Registration Dossier

Diss Factsheets

Toxicological information

Exposure related observations in humans: other data

Currently viewing:

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication meeting generally accepted scientific principles.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Styrene-7,8-oxide in blood of workers exposed to styrene
Author:
Korn M., et al.
Year:
1994
Bibliographic source:
Arch Toxicol 68: 524-527
Reference Type:
secondary source
Title:
European risk assessment report, Styrene CAS No. 100-42-5, EINECS No. 202-851-5, Draft for submission to SCHER, November 2007.
Author:
European Union
Year:
2007

Materials and methods

Type of study / information:
A field study was carried out on 13 workers exposed to styrene vapours at time-weighted average concentrations between 10 and 73 ppm. The reactive intermediate styrene-7,8-oxide was determined in blood samples.
Endpoint addressed:
basic toxicokinetics
Principles of method if other than guideline:
This field study aimed to determine directly and quantitatively styrene-7,8-oxide in blood of styrene-exposed workers.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Styrene
EC Number:
202-851-5
EC Name:
Styrene
Cas Number:
100-42-5
Molecular formula:
C8H8
IUPAC Name:
ethenylbenzene
Details on test material:
- Name of test material (as cited in study report): styrene
- Analytical purity: no data

Method

Details on study design:
13 male workers (19-51 years) who were engaged in the production of reinforced polyester resins, and 3 male unexposed healthy volunteers from the laboratory staff (29-39 years)as controls were included in the study.
Details on exposure:
Styrene in ambient workplace air was monitored using an active personal air sampler with a charcoal tube fixed to the collar and combined with a portable unlined air pump. The charcoal tubes were desorbed by benzyl alcohol and analyzed by headspace GC. Time weighted average concentrations were calculated for individual exposure periods which have been divided into 4 sampling intervals. Determination of styrene in alveolar air was performed as described in Korn et al. (1994). Alveolar air samples were collected in glass vials and analysis was carried out by capillary gas chromatography.
Blood samples from the median cubital vein were taken into glass culture tubes containing heparin, the tubes were thereafter immediately placed on ice. Measurement of styrene in blood was done using a headspace gaschromatographic method.
Styrene-7,8-oxide was determined by means of capillary gas chromatography. Instantaneously after collection, 2 ml of the heparinized blood was transfereed to an ice-cold glass tube containing 12 ng (1R,2R)-(+)-1-phenylpropene oxide as internal standard. Because of the rapid decomposition of styrene-7,8-oxide in blood, samples were immediately extracted with hexane.

Results and discussion

Results:
Time-weighted average exposure concentrations of styrene in the ambient air of the workplace during time periods of 248-325 min were between 10 and 73 ppm. At the end of the exposure periods, styrene concentrations in alveolar air and in blood were within ranges of 0.54-1.58 ppm and of 78-836 µg/l, respectively. In unexposed controls, styrene concentrations were below the detection limits of 0.02 ppm in alveolar air and 20 µg/l in blood. Linear regression analysis gave a significant correlation between styrene concentrations in alveolar and ambient air. The correlation between styrene in venous blood and in ambient air was also significant. From the ratios of styrene in ambient air to styrene in alveolar air and blood, respectively, it can be deduced that exposure to styrene according to the German MAK value of 20 ppm (Henschler 1987) results in steady state styrene concentrations of about 0.5 ppm in alveolar air and 200 µg/l in blood.
In all blood samples of workers exposed to styrene the metabolite styrene-7,8-oxide was found, the concentrations lying between 0.9 µg/l (detection limit) and 4.1 µg/l. No styrene-7,8-oxide was found in control blood samples. Styrene-7,8-oxide in blood was correlated linearly with styrene in ambient air and blood. An exposure concentration of 20 ppm styrene results in a steady state level of styrene-7,8-oxide in venous blood of about 1 µg/l. Blood concentrations of styrene-7,8-oxide and its metabolic precursor styrene differ by more than two orders of magnitude.

Applicant's summary and conclusion