Diisopropylamine

Endpoint summary

Description of key information

The acute toxicity studies in rats with Diisopropylamine (DIPA) determined an oral LD50 of 420 (277-563) mg/kg, a 4-hour inhalation LC50 of 5.35 mg/l and a dermal LD50 higher than 2000 mg/kg and lower than 5000 mg/kg.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline Study

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. Wilmington Massachussets 01887
- Age at study initiation: 9-12 weeks old
- Weight at study initiation: 273-340 g (males) 232-263 g (females)
- Fasting period before study: yes (18 hours)
- Housing: 6/cage during acclimation; 1/cage during study
- Diet (e.g. ad libitum): ad libitum Purina Laboratory Chow 5001
- Water (e.g. ad libitum): ad libitum municipal water
- Acclimation period: 15-22 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24°C (67-76°F)
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Dose-Volume: 10 ml/kg

Doses:

50, 250, 500, 1000 mg/kg

No. of animals per sex per dose:

5 males and 5 females per group except the high dose group (5 males only)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were checked for viability twice daily. Pharmacologic and toxicologic signs were recorded approx. 1, 2 and 4 hours after dosing and daily thereafter. Animals were weighted prefast, post fast (just prior dosing) and on days 7 and 14.
- Necropsy of survivors performed: yes
Gross postmortem examination were performed on all animals.

Statistics:

LD50 and 95% confidence limits were calculated using Miller's method (1944)

Sex:

male/female

Dose descriptor:

LD50

Effect level:

420 mg/kg bw

95% CL:

277 - 563

Sex:

female

Dose descriptor:

LD50

Effect level:

310 mg/kg bw

95% CL:

198 - 422

Sex:

male

Dose descriptor:

LD50

Effect level:

540 mg/kg bw

95% CL:

242 - 838

Mortality:

See the table below

Clinical signs:

other: Signs seen during the 24 hours after dosing in groups receiving doses of 250, 500 and 1000 mg/kg included ataxia and/or tremors, hypoactivity, wet rales, food consumption decrease, dyspnea, hypopnea and ocular, oral and nasal discharge. Some animals exhi

Gross pathology:

In animals found dead: changes in lungs and gastrointestinal tract.
Some animals exhibited changes in the stomach and intestine which were suggestive of an irritant effect (presence of red or black fluid, discoloration of walls).
Some animals were also noted to have red fluid in hte body cavity and urinary bladder.
One animal in the 500 mg/kg group which survived until study termination had adhesions of the stomach to the liver and abdominal walls.

Preliminary study mortality results
Dose level (mg/kg)	Mortality
	Male	Female
80	1/1	1/1
120	1/1	1/1
170	1/1	1/1
250	1/1	1/1
350	1/1	1/1
500	0/1	1/1
710	1/1	1/1
1000	1/1	1/1
1420	1/1	1/1

Definitive study

Dose level (mg/kg)	Mortality			Time of death
	Male	Female	Total
50	0/5	0/5	0/10	-
250	0/5	1/5	1/10	day 8
500	2/5	5/5	7/10	3hours, day 6
1000	5/5	-	5/5	1-3 hours

Interpretation of results:

harmful

Remarks:

Migrated information Toxicity Category IV Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008

Conclusions:

Under these experimental conditions, rat oral LD50 is 420mg/kg.

Executive summary:

The Acute oral toxicity of Diisopropylamine (DIPA) was evaluated in rats according to the EPA OPP 81-1 guideline. After a preliminary dose range-finding test, groups of 5 male and 5 female Sprague Dawley rats (except the high dose group, constituted of 5 males only) were given a single oral dose of DIPA at doses of 0, 50, 250, 500, 1000 mg/kg. Following treatment, rats were observed daily and weighted weekly. A gross necropsy examination was performed at the time of scheduled euthanasia (Day 14).

All animals died on day 1 after administration of 1000 mg/kg (5 males). 5/5 females and 2/5 males died after treatment with 500 mg/kg. 1/5 female only died in the 250 mg/kg group and no mortality was observed in the low dose group (50 mg/kg)

Signs seen during the 24 hours after dosing in groups receiving doses of 250, 500 and 1000 mg/kg included ataxia and/or tremors, hypoactivity, wet rales, food consumption decrease, dyspnea, hypopnea and ocular, oral and nasal discharge. Some animals exhibited decreased food consumption and/or emiaciation for up to 8 days after dosing. Animals in the 50 mg/kg group were generally free of abnormalities.

Under these experimental conditions, the oral LD50 of DIPA is 420 mg/kg (277-563 mg/kg) in Sprague Dawley rats with 95% confidence interval limits.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

420 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable study report which meets generally accepted scientific principles. Study is well documented, before OECD TG and GLP existed. The study is fully sufficient for endpoint evaluation.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Remarks:

GLP was not compulsory at the time the study was conducted

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: WIGA, Sulzfeld, Germany
- Weight at study initiation: 185 +/- 15 g
- Diet: Herilan MRH (H. Eggersmann KG, Rinteln/Weser, Germany), ad libitum
- Water: tap water, ad libitum

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The exposure apparatus was a whole body inhalation system:
An infusion pump (Unita I, B. Braun, Melsungen) was used to transport a constant amount of the test material to an evaporator, which had a temperature of 36 °C. The arising vapours were mixed with a stream of fresh air and then poured into an inhalation chamber with a volume of ca. 180 l. After a prestreaming period of ca. 20 minutes the animals were transferred inward by using two locks.
The animals were exposed to the inhalation mixture for 4 hours.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Analytic verification of the test atmosphere concentrations was conducted with a HP5840A gas chromatograph. The samples were taken near the noses of the animals, 1 l per min was taken out using a 4 mm diameter sample probe

Duration of exposure:

4 h

Concentrations:

nominal: 14.3, 8.6, 4.3, 1.1 mg/l (Group 1, 2, 3, 4)
analytic: 9.1, 5.3, 3.2, 0.86 mg/l

No. of animals per sex per dose:

10 animals per sex per dose.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: at study initiation, on day 7 and 14
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, body weight,organ weights, histopathology

Statistics:

Probit-Analysis according to Finney (p. 1-150, Cambridge University Press, 1971)

Sex:

male/female

Dose descriptor:

LC50

Effect level:

5.35 mg/L air (analytical)

Exp. duration:

4 h

Mortality:

In group 1, 10/10 females and 8/10 males died, in group 2, 7/10 males and 3/10 females died, in group 3, 2/10 males and 0/10 females died and in group 4, 0/10 males and 0/10 females died. No mortality was seen in the control group.
The death of the animals occured between day 1 to day 7 after exposure to the test material.

Clinical signs:

other: All animals in all dose groups showed clinical signs of toxicity: In the groups 1 to 3 closed eyelids, aqueous to red coloured nasal discharge, corneal opacity, dyspnea, spastic walk, a crouched down position, tremor, unkempt fur and ventral position was

Body weight:

In the male dose groups a clearly reduced body weight gain was recorded when compared to control animals. For the females in groups 2 and 3 the same finding was seen, whereas the the body weight in group 3 was widely adapted to the controls.
The body weights of group 4 did not differ compared to the control group.

For further details see table 1.

Gross pathology:

Animals that died during the study:
In the groups 1 to 3 an acute dilatation in the heart was seen as well as an acute congestional hyperemia was seen, in the lung an acute exhalation was observed and in the liver there were sporadic peripheral lobe structures.

Table 1: Absolute body weights of male and female rats:

Mean body weight	day 0		day 7		day 14
	male	female	male	female	male	female
Group 1 weight (g) / number of animals	186 / 10	180 / 10	167 / 10	- / -	190 / 2	- / -
Group 2 weight (g) / number of animals	177 / 10	173 / 10	173 / 3	143 / 7	218 / 3	169 / 7
Group 3 weight (g) / number of animals	181 / 10	181 / 10	168 / 8	174 / 10	230 / 8	204 / 10
Group 4 weight (g) / number of animals	178 / 10	170 / 10	198 / 10	190 / 10	226 / 10	199 / 10
Control Group weight (g) / number of animals	188 / 10	178 / 10	223 / 10	198 / 10	264 / 10	208 / 10

Interpretation of results:

toxic

Remarks:

Migrated information Toxicity Category III Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions of this test for acute toxicity after inhalation, a LC50 of 5.35 mg/l air was obtained for male and female rats after 4 hours of whole body exposure to vapour containing DIPA.

Executive summary:

The acute inhalation toxicity of Diisopropylamine (DIPA) was evaluated in a 4-hour, single-exposure study in rats according to a protocol similar to the OECD Guideline 403.

DIPA was administered to a single group of five male and five female Sprague Dawley rats via whole-body vapor exposure at nominal concentrations of 14.3, 8.6, 4.3, 1.1 mg/l (Group 1, 2, 3, 4, respectively), leading to analytic concentrations of 9.1, 5.3, 3.2, 0.86 mg/l.

Mortality, clinical observations for clinical signs and body weight changes were evaluated over a 14-day observation period. All animals were subjected to a gross necropsy.

In group 1, 10/10 females and 8/10 males died, in group 2, 7/10 males and 3/10 females died, in group 3, 2/10 males and 0/10 females died and in group 4, 0/10 males and 0/10 females died. No mortality was seen in the control group. The death of the animals occurred between day 1 to day 7 after exposure to DIPA.

All animals in all dose groups showed clinical signs of toxicity: In the groups 1 to 3 closed eyelids, aqueous to red colored nasal discharge, corneal opacity, dyspnea, spastic walk, a crouched down position, tremor, unkempt fur and ventral position was observed. In group 4 closed eyelids, snout-wiping and intermittent breath was seen. After 2 days there were no more symptoms recorded.

In the male dose groups a clearly reduced body weight gain was recorded when compared to control animals. For the females in groups 2 and 3 the same finding was seen, whereas the body weight in group 3 was widely adapted to the controls. The body weights of group 4 did not differ compared to the control group.

In the groups 1 to 3 an acute dilatation in the heart was seen as well as an acute congestional hyperemia was seen, in the lung an acute exhalation was observed and in the liver there were sporadic peripheral lobe structures.

Based on the results of this study, the LC50 of DIPA was calculated to be 5.35mg/l when male and female rats were exposed whole-body to a vapor of DIPA for a single, 4-hour period.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

5 350 mg/m³ air

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable study report which meets generally accepted scientific principles. Study is well documented, before OECD TG and GLP existed. The study is fully sufficient for endpoint evaluation.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Some details were not reported including the age of animals as well as further details on test animals and environmental conditions. No information was avaliable in terms of the type of coverage used.

GLP compliance:

no

Remarks:

; GLP was not compulsory at the time the study was conducted.

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Wiga
- Average weight at study initiation: males ca. 150 g; females ca. 130 g
- Diet: Ssniff - Herilan MRH

Type of coverage:

not specified

Vehicle:

other: no vehicle was used, except for 400 mg/kg bw dose (50 % olive oil)

Details on dermal exposure:

TEST MATERIAL
- Concentration (if solution): 100 % of the test material was applied, except for the 400 mg/kg bw dose: here the test material was diluted in 50 % olive oil
- Constant volume or concentration used: no

Duration of exposure:

14 days

Doses:

5000, 2000, 1000 and 400 mg/kg bw.

No. of animals per sex per dose:

2000, 1000 and 400 mg/kg bw: 5 animals per sex per dose
5000 mg/kg bw: 3 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 1h, day 1, then daily on working days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 - < 5 000 mg/kg bw

Mortality:

5000 mg/kg bw: 3/3 males and 3/3 females died after 24 hours.
2000 mg/kg bw: 0/5 males and 0/5 females died within 14 days.
1000 mg/kg bw: 0/5 males and 0/5 females died within 14 days.
400 mg/kg bw: 0/5 males and 0/5 females died within 14 days.

Clinical signs:

other: 5000 mg/kg bw: grey to green soft necroses were seen in all animals after 24 hours. 2000 mg/kg bw: After application of the test material, all animals screamed and slight apathy was observed during 12 further days. After 24 hours, red discharge in the eye

Gross pathology:

5000 mg/kg bw: cadaverous
2000 mg/kg bw: the organs were without any findings.
1000 mg/kg bw: the organs were without any findings.
400 mg/kg bw: the organs were without any findings.

Other findings:

Necroses were seen in all animals on the application sites from 24 h after application of the test material until the end of the observation period.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008

Executive summary:

The acute dermal toxicity of Diisopropylamine (DIPA) was evaluated in rats according to a protocol similar to the OECD N° 402 guideline. DIPA was applied to the skin of groups of 5 male and 5 female Sprague Dawley rats at doses of 2000, 1000 and 400 mg/kg and 3 male and 3 female Sprague Dawley rats at 5000 mg/kg. Animals were observed 1 hour after application and then daily for 14 days.

Necroses were seen in all animals on the application sites from 24 h after application of the test material until the end of the observation period.

At 5000 mg/kg, 3/3 males and 3/3 females died after 24 hours.

At 2000 mg/kg, 0/5 males and 0/5 females died within 14 days.

At 1000 mg/kg, 0/5 males and 0/5 females died within 14 days.

At 400 mg/kg, 0/5 males and 0/5 females died within 14 days.

At 5000 mg/kg, grey to green soft necroses were seen in all animals after 24 hours.

After application of 2000 mg/kg, all animals screamed and slight apathy was observed during 12 further days. After 24 hours, red discharge in the eyes of the animals was observed.

From 24 hours after application of 1000 mg/kg of DIPA until day 14, the animals appeared lively.

From 24 hours after application of 400 mg/kg of DIPA until day 14, the animals appeared lively.

At 5000 mg/kg, organs looked cadaverous. At 2000 mg/kg and below, the organs were without any findings.

Under these experimental conditions, the dermal LD50 of DIPA is higher than 2000 mg/kg and lower than 5000 mg/kg in Sprague Dawley rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity

The Acute oral toxicity of Diisopropylamine (DIPA) was evaluated in rats according to the EPA OPP 81-1 guideline (Auletta, 1985). After a preliminary dose range-finding test, groups of 5 male and 5 female Sprague Dawley rats (except the high dose group, constituted of 5 males only) were given a single oral dose of DIPA at doses of 0, 50, 250, 500, 1000 mg/kg. Following treatment, rats were observed daily and weighted weekly. A gross necropsy examination was performed at the time of scheduled euthanasia (Day 14). All animals died on day 1 after administration of 1000 mg/kg (5 males). 5/5 females and 2/5 males died after treatment with 500 mg/kg. 1/5 female only died in the 250 mg/kg group and no mortality was observed in the low dose group (50 mg/kg). Signs seen during the 24 hours after dosing in groups receiving doses of 250, 500 and 1000 mg/kg included ataxia and/or tremors, hypoactivity, wet rales, food consumption decrease, dyspnea, hypopnea and ocular, oral and nasal discharge. Some animals exhibited decreased food consumption and/or emiaciation for up to 8 days after dosing. Animals in the 50 mg/kg group were generally free of abnormalities. The oral LD50 of DIPA is 420 mg/kg (277-563 mg/kg) in Sprague Dawley rats with 95% confidence interval limits.

Smyth (1954) supports this result in an acute oral toxicity study realised in male rat (range-finding test). One group of 5 Carworth-Wistar rats was treated once orally and then observed during 14days. The oral LD50 of DIPA is 770mg/kg (610-940mg/kg) in male.

Acute inhalation toxicity

The acute inhalation toxicity of Diisopropylamine (DIPA) was evaluated in a 4-hour, single-exposure study in rats according to a protocol similar to the OECD Guideline 403 (BASF 1979). DIPA was administered as vapor to a single group of five male and five female Sprague Dawley rats via whole-body vapor exposure at nominal concentrations of 14.3, 8.6, 4.3, 1.1 mg/l (Group 1, 2, 3, 4, respectively), leading to analytic concentrations of 9.1, 5.3, 3.2, 0.86 mg/l. Mortality, clinical observations for clinical signs and body weight changes were evaluated over a 14-day observation period. All animals were subjected to a gross necropsy. In group 1, 10/10 females and 8/10 males died, in group 2, 7/10 males and 3/10 females died, in group 3, 2/10 males and 0/10 females died and in group 4, 0/10 males and 0/10 females died. No mortality was seen in the control group. The death of the animals occurred between day 1 to day 7 after exposure to DIPA. The LC50 of DIPA was calculated to be 5.35 mg/l when male and female rats were exposed whole-body to a vapor of DIPA for a single, 4-hour period. In males only, the LC50 was calculated at 4.76 mg/l.

Smyth (1954) exposed 6 Carworth-Wistar rats to 1439 mg/m3 for 4 hours and observed animals for 14 days. Two deaths were recorded and the LC50 was determined as above 1439 mg/m3.

Groups of 10 rats (five of each sex) were exposed to 961, 1760, and 5,120 ppm of Diisopropylamine vapor for 30 min (Price et al., 1979). Three separate control groups were used. The rats were observed for 14 days. Necropsy was performed on the animals either at time of death or when they were killed at the end of the study. No deaths occurred in the groups exposed to 961 ppm Diisopropylamine. Signs of toxicity included nasal/lacrymal irritation, which progressed to dyspnea, generalized depressed activity, and eyelid closure by 15 min; these symptoms persisted for 4 h. Other significant changes were reduced body weights in the female rats and increased weight of the lungs. No significant histopathological changes were found. Animals exposed to 1,760 ppm of Diisopropylamine had the same signs oftoxicity as those exposed to 961 ppm. The body weights of the rats were significantly lower than those of controls, and heart weights of the male rats were also significantlylower. One rat died either during or a few minutes after exposure and had pulmonary congestion, inflammation, hemorrhage, and edema.. No other lesions were observed in the other animal. All rats exposed to 5,120 ppm of Diisopropylamine died during exposure with apparent respiratory distress. At histopathological evaluation, the rats had degeneration of the renal proximal tubular epithelium and bronchial epithelium. The calculated LC50 was 2568 ppm.

In a earlier study realised by BASF in 1977, rats (3/group) were exposed to saturated atmosphere for a 3-min period for a Inhalation hazard test. All animals exposed to the test material died. 11/12 animals died within the experiment during exposure, 1 remaining male died 24 hours later. The LC100 for acute toxicity after inhalation of the test material to male and female rats was 495 mg/l air.

The nasal irritation produced by Diisopropylamine was studied using male Swiss OF₁mice (Gagnaire et al., 1989). Groups of six mice each were exposed to concentrations of Diisopropylamine ranging from 88 to 351 ppm in air for 15 min to determine the concentration at which the respiratory rate was decreased by 50% (RD₅₀). The head of each mouse was isolated in an inhalation chamber, and the breathing frequency was measured with a pressure transducer before and during the exposure period. The RD₅₀for Diisopropylamine was 161 ppm, and maximal effects were observed within 0.5 to 1 min.The authors also exposed groups of mice to 29 to 207 ppm of Diisopropylamine via tracheal cannulation for 120 min. The concentration that caused a 50% decrease in respiratory rate via this route (RD₅₀TC) was compared with the RD50 (161 ppm). The RD₅₀TC was 102 ppm, and maximal effects were observed after 120 min of exposure. The authors noted that the RD₅₀TC/RD₅₀ratio was less than 1 (0.6), which indicated that Diisopropylamine primarily caused lower airway effects.

Acute dermal toxicity

The acute dermal toxicity of Diisopropylamine (DIPA) was evaluated in rats according to a protocol similar to the OECD N° 402 guideline (BASF AG, 1977). DIPA was applied to the skin of groups of 5 male and 5 female Sprague Dawley rats at doses of 2000, 1000 and 400 mg/kg and 3 male and 3 female Sprague Dawley rats at 5000 mg/kg. Animals were observed 1 hour after application and then daily for 14 days. Necroses were seen in all animals on the application sites from 24 h after application of the test material until the end of the observation period. At 5000 mg/kg, 3/3 males and 3/3 females died after 24 hours. At 2000 mg/kg, 0/5 males and 0/5 females died within 14 days. At 1000 mg/kg, 0/5 males and 0/5 females died within 14 days. At 400 mg/kg, 0/5 males and 0/5 females died within 14 days. The dermal LD50 of DIPA is higher than 2000 mg/kg and lower than 5000 mg/kg in Sprague Dawley rats.

Justification for selection of acute toxicity – oral endpoint
Key study

Justification for selection of acute toxicity – inhalation endpoint
Key study

Justification for selection of acute toxicity – dermal endpoint
Key study

Justification for classification or non-classification

Acute oral toxicity:

The oral LD₅₀ of DIPA was 420 mg/kg in rats. In accordance with Regulation (EC) No 1272/2008 DIPA shall be classified as Acute Tox. 4 (Hazard statement: H302; Harmful if swallowed) and in accordance with Annex VI of Commission Directive 2001/59/EC, DIPA shall be classified as being harmful if swallowed (R22).

Acute inhalation toxicity:

The LC₅₀ of DIPA was 5.35 mg/L. On the basis of this study and in accordance with Regulation (EC) No 1272/2008 DIPA shall be classified as Acute Tox. 3 (Hazard statement: H331; Toxic if inhaled) and in accordance with Annex VI of Commission Directive 2001/59/EC, DIPA shall be classified as being harmful by inhalation (R20).

Acute dermal toxicity:

The percutaneous LD₀ of DIPA was greater than 2000 mg/kg in rats. On this basis and in accordance with Regulation (EC) No 1272/2008 and in accordance with Annex VI of Commission Directive 2001/59/EC, DIPA shall not be classified with respect to acute dermal toxicity.