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

Grandjean P, Budtz-Jørgensen E - Environ Health (2013)

Bottom Line: 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%.The benchmark dose results obtained are in accordance with recent data on toxicity in experimental models.

View Article: PubMed Central - HTML - PubMed

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.

Show MeSH

Related in: MedlinePlus

Estimated dose–response functions for the relationship between PFOS and the diphtheria-antibody concentration. Curve A is estimated as a generalized additive model. Curve B is the log-function, C is piecewise linear, and D is linear. The low-dose threshold models (see Table 3) assume a flat curve below the lowest observed dose indicated by the dotted vertical line, i.e., that a threshold exists at the lowest serum-PFOS concentration observed. The bars on the horizontal scale indicate the serum-PFOS concentration of each participating cohort member.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3643874&req=5

Figure 1: Estimated dose–response functions for the relationship between PFOS and the diphtheria-antibody concentration. Curve A is estimated as a generalized additive model. Curve B is the log-function, C is piecewise linear, and D is linear. The low-dose threshold models (see Table 3) assume a flat curve below the lowest observed dose indicated by the dotted vertical line, i.e., that a threshold exists at the lowest serum-PFOS concentration observed. The bars on the horizontal scale indicate the serum-PFOS concentration of each participating cohort member.

Mentions: As a consequence of the relatively steep dose–response relationships, the BMDs were sometimes lower than the minimum observed exposure, and some results therefore depended on a part of the dose–response curve, for which the data does not hold any information. As a sensitivity analysis, we therefore developed a low-dose threshold version of each of the dose–response models used. Each of these models was identical to the original dose–response model within the observed dose range, but with a flat dose–response slope below the lowest dose observed (Figure 1).


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

Grandjean P, Budtz-Jørgensen E - Environ Health (2013)

Estimated dose–response functions for the relationship between PFOS and the diphtheria-antibody concentration. Curve A is estimated as a generalized additive model. Curve B is the log-function, C is piecewise linear, and D is linear. The low-dose threshold models (see Table 3) assume a flat curve below the lowest observed dose indicated by the dotted vertical line, i.e., that a threshold exists at the lowest serum-PFOS concentration observed. The bars on the horizontal scale indicate the serum-PFOS concentration of each participating cohort member.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643874&req=5

Figure 1: Estimated dose–response functions for the relationship between PFOS and the diphtheria-antibody concentration. Curve A is estimated as a generalized additive model. Curve B is the log-function, C is piecewise linear, and D is linear. The low-dose threshold models (see Table 3) assume a flat curve below the lowest observed dose indicated by the dotted vertical line, i.e., that a threshold exists at the lowest serum-PFOS concentration observed. The bars on the horizontal scale indicate the serum-PFOS concentration of each participating cohort member.
Mentions: As a consequence of the relatively steep dose–response relationships, the BMDs were sometimes lower than the minimum observed exposure, and some results therefore depended on a part of the dose–response curve, for which the data does not hold any information. As a sensitivity analysis, we therefore developed a low-dose threshold version of each of the dose–response models used. Each of these models was identical to the original dose–response model within the observed dose range, but with a flat dose–response slope below the lowest dose observed (Figure 1).

Bottom Line: 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%.The benchmark dose results obtained are in accordance with recent data on toxicity in experimental models.

View Article: PubMed Central - HTML - PubMed

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.

Show MeSH
Related in: MedlinePlus