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Immunotoxicity of perfluorinated alkylates: calculation of benchmark doses based on serum concentrations in children

Philippe Grandjean12* and Esben Budtz-Jørgensen3

Author Affiliations

1 Department of Environmental Medicine, University of Southern Denmark, Odense, Denmark

2 Department of Environmental Health, Harvard School of Public Health, Boston, MA 02215, USA

3 Department of Biostatistics, University of Copenhagen, 2100, Copenhagen, Denmark

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Environmental Health 2013, 12:35  doi:10.1186/1476-069X-12-35

Published: 19 April 2013

Abstract

Background

Immune suppression may be a critical effect associated with exposure to perfluorinated compounds (PFCs), as indicated by recent data on vaccine antibody responses in children. Therefore, this information may be crucial when deciding on exposure limits.

Methods

Results obtained from follow-up of a Faroese birth cohort were used. Serum-PFC concentrations were measured at age 5 years, and serum antibody concentrations against tetanus and diphtheria toxoids were obtained at age 7 years. Benchmark dose results were calculated in terms of serum concentrations for 431 children with complete data using linear and logarithmic curves, and sensitivity analyses were included to explore the impact of the low-dose curve shape.

Results

Under different linear assumptions regarding dose-dependence of the effects, benchmark dose levels were about 1.3 ng/mL serum for perfluorooctane sulfonic acid and 0.3 ng/mL serum for perfluorooctanoic acid at a benchmark response of 5%. These results are below average serum concentrations reported in recent population studies. Even lower results were obtained using logarithmic dose–response curves. Assumption of no effect below the lowest observed dose resulted in higher benchmark dose results, as did a benchmark response of 10%.

Conclusions

The benchmark dose results obtained are in accordance with recent data on toxicity in experimental models. When the results are converted to approximate exposure limits for drinking water, current limits appear to be several hundred fold too high. Current drinking water limits therefore need to be reconsidered.

Keywords:
Benchmark dose; Developmental exposure; Immunotoxicity; Perfluorinated compounds; Risk assessment