Estimation of a possible tumorigenic risk of styrene from daily intake via food and ambient air

Johannes G. Filser; Winfried Kessler; György A. Csanády

doi:10.1016/S0378-4274(01)00420-9

Estimation of a possible tumorigenic risk of styrene from daily intake via food and ambient air

Johannes G. Filser, Winfried Kessler, György A. Csanády

Helmholtz Zentrum München German Research Center for Environmental Health

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

Concerns of a tumorigenic risk of styrene (ST) originate from the findings that styrene (ST) is metabolized to the genotoxic intermediate styrene-7,8-oxide (SO). Therefore, it was hypothesized that results of animal long-term studies with ST and SO together with the SO tissue burden are sufficient for conducting a 'worst case' estimate of the tumorigenic risk of ST. On this basis we predicted the excess human lifetime risk for lung tumors (ρ_EXL) and the highest possible risk for other systemic tumors (ρ_HPS) resulting from daily intake of ST via food and ambient air. As measures for ρ_EXL the mean lifetime concentration of SO in the transitional zone of the lung and for ρ_HPS the mean lifetime concentration of SO in blood were calculated using a physiological toxicokinetic model. For a daily oral intake of 12 μg ST, ρ_EXL was obtained to be between 5×10^-9 and 2×10^-8 and ρ_HPS to be between 7×10^-9 and 2×10^-8. Lifetime risks calculated for continuous exposure to 3 μg/m³ ST in ambient air were between 8×10^-7 and 3×10^-6 (ρ_EXL) and between 2×10^-8 and 4×10^-8 (ρ_HPS). Although these values indicate very low risks, the actual risks are expected to be even by far smaller. This is discussed in detail for lung tumorigenesis.

Original language	English
Pages (from-to)	1-18
Number of pages	18
Journal	Toxicology Letters
Volume	126
Issue number	1
DOIs	https://doi.org/10.1016/S0378-4274(01)00420-9
State	Published - 5 Jan 2002
Externally published	Yes

Keywords

Food
Human
Inhalation exposure
Mouse
Oral intake
Physiological toxicokinetic model
Rat
Rodent bioassay
Species extrapolation
Styrene
Styrene-7,8-oxide
Toxicokinetics
Tumorigenic risk

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10.1016/S0378-4274(01)00420-9

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title = "Estimation of a possible tumorigenic risk of styrene from daily intake via food and ambient air",

abstract = "Concerns of a tumorigenic risk of styrene (ST) originate from the findings that styrene (ST) is metabolized to the genotoxic intermediate styrene-7,8-oxide (SO). Therefore, it was hypothesized that results of animal long-term studies with ST and SO together with the SO tissue burden are sufficient for conducting a 'worst case' estimate of the tumorigenic risk of ST. On this basis we predicted the excess human lifetime risk for lung tumors (ρEXL) and the highest possible risk for other systemic tumors (ρHPS) resulting from daily intake of ST via food and ambient air. As measures for ρEXL the mean lifetime concentration of SO in the transitional zone of the lung and for ρHPS the mean lifetime concentration of SO in blood were calculated using a physiological toxicokinetic model. For a daily oral intake of 12 μg ST, ρEXL was obtained to be between 5×10-9 and 2×10-8 and ρHPS to be between 7×10-9 and 2×10-8. Lifetime risks calculated for continuous exposure to 3 μg/m3 ST in ambient air were between 8×10-7 and 3×10-6 (ρEXL) and between 2×10-8 and 4×10-8 (ρHPS). Although these values indicate very low risks, the actual risks are expected to be even by far smaller. This is discussed in detail for lung tumorigenesis.",

keywords = "Food, Human, Inhalation exposure, Mouse, Oral intake, Physiological toxicokinetic model, Rat, Rodent bioassay, Species extrapolation, Styrene, Styrene-7,8-oxide, Toxicokinetics, Tumorigenic risk",

author = "Filser, {Johannes G.} and Winfried Kessler and Csan{\'a}dy, {Gy{\"o}rgy A.}",

note = "Funding Information: The financial support by the Styrene Steering Committee of the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) is gratefully acknowledged. The authors thank Dr Hans-Dieter Hoffmann, BASF, for valuable discussions. ",

year = "2002",

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doi = "10.1016/S0378-4274(01)00420-9",

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T1 - Estimation of a possible tumorigenic risk of styrene from daily intake via food and ambient air

AU - Filser, Johannes G.

AU - Kessler, Winfried

AU - Csanády, György A.

N1 - Funding Information: The financial support by the Styrene Steering Committee of the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) is gratefully acknowledged. The authors thank Dr Hans-Dieter Hoffmann, BASF, for valuable discussions.

PY - 2002/1/5

Y1 - 2002/1/5

N2 - Concerns of a tumorigenic risk of styrene (ST) originate from the findings that styrene (ST) is metabolized to the genotoxic intermediate styrene-7,8-oxide (SO). Therefore, it was hypothesized that results of animal long-term studies with ST and SO together with the SO tissue burden are sufficient for conducting a 'worst case' estimate of the tumorigenic risk of ST. On this basis we predicted the excess human lifetime risk for lung tumors (ρEXL) and the highest possible risk for other systemic tumors (ρHPS) resulting from daily intake of ST via food and ambient air. As measures for ρEXL the mean lifetime concentration of SO in the transitional zone of the lung and for ρHPS the mean lifetime concentration of SO in blood were calculated using a physiological toxicokinetic model. For a daily oral intake of 12 μg ST, ρEXL was obtained to be between 5×10-9 and 2×10-8 and ρHPS to be between 7×10-9 and 2×10-8. Lifetime risks calculated for continuous exposure to 3 μg/m3 ST in ambient air were between 8×10-7 and 3×10-6 (ρEXL) and between 2×10-8 and 4×10-8 (ρHPS). Although these values indicate very low risks, the actual risks are expected to be even by far smaller. This is discussed in detail for lung tumorigenesis.

AB - Concerns of a tumorigenic risk of styrene (ST) originate from the findings that styrene (ST) is metabolized to the genotoxic intermediate styrene-7,8-oxide (SO). Therefore, it was hypothesized that results of animal long-term studies with ST and SO together with the SO tissue burden are sufficient for conducting a 'worst case' estimate of the tumorigenic risk of ST. On this basis we predicted the excess human lifetime risk for lung tumors (ρEXL) and the highest possible risk for other systemic tumors (ρHPS) resulting from daily intake of ST via food and ambient air. As measures for ρEXL the mean lifetime concentration of SO in the transitional zone of the lung and for ρHPS the mean lifetime concentration of SO in blood were calculated using a physiological toxicokinetic model. For a daily oral intake of 12 μg ST, ρEXL was obtained to be between 5×10-9 and 2×10-8 and ρHPS to be between 7×10-9 and 2×10-8. Lifetime risks calculated for continuous exposure to 3 μg/m3 ST in ambient air were between 8×10-7 and 3×10-6 (ρEXL) and between 2×10-8 and 4×10-8 (ρHPS). Although these values indicate very low risks, the actual risks are expected to be even by far smaller. This is discussed in detail for lung tumorigenesis.

KW - Food

KW - Human

KW - Inhalation exposure

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KW - Oral intake

KW - Physiological toxicokinetic model

KW - Rat

KW - Rodent bioassay

KW - Species extrapolation

KW - Styrene

KW - Styrene-7,8-oxide

KW - Toxicokinetics

KW - Tumorigenic risk

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DO - 10.1016/S0378-4274(01)00420-9

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AN - SCOPUS:0037021810

SN - 0378-4274

VL - 126

SP - 1

EP - 18

JO - Toxicology Letters

JF - Toxicology Letters

IS - 1

ER -

Estimation of a possible tumorigenic risk of styrene from daily intake via food and ambient air

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Keywords

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