Experimental neoplasia in rats from oral administration of 3,3′-dichlorobenzidine, 4,4′-methylene-bis(2-chloroaniline), and 4,4′-methylene-bis(2-methylaniline)

Stula, Edwin F.; Sherman, H. C.; Zapp, John A.; Clayton, J. W.

doi:10.1016/0041-008x(75)90064-2

Cited by 80 publications

(18 citation statements)

References 8 publications

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“…A dose-dependent increase in lung tumours was observed in Sprague-Dawley rats fed 12.5, 25, or 50 mg/kg/day MBOCA for 18 months, and the incidence of lung tumours was 23%, 37%, and 70%, respectively [23]. A similar observation (presence of lung adenocarcinomas) was made in Charles River rats fed 50 mg/kg/day MBOCA for 2 years [11]. In another study, male Charles River CD-1 rats were fed 25 or 50 mg/kg/day MBOCA for 18 months.…”

Section: Discussionsupporting

confidence: 55%

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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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Section: Discussionsupporting

confidence: 55%

“…The MBOCA was dissolved in DMSO and diluted with 60% alcohol. The mice were treated with 50 mg/kg, 100 mg/kg and 200 mg/kg via different routes [2] [11]. There were 6 -10 mice per dose in each experiment as follows:…”

Section: Animal Modelsmentioning

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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show abstract

“…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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“…However, concern has been expressed following the observation that some of these dyes have proved to be metabolised to the parent amines in animals and humans (Lynn et al 1980;Bowman et al 1982;Cerniglia et al 1982;Kennelly et al 1982;Nony et al 1983a, b). Benzidine is a proven human carcinogen (DFG 1989) and 3,3'-dichlorobenzidine has been shown to be carcinogenic in several animal species (Pliss 1959;Sellakumar et al 1969;Stula et al 1975Stula et al , 1978. Direct Black 38, Direct Blue 6 and Direct Brown 95 (benzidine-based azo dyes) were found to be liver carcinogens in rats after administration for 13 weeks (Robens et al 1980).…”

Section: Introductionmentioning

confidence: 97%

Investigation of possible metabolism of Pigment Yellow 17, a 3,3′-dichlorobenzidine-based pigment, after inhalation exposure in rats

Hofmann

Schmidt

1993

Arch Toxicol

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Rats were exposed by inhalation to the technically highest administrable concentration of 230 mg Pigment Yellow 17/m3 air for 4 h. Inhalability of the dust was guaranteed by a mass-median aerodynamic diameter of 1.0-1.1 microns. For 14 days after exposure, urine and serum samples were analysed for 3,3'-dichlorobenzidine, the parent carcinogenic amine of the test compound. No 3,3'-dichlorobenzidine could be detected either in urine or blood, the detection limit being 5 ng/ml for both media. Based on the results of this study there is no evidence for metabolic cleavage of Pigment Yellow 17 to 3,3'-dichlorobenzidine in the rat.

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Experimental neoplasia in rats from oral administration of 3,3′-dichlorobenzidine, 4,4′-methylene-bis(2-chloroaniline), and 4,4′-methylene-bis(2-methylaniline)

Cited by 80 publications

References 8 publications

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

Investigation of possible metabolism of Pigment Yellow 17, a 3,3′-dichlorobenzidine-based pigment, after inhalation exposure in rats

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