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Administrative data

Description of key information

Dimethylolpropionic acid is not irritating to skin, however the results of one study indicate that it is an eye irritant. Experience from a single accidental high exposure indicate that the substance may cause respiratory irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
4 to 18 June 2007
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Recent GLP guideline compliant study, reported in summary form
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
The animals were male and female New Zealand White rabbits, supplied by Velaz (Prague). At the start of the study animals weighed 2-2.5 kg. The rabbits were acclimatised for 21 days, during which time the health status of the rabbits was observed. The animals were housed individually in suspended metal cages, and had free access to mains drinking water and food. The animal room was maintained at a temperature of 17-20°C, and relative humidity of 49-56%. The animals were subjected to a 12 hour light: 12 hour dark cycle.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
500 mg of the test material was applied to the skin
Duration of treatment / exposure:
Four hours
Observation period:
72 hours following patch removal
Number of animals:
2 males and 1 female.
Details on study design:
The study was conducted according to OECD guideline 404. The day before the test the dorsal flank of each rabbit was clipped free of fur using veterinary clippers. Only animals with a healthy intact epidermis (assessed by gross observation) were selected for the study.
On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 500 mg of the test material was introduced under a 2.5x2.5 cm gauze patch and placed in position of the shaved skin. The patch was secured in position with a strip of surgical adhesive tape.
Four hours after application the patches were removed and any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water. The test sites were examined for signs of primary irritation 1 hour after patch removal, and 24, 48 and 72 hours later.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 hours
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 hours
Score:
0
Max. score:
0
Remarks on result:
other: No effects seen
Irritant / corrosive response data:
The test substance produced a very slight erythema in all 3 rabbits, noticeable 24 hours after patch removal and persisting for 3-4 days following patch removal. No other signs of irritation were noted.
Other effects:
None reported.

Dermal reactions

Observation

Timepoint

1h

24h

48h

72h

Mean (24-72h)

4d

5d

Erythema

0,0,0

1,1,0

1,1,0

1,1,0

0.67

1,0,0

0,0,0

Oedema

0,0,0

0,0,0

0,0,0

0,0,0

0.00

0,0,0

0,0,0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance was not irritating to the skin.
Executive summary:

Dimethylolpropionic acid was applied to the shaved intact skin of 3 New Zealand White rabbits, under a semi-occlusive patch. The patch was left in place for 4 hours; upon removal of the patch any residual test material was removed by gently swabbing the skin with cotton wool soaked in distilled water. The test sites were examined for signs of primary irritation 1 hour after patch removal, and 24, 48 and 72 hours later. The test substance produced a very slight erythema in all 3 rabbits, noticeable 24 hours after patch removal and persisting for 3-4 days following patch removal. No other signs of irritation were noted. Data were not shown but the author reported that the substance congested and degreased the skin following repeat application.

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:
25 May to 21 June 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Proprietary GLP guideline-compliant study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes
Remarks:
OECD
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
The animals were young adult male Himalayan Chbb: HM (outbred strain) rabbits, obtained from Boehringer Ingelheim Pharma KG. The rabbits were acclimatised for at least 1 week. The rabbits weighed 2.42-2.66 kg.
The animals were housed in fully air-conditioned rooms . Central air-conditioning guaranteed a range of 20 - 24°C for temperature and of 30 - 70% for relative humidity. Light was provided on a 12 hour light/dark cycle. The rabbits were singly housed in stainless steel wire mesh cages with grating, with a floor area of 3000 cm². Bedding was not provided in the cages, wood shavings were placed in the waste trays. Individuals were identified by ear tattoo. The rabbits were provided with approximately 250 ml tap water per animal per day, and approximately 130 g food per animal per day (Kliba-Labordiaet, Switzerland).
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 ml bulk volume (approximately 33g of the comminuted test substance).
Duration of treatment / exposure:
The test substance was applied in a single dose to the conjunctival sac of the right eyelid, the substance was washed out with tap water about 24 hours after application (before the 24 h reading).
Observation period (in vivo):
14 days: readings were taken at 1 h, 24 h, 48 h, 72 h, 7 d and 14 d after application.
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
The test substance was applied in a single dose to the conjunctival sac of the right eyelid, the substance was washed out with tap water about 24 hours after application (before the 24 h reading). The left eye remained untreated to serve as a negative control.
Checks for dead or moribund animals were made twice each workday and once on weekends and public holidays.
Ocular lesions were assessed according to the scoring system defined in the OECD test guideline 405. The mean values were calculated according to 93/21/EEC (for calculation of the means of corneal opacity, iris, redness and swelling of the conjunctiva only the readings of 24, 48 and 72 hours are used).
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 & 72 hours
Score:
0.78
Max. score:
1
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 & 72 hours
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24, 48 & 72 hours
Score:
2.56
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 & 72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
1 rabbit showed suppuration at the 24, 48 and 72 hour readings. At the 48 and 72 hour readings this rabbit had also developed a contracted pupil and discharge of blood. A second rabbit displayed suppuration, contracted pupil and discharge of blood at the 48 and 72 h readings. These symptoms had disappeared by the 7 day reading. Data are presented in Table 1.
Other effects:
No other effects reported.

Irritant response data.

Reading

Rabbit

Cornea

Iris

Conjunctiva

Symptoms

Opacity

Area

Redness

Chemosis

Discharge

1 h

1

0

0

0

1

2

3

 

2

0

0

0

1

2

2

 

3

0

0

0

2

2

3

 

24 h

1

1

1

0

2

2

3

 

2

1

1

1

2

3

3

 

3

1

1

1

3

2

3

S

48 h

1

0

0

0

2

1

2

 

2

1

1

1

3

3

3

S, PC, DB

3

1

1

1

3

2

3

S, PC, DB

72 h

1

0

0

0

2

1

2

 

2

1

3

1

3

2

3

S, PC, DB

3

1

3

1

3

2

3

S, PC, DB

7 d

1

0

0

0

1

0

1

 

2

0

0

0

2

1

0

 

3

0

0

1

2

1

0

 

14 d

1

0

0

0

0

0

0

 

2

0

0

0

0

0

0

 

3

0

0

0

0

0

0

 

Mean

1

0.33

 

0.00

2.00

1.33

 

 

2

1.00

 

1.00

2.67

2.67

 

 

3

1.00

 

1.00

3.00

2.00

 

 

Mean

 

0.78

 

0.67

2.56

2.00

 

 

Key

S = suppuration

PC = pupil contracted

DB = discharge of blood

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The authors concluded that the results obtained indicate that 2,2-Bis(hydroxymethyl)propanoic acid is irritating to the eye.
Executive summary:

The eye irritant potential of 2,2 -Bis(hydroxymethyl)propanoic acid was assessed in 3 Himalayan rabbits. The test substance was applied to the right eye in a single application of 0.1 ml bulk volume, and washed out with tap water 24 hours later. Irritant reactions were scored at 24 h, 48 h, 72 h, 7 d and 14 d after application. The average score (24 to 72 hours) for irritation was calculated to be 0.78 for corneal opacity, 0.67 for iris, 2.56 for conjunctival redness and 2.00 for chemosis. The findings were reversible in all animals within 14 days after application. Symptoms observed included suppuration, contracted pupil and discharge of blood. The authors concluded that the results obtained indicate that 2,2-Bis(hydroxymethyl)propanoic acid is irritating to the eye.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The skin irritant potential of Bis-MPA (dimethylolpropionic acid) was evaluated in a GLP study conducted according to OECD Guideline 404 (Szokolayova, 2007). The test substance was applied to the shaved intact skin of 3 New Zealand White rabbits, under a semi-occlusive patch. The patch was removed after 4 hours and residual test material was removed with water. The test substance produced a very slight erythema in all 3 rabbits, noticeable 24 hours after patch removal and persisting for 3 -4 days after patch removal. No other signs of irritation were noted. It was concluded that the test substance was not irritating to skin.

Eye irritation

The eye irritant potential of Bis-MPA was evaluated in a GLP study conducted according to OECD guideline 405 (Szokolayova, 2007). Dimethylolpropionic acid was administered to the eyes of male and female New Zealand White rabbits. Slight corneal opacity, swelling and red conjunctivae were noted, but all symptoms had disappeared by day 4. The substance was considered to be mildy irritating to the eye, but the effects were fully reversible.

Wiemann & Hellwig (1999) assessed the eye irritant potential of Bis-MPA in 3 Himalayan rabbits in a GLP study conducted according to OECD 405. The test substance was applied to the right eye, and washed out with tap water 24 hours later. The average score (24 to 72 hours) for irritation was calculated to be 0.78 for corneal opacity, 0.67 for iris, 2.56 for conjunctival redness and 2.00 for chemosis. The findings were reversible in all animals within 14 days after application. Symptoms observed included suppuration, contracted pupil and discharge of blood. It was concluded that Bis-MPA is an eye irritant.

Respiratory irritation

No study is available. Experience from accidental high exposure to workers during maintenance work indicate that the substance might be irritating to mucous mebranes in the upper respiratory tract. As a precautionary measure the substance is classified as a respiratory irritant.


Justification for selection of skin irritation / corrosion endpoint:
Only study available for this endpoint

Justification for selection of eye irritation endpoint:
Study reporting the more severe effects

Effects on eye irritation: irritating

Justification for classification or non-classification

Dimethylolpropionic acid was not found to be a skin irritant, and therefore does not require classification according to Regulation (EC) No 1272/2008. Dimethylolpropionic acid was found to be irritating to eyes however, and is classified as a Category 2 Eye Irritant.

Experience from accidental high exposure indicate that the substance might be irritating to mucous mebranes in the upper respiratory tract. Therefore the substance is classified on a precautionary basis as STOT SE3. H335: May cause respiratory irritation.