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Description of key information

Methylparaben has been tested in three skin sensitization studies (two similar to the Guinea pig maximization test and one according to the Bühler method) to assess the sensitising potential of the test item.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

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Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no stated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Important aspects (intradermal induction, intradermal/epidermal challenge) in line with and induction period longer than current OECD guideline. The deviations from the regarding guideline (OECD406) lead to an even more rigid study design.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
induction: 10 intradermal injections, no dermal application; 2 challenges: 1 intradermal (14 days after last induction), 1 by epidermal route (24 days after last induction)
Principles of method if other than guideline:
n.a.
GLP compliance:
no
Remarks:
performed before GLP-guideline
Type of study:
Maurer optimisation test
Justification for non-LLNA method:
Study performed before implementation of LLNA
Species:
guinea pig
Strain:
other: Pribright white
Sex:
male/female
Details on test animals and environmental conditions:
For details on conditions please refer to Th. Maurer, P. Thomann, E.G. Weirich and R. Hess, Contact Dermatitis, 4 (1978) 321
Route:
intradermal
Vehicle:
no data
Concentration / amount:
0.1% intradermal induction
0.1% intradermal challenge
5% epidermal challenge
Route:
intradermal and epicutaneous
Vehicle:
no data
Concentration / amount:
0.1% intradermal induction
0.1% intradermal challenge
5% epidermal challenge
No. of animals per dose:
20 (10 males/10 females)
Details on study design:
- Induction period: 3 weeks (10 intracutaneous applications)
- Intradermal challenge (week 6)
- epidermal challenge (week 8)

Induction:
The animals received 1 injection into the skin every other day of a freshly prepared 0.1 % methyl parabene suspension. During the first week the skin fold thickness at the injection site was measured before the application with a skinfold caliper. During the second and third weeks the test compound was incorporated at 0.1 % in a mixture of Freund´s complete adjunvant and physiological saline (adjuvant/saline 1:1 v/v).

Challenges:
The animals were challenged with methyl parabene 14 days after the last induction application using the same procedure as that during the first induction week. After a further rest period of 10 days the animals were again challenged, but this time by epidermal route. In this case the maximal subirritant concentration (5 %) of the test compound was applied in soft white petrolatum under occlusive dressings. The filter patches were removed 24 h after application.

Assessment of reactions after intradermal application:
24 h after the application during the first induction week as well as after the intradermal challenge the reaction sites were chemically depilated; 3 h later the reactions were assessed. The 2 greatest perpendicular diameters and the skinfold thickness were measured (in mm). By multiplying the diameters with the increase in skinfold thickness an approx. "reaction volume" (in µL) was obtained for each reaction in each animal. For the individual animal the mean reaction volume for the first induction week was calculated and one standard deviation added. The value thus obtained, the individual threshold value, represented the skin irritation reactivity of each animal to the induction applications. Any challenge reaction greater than the induction threshold value was considered an allergic reaction, and the animal was termed "positive". The number of positive animals in the test group was compared statistically with the number of "pseudo positive" animals in the control group treated with the vehicle alone using the Fisher test.

Assessment of reactions after epidermal challenge:
At 21 h after removing the bandages, the reaction sites were also chemically depilated. 3 h later the epidermal reactions were evaluated according to the Draize scale for primary irritation. The significance of differences in the number of positive animals between the treated group and the controls was assessed by the Fisher test.

Negative control: sodium chloride solution
Challenge controls:
no data
Positive control substance(s):
yes
Remarks:
other substances (e.g. cinnamic aldehyde, chlorocresol etc) were tested in parallel
Positive control results:
Cinnamic aldehyde (0.1 % intradermal; 3 % epidermal applied)
- incidence after intradermal challenge: 20 of 20 animals positive
- incidence after epidermal challenge: 19 of 20 animals positive
Key result
Reading:
other: reading after intradermal challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 %
No. with + reactions:
3
Total no. in group:
20
Clinical observations:
no data
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: reading after epidermal challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
5 %
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
no data
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: reading after intradermal challenge
Hours after challenge:
24
Group:
negative control
Dose level:
no data
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no data
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: reading after epidermal challenge
Hours after challenge:
24
Group:
negative control
Dose level:
no data
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no data
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: reading after intradermal challenge
Hours after challenge:
24
Group:
positive control
Dose level:
0.1 %
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
other: reading after epidermal challenge
Hours after challenge:
24
Group:
positive control
Dose level:
3 %
No. with + reactions:
19
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
In a guinea pig sensitization study according to Maurer Optimization Test Methylparaben caused allergic reaction in a few animals (4/20). The number of affected guinea pigs was not high enough to be significant. Methylparaben is not considered to be a skin sensitiser.
Executive summary:

Testing for sensitising properties of Methylparaben was performed in male and female guinea pigs according to the Maurer Optimization Test. Intradermal induction was performed using 0.1 % Methylparaben (10 injections). The first challenge was carried out with 0.1% Methylparaben (intradermal) 14 days after the last induction application and the second challenge was conducted with 5% Methylparaben (epidermal) in soft white petrolatum after further 10 days rest.

Methylparaben induced allergic reactions in a few animals, but according to the standard evaluation, not significant and therefore the test substance is not considered to have sensitising properties.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Important aspects ( induction and challenge procedures) are in line with the current OECD guideline or even more rigid, but quality of the study reporting is restricted.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
induction: 10 intradermal injections, no dermal application, challenge: intradermal (2 weeks after the last induction)
GLP compliance:
no
Remarks:
performed before GLP guidelines
Type of study:
other: similar to Maurer optimisation test
Species:
guinea pig
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
body weight: approximately 400 g
for further details please refer to :
Lehman et al., Food, Drug, Cosmetic Law Quart., 4, 412-434 (1949)
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.1%
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.1%
No. of animals per dose:
not stated
Details on study design:
Induction:
A solution of Methylparaben at a concentration of 0.1% in physiological saline was prepared using sodium hydroxide to solubilize the ester when necessary. 100 µL of this solution was injected intracutaneously into the backs and upper flanks of male guinea pigs at intervals of 3 times weekly (resulting in 10 injections).

Challenge:
2 weeks after the 10th injection a challenge injection of a freshly prepared solution of the Methylparaben was made in the area adjacent to the site of the sensitising injection. The guinea pigs were closely observed for a reaction during the next 48 hours.
Challenge controls:
no data
Positive control substance(s):
not specified
Positive control results:
not stated
Reading:
other: close observation during 48 hours after challenge injection
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1%
Clinical observations:
no allergic response in any case
Remarks on result:
other: Reading: other: close observation during 48 hours after challenge injection. . Hours after challenge: 24.0. Group: test group. Dose level: 0.1%. Clinical observations: no allergic response in any case.
Reading:
other: close observation during 48 hours after challenge injection
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1%
Clinical observations:
no allergic response in any case
Remarks on result:
other: Reading: other: close observation during 48 hours after challenge injection. . Hours after challenge: 48.0. Group: test group. Dose level: 0.1%. Clinical observations: no allergic response in any case.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
In a guinea pig sensitisation study similar to Maurer Optimization Test Methylparaben did not cause any allergic reaction. Methylparaben is not considered to be skin sensitiser.
Executive summary:

Testing for sensitising properties of Methylparaben was performed in male guinea pigs (body weight approx. 400 g) similar to Maurer Optimization Test. Intradermal induction was performed using 0.1% Methylparaben (10 injections) in physiological saline. No reaction was noted 24 hours after the first injection. The challenge was carried out with 0.1.% Methylparaben (intradermal) 2 weeks after the 10th intradermal induction.

Methylparaben did not induce allergic reactions in any test animal and therefore the substance is not considered to have sensitising properties.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
no data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Study summary
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
10 animals used, induction: 9 topical applications, observations upon patch removal, 2 h and 24 h later
GLP compliance:
no
Remarks:
performed before GLP guideline
Type of study:
Buehler test
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
Age: 3 months
Body weight: 250-400g
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% hairdressing product was tested. Methyl paraben concentration was 0.2%.
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% hairdressing product was tested. Methyl paraben concentration was 0.2%.
No. of animals per dose:
10
Details on study design:
Modified Bühler Method. A dose of 0.5 mL test item was administered topically on the shaved backs of the animals under a 2x3 inch piece of gauze consisiting of 2 layers which was then covered by wrapping the trunk with a strip of Dermicel hypoallergenic tape. This patch remained in place for 6 h. Applications were made 3 times per week for a total of nine. 14 days after the last application the animals received a challenge application at the same site and on a virgin site in the same manner. The sites were scored according to the draize scale upon patch removal, and 2 h later. The challenge sites were also scored at 24 h.
Challenge controls:
no data
Positive control substance(s):
not specified
Positive control results:
no data
Reading:
1st reading
Hours after challenge:
2
Group:
test chemical
Dose level:
0.2%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
slight irritation during induction
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 2.0. Group: test group. Dose level: 0.2%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: slight irritation during induction.
Reading:
2nd reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.2%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.2%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Methylparaben (0.2% in formulation) caused no skin sensitization in guinea pig sensitization test according to Bühler.
Executive summary:

Testing for sensitising properties of Methylparaben was performed in male and female guinea pigs according to the method of Bühler. Topical induction (9 applications) was performed using a formulation containing 0.2% Methylparaben. The challenge treatment did not cause any skin reaction in the 10 test animals. Based on these results Methylparaben showed no evidence for sensitising properties.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Methylparaben has been tested in three skin sensitization studies (two similar to the Guinea pig maximization test and one according to the Bühler method) to assess the sensitising potential of the test item. In one maximization study Methylparaben induced allergic reactions in 4/20 animals. According to the standard evaluation, this number is not high enough to be significant. In the second maximization test Methylparaben did not induce allergic reactions. The study according to the Bühler method did not reveal any allergic response.

 

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There are no respiratory sensitization properties of the substance known in literature. Beyond this there is no hint of any sensitization property of the compound from the conducted skin sensitization studies. Therefore, it is concluded that the subsance is not a respiratory sensitizer.


Based on the existing data it is concluded that the substance is not a respiratory sensitizer.

Justification for classification or non-classification

Methylparaben has been tested in three skin sensitization studies (two similar to the Guinea pig maximization test and one according to the Bühler method) to assess the sensitising potential of the test item. None of them resulted in a statistically significant allergical response. Furthermore, allergic skin reactions or case reports of acute contact dermatitis to Methylparaben alone have not been described in the literature. Therefore, the substance does not have to be classified as a skin sensitizer.

A classification concerning respiratory sensitizing properties is not warranted as the classification criteria according to EU regulation 1272/2008 and 67/548 are not met.