N,N-dimethylisopropylamine

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Dimethylethylamine in mould core manufaturing: exposure, metabolism, and biological monitoring

Author:

Lundh T, Stahlbom B, Akessson B

Year:

1991

Bibliographic source:

Br. J. Ind. Med., 48, 203-207

Materials and methods

Objective of study:

other: metabolism and excretion

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The exposure and metabolism of dimethylethylamine was studied in 12 mould core makers in four different foundries using the Ashland cold box technique.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Ethyldimethylamine

EC Number:

209-940-8

EC Name:

Ethyldimethylamine

Cas Number:

598-56-1

Molecular formula:

C4H11N

IUPAC Name:

N,N-dimethylethanamine

Radiolabelling:

no

Test animals

Species:

human

Sex:

not specified

Details on test animals or test system and environmental conditions:

10 men and 2 women,
Age: 23-62 years old (mean 38),
working in 4 different foundries.

Administration / exposure

Route of administration:

inhalation

Details on exposure:

The time weight average (TWA) exposure to DMEA was measured in each worker, in his or her personal breathing zone by absorption in impringer flasks during the full work shift (eight hours) divided into about one hour sampling periods.
Workers were exposed to 0.003 - 0.007 mg/l inhaled dimethylethylamine.
The mean TWA full work shift DMEA exposure concentration in the foundries studied was 3.7 (range 0.5-14) mg/m3.

No. of animals per sex per dose / concentration:

10 men and 2 women were studied.

Control animals:

no

Positive control reference chemical:

none

Details on dosing and sampling:

PHARMACOKINETIC STUDY
- Tissues and body fluids sampled: urine, blood
Blood samples (20ml) were collected by venepuncture bofore the start of exposure, and immediately after the end of exposure.
Urine samples were collected for 24 hours during two periods before the start of exposure, four two hours period during exposure, and six periods after the end of exposure.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:

Inhaled dimethylethylamine was excreted in urine as the original amine and as its metabolite dimethylethylamine-N-oxide.
DMEA was readily absorbed and eliminated into urine as DMEA and DMEAO.
After star of exposure, the DMEA and DMEAO excretion in urine increased until the end of exposure, and the decreased again.
The mean DMAEO fraction in the urine was 81% (range 18-93%). In the two women (sisters) studied, DMAEO fractions were considerably lower (18% and 63%) compared with men (84-93%).
The data indicate half lives after the end of exposure for DMEA in urine of 1.5 hours.

Toxicokinetic parameters

Toxicokinetic parameters:

other: Before exposure, the average concentrations of DMEA and DMEAO in plasma were below the detection limits (0.04µmol/l for DMEA and 0.07µmol/l for DMEAO). Postshift the concentrations were 0.21 and 1.8 µmol/l for DMEA and DMEAO.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

dimethylethylamine-N-oxide.

Applicant's summary and conclusion

Executive summary:

The exposure and metabolism of dimethylethylamine (DMEA) was studied in 12 mould core makers in four different foundries using the Ashland cold box technique. The mean time weighted average (TWA) full work shift DMEA exposure concentration was 3.7 mg/m3. Inhaled DMEA was excreted into urine as the original amine and as its metabolite dimethylethylamine-N-oxide (DMEAO). This metabolite made up a median of 87 (range 18-93) % of the sum of DMEA and DMEAO concentrations excreted into the urine. Occupational exposure did not significantly increase the urinary excretion of dimethylamine or methylethylamine. The data indicate half lives after the end of exposure for DMEA in urine of 1.5 hours and DMEAO of three hours. The postshift summed concentration of DMEA and DMEAO in plasma and urine is a good indicator of the TWA concentration in air during the workday, and might thus be used for biological monitoring. An air concentration of 10 mg/m3 corresponds to a urinary excretion of the summed amount of DMEA and DMEAO of 135 mmol/mol creatinine.