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Cited by 35Intramuscular injections and effectsImmunotoxicology and immune responsesPharmaceutical studies and practices

Pharmacokinetic modeling as an approach to assessing the safety of residual formaldehyde in infant vaccines

Mitkus, Robert J., Hess, Maureen A., Schwartz, Sorell L.·2013·Vaccine
DOI 10.1016/j.vaccine.2013.03.071
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Abstract

Formaldehyde is a one-carbon, highly water-soluble aldehyde that is used in certain vaccines to inactivate viruses and to detoxify bacterial toxins. As part of the manufacturing process, some residual formaldehyde can remain behind in vaccines at levels less than or equal to 0.02%. Environmental and occupational exposure, principally by inhalation, is a continuing risk assessment focus for formaldehyde. However, exposure to formaldehyde via vaccine administration is qualitatively and quantitatively different from environmental or occupational settings and calls for a different perspective and approach to risk assessment. As part of a rigorous and ongoing process of evaluating the safety of biological products throughout their lifecycle at the FDA, we performed an assessment of formaldehyde in infant vaccines, in which estimates of the concentrations of formaldehyde in blood and total body water following exposure to formaldehyde-containing vaccines at a single medical visit were compared with endogenous background levels of formaldehyde in a model 2-month-old infant. Formaldehyde levels were estimated using a physiologically-based pharmacokinetic (PBPK) model of formaldehyde disposition following intramuscular (IM) injection. Model results indicated that following a single dose of 200 μg, formaldehyde is essentially completely removed from the site of injection within 30 min. Assuming metabolism at the site of injection only, peak concentrations of formaldehyde in blood/total body water were estimated to be 22 μg/L, which is equivalent to a body burden of 66 μg or <1% of the endogenous level of formaldehyde. Predicted levels in the lymphatics were even lower. Assuming no adverse effects from endogenous formaldehyde, which exists in blood and extravascular water at background concentrations of 0.1 mM, we conclude that residual, exogenously applied formaldehyde continues to be safe following incidental exposures from infant vaccines.

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  • Except in the case of allergy to any of these components, there is no evidence of risk to human health from trace components of some vaccines.

    “Except in the case of allergy to any of these components, there is no evidence of risk to human health from these trace components of some vaccines19,20.”

    From A guide to vaccinology: from basic principles to new developments (2021) · cites this paper as [19]

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Authors
Mitkus, R. J., Hess, M. A., & Schwartz, S. L.
Affiliations
Center for Biologics Evaluation and Research (US)
Corresponding author
Mitkus, Robert J.
ORCID
Schwartz, Sorell L.
Venue
Vaccine
Publisher
Elsevier BV
Published
2013-06
Volume
31
Issue
25
Pages
2738-2743
ISSN
0264-410X (ISSN-L)
DOI
10.1016/j.vaccine.2013.03.071
OpenAlex
W1978385213
Cited by
35
References
59
Citations by year
2025: 1 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 2 · 2020: 6 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 5 · 2014: 2 · 2013: 1
FWCI
2.96
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Vaccine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Emergency Medicine › Intramuscular injections and effects
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Keywords
formaldehyde, residual formaldehyde, pharmacokinetic modeling, physiologically based pharmacokinetic modeling, vaccine safety, endogenous formaldehyde, body burden, intramuscular injection, lymphatic clearance, risk assessment, vaccine adjuvants
MeSH terms
Cross-Linking Reagents, Formaldehyde, Humans, Infant, Injections, Intramuscular, Models, Biological, Poliovirus Vaccine, Inactivated, Diphtheria-Tetanus-Pertussis Vaccine, Hepatitis B Vaccines, Haemophilus Vaccines, Risk Assessment

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