DEQ-CFW_00074109

west virginia department of environmental protection
Office of Environmental Remediation
131A Peninsula Street
Wheeling, WV 26003
Phone: [phone]/Fax: [phone]
MEMORANDUM
To: Yogesh Patel
Matthew Sweeney ` Q
From: Lawrence P. Sirinek, Ph.D. t,.
Date: January 31, 2012
Subject: DuPont GenX Toxicity
CC: Pat Campbell
Scott Mandirola
Ken Ellison
Don Martin
Earl Ray Tomblin, Governor
Randy C. Huffman, Cabinet Secretary
www.dep.wv.gov
I have completed my review of the documentation provided by DuPont regarding the toxicity of
GenX Compound A and Compound B. As I requested redacted documents, the identities and
chemical differences between the substances were not provided; however, most of the
toxicological studies appear to involve compound B. For this reason I have focused my
discussion on this compound. The relevance of the different compounds as they relate to
permitted discharges should be clarified with DuPont.
With regard to ecological endpoints, I concur with the points provided in the documents
provided by DuPont. Thus, 4.2 mg/L, reported as the 21 day NOEC (no observed effect
concentration) for Daphnia magna seems to be an appropriate endpoint for use in determining
discharge levels that would protect aquatic receptors.
With regard to human health effects, there were no data from chronic studies performed in either
rats or primates contained in the material provided by DuPont. Chronic studies in both rats and
mice are apparently ongoing, however data was not provided. While these data would be
preferable, derivation of an appropriate toxicity criterion for human health can be based on a
subchronic (90 day) study performed in rats. In this particular study, DuPont indicates a
NOAEL (no observed adverse effect level) at 10 mg/kg/day, based on evidence of regenerative
anemia in males at 100 mg/kg/d and females at 1000 mg/kg/d. Other effects were reported, but
are likely attributable to mechanisms that are often considered irrelevant to potential human
toxicity (e.g. PPARa agonists).
With regard to the NOAEL, it must be noted that male rats exposed at this concentration (10
mg/kg/day) did exhibit significant decreases in erythrocyte (red blood cell) counts, hematocrit,
and hemoglobin levels that are also indicative of anemia. DuPont considers the anemia
Promoting a healthy environment.
DEQ-CFW 00074109

DuPont GenX Review
January 31, 2012
Page 2
described by these parameters as non -adverse in this group, since the animals lacked evidence of
compensatory erythrocyte production (e.g. elevated reticulocyte counts). On the other hand,
while the reticulocyte counts were not significantly elevated in this group, there was a clear,
dose -dependent trend in the mean reticulocyte count at week 13. Unfortunately it cannot be
determined whether continued dosing beyond this time point would have resulted in more
dramatic indications of a compensatory response, or whether the impact was sufficiently limited
at the 10 nig/kg/day dose, such that no compensatory response was needed. Absent more
definitive data; the depressed red cell counts, hematocrit and hemoglobin levels should be
sufficient to constitute a health -protective endpoint for purposes of assessing the potential
impacts from chronic exposure to the test compound. Additional consideration should be made
when results of the chronic study are provided.
On the basis of a revised NOAEL of 0.1 mg/kg/day, and applying relevant uncertainty factors for
chronic to subchronic extrapolation (10) and rat to human extrapolation (10), the oral reference
dose (RfDo) = 0.001 mg/kg/day. Based upon this value, a reasonable risk -based drinking water
equivalent level (DWEL) assuming total intake of the substance from a contaminated source
would be 351Ag/L. As discussed in subsequent communications, a source adjustment of 50%
could reasonably be applied to this value to allow for potential intake from other sources. Use of
this adjustment would result in a final DWEL of 18 µg/L. Based upon the information provided
by DuPont, I believe this value would protect both human health and the environment.
I hope this discussion is helpful. Please contact me should you require further discussion or
clarification.
DEQ-CFW 00074110