[Code of Federal Regulations]
[Title 40, Volume 31]
[Revised as of July 1, 2006]
From the U.S. Government Printing Office via GPO Access
[CITE: 40CFR799.3300]
[Page 258-261]
TITLE 40--PROTECTION OF ENVIRONMENT
CHAPTER I--ENVIRONMENTAL PROTECTION AGENCY (CONTINUED)
PART 799_IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE
TESTING REQUIREMENTS--Table of Contents
Subpart B_Specific Chemical Test Rules
Sec. 799.3300 Unsubstituted phenylenediamines.
(a) Identification of test substance. (1) The unsubstituted
phenylenediamines (pda's), para-phenylenediamine (p-pda, CAS No. 106-50-
3), or its sulfate salt (p-pda.H2SO4, CAS No.
1624-57-75), meta-phenylenediamine (m-pda, CAS No. 108-45-2), or its
sulfate salt (m-pda.H2SO4, CAS No. 54-17-08), and
ortho-phenylenediamine (o-pda, CAS No. 95-54-5) shall be tested in
accordance with this section.
(2) p-Pda, m-pda, and o-pda of at least 98 percent purity shall be
used as the test substances. Either the hydrochloride or sulfate salt of
m-pda shall be used as the test substances. Either the hydrochloride or
sulfate salt of m-pda shall be used as a test substance in the
oncogenicity test in paragraph (c)(2) of this section if the free base
proves to be unstable under the conditions of this study. Either the
hydrochloride or sulfate salt of o-pda, p-pda, or m-pda shall be used as
a test substance in the 90-day subchronic neurotoxicity studies in
paragraph (c)(3)(B) of this section if the free base proves to be
unstable under the conditions of these studies. The salt(s) shall be of
at least 98 percent purity.
(b) Persons required to submit study plans, conduct tests, and
submit data. (1) All persons who manufacture (including import or by-
product manufacture) or process m-pda or m-
pda.H2SO4, or intend to manufacture or process m-
pda or m-pda.H2SO4, after the effective date of
this rule to the end of the reimbursement period shall submit letters of
intent to test, submit study plans, conduct tests, and submit data, or
submit exemption applications as specified in paragraphs (c), (d), and
(e) of this section, subpart A of this part, and parts 790 and 792 of
this chapter for single-phase rulemaking.
(2) All persons who manufacture (including import or by-product
manufacture) or process p-pda, or p-pda.H2SO4, or
intend to manufacture or process p-pda, or p-pda
H2SO4, after the effective date of this rule to
the end of the reimbursement period shall submit letters of intent to
test, submit study plans, conduct tests, and submit data, or submit
exemption applications as specified in paragraphs (c)(3), (d), and (e)
of this section, subpart A of this part and parts 790 and 792 of this
chapter for single-phase rulemaking.
(3) All persons who manufacture (including import or by-product
manufacture) or process o-pda, or intend to manufacture or process o-pda
after the effective date of this rule to the end of the reimbursement
period shall submit letters of intent to test, submit study plans,
conduct tests, and submit data, or submit exemption applications as
specified in paragraphs (c)(3), (d), and (e) of this section, subpart A
of this part, and parts 790 and 792 of this chapter for single-phase
rulemaking.
[[Page 259]]
(c) Health effects testing--(1) Mutagenicity testing--(i) Required
testing. (A) The sex-linked recessive lethal (SLRL) assay shall be
conducted, by injection, in Drosophila melanogaster with m-pda in
accordance with Sec. 798.5275 of this chapter.
(B) If the SLRL assay conducted pursuant to paragraph (c)(1)(i)(A)
of this section is positive, either the mouse visible specific locus
test (MVSL) or the mouse biochemical specific locus test (MBSL) shall be
conducted for m-pda by gavage in accordance with Sec. Sec. 798.5200 or
798.5195 of this chapter, if after public program review, EPA issues a
Federal Register notice or sends a certified letter to the test
sponsor(s) specifying that testing shall be initiated. The test sponsor
shall notify EPA of its choice in writing in its first interim report.
(C) The mouse bone marrow cytogenetics: micronucleus (MBMC) assay
shall be conducted on m-pda in accordance with Sec. 798.5395 of this
chapter.
(D) If the MBMC assay conducted pursuant to paragraph (c)(1)(i)(C)
of this section is positive, the dominant lethal assay (DL) in mice
shall be conducted on m-pda pursuant to Sec. 798.5450 of this chapter.
(E) If the DL conducted pursuant to paragraph (c)(1)(i)(D) of this
section is positive, heritable translocation (HT) testing in the mouse
on m-pda shall be conducted pursuant to Sec. 798.5460 of this chapter,
if after a public program review, EPA issues a Federal Register notice
or sends a certified letter to the test sponsor(s) specifying that
testing shall be initiated.
(ii) Reporting requirements. (A) The tests shall be completed and
the final reports for the MBMC assay shall be submitted to the EPA no
later than January 16, 1991. The final report for the SLRL in Drosophila
melanogaster shall be submitted no later than April 15, 1991.
(B) If required, the DL test shall be completed and the final report
shall be received by EPA no later than 24 months after the effective
date of this final rule.
(C) If required, the MVSL or the MBSL shall be completed and the
final report shall be received by EPA no later than 51 months after EPA
issues a Federal Register Notice or sends a certified letter to the test
sponsor(s) identified under paragraph (c)(1)(i)(B) of this section
specifying that testing shall be initiated.
(D) If required, the HT test shall be completed and the final report
shall be submitted to EPA not later than 36 months after the date on
which EPA notifies the test sponsor under paragraph (c)(1)(i)(E) of this
section to begin testing.
(E) Interim reports for the SLRL assay and MBMC are required at 6-
month intervals beginning 6 months after the effective date of this
section. If the DL is triggered, interim reports are required at 6 month
intervals beginning with the date of initiation of the study.
(F) Interim reports for the HT and either the MBSL or MVSL are
required at 6-month intervals beginning 6 months after the date of
notification by EPA that testing shall be initiated, and ending when the
final report is submitted.
(2) Oncogenicity--(i) Required testing. A 2-year dermal oncogenicity
bioassay shall be conducted with m-pda if, after public program review,
EPA issues a Federal Register notice specifying that the testing shall
be initiated.
(ii) [Reserved]
(iii) Reporting requirements. (A) The final results and final report
for the oncogenicity bioassay shall be submitted to EPA no later than 53
months after EPA issues a Federal Register notice or sends a certified
letter to the test sponsor under paragraph (c)(2)(i) of this section
specifying that the testing shall be initiated.
(B) Interim reports for the oncogenicity study are required at 6-
month intervals beginning 6 months after the date of notification by EPA
that testing shall be initiated and ending when the final report is
submitted.
(3) Neurotoxicity--(i) Required testing. (A) Acute neurotoxicity
testing in the neurotoxicity functional observational battery (FOB) in
accordance with Sec. 798.6050 of this chapter, and the motor activity
test (MAT) in accordance with Sec. 798.6200 of this chapter, shall be
conducted for o-, m-, and p-pda.
[[Page 260]]
The test chemicals shall be administered in a single oral dose. Clinical
observations shall be made at a minimum of 1, 4, 24, and 48 hours and at
7 days after dosing.
(B) If neurotoxic effects are observed at 24 hours, or longer,
during the testing conducted pursuant to paragraph (c)(3)(i)(A) of this
section, then 90-day subchronic neurotoxic FOB and MAT tests shall be
conducted in accordance with Sec. Sec. 798.6050 and 798.6200 of this
chapter, respectively, for each isomer showing such effects. At the end
of these tests, the animals shall be sacrificed and the nervous tissue
preserved and examined as described in the neuropathology test standard,
Sec. 798.6400 of this chapter.
(ii) Reporting requirements. (A) The acute neurotoxicity tests shall
be completed and the final report submitted to EPA no later than
September 15, 1990. If triggered, the final report of the subchronic
neurotoxicity testing and the neuropathological examination shall be
submitted to EPA on the following schedules. If one isomer is triggered,
the reporting deadline is July 15, 1990. If two isomers are triggered,
the reporting deadline is January 15, 1992. If three isomers are
triggered, the reporting deadline is July 15, 1992.
(B) [Reserved]
(d) Chemical fate testing--(1) Indirect photolysis testing--(i)
Required testing. Indirect photolysis studies shall be conducted with p-
, m-, and o-pda to determine the half-life in water of each of the three
unsubstituted pda's in accordance with Sec. 795.70 of this chapter.
(ii) Reporting requirements. (A) The final report shall be submitted
to EPA no later than 8 months after the effective date of the final
rule.
(B) The final report shall include a calculation of the predicted
environmental concentration (PEC), 100xPEC, and 1,000xPEC for each
isomer. PEC shall be calculated by using results from the indirect
photolysis studies and solving the following equations for the
appropriate isomer: o-pda: PECo = 0.3629 + 1.0468 log t 1/2; m-pda: PECm
= 0.6830 + 1.9702 log t 1/2; p-pda: PECp = 0.0085 + 0.0024 log t 1/2,
where PEC is the predicted concentration in ppb and t 1/2 is the half-
life for oxidation (i.e., indirect photolysis) expressed in minutes.
PEC, 100xPEC, and 1,000xPEC shall be used in the decision logic
described in paragraph (e) of this section.
(2) [Reserved]
(e) Environmental effects testing--(1) Acute toxicity testing--(i)
Required testing. (A) Flow-through fish acute toxicity tests in the
rainbow trout (Salmo gairdneri) shall be conducted with o-, m-, and p-
pda in accordance with Sec. 797.1400 of this chapter.
(B) Acute flow-through studies on the freshwater invertebrate
Gammarus shall be conducted with o-, m-, and p-pda in accordance with
Sec. 795.120 of this chapter.
(C) If the concentration affecting 50 percent of the population
(LC50 or EC50) for any study conducted pursuant to
paragraphs (e)(1)(i)(A) and (B) of this section is less than or equal to
100xPEC, less than or equal to 1 milligram/liter (mg/L), or less than or
equal to 100 mg/L and shows indications of chronicity, chronic toxicity
testing shall be conducted pursuant to paragraph (e)(2) of this section.
Indications of chronicity shall be the following: for fish or aquatic
invertebrates, the ratio of 24 hour/96 hour LC50s is greater
than or equal to 2; for gammarids, the ratio of 24 hour/48 hour
EC50s is greater than or equal to 2.
(ii) Reporting requirements. The final reports for acute toxicity
testing shall be submitted as follows:
(A) Testing on the rainbow trout shall be completed and submitted to
EPA 9 months after the effective date of the final rule for o-pda and p-
pda. Testing for m-pda shall be completed and submitted by January 15,
1991.
(B) The acute toxicity testing in freshwater Gammarus shall be
completed and submitted no later than January 15, 1991.
(2) Chronic toxicity testing--(i) Required testing. (A) A fish
partial life-cycle flow-through test shall be conducted in the more
sensitive fish species, either Pimephales promelas or Salmo gairdneri,
with each isomer, o-, m-, and p-pda, demonstrating an LC50,
determined by testing of fish pursuant to paragraph (e)(1)(i)(A) of this
section, equal to or less than 100xPEC; or less than 1 mg/L; or less
than 100 mg/L with indications of chronicity. Chronicity indicators are
defined in paragraph
[[Page 261]]
(e)(1)(i)(C) of this section. Testing shall be conducted in accordance
with Sec. 797.1600 of this chapter.
(B) An invertebrate life-cycle flow-through toxicity test shall be
conducted in Daphnia magna for o- and p-pda in accordance with Sec.
797.1330 of this chapter.
(ii) Reporting requirements. (A) The fish partial life-cycle flow-
through test shall be completed and final results shall be submitted to
EPA no later than December 1, 1992.
(B) The invertebrate life-cycle flow-through toxicity test shall be
completed and the final report submitted to EPA no later than January
15, 1993.
(C) Progress reports shall be submitted at 6 month intervals after
the effective date of the final rule.
(f) Effective dates. (1) The effective date of this final rule is
January 16, 1990, except for paragraphs (c)(1)(i)(B), (c)(1)(ii)(A),
(c)(1)(ii)(C), (c)(1)(ii)(F), (c)(3)(ii)(A), (e)(1)(ii), (e)(2)(ii)(A),
and (e)(2)(ii)(B) of this section. The effective date for paragraphs
(c)(1)(i)(B), (c)(1)(ii)(C), and (c)(1)(ii)(F) of this section is May
21, 1990. The effective date for paragraphs (c)(1)(ii)(A),
(c)(3)(ii)(A), and (e)(1)(ii), of this section is May 21, 1991. The
effective date for paragraph (e)(2)(ii)(A) is June 12, 1992. The
effective date for paragraph (e)(2)(ii)(B) is May 28, 1993.
(2) The guidelines and other test methods cited in this rule are
referenced as they exist on the effective date of the final rule.
[54 FR 49294, Nov. 30, 1989, as amended at 55 FR 12644, Apr. 5, 1990; 56
FR 23231, May 21, 1991; 57 FR 24961, June 12, 1992; 58 FR 30992, May 28,
1993; 58 FR 34205, June 23, 1993]