Diisobutyl phthalate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Early non-guideline non-GLP study.

Data source

Reference

Reference Type:

publication

Title:

Hydrolysis of phthalate esters by purified rat and human liver carboxyesterases

Author:

Mentlein, R and Butte, W

Year:

1989

Bibliographic source:

Biochem Pharmacol 38, 3126-3128

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Three carboxyesterases isolated from rat liver (pI 5.6; pI 6.0; pI 6.2/6.4) and one from human liver. Enzymatic hydrolysis of diisobutyl phthalate (5 mM) was determined with 100 ul of purified enzyme (pH 8.0, 37 degrees C; pH-stat method).

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Diisobutyl phthalate

EC Number:

201-553-2

EC Name:

Diisobutyl phthalate

Cas Number:

84-69-5

Molecular formula:

C16H22O4

IUPAC Name:

1,2-bis(2-methylpropyl) benzene-1,2-dicarboxylate

Details on test material:

- Name of test material (as cited in study report): diisobutyl phthalate, purity not stated, supplied by BASF

Radiolabelling:

no

Test animals

Species:

other: rat, human

Results and discussion

Metabolite characterisation studies

Details on metabolites:

Hydrolysis of DIBP by human liver carboxyesterase (1.2 umol/min/mg protein) was intermediate between that of 2 rat liver carboxyesterases (0.7-7.4 umol/min/mg protein). Hydrolysis of other dialkyl phthalates also demonstrated but no metabolism of monophthalate esters found.

Any other information on results incl. tables

Hydrolysis of diisobutyl phthalate by human liver carboxyesterase = 1.2 umol/min/mg protein Hydrolysis of diisobutyl phthalate by rat liver carboxyesterase: - carboxyesterase pI 5.6 = 0.7 umol/min/mg protein - carboxyesterase pI 6.2/6.4 = 7.4 umol/min/mg protein - carboxyesterase pI 6.0 not tested Hydrolysis of other dialkyl phthalates (e.g. dimethyl, diethyl, diallyl, dibutyl etc) was also confirmed in these studies however no metabolism of monophthalate esters (e.g. monomethyl, monoethyl) was detected. The authors conclude that liver esterases hydrolyse only one ester bond present in phalate diesters.

Applicant's summary and conclusion

Conclusions:

Rat and human that liver carboxyesterases hydrolyse only one of the two ester bonds present in phthalate diesters i.e. convert diisobutyl phthalate to monoisobutyl phthalate.

Executive summary:

Enzymatic hydrolysis of diisobutyl phthalate by carboxyesterase purified from rat or human liver microsomal fractions was investigated in vitro using a pH-stat method. The highly purified enzymes were confirmed to have acceptable activity toward the model substrates phenyl butyrate (rat isozymes) and methyl butyrate / 4-nitrophenyl acetate (human enzyme). The human and rat liver carboxyesterases exhibited clear activity toward diisobutyl phthalate and other other dialkyl phthalates included in these experiments (e.g. dimethyl, diethyl, diallyl, dibutyl etc), however no metabolism of monophthalate esters (e.g. monomethyl, monoethyl) was found. The authors conclude that liver carboxyesterases hydrolyse only one of the two ester bonds present in phthalate diesters.