Pyrrolidine

Endpoint summary

Description of key information

Acute oral toxicity:
In an acute oral toxicity study performed similar to OECD Guideline 401, the LD50 for male and female rats after oral application was determined to be 430 mg/kg bw.
Acute inhalation toxicity: 
In the key acute inhalation study (BASF 83/123, 1985) an LC50 of 11.7 mg/L for both sexes combined (confidence interval 10.6 - 12.9) was determined.
Acute dermal toxicity:
Pyrrolidine was found to be corrrosive to the skin, therefore no testing is required for toxicity via the dermal route according to (EC) Regulation No 1907/2006.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

430 mg/kg bw

Quality of whole database:

Three studies are available that were conducted before GLP principles and OECD guidelines were in place. Several doses were studied in a limited number of animals, all studies have a reliability 2. Next to a rat study, two studies are available in which respectively cats and rabbits are used. Toxicity data of the three available studies are in the same range.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

11 700 mg/m³

Quality of whole database:

Four studies are available, not performed under GLP principles and OECD guidelines. Studies are however valuable since they were performed comparable to current OECD guidelines and have a Klimisch score 2. The results from the key study are in agreement with the other studies.

Acute toxicity: via dermal route

Endpoint conclusion

Quality of whole database:

Two studies are available with Klimisch score 4. In both studies severe skin effects are recorded (necrosis).

Additional information

Acute oral toxicity:

In principle, the methods described in OECD Guideline 401 were used in the key study (BASF AG IX/409 with rats). Several groups of rats were treated simultaneously by gavage with preparations of the test substance in water. The concentrations of these preparations were used to achieve comparable volumes per kg body weight. Group-wise documentation of clinical signs was performed over the 7-day study period. The following clinical signs were observed: accelerated respiration, hindered respiration, latero-abdominal position, apathy, flaccid tonus, bloody crust formation at noses and eyes, and no food intake for several days after treatment. At necropsy, the following observations were made in deceased animals: chemical burns to the stomach and duodenum, strongly injected gastro-intestinal vessels, focal pneumonia, hemothorax, and fragile, thickened stomach wall, partly conjoined with the peritoneum. The LD50 for male and female rats after oral application was determined to be 430 mg/kg bw.

In a study with cats, several groups of cats were treated simultaneously by gavage with preparations of the test substance in water at 86, 172, 430, and 859 mg/kg bw. Zero out of two animals died in the 86 mg/kg bw group died. In the 172 mg/kg bw group one out of two females was sacrificed in a moribund state on study day 8, one out of two males died four days after treatment. In the 430 mg/kg bw group only one male animal was treated. This animal was sacrificed in a moribund state on study day 8. In the 859 mg/kg bw group only one female animal was treated. This animal died 5 days after treatment. An LD50 was not determined in this study.

In a study with rabbits, several groups of rabbits were treated simultaneously by gavage with preparations of the test substance in water at 86, 172, and 430 mg/kg bw. No animals of the 86 mg/kg bw group died. In the 172 mg/kg bw group two out of two females died within one hour and 2 days after treatment, zero out of two males died in this group. In the 430 mg/kg bw group the only one female animal was treated. This animal died within one hour after treatment. An LD50 was not determined in this study.

Acute inhalation toxicity:

In the key acute inhalation study (BASF 83/123, 1985) four vapour concentrations of the test substance in the range of 8.9 -15.6 mg/L were tested in 10 Wistar rats per sex and concentration group using 4-hour exposures. The concentrations were determined analytically by gas chromatography and the effectiveness of vapor generation analytical concentration/nominal concentrations was about 50%. The study resulted in a LC50 of 11.7 mg/L for both sexes combined (confidence interval 10.6 - 12.9). The observed clinical signs and necropsy findings can be attributed to the corrosive property of the test item.

In a supporting acute inhalation study (BASF 77/699, 1979) a single vapour concentration of 4.54 mg/L of the test substance was tested in 10 Spraque Dawley rats per sex. The concentration was determined analytically by gas chromatography and the effectiveness of vapor generation analytical concentration/nominal concentration was about 66%. The exposure duration was 4 hours. No lethality occurred in this study (LC0 = 4.54 mg/L).

An inhalation hazard test with rats (BASF 77/699, 1979) using saturated vapor concentration at 20°C was performed. The mean nominal concentration of the test substance was about 178 mg/L. The nominal concentration is in good agreement with the saturated vapor concentration estimated from the vapor pressure of this substance. Four out of twelve animals died after an exposure period of three minutes (mortality rate 33%). Eight out of twelve animals died after an exposure period of five minutes (mortality rate 66%).

An inhalation hazard test with rats (BASF IX/409, 1959) using saturated vapor concentration at 20°C was performed. The mean nominal concentration of the test substance was about 144 mg/L. The nominal concentration is in good agreement with the saturated vapor concentration estimated from the vapor pressure of this substance. Four out of six animals died after an exposure period of two minutes (mortality rate 67%). Six out of six animals died after an exposure period of eight minutes (mortality rate 100%).

Acute dermal toxicity:

One study is available with a Klimisch score 4 (performed according to OECD guideline, but not according to GLP principles). In this study, two exposed and one control rabbit suffered from diarrhoea and died. It cannot be excluded that the health status of the other test animals was affected as well. Animals in highest dose group (0.7 ml/kg bw) had to be killed because of local toxicity (bleeding).

In an acute dermal toxicity study performed as a non-GLP study equivalent or similar to OECD Guideline, five Vienna White rabbits per sex were dermally exposed (clipped skin of the back and flanks) to the undiluted test item for 24 hours at 200 mg/kg body weight with an occlusive coverage (BASF 77/699, 1979). After the exposure period the test item was removed by washing. The animals were then observed for 8 days. No mortality occurred. No treatment related clinical signs or necropsy findings were observed. The acute dermal LD50 of the test item in male and female rabbits was determined to be > 200 mg/kg body weight.

Acute toxicity after intraperitoneal exposure:

In this study, the test substance was injected into the peritoneal cavity of young adult laboratory mice. Several groups of male and female mice were treated simultaneously with preparations of the test substance in water in a dose range of 23 – 1374 mg/kg bw. The concentrations of these preparations were used to achieve comparable volumes per kg body weight. Group-wise documentation of clinical signs was performed over the 7 day study period. Body weight was determined before the start of the study only, as it was needed for determination of dose. The LD50 was determined to be 30 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Study conducted with rats, and the only study in which the number of animals was sufficient to calculate an LD50.

Justification for selection of acute toxicity – inhalation endpoint
In this study an LC50 in rats was calculated.

Justification for selection of acute toxicity – dermal endpoint
Since pyrrolidine was found to be corrrosive to the skin, no testing is required for toxicity via the dermal route according to (EC) Regulation No 1907/2006.

Justification for classification or non-classification

The LD50 for female rats after oral application was determined to be 430 mg/ kg bw, therefore pyrrolidine is classified in category 4 for oral toxicity according to regulation (EC) No 1272/2008.

The inhalation LC50 of pyrrolidine was found to be 11.7 mg/L, therefore this substance is classified in category 4 for inhalation toxicity according to regulation (EC) No 1272/2008.