Triethylamine

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication, which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Effects of ethanol ingestion and urinary acidity on the metabolism of triethylamine in man

Author:

B Akesson and S Skerfving

Year:

1990

Bibliographic source:

Int Arch Occup Environ Health ( 1990) 62: 89-93

Materials and methods

Type of study / information:

Effects of ethanol intake on the metabolism of TEA were investigated by determination of the total clearance (CL), the renal clearance (CLR) and the nonrenal clearance (CLNR). Additionally the half-life in urine was determined.

Principles of method if other than guideline:

4 human volonteers, aged 48 to 52 (mean 50), body weights 80 to 92 (mean 87) kg, height 1.80 to 1.84 (mean 1 82) m
All non-smokers, and moderate alcohol intake
all 4 exposed by inhalation ( 20 mg/m3 , 8 h, with 4 short interruptions of a few minutes for urine and blood sampling) to TEA,

in a first experiment: subjects were exposed to TEA only, see below
before each experiment: ingestion of 400 ml orange juice with ice (later with or without 0,6 g/kg ethanol)
during the experiment ingestion of an additional 600 ml orange juice (in case of alcohol administration: hourly orange juice with 0.15 g/kg ethanol)
Subjects 3 and 4 were exposed a third time, to TEA and ethanol, with the addition of a 3-g portion of sodium hydrogen carbonate (SBC), before and at 2, 4, and 6 h after start of exposure.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Triethylamine

EC Number:

204-469-4

EC Name:

Triethylamine

Cas Number:

121-44-8

Molecular formula:

C6H15N

IUPAC Name:

triethylamine

Details on test material:

Triethylamine

Results and discussion

Any other information on results incl. tables

The mean serum ethanol concentration during exposure, and in the first hour after the end of exposure, was 25 mmol/l ( 1.2 per mille), with a range of 16-35 mmol/I ( 0.7 -1.6 per mille) After the end of exposure, the mean ethanol level decreased linearly, with an average half-life of 1.6 h The serum ethanol concentrations were, in all subjects, below the detection limit 15 h after the end of exposure.

TEA was readily absorbed during the exposure and partly oxygenated into TEAO.

Compared to the experiments with TEA only (TEA/-/-), the concentrations in plasma of TEA at the end of exposure were lower in the experiments with ethanol intake (TEA/Et OH/-).

TEA plus ethanol plus sodium bicarbonate (TEA/Et OH/SBC) caused the highest levels.

Only minor TEA amounts were exhaled: In all experiments employing all three exposure conditions (TEA/-/-, TEA/Et OH/-, and TEA/Et OH/SBC), the concentrations of TEA in exhaled air during exposure were within the range of 12 to 18 % of the air TEA level ( 2.4 -3.6, mean 2 8 mg/m 3) One and two hours after the end of exposure, the mean concentrations were much lower (means 0.1 and 0.06 mg/m 3 , respectively).

The half-lives of TEA in urine were similar in experiments TEA/-/ and TEA/Et OH/- (average 3 2 h, both experiments)

However, intake of SBC clearly increased the half-lives (average 4.4 h).

The amounts of TEA and TEAO excreted in the urine during and after exposure ( 32 h) averaged 1040 g mol (TEA/-/-), 960 gmol (TEA/Et OH/-), and 940 jmol (TEA/Et OH/SBC).

The CLNR of TEA was decreased by ethanol intake in all four subjects (13, 11, 17, and 141/h, vs 11, 8, 15, and 111/h, respectively).

SBC did not affect the nonrenal clearance (15 and 111/h in Subjects 3 and 4, respectively).

The p H in urine was lower for the TEA/Et OH/- experiments than for TEA/-/-, while in the TEA/ Et OH/SBC experiments, the pH was about two units higher than in the TEA/Et OH/ experiments.

There was a marked decrease of renal clearance of TEA with rising urinary p H from the TEA/Et OH/-, over the TEA/-/-, to the TEA/Et OH/SBC experiments.

SBC increased the oxygenation by a factor of two.

The fraction of the sum TEA plus TEAO excreated as TEAO rose with increasing average urinary pH.

Applicant's summary and conclusion

Conclusions:

The present experiments strongly indicated an inhibiting effect of ethanol on the rate of oxygenation of TEA.

Executive summary:

The present experiments strongly indicated an inhibiting effect of ethanol on the rate of oxygenation of TEA.

Ethanol caused a slight decrease of urinary pH, which is in accordance with earlier reports of a metabolic acidosis by ethanol (Ylikahri et al 1974), while, of course, SBC caused a marked increase of pH.

Urinary pH profoundly affected TEA metabolism.

TEA, which is a strong base (pKa 11), is obviously pH sensitive as to its excretion. Thus, there was a close association between rising CLR of TEA and decreasing urinary pH; a decrease of the urinary pH by one unit increased the renal clearance of TEA by a factor two. When the urinary pH was high, TEA was retained in the body and was thus available for oxigenation for a longer period.

The SBC probably increased the stomach pH, and thus decreased the gastric excretion, thereby further increasing the TEA available for oxigenation.

Theoretically, the ethanol intake and varying urinary pH may affect the possibility of monitoring TEA exposure by use of biological samples. Thus, end-shift plasma levels of TEA, or TEA plus TEAO, are decreased by ethanol, while post-shift urinary excretion levels are increased. A high urinary pH causes the opposite effect.