Diiodomethyl-p-tolylsulfone: Evaluation of the mode of action for reproductive toxicity

The mode of action (MOA) underpinning the reproductive toxicity of diiodomethyl-p-tolylsulfone (DIMPTS) is excess systemic iodine levels, resulting in hypothyroidism. This MOA evaluation also addresses the potential for toxicity and adverse health outcomes during critical windows of development for different tissues. The data indicate that testicular development in the neonate represents the tissue and life-stage that are most sensitive to iodine toxicity. Life-stage specific dosimetry appears to be a major determinant of this sensitivity, with the neonate being exposed to higher levels of iodine than the fetus during the period of testicular development, in particular Sertoli cell maturation and differentiation. While no reports could be found in the literature linking excess iodine exposure in humans to testicular toxicity, there is evidence that neonates born to mothers with excessive iodine intake do exhibit signs of transient hypothyroidism. Although there are major physiological and temporal differences in testicular development and Sertoli cell replication between the rat and human, it is not inconceivable that continuous long term exposures to excess iodine first from maternal milk and then in the diet through to the onset of puberty could affect testicular development. However, exposures to iodinated substances – such as DIMPTS – contribute less than 1% of the required daily iodine intake for normal fetal and neonatal development and, consequently, continuous exposure to excess iodine during the pre-pubertal period is unlikely. As exposures to DIMPTS are both very low and sporadic in nature it is not likely that they represent any risk to health at any life-stage.