Metabolism of di(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) in rats: in vivo and in vitro dose and time dependency of metabolism

Journal Article · Thu Aug 01 00:00:00 EDT 1985 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(85)90096-1· OSTI ID:5022841

Lhuguenot, J C; Mitchell, A M; Milner, G; Lock, E A; Elcombe, C R

This study investigated the in vivo metabolism of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate (MEHP) in rats after multiple dosing, the metabolism of MEHP in primary rat hepatocyte cultures for periods of up to 3 days, and the biotransformation of some major metabolites of MEHP. Rats were orally administered (/sup 14/C)DEHP or (/sup 14/C)MEHP at doses of 50 and 500 mg/kg body wt for three consecutive days. Urine was collected at 24-hr intervals, and metabolite profiles were determined. After a single dose of either compound, urinary metabolite profiles were similar to those previously reported. However, after multiple administration of both DEHP and MEHP at 500 mg/kg, increases in omega-/beta-oxidation products (metabolites I and V, mono(3-carboxy-2-ethylpropyl) phthalate and mono(5-carboxy-2-ethylpentyl) phthalate, respectively) and decreases in omega - 1-oxidation products (metabolites VI and IX, mono(2-ethyl-5-oxohexyl) phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate, respectively) were seen. At the low dose of 50 mg/kg little or no alteration in urinary metabolite profiles was observed. At 500 mg/kg of MEHP a 4-fold stimulation of CN- -insensitive palmitoyl-CoA oxidation (a peroxisomal beta-oxidation marker) was seen after three consecutive daily doses. At the low dose of 50 mg/kg only a 1.8-fold increase was noted. Similar observations were made with rat hepatocyte cultures. MEHP at concentrations of 50 and 500 microM was extensively metabolized in the rat hepatocyte cultures. Similar metabolic profiles to those seen after in vivo administration of MEHP were observed. At the high (500 microM) concentration of MEHP, changes in the relative proportions of omega- and omega- 1-oxidized metabolites were seen.

• Research Organization: Imperial Chemical Industries PLC, Cheshire, England
• OSTI ID: 5022841
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Vol. 1
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
PHTHALATES
METABOLISM
CARBON 14 COMPOUNDS
DOSE-RESPONSE RELATIONSHIPS
IN VITRO
LIVER
METABOLITES
ORAL ADMINISTRATION
RATS
TIME DEPENDENCE
TRACER TECHNIQUES
URINE
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY
BODY FLUIDS
CARBOXYLIC ACID SALTS
DIGESTIVE SYSTEM
GLANDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
ORGANS
RODENTS
VERTEBRATES
WASTES
550501* - Metabolism- Tracer Techniques