Metabolic fate of 1,4-cyclo[14C]hexanedimethanol in rats

DiVincenzo, G.D.; Ziegler, Donald A.

doi:10.1016/0041-008x(80)90241-0

Cited by 9 publications

(9 citation statements)

References 2 publications

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“…For example, the LD 50 of 1,4-cyclohexanedimethanol in rats is 3200 mg/kg for an oral dosage. 1,4-cyclohexanedimethanol also does not undergo significant enzymatic transformations in vivo; for example, a 400 mg/kg peritoneal gavage of 1,4-cyclohexanedimethanol in rats led to 97.5% of it being excreted intact (20). In addition, 1,4-cyclohexanedimethanol is a commonly used food packaging material and has approval for human consumption as an indirect food additive (Food Contact Notification (FCN) no.…”

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confidence: 99%

Polyketal Microparticles: A New Delivery Vehicle for Superoxide Dismutase

et al. 2006

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There is currently great interest in developing microparticles that can enhance the delivery of proteins to macrophages. In this communication, we present a new acid-sensitive polymer for drug delivery, poly(cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK). PCADK is designed to hydrolyze, after phagocytosis by macrophages, in the acidic environment of the phagosome and enhance the intracellular delivery of phagocytosed therapeutics. Other key attributes of PCADK for drug delivery are its well-characterized degradation products and straightforward synthesis. PCADK hydrolyzes into 1,4-cyclohexanedimethanol, a compound used in food packaging, and acetone, a compound on the FDA GRAS list. PCADK was synthesized using the acetal exchange reaction between 1,4-cyclohexanedimethanol and 2,2-dimethoxypropane, and could be obtained on a multigram scale in one step. The hydrolysis kinetics of the ketal linkages in PCADK were measured by 1 H NMR and were determined to be pH-sensitive, having a half-life of 24.1 days at pH 4.5 and over 4 years at pH 7.4. The therapeutic enzyme superoxide dismutase (SOD), which scavenges reactive oxygen species, was encapsulated into PCADKbased microparticles using a double emulsion procedure. Cell culture experiments demonstrated that PCADKbased microparticles dramatically improved the ability of SOD to scavenge reactive oxygen species produced by macrophages. We anticipate numerous applications of PCADK in drug delivery, based on its acid sensitivity, well-characterized degradation products, and straightforward synthesis.

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confidence: 99%

Polyketal Microparticles: A New Delivery Vehicle for Superoxide Dismutase

et al. 2006

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“…The actual degradation products are not specified, nor are the data suggesting estrogenicity shown in their report. However, CHDA is the primary metabolite of CHDM in rats (DiVincenzo and Ziegler, 1980) and our data show that CHDA has no endocrine activity in any of the assays performed. DMCD is considered to be an acceptable surrogate for CHDA.…”

Section: Discussionmentioning

confidence: 60%

Polyester monomers lack ability to bind and activate both androgenic and estrogenic receptors as determined by In Vitro and In Silico methods

Osimitz¹,

Welsh²,

Ni³

et al. 2015

Food and Chemical Toxicology

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The paper presents results from the screening of seven monomers used by Eastman Chemical to make various polymers. Ethylene glycol, diethylene glycol, polytetramethylene glycol, isophthalic acid, monosodium-5-sulfoisophthalic acid, 1,4-cyclohexanedicarboxylic acid, and dimethylcyclohexanedicarboxylate were screened for potential androgenicity or estrogenicity. The following studies were conducted: QSAR for binding to the AR and ER, in vitro Androgen Receptor Binding Assay, in vitro Estrogen Receptor Binding Assays (alpha and beta isoforms), in vitro Androgen Receptor Transactivation Assay in human cells, and in vitro Estrogen Receptor Transactivation Assay in human cells. None of the QSAR models predicted that any of the monomers possessed appreciable binding affinity for either AR or ER. Binding assays showed no evidence of interaction with either the AR or the alpha or beta ER receptors. Similarly, the AR and ER transactivation assays were negative. Moreover, six of the seven monomers have been subjected to 13-week and developmental toxicity studies in rats with no androgen- or estrogen-related effects being noted. Given the negative results of the in vitro screening assays (except PMG which demonstrated cytotoxicity) as well as available repeated dose and developmental and reproductive studies, the data suggest that none of the monomers tested exhibit androgenic or estrogenic hazards.

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“…Radiolabeled [ 14 C] 1,4-cyclohexanedimethanol (70% trans, 30% cis-isomers), a component of crude MCHM, was rapidly absorbed from the gastrointestinal tract in male and female Charles River Sprague Dawley rats. 15 Of the administered dose (40 or 400 mg/kg), 95% was eliminated in the urine and 2.5% in the feces 48 hours postexposure. The half-life of 1,4cyclohexanedimethanol in plasma following a dose of 400 mg/kg was approximately 13 minutes.…”

Section: Absorption Distribution Metabolism and Excretion Experimental Animalsmentioning

confidence: 99%

NTP Immunotoxicity Technical Report on the Dermal Hypersensitivity and Irritancy Studies of 4-Methylcyclohexanemethanol (CASRN 34885-03-5) and Crude 4-Methylcyclohexanemethanol Administered Topically to Female BALB/c Mice

2020

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Metabolic fate of 1,4-cyclo[14C]hexanedimethanol in rats

Cited by 9 publications

References 2 publications

Polyketal Microparticles: A New Delivery Vehicle for Superoxide Dismutase

Polyketal Microparticles: A New Delivery Vehicle for Superoxide Dismutase

Polyester monomers lack ability to bind and activate both androgenic and estrogenic receptors as determined by In Vitro and In Silico methods

NTP Immunotoxicity Technical Report on the Dermal Hypersensitivity and Irritancy Studies of 4-Methylcyclohexanemethanol (CASRN 34885-03-5) and Crude 4-Methylcyclohexanemethanol Administered Topically to Female BALB/c Mice

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