potassium 4-iodo-2-sulfonato-benzoic acid

Endpoint summary

Additional information

The following toxicological tests, which provide also some information on the toxicokinetic properties, were conducted on the substance:

LD 50 oral rat

LD 50 dermal rat

skin irritation

rabbit eye

irritation rabbit sensitization (M&K) guinea pig

Ames test

28 day oral (gavage) rat

The substance is obviously absorbed from the gastrointestinal tract to a certain degree as can be concluded from signs of intoxication (both sexes) and lethal effects (only females) at dose levels of 2000 mg/kg bw and above applied by gavage. The dose response curve seems to be relatively steep at doses around 2000 mg/kg bw, since in females 1600 mg/kg did not even induce symptoms of intoxication whereas lethal effects were already seen with an increase of only 400 mg/kg.

There is no particular potential of increased dermal absorption, since no systemic signs of intoxication were seen after occlusive administration of 2000 mg/kg bw to the rat skin. This view is supported by the results of a skin irritation test in rabbits and by an investigation for sensitizing properties in guinea pigs.

The repeated administration (according to the standard treatment schedule) of the compound did not produce signs of systemic intoxication and no allergenic response in guinea pigs.

The results of a 28 day study using gavage administration of 0 (control), 62.5 or 250 or 1000 mg/kg bw indicate rapid elimination of the compound, since the top dose of 1000 mg/kg bw which is roughly half of the oral acute LD50 did not cause treatmentrelated systemic effects. Cumulation can be excluded.

No cytotoxicity was seen in a standard Ames test. Cytotoxicity as observed without metabolic activation at the highest concentrations of 2500 and 3200 ug/ml was slightly reduced in a V 79 system when a rat liver S-9 mix was added in a chromosome aberration assay. It is not clear whether the difference is due to metabolic detoxification or unspecific protective (buffering) activities of the S-9 mix. There was at least no indication that metabolites are formed which are significantly more toxic than the parent compound.

No investigation on metabolism in animals of the monoiodo-aromatic compound is available. However testing of the complete sulfonylurea which is synthesized from this substance indicates that cleavage of the iodo-group does not play a major role during metabolism of the sulfonylures in animals and no depletion of the complete sulfonylurea or of the iodo-containing subparts of the molecule was detected in the thyroid or other organs in absorption, distribution and excretion studies.

Summary: The available biological data and chemical properties of the relatively small and hydrophilic molecule suggest absorption and rapid excretion. No increased potential for dermal absorption or possible cumulative properties were identified.