2,2-bis(hydroxymethyl)propionic acid

Endpoint summary

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:

04 June 2007 to 19 June 2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes

Specific details on test material used for the study:

- Name of the test material used in the study report: Dimethylpropionic acid
- Batch no.: not given
- Purity: not given
- Appearance: not given
- Expiry date: not given
- Storage conditions: not given

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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 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:

5 days 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 after patch removal 1, 24, 48 hours and 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 days later.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 5 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 4 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 5 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effect observed

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effect observed

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects observed

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. The very slight erythema observed in all animals was fully reversible within 5 days.

Other effects:

None reported.

Table 1: Dermal reactions

 

Observation	Timepoint
	1h	24h	48h	72h	Mean (24-72h)	4d	5d
Erythema	0,0,0	1,1,1	1,1,1	1,1,1	1	1,0,1	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:

GHS criteria not met

Conclusions:

The substance was not irritating to the skin.

Executive summary:

In a primary dermal irritation study (conducted according to OECD TG 404), New Zealand White rabbits (2 male and 1 female) were dermally exposed to 500 mg of Dimethylolpropionic acid for 4 hours under a 2.5 x 2.5 semi-occlusive patch. Upon removal of the patch any residual test material was removed and the test sites were examined for signs of primary irritation at 1, 24, 48 hours and 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14 days. 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. This very slight erythema observed in all animals was fully reversible within 5 days. In this study, Dimethylolpropionic acid is not a dermal irritant.

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 1999 to 07 December 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

GLP compliance:

yes

Specific details on test material used for the study:

- Name of the test material used in the study report: 2,2-Bis(hydroxymethyl)propanoic acid
- Batch no.: SE 8069
- Purity: 99.4 g/100 g (Potentiometric titration)
- Appearance: Solid, white
- Expiry date: not given
- Storage conditions: Room temperature

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 acclimatized 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 temperature and 30 - 70% 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 gm 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 33 gm 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:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects observed

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

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.

Table1: 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:

Category 2 (irritating to eyes) based on GHS criteria

Remarks:

Eye Irritation 2 (H319) according to CLP Regulation 1272/2008 (based on mean irritation, conjunctival redness and chemosis scores >/= 2).

Conclusions:

The authors concluded that the results obtained indicate that 2,2-Bis(hydroxymethyl)propanoic acid is irritating to the eye.

Executive summary:

In a primary eye irritation study (conducted according to OECD TG 405), 0.1 ml of 2,2-Bis(hydroxymethyl)propanoic acid (purity 99.4%) was instilled into the conjunctival sac of 3 young adult Himalayan rabbits (3/males) for 24 hours. The eyes were washed out with tap water 24 hours later. Animals then were observed for 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. In this study, 2,2-Bis(hydroxymethyl)propanoic acid is classified as eye irritant 2 (H319) according to CLP Regulation 1272/2008 (based on mean irritation, conjunctival redness and chemosis scores >/= 2).

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 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 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.