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Description of key information

Acute toxicity data indicate low toxicity: In rats the oral LD50 was 2813 mg/kg bw, in rabbits the dermal LD50 was approximately 1851 mg/kg bw. An acute inhalation according to OECD403 is not available, but the endpoint is assessed from the available toxicological data in rats and mice (WoE). An acute inhalatory exposure study in rats for 6 hours at a concentration of 1126 ppm (3460 mg/m3) failed to cause any deaths in rats (LC50 was not determined).

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:
06. Oct 1965 - 25. Oct 1965
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
conducted according to an internal BASF method
Deviations:
not applicable
Principles of method if other than guideline:
BASF-Test: The study was conducted according to an internal BASF method which in principle is comparable to the OECD Guideline 401.
A test group consisting of 5 animals/sex was treated by single gavage application with an aqueous solution of the test substance. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy.
GLP compliance:
no
Test type:
other: BASF-test
Limit test:
no
Specific details on test material used for the study:
- purity: 98%
Species:
rat
Strain:
other: US-rats
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: male: 142-220 g (mean); female: 136-194 g (mean)
Route of administration:
oral: gavage
Vehicle:
water
Doses:
0.2, 1.6, 2.0, 2.5, 3.2, 6.4 mL/kg bw (194, 1552, 1940, 2425, 3104, 6208 mg/kg bw ; conversion in mg/kg bw was calculated from the original ml/kg values by using the density of 0.97g/cm3 (according to the BASF MSDS).
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, histopathology
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 813 mg/kg bw
Remarks on result:
other: The LD50 was calculated from the original mL/kg values by using the density of 0.97g/cm3
Mortality:
See details in table 1 on any other information.
Clinical signs:
After the application the high dose animals showed restlessness, stagger, creep, slight abdominal position, anemia and mouth discharge. At all dose groups compulsive chewing, dyspnoea and apathy were observed. In the middle groups also tonic-clonic convulsions were noted.
Exitus occurred overnight. The surviving animals recovered only slowly and showed apathy, dyspnoea, partly slight stagger and decelerated motion
Body weight:
no data
Gross pathology:
6208 mg/kg: red discoloration of abdominal viscus.
3104 mg/kg: 2 animals showed reddish livid discoloration of the abdominal viscus.
2425 mg/kg: 2 animals showed irritation of the bowel and 1 animal dilatation of the stomach.
1940 mg/kg: 1 animal showed bronchitis and bronchiectasia.
1557 mg/kg: no abnormalities.
194 mg/kg: 2 animals showed bronchitis and bronchiectasia.
Other findings:
The test substance caused systemic toxicity, including mortality, after a single ingestion.

Table 1: Mortality observed in animals during the study.

Dose (mg/kg bw)  Conc.(%) 1h 24 h 48 h 7 days 14 days                
  6208  30  0/10  10/10  10/10  10/10  10/10                
  3104  30  1/10  7/10  7/10  7/10  -                
  2425  20  0/10  2/10  2/10  2/10  2/10                
  1940  20  0/10  1/10  1/10  1/10  1/10                
  1557  20  0/10  0/10  0/10  0/10  0/10                
194  2  0/10  0/10  0/10  0/10  0/10              

The 3 surviving animals of the 3104 mg/kg bw group were sacrificed on day 7.

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance caused deaths from doses of 1,940 mg/kg bw to 6,208 mg/kg bw. More than half of the animals dies at doses of 3,04 mg/kg bw and 6,208 mg/kg bw.
Based on the LD50 = 2,813 mg/kg bw a classification according to GHS within REACH is not met. However, based on the GHS UN, a classification for Cat. 5 for acute toxicity is reasonable.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 813 mg/kg bw

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
The exposure period is longer than required by the guideline. This can be regarded as a worst-case scenario.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals and environmental conditions:
No data
Route of administration:
inhalation: aerosol
Duration of exposure:
6 h
Concentrations:
Nominal concentration 1126 ppm (3460 mg/m3)
No. of animals per sex per dose:
6
Details on study design:
- 14-day observation period
- Examinations: mortality, clinical signs, body weight (frequency not indicated); macroscopy
Sex:
male
Dose descriptor:
LC50
Effect level:
> 3 460 mg/m³ air
Exp. duration:
6 h
Mortality:
no mortality occurred
Clinical signs:
other: no adverse effects
Body weight:
no treatment related effects
Gross pathology:
slightly enlarged livers (2/6)
Interpretation of results:
GHS criteria not met
Conclusions:
The LC50 is > 1126 ppm (3460 mg/m3) under these test conditions.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
3 460 mg/m³

Acute toxicity: via dermal route

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Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Principles of method if other than guideline:
no further details
GLP compliance:
no
Test type:
other: acute method, no further details
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Vehicle:
not specified
Duration of exposure:
2 weeks
Doses:
630 - 5000 mg/kg
No. of animals per sex per dose:
no data
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
1 851 mg/kg bw
Mortality:
Mortality was observed in animals but no detailed information are given.
Clinical signs:
Marked redness, moderate swelling, and marked necrosis of the skin were observed.
At all doses, rabbits were lethargic. At doses of 630 and 1300 mg/kg, anorexia was observed, and at a dose of 1300 mg/kg, diarrhea was observed.
Gross pathology:
At necropsy at the end of a 2-week observation period, no treatment-related changes were noted.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the LD50 value and in combination with the observed clinical effects in animal, the substance is suggested to be of low dermal acute toxicity.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 851 mg/kg bw

Additional information

Oral toxicity

In an acute oral toxicity study, comparable to OECD TG 401, US-rats (5/sex/dose) were administered MIPA at 194-6208 mg/kg bw by single dose (gavage) followed by a 14-days observation period. Clinical signs included restlessness, stagger, creep, slight abdominal position, anemia, mouth discharge, compulsive chewing, dyspnoea, apathy, tonic-clonic convulsions, and overnight exitus. Surviving animals recovered slowly and showed apathy, dyspnoea, partly slight stagger and decelerated motion. Findings at necropsy included red discoloration of abdominal viscus (6208 mg/kg bw dose group), reddish livid discoloration of the abdominal viscus (at 3104 mg/kg bw), bowel irritation and dilation of the stomach (at 2425 mg/kg bw), bronchitis, and bronchiectasia. The LD50 was 2813 mg/kg bw.

In a second study, 6 male CDF albino rats were orally gavaged with test substance given in the vehicle corn oil at doses of 500, 2000, 3500 mg/kg. The observation period was 2 weeks. Examination parameters were mortality, clinical signs, body weight and macroscopically observations. Lethargy, diarrhea and rough hair coats were observed in all rats. One death occurred in the 2000 mg/kg exposure group and all animals died in the 3500 mg/kg exposure group. There were no adverse effects observed for animal body weights or for pathological observations.

Inhalation toxicity

Due to its relatively low volatility, there is a lack of data documenting the acute inhalation toxicity. Hence, the endpoint is assessed in a weight of evidence approach from the available toxicological data. According to REACH annex XI, section 1 a testing does not appear scientifically necessary, using the available toxicological data with MIPA.

One report describes a study with Fischer F344 rats that inhaled 1126 ppm (3460 mg/m3) of the test substance ad an aerosol for 6 hours with a 14 day observation period. There were no animals found dead and no clinical effects were described. In 2/6 animals, only slightly enlarged livers were observed at the end of the study period. Deficiencies in the data entry contradict the approach of a key study and in the weight of evidence approach, two further studies are consulted. One report stated that whole-body exposure of rats to a saturated MIPA atmosphere (concentration not given) at 20°C for 8 hours failed to cause any deaths, therefore no LC50 value has been determined for this compound. Besides, neither clinical nor pathological effects were observed during the study. In a third study on respiratory irritation, Swiss webster mice were exposed to an aerosol with concentrations of 230 to 1005 mg/m3MIPA. The 3-hour exposure caused sensory irritation (immediate onset) and little pulmonary irritation (delayed onset). No mortality was observed. Post-exposure recovery of the breathing frequency was moderate to good.

Dermal toxicity

In an acute percutaneous absorption test in rabbits, MIPA was applied at doses of 630 - 5000 mg/kg bw. Marked redness, moderate swelling, and marked necrosis of the skin were observed. At all doses, rabbits were lethargic. At doses of 630 and 1300 mg/kg bw, anorexia was observed, and at a dose of 1300 mg/kg bw, diarrhea was observed. At necropsy at the end of a 2-week observation period, no treatment-related changes were noted. The LD50 was 1851 mg/kg bw.

Justification for classification or non-classification

The available experimental test data for acute oral and inhalation toxicity studies are reliable and suitable for classification purposes under Regulation 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776. As a result the substance is not considered to be classified for oral and inhalatory acute toxicity under Regulation (EC) No. 1272/2008.

The limited available dermal acute toxicity data warrants classification with Cat. 4; H312 according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.