Registration Dossier

Administrative data

Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics in vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:

Description of key information

Isothiocyanates including AITC are readily cleared from rat and mouse tissues so that within 24 hours after administration less than 5% of the total dose was retained in tissues. Generally, the highest concentration of AITC was observed in male rat urinary bladder tissue. Clearance was primarily via the urine. In the mouse, hydrolysis of AITC to thiocyanate was the major metabolic pathway, whereas in the rat glutathione conjugation followed by further metabolism to the mercapturic acid was the major route. In human studies, the mercapturic acid conjugate was found to be a major urinary metabolite. The major portion of this metabolite was excreted within 8 hours. Overall, the available studies indicate that isothiocyanates are readily conjugated to glutathione with the glutathione conjugates being further transformed successively into the corresponding cysteine conjugates and mercapturic acids. Since the mercapturic acid conjugate of AITC was the major urinary metabolite in humans and rats, the rat appears to resemble humans more than mice in AITC metabolism. However, rats have a much slower clearance of AITC than humans (biological half-lives of 140vs2 hours).

(EFSA, 2010)

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

In rodents, isothiocyanates are readily absorbed and distributed to all the tissues.