Diethylammonium chloride

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Scientific publication that meets documentation requirements.

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Objective of study:

other: ADME

Test guideline

Qualifier:

no guideline followed

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Diethylamine

EC Number:

203-716-3

EC Name:

Diethylamine

Cas Number:

109-89-7

Molecular formula:

C4H11N

IUPAC Name:

N-ethylethanamine

Radiolabelling:

no

Applicant's summary and conclusion

Executive summary:

Excerpt from NTP Report about ADME of diethylamin:

Very little information on the disposition and metabolism of diethylamine in experimental animals or humans was found in a review of the literature. The reaction of dietary amines with nitrite to produce nitrosamines, which are potential carcinogens, has been demonstrated both in vitro and in vivo (Sander, 1967; Sander et al., 1968; Mirvish, 1975). However, in Wistar rats administered 600 ppm diethylamine and sodium nitrite in the diet, diethylnitrosamine could not be detected (Galea et al., 1975). Diethylnitrosamine was not detected in blood or milk of goats fed kale containing 3% potassium nitrate followed by administration of a single oral dose of 200 mg/kg diethylamine hydrochloride (Juskiewicz and Kowalski, 1976). Monoamine oxidase is assumed to play an important role in the metabolism and detoxification of the aliphatic amines. Monoamine oxidase catalyzes the deamination of primary, secondary, and tertiary amines. Monoamine oxidase is widely distributed in tissues and is most concentrated in the liver, kidney, and intestinal mucosa (Beard and Noe, 1981). Traces of diethylamine (less than 0.5% of the dose) were detected in the urine of human volunteers following oral doses of triethylamine (Åkesson et al., 1989). Diethylamine was also found in the gastro-intestinal tract after oral doses of triethylamine-N-oxide, the oxidative metabolite of triethylamine, indicating that triethylamine-N-oxide is dealkylated in the gastro-intestinal tract to diethylamine. There was no evidence that diethylamine produced from triethylamine-N-oxide was subsequently metabolized to N-nitrosodiethylamine in the stomach.

References:

Åkesson, B., Vinge, E., and Skerfving, S. (1989). Pharmacokinetics of triethylamine and triethylamine-N-oxide in man. Toxicol. Appl. Pharmacol. 100, 529-538.

Beard, R.R., and Noe, J.T. (1981). Aliphatic and alicyclic amines. In Patty’s Industrial Hygiene and Toxicology, 3rd ed. (D.G. Clayton and F.E. Clayton, Eds.), Vol. 2B, pp. 3135-3173. Wiley-Interscience Publication, New York, NY.

Galea, V., Preda, N., and Simu, G. (1975). Experimental production of nitrosamines in vivo. IARC Sci. Publ. (N-Nitroso Compd. Environ. Proc. Work Conf.) 9, 121-122.

Juskiewicz, T., and Kowalski, B. (1976). An investigation of the possible presence or formation of nitrosamines in animal feeds. IARC Sci. Publ. (N-Nitroso Compd. Environ. Proc. Work Conf.) 14, 375-393.

Mirvish, S.S. (1975). Blocking the formation of N-nitroso compounds with ascorbic acid in vitro and in vivo. Ann. N. Y. Acad. Sci. 258, 175-180.

Sander, J. (1967). [A method for the demonstration of nitrosamines.] [article in German]. Hoppe Seylers Z. Physiol. Chem. 348, 852-854.

Sander, J., Schweinsberg, F., and Menz, H.P. (1968). [Studies on the origin of carcinogenic nitrosamines in the stomach.] [article in German]. Hoppe Seylers Z. Physiol. Chem. 349, 1691-1697.