Myelotoxicity Induced inFemaleB6C3F1 MicebyInhalation ofMethyl Isocyanate

Theeffects ofa4-day inhalation exposure (6hr/day) to0,1,and3ppmmethyl isocyanate (MIC)on bonemarrowparameters infemale micewereexamined at5,8,and21daysfollowing exposure. TheMIC exposure wasassociated withmyelotoxicity asevidenced byhypocellularity, suppression ofpluripotent stemcells (CFU-S), granulocyte-macrophage progenitors (CFU-GM) anderythroid precursors (CFU-E) inbothdosegroups. Hematopoietic parameters returned tonormal by21daysinthe1ppmdosegroup, butnotinthe3ppmdosegroup. Thisindicates that thealterations inthebonemarrowparameters persist forarelatively longperiod atdoselevels wherethere arelittle ornochanges inbodyweight, clinical pathology, orimmunological parameters, suggesting thatthebonemarrowmaybeasensitive endpoint forMICexposure inmice. MICisahighly reactive chemical thatappears toexert itseffect directly on thelining epithelium ofthenasal cavity andmajor airways; there wasnohistological evidence ofasystemic effect. Thepathogenesis ofthebonemarrowdepression isunknown; however, there werechronic bronchitis andbronchial fibrosis inthe3ppmdosegroup. Onepossible explanation isthatthecell injury induced inthelungisassociated withtherelease ofinhibitory factors forhematopoiesis, astherodent lungisa potent source ofbothstimulatory andinhibitory growth factors forbonemarrowprogenitor cells. Asecond possibility isthatthethymic atrophy found inMIC-exposed micemightberelated tomyelotoxicity. The pathogenesis ofmyelotoxicity inMICexposure anditsrelationship withpulmonary injury require further study.