The carcinogenic effect of 4,4′-methylene-bis-(2-chloroaniline) in mice and rats

Russfield, Agnes B.; Homburger, F.; Boger, Eliahu; Dongen, C. G. Van; Weisburger, Elizabeth K.; Weisburger, John H.

doi:10.1016/0041-008x(75)90050-2

Cited by 77 publications

(12 citation statements)

References 7 publications

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“…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].…”

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confidence: 99%

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

1978

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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

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confidence: 99%

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

1978

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“…In another study, male Charles River CD-1 rats were fed 25 or 50 mg/kg/day MBOCA for 18 months. The authors reported lung adenocarcinoma in 1/22 and 1/19 animals, respectively [2], although this finding was not statistically significant. Oral administration of MBOCA to male and female rats increased the incidence of hepatomas and lung tumours [24].…”

Section: Discussionmentioning

confidence: 78%

“…Workers may inhale small particles of MBOCA in the air or absorb the agent through the skin if they come into contact with MBOCA dust or vapour. Acute exposure to high levels of MBOCA can cause eye and skin irritation in humans [2] [3]. The most notable risk factor for the development of lower urinary tract cancers is occupational exposure to aromatic amines, first noted in England in 1895 [4].…”

Section: Introductionmentioning

confidence: 99%

4,4’-Methylenebis(2-chloroaniline) (MBOCA) May Be Highly Toxic and a Carcinogen Based on an Experimental Study with Mice

Chen¹,

Chi²,

Ko³

et al. 2014

ABC

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Abstract4,4'-Methylenebis(2-chloroaniline) (MBOCA) is a probable human carcinogen. Few studies have been performed regarding the genotoxicity of MBCOA, and the MBOCA metabolic pathway is not fully understood. We treated four-week-old ICR male mice weighing 25 -30 g with MBOCA and observed the effects of MBOCA on the internal organs. It can be concluded that MBOCA is a carcinogen and also affects gene regulation. Oral or topical administration of 50 mg/kg, 100 mg/kg or 200 mg/kg MBOCA resulted in 56% -81% of mice showing unusual inflammation, degeneration, and dysplasia in kidney, liver, stomach, intestine and urinary bladder based on histology. Furthermore, we investigated the association between oxidative DNA damage and MBOCA exposure by measuring plasma level of 8-hydroxydeoxyguanosine (8-OHdG). The results showed that the MBOCA-treated mice had significantly higher 8-OHdG levels than the control mice. This study confirms that MBOCA is potentially carcinogenic and highly toxic to both animals and humans.

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“…After oral administration of MOCA, mice developed haemangiosarcomas and hepatomas (IARC monographs 1974;Russfield et ai. 1975), rats developed lung, liver, mammary gland and Zymbal gland tumours and haemangiosarcoma (IARC Monographs 1974;Russfield et al 1975;Stula et al 1975;Kommineni et al 1978).…”

Section: Introductionmentioning

confidence: 96%

Quantification of haemoglobin binding of 4,4′-methylenebis(2-chloroaniline)(MOCA) in rats

Sabbioni

Neumann

1990

Arch Toxicol

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4,4'-Methylenebis(2-chloroaniline) (MOCA) is used as a curing agent in the production of polyurethane. MOCA is carcinogenic in experimental animals. Haemoglobin adducts have been proposed as dosimeters of aromatic amines for biological monitoring. A quantitative method to determine the adduct has now been worked out in female Wistar rats dosed per os with 3.82, 14.2 and 16.2 mumol/kg 14C-ring labeled MOCA or 0.25 and 0.50 mmol/kg unlabeled MOCA. MOCA bound in decreasing amounts to DNA, RNA and proteins of the lung, liver and kidney. Fractions of 0.19% and 0.026% of the dose were bound to the blood proteins haemoglobin and albumin, respectively. MOCA released by hydrolysis from haemoglobin was determined by HPLC with electrochemical detection or by GC-MS. Albumin did not form any hydrolysable adducts with MOCA.

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The carcinogenic effect of 4,4′-methylene-bis-(2-chloroaniline) in mice and rats

Cited by 77 publications

References 7 publications

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

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

4,4’-Methylenebis(2-chloroaniline) (MBOCA) May Be Highly Toxic and a Carcinogen Based on an Experimental Study with Mice

Quantification of haemoglobin binding of 4,4′-methylenebis(2-chloroaniline)(MOCA) in rats

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