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.

Advances in Inhalation Dosimetry Models and Methods for Occupational Risk Assessment and Exposure Limit Derivation

“…PBPK models have been used to improve dosimetry for risk analysis of numerous chemicals, e.g., PBPK models of trichloroethylene, ( 37 ) glycol ethers, ( 38 – 41 ) or methyl iodide. ( 42 , 43 ) These PBPK models were used to estimate internal dose and to estimate safe exposure levels or OELs based on, respectively: the sum of the parent compound (trichloroethylene) and metabolite concentration in blood; the average daily area under the blood concentration of metabolites and time curve (AUC) (glycol ethers); and separate dose estimates based on MOA for different endpoints extrapolated from animal data, including maximum concentration of methyl iodide in the brain for neurotoxic effects and fetal blood iodide AUC for developmental effects.…”

Fumigant methyl iodide can methylate inorganic mercury species in natural waters

“…With the phase out of CH 3 Br, the use of CH 3 I is expected to increase dramatically in the future. CH 3 I is a pulmonary and dermal irritant 26 , and is also suspected to be carcinogenic 34 , neurotoxic 18,26 and endocrine disrupting 4 . This study shows that CH 3 I could also indirectly threaten the health of humans and wildlife by forming a toxic chemical, CH 3 Hg þ , suggesting the necessity of a more comprehensive risk assessment of CH 3 I use as a fumigant.…”

“…The potentially negative impact of using CH 3 I has not been adequately addressed 4 , despite its increasing use on farmland. Compared with CH 3 Br, CH 3 I degrades more slowly in soil, hence increasing its chance of being transported to an aquatic environment via runoff 5,6 .…”

S‐Adenosyl‐Methionine‐Dependent Methyltransferases: Highly Versatile Enzymes in Biocatalysis, Biosynthesis and Other Biotechnological Applications

“…Traditionally, methylation reactions are carried out with methyl iodide. However, the harsh reaction conditions36, 37 together with the environmental38 and safety considerations39 associated with the use of methyl iodide are far from ideal. In addition, such chemical methylation reactions often lack chemo‐, regio‐ and stereoselectivity, which necessitates the use of complex and expensive synthetic strategies.…”