|
 |
|
EDRI Federal Project Inventory:
Toxic Effects of Butylated Triphenyl Phosphate-based Hydraulic Fluid
- Sponsor Organization: AIR FORCE
- Project Title: TOXIC EFFECTS OF BUTYLATED TRIPHENYL PHOSPHATE-BASED HYDRAULIC FLUID.
- Project Focus: HUMAN HEALTH EFFECTS, EXPOSURE ASSESSMENT
- Description: Triaryl phosphates (TPs), including tricresyl phosphate (TCP) and
butylated triphenylphosphate (BTP), are used in the commercial
manufacture of plastics, lubricants, andhydraulic fluids. The
Department of Defense uses large quantities of triaryl phosphate-based
hydraulic fluids. Recent reports implicate these compounds as
endocrinetoxicants. TC s cause cholesteryl lipidosis in
adrenocortical cells of rats resulting inaltered metabolism of
cholesterol, the precursor of steroid hormone biosynthesis.Human
synthesis of adrenocortical steroid hormones likewise requires
cholesterol. Thetoxic mechanism in the rat is inhibition of cytosolic
neutral cholesteryl ester hydrolase(nCHE) by these organophosphates,
disrupting serum uptake from lipoproteins (theprincipal source) and
utilization of cholesterol for steroid biosynthesis. These cells
canapparently still synthesize enough cholesterol de novo (a less used
pathway) toprevent adrenocortical insufficiency when stress is not a
significant factor, butprolonged stress may result in adrenocortical
insufficiency, because the major sourceof cholesterol is blocked by
these xenobiotics. Humans also rely on serum uptake ofcholesterol from
lipoproteins for adrenocortical hormone biosynthesis. If TC s
alsoinhibit uptake in humans, prolonged stress such as a combat
scenario in conjunctionwith TC s exposure could result in
adrenocortical insufficiency, a potentially fatalcondition. Humans
require lysosomal acid cholesteryl ester hydrolase (aCHE)(notcytosolic
nCHE like the rat) for uptake/utilization of serum cholesterol in the
adrenalgland. The effect of TC s on aCEH is unknown. Our studies will
address human healthrisk by studying 1) TC effects on aCHE and 2) TC
effects in conjunction with prolongedstress on adrenocortical
function.
- References: Latendresse JR, Brooks CL, Flemming CD, and Capen CC (1994)
Reproductivetoxicity of Butylated Triphenyl Phosphate and Tricresyl
Phosphate Fluids in F344 Rats.Fundamental and Applied Toxicology .
22:392-399.Latendresse JR, Azhar S, Brooks CL, and Capen CC (1993)
Pathogenesis ofCholesteryl Lipidosis of Adrenocortical and Ovarian
Interstitial Cells in F344 ratsCaused Tricresyl Phosphate and
Butylated Triphenyl Phosphate. Toxicology andApplied Pharmacology
122, 281-289.
- Category: MEASUREMENTS, METHODS
- Subcategory: BASIC RESEARCH, HAZARD IDENTIFICATION
- Keywords for Experimental System/Species: IN VIVO, MAMMALIAN, LABORATORY STUDY
- Keywords for Experimental Endpoints: REPRODUCTIVE, FEMALE, MALE, HORMONAL MEASURES, SEX STEROIDS,
XENOBIOTICMETABOLISM
- Chemical Agents: Butylated triphenyl phosphates
- Performing Institution: Toxicology Division; Armstrong Laboratory; 2856 G St; Wright-Patterson
AFB; OH45422-7400
- Contact: CAPT Kenneth R. Still MSC, USN; Comm: (513) 255-6058, DSN: 785-6058;
E-Mail:kstill@navy.al.wpafb.af.mil
|
|
