2,2,3,3,4,4,5,5-octafluoropentyl methacrylate

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

23-Jun-2008 to 31-Jul-2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Remarks:

Skin Irritation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

23-Jun-2008 to 31-Jul-2008

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Justification for type of information:

This endpoint study record is part of a Weight of Evidence approach comprising a direct observation from RIPT studies, dermal irritation reported during developmental toxicity studies, irritation reported during an LLNA study and the results of an in vitro dermal adsorption study. The data sources are in agreement regarding dermal irritation and are sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to same study

Study type:

study with volunteers

Endpoint addressed:

skin irritation / corrosion

skin sensitisation

Guideline:

other: Repeated Insult Patch Test

Principles of method if other than guideline:

Two products, AF-2(08-1-14) and AF-3(08-1-23) were evaluated neat to determine its ability to sensitize the skin of volunteer subjects with normal skin using an occlusive repeated insult patch study. Erythema and edema reported during induction phases assessed for skin irritation.

GLP compliance:

no

Specific details on test material used for the study:

Two products containing 2% of test material:
AF-2 (08-1-14) - a hair spray formulation containing 2% OFPMA
AF-3 (08-1-23) - a hair cream formulation containing 2% OFPMA

Type of population:

general

Subjects:

- Number of subjects exposed: 50 subjects
- Sex: males and females
- Age: 18 years of age or older
- Race: any skin type or race, providing the skin pigmentation would allow discernment of erythema (3.4% asian, 25.9% black, 50.0% caucasian, 20.7% hispanic)
- Demographic information: were free of any systemic or dermatological disorder which, in the opinion of the investigative personnel, would have interfered with the study results or increased the risk of adverse events
- Known diseases: in general good health and had completed a medical screening procedure
- Other: Prior to study entry, the subjects were screened to assure that they met the inclusion/exclusion criteria.

Ethical approval:

not specified

Route of exposure:

dermal

Reason of exposure:

intentional

Exposure assessment:

measured

Remarks:

0.2 mL for AF-2(08-1-14), 0.2 g for AF-3(08-1-23)

Details on exposure:

The induction phase consisted of 9 consecutive applications of the study material and subsequent evaluations of the patch sites. Prior to application of the patches, the sites were outlined with a skin marker. Patches were applied on Mondays, Wednesdays and Fridays for 3 consecutive weeks. The subjects were required to remove the patches approximately 24 hours after application. They returned to the facility at 48-hour intervals to have the sites evaluated and identical patches applied to the same sites. Patches applied on Friday were removed by subjects after 24 hours. The sites were evaluated on the following Monday, i.e., 72 hours after patch application. A Monday or Friday holiday resulted in evaluation at 96 hours after patch application.

Following the ninth evaluation, the subjects were dismissed for a rest period of approximately 10-15 days.

Subjects who were absent once during the induction phase received a make-up (MU) patch at the last induction visit. The MU applications were graded 48 hours later at the MU visit, or were recorded as N9G (no ninth grading). Subjects who missed the ninth evaluation but have had 9 patch applications were considered to have completed the induction phase.

The challenge phase was during the sixth week of the study. Identical patches were applied to sites previously unexposed to the study material. The patches were removed by subjects after 24 hours and the sites graded after additional 24-hour and 48-hour periods (i.e., 48 and 72 hours after application). Following a negative induction, a 48/72-hour sequence of “-/+”, “?/+” or “+/+” resulted in an additional reading being performed at the 96-hour interval. Re-challenge was performed whenever there was evidence of possible sensitization.

To be considered a completed case, a subject must have had 9 applications and no fewer than 8 subsequent reading during induction, and a single application and 2 readings during challenge. Only completed cases were used to assess sensitization.

Test material was applied to the patch and the patch was applied to the infrascapular area of the back, either to the right or left of the midline, or to the upper arm.

Examinations:

The subjects returned to the facility at 48-hour intervals to have the sites evaluated and identical patches applied to the same sites during the induction phase. During the challenge phase, the pat ches were removed by subjects after 24 hours and the sites graded after additional 24-hour and 48-h our periods (i.e., 48 and 72 hours after application).

Clinical signs:

Fifty-eight subjects between the ages of 20 and 67 were enrolled and 50 completed the study. There were 3 non-serious adverse events (AEs) reported, which were unrelated or unlikely to be related to the study products.

Results of examinations:

Under the conditions employed in this study, there was no evidence of sensitization to AF-2(08-1-14) in 50 out of 50 individuals. Also, during induction there was no dermatologic response to exposure observed in 96% of individuals and in 2% slight to doubtful dermatologic response was seen, and only in 2% (1 individual) a clear erythema (no edema) was observed. Under the conditions employed in this study, there was no evidence of sensitization to AF-3(08-1-23) in 50 out of 50 individuals. During induction there was no dermatologic response to exposure observed in 90% of individuals and in 8% slight to doubtful dermatologic response was seen, and only in 2% (1 individual) a clear erythema (no edema) was observed

Outcome of incidence:

Under the conditions employed in this study, there was no evidence of sensitization to AF-2(08-1-14) and AF-3(08-1-23).

Table 1: Summary of Dermatologic Response Grades – AF-2(08-1-14)
	No reaction (-)	Minimal or doubtful response, slightly / different from surrounding normal skin (?)	Definite erythema, no edema (+)	Total evaluable	Number absent	Number discontinued
Induction Readings
1	54	0	0	54	3	1
2	51	0	0	51	2	5
3	50	1	0	51	2	5
4	49	0	1	50	1	7
5	50	1	0	51	0	7
6	50	1	0	51	0	7
7	49	1	0	50	0	8
8	44	2	0	46	4	8
9	47	1	0	48	2	8
Make Up (MU)	7	0	0	7		8
Challenge phase
48 hours	50	0	0	50	0	8
72 hours	50	0	0	50	0	8

 

Table 2: Maximum elicited response during induction: AF-2(08-1-14)
Response	N(%) subjects
- (no reaction)	48 (96%)
? (minimal or doubtful response, slightly / different from surrounding normal skin)	1 (2%)
+ (definite erythema, no edema)	1 (2%)

 

Table 3: Summary of Dermatologic Response Grades – AF-3(08-1-23)
	No reaction (-)	Minimal or doubtful response, slightly / different from surrounding normal skin (?)	Definite erythema, no edema (+)	Total evaluable	Number absent	Number discontinued
Induction Readings
1	51	3	0	54	3	1
2	48	2	1	51	2	5
3	48	2	1	51	2	5
4	47	2	1	50	1	7
5	48	2	1	51	0	7
6	50	0	1	51	0	7
7	48	1	1	50	0	8
8	45	1	0	46	4	8
9	47	1	0	48	2	8
Make Up (MU)	7	0	0	7
Challenge phase
48 hours	49	1	0	50	0	8
72 hours	50	0	0	50	0	8

 

Table 4: Maximum elicited response during induction: AF-3(08-1-23)
Response	N(%) subjects
- (no reaction)	45 (90%)
? (minimal or doubtful response, slightly / different from surrounding normal skin)	4 (8%)
+ (definite erythema, no edema)	1 (2%)

 

Conclusions:

Under the conditions employed in this study, there was no evidence of sensitization to AF-2(08-1-14) and AF-3(08-1-23). Examination of the data also indicate an absence of irritation reactions.

Executive summary:

Two products containing 2% OFPMA, AF-2(08-1-14) and AF-3(08-1 23), were evaluated neat to determine its ability to sensitize the skin of volunteer subjects with normal skin using an occlusive repeated insult patch study. Fifty subjects completed the study. Under the conditions employed in this study, there was no evidence of sensitization to AF-2(08-1-14) and AF-3(08-1-23). Also, an examination of the data also indicate an absence of irritation reactions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Test guideline

Guideline:

other: Repeated Insult Patch Test

Principles of method if other than guideline:

Two products, AF-2(08-1-14) and AF-3(08-1-23) were evaluated neat to determine its ability to sensitize the skin of volunteer subjects with normal skin using an occlusive repeated insult patch study.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,2,3,3,4,4,5,5-octafluoropentyl methacrylate

EC Number:

206-596-0

EC Name:

2,2,3,3,4,4,5,5-octafluoropentyl methacrylate

Cas Number:

355-93-1

Molecular formula:

C9H8F8O2

IUPAC Name:

2,2,3,3,4,4,5,5-octafluoropentyl 2-methylprop-2-enoate

Test material form:

liquid

Specific details on test material used for the study:

Two products containing 2% of test material:
AF-2 (08-1-14) - a hair spray formulation containing 2% OFPMA
AF-3 (08-1-23) - a hair cream formulation containing 2% OFPMA

Method

Type of population:

general

Ethical approval:

not specified

Subjects:

- Number of subjects exposed: 50 subjects
- Sex: males and females
- Age: 18 years of age or older
- Race: any skin type or race, providing the skin pigmentation would allow discernment of erythema (3.4% asian, 25.9% black, 50.0% caucasian, 20.7% hispanic)
- Demographic information: were free of any systemic or dermatological disorder which, in the opinion of the investigative personnel, would have interfered with the study results or increased the risk of adverse events
- Known diseases: in general good health and had completed a medical screening procedure
- Other: Prior to study entry, the subjects were screened to assure that they met the inclusion/exclusion criteria.

Clinical history:

Individuals excluded from participation in the study were those who:
1. had any visible skin disease at the study site which, in the opinion of the investigative personnel, would have interfered with the evaluation;
2. were receiving systemic or topical drugs or medication which, in the opinion of the investigative personnel, would have interfered with the study results;
3. had psoriasis and/or active atopic dermatitis/eczema;
4. were females who were pregnant, planning to become pregnant during the study, or breastfeeding; and/or
5. had a known sensitivity to cosmetics, skin care products, or topical drugs as related to the material being evaluated.

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: 2 cm x 2 cm Webril pad attached to a non-porous, plastic film adhesive bandage (3M medical tape).
- Vehicle / solvent: None (tested neat)
- Volume applied: 0.2 mL for AF-2(08-1-14) and 0.2 g for AF-3(08-1-23)

EXAMINATIONS
- Grading/Scoring system: The symbols found in this scoring scales below were used to express the response observed at the time of examination:
- = no reaction
? = minimal or doubtful response, slightly different from surrounding normal skin
+ = definite erythema, no edema
++ = definite erythema, definite edema
+++ = definite erythema, definite edema and vesiculation
- Statistical analysis: In the absence of any sensitization reactions in this sample size (50 evaluable subjects), a 95% upper confidence bound on the population rate of sensitization would be 4.9%

Results and discussion

Results of examinations:

SYMPTOMS
- Frequency, level, duration of symptoms observed: There were 3 non-serious adverse events (AEs) reported, which were unrelated or unlikely to be related to the study products.

Number enrolled: 58
Number discontinued: 8
Reasons for discontinuation: Lost to follow-up (3); voluntary withdrawal (2); adverse event (3)
Number completed: 50

Any other information on results incl. tables

Table 1: Summary of Dermatologic Response Grades – AF-2(08-1-14)
	No reaction (-)	Minimal or doubtful response, slightly / different from surrounding normal skin (?)	Definite erythema, no edema (+)	Total evaluable	Number absent	Number discontinued
Induction Readings
1	54	0	0	54	3	1
2	51	0	0	51	2	5
3	50	1	0	51	2	5
4	49	0	1	50	1	7
5	50	1	0	51	0	7
6	50	1	0	51	0	7
7	49	1	0	50	0	8
8	44	2	0	46	4	8
9	47	1	0	48	2	8
Make Up (MU)	7	0	0	7		8
Challenge phase
48 hours	50	0	0	50	0	8
72 hours	50	0	0	50	0	8

 

Table 2: Maximum elicited response during induction: AF-2(08-1-14)
Response	N(%) subjects
- (no reaction)	48 (96%)
? (minimal or doubtful response, slightly / different from surrounding normal skin)	1 (2%)
+ (definite erythema, no edema)	1 (2%)

 

Table 3: Summary of Dermatologic Response Grades – AF-3(08-1-23)
	No reaction (-)	Minimal or doubtful response, slightly / different from surrounding normal skin (?)	Definite erythema, no edema (+)	Total evaluable	Number absent	Number discontinued
Induction Readings
1	51	3	0	54	3	1
2	48	2	1	51	2	5
3	48	2	1	51	2	5
4	47	2	1	50	1	7
5	48	2	1	51	0	7
6	50	0	1	51	0	7
7	48	1	1	50	0	8
8	45	1	0	46	4	8
9	47	1	0	48	2	8
Make Up (MU)	7	0	0	7
Challenge phase
48 hours	49	1	0	50	0	8
72 hours	50	0	0	50	0	8

 

Table 4: Maximum elicited response during induction: AF-3(08-1-23)
Response	N(%) subjects
- (no reaction)	45 (90%)
? (minimal or doubtful response, slightly / different from surrounding normal skin)	4 (8%)
+ (definite erythema, no edema)	1 (2%)

Applicant's summary and conclusion

Conclusions:

Under the conditions employed in this study, there was no evidence of sensitization to AF-2(08-1-14) and AF-3(08-1-23).

Executive summary:

Two products, AF-2(08-1-14) and AF-3(08-1-23), containing 2% OFPMA each, were evaluated neat to determine its ability to sensitize the skin of volunteer subjects with normal skin using an occlusive repeated insult patch study. Fifty subjects completed the study. Under the conditions employed in this study, there was no evidence of sensitization to AF-2(08-1-14) and AF-3(08-1-23).