Hyaline droplet nephropathy resulting from exposure to 3,5,5-trimethylhexanoyloxybenzene sulfonate

Journal Article · Thu Feb 28 23:00:00 EST 1991 · Toxicology and Applied Pharmacology; (USA)

DOI:https://doi.org/10.1016/0041-008X(91)90306-Y· OSTI ID:5950607

Lehman-McKeeman, L D; Rodriguez, P A; Caudill, D; Fey, M L; Eddy, C L; Asquith, T N ^[1]

---

1. Procter and Gamble Company, Cincinnati, OH (USA)

Acute oral dosing of 3,5,5-trimethylhexanoyloxybenzene sulfonate (THBS) to adult male and female rats causes a male rat-specific nephrotoxicity manifested as exacerbation of hyaline droplet formation. This chemical is structurally distinct from the volatile hydrocarbons known to cause male rat-specific kidney lesions. Therefore, to classify THBS as a hyaline droplet-inducing agent, experiments were conducted to determine whether (14C)THBS equivalents bound to alpha 2 mu-globulin and caused the protein to accumulate in male rat kidney cortex. Two-dimensional gel electrophoretic separation of male rat kidney proteins indicated that alpha 2u-globulin levels in kidney increased 24 hr after a single oral dose of THBS (500 mg/kg). Furthermore, a sex-dependent retention THBS was noted as there was approximately 10 times more THBS equivalents in male rat kidney than in female rat kidney. Equilibrium dialysis experiments indicated that 40% of THBS equivalents bound reversibly to male rat kidney proteins, whereas no interaction between THBS and female rat kidney proteins was detected. Specific binding of THBS to alpha 2mu-globulin was determined by anion-exchange HPLC after which metabolites in the alpha 2u-globulin fraction were identified by gas chromatography with parallel radioactivity-mass spectrometry and mass spectrometry-matrix isolation Fourier-transform infrared analysis. Four metabolites of THBS were found in this protein fraction, and the major component (approximately 70%) was identified as the cis gamma-lactone of 3,5,5-trimethylhexanoic acid. Experiments were also conducted in mice to determine whether THBS bound to any mouse kidney proteins, particularly mouse urinary protein. The results indicated that there was no interaction between THBS and mouse urinary protein, a protein which shares significant homology with alpha 2u-globulin.

• OSTI ID: 5950607
• Journal Information: Toxicology and Applied Pharmacology; (USA), Journal Name: Toxicology and Applied Pharmacology; (USA) Vol. 107:3; ISSN TXAPA; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACUTE EXPOSURE
ANIMALS
BODY
CARBON 14 COMPOUNDS
CHROMATOGRAPHY
DISEASES
ELECTROPHORESIS
FOURIER TRANSFORMATION
GLOBULINS
INTEGRAL TRANSFORMATIONS
ISOTOPE APPLICATIONS
KIDNEYS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MASS SPECTROSCOPY
METABOLISM
METABOLITES
MICE
ORAL ADMINISTRATION
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PROTEINS
RATS
RODENTS
SENSITIVITY
SEPARATION PROCESSES
SEX DEPENDENCE
SPECTROSCOPY
SULFONATES
TOXICITY
TRACER TECHNIQUES
TRANSFORMATIONS
UROGENITAL SYSTEM DISEASES
VERTEBRATES