3-isopropoxypropylamine

Endpoint summary

Description of key information

In acute oral toxicity studies with isopropoxypropylamine, LD50 of 909 and ca. 1050 mg/kg bw were determined in rats. By inhalation exposure of rats to saturated vapors of isopropoxypropylamine generated at 20°C showed 5/6 deaths after exposure for 8 hours, 1/6 death after exposure for 3 hours and 0/12 death after exposure for 1 hour. There is no acute dermal toxicity study on isopropoxypropylamine, but the acute toxicity by dermal route of the analogue substance 3-methoxypropylamine was estimated to be 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

909 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Read across to 3-methoxypropylamine

Additional information

Oral exposure

In a Key study, the acute oral toxicity of 3-isopropoxypropylamine was evaluated in male and female rats according to OECD N°401 guideline (Acute Toxic Standard Method) (Manciaux, 1988). All animals died on day 1 after administration of 2000 mg/kg. They showed hypoactivity, sedation, piloerection, tremors, lateral recumbency and dyspnoea prior to death. After administration of 1000 mg/kg, 2/5 rats showed sedation, tonico-clonical convulsions and lateral recumbency prior to death on day 1. Theses clinical signs were less severe in surviving animals. At 500mg/kg, 1/5 animal showed sedation, piloerection and lateral recumbency and then died on day 2. The oral LD50 of 3-isopropoxypropylamine was 909 mg/kg (417-1755 mg/kg) in female rats with 95% confidence interval limits.

In a supporting study conducted according to an internal BASF, method which is comparable to the OECD Guideline 401 (BASF, 1970a), test groups consisting of 10 animals/sex were treated by single gavage application of an aqueous solution of the isopropoxypropylamine at the dose levels of 168, 336, 672, 840, 1050, 1344 mg/kg bw. 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. The LD50 value was estimated on the basis of the observed mortalities. At 1344 mg/kg, 4 males and 7 females died within 1h, the remaining animals died within 24 h. At 1050 mg/kg, 6 males and 3 females died within 24 h. At dose levels of 1344, 1050 and 840 mg/kg, immediately after application calm behaviour, mouth discharge, exopthalmus, partially slight dyspnoea and ruffled fur were observed. The animals in the highest dose group additionally showed convulsive tremors 30 min post application. The surviving animals showed 24 h post application accelerated respiration, squatting posture and ruffled, partially smeared fur. At 672 and 336 mg/kg, immediately after application calm behaviour, mouth discharge and exopthalmus were observed. On the following days the animals have a calm behaviour, a slightly accelerated respiration and a ruffled fur. At 168 mg/kg, immediately after application calm behaviour and ruffled fur and on the following day calm behaviour were observed. At necropsy, liquid filled intestinal tract were observed in 8 rats treated with 1050 mg/kg. At 336 mg/kg, paleness of kidneys, cortex littered with white-yellowish nodes was observed in one animal. The dermal LD50 was estimated at ca. 1050 mg/kg bw.

Inhalation exposure

In a test to demonstrate the toxicity of an atmosphere saturated with vapours of the volatile components of isopropoxypropylamine at the temperature chosen for vapour generation (20 °C) (BASF, 1970b), 3 rats per sex were exposed sequentially to the vapours, generated by bubbling 200 l/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 1 h, 3 h or 8 h. The documentation of clinical signs was performed over a period of 7 days. During the 3 h exposure, 1/6 animal died within 2 h of exposure and for the 8 h exposure, 3/6 animals died within 4.5 h of exposure and 2/6 further animals died within the end of exposure. Escape attempts, irritation of the mucous membranes and dyspnoea were observed initially. After the 3 and 8 h exposure, convulsions, staggering, corrosion of eyes and noses were also noted. 48 h post exposure in the 8 h exposure group intermittent respiration, respiratory sounds and ruffled fur were noted. All surviving animals gained weight. For the 8 h exposure, bloody nose crusts, lungs filled with blood, corroded snouts, and sodden fur were observed in 5 rats.

Dermal exposure

There is no acute dermal toxicity study on isopropoxypropylamine, but an acute toxicity by dermal route was performed on the analogue substance 3-methoxypropylamine.

The acute toxicity by dermal route of methoxy-3-propylamine was evaluated in rats according to the OECD Guideline No. 402 (Clouzeau, 1992). In a first assay, the test substance was applied in its original form directly to the skin of 10 Sprague-Dawley rats (5 males and 5 females) at a dose level of 2000 mg/kg, at a volume taking into consideration that the specifie gravity (SG) of the test substance was 0.871. In a second assay, the test substance was solubilised in water, prepared on a dry compress at a dose level of 400 mg/kg and then applied to the skin of 10 Sprague-Dawley rats {5 males and 5 females) at a volume of 5 ml/kg. After 24 hours under a semi-occlusive dressing, no residual test substance was observed at removal of the dressing. The animals were checked for clinical signs, mortality and body weight gain for a period of 4 days (2000 mg/kg) or 14 days (400 mg/kg) after the single application of the test substance. A necropsy was performed on each animal sacrificed at the end of the study. At 400 mg/kg, the general behaviour and body weight gain of the animals were not affected by the treatment. No deaths occurred at the dose level of 400 mg/kg. The macroscopic examination revealed no abnormalities in the animals sacrificed at the end of the study. At 2000 mg/kg, 4 females died between days 2 and 4. Cutaneous signs of necrosis and ulceration appeared between days 2 and 5. The animals were sacrificed for humane reasons on day 5. Under these experimental conditions, the LD50 of methoxy- 3-propylamine when administered by dermal route in rats was higher than 400 mg/kg. No signs of toxicity were observed at this dose level. The LD50 was estimated at 2000 mg/kg. In order to comply with ethic and scientific recommendations concerning the LD50, a more precise determination was not necessary

 

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

- According to CLP criteria:

Acute oral category 4, H302: Harmful if swallowed

- According to DSD criteria

Xn, R22, harmful if swallowed