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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

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Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no stated
Reliability:
1 (reliable without restriction)
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 conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There are no data available on skin sensitisation for sodium methyl 4 -hydroxybenzoate. However, there are reliable data on the structurally related substance methylparaben. Based on these data and a QSAR calculation on the target substance itself, sodium methylparaben is considered to be not skin sensitising.

Three in vivo studies are available addressing skin sensitising properties of methylparaben as target substance.

Methylparaben was investigated in a Maurer Optimization Test equivalent to OECD 406 (Maurer, 1980). 20 guinea pigs (10 male/10 female) received an injection of 0.1% methylparaben on every second day for 3 weeks. After 3 further weeks, the intradermal challenge was conducted, using 0.1% methylparaben. After 24 h, 3/20 animals of the test substance group and no animals of the negative control showed positive reactions. All positive control animals (treated with 0.1% cinnamic aldehyde) showed positive reactions. For the epidermal challenge 2 weeks later, 5% methylparaben were applied. After 24 h, positive reactions were noted in 4/20 animals of the test substance group and no animals of the negative control. The positive control animals were treated with 3% cinnamic aldehyde. After 24 h, 19/20 animals showed positive reactions.

Under the test conditions, the test substance was not considered to be a skin sensitiser.

 

In a further study, performed similar to the Maurer Optimization test and OECD 406, male guinea pigs were treated 3 times a week with an injection of 0.1% methylparaben in physiological saline for induction (Sokol, 1952). Two weeks after the last injection, the guinea pigs got a challenge injection with 0.1% methylparaben in physiological saline. The readings at 24 and 48 h after the challenge revealed no allergic response in any animal.

 

In another study, methylparaben was examined in 10 guinea pigs in a Buehler test according to OECD 406 (Anon., 1981). The test item was a hairdressing formulation with a methylparaben concentration of 0.2%. For induction, applications on the shaved back of the animals were made 3 times per week for a total of 3 weeks. During the induction phase, a slight irritation was observed. Two weeks after the last induction application, the animals received a challenge application. At the reading time points, 2 and 24 h after patch removal, no positive reactions in any animal were observed. 

 

There are no further animal or human data available on the skin sensitising potential of methylparaben.

By calculating the likelihood of interactions of sodium methylparaben with skin proteins, no structural alerts were found (DR. KNOELL CONSULT, 2012). Therefore, no interactions of sodium methylparaben with skin proteins are expected.

Furthermore, there is no evidence of chemically reactive properties of sodium methylparaben under in vitro test conditions. This is confirmed by studies on genetic toxicity in vitro (Ames test, gene mutation in mammalian cells in vitro) which were all negative.


Migrated from Short description of key information:
Skin sensitization: not sensitizing

Justification for selection of skin sensitisation endpoint:
Hazard assessment is based on the weight of evidence from all available studies and a QSAR calculation.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data on skin sensitisation of the test substance does not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and is therefore conclusive but not sufficient for classification.