Allyl isothiocyanate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

review

Type of information:

other: review

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Data source

Reference

Reference Type:

review article or handbook

Title:

Scientific Opinion on the safety of allyl isothiocyanate for the proposed uses as a food additive.

Author:

EFSA

Year:

2010

Bibliographic source:

EFSA Journal 2010;8(12):1943

Materials and methods

Principles of method if other than guideline:

review of toxicokinetics

Test material

Test material information

Constituent 1

Reference substance name:

Allyl isothiocyanate

EC Number:

200-309-2

EC Name:

Allyl isothiocyanate

Cas Number:

57-06-7

Molecular formula:

C4H5NS

IUPAC Name:

3-isothiocyanatoprop-1-ene

Test material form:

liquid

Applicant's summary and conclusion

Conclusions:

Overall, the fate of isothiocyanate has been investigated in rodents and in humans. In animals, the doses of 14C-radiolabelled isothiocyanates administered ranged from 2.5 to 25 mg/kg bw. Humans received isothiocyanate as mustard or horseradish preparations corresponding to dietary doses of only 0.065 to 0.130 mg isothiocyanate/kg bw. In rodents, isothiocyanates are readily absorbed and distributed to all the tissues. At comparable doses, there are clear sex- and species-specific differences in the distribution, metabolism and excretion of substituted isothiocyanates. Tissue distribution is characterized by high levels of radioactivity in urinary bladder tissue of rats. Metabolic studies in humans, mice and rats indicate that isothiocyanates react readily with reduced glutathione to form a glutathione conjugate as the principal metabolite. This conjugate is further metabolised to a cysteine conjugate and finally to the mercapturic acid N-acetyl-S-(N-allylthiocarbamoyl)-L-cysteine before excretion in the urine (Figure 2). In mice, this mercapturate represents less than 20% of the urinary radioactivity whereas it was the major metabolite in humans and rats. Thus, the rat appears to resemble humans more than mice in AITC metabolism. By considering the rate of urinary excretion of metabolites and disregarding differences in doses, rats have a slower clearance of AITC than mouse and a much slower clearance than humans. The lability of the mercapturic acid N-acetyl-S-(Nallylthiocarbamoyl)-L-cysteine under the conditions present in the rodent bladder may lead to formation of unconjugated isothiocyanate (Bruggeman et al., 1986), which would increase irritation of the rat bladder epithelium, mainly in male rats exposed to high AITC intake.