Two-day inhalation toxicity study of methyl iodide in the rat.
The effects of inhaled methyl iodide (MeI) on clinical pathology parameters, glutathione (GSH) tissue levels, serum thyroid hormone and inorganic iodide concentrations, S-methylcysteine hemoglobin concentrations, and liver UDP-glucuronyltransferase activity were studied in the rat. Male rats were exposed by whole-body inhalation to 0, 25, or 100 ppm MeI, 6 h/day for up to 2 days. Serum cholesterol concentrations (both high-density lipoprotein [HDL] and low-density lipoprotein [LDL] fractions) were increased and triglycerides were decreased at both exposure levels. Serum thyroid-stimulating hormone (TSH) concentrations were increased at 25 and 100 ppm, and serum triiodothyronine (T(3)) and thyroxine (T(4)) concentrations were decreased at 100 ppm. There was no change in either reverse triiodothyronine (rT(3)) or UDP-glucuronyltransferase activity at either exposure level. A dose- and time-dependent reduction in GSH levels in blood, kidney, liver, and nasal tissue was observed, with the greatest reduction in nasal tissue (olfactory and respiratory epithelium). MeI exposure also resulted in a substantial dose- and time-dependent increase in both serum inorganic iodide and red blood cell S-methylcysteine hemoglobin adducts. These results indicate that following inhalation exposure, MeI is rapidly metabolized in blood and tissue of rats, resulting in methylation products and release of inorganic iodide.
Himmelstein
Matthew W
MW
E. I. du Pont de Nemours and Company, Haskell Global Centers for Health and Environmental Sciences, Newark, Delaware 19714, USA. matthew.w.himmelstein@usa.dupont.com
Kegelman
Thomas A
TA
DeLorme
Michael P
MP
Everds
Nancy E
NE
O'Connor
John C
JC
Kemper
Raymond A
RA
Nabb
Diane L
DL
Mileson
Beth E
BE
Bevan
Christopher
C
D000280:Administration, Inhalation; D000818:Animals; D006847:Hydrocarbons, Iodinated / Q000008:administration & dosage* / Q000097:blood / Q000633:toxicity*; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
D006847:Hydrocarbons, Iodinated; C014055:methyl iodide