The Goitrogenic Effect of 4,4'-Oxydianiline in Rats and Mice

Abstract

Abs tract. Fischer 344 rats an d B6C3F t mice were fed diets that conta ined 0.03, 0.06, 0. 1 and 0.2% 4,4'-oxydianiline for 13 week s. The 0. 1 to 0.2% diet caused 40 to 70% mort al ity in female rat s. Altho ug h mice ate abo ut 3.5 time s more ch emi cal tha n rats, no mice died . Alopec ia, dyspn ea a nd cya nosis in rats, an d letha rgy in both species occur red in the 0. 1 to 0.2% gro ups. Goi te r was fou nd in rats tha t d ied as ea rly as the 4th to 5th week of study in th e gro u ps given the 0.06 to 0. 1% d iet. At the end of th e study , diffuse par ench ymatou s goi ter was seen in all rats given th e 0.06% and higher co ncentra tion diet s and in most mice given th e 0.2% diet. In rat s, the th yroid s also were heavil y encapsulated and had interstiti al fibr osis and vascular degen eration . There was co nco mita nt hyperpl asia of pituitar y basophils in both species, but an increase of cells th at secrete th yrot rop in was seen in rats only.Di-(4-amino phenyl)ether, kn own also as 4,4'-oxydi aniline, an intermediate in synthesis of polyimide ad hesive, was selected for in vivo testin g as part of the Na tional Cance r Institute's (NC I) carcinoge nes is bioassay program . T his co mpo und was chose n by NC I becau se its struc tural config ura tion indicat ed potent ial ca rcinogenic activity and becau se earlier studies with thi s chemica l in a nima ls were co nside red inadequate [4,5]. More recent stud ies, however, revealed weak carcinogenicity in ra ts and mice [1]. Related aro matic amines, nam ely cur ing agents for liqu id cas table polyurethan e elasto mers and epoxy resins, were proven carcinoge nic in lab oratory animals. O ra l ad ministra tion of either 4,4'-methy lene-bis-(2-chloroaniline) or 4,4'-methylene -b is-(2-meth ylaniline) to mice and rat s ind uced liver tumors in both species and lung tumors in rats [6,9,12,15,16]. An other dianiline derivative, 4,4'-di aminodi ph en yl-m eth an e was eq uivoca lly car cinogeni c in rats, the only species tested [9,14].Th e goa l of this investigation is to determi ne if this chemica l is ca rcinoge nic in ani mals. This rep ort present s result s of the subchronic ph ase of study in which goitr ou s cha nges were found in rat s and mice. Materials and MethodsOn e hundred 28-day-old male and fem ale Fisc he r 344 rat s were obtai ned from Litton Bion erics, Fre derick Ca ncer Resea rch Ce nter, Frede rick, Md . All rat s were in goo d cond ition aft er isolati on and obse rva tion for 7 days. Before testin g, 5-wee k-old rat s wer e weighed and th ose at eithe r extrem e of the weig ht ran ge were d iscar ded . Fifty rat s of eac h sex were 649

Pituitary and Thyroid Gland Lesions Induced by 2-Mercaptobenzimidazole (2-MBI) Inhalation in Male Fischer-344 Rats

“…These lesions are consistent with those observed subsequent to chemical or physical thyroidectomy ( 1,3,10,11,15,17,27,29). It has previously been reported that the serum concentrations of T3 and T4 in rats exposed to 12.5 or 50.0 Mg/M3 of 2-MBI were significantly decreased (12).…”

“…Hypertrophic thyrotrophs from the 2-MBI-treated rats closely resembled thyrotrophs from thyroparathyroidectomized rats, as well as those previously described in rats and mice rendered hypothyroid by various means (3,11,15,27). Interestingly, not all hypertrophic thyrotrophs from our study or in previous studies stained immunohistochemically for the 0-chain of TSH.…”

4,4′‐Oxydianiline [MAK Value Documentation, 1993]

“…hormone [1]. Histological examination has revealed hyperplastic and neoplastic changes in the follicular cells with parallel development of pituitary hyperplasia.…”

“…In addition, bone marrow hypoplasia and renal microlithiasis developed in the rats; these effects, however, were not dose-dependent. In many of the highest dose group rats the lobular pattern of the liver was accentuated and the pancreas was embedded in clear gelatinous tissue [1,4].…”