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At least 19 recordsLinked to original sources
PubMed1988

Metabolism of 4,4'-methylene-bis-2-chloroaniline (MOCA) by rats in vivo and formation of N-hydroxy MOCA by rat and human liver microsomes.

The metabolism of 4,4'-methylene-bis-2-chloroaniline (MOCA) was investigated because it is an animal carcinogen to which humans have been exposed. In CD rats, where MOCA is a hepatocarcinogen, less than or equal to 0.2% of an oral dose of [14C]MOCA was recovered unchanged in the urine; enzymatic hydrolysis and extraction of urinary radioactivity indicated the presence of glucuronide and sulfate conjugates. In rat bile, the predominant metabolite was N-glucuronyl MOCA. Liver microsomes from male CD rats or human males (surgical specimens) were incubated in vitro with [14C] MOCA. Metabolite formation, which was dependent upon reduced pyridine nucleotides and intact microsomes, was quantitated by TLC and HPLC using appropriate chemically synthesized standards. N-Hydroxylation of MOCA occurred at a rate of 335 +/- 119 pmol/min/mg rat microsomal protein (n = 3) versus 230 or 765 (n = 2) with microsomes from humans; the product was identified by isotopic dilution for both species. The rates of 5-hydroxy-MOCA (o-aminophenol) formation were 92 +/- 33 (rats) and 7, 35 (human); rates for the benzhydrol derivative were 82 +/- 12 (rats) and 60, 160 (human). In rats, all three rates were elevated 4- to 8-fold by pretreatment with phenobarbital, which also enhanced the formation of partially characterized polar derivatives that appeared to result from oxidation and cleavage at the methylene carbon. The latter pathway typically amounted to 50-100% of the 4,4'-diamino-3,3'-dichlorobenzhydrol value in control or pretreated animals. Thus, rats metabolize MOCA extensively and the pathways include N-hydroxlation, which is regarded as an obligatory step in metabolic activation of arylamines. The presence of MOCA N-hydroxylase in human liver supports the hypothesis that exposure of humans to MOCA entails a carcinogenic risk.

Animals↗
PubMed1991

4,4'-Methylenebis(2-chloroaniline) (MOCA): the effect of multiple oral administration, route, and phenobarbital induction on macromolecular adduct formation in the rat.

The effect of multiple oral administration of MOCA, a suspect human carcinogen, was studied in the adult male rat. As many as 28 consecutive daily doses of [14C]MOCA at 28.1 mumol/kg body wt (5 microCi/day) were administered and rats were euthanized at weekly intervals for 7 weeks. MOCA adduct formation for globin and serum albumin was evaluated by determination of [14C]MOCA covalent binding. The covalent binding associated with globin showed a linear increase over the 28-day exposure period with 342 fmol/mg globin 24 hr after the final dose. More extensive covalent binding was detected for albumin with 443 fmol/mg albumin after the final dose, but increases were not linear. After cessation of dosing, the albumin adduct levels decreased rapidly (t1/2 = 4.6 days) in relation to globin adduct levels (t1/2 = 16.1 days). The MOCA-globin adduct t1/2 is consistent with that determined after a single 281 mumol/kg oral dose of MOCA. Significant differences related to route of administration were detected for 24-hr globin covalent binding with ip greater than po greater than dermal. Distribution of undifferentiated [14C]MOCA was highest in the liver at 24 hr with tissue levels for liver greater than kidney greater than lung greater than spleen greater than testes greater than urinary bladder. Induction of cytochrome P450 enzymes by administration of phenobarbital (100 mg/kg/day/3 days) resulted in a significant (p less than 0.05) increase in MOCA-globin adduct formation detected with 33.5 pmol/mg globin for induced rats versus 13.6 pmol/mg globin for control rats. Although MOCA-globin and albumin adducts show differing stability, quantification of such MOCA adducts may be useful for long-term industrial biomonitoring of MOCA.

Administration, Oral↗
PubMed1990

4,4'-Methylene-bis(2-chloroaniline) (MOCA): comparison of macromolecular adduct formation after oral or dermal administration in the rat.

The macromolecular binding of 4,4'-methylenebis(2-chloroaniline) (MOCA), a suspect human carcinogen, was studied in the adult male Sprague-Dawley rat after both oral and dermal administration. Rats were euthanized 1, 3, 7, 10, 14, and 29 days after a single 281 mumol/kg body wt dose of [14C]MOCA (oral, 213 muCi/kg; dermal, 904 muCi/kg). DNA from various tissues and hemoglobin were isolated for determination of the time course of MOCA macromolecular binding. After oral administration adduct formation was rapid with maximum levels appearing at 24 hr. The 24-hr covalent binding associated with the globin was 7.84 pmol/mg globin (t1/2 = 14.3 days). More extensive 24-hr covalent binding was detected for liver DNA with 49.11 pmol/mg DNA (t1/2 = 11.1 days). After dermal administration of MOCA the major portion of the dose, 86.2%, remained at the application site throughout the study. For these rats the 24-hr covalent binding determined for liver DNA was 0.38 pmol/mg DNA (t1/2 = 15.6 days). Although lower levels were detected after dermal application, similar stability of MOCA-DNA adducts indicates that quantification of such MOCA adducts may be useful for the long-term industrial biomonitoring of MOCA exposure and for the evaluation of human DNA-MOCA adduct formation, a lesion thought to be associated with the production of cancer.

Administration, Cutaneous↗
PubMedDate not supplied

Urinary bladder tumors in dogs from 4,4'-methylene-bis (2-chloroaniline) (MOCA).

Six female beagle dogs were given a daily dose of 100 mg MOCA, by capsule, 3 days per week for the first 6 weeks and then 5 days per week continuously for periods up to 9.0 years. The dose varied from 8 to 15 mg/kg body weight/day among the dogs. Six female beagle dogs were kept as untreated controls. The test was terminated after 9.0 years of treatment. The average plasma glutamic-pyruvic transaminase activity of the dogs fed MOCA was higher than that of the controls during the first and last two years on test. During the eighth and ninth years the urine sediment from MOCA dogs contained excessive numbers of erythrocytes, leukocytes, and epithelial cells. Some epithelial cells contained abnormalities that suggested neoplasia in the genitourinary tract. One MOCA dog, sacrificed after 8.3 years on test was found to have a papillary transitional cell carcinoma of the urinary bladder. Of four MOCA dogs sacrificed after 9.0 years on test, three were found to have papillary transitional cell carcinomas of the urinary bladder and one had a combined transitional cell carcinoma and adenocarcinoma of the urethra. The urethral tumor had metastasized to the liver, but the papillary transitional cell carcinomas found in the other four dogs did not invade the muscle layers of the bladder wall and did not metastasize. Since no urinary bladder tumors were found in the six control dogs, MOCA was considered to be carcinogenic for the urinary bladder of dogs under the conditions employed (p less than 0.025, Fisher's Exact Test, one tail). Three of five MOCA dogs contained hyperplastic nodules in the liver with no such nodules in six control dogs (p greater than 0.05, Fisher's Exact Test, one tail). This was considered to be suggestive of an effect of MOCA treatment.

Animals↗
PubMed1990

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

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.

Animals↗
PubMed1985

Assessment of occupational exposure to 4,4'-methylene-bis-(2-chloroaniline) "MOCA" by a new sensitive method for biological monitoring.

A new specific and sensitive method for the urinary determination of 4,4'-methylene-bis-(2-chloroaniline) ("MOCA"), a known carcinogen in rats, mice and dogs, has been developed. After a brief study on rats to determine some peculiarities in "MOCA" urinary excretion, this method was used to assess occupational exposure in French industrial firms. Both the manufacture of "MOCA" and its use as a curing agent in the production of polyurethane elastomers were surveyed. "MOCA" excretion levels were distributed from non-detectable (less than 0.5 microgram/l) up to 1600 microgram/l. Concentrations of N-acetyl metabolites, when present, were largely lower than "MOCA" levels. The results seemed to reflect workers' overall exposure fairly. Preventive measures following analytical determinations often led to an obvious lowering of excretion levels.

Animals↗
PubMed1987

DNA binding of 4,4'-methylene-bis(2-chloroaniline) (MOCA) in explant cultures of human and dog bladder.

The binding to DNA of 4,4'-methylene-bis(2-chloroaniline) (MOCA) in explant cultures of human and dog bladder was compared. The DNA binding of MOCA in both human and dog bladder explants increased with the concentration of MOCA in the medium. In both species, there appeared to be a population with high DNA binding activity and another with low DNA binding activity. Furthermore, the binding of MOCA to human bladder DNA appeared to be higher than to dog bladder DNA. The results indicate the potential of MOCA to induce genetic damage in human bladder and suggest caution in the occupational exposure of humans to this chemical.

Animals↗
PubMed1985

Mutagenicity of 4,4'-methylene-bis-(2-chloroaniline) "MOCA" and its N-acetyl derivatives in S. typhimurium.

4,4'-methylene-bis-(2-chloroaniline) ("MOCA") and two identified urinary N-acetyl and N,N'-diacetyl derivatives were tested in a Salmonella/mammalian microsome assay. No mutagenic activity was observed without rat liver S9 mix activation. In the presence of rat liver S9 mix, the chemicals were mutagens, but the mutagenicity of N-acetyl derivatives to strain TA100 was reduced when compared to that of "MOCA", and a greater amount of S9 was required to exhibit the mutagenicity of the N,N'-diacetyl-"MOCA". These data suggest that N-acetylation does not account for the mutagenic effectiveness of "MOCA".

Acetylation↗
PubMed1975

Sulfamic acid cleaning solution for 4,4'-methylene-bisorthochloroaniline (MOCA).

Laboratory tests have shown that an aqueous solution of 1.0 wt.% sulfamic acid-0.5 vol.% surfactant can be used for decontaminating MOCA-contaminated surfaces to less than the analytical detectable limits for MOCA, without any flammability hazards. Nuclear magnetic resonance spectra have shown that a different compound is formed when sulfamic acid is reacted with MOCA, as evidenced by the disappearance of the NH2 peak from the MOCA spectrum.

Amines↗
PubMed1992

Biological and biological-effect monitoring of workers exposed to 4,4'-methylene-bis(2-chloroaniline).

4,4'-Methylene-bis(2-chloroaniline) (MOCA), a curing agent used in polyurethane manufacture, is a genotoxic and carcinogenic amine. This study aimed to assess occupational exposure to MOCA using as indices: (1) the post-work urinary output of MOCA; (2) urinary thioethers, assuming that conjugation with glutathione might be a significant pathway for the elimination of putative electrophilic metabolites of MOCA; and (3) sister-chromatid exchange (SCE) frequency in peripheral lymphocytes as an indicator of genetic damage. Process workers at a polyurethane production unit were found to have up to 38 mumol MOCA mol-1 creatinine in their urine at the end of a work shift. Smaller quantities were found in the urine of laboratory and supervisory staff, but none was detected in the urine of a group of office and sales staff from an unrelated industry, who served as unexposed controls. There was no evidence of MOCA-related urinary thioether output. There was a graded increase in SCE frequency from controls to process workers, consistent with their apparent exposure to MOCA. Administration of MOCA to rats (5 daily i.p. injections of 125 or 250 mg kg-1 resulted in dose-related increases in MOCA excretion and in lymphocyte SCE frequency, but there was no change in thioether output. These results indicate that urinary thioether excretion is inappropriate for monitoring MOCA exposure, but that where MOCA exposure can be demonstrated, by the presence of MOCA in urine, this is associated with genetic damage in both man and in the rat.

Adult↗
PubMedDate not supplied

Determination of the tumorigenic potential of methylene-bis-orthochloroaniline.

Methylene-bis-orthochloroaniline (MOCA) induced a wide spectrum of neoplasms in male rats fed either a protein-adequate (27 percent casein) or a protein-deficient (8 percent casein) diet. The concentrations of MOCA used were 125, 250, 500 and 1000 ppm. Increasing doses of MOCA in either diet resulted in decreased survival times. MOCA induced pulmonary adenomas, adenocarcinomas, mammary gland adenocarcinomas, Zymbal gland carcinomas, hepatocellular carcinomas, and hemangiosarcomas. In both diet groups the lungs were the most sensitive organs to the induction of neoplasms by MOCA. The incidence of primary pulmonary neoplasms in the lowest dose tested (125 ppm) was 6 percent (p less than or equal to 0.01), while in the highest dose (1000 ppm) it was 70 percent (p less than or equal to 0.01). The hepatocellular carcinoma incidence in rats fed a protein-deficient diet with 500 ppm MOCA was 18 percent, whereas in rats fed a protein-adequate diet with the same MOCA concentration this incidence was only 4 percent. The mean urinary concentration of MOCA in the group of rats fed the lowest dose (125 ppm-PD) was 0.63 ppm, a concentration comparable to that measured in the urine of workers exposed to MOCA.

Adenocarcinoma↗
PubMed1992

Contributions of human liver cytochrome P450 enzymes to the N-oxidation of 4,4'-methylene-bis(2-chloroaniline).

4,4'-Methylene-bis(2-chloroaniline) (MOCA) can produce tumors in rodents and dogs and an increased incidence of bladder tumors has been reported in exposed workers. It is therefore of interest to identify the human cytochrome P450 (P450) enzymes involved in MOCA N-oxidation, the primary reaction involved in the formation of an electrophilic product. Human liver microsomes were fractionated and MOCA N-oxidation activity was monitored through the procedure. The most active enzyme fraction corresponded to P450 3A4, as determined by immunochemical assays and N-terminal amino acid sequence analysis. Yeast recombinant P450 3A4 also had MOCA N-oxidation activity. Purified human liver P450 2A6 showed catalytic activity; however, anti-P450 2A6 inhibited less than 20% of the microsomal activity while anti-P450 3A4 inhibited up to 75%. Levels of marker activities of both P450 3A4 (nifedipine oxidation) and P450 2A6 (coumarin 7-hydroxylation) were measured in a set of human liver microsomes and both were correlated with MOCA N-oxidation rates. Gestodene and troleandomycin inhibited up to half of the microsomal MOCA N-hydroxylation activity but 7,8-benzoflavone showed only slight inhibition. Anti-P450 3A4 inhibited (up to 80% of) the microsomal transformation of MOCA to a product genotoxic as judged by bacterial SOS response. The work indicates that P450 3A4 makes a major contribution to human liver microsomal MOCA N-oxidation, and P450 2A6 has a minor role. P450 1A2, which catalyzes the hydroxylation of many arylamines, does not contribute to a great extent.

Benzoflavones↗
PubMed2026

Comparing the Efficacy of Mechanochemical Ablation Versus Radiofrequency Ablation for Treating Great Saphenous Vein Incompetence: A Meta-Analysis.

BACKGROUND: The objective of this meta-analysis was to compare the efficacy of mechanochemical ablation (MOCA) and radiofrequency ablation (RFA) in the treatment of great saphenous vein (GSV) incompetence. METHODS: Online databases including PubMed, Cochrane Library, Embase, and Web of Science were searched to collect randomized controlled trials (RCTs) and cohort studies comparing MOCA and RFA in the treatment of varicose veins in lower extremities from database inception to October 2025. Primary outcome was anatomic success. Secondary outcomes were visual analog scale (VAS), Aberdeen Varicose Vein Questionnaire score (AVVQ), and complications. Two reviewers independently screened the retrieved literature, extracted data, and assessed the risk of bias in the included studies. Subsequent analysis was performed using RevMan 5.3. RESULTS: A total of four RCTs, one cohort study and retrospective cross-sectional study involving 737 patients (380 MOCA patients and 357 RFA patients) were included. The meta-analysis results showed that the RFA group was significantly better than the MOCA group in short term and long term of anatomical success rate [(odds ratio [OR] = 0.38; 95% confidence interval [CI] (0.20, 0.71), P = 0.003), (OR = 0.17, 95% CI (0.06, 0.45), P = 0.0003)], but patients in the MOCA group had significantly lower perioperative period pain (mean difference [MD] = -4.48, 95% CI (-7.58, -1.37), P = 0.005] and required fewer days to return to normal activities (MD = -0.76, 95% CI, (-0.95, -0.57), P < 0.001). No significant differences were observed between the two groups in minor and major complications [(OR = 0.93, 95% CI (0.66, 1.33), P = 0.70), (OR = 1.30, 95% CI (0.32, 5.28), P = 0.72)] or quality of life scores (MD = -0.45, 95% CI (-2.53 to 1.63), P = 0.67). CONCLUSION: MOCA of GSV incompetence is an effective and safe method. Compared with RFA, it has lower postoperative pain score and faster recovery time. However, the anatomical success rates were significantly lower with MOCA than with RFA. Therefore, long-term follow-up to evaluate the impact on clinical results is required.

Humans↗