Note from FAN: See the first review by CA OEHHA, March 2009
See also the Environmental Working Group submission to OEHHA in May 2009

Perfluorooctane sulfonate (PFOS) and Its Salts and Transformation and Degradation Precursors

Perfluorooctane sulfonate (PFOS) and its salts are perfluorinated organic
compounds with surfactant properties. Common salts of PFOS include the
ammonium, diethanolamine, potassium, and lithium forms. PFOS can be
released from several fluorochemicals, such as perfluorooctane sulfonamide
(PFOSA), N-ethyl perfluorooctane sulfonamidoethanol (N-EtFOSE), and
Nethylperfluorooctane sulfonamide (N-EtFOSA) by transformation or degradation
processes.

PFOS and its salts and precursors are used in the manufacture of a wide array of
industrial and household products, including fire fighting foams, and coatings for
fabrics, leather, food packaging and paper products. PFOS has not been
produced in the U.S. since 2000; however, there is continued production and use
of chemicals that can be transformed or degraded to release PFOS.

PFOS is resistant to thermal, chemical and biological degradation and is
persistent in the environment. It is readily absorbed into biota and has a
tendency to accumulate with repeated exposure. It is present in fish and other
foods. Human biomonitoring studies indicate widespread exposure of the
population to PFOS. For example, PFOS was detected in all 1562 serum
samples analyzed from participants in the 1999-2000 National Health and
Nutrition Examination Survey (NHANES) (Calafat et al., 2007). PFOS crosses
the placenta, accumulates in amniotic fluid (Midasch et al., 2007), and has been
detected in umbilical cord blood (Apelberg et al., 2007).

PFOS and its salts and transformation and degradation precursors passed the
animal data screen, underwent a preliminary toxicological evaluation, and are
being brought to the Carcinogen Identification Committee for consultation. This
is a compilation of the relevant studies identified during the preliminary toxicological evaluation.

Epidemiological data

• Retrospective occupational cohort studies
— Mortality study of workers at a perfluorooctanesulphonyl fluoride-based flurochemicals production facility in Decatur, Alabama: Alexander et al. (2003); EFSA (2008, p. 77)
—- Increased risk of death from bladder cancer seen in exposed workers (based on three cases)
— Bladder cancer incidence in workers at a perfluorooctanesulphonyl fluoride-based flurochemicals production facility in Decatur, Alabama: Alexander and Olson (2007); EFSA (2008, p. 77)
— No increased risk of bladder cancer associated with PFOS exposure

Animal carcinogenicity data

• Long-term feeding studies
* 104-week studies in male and female Crl:CD (SD) IGS BR rats: (reviewed by OECD, 2002, pp. 34-37).
— Increase in hepatocellular adenoma in males (by pairwise comparison and trend)
— Increases in hepatocellular adenoma and carcinoma combined in females (by pairwise comparison and trend), and increases in thyroid follicular cell adenoma and carcinoma combined, and mammary fibroadenoma/adenoma and carcinoma combined in females (by pairwise comparisons)
* 52-week exposure and additional observation until death in male Crl:CD (SD) IGS BR rats
— Increase in thyroid follicular cell adenomas (by pairwise comparison)

Other relevant data

• Genotoxicity

* Review: EFSA, (2008, p. 73)
— Mutagenicity in Salmonella typhimurium, Saccharomyces cerevisiae and E. coli (negative)
— Chromosome aberrations in human peripheral blood lymphocytes (negative)
— In vivo mouse bone marrow micronucleus assay (negative)
— Unscheduled DNA synthesis in rat liver primary cultures (negative)

• Immune system effects
* 10-day dietary exposure in C57BL/6 male mice: Qazi et al. (2009a, 2009b)
— Thymus and spleen atrophy, decreased CD45+CD8+ thymocyte and splenic B lymphocyte counts, increased production of TNF-alpha and IL-6 by peritoneal macrophages treated with LPS in vitro
* Seven-day gavage exposure in male C57BL/6 mice: Zheng et al. (2009)
— Decreased lymphocyte counts, decreased plaque forming cell response, decreased natural killer (NK) cell activity, and decreased lymphocyte proliferation response
— Gestation exposure on days 1-17 in B6C3F1 mice: Keil et al. (2008)
— Decreased NK function and IgM antibody production
* 28-day gavage exposure in male and female B6C3F1 mice: Peden-Adams et al. (2008)
— Reduced NK activity in males
— Altered T cell subpopulations, reduced sheep red blood cells, PFC response and TNP-LPS IgM titer in males and females
• Neuroendocrine system effects
* Two-week intraperitoneal exposure study in female Sprague- Dawley rats: Austin et al. (2003)
— Altered estrous cycle (irregular/persistent)
— Increase in serum corticosterone
— Decrease in serum leptin
— Increased norepinephrine concentration in hypothalamus
• Structure activity considerations
— Similar in structure to perfluorooctanoic acid (PFOA, C8), another eight carbon perfluorinated compound that increased testicular Leydig cell, pancreatic acinar cell and hepatocellular tumor incidence in rats.

References
Excerpts or the complete publication (presenting epidemiology or toxicology information)
have been provided to members of the Carcinogen Identification Committee, in the order in
which they are discussed in this document.

Alexander BH, Olsen GW (2007). Bladder cancer in perfluorooctanesulfonyl
fluoride manufacturing workers. Ann Epidemiol 17:471-478.

Alexander BH, Olsen GW, Burris JM, Mandel JH, Mandel JS (2003). Mortality of
employees of a perfluorooctanesulphonyl fluoride manufacturing facility. Occup
Environ Med 60:722-729.

Apelberg BJ, Witter FR, Herbstman JB, Calafat AM, Halden RU, Needham LL,
Goldman LR (2007). Cord serum concentrations of perfluorooctane sulfonate
(PFOS) and perfluorooctanoate (PFOA) in relation to weight and size at birth.
Environ Health Perspect 115:1670-1676.

Austin ME, Kasturi BS, Barber M, Kannan K, MohanKumar PS, MohanKumar SM
(2003). Neuroendocrine effects of perfluorooctane sulfonate in rats. Environ
Health Perspect 111:1485-1489.

Calfat AM, Kuklenyik Z, Reidy A, Caudill SP, Tully JS, , Needham LL (2007).
Serum concentrations of 11 polyfluoroalkyl compounds in the U.S. population:
data from the National Helath and Nutrition Examination Survey (NHANES).
Environ Sci Technol 41:2237-2242.

European Food Safety Authority (EFSA, 2008). Opinion of the Scientific Panel
on Contaminants in the Food Chain on Perfluorooctane sulfonate (PFOS),
Perfluorooctanoic acid and their salts. The EFSA Journal 653:1-131.

Keil DE, Mehlmann T, Butterworth L, Peden-Adams MM (2008). Gestational
exposure to perfluorooctane sulfonate suppresses immune function in B6C3F1
mice. Toxicol Sci 103:77-85.

Midasch O, Drexler H, Hart N, Beckmann MW, Angerer J (2007). Transplacental
exposure of neonates to perfluorooctanesulfonate and perfluorooctanoate: a
pilot study. Int Arch Occup Environ Health 80:643-648.

OECD (2002) Hazard assessment of perfluorooctane sulfonate (PFOS) and its
salts. ENV/JM/RD (2002). 17/Final. Joint meeting of the chemical committee
and the working party of chemicals, pesticides and biotechnology.

Peden-Adams MM , Keller JM, EuDaly Jg, Berger J, Gilkeson GS, Keil DE.
(2008). Suppression of humoral immunity following exposure to the
perfluorooctane sulfonate. Toxicol Sci.144-54.

Quazi MR, Bogdanska J, Butenhoff JL, Nelson BD, DePierre JW,
Abedicalugerdi M (2009a). High dose short term exposure of mice to
perfluorooctanesufonate (PFOS) or perfluoroocanoate (PFOA) affects the
number of neutophils differently, but enhances the inflammatory response of
macrophage to lipopolysaccharide (LPS) in a similar fashion. Toxicology
262:207-214.

Qazi MR, Xia Z, Bogdanska J, Chang SD, Ehresman DJ, Butenhoff JL, Nelson
BD, DePierre JW, Abedi-Valugerdi M. (2009b). The atrophy and changes in the
cellular compositions of the thymus and spleen observed in mice subjected to
short-term exposure to perfluorooctanesulfonate are high-dose phenomena
mediated in part by peroxisome proliferator-activated receptor-alpha (PPAR
alpha). Toxicology 260:68-76.

Zheng L, Dong GH, Jin YH, He QC (2009). Immunotoxic changes associated
with a 7-day oral exposure to perfluorooctanesulfonate (PFOS) in adult male
C57BL mice. Arch Toxicol 83:679-689.

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