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Description of key information

Short description of key information on bioaccumulation potential result: 
About half of the dose administered intraperitoneally was excreted in the urine. A small amount of ethylenimine was excreted, as such, in the urine, but the major portion of the excreted radioactivity was found in a number of unidentified products. Kinetic data indicate that the activity retained in the tissues of the rat after 24 hours was essentially unavailable for further metabolism.

Key value for chemical safety assessment

Additional information

The metabolic fate of C14 -labeled ethylenimine has been studied in rats (Wright et al., 1967). About half of the dose administered intraperitoneally was excreted in the urine. A small amount of ethylenimine was excreted, as such, in the urine, but the major portion of the excreted radioactivity was found in a number of unidentified products. Three to five percent of the dose was expired as CO2, and 1-3% was expired as a volatile, basic material, probably ethylenimine. Radioactivity was widely distributed with the highest values found in the liver, intestines, cecum, spleen, and kidney. This is confirmed in the repeated dose studies as the major effects in these studies are kidney effects (e.g. pappilary necrosis, papilledema, pappilary bleeding, necrosis of the medula renalis and oedema). Fat depots were not highly labeled. Kinetic data indicate that the activity retained in the tissues of the rat after 24 hours was essentially unavailable for further metabolism.

Physico-chemical properties

The substance is a liquid with a molecular weight of 43.07.

 

Mammalian toxicity

Acute toxicity:

The oral and dermal LD50are 4.9 and 12.45 mg/kg bw, respectively. An inhalation LC50has not been determined.

 

Repeated dose toxicity:

In an oral repeated dose study with rabbits a NOAEL could not be derived as effects were also observed at the lowest dose level. The effect seen in surviving animals was renal papillary necrosis. Effects seen in animals that died during the study were apathy, atony, and proteinuria.

 

In a 10 day dermal repeated dose study with rabbits a NOAEL could not be identified. Effects seen in surviving animals were skin edema and red-brown, widespread parchment-like necrosis with confluent blood discharge.

 

Regarding inhalation exposure, Sprague-Dawley rats that were exposed 5 hours/day, 5 days/week for 27 weeks or until death a NOAEC could not be identified. Exposure to the test substance caused reduced lifespan of the rats, histopathological changes in kidney and trachea and an increased incidence of tumours in trachea, lung, skin and breast.

 

Genetic toxicity:

The Ames test was performed with and without metabolic activation using induced male Sprague Dawley rat liver S9 (RLI) or induced male Syrian hamster liver S9 (HLI). Without metabolic activation, concentrations >= 1000 µg/plate of the test substance were cytotoxic. In this study it was clearly shown that the number of reverse mutations increased in the strain TA100 with increasing amounts of the test substance. Using 10 µg/plate of the test substance the number of reverse mutations was about 3-fold (without activation) and 4.4-fold (30%RLI) or 5-fold (30%HLI) higher than in the control.

 

In an in vivo micronucleus test, 2.9 or 1.16 µL of the test substance was applied intraperitoneally. After single application of the test substance, the rats were sacrificed 4, 24 or 48h after application. After repeated application (5 times) of the test substance, the rats were sacrificed 4h after the last application. The test substance showed a chromosome damaging effect under the experimental conditions used.

 

In an in vivo chromosome aberration test, 2.9 or 1.16 µL/kg bw of the test substance were applied intraperitoneally. After single application of the test substance rats were sacrificed 6, 24 or 48h after application. After repeated application (5 times) of the test substance, the rats were sacrificed 6h after the last application. The test substance had a slight clastogenic effect under the test conditions chosen.

Carcinogenicity:

From an inhalation study with Sprague-Dawley rats it can be concluded that ethyleneimine causes histopathological changes in kidney and trachea and an increased incidence of tumours in trachea, lung, skin and breast. The animals were exposed to 8.9 µg/L for 27 weeks or until death (approximately 66 weeks).

 

Toxicity to reproduction:

In a teratogenicity study, 1.24 or 3.1 µL/kg bw (corresponding to approx. 1.03 and 2.57 mg/kg bw) of the test substance were given to rats (17-34 rats per group) by gavage on days 6 to 15 of pregnancy.

A dose of 2.57 mg/kg bw had a toxic effect on the rats and consequently an embryolethal and fetotoxic effect. The developmental toxic effects were also due to the toxic effect on the pregnant rats. A dose of 1.03 mg/kg bw of the test substance did not cause any clinical symptoms. No embryolethal, fetotoxic or teratogenic effects were observed at this dose level.

Discussion on bioaccumulation potential result:

The metabolic fate of C14-labeled ethylenimine has been studied in rats (Wright et al., 1967). About half of the dose administered intraperitoneally was excreted in the urine. A small amount of ethylenimine was excreted, as such, in the urine, but the major portion of the excreted radioactivity was found in a number of unidentified products. Three to five percent of the dose was expired as CO2, and 1-3% was expired as a volatile, basic material, probably ethylenimine. Radioactivity was widely distributed with the highest values found in the liver, intestines, cecum, spleen, and kidney. Fat depots were not highly labeled. Kinetic data indicate that the activity retained in the tissues of the rat after 24 hours was essentially unavailable for further metabolism.