Toxicological Effects Of Perfluoroalkyl And Polyfluoroalkyl Substances Pdf

File Name: toxicological effects of perfluoroalkyl and polyfluoroalkyl substances .zip
Size: 10065Kb
Published: 31.03.2021

This book serves as a timely and comprehensive overview of the latest science for perfluoroalkyl and polyfluoroalkyl substances PFASs , covering the development of methods for assessing PFASs in biological fluids and tissues as well as the current knowledge regarding their toxicity to vertebrate organisms. Toxicological Effects of Perfluoroalkyl and Polyfluoroalkyl Substances provides critical assessments of the most controversial topics surrounding toxicological evaluation of PFASs to give readers an expert perspective on the issues. Emphasis is placed on the integration of modes and mechanisms of action with functional endpoints that are relevant to human and wildlife health.

Perfluoroalkyl and polyfluoroalkyl substances PFAS are found widespread in drinking water, foods, food packaging materials and other consumer products. Several PFAS have been identified as endocrine-disrupting chemicals based on their ability to interfere with normal reproductive function and hormonal signalling. This review summarises human population and toxicological studies on the association between PFAS exposure and ovarian function. A comprehensive review was performed by searching PubMed. Search terms included an extensive list of PFAS and health terms ranging from general keywords e.

Toxicological Effects of Perfluoroalkyl and Polyfluoroalkyl Substances

Perfluoroalkyl acids PFAAs , a group of synthetic organic chemicals with industrial and commercial uses, are of current concern because of increasing awareness of their presence in drinking water and their potential to cause adverse health effects. PFAAs are distinctive among persistent, bioaccumulative, and toxic PBT contaminants because they are water soluble and do not break down in the environment. This commentary discusses scientific and risk assessment issues that impact the development of drinking water guidelines for PFAAs, including choice of toxicological endpoints, uncertainty factors, and exposure assumptions used as their basis.

In experimental animals, PFAAs cause toxicity to the liver, the immune, endocrine, and male reproductive systems, and the developing fetus and neonate. Low-dose effects include persistent delays in mammary gland development perfluorooctanoic acid; PFOA and suppression of immune response perfluorooctane sulfonate; PFOS. In humans, even general population level exposures to some PFAAs are associated with health effects such as increased serum lipids and liver enzymes, decreased vaccine response, and decreased birth weight.

Ongoing exposures to even relatively low drinking water concentrations of long-chain PFAAs substantially increase human body burdens, which remain elevated for many years after exposure ends. This information, as well as emerging data from future studies, should be considered in the development of health-protective and scientifically sound guidelines for PFAAs in drinking water.

PLoS Biol 15 12 : e Editor: Linda S. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

The DWQI recommends drinking water standards for contaminants of concern in NJ based on relevant scientific information. Perfluoroalkyl acids PFAAs , a group of persistent organic pollutants, are the focus of current attention because of their detection in drinking water and a rapid increase in evidence for their adverse health effects. This commentary discusses PFAAs as emerging drinking water contaminants, and key scientific data and risk assessment issues for development of health-protective and scientifically sound PFAA drinking water guidelines.

PFAAs often referred to by the broader term, perfluorinated chemicals [PFCs] are anthropogenic compounds with a totally fluorinated carbon chain and a negatively charged functional group such as carboxylate or sulfonate Fig 1.

They are part of the larger group, per- and polyfluoroalkyl substances PFAS , that encompasses many other aliphatic substances containing at least one totally fluorinated carbon atom [ 1 ]. PFAAs have been produced for over 60 years. They are used commercially and in industrial processes because they repel both oil and water, withstand elevated temperatures, and are highly resistant to chemical reactions.

Commercial applications include stain-resistant coatings for upholstery and carpeting, water-resistant breathable outdoor clothing, and greaseproof food packaging. They are used in the manufacture of fluoropolymers such as polytetrafluoroethylene in non-stick cookware and fluoroelastomers high-performance synthetic rubber , but are not intentionally present in these finished products [ 1 , 5 ].

PFAAs differ from other environmental contaminants in several important ways. They persist indefinitely in the environment because of the strength of their carbon-fluorine bonds.

PFAAs are highly water-soluble while other well-known persistent, bioaccumulative, and toxic PBT organic pollutants such as polychlorinated dioxins and polychlorinated biphenyls have low water solubility.

Sources of PFAAs in the environment include industrial facilities where they are made or used, release of AFFF during training or firefighting, industrial and domestic wastewater treatment plant effluent, land application of biosolids sludge , and leachate from industrial waste or consumer products disposed of in landfills [ 8 ]. However, environmental contamination is expected to continue due to their environmental persistence, continued formation from precursors, and ongoing production by nonparticipating manufacturers especially overseas, particularly in China and India [ 5 , 10 ].

Of particular note, PFAAs that reach groundwater may remain there indefinitely, impacting drinking water sources for generations to come [ 11 ]. While not the focus of this paper, it is important to mention current concerns about the numerous compounds that have been introduced as replacements for the phased-out long-chain PFAAs, including shorter chain PFAAs and other types of PFAS such as perfluoroethers [ 12 ].

While these replacements are generally less bioaccumulative than long-chain PFAAs, they are similarly environmentally persistent, may be more mobile in the environment, and are less efficiently removed from drinking water by standard treatment processes [ 13 , 14 ]. They are not detected by standard analytical methods but have been found in drinking water at levels of potential concern in research studies [ 15 , 16 ].

Furthermore, some replacements cause toxic effects similar to long-chain PFAAs [ 17 ], while the toxicity of others may not have been adequately studied [ 13 ]. UCMR3 reporting thresholds were much higher e. Additionally, PFAAs have been detected in private drinking water wells adjacent to sources e. Body burdens of these compounds result from exposures to both the compounds themselves and conversion of precursors in the body [ 25 ].

These long-chain PFAAs are not metabolized and are slowly excreted with human half-lives of several years. Thus, PFAA serum levels remain elevated for many years after exposure ends. While general population exposure to PFAAs and precursors comes from sources including diet and consumer products, studies of exposed communities and predictions based on toxicokinetic factors show that low levels of PFAAs in drinking water i.

These empirical observations and toxicokinetic models Fig 2 consistently demonstrate that serum PFOA levels in adults increase on average by more than times the drinking water concentration [ 8 , 28 ], with greater predicted increases for PFOS and PFNA.

Notably, serum PFOA and PFOS were significantly higher among individuals residing in zip codes with UCMR3 detections than in other zip codes, although the study design tended to minimize differences between these two groups [ 29 ]. Predictions are based on the clearance factor for PFOA 0. Health-based guidelines for drinking water contaminants are developed with risk assessment approaches that consider toxicological, epidemiological, and mode of action data, and they are most often primarily based on toxicological data from laboratory animals.

However, for some PFAAs of concern in drinking water, particularly PFHxS, additional toxicological studies are likely needed before guidelines can be developed. Numerous human studies have examined associations between PFAAs and many health endpoints.

For example, over such studies of PFOS were published through A strength of most of these studies is that associations are based on blood serum PFAA levels that reflect individual variations in both external exposure e. Exposure assessments based on serum PFAA levels are therefore less uncertain than external exposure measures such as residential drinking water concentrations. Finally, health effects of several PFAAs were studied in occupationally exposed workers [ 34 ].

For PFOA, the PFAA with the largest epidemiological database, associations are generally consistent for increases in cholesterol, certain liver enzymes, and uric acid in blood serum; decreased fetal growth; and decreased vaccine response [ 31 ].

For other effects, no associations were found, or the data may be too limited to make firm conclusions [ 31 ]. A distinctive feature of the dose-response curves for several effects e. Although some effects linked to PFOA are relatively small in magnitude, they present a public health concern because such population-level changes can shift the overall distribution, thereby increasing the number of individuals with clinically abnormal values.

Additionally, small changes in a clinical measure such as birth weight may be indicative of other effects that were not evaluated such as changes in subtler developmental parameters [ 31 , 37 ]. Laboratory animal studies identify multiple targets for PFAA toxicity including the liver, immune system, endocrine system, male reproductive system, and developing fetus and neonate [ 31 , 38 , 39 ].

Toxicological effects are generally concordant with human epidemiology data, and recent studies suggest that dietary factors high-fat Western human diet versus low-fat standard laboratory rodent diet may contribute to differences in effects on lipid metabolism observed in rodents versus humans [ 40 , 41 ].

Toxicity that persists into adulthood from low-dose prenatal or neonatal exposures to some PFAAs is of particular concern. For PFOA, such effects, including changes in mammary gland development and persistent liver toxicity, are the most sensitive known toxicological endpoints [ 31 ]. Understanding the mode of action is crucial to the risk assessment process used to develop health-based guidelines, particularly in evaluating whether laboratory animal data are relevant to humans.

An important mode of action for PFAAs is activation of cellular receptors that regulate expression of genes controlling many biological pathways [ 43 ]. Activation can occur from even very low concentrations of compounds with high specificity for the receptor. Drinking water guidelines for PFAAs differ based on the choice of toxicological endpoint, uncertainty factors, drinking water exposure assumptions e. Although detailed discussion of the basis of the various guidelines is beyond the scope of this commentary, several important issues in development of drinking water guidelines for PFAAs should be mentioned.

Human studies are preferred as the basis for drinking water guidelines when suitable data are available. However, there is a high bar for use of human epidemiology in quantitative risk assessment due to its observational nature. However, limitations in the current human database, such as inability to determine the dose-response relationships for individual PFAAs due to co-occurrence of other PFAAs, preclude the use of human data as the primary basis for PFAA drinking water guidelines.

Accordingly, animal data are the primary basis for all PFAA drinking water guidelines developed so far by governmental organizations. This approach should be reconsidered if future studies provide further support for use of human data. Although current guidelines are not based on human data, considerable evidence linking some PFAAs with multiple human health effects even within the general population exposure range indicates the need for caution about additional exposure from drinking water [ 31 ].

Therefore, health-protective guidelines for PFAAs must consider the resulting increase in blood serum levels Fig 2. Links with several health effects at lower serum levels indicate that increases of this magnitude are not desirable and may not be protective of public health. An important consideration in risk assessments is the choice of the toxicological endpoint s used as their basis. Drinking water guidelines for PFAAs are generally based on non-cancer effects, and guidelines based on sensitive non-cancer PFOA endpoints, such as the value recommended by the New Jersey Drinking Water Quality Institute [ 31 ], protect for carcinogenicity at the one-in-one-million lifetime risk level.

For PFOA, hepatic effects, delayed bone formation, and accelerated puberty are the primary basis for recent guidelines [ 31 , 58 ], while more sensitive developmental endpoints such as delayed mammary gland development would result in much lower values [ 8 , 31 , 59 , 60 ]. Delayed mammary gland development from low doses of PFOA is well established, and several studies linking PFOA with shorter duration of breastfeeding support potential human relevance [ 31 ].

If additional studies provide further support for this or other emerging toxicological endpoints, their use as the primary basis for PFOA risk assessment should be reconsidered. Because PFAA half-lives are much longer in humans than animals, serum levels are much greater in humans than animals given the same dose.

The default uncertainty factor of 3 for interspecies toxicokinetic variability is insufficient to account for this large difference. Therefore, comparison of animals and humans is based on internal doses, as indicated by blood serum levels, in most current drinking water guidelines for long-chain PFAAs e.

Serum PFAA levels in breastfed infants are typically several fold higher than in older individuals using the same contaminated drinking water source; infants consuming formula prepared with contaminated water also receive higher exposures than adults reviewed in [ 31 , 39 ]. This is of concern because developmental effects from early life exposures are sensitive endpoints for PFAA toxicity. However, this approach is uncertain because PFAA risk assessments are based on steady-state serum levels from constant doses over many years, while infant exposures vary with age and occur over a period too short to reach steady-state.

Most drinking water guidelines for PFAAs use the default RSC because it is the most public health-protective option and because non-drinking water exposures in communities with drinking water contamination are not fully characterized e. However, some guidelines use higher chemical-specific RSCs based on the assumption that 95th percentile general population serum PFAA concentrations represent an upper limit for non-drinking water exposures [ 39 , 61 , 62 ].

Finally, multiple PFAAs with potentially additive or synergistic toxicities often co-occur in drinking water. Because the dose-response for some effects is steepest at low exposures and approaches a plateau at higher exposures, dose-response for mixtures may be complex and dose-dependent. PFAAs that have drinking water guidelines may also co-occur with other PFAS not included in routine analysis that are detected only by research analytical methods [ 15 ].

An important but frequently overlooked benefit of addressing exceedances of PFAA drinking water guidelines is that treatment removal processes intended to remove the compound s of concern may also partially or totally remove other PFAAs and PFAS, as well as unrelated contaminants, that may be present at levels of public health concern [ 31 ]. In conclusion, long-chain PFAAs cause low-dose toxicological effects in animals and some are associated with human health effects at general population exposure levels.

Ongoing exposure to even relatively low drinking water concentrations of long-chain PFAAs substantially increases human body burdens, which remain elevated for many years after exposure ends. Additionally, infants, a sensitive subpopulation, receive much higher exposures than adults from the same drinking water source. This information, along with other considerations presented above and additional data from future studies, should be considered in the development of PFAA drinking water guidelines to ensure that they are health-protective and scientifically sound.

Abstract Perfluoroalkyl acids PFAAs , a group of synthetic organic chemicals with industrial and commercial uses, are of current concern because of increasing awareness of their presence in drinking water and their potential to cause adverse health effects.

Funding: The authors received no specific funding for this work. Introduction Perfluoroalkyl acids PFAAs , a group of persistent organic pollutants, are the focus of current attention because of their detection in drinking water and a rapid increase in evidence for their adverse health effects. Download: PPT. Why are PFAAs in drinking water a current concern? Fig 2. Scientific information considered in developing PFAA drinking water guidelines Health-based guidelines for drinking water contaminants are developed with risk assessment approaches that consider toxicological, epidemiological, and mode of action data, and they are most often primarily based on toxicological data from laboratory animals.

Table 1. References 1. Perfluoroalkyl and polyfluoroalkyl substances in the environment: terminology, classification, and origins.

Toxicological and Health Effects of Per- and Polyfluoroalklyl Substance (PFAS) Mixtures

It seems that you're in Germany. We have a dedicated site for Germany. This book serves as a timely and comprehensive overview of the latest science for perfluoroalkyl and polyfluoroalkyl substances PFASs , covering the development of methods for assessing PFASs in biological fluids and tissues as well as the current knowledge regarding their toxicity to vertebrate organisms. Toxicological Effects of Perfluoroalkyl and Polyfluoroalkyl Substances provide critical assessments of the most controversial topics surrounding toxicological evaluation of PFASs to give readers an expert perspective on the issues. Emphasis is placed on the integration of modes and mechanisms of action with functional endpoints that are relevant to human and wildlife health. This book will be a useful resource for toxicologists, environmental chemists, risk assessors and researchers with an interest in the class of compounds known as perfluoroalkyl and polyfluoroalkyl substances.

Per- and polyfluoroalkyl substances

The combined effects and toxicological interactions of perfluoroalkyl and polyfluoroalkyl substances PFAS mixtures remain largely unknown even though they occur as complex mixtures in the environment. The Combination Index CI -isobologram equation method was used to determine the toxicological interactions of PFAS in binary, ternary and multi-component mixtures. The results indicated that the cytotoxicity of individual PFAS to HepG2 cells increased with increasing carbon chain lengths when separated into non-sulfonated and sulfonated groups. These cytotoxicity results may have an implication on the health risk assessment of PFAS mixtures.

Once production of your article has started, you can track the status of your article via Track Your Accepted Article. Help expand a public dataset of research that support the SDGs. Christopher Lau, Dr. Cynthia Rider and Dr. Dieter Schrenk.

Per- and polyfluoroalkyl substances PFASs , also perfluorinated alkylated substances are synthetic organofluorine chemical compounds that have multiple fluorine atoms attached to an alkyl chain. As such, they contain at least one perfluoroalkyl moiety , —C n F 2n —. They are more effective at reducing the surface tension of water than comparable hydrocarbon surfactants. They include the perfluorosulfonic acids such as the perfluorooctanesulfonic acid PFOS and the perfluorocarboxylic acids such as the perfluorooctanoic acid PFOA. Fluorosurfactants can reduce the surface tension of water down to a value half of what is attainable by using hydrocarbon surfactants.

Perfluoroalkyl acids PFAAs , a group of synthetic organic chemicals with industrial and commercial uses, are of current concern because of increasing awareness of their presence in drinking water and their potential to cause adverse health effects. PFAAs are distinctive among persistent, bioaccumulative, and toxic PBT contaminants because they are water soluble and do not break down in the environment. This commentary discusses scientific and risk assessment issues that impact the development of drinking water guidelines for PFAAs, including choice of toxicological endpoints, uncertainty factors, and exposure assumptions used as their basis. In experimental animals, PFAAs cause toxicity to the liver, the immune, endocrine, and male reproductive systems, and the developing fetus and neonate.

 - В чем разница. Должна же она. - Да! - Соши ткнула пальцем в свой монитор.  - Смотрите.