HomeMy WebLinkAbout2021.03.09_CCO.p14_DEQCommentsOnEcoToxicologyMasterProtocols
March 9, 2021
DEQ reviewed the following aquatic (eco) toxicology master protocols received in
December 2020 from Chemours pursuant to paragraph 14 of the Consent Order.
• Algae: 96-hour toxicity test with the freshwater alga (Raphidocelis subcapitata) OECD 201;
EU Directive 92/69/EEC, Method C.3.; EPA OCSPP Number 850.4500
• Daphnid acute: 48-hour static acute toxicity test with the cladoceran (Daphnia magna)
OECD 202, EPA OCSPP 850.1010
• Daphnid chronic: semi-static life-cycle toxicity test with the cladoceran (Daphnia magna)
OECD 211, EPA OCSPP 850.1300
• Fish acute: 96-hour static acute toxicity test with the fathead minnow (Pimephales
promelas) OECD 203, EPA OCSPP 850.1075
• Sediment 10-day not yet received.
1) Comments on toxicity study work plans: DEQ has previously provided comments on the
toxicity study work plan in a letter dated 5/03/19 (RE: Comments on Draft Plan for Toxicity
Studies) and an email dated 12/17/19 (RE: Toxicologist Meeting Minutes). These
expectations still apply. Chemours has requested to submit components of the toxicity study
work plan and supporting information separately. DEQ has agreed to receive and review
these items separately, but reminds Chemours that each of the following items are needed
before DEQ can approve the final studies:
a. Revised master protocols must be provided to DEQ with requested modifications
and/or additional supporting information. DEQ will review and approve these
protocols to enable development of the compound specific protocols.
b. DEQ is requesting that Chemours submit any previously existing toxicity
information available on these compounds. If toxicity data for these compounds and
these species do not already exist then DEQ requires that range-finding toxicity tests
be conducted.
c. The final studies will be described by the compound specific protocols, and these
must be reviewed and approved by DEQ. Compound specific protocols will be the
same in every way as the master protocols except for compound specific
information like chemical name, CAS#, and dose levels to be administered. Acute
studies must be designed to bracket EC50 values and chronic studies must be
designed to bracket LOEL and NOEL values. Additional work plan comments were
provided in the 5/03/19 letter from DEQ. Range finding results and other data used
to develop dose levels targeting these response levels must be provided before DEQ
can approve the dose levels for the final studies.
d. Analytical chemistry methods and reporting limits for each media to be analyzed for
the toxicity studies must be reviewed and approved by DEQ for this work. DEQ is
outlining requirements for describing modified methods in a separate document
and will provide this shortly. Information provided should be consistent with
guidelines in Appendix 1.
e. PFAS reference materials used for these toxicity studies are not commercially
available and additional information must be provided to DEQ:
i. Describe production and handling of all batches of reference material to be
used. Samples from each batch must be made available to DEQ for
independent analysis.
ii. A third-party laboratory must characterize the reference materials as
described below and provide information to DEQ and laboratories
contracted for the toxicity studies.
1. Certificate of analysis including but not limited to: identity (including
isomer structure), purity, and composition. Information provided
should be consistent with guidelines in Appendix 1.
2. Homogeneity and stability tests must be conducted for each
compound in all solvents and stock solutions that will be used in the
toxicity studies. Work by other investigators showing potential for
instability in certain solvents should be reviewed (Liberatore et al.
2020).
iii. DEQ is outlining requirements for characterizing reference materials in a
separate document and will provide this shortly.
f. A work plan with key milestones and approval status for each of these requested
items must be provided to DEQ for approval prior to the commencement of the final
studies.
2) Comments on protocols
a. General comments on protocols proposed:
i. As specified in EPA-821-R-02-012, Subsection 4.7.2 "... the testing laboratory
must perform at least one acceptable reference toxicant test per month for
each toxicity test method conducted in that month (Subsection 4.15). If a test
method is conducted only monthly, or less frequently, a reference toxicant
test must be performed concurrently with each effluent toxicity test." DEQ
requests submission of the lab’s in-house reference toxicant testing for all
the test protocols and also submittal of the reference toxicity test
information that is provided by the biological supplier from which all test
species are purchased.
ii. In the different protocols, the word “indiscriminately” is being used instead
of randomly. EPA-821-R-02-013, Subsection 9.4.4.1 states that “Statistical
independence among observations is a critical assumption in all statistical
analysis of toxicity data. One of the best ways to ensure independence is to
properly follow rigorous randomization procedures. Randomization
techniques should be employed at the start of the test, including the
randomization of the placement of test organisms in the test chambers and
randomization of the test chamber location within the array of chambers...”
Examples of randomization procedures are using a template for
randomization or by using a table of random numbers as stated in
Subsection 11.3.4.5.1. DEQ is asking for a more in-depth explanation of what
“indiscriminately” means.
iii. Each proposed protocol states that changes to protocols and final reports
will be made in the form of an amendment, signed by the Study Director, and
approved by the Sponsor. Chemours must provide such amendments to DEQ
for review and approval. Changes to the protocols are to be approved by
DEQ before starting the experiments and changes to the reports are to be
approved by DEQ prior to completing the writing of the final report.
iv. DEQ has a preference for following guidelines within EPA 821-R-02-012 and
EPA 821-R-02-013 where feasible in order to be consistent with NC Whole
Effluent Testing guidelines.
b. Algae: 96-hour toxicity test with the freshwater alga (Raphidocelis subcapitata)
OECD 201; EU Directive 92/69/EEC, Method C.3.; EPA OCSPP Number 850.4500
i. The Raphido protocol states "Test chambers will be held at 24 ± 2°C under
continuous fluorescent lighting…" The EPA-821-R-02-013, Subsection
14.10.3.1 states that "Test flasks are incubated under continuous
illumination at 86 ± 8.6 µE/m2/s (400 ± 40 ft-c), at 25 ± 1°C, and should be
shaken continuously at 100 cpm on a mechanical shaker or twice daily by
hand…” DEQ is requesting the protocol be updated to be consistent with EPA
recommendations or that an explanation be provided for why the alternate
temperature range is proposed.
ii. The EPA-821-R-02-013, Subsection 14.10.3.1 also states that the “Flask
positions in the incubator should be randomly rotated each day to minimize
possible spatial differences in illumination and temperature on growth rate.
If it can be verified that test specifications are met at all positions, this need
not be done." DEQ is requesting an explanation of how the protocol ensures
that all flasks are exposed to the desired light intensity and temperature
ranges.
c. Daphnid acute: 48-hour static acute toxicity test with the cladoceran (Daphnia
magna) OECD 202, EPA OCSPP 850.1010
i. DEQ is recommending the use of Ceriodaphnia dubia instead of Daphnia
magna because C. dubia is a more sensitive species of the two. EPA-821-R-
02-012 (Subsection 2.1) states that “D. magna distribution appears to be
absent from the eastern United States (except for Northern New England)
and Alaska”. DEQ has a preference to use C. dubia, but also has a preference
for using test species that the lab has expertise with. Please re-evaluate
species choice and provide explanation for species selected.
ii. The Daphnia acute and chronic protocols are using the well water with a
hardness of ~140mg/L as a dilution test water. EPA typically recommends a
hardness of 160-180mg/L as CaCO3 for D. magna culturing (EPA-821-R-02-
012, Subsection 4.2.1), but based on the language in EPA-821-R-02-012,
Subsection 7.1.1.2, it may be acceptable as long the lab is culturing the
organisms in the dilution water before testing, which the lab is intending to
do. However, if a decision is made to switch to C. dubia, then the desired
range is 80-100mg/L for reconstituted water and 30-50mg/l for surface
water as stated in the NC rule 15A NCAC 02H .1111(a)(13). DEQ is
recommending that the lab match species with the recommended hardness
levels in these EPA guidelines. DEQ is recommending use of C. dubia in
order to be more consistent with what we require for the NC Whole Effluent
Toxicity Program.
iii. The daphnia acute protocol states that “loading in each test chamber during
test will be at least 20 mL of test solution per daphnid”. In Table 13 of the
EPA-821-R-02-012 manual, the test conditions listed for the acute testing
with D. magna includes the minimum recommended test solution volume of
25ml. Please provide comment and explanation for this test solution volume.
iv. The daphnia acute protocol states "Adults will be fed during the 24-hour
period prior to test initiation, but neonates will not be fed during the test."
DEQ is requesting that the protocol be updated to be consistent with EPA-
821-R-02-012 (Table 13); newly released young should have food available
a minimum of 2 hrs prior to use in a test".
v. The daphnia acute protocol states "Prior to test initiation, neonate daphnids
<24 hours old will be collected from cultures and indiscriminately
distributed one or two at a time to transfer containers until each contains its
complement of five daphnids." DEQ is requesting more information
regarding the methodology of obtaining organisms from the culture. Is the
lab doing the pooling or blocking method? What are the measures taken to
avoid cross-contamination when populating the tests chambers?
vi. The daphnia acute protocol states "The dissolved oxygen concentration will
be ≥3 mg/L throughout the test." EPA-821-R-02-012 (Subsection 9.14.1)
states that "the DO in the test solution should not be permitted to fall below
4.0 mg/L for warm water species and 6.0 mg/L for cold water species." This
validation criterion should be set at ≥4 mg/L DO, not 3 mg/L.
d. Daphnid chronic: semi-static life-cycle toxicity test with the cladoceran (Daphnia
magna) OECD 211, EPA OCSPP 850.1300
i. DEQ is recommending the use of Ceriodaphnia dubia instead of Daphnia
magna because C. dubia is a more sensitive species of the two. EPA-821-R-
02-012 (Subsection 2.1) states that “D. magna distribution appears to be
absent from the eastern United States (except for Northern New England)
and Alaska". Please use C. dubia or provide explanation of why using D.
magna instead of C. dubia.
ii. Proposed protocol specifies that test will be initiated with neonates <24
hours old. EPA 821-R-02-012 specifies <24 hours and born within 8 hours of
each other for C. dubia. If C. dubia is used, add to the chronic protocol that
neonates used will have been born within 8 hours of each other.
iii. The Daphnia acute and chronic protocols are using the well water with a
hardness of ~140mg/L as a dilution test water. EPA typically recommends a
hardness of 160-180mg/L as CaCO3 for D. magna culturing (EPA-821-R-02-
012, Subsection 4.2.1) but based on the language in EPA-821-R-02-012,
Subsection 7.1.1.2, it may be acceptable as long the lab is culturing the
organisms in the dilution water before testing, which the lab is intending to
do. However, if a decision is made to switch to C. dubia, then the desired
range is 80-100mg/L for reconstituted water and 30-50mg/L for surface
water as stated in the NC Statute 15A NCAC 02H .1111(a)(13). DEQ is
recommending that the lab match species with the recommended hardness
levels in these EPA guidelines. DEQ is recommending use of C. dubia in
order to be more consistent with what we require for the NC Whole Effluent
Toxicity Program.
e. Fish acute: 96-hour acute toxicity test with the fathead minnow (Pimephales
promelas) OECD 203, EPA OCSPP 850.1075.
i. The fathead minnow acute protocol states that organisms will be purchased
from a supplier. DEQ notes that hardness of the shipping water may be
lower than the hardness in the well water (~140mg/L) used as dilution
water. What is the acclimation process and period used to change the fish
from the shipping water to the lab dilution water?
ii. The fathead minnow acute protocol states "Fathead minnows will be held
for at least 14 days prior to the test in water from the same source and at
approximately the same temperature as used during the test." DEQ is
concerned that waiting until the fish are older (>14 days) the test may miss
the more sensitive life stage. Additionally, keeping fish age at 1-14 days old
would be more consistent with what DEQ requires for the NC Whole Effluent
Toxicity Program. DEQ is requesting that protocols be updated to be
consistent with EPA guidance as per EPA-821-R-02-012 (Table 14); the age
of test organisms required for the acute toxicity test is 1-14 days old with
less than or equal to 24-h range in age.
iii. The fathead minnow acute protocol states "Fish will not be fed for at least
one day prior to the test or during the test." DEQ is requesting that protocols
be updated to be consistent with EPA-821-R-02-012 (Table 14, and
Subsection 9.11.1), which states that "food is made available to test
organisms while holding before they are placed in the test chambers."
iv. The fathead minnow acute protocol states "Specifications for acceptable
levels of contaminants in fish diets have not been established." The EPA-
821-R-02-012, Subsection 4.8.3 provides guidance of the allowable levels of
contaminants in fish food, "If the concentration of total organochlorine
pesticides exceeds 0.15 µg/g wet weight, or the concentration of the total
organochlorine pesticides plus PCBs exceeds 0.30 µg/g wet weight, or toxic
metals (Al, As, Cr, Co, Cu, Pb, Ni, Zn, expressed as total metal) exceed 20 µg/g
wet weight, the food should not be used…”. Every batch of fish food should
be analyzed to meet these guidelines before using for toxicity tests.
v. The fathead minnow acute protocol states "The test will be conducted at a
target water temperature of 22 ± 1°C." DEQ is requesting more information
about the culturing conditions and other factors contributing to this
decision. EPA-821-R-02-012 (Table 14) recommends the use of either
20±1°C or 25±1°C. A 25±1°C temperature would be more consistent with
what DEQ requires for the NC Whole Effluent Toxicity Program.
vi. The fathead minnow acute protocol states "Prior to test initiation, juvenile
fathead minnows will be collected from holding tanks. To initiate the test,
the fish will be indiscriminately distributed one or two at a time to the test
chambers until each contains its complement of ten fish." DEQ is requesting
more details on the measures taken to avoid cross-contamination when
populating the tests chambers, and also to minimize test dilution with water
from fish population. When populating test organisms into test chambers it
is recommended to rinse the transfer apparatus between the different test
concentrations, and minimize the amount of water introduced into each test
chamber while transferring the tests organisms.
vii. Protocol describes several potential test chambers options, one of which is
Teflon-lined. DEQ recommends not using Teflon due to potential for
contributing PFAS to the test system.
a. Sediment 10-day: Chemours asked DEQ to identify the specific OECD guideline.
Please use Sediment-Water Lumbriculus Toxicity Test Using Spiked Sediment
toxicity study – OECD 225 and refer to previous communications about this method
(See 3/27/19 Chemours letter Re: Work Plan for Toxicity Studies Pursuant to
Consent Order Paragraph 14. See 5/03/19 DEQ Comments on Chemours’ Proposed
Toxicity Study Work Plan Pursuant to Paragraph 14 of the Consent Order, dated
3/27/2019).
3) Additional protocols requested
• CRITICAL NEED - Bioaccumulation in Fish: Aqueous and Dietary Exposure – EPA (OCSPP)
850.1730; This is study critical for DEQ to establish water supply and fish consumption
surface water standards. PFAS do not accumulate using the same mechanisms as other
organic chemicals so modeling is not the preferred approach. Paragraph 14 of the Consent
Order states that this testing should be “… sufficient to aid in development of surface water
and groundwater regulatory standards…”
• Fish Early Life-Stage Test – EPA (OCSPP) 850.1400; Using Pimephales promelas; 28-day
study focused on embryonic through early juvenile life-stage effects.
• Fish Sexual Development Test – OECD 234; 60-day study focused on endocrine disrupting
effects.
• Amphibian Metamorphosis Assay – OECD 231; 21-day exposure study provides information
on development in tadpoles. This is important to consider as amphibians are often
underrepresented in ecotoxicity studies.
• Empirically derived chemical characteristics including; half-life in water, octanol:water
coefficient (logP).
4) References
DEQ letter to Chemours 5/03/19. “Comments on Draft Plan for Toxicity Studies”
Accessed via https://files.nc.gov/ncdeq/GenX/consentorder/paragraph14/05032019-
Holman-to-Long-Letter-Re-Comments-on-Draft-Toxicity-Study-Paragraph-14-of-CO.pdf
Liberatore, H., S. Jackson, M. Strynar, and J. McCord. 2020. Solvent Suitability for HFPO-
DA (GenX” Parent Acid) in Toxicological Studies. Environ Sci Technol Lett. 18;7(7):477-
481
USEPA. 2002. Methods for Measuring the Acute Toxicity of Effluents and Receiving
Waters to Freshwater and Marine Organisms. Fifth Edition. U.S. U.S. Environmental
Protection Agency, Washington, DC 20460. EPA-821-R-02-012.
USEPA. 2002. Short-term Methods for Estimating the Chronic Toxicity of Effluents and
Receiving Waters to Freshwater Organisms. Fourth Edition. U.S. Environmental
Protection Agency, Washington, DC 20460. EPA-821-R-02-013.