Triethylamine

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
TEA has a bioavailability of near 100 %, is widely distributed throughout the body and is mainly excreted via urine as TEA. About 27% are excreted via urine as TEAO, and no metabolism to DEA occurs. Neither first pass effect nor an excretion via exhalation was to be found.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

TEA has a bioavailability of near 100 % and widely distributed throughout the body. In humans, following exposure to triethylamine by inhalation, ingestion, or i.v. injection, triethylamine was excreted in urine largely unchanged, to a lesser extent as triethylamine-oxide (TEAO) (about 27%) and, in trace amounts, as diethylamine. The average plasma and urine half-lives for triethylamine was 3 to 4 hours. No first pass effect nor an excretion via exhalation was to be found.

Discussion on bioaccumulation potential result:

Akesson and coworkers investigated the fate of TEA in humans (Akesson, 1988). Triethylamine, is readily absorbed when inhaled (about 80%, as a result of dead space 20% are not absorbed). The plasma concentration increased during 4 to 8 hours following the intake of TEA, indicating that no saturation took place during the inhalation of 20 and 10 mg/m³. One hour after the end of exposure the plasma TEA decreased in all experiments. The major part is excreted via urine as TEA. In part TEA is metabolized (24 %) to triethylamine-N-oxide, which is measurable in the plasma and then excreted via urine. The amount of TEA and TEAO excreted via urine corresponds to an average of 97%. During exposure the urinary TEA-level continuously increased in all experiments. After the end of exposure the elimination rapidly takes place (half life 3.2 hours). Elimination is mainly conducted via urine and only a minor excretion occurs via exhalation. The detection limit was not reached in the urine samples within the time period monitored, so elimination occurs slowly. Additionally visual disturbances occurred in one subject exposed to an air level of TEA of 53 mg/m³ for four hours, in two subjects exposed to an air level of 35 mg/m³, and in four of five subjects exposed to 20 mg/m³ for eight hours. The urinary determination is a possibility for biological monitoring concerning TEA exposure. But considering the extreme water solubility of the compound, it is probable that the absorption is proportional to ventilation. At moderately heavy work (ventilation 10 cm³/8h), an Air-TEA of 40 mg/ m³ would then correspond to an U-TEA of 320 mmol/ mol creatinine. Data on visual disturbances presented here and earlier, however, indicate that 40 mg/m³ is too high a TLV; 10 mg/m³ would be more reasonable. This would correspond to an average U-TEA of about 40 mmol/mol creatinine in a resting worker and 80 mmol/mol creatinine in moderately heavy industrial work. . Another study was carried out in a polyurethane foam-producing plant, where 20 workers were exposed to TEA. The workers inhaled an average of approximately 500 µmol triethylamine per day, approximately 53% of the dose was excreted in urine as unchanged triethylamine and approximately 27% was excreted as TEAO during a 24 -hour period. There the above mentioned results were reproduced, and the information added that the excretion was not complete even next morning, so there seems to exist a slight tendency of accumulation during the work week. However, over the weekend, the body should be completely cleared of the agent. Additionally, they found no statistically significant differences between man and women concerning the half-life of TEA (means 3.0 vs. 2.7) and they noted an increasing fractional excretion of TEAO with rising age. They investigated also the metabolic fate of TEA and proved that TEA in not metabolized in vivo to DEA (less than 0,3 %) (Akesson, 1989a). The same group investigated the fate of TEA after intravenous and oral administration and could reproduce many of the abovementioned results. After i.v. administration at least 90 - 97 % could be found in the urine, also after oral administration the bioavailability was almost complete. The distribution of TEA was rapid in both cases and Vz after oral administration was about 3 to 4 times the body water content. The mean maximal plasma concentration was 1.17µmol/L and was reached 45 min-1 hour after exposure. Triethylamine-N-Oxide was also identified in the plasma (Cmax =0.75 µmol/L short period of distribution, then plasma concentrations and urinary excretion decreased to a constant rate. The apparent volume of distribution during the terminal elimination phase (V,) calculated for TEA after the iv dose was 192 liters, and after oral doses, 196 liters (range 180-208 liters, assuming 100% bioavailability). No significant first pass metabolism occurred. The high renal clearance values for both TEA and TEAO indicate that they are excreted into the urine not only by glomerular filtration but also by tubular secretion. Renal clearance, A,/AUC, for TEA averaged 27.9 liters/hr and for TEAO 22.5 liters/hr. Additionally, they could show that TEA was excreted into the gastric juice (about 30 times the level in plasma). As TEA was absorbed efficiently from the GI tract after ingestion, there was probably an almost total reabsorption of TEA, and thus a gastroenteric circulation.