Perfluorooctanesulfonate [PFOS; CF3(CF2)7SO3−] and its acid salts were derived from perfluorooctanesulfonyl fluoride [POSF; CF3(CF2)7SO2F]. Major product applications were developed using POSF through formation of N-alkylsulfonamides that were used in surfactants, paper and packaging treatments, and surface protectants (e.g., carpet, upholstery, textiles). Depending on the specific functional derivitization or polymerization, these POSF-based products may have degraded or metabolized, to an undetermined degree, to PFOS, a stable and persistent end product that has a widespread presence in the general population (Butenhoff et al. 2006) and wildlife (Houde et al. 2006).

Salts of perfluorooctanoic acid, in particular ammonium perfluorooctanoate (APFO), have been used as surfactants and processing aids in the production of fluoropolymers and fluoro-elastomers. Industrial production of the salts of perfluorooctanoic acid occur through electrochemical fluorination and telomerization. Perfluorooctanoate [PFOA; CF3(CF2)6COO−], the dissociated carboxylate anion, has been measured in humans worldwide but generally at lower nanogram per milliliter concentrations than PFOS (Houde et al. 2006).

In rats, PFOS and PFOA are not metabolized and enter into the enterohepatic circulation (Johnson et al. 1984; Kemper 2003; Kuslikis et al. 1992; Vanden Heuvel et al. 1991). Because of the stability of the carbon–fluorine bond and the high electronegativity of perfluorinated alkyl acids, metabolism would not be favored; thus, perfluorohexanesulfonate (PFHS) is also not expected to be metabolized.

Based on the determination of volumes of distribution from single-dose intravenous studies in cynomolgus monkeys, the distributions of PFOS, PFHS, and PFOA are primarily extracellular (Butenhoff et al. 2004; Noker and Gorman 2003a, 2003b). Kerstner-Wood et al. (2003) found PFOS, PFHS, and PFOA to be highly bound in rat, monkey, and human plasma over a concentration range of 1–500 μg/mL. When incubated with human plasma protein fractions, all three compounds were highly bound (99.7 to > 99.9%) to albumin, and showed affinity for β-lipoproteins (95.6, 64.1, and 39.6% for PFOS, PFHS, and PFOA, respectively). Some binding to α - and γ -globulin fractions and minor interactions with transferrin (PFHS and PFOA) were also noted. PFOS and PFOA have been shown to compete for fatty acid binding sites on liver fatty acid binding protein, with PFOS giving the stronger response (Luebker et al. 2002).

The elimination rates of PFOS and PFHS have been studied in male and female cynomolgus monkeys after intravenous dosing (Noker and Gorman 2003a, 2003b) and for PFOS after repeated oral dosing (Seacat et al. 2002). Noker and Gorman (2003a, 2003b) reported mean (± SD) terminal elimination half-lives, ranging from 88 to 146 days (132 ± 13 days for males and 110 ± 26 days for females) for PFOS and 49 to 200 days (141 ± 52 days for males and 87 ± 47 days for females) for PFHS, after intravenous dosing of three male and three female cynomolgus monkeys in separate experiments, with no significant difference between males and females or between the two compounds. Seacat et al. (2002) reported an approximate terminal elimination half-life of 200 days for PFOS in male and female cynomolgus monkeys during 1 year immediately following 6 months of daily oral dosing with either 0.15 or 0.75 mg/kg PFOS.

Elimination rates in species other than the monkey have been determined for PFOS and PFOA. Within 89 days after a single intravenous dose of 14C-PFOS, 30% of the 14C was excreted in the urine and 12% in the feces of male rats (Johnson et al. 1979). For PFOA, significant interspecies differences have been observed (Hundley et al. 2006; Kudo and Kawashima 2003), and differential expression of organic anion transporters in renal proximal tubule cells have been suggested as an explanation for sex differences in the rat (Kudo et al. 2002) and low elimination rates in humans (Andersen et al. 2006).

The purpose of the present study was to estimate the serum elimination half-life of PFOS, PFHS, and PFOA in humans through the long-term follow-up of retired fluoro-chemical production workers. Although these retirees were no longer occupationally exposed, their serum concentrations were expected to be considerably higher than those of the general population.

Half-life of serum elimination of perfluorooctanesulfonate,perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers.

Titanium dioxide (TiO2) nanoparticles (NPs) are manufactured worldwide in large quantities for use in a wide range of applications. TiO2 NPs possess different physicochemical properties compared to their fine particle (FP) analogs, which might alter their bioactivity. Most of the literature cited here has focused on the respiratory system, showing the importance of inhalation as the primary route for TiO2 NP exposure in the workplace. TiO2 NPs may translocate to systemic organs from the lung and gastrointestinal tract (GIT) although the rate of translocation appears low. There have also been studies focusing on other potential routes of human exposure. Oral exposure mainly occurs through food products containing TiO2 NP-additives. Most dermal exposure studies, whether in vivo or in vitro, report that TiO2 NPs do not penetrate the stratum corneum (SC). In the field of nanomedicine, intravenous injection can deliver TiO2 nanoparticulate carriers directly into the human body. Upon intravenous exposure, TiO2 NPs can induce pathological lesions of the liver, spleen, kidneys, and brain. We have also shown here that most of these effects may be due to the use of very high doses of TiO2 NPs. There is also an enormous lack of epidemiological data regarding TiO2 NPs in spite of its increased production and use. However, long-term inhalation studies in rats have reported lung tumors. This review summarizes the current knowledge on the toxicology of TiO2 NPs and points out areas where further information is needed.

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Titanium dioxide nanoparticles: a review of current toxicological data

Toxicity of nanoparticles of CuO, ZnO and TiO2 to microalgae Pseudokirchneriella subcapitata

NanoGenotoxicology: The DNA damaging potential of engineered nanomaterials

Perfluorinated acids, including perfluorinated carboxylates (PFCAs), and perfluorinated sulfonates (PFASs), are environmentally persistent and have been detected in a variety of wildlife across the globe. The most commonly detected PFAS, perfluorooctane sulfonate (PFOS), has been classified as a persistent and bioaccumulative substance. Similarities in chemical structure and environmental behavior of PFOS and the PFCAs that have been detected in wildlife have generated concerns about the bioaccumulation potential of PFCAs. Differences between partitioning behavior of perfluorinated acids and persistent lipophilic compounds complicate the understanding of PFCA bioaccumulation and the subsequent classification of the bioaccumulation potential of PFCAs according to existing regulatory criteria. Based on available research on the bioaccumulation of perfluorinated acids, five key points are highlighted in this review: (1) bioconcentration and bioaccumulation of perfluorinated acids are directly related to the ...

Are PFCAs Bioaccumulative? A Critical Review and Comparison with Regulatory Criteria and Persistent Lipophilic Compounds

Development of a base set of toxicity tests using ultrafine TiO2 particles as a component of nanoparticle risk management.

Comparative responses of rats and mice exposed to linear/branched, linear, or branched ammonium perfluorooctanoate (APFO).

A Gene-Shuffled Glyphosate Acetyltransferase Protein from Bacillus licheniformis (GAT4601) Shows No Evidence of Allergenicity or Toxicity

The object of this study was to evaluate the toxicity of norbornene fluoroalcohol (NBFOH), which is used as an intermediate in the production of fluorinated monomers and polymers. NBFOH was evaluated for acute oral, dermal, and inhalation toxicity, dermal sensitization using the Local Lymph Node Assay (LLNA), mutagenesis by the Ames assay, and subchronic toxicity in a 4-week inhalation rat study. NBFOH demonstrated slight acute toxicity in oral, dermal, and inhalation studies. Approximate lethal doses of 3400 and > 5000 mg/kg for the oral and dermal routes, respectively, and an approximate lethal concentration of 4300 mg/m3 were determined. NBFOH demonstrated moderate skin irritation, was a severe eye irritant, produced dermal sensitization, but did not cause bacterial mutagenicity either in the presence or absence of S9 activation. Male and female rats were exposed nose only to airborne NBFOH at levels of 0, 410, 1400, and 1500 mg/m3, 6 h/day, 5 days/week for 4 weeks with clinical and histopathology spec...

Acute, Subchronic, and Mutagenicity Studies with Norbornene Fluoroalcohol

Kapton ® Film is a polymer with high strength and thermal resistance finding use in a wide variety of applications. In the preparation of this film, the uncured material could contain up to 30% dimethylacetamide (DMAC). Note that the final product Kapton Film has been thermally cured with the DMAC removed. During processing, dermal contact with the film is anticipated, and the possibility exists of DMAC transfer from the uncured film, to and through the skin. In this study, 2 2 2-inch pieces of film were applied to the skin of a group of rabbits and secured in place for a single 4-hour contact time. An amount of liquid DMAC corresponding to the amount contained in the 2-inch square was applied to the skin of a separate group of rabbits for 4 hours. Urine samples were collected over the intervals of application to 4 hours post application (8 hours total) or 4 to 20 hours post application (16 hours). The amount of the urinary metabolite monomethylacetamide (MMAC) was determined analytically in these samples...

Carol Finlay

Papers

Development of a base set of toxicity tests using ultrafine TiO2 particles as a component of nanoparticle risk management.

Comparative responses of rats and mice exposed to linear/branched, linear, or branched ammonium perfluorooctanoate (APFO).

A Gene-Shuffled Glyphosate Acetyltransferase Protein from Bacillus licheniformis (GAT4601) Shows No Evidence of Allergenicity or Toxicity

Acute, Subchronic, and Mutagenicity Studies with Norbornene Fluoroalcohol

Absorption of dimethylacetamide (DMAC) following application of a polymer film to the skin of rabbits.