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Administrative data

Description of key information

Skin irritation:
3 studies (1 key study/2 supporting studies) available: mildly/not irritating
Eye irritation:
1 study available: minimally transient irritant

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
December 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to primary skin irritation test design in effect since 1976, but not according to OECD Guideline.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Primary skin irritation test design in effect since 1976.
The method is a modification of the Draize technique and is similar to that used in grading skin irritation in the Human Patch Test. The highest grade at either the 2 or 24 hour reading is used to calculate the Primary Irritation Index (PII).
GLP compliance:
no
Remarks:
study performed before GLP guidelines
Species:
rabbit
Strain:
other: Albino
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Specie: Albino rabbit
- Sex: female
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: no data
- Diet (e.g. ad libitum): no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Photoperiod (hrs dark / hrs light): no data
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Frequency: once
- Product type: per se
- Concentration tested: 100%

VEHICLE: none
Duration of treatment / exposure:
24 hrs
Then the occlusive dressing was removed.
Observation period:
24 and 72 hrs after contact
Number of animals:
9
Details on study design:
METHODS:
Nine healthy female albino rabbits were used to study each material.
The test material was applied to a 1" filter disc which was held in contact with the clipped skin of the back of the animal by Blenderm tape. The trunk of each animal was then wrapped with an occlusive plastic sheet and secured with Elastoplast tape.

OBSERVATIONS:
The occlusive dressing was removed after 24 hours of contact, and the skin sites graded for irritation and edema after 24 and 72 hours according to the scoring system based on a maximum of

PSI Scores:
0 = no evidence of any effect
1/2 = (Barely Perceptible) = minimal faint uniform or spotty erythema
1 = (Mild) = pink uniform erythema covering most of contact site
2 = (Moderate) = Pink-red erythema visibly uniform in entire contact area
3 = (Marked) = Bright red erythema with accompaning edema, petachiae or papules
4 = (Severe) = Deep red erythema with vesiculation or weeping with or withourt edema

PSI = Primary Skin Irritation Score, Maximum Score = 4.0
PII = Primary Irritation Index - a value depicting the average skin response of the test panel as a whole. It is calculated by adding the Irritation Scores and dividing by the total number of test subjects.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
no data
Remarks on result:
other: test item; readings performed after 24 and 72 h
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
0.44
Max. score:
4
Reversibility:
no data
Remarks on result:
other: control; readings performed after 24 and 72 h
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: n.a.
Remarks on result:
other: no evidence of any effect; readings performed after 24 and 72 h
Irritation parameter:
erythema score
Basis:
animal: 2-7
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: minimal faint uniform or spotty erythema; readings performed after 24 and 72 h
Irritation parameter:
erythema score
Basis:
animal: 8
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: pink uniform erythema covering most of contact site
Irritation parameter:
erythema score
Basis:
animal: 9
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: pink-red erythema visibly uniform in entire contact area
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: n.a.
Remarks on result:
other: readings performed after 24 and 72 h

 SCORE  0  1/2  1  2  3  4
 Number of Animals Test  1  6  1  1  0  0
  Control  4  2  3  0  0  0
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material, when evaluated for primary skin irritation by a 24-hour patch test conducted on intact skin, was found to be not irritating.
Executive summary:

The test material, when evaluated for primary skin irritation by a 24-hour patch test conducted on intact skin, was found to be not irritating to skin.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1956
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: only discussion of experimental results, but no detailed data available
Qualifier:
no guideline followed
Principles of method if other than guideline:
application of methylparabene dissolved in propylene glycol to the skin of 50 human subjects
GLP compliance:
no
Remarks:
study performed before GLP guidelines
Species:
human
Strain:
not specified
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
other: propylene glycol
Controls:
no
Amount / concentration applied:
5% solution of methylparaben in propylene glycol;
amount: no data
Duration of treatment / exposure:
Application during a period from four to eight hours every other day and a total of ten applications.
Observation period:
no data
Number of animals:
50 human subjects
Details on study design:
The methyl ester of p-hydroxybenzoic acid was dissolved in propylene glycol in increasing concentrations, and applied to the skin of 50 human subjects. It was found that the following concentration produced no irritation when applied during a period from four to eight hours every other day and a total of ten applications.: 5%. Higher concentrations produced some evidence of irritation.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: not defined
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
other: not defined
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation

No irritation was observed up to a concentration of 5%.

Higher concentrations produced some evidence of irritation.

Interpretation of results:
not irritating
Remarks:
Migrated information in concentrations up to 5% in propylene glycol Criteria used for interpretation of results: not specified
Conclusions:
Methylparaben was found to be not irritant when applied dissolved in propylene glycol in concentrations up to 5% to the skin of humans.
Executive summary:

Methylparaben was found to be not irritant when applied dissolved in propylene glycol in concentrations up to 5% to the skin of humans.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1952
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: only discussion of experimental results, but no detailed data available
Qualifier:
no guideline followed
Principles of method if other than guideline:
10% paste of methylparaben in a hydrophilic ointment base were applied to the skin of rabbits.
GLP compliance:
no
Remarks:
study performed before GLP guidelines
Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
test animal: white rabbits
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
other: hydrophilic ointment base
Controls:
no
Amount / concentration applied:
10% hydrophilic ointment base
Duration of treatment / exposure:
48 hours
Observation period:
no data
Number of animals:
no data
Details on study design:
10 per cent pastes of methyl 4-hydroxybenzoate in a hydrophilic ointment base were applied to the skin of the backs of white rabbits.
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
4

There was no noticable irritation detected after forty-eight hours.

Upon sacrificing the animals, no Parasepts or degredation products thereof were detected in the kidneys.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: not specified
Conclusions:
Methylparaben was found to be not irritating when applied as 10% paste in hydrophilic ointment to the skin of white rabbits.
Executive summary:

Methylparaben was found to be not irritating when applied as 10% paste in hydrophilic ointment to the skin of white rabbits.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
December 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to Eye irritation test design (modified Draize), but not according to OECD Guideline.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Eye irritation test design (modified Draize).
Examinations for injuries or irritation will be made until all eyes are negative or for seven days, whichever occurs first.
GLP compliance:
no
Remarks:
study performed before GLP Guidelines
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Specie: Albino rabbit/New Zealand
- Sex: males and/or females
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: no data
- Diet (e.g. ad libitum): no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Photoperiod (hrs dark / hrs light): no data
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Frequency: once
- Product type: per se
- Concentration tested: 100%

VEHICLE: none
Duration of treatment / exposure:
no data
Observation period (in vivo):
48 hours
Number of animals or in vitro replicates:
6
Details on study design:
METHODS:
Six healthy albino rabbits, males and/or females, were used.
The test material was instilled into one eye of each animal; the other eye served as the control.

OBSERVATIONS:
Examinations for injuries were made at 24, 48, and 72 hours and at four and seven days.
Observations of injuries or irritation resulting from contact with these substances were made on the cornea, iris, and conjunctiva.
Eye irritation was graded and scored according to the scoring system of Draize, J. H., from the Appraisal of the Safety of Chemicals in Foods, drugs, and Cosmetics, association of Food and Druf Officials of the U.S., Austin, Texas, 1959.
Maximum score = 110
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: Day 1
Score:
1
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: Day 2
Score:
0
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: mean score on cornea opacity, iris, chemosis and conjunctivae
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: mean score on cornea opacity, iris, chemosis and conjunctivae
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: mean score on cornea opacity, iris, chemosis and conjunctivae
Irritation parameter:
iris score
Basis:
mean
Time point:
24 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: mean score on cornea opacity, iris, chemosis and conjunctivae
Irritation parameter:
iris score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: mean score on cornea opacity, iris, chemosis and conjunctivae
Irritation parameter:
iris score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: mean score on cornea opacity, iris, chemosis and conjunctivae
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: mean score on cornea opacity, iris, chemosis and conjunctivae
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: mean score on cornea opacity, iris, chemosis and conjunctivae
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: mean score on cornea opacity, iris, chemosis and conjunctivae
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: mean score on cornea opacity, iris, chemosis and conjunctivae
Irritation parameter:
chemosis score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: mean score on cornea opacity, iris, chemosis and conjunctivae
Irritation parameter:
chemosis score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: mean score on cornea opacity, iris, chemosis and conjunctivae
Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: not specified
Conclusions:
Methylparaben produced slight transient irritation with an eye irritation score of 1/110 on Day 1 when applied to the eyes of rabbits which was fully reversible within 48 h.
Executive summary:

Methylparaben produced slight transient irritation with an eye irritation score of 1/110 on Day 1 when applied to the eyes of rabbits. This effect was fully reversible within 48 h.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Three studies are available that examined the skin irritancy potential of Methylparaben. For two of them only basic facts are reported but one detailed study clearly demonstrates that the skin irritation potential is minimal to negligible. This conclusion is consistently supported by the other studies which did not show any skin irritation after Methylparaben treatment in humans and rabbits.

There is limited data available on the eye irritancy potential. The study was performed according to the Eye Irritation Test Design (modified Draize) and reported in sufficient detail to be able to ascertain that the substance has very low eye irritancy potential (irritation score 1/110, 6 animals), with effects disappearing within 48 hours of instillation of the substance into rabbit eyes.

Justification for classification or non-classification

The substance is not irritating to the skin following single application and does not meet the criteria for classification as a skin irritant.

There is limited but sufficient data available on the eye irritancy potential to conclude that the substance does not meet the criteria to be classified as irritating to the eye.

It can reasonably be deduced that Methylparaben does not cause respiratory tract irritation and thus does not have to be classified, because the substance did cause only slight, fully reversible irritative effects in the eyes and the skin. It does not have to be classified as either skin or eye irritating. Therefore, Methylparaben, in the unlikely event of being inhaled as a dust, is considered not to cause severe effects, due to its not- irritating properties on skin and eye. A harmful interaction with living cells and tissues is very unlikely (as demonstrated by the in vivo skin and eye irritation studies).