1-ethylpiperazine

Endpoint summary

Description of key information

There was no data available for the determination of toxicokinetics, metabolism and distribution. An assessment was done based on physico-chemical properties of the test substance and available data on acute toxicity.

Additional information

There is no data available for the determination of toxicokinetics, metabolism and distribution.

Assessment of Toxicokinetic Behaviour 

1 -Ethylpiperazine (CAS-No. 5308-20-7) is a colorless to yellowish liquid with a molecular weight of 114.19 g/mol and a vapour pressure of 2.48 hPa (20°C). It is miscible with water at room temperature in any ratio, the log Pow is -0.1 (at 20°C) indicating that bioaccumulation of the test substance is not expected.

Absorption

Data for absorption can be taken from acute (oral and inhalative) toxicity studies.

In an acute oral toxicity study (1988), Wistar rats were administered 464, 1000 and 2000 mg/kg bw/day of the test substance. Dyspnea, apathy, staggering, piloerection and poor general state were observed post treatment (4 hours) and up to 2 days after treatment in all animals of the 2000 mg/kg bw dose group. Twitching was observed 4 hours after treatment in the female animals. No clinical signs were observed in the 464 and 1000 mg/kg bw dose groups. 4 male and 4 female animals of the 2000 mg/kg bw dose group died during the first two days post treatment. No further mortality was observed. At necropsy, general congestion, atonic and reddened mucosa of stomach and intestine as well as bloody liquid contents were observed. The LD50 was set at 1000 - 2000 mg/kg bw.

In a second acute oral toxicity study (Bomhard, 1997) seven groups of 5 male and 5 female young adult Wistar rats each were dosed at 500, 1000, 2000, 2300, 2500, 2800 and 4000 mg/kg bw/day (the test substance was solved in water). Corresponding mortality was 0, 0, 40, 50, 70, 100 and 100%, respectively. Clinical signs included poor general condition, sedation and nausea. Onset of symptoms was 30 min after administration. On day 3 all clinical signs disappeared. Deaths occurred from 3 to 24 h after administration. Necropsy of dead animals showed reddening of the lungs and of the gastric and intestinal mucosa. The stomach was filled with a dark-red fluid and was partly distended. No findings were observed at final necropsy except one female of the 2300 mg/kg group which showed a strongly stunted growth of the spleen. The calculated acute oral rat LD50 combined for male and female rats is 2158 mg/kg (95% confidence interval: 1947 - 2393 mg/kg).

From this study, systemic exposure to the test substance is indicated, possibly mediated by passive diffusion along the gastrointestinal tract (ECHA guidance document 7c, 2008). However, the results might be more indicative for local corrosive effects of the test substance rather than systemic availability.

In an inhalation hazard test (IHT, 1989), Wistar rats were exposed to a saturated vapour atmosphere of the test substance for 7 hours. The mean nominal concentration of the test substance was 10.43 mg/L. During the exposure, irritating effects to the eyes and the respiratory tract (accelerated/intermittent respiration, eyelid closure, wiping of snouts, salivation, nasal discharge, reddish nasal/eye discharge) were observed. Immediately after exposure, accelarated respiration, reddish nasal/eye discharge, squatting posture, piloerection, urine-contamined fur and high-stepping gait were observed in male and female animals. On the first day post exposure piloerection was observed in all animals and aggressiveness in all male animals. At necropsy, no pathologic findings were observed.

Additionally, acute inhalation toxicity was analyzed in a study performed equivalent to OECD Guideline 403 (Bomhard, 1997). Four groups of 5 male and 5 female young adult Wistar rats were subjected to a single 4-hour head-nose exposure to analytical vapour concentrations of 0.448, 1.209, 3.889, and 9.219 mg/L air. No mortality was observed. The animals of the 0.448, 1.209, and 3.889 mg/L groups showed red noses and serous nasal discharge after exposure. These findings disappeared on day 1. In addition bradypnoea was seen in the 3.889 and 9.219 mg/L group .Besides this, in the highest dose-group decreased motility, bloody and necrotic rhinarium as well as liver-like changes in the lungs at final necropsy were seen. All other animals showed no dose-related pathological signs or changes at final necropsy. The acute inhalation 4h-LC50 for male and female rats was > 9.119 mg/L.

Local effects as observed in both inhalation toxicity studies supplement the results of skin and eye irritation studies (1988; Bomhard, 1997) in which the test substance showed a corrosive potential. Due to results of the acute inhalation toxicity studies the local effects seemed to be more important than the systemic effects.

No acute dermal toxicity studies were performed. As the substance is a skin corrosive, damage to the skin surface may enhance penetration, but also for the dermal route local effects seem to be the major mode of action.

Taken together, the test substance might be systemic available via the oral route of exposure. However, as the test substance is also caustic the existing data indicate that corrosion and also irritation of the respiratory tract (local effects) are the primary effects.

Studies on genotoxicity resulted in negative results, i.e. there is no indication of a reactivity of the test substance or its metabolites under the test conditions.

Excretion

Due to its molecular weight, the test substance is expected to be excreted predominantly via the urine (ECHA guidance document 7c, 2008).