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Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

Absorption

Based on the available data, TAME is absorbed efficiently from the rat intestine. Hepatic first-pass metabolism was not observed. TAME is rapidly absorbed from the lungs; in a study with human volunteers, the respiration uptake was approximately 50%. The maximum plasma concentration of humans after 50 ppm TAME exposure for 4 hours was about 13 umol/L.

Distribution and elimination

In rat, TAME is distributed evenly throughout the body and is eliminated via respiration, urine and faeces. Urine represents the main route of elimination while excretion in faeces is only a few percent at most. The elimination from human blood was rapid after the end of inhalation exposure and it occurred in two phases. The blood half-lives were between 1.2 and 6.3 hours with relatively big individual differences between test subjects. The limit of TAME detection was reached after 12 hours. In rat, the removal via respiration increases with higher doses.

The kinetics of excretion of TAME were identical after ingestion and inhalation exposure.

Metabolism

In humans, TAME is metabolised to tert-amyl alcohol (TAA) primarily by cytochrome 2A6 mainly present in liver. The first metabolic step releases tert-amyl alcohol and formaldehyde. The main metabolites in human urine are 2-methyl-2,3-butanediol, 2-hydroxy-2-methylbutyrate and 3-hydroxy-3-methylbutyrate. Free and conjugated TAA and TAME were only minor metabolites in urine. In rats, 2-methyl-2,3-butanediol and its glucuronide were major TAME metabolites recovered in urine.

The metabolic pathway of TAME is identical after ingestion and inhalation exposure.

Information used for DNEL derivation

The inhalation and dermal absorption percentages used for DNEL derivation (in case of applying route-to-route extrapolation) are 50% and 0.4%, respectively.