Iodomethane human health risk characterization

Abstract

Iodomethane is a new pre-plant soil fumigant approved in the United States. Human exposure may occur via inhalation due to the high vapor pressure of iodomethane. A quantitative human health risk assessment was conducted for inhalation exposure. The critical effects of acute duration iodomethane exposure are: (1) fetal losses in rabbits, (2) lesions in rat nasal epithelium, and (3) transient neurotoxicity in rats. Chronic exposure of rats resulted in increased thyroid follicular cell tumors from sustained perturbation of thyroid hormone homeostasis. A physiologically based pharmacokinetic (PBPK) model for iodomethane was developed to characterize potential human health effects from iodomethane exposure. The model enabled calculation of human equivalent concentrations (HECs) to the animal no-observed-adverse-effect levels (NOAELs) using chemical-specific parameters to determine the internal dose instead of default assumptions. Iodomethane HECs for workers and bystanders were derived using the PBPK model and NOAELs for acute exposure endpoints of concern. The developmental endpoint NOAEL was 10 ppm and corresponding bystander HEC was 7.4 ppm. The nasal endpoint NOAEL was 21 ppm and the HEC was 4.5 ppm. The transient neurotoxicity endpoint NOAEL was 27 ppm and the HEC was10 ppm. Data demonstrated that humans are less sensitive to the effect that causes developmental toxicity in rabbits and the PBPK model incorporated this information, resulting in a higher HEC for the developmental endpoint than for the nasal endpoint. Nasal olfactory degeneration is the primary endpoint for risk assessment of acute exposure to iodomethane.

Acknowledgement

This work was funded by Arysta LifeScience North America, LLC.

Declaration of interest: The authors were hired as consultants or employees of Arysta LifeScience North America, LLC, the organization that funded the work and the iodomethane registrant in the United States.

Notes

¹ A full mass spectrum of the internal standard, N7-methyl-D₃-guanine, which was labeled with three deuterium atoms on the guanine moiety, is shown in Figure 4 of Gansewendt et al. (1991a). The derivatized molecular ion has as a mass of 312 amu, while the largest ion fragment is 297 amu, corresponding to loss of the methyl group leaving the deuterated guanine ion. In the middle frame of Figure 4 of the paper, the authors measured the presence of N7-methylguanine adduct with a guanine moiety of 296 amu, which corresponds to a radiolabeled guanine ion containing a ¹⁴C in place of an unlabeled carbon with a molecular weight of 12. Thus, this spectrum confirms that the location of the ¹⁴C is in the guanine not the methyl group.