2,2-bis(hydroxymethyl)propionic acid

Endpoint summary

Description of key information

The acute oral LD50 of Bis-MPA (dimethylolpropionic acid) in rats is >2000 mg/kg bw. The acute dermal LD50 of Bis-MPA (dimethylolpropionic acid) in rats in >2000 mg/kg bw. A waiver is proposed for acute inhalation toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

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

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals were male and female Wistar SPF rats, obtained from Velaz Prague. Both males and females weighed 180-220 g. They were acclimatised for 7 days, during which time the health status of the rats was monitored continuously. On arrival, the rats were placed 3 to a cage (same sex groups). Surplus animals were discarded from those with outlying bodyweight. They were housed in Type T-4 cages (Velaz, Prague), cage racks and other equipment were sanitised twice a week. Potable mains tap water was supplied via glass bottles with stainless steel sipper tubes. Standard diet KKZ-P/M (ÚEF SAV, Dobrá Voda) was supplied ad libitum. The study was carried out under SPF conditions. The temperature and relative humidity of the animal rooms were maintained at 22±2°C and 30-70%. The animals were subjected to a 12 hour light: 12 hour dark cycle.

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

A single dose of 2000 mg/kg bw was administered orally

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 rats/sex

Control animals:

no

Details on study design:

The study followed OECD guideline 423. Rats with outlying bodyweights were not used in the study. A single limit dose of 2000 mg/kg bw was administered to 3 male and 3 female rats. Rats were observed for 2 weeks following administration; body weights were recorded on days 1, 7 and 15.

Statistics:

Not applicable.

Preliminary study:

No information available.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality at the limit dose

Mortality:

No mortality occurred.

Clinical signs:

other: Not reported.

Gross pathology:

No findings reported

Other findings:

None reported.

Table 1: Body weight changes

 

	Female Body Weights (g)			Male Body Weights (g)
Animal No.	1	2	3	4	5	6
Day 1	175	180	180	180	175	180
Day 7	185	185	180	185	185	185
Day 15	185	190	185	190	190	195

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of dimethylolpropionic acid in Wistar rats is > 2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study (conducted according to OECD TG 423), groups of 3 male and 3 female Wistar rats were given a single oral dose by gavage of dimethylolpropionic acid in olive oil at the limit dose of 2000 mg/kg bw and observed for 2 weeks. No deaths occurred during the 2 week observation period. The combined acute oral LD50 is >2000 mg/kg bw. There were no treatment related necropsy findings or changes in body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

A modern GLP and guideline-compliant acute oral toxicity study is available for the substance

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study technically not feasible

Justification for data waiving:

other:

Clinical signs:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

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

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals were male and female Wistar SPF rats, obtained from Velaz Prague. Both males and females weighed 180-220 g. They were acclimatised for 7 days, during which time the health status of the rats was monitored continuously. On arrival, group of three rats were placed in one cage (same sex groups). Surplus animals were discarded from those with outlying body weight. They were housed in Type T-4 cages (Velaz, Prague), cage racks and other equipment were sanitised twice a week. Potable mains tap water was supplied via glass bottles with stainless steel sipper tubes. Standard diet KKZ-P/M (ÚEF SAV, Dobrá Voda) was supplied ad libitum.
The study was carried out under SPF conditions. The temperature and relative humidity of the animal rooms were maintained at 22±2°C and 30-70%. The animals were subjected to a 12 hour light: 12 hour dark cycle.

Type of coverage:

not specified

Vehicle:

olive oil

Details on dermal exposure:

The study was carried out according to OECD guideline 402, no further information is available in the report.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 rats/sex

Control animals:

no

Details on study design:

The study followed OECD guideline 402. Rats with outlying body weights were not used in the study. A single limit dose of 2000 mg/kg bw dimethylolpropionic acid in olive oil was applied dermally to 5 male and 5 female rats. Rats were observed for 2 weeks; body weights were recorded on Day 1, 7 and 15.

Statistics:

Not applicable.

Preliminary study:

No information available.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality observed in the study

Mortality:

No mortality occurred

Clinical signs:

other: Not reported

Gross pathology:

Necropsies were not reported

Other findings:

None reported.

Table 1: Body weight changes.

 

	Female Body Weights (g)					Male Body Weights (g)
Animal No.	1	2	3	4	5	6	7	8	9	10
Day 1	180	185	185	180	180	195	200	200	195	205
Day 7	185	195	190	185	185	210	205	205	200	210
Day 15	190	200	195	190	195	215	215	210	210	215

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 of dimethylolpropionic acid in Wistar rats is > 2000 mg/kg bw.

Executive summary:

In an acute dermal toxicity study (conducted according to OECD TG 402), groups of 5 male and 5 female Wistar rats were dermally exposed to Dimethylolpropionic acid in olive oil for at the limit dose of 2000 mg/kg bw. Animals were then observed for 2 weeks. No deaths occurred at the limit dose during this 2 week observation period. There were no treatment related changes in body weight. The acute dermal LD50 of dimethylolpropionic acid is > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

A modern GLP and guideline-compliant acute dermal toxicity study is available for the substance.

Additional information

Acute oral toxicity

The acute oral toxicity of Bis-MPA (dimethylolpropionic acid) was determined in a GLP study conducted according to OECD Guideline 423 (Szokolayova, 2007). The test substance was administered orally by gavage in olive oil to 3 male and 3 female Wistar rats, at the limit dose of 2000 mg/kg bw. No deaths occurred during the 2 week observation period, and all rats gained weight. Gross necropsy did not reveal any treatment-related findings. The acute oral LD50 of Bis-MPA (dimethylolpropionic acid) in Wistar rats is therefore > 2000 mg/kg bw.

 

Acute inhalation toxicity

Bis-MPA (dimethylolpropionic acid) is produced as a fine powder with particle sizes within the inhalable range, in average less than 10% (volume). However the substance is hygroscopic and attempts to generate a respirable atmosphere have failed due to particle clumping resulting in a relatively large particle size and equipment blockage. A waiver is therefore proposed for this endpoint due to the technical difficulties encountered in generating an appropriate atmosphere. The substance is likely to behave in a similar fashion under the normal conditions of use, therefore significant inhalation exposure is not predicted. The substance is of inherently low acute toxicity, as shown by the results of the oral and dermal studies - the combination of low toxicity and low exposure does not raise concerns.

 

Acute dermal toxicity

The acute dermal toxicity of Bis-MPA (dimethylolpropionic acid) was determined in a GLP study conducted according to OECD Guideline 402 (Szokolayova, 2007). The test substance was applied dermally in olive oil to 5 male and 5 female Wistar rats, at the limit dose of 2000 mg/kg. No deaths occurred during the 2 week observation period, and all rats gained weight. The acute dermal LD50 of Bis-MPA (dimethylolpropionic acid) in Wistar rats is therefore > 2000 mg/kg.

Justification for classification or non-classification

No classification for acute toxicity is required, based on the available data, according to Regulation (EC) No 1272/2008.