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3M Comments on Human Health Hazard Tier II report on Perfluoroalkyl sulfonates (PFAS)
(>C8) and their direct precursors
Page 7, Toxicokinetics:
The second sentence “The mean elimination half-life of PFOS in humans was estimated to be at
8.7 years (2.3 – 21 years) based on the serum PFOS levels determined in retirees who had been
exposed to PFOS during working life” is incorrect. It is 4.8 years (geometric mean) or 5.4 years
(arithmetic mean) for PFOS. The 95% confidence intervals were 95% CI 4.0 – 5.8 (years) and
95% CI 3.9 – 6.9 (years), respectively. Also, these retirees were the fluorochemical workers that
were exposed to PFOS and other fluorochemicals.
Page 7, Carcinogenicity:
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The IMAP assessment on PFOS carcinogenicity was based on the 2-year dietary cancer
study that 3M did back in the early 2000's. It is either being referred to as Thomford
2002 (final study report from Covance Laboratories) or Butenhoff et al. 2012 Toxicology
293, 1-15 (in which entire cancer study was published as a manuscript in a peer-review
journal).
In laboratory studies, the event(s) to which a compound is to be considered as a
carcinogen is the dose-dependent pathological finding of carcinoma (non-reversible,
invasive, malignant tumor). In Butenhoff et al. (2012), there was only one female rat
(out of 60) from the 20 ppm high dose group that had hepatocelluar carcinoma; and this
was not in and of itself considered significant. Other tumors observed in the study were
benign (adenoma). That included liver, mammary gland, and thyroid gland. The
following mode-of-action should be taken into account:
o Liver: It has been well-documented that nuclear receptor activation in rodents
such as PPAR alpha and CAR/PXR can lead to hepatocelluar hypertrophy such as
tumor formation but its relevance to human risk assessment is questionable
(since this has been recognized as a rodent-specific event). PFOS is a known
activator for the nuclear receptors mentioned above hence the observation of
liver adenoma observed in the 2-year PFOS cancer study is not expected to be of
human relevance (USEPA HED_Guidance_Doc G0201 Hepatocellular
Hypertrophy).
o Mammary gland: The biological significance of mammary fibroadenomas is
questionable, given that there was no dose-response. Statistical significant
increase in mammary fibroadenoma relative to control was only observed in low
dose group females at 0.5 ppm; there were no statistical significant increases in
2, 5, or 20 ppm group.
o Thyroid: The biological significance of thyroid follicular adenomas is also of
question, given that there was no dose-response. Thyroid follicular cell
adenoma is commonly seen in aging rats and in this study, it was only observed
in males receiving 20 ppm PFOS for 52 weeks but not in the males receiving 20
ppm PFOS for 104 weeks or in females. The authors concluded that it was a
spurious finding.
Page 8, Critical Health Effects under Risk Characterisation:
The scientific evidence provided above did not support carcinogenicity potential.
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Although bladder cancer mortality was reported to be elevated among workers with
exposure to PFOS (3 deaths, 0.2 expected, SMR = 12.8, 95% CI 2.6 – 37.4 (Alexander et
al. Occup Environ Med 2003), a subsequent follow-up of bladder cancer incidence (not
just mortality) did not confirm any substantive risk for bladder cancer in this same
worker population (Alexander and Olsen, Annals Epidemiol 2007). There were 11 cases
of bladder cancer versus 8.6 expected (Standardized Incidence Ratio = 1.3, 95% CI 0.6 –
2.3). Among those who ever worked in a high exposed PFOS job the bladder cancer the
SIR was 1.7 (95% CI 0.6 – 3.8). Authors concluded there was little support for an
association between bladder cancer and PFOS exposure, but the limited size of the
worker population prohibited a conclusive exposure response analysis. Subsequent to
this investigation, Eriksen et al. (J Natl Cancer Inst, 2009) conducted a case-cohort study
of bladder cancer cases (n = 332 cases) in a Danish general population study and did not
find any risk for bladder cancer and PFOS. By increasing quartile of exposure of PFOS,
the incidence rate ratios for bladder cancer were 1.00 (referent), 0.8, 0.9, and 0.7.
Page 9, (Regulatory Controls, Work Health and Safety):
Based on the comments provided above in relation to Carcinogenicity 3M does not believe that
it is appropriate to assign a Carcinogenicity classification to this group of chemicals. The
carcinogenicity classification should be removed.