Phthalic anhydride

Health surveillance data

Administrative data

Endpoint:

health surveillance data

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Limited documentation, no further information on half-life estimation

Data source

Reference

Reference Type:

publication

Title:

Phthalic acid excretion as an indicator of exposure to phthalic anhydride in the work atmosphere

Author:

Pfaeffli P

Year:

1986

Bibliographic source:

Int. Arch. Occup. Environ. Health 58, 209-216.

Materials and methods

Study type:

health record from industry

Endpoint addressed:

basic toxicokinetics

Principles of method if other than guideline:

no Guideline follwoed

Test material

Test material information

Constituent 1

Reference substance name:

Phthalic anhydride

EC Number:

201-607-5

EC Name:

Phthalic anhydride

Cas Number:

85-44-9

Molecular formula:

C8H4O3

IUPAC Name:

1,3-dihydro-2-benzofuran-1,3-dione

Method

Type of population:

occupational

Ethical approval:

not applicable

Details on study design:

The excretion of phthalic anhydride in humans has been investigated in a study where urine samples were collected from nine subjects occupationally exposed to phthalic anhydride, primarily by the inhalation route. Samples were taken pre-shift (7:00 hours), on-shift, post-shift (15:00 hours) and in the evening and the next morning after work day. Airborne phthalic anhydride levels ranged from 0.03 to 10.5 mg/m3 (mean value, MMAD not stated), determined from personal air samples from the worker breathing zone. Urine was also taken from a control group of 22 persons not occupational exposed to phthalic anhydride. Phthalic anhydride is converted to phthalic acid in the presence of water. Phthalic acid concentration in the urine was measured after esterification with methanol by electron capture gas chromatography, and expressed in terms of urinary creatinine. Urine samples were also subjected to acid, alkaline, and enzymatic hydrolysis by beta-glucuronidase or aryl sulphatase.

Results and discussion

Results:

Workers occupationally exposed to atmospheric phthalic anhydride absorbed the substance with some being excreted in the urine as unconjugated phthalic acid.
Details on excretion:
At low atmospheric phthalic anhydride concentrations (mean +/- SD; 0.15 +/- 0.15 mg/m3, range 0.03 - 0.33 mg/m3, n=5) the excretion of phthalic acid increased from the pre-shift (7:00 hours) concentration to the post-shift (15:00 hours) concentration and decreased then until the pre-shift concentration was again reached. The pre-shift phthalic acid concentration in the urine (0.49 +/- 0.15 µmol/mmol creatinine) were not significantly different from those of occupationally unexposed people (0.34 +/- 0.25 µmol/mmol creatinine, range 0.02-0.089 µmol/mmol creatinine, n=22). Exposure to higher concentrations of phthalic anhydride in air (1.63 +/- 0.13 mg/m3, n=2) resulted in a body load of phthalic acid which was not totally cleared overnight, and with pre-shift phthalic acid concentrations in the urine with a mean value three times the mean control value (1.02 +/- 0.25 µmol/mmol creatinine). One worker exposed to high concentration of phthalic anhydride (10.2 mg/m³) had a pre-shift urinary concentration of 4.8 µmol of phthalic acid /mmol creatinine; approximately 14 times that of the control group. The concentration of phthalic acid in the urine was found to increase from the pre-shift level to a maximum in the immediate post-shift or evening urine sample. The concentration then decreased, with a half-life of approx. 14 hours (no further information on half-life estimation).
Half-life: approx. 14 hours
Metabolites: unconjugated phthalic acid

Applicant's summary and conclusion

Executive summary:

The excretion of phthalic anhydride in humans has been investigated in a study where urine samples were collected from nine subjects occupationally exposed to phthalic anhydride, primarily by the inhalation route.

At low atmospheric phthalic anhydride concentrations (mean +/- SD; 0.15 +/- 0.15 mg/m³, range 0.03 - 0.33 mg/m³, n=5) the excretion of phthalic acid increased from the pre-shift (7:00 hours) concentration to the post-shift (15:00 hours) concentration and decreased then until the pre-shift concentration was again reached. The pre-shift phthalic acid concentration in the urine (0.49 +/- 0.15 µmol/mmol creatinine) were not significantly different from those of occupationally unexposed people (0.34 +/- 0.25 µmol/mmol creatinine, range 0.02-0.089 µmol/mmol creatinine, n=22). Exposure to higher concentrations of phthalic anhydride in air (1.63 +/- 0.13 mg/m³, n=2) resulted in a body load of phthalic acid which was not totally cleared overnight, and with pre-shift phthalic acid concentrations in the urine with a mean value three times the mean control value (1.02 +/- 0.25 µmol/mmol creatinine). The concentration of phthalic acid in the urine was found to increase from the pre-shift level to a maximum in the immediate post-shift or evening urine sample.

The concentration then decreased, with a half-life of approx. 14 hours. No evidence was seen of conjugate formation.