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Description of key information

Skin sensitisation:

Based on the presented data, acrylic acid does not have a skin sensitizing potential in animal studies. Positive test results obtained with commercial grade samples of the compound were caused by the presence of the impurity DAPA. Recent investigations on the occurrence of DAPA in industrial acrylic acid have shown that DAPA is not present (at a detection limit of 20 ppm) in current commercial samples of acrylic acid (Elf Atochem 1998, EU Risk Assessment 2002). (see Chapter 7.12 Additional Toxicological Information).

Respiratory sensitisation:

Respiratory sensitisation has not been observed in humans (EU RAR 2002).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Modified Maguire Method
GLP compliance:
no
Type of study:
split adjuvant test
Justification for non-LLNA method:
A reliable in vivo test was available before the implementation of the OECD 429 method.
Specific details on test material used for the study:
- Name of test material (as cited in study report): Acrylic acid
- Analytical purity: no data
Species:
guinea pig
Strain:
Hartley
Sex:
male
Route:
epicutaneous, occlusive
Vehicle:
no data
Concentration / amount:
Induction: 0.1 mL aliquot of the test substance
Route:
epicutaneous, occlusive
Vehicle:
no data
Concentration / amount:
not specified
No. of animals per dose:
10
Details on study design:
- Positive control:
For induction, 10 guinea pigs were routinely subjected to the same dosing regimen with the diglycidyl ether of 2,2-di-(p,p'-hydroxyphenyl)propane (DER* 331 Epoxy Resin -- Dow Chemical U .S .A .), a known sensitizer to serve as a positive control . Challenge was performed two weeks after the last injection of the induction series.
Positive control substance(s):
yes
Remarks:
2,2-Di-(p,p'-hydroxyphenyl)propane didlycidyl ether (DER* 331 Epoxy Resin -- Dow Chemical U .S .A .)
Positive control results:
The positive reference substance ( DER* 331 Epoxy Resin) induced moderate skin sensitization.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 mL
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
no data
No. with + reactions:
7
Total no. in group:
10
Group:
negative control
Remarks on result:
not measured/tested

Preliminary study:

Prior to conducting the sensitization test, the test material was applied as received to the clipped flanks of animals to determine if primary irritation would occur. If significant irritation was observed, dilutions of the test material were made in a suitable solvent. The highest concentration which did not cause primary irritation was used for the sensitization test.

Test group:

Substance

animals tested

animals sensitized

Acrylic acid (0.1 mL aliquot)

10

0

Sensitization with the test substance was not observed in this test.

Interpretation of results:
GHS criteria not met
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study was conducted according to the method described by Klecak (1977) and Klecak and Geleick (1977). Klecak (1977), Dermatoxicology and Pharmacology. Eds, Marzulli F N, Maibach H I. New York: John Wiley & Sons.
Klecak and Geleick (1977), Journal of the Society of Cosmetic Chemists, 28: 53.
GLP compliance:
no
Type of study:
Freund's complete adjuvant test
Justification for non-LLNA method:
A reliable in vivo test was available before the implementation of the OECD 429 method.
Specific details on test material used for the study:
- Name of test material (as cited in study report): Acrylic acid
- Analytical purity: 55% (gas chromatigraphy) / >98% after destillation procedure.
- Impurities (concentrations): 45% (gas chromatography) / < 2% after destillation procedure.
Species:
guinea pig
Strain:
other: Himalayan white and Dunkin-Hartley (two strains due to the shortage of animals)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Himalayan white (Inst. for Biomedical Research, Füllinsdorf, Switzerland) / Dunkin-Hartley (Olac Ltd., Bicester, England)
- Weight at study initiation: 350-450 g
- Housing: in pairs
- Diet (ad libitum): Pellet
- Water (ad libitum): water containing vitamin C


Route:
intradermal
Vehicle:
other: Refer to Details on study design (Traditional tests)
Concentration / amount:
Induction: 0.5 M
Day(s)/duration:
On days 0, 2, 4, 7 and 9
Route:
epicutaneous, open
Vehicle:
other: Refer to Details on study design (Traditional tests)
Concentration / amount:
no concentration given
Day(s)/duration:
day 21 (right flank) and day 35 (left flank)
No. of animals per dose:
8
Details on study design:
RANGE FINDING TESTS:
Skin irritation caused by a single open application was determined for Acrylic acid in FCA pretreated animals (not participating in the sensitization procedure). On the clipped flank of 8 animals 0.025 mL of the test substance was applied with a pipette in progressively diluted (one third) concentrations, each in areas of 2 cm2 marked with a circular stamp. A mixture of 2 parts methyl ethyl ketone and 1 part of peanut oil by volume (Aramek) was used as a solvent. The reactions were read after 24 and 48 h. The maximum nonirritating concentration (m.n.i.c.) was determined, which is the highest concentration not causing a macroscopic reaction in any of the animals.

MAIN STUDY
A. INDUCTION EXPOSURE
After the acid was emulsified in FCA, an equal volume of distilled water was added. On days 0, 2, 4, 7 and 9 intradermal injections with 0.1 mL of this emulsion were given in the shoulder area from the left to the right paw. Control animals were similarly treated with FCA, blended with an equal volume of distilled water.

B. CHALLENGE EXPOSURE
All the animals were tested epicutaneously on day 21 (right flank) and day 35 (left flank). On day 21 right flank and on day 35 left flank of both groups were shaved. The test substance and the vehicle was applied in an amount of 0.025 mL with a pipette on an area of 2 cm2, marked with a circular stamp. The test sites were left uncovered and read at 24 h and 48 h.
Positive control substance(s):
yes
Remarks:
various monoacrylates
Key result
Reading:
1st reading
Group:
test chemical
Dose level:
no data
No. with + reactions:
0
Total no. in group:
8
Remarks on result:
other: Test group (Acrylic acid (destillate, >98%)
Key result
Reading:
1st reading
Group:
test chemical
Dose level:
no data
No. with + reactions:
8
Total no. in group:
8
Remarks on result:
other: Test group (Acrylic acid containing an unidentified impurity of 45%)
Key result
Reading:
1st reading
Group:
negative control
Dose level:
no data
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Group:
positive control
Dose level:
no data
No. with + reactions:
8
Total no. in group:
8
Remarks on result:
positive indication of skin sensitisation
Remarks:
various acrylates have been tested and were positive (result from n-hexyl acrylate)
Interpretation of results:
GHS criteria not met
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study was conducted according to the method described by Klecak (1977) and Van der Walle (1983). Klecak (1977), Dermatoxicology and Pharmacology. Eds, Marzulli F N, Maibach H I. New York: John Wiley & Sons. Van der Walle H. B., Waegemaekers T. H., Bensink T. (1983), Contact Dermatitis 9: 10-20.
GLP compliance:
no
Type of study:
other: modified Freund's complete adjuvant test
Justification for non-LLNA method:
At the time of the study there was only the maximization test available and was recommended by regulatory authorities.
Specific details on test material used for the study:
- Name of test material (as cited in study report): Acrylic acid from Merck Schuchardt, impure
- Analytical purity: < 93% (GC)
- Impurities (identity and concentrations): alpha, beta-Diacryloxypropionic acid, 7% (analytically determined), 5-hexenoic acid (identified but not quantified)

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Hartley outbred
- Source: Broekman Institute, Netherlands
- Weight at study initiation: 400 g
- Housing: in pairs in steel cages.
- Diet (ad libitum): Pellet food (Hope Farms, Netherlands)
- Water (ad libitum): yes
Route:
intradermal
Vehicle:
water
Remarks:
distilled
Concentration / amount:
1.2% / 0.1 mL
Day(s)/duration:
Day 0, 5, and 9
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, open
Vehicle:
methyl ethyl ketone
Remarks:
2 parts methyl ethyl ketone and one part of peanut oil by volume
Concentration / amount:
0.3 M / 0.025 mL
Day(s)/duration:
Day 21. Readings were performed after 24 and 48 h of administration.
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
epicutaneous, open
Vehicle:
methyl ethyl ketone
Remarks:
2 parts methyl ethyl ketone and one part of peanut oil by volume
Concentration / amount:
0.3 M / 0.025 mL
Day(s)/duration:
Day 35. Readings were performed after 24 and 48 h of administration.
Adequacy of challenge:
highest non-irritant concentration
No.:
#3
Route:
epicutaneous, open
Vehicle:
methyl ethyl ketone
Remarks:
2 parts methyl ethyl ketone and one part of peanut oil by volume
Concentration / amount:
0.3 M / 0.025 mL
Day(s)/duration:
Day 49. Readings were performed after 24 and 48 h of administration.
Adequacy of challenge:
highest non-irritant concentration
No.:
#1
Route:
epicutaneous, open
Vehicle:
methyl ethyl ketone
Remarks:
2 parts methyl ethyl ketone and one part of peanut oil by volume
Concentration / amount:
1 M / 0.025 mL
Day(s)/duration:
Day 21. Readings were performed after 24 and 48 h of administration
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
epicutaneous, open
Vehicle:
methyl ethyl ketone
Remarks:
2 parts methyl ethyl ketone and one part of peanut oil by volume
Concentration / amount:
1 M / 0.025 mL
Day(s)/duration:
Day 35. Readings were performed after 24 and 48 h of administration
Adequacy of challenge:
highest non-irritant concentration
No.:
#3
Route:
epicutaneous, open
Vehicle:
methyl ethyl ketone
Remarks:
2 parts methyl ethyl ketone and one part of peanut oil by volume
Concentration / amount:
1 M / 0.025 mL
Day(s)/duration:
Day 49. Readings were performed after 24 and 48 h of administration.
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
8
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Three
- Exposure period: day 0, 5, and 9
- Test groups: impure acrylic acid, 5-hexenoic acid, a,b-diacryloxypropionic acid
- Control group: no substance was added
- Site: in the shaved nuchal area
- Frequency of applications: not specified
- Duration: 9 days
- Concentrations: 0.17 M for all test substances

B. CHALLENGE EXPOSURE
- No. of exposures: Three
- Day(s) of challenge: Day 21, 35, and 49
- Exposure period: 28 days
- Test groups: impure acrylic acid, 5-hexenoic acid, a,b-diacryloxypropionic acid (DAPA)
- Control group: all test compounds
- Site: shaved contralateral flank
- Concentrations: impure acrylic acid (0.3 M, 1 M), DAPA (0.01 M, 0.03 M), 5-hexenoic acid (1 M, 3 M)
- Evaluation (hr after challenge): 24 h and 48 h
Challenge controls:
Challenge controls received all tested compounds, i.e. impure acrylic acid, DAPA (a,b-diacryloxypropionic acid), and 5-hexenoic acid. Concentrations of the challenge for the control group are not specified.
Reading:
other: Day 21
Group:
test chemical
Dose level:
1 M
No. with + reactions:
8
Total no. in group:
8
Clinical observations:
not specified
Remarks on result:
positive indication of skin sensitisation
Remarks:
impure acrylic acid
Reading:
other: Day 35
Group:
test chemical
Dose level:
1 M
No. with + reactions:
8
Total no. in group:
8
Clinical observations:
not specified
Remarks on result:
positive indication of skin sensitisation
Remarks:
impure acrylic acid
Reading:
other: Day 21
Group:
test chemical
Dose level:
0.3 M
No. with + reactions:
1
Total no. in group:
8
Clinical observations:
not specified
Remarks on result:
positive indication of skin sensitisation
Remarks:
impure acrylic acid
Reading:
other: Day 49
Group:
test chemical
Dose level:
0.3 M
No. with + reactions:
7
Total no. in group:
8
Clinical observations:
not specified
Remarks on result:
positive indication of skin sensitisation
Remarks:
impure acrylic acid
Reading:
other: Day 21
Group:
negative control
Dose level:
no data
No. with + reactions:
0
Total no. in group:
8
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Dose level:
no data
Remarks on result:
not measured/tested

Sensitizing potential in the modified Freund's Adjuvant Test

Test substance

Induction

Challenge concentration*)

Number of sensitized animals/number of tested animals

Day 21

Day 35

Day 49

Acrylic acid, from Merck Schuchardt

3•0.17 M

(= 1.2%)

1 M

0.3 M

8/8

1/8

8/8

N.T.

N.T.

7/8

DAPA

1•0.17 M**)

(= 3.6%)

0.03 M

0.01 M

8/8

7/8

N.T.

7/8

N.T.

7/8

5-hexenoic acid

3•0.17 M

(= 1.9%)

3 M

1 M

0/8

0/8

0/8

0/8

0/8

0/8

controls

3•FCA dist. water

All the above compounds

0/8

0/8

0/8

N.T. = not tested

*) = In Aramek, 2 parts methyl ethyl ketone, one part peanut oil by volume

**) = Different induction procedure

Interpretation of results:
study cannot be used for classification
Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A WoE approach is conducted to investigate the skin sensitising potential of acrylic acid:

Eight acrylates and methacrylates including acrylic acid and an additional 64 substances were tested in guinea pigs using a modified Split Adjuvant Test procedure. The purity of the test substances was not mentioned. The highest concentration which did not cause primary irritation was used but no data were given on the test concentrations. Ten animals per test received a 0.1 mL aliquot of the test material to the backs four times in 10 days. At the time of the third application, 0.2 mL Freund's adjuvant was injected at one point adjacent to the insult site. After a 2-week rest period, the guinea pigs were challenged with the test material on one flank and a solvent (if used) on the other flank. The challenge site was evaluated for erythema and oedema at 24 and 48 hours. Acrylic acid was negative (0/10) (Rao et al. 1981).

 

Van der Walle et al.(1982) reported a sample of commercial grade acrylic acid to be sensitizing in a Freund’s Complete Adjuvant test. 8/8 guinea pigs were sensitized. However, analysis by gas chromatography revealed an impurity of 45 % in this sample. The sample of acrylic acid was distilled in vacuo and the sensitized animals were tested with the distillate (containing >98% acrylic acid) and with the residue. None of the animals reacted to the distillate but all the animals reacted to the residue. The identity of the allergen in this residue was under investigation at the time of publication of this paper.

 

In a modified Freund's Complete Adjuvant test 8 guinea pigs/group received 3 intradermal injections during the induction phase on days 0, 5 and 9 (the test substance was mixed with FCA in a volume of 0.1 mL). Non-irritant test concentrations were used for challenge at day 21. The test concentrations for intradermal injections were 3 x 0,17 M (1.2%) in water and for challenge 1 and 0.3 M in Aramek, a mixture of 2 parts methyl ethyl ketone and 1 part of peanut oil. Distilled acrylic acid was negative but commercial acrylic acid proved to be a strong skin sensitizer. The skin reactions were due to the presence of varying quantities (up to 7%) of a,ß-diacryloxypropionic acid (DAPA). Positive skin reactions were still present after a third challenge on day 49 (Waegemakers and Van der Walle 1984).

Conclusion: Based on the presented data, acrylic acid does not have a skin sensitizing potential in animal studies. Positive test results obtained with commercial grade samples of the compound were caused by the presence of the impurity DAPA. Recent investigations on the occurrence of DAPA in industrial acrylic acid have shown that DAPA is not present (at a detection limit of 20 ppm) in current commercial samples of acrylic acid (Elf Atochem 1998, EU Risk Assessment 2002). (see Chapter 7.12 Additional Toxicological Information).

Further studies have been performed to investigate the skin sensitizing potential of the test item. However, in all these studies the content of the skin sensitizing impurity alpha, beta-diacryloxypropionic acid in the test substance was not given or the documentation was insufficient for classification purposes: In a GPMT performed, 21 animals out of 25 showed positive skin reactions (Magnusson 1969). In a further study, the sensitizing potential of the tested acrylic acid sample in the guinea pig could be demonstrated by the Polak method (Parker, 1983). The animals showed positive skin reactions after the 4th treatment with 5 % AA (skin test reading at 28 days after start of challenge). The average skin reactions in all six tested animals were graded 0.5 based on the grading system by Parker & Turk (Immunology 47(1): 61-6, 1982). In a BASF-test (BASF AG, 1958) the test substance was applied on the shaved skin of guinea pigs (approx. 0.1 mL). The procedure was repeated daily till signs of skin irritation were observed. After a rest period of 11 days during which all skin changes disappeared, both flanks were shaved again. 24 h later, the untreated right flank was degreased with ether and treated with 10 times weaker test substance solution. Skin reactions were observed after 8, 12 and 24 h. One animal died during the induction period after 3 treatments. Repeated application of the 20 % aqueous acrylic acid solution caused necrosis and degeneration of the skin with subsequent formation of crusts and later superficial scars. Thus, the test substance was corrosive, but not skin sensitizing under the conditions of the test. A further study conducted according to the method described by Sanocki IV (Majka 1974) revealed no sensitizing effects on the skin, neither after rubbing with a 5% solution or after application of the initial doses.

 

 



Respiratory sensitisation

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

There is no information available on the potential of acrylic acid to produce respiratory sensitisation in animals. Respiratory sensitisation has not been observed in humans (EU RAR 2002).


Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this information, the substance is not considered to be classified for skin sensitisation under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.