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Toxicological information

Basic toxicokinetics

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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

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Results and discussion

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.