Immunotoxicity of perfluorinated alkylates: calculation of benchmark doses based on serum concentrations in children.
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Immunotoxicity of perfluorinated alkylates: calculation of benchmark doses based on serum concentrations in children. / Grandjean, Philippe; Budtz-Joergensen, Esben.
I: Environmental Health, Bind 12, Nr. 1, 19.04.2013, s. 35.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Immunotoxicity of perfluorinated alkylates: calculation of benchmark doses based on serum concentrations in children.
AU - Grandjean, Philippe
AU - Budtz-Joergensen, Esben
PY - 2013/4/19
Y1 - 2013/4/19
N2 - 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 ages 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 dose 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.
AB - 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 ages 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 dose 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.
KW - benchmark dose
KW - developmental exposure
KW - immunotoxicity
KW - perfluorinated compounds
KW - risk assessment
U2 - 10.1186/1476-069X-12-35
DO - 10.1186/1476-069X-12-35
M3 - Tidsskriftartikel
C2 - 23597293
VL - 12
SP - 35
JO - Environmental Health
JF - Environmental Health
SN - 1476-069X
IS - 1
ER -
ID: 136715145