Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only secondary literature available

Data source

Reference
Reference Type:
secondary source
Title:
SIAP for phthalic anhydride, CAS-No. 85-44-9. SIAM 20. Original article: Phtalic acid excretion as an indicator of exposure to phthalic anhydride in the work atmosphere (Int. Arch. Occup. Environ. Health 58, 209-216).
Author:
OECD
Year:
2005
Bibliographic source:
OECD SIAM 20 (2005)
Report Date:
2005

Materials and methods

Objective of study:
excretion
Principles of method if other than guideline:
see details in remarks on material and methods
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): phthalic anhydride
Radiolabelling:
no

Test animals

Species:
human

Administration / exposure

Route of administration:
inhalation
Vehicle:
unchanged (no vehicle)
Doses / concentrations
Remarks:
Doses / Concentrations:
0.03-10.5 mg/m3
No. of animals per sex per dose:
9 humans
Control animals:
yes
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine
- Time and frequency of sampling: 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.

Results and discussion

Any other information on results incl. tables

At low atmospheric phthalic anhydride concentrations (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). No evidence was seen of conjugate formation.

 

Thus, workers occupationally exposed to atmospheric phthalic anhydride absorbed the substance with some being excreted in the urine as unconjugated phthalic acid.

Applicant's summary and conclusion