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Description of key information

The acute oral LD50 of dimethylolpropionic acid in rats is >2000 mg/kg bw. The acute dermal LD50 of 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 to 18 June 2007
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Recent GLP guideline compliant study, reported in summary form only
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
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
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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: unspecified
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:
Not reported.
Body weight:
All rats gained weight during the 2 week observation period (Table 1).
Gross pathology:
No findings reported
Other findings:
None reported.

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:
Toxicity Category V
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of dimethylpropionic acid in Wistar rats is > 2000 mg/kg bw.
Executive summary:

Dimethylolpropionic acid 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 treatmnet-related findings. The acute oral LD50 of dimethylpropionic acid in Wistar rats is therefore > 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
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

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:
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 only
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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.
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.
Duration of exposure:
Not reported.
Doses:
2000 mg/kg
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 bodyweights 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:
Not reported
Body weight:
All rats gained weight throughout the observation period (Table 1).
Gross pathology:
Necropsies were not reported
Other findings:
None reported.

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:
Toxicity Category V
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 of dimethylolpropionic acid in Wistar rats is > 2000 mg/kg bw.
Executive summary:

Dimethylolpropionic acid was applied dermally in olive oil to 5 male and 5 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. The acute dermal LD50 of dimethylpropionic acid in Wistar rats is therefore > 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
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 dimethylolpropionic acid (Bis-MPA) 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 dimethylolpropionic acid in Wistar rats is therefore > 2000 mg/kg bw.

Acute inhalation toxicity

Bis-MPA 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 esposure does not raise concerns

Acute dermal toxicity

The acute dermal toxicity of dimethylpropionic 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 LD50of dimethylpropionic acid in Wistar rats is therefore > 2000 mg/kg.


Justification for selection of acute toxicity – oral endpoint
Only study available for this endpoint

Justification for classification or non-classification

No classification for acute toxicity is required, based on the available data, according to EEC Council Directive 79/831/EEC Annex VI, Part II (D) as described in Commission Directive 93/21/EEC or Regulation (EC) No 1272/2008.