjects. Mean scores of the test item were 0.12 and 0.07 on Day 3, 0.08 and 0.29 on Day 5 and 0.08 and 0.26 on Day 8 for Grade 2 and Grade 1 of the registered substance, respectively. The negative control substance (water) resulted in mean scores of 0.07, 0.03 and 0.05 on Day 3, Day 5 and Day 8, respectively. Sodium lauryl sulfate (SLS) produced mean scores of 1.67, 1.69 and 1.13 on Day 3, Day 5 and Day 8, respectively.

Applicant's summary and conclusion

Conclusions:
It can be concluded that Grade 2 of the registered substance elicited no more than minimal irritation, whereas Grade 1 induced slight irritation in the human volunteers under the conditions of this patch test.