33400 Federal Register / Vol. 54, No. 155 / Monday, August 14, 1989 / Rules and Regulations'

ENVIRONMENTAL PROTECTION

AGENCY

40 CFR Parts 795 and 799

[OPTS-42100B; FRL-3627-4]

TrIbutyl Phosphate; Final Test Rule

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Final rule.

SUMMARY: EPA is issuing a final test rule

under section 4 of the Toxic Substances

Control Act (TSCA) requiring

manufacturers and processors of tributyl

phosphate (TBP, CAS No. 126-73-8) to

perform testing for health effects

(oncogenicity, neurotoxicity,

reproductive and developmental

toxicity, mutagenicity, dermal

sensitization, and oral/dermal

pharmacokinetics), environmental

effects (acute effects on algae, fish and

aquatic invertebrates, and triggered

chronic effects on fish and aquatic

invertebrates and sediment bioassay),

and chemical fate (vapor pressure, Koc,

and hydrolysis rate). This rule is in

response to the TSCA Interagency

Testing Committee's (ITC) designation

of TBP for priority health effects,

chemical fate, and environmental effects

testing.

DATES: This rule shall become effective

on September 27, 1989. For purposes of

judicial review, in accordance with 40

CFR 23.5, this rule shall be promulgated

at 1 p.m. eastern fstandard or daylight

as appropriate) time on August 28, 1989.

The incororation by reference in this

rule is approved by the Director of the

Federal Register as of September 27,

1989.

FOR FURTHER iNFORMATION CONTACT:

Michael M. Stahl, Director, TSCA

Assistance Office (TS-799), Office of

Toxic Substances, Room EB-44, 401 M

Street SW., Washington, DC 20460, (202)

554-1404, TDD (202) 554-0551.

SUPPLEMENTARY INFORMATION: EPA is

promulgating a final test rule under

section 4(a) of TSCA requiring health

effects, environmental effects and

chemical fate testing of TBP.

I. Introduction

A. Test Rule Development Under TSCA

This final rule is part of the overall

implementation of section 4 of TSCA

(Pub. L. 94-469, 90 Stat. 2003 et seq., 15

U.S.C. 2601 et seq.), which authorizes

EPA to require the development of data

relevant to assessing the risk to health

and the environment posed by exposure

to particular chemical substances or

mixtures (chemicals).

Under section 4(a) of TSCA, EPA must

require testing of a chemical to develop

data if the Administrator makes certain

findings as described in TSCA under

section 4(a)(1)(A) or (B). Detailed

discussions of the statutory section 4

findings are provided in the EPA's first

and second proposed test rules

published in the Federal Register's of

July 18, 1980 (45 FR 48510) and luneS,

1981 (46 FR 30300).

B. Regulatory listory

The ITC recommended TBP with

intent-to-designate in its eighteenth

report published in the Federal Register

of May 19, 1986 (51 FR 18368), and

designated TBP for priority testing

consideration in its nineteenth report

published in the Federal Register of

November 16, 1986 (51 FR 41417). In

response to this designation, EPA issued

a proposed test rule in the Federal

Register of November 12 1987 (52 FR

43346) which would require that

manufacturers and processors of TBP

test the chemical for various health and

environmental effects, under sections

4(a)(1)(A) and (B) of TSCA.

II. Response to Comments

EPA received written comments on

the TBP proposed test rule from the

Tributyl Phosphate Task Force (TBPTF

of the Synthetic Organic Chemical

Manufacturers Association (SOCMA) on

January 12, 1988 (Ref. 1). The TBPTF

also requested a public meeting on their

comments which was held on April 7.

1988. The comments received by EPA in

response to the proposed rule for TBP

are given below.

A. Exposwie

1. TBPTF exposure survey. The TBPTF

commented that the exposure

information available to EPA was

insufficient to support a finding of

significant or substantial human

exposure since the data were merely

suggestive. The TBPTF proposed to do

an industry-wide. survey of U.S. sites

distributing, processing, and using TSP

and products containing TBP to

determine the uses, use conditions, and

potential worker exposure associated

with TBP. EPA agreed to consider the

study results in its deliberations for a

final rule. TBPTF commissioned Temple,

Barker, Sloane, Inc., to conduct and

validate the survey. On April 7, 1988, the

TBPTF presented EPA with the first part

of a report, "1987 U.S Survey of Tributyl

Phosphate Users, Potential Exposure

and Safety Procedures" (Ref. 2). The

report did not contain an estimate of the

number of workers potentially exposed

to aircraft hydraulic fluid, a product that

accounts for a major part of TBP usage

(89 percent by volume). After a public

meeting with the TBPTF, EPA granted

TBPTF a brief period to estimate the

numbers and extent of potential worker

exposure to aircraft hydraulic fluid

containing TBP from survey and

additional data. On July 11, 1988, TBPTF

submitted a report to EPA on estimated

exposure to TBP-containing aircraft

hydraulic fluid (Ref. 3).

The TBPTF reported that the greatest

number of workers potentially exposed

was in the use of aircraft hydraulic fluid.

The three primary uses include aircraft

manufacturing, hydraulic system

component manufacturing, and

commercial airline operations

(passenger and freight). The TBPTF

reported each type of user exposure in

terms of estimated numbers of

employees potentially exposed on an

infrequent basis (less than once per

week for less than one hour) and on a

more frequent or routine basis. On the

basis of confidential discussions with

two major aircraft manufacturers,

TBPTF estimates that 740 workers in

this industry may be infrequently

exposed to fluid, and 241 workers may

be frequently exposed to hydraulic fluid

containing TBP. On the basis of survey

responses from aircraft component

manufacturers, the TBPTF estimates that

176 employees in this industry may be

frequently exposed to aircraft hydraulic

fluid containing TBP, and 411 employees

may be infrequently exposed. On the

basis of confidential estimates by one of

the major airlines, TBPTF estimates that

2,200 employees in this industry are

routinely exposed to aircraft hydraulic

fluid containing TBP and approximately

43,000 aircraft mechanics at some time

oould be exposed to aircraft hydraulic

fluid. The activities potentially causing

exposure include: Venting of pressurized

systems at service sites, removal and

repair of components, and testing and

inspection of components. Aircraft

manufacturers report that they require

mechanics to use protective equipment

(gloves, aprons, sleeve shields, goggles/

face shields).

In the survey, the other two types of

hydraulic fluid users report these and

other methods of protection. However,

the survey report indicates that in

practice, aircraft mechanics only take

minimal precautions to prevent contact

even though they are aware of the

irritating properties of hydraulic fluid.

Also, according to the survey, aircraft

mechanics do not wear protective

gloves.

Survey respondents reported that 100

distributor workers for 296 worker-hours

per -year and 200 processor workers for
Federal Register I Vol', 54,, No. 155, / Monday, August 14, i989 / Rules and Regulations

108,358 worker-hours per year have

direct exposure to TBP.

An estimated total of 245 distributor

workers (estimated from survey

respondents and non-respondents) are

potentially exposed for 502 workerhours per year according to the survey.

An estimated total of 345 processor

workers (estimated from survey

respondents and non-respondents) are

potentially exposed for 183,382 workerhours per year.

Other uses of TBP involve partially

enclosed or open operations, and the

concentration of TBPin these products

is under 10 percent Of these

miscellaneous uses, paint spraying

operations represent the most likely

exposure potential, but spray booths are

often used and the paint is used only by

original equipment manufacturers,

suggesting that exposure is limited to

manufacturing use.

2. EPA 's response to TBPTFs

exposure survey. EPA reviewed the

exposure survey performed by the

TBPTF and finds the conclusions

regarding potential occupational

exposure to TBP to be reasonable. EPA

has concerns about the completeness

and accuracy of the survey but these do

not interfere with the adequacy of the

study for present purposes (Refs. 4 and

5). The survey results simply confirm

EPA's earlier conclusion that potential

human exposure to TBP is substantial.

B. Testing

. 1. Genotoxicity. The TBPTF

commented that studies of gene

mutation in mammalian cells. in culture

and in vivo cytogenetics, specifically the

mouse micronucleus test, should be

conducted to determine potential

clastogenic effects, and that a program

review of the entire genotoxicity data

base should precede any considerations

for further genotoxicity testing.

EPA agrees that a study of gene

mutation in somatic cells in culture is

necessary as an early tier teset for gene

mutation effects of TBP. However, EPA

believes that an in vitro mammalian

cytogenetics test and in vivo

mammalian bone marrow cytogenetics

chromosomal analysis test are

necessary early tier tests for

cytogenetics effects. EPA is reviewing

the mouse micronucleus test as a

potential alternative teat for cytogenetic

effects in future test rules.

2. Pharmacokinetics. The TBPTF

commented that the rat oral and dermal

absorption, distribution and excretion

pharmacokinetics, and oral metabolism

studies should be performed as

proposed. However, the TBPTF

recommended dermal absorption testing

in the pig (mini-pig or weanling swine)

rather than the guinea pig, because pig

skin is a better model for human skin

than guinea pig skin.

EPA has reviewed the evidence the

TBPTF has submitted to support testing

the pig over the guinea pig and EPA

agrees that the pig (mini-pig or weanling

pig) is an acceptable substitute testing

model for the guinea pig for dermal

absoprption testing (Refa. 6 through 9).

3. Oncogenicity. The TBPTF

commented that, because potential

worker exposure is significant only by

the dermal route as indicated by the

exposure survey, a pilot 28-day dermal

study in the rat should be conducted

first to evaluate the feasibility of

performing chronic efforts and

oncogenicity studies by that route. The

TBPTF believes that a decision

regarding oncogenicity studies should be

deferred pending results of the proposed

pilot dermal studies and the completion

of pharmacokinetics studies.

EPA reported in the proposed rule that

the available data suggest TBP may

have oncogenic potential. EPA is

requiring an oncogenicity study by the

oral route because the comparative

oral/dermal pharmacokinetics data will

allow analysis of effects related to

differences in route of administration.

Protocol design for dermal bioassays

present many problems including:

Selection of appropriate species;

estimation and demonstration of

absorbed versus applied dose, criteria

for defining the maximum tolerated

dose, e.g., whether based on skin or

systemic effects. EPA is assessing the

literature on this subject and has

sponsored 'a workshop on dermal

carcinogenesis bioassay problems and

protocol development. In the near future

EPA hopes to publish a generic protocol

for dermal bioassays and publish

guidelines on when testing should be

done by that route.

4. Dermal sensitization. TBPTF

commented that additional dermal

sensitization testing is unnecessary

because a mixture containing TBP has

been tested in a human study and no

sensitization occurred. TBPTF believes

that if TBP were a sensitizer some

reaction would have occurred and

results of (any) human study should take

precedence over those obtained in

animal (guined pig) studies (Ref 1].

EPA is requiring a dermal

sensitization study because

photosensitization was not evaluated in

the available human study, and the

exact TBP concentration in the test

mixture was unknown and may have

been too low (reported as "less thanf 25

percent") to have elicited a reaction

5, Developmental toxicity. TBPTF

comments that because the exposure

survey indicates there is insignificant

exposure potential for women of childbearing age and because of irritant

warning properties and low exposure

levels, developmental toxicity testing

should not be required.

For purposes of requiring testing

under section 4 of TSCA, EPA is not,

required to take into account genderspecific exposure patterns in its

deliberations. EPA does not assume that

gender-specific exposure patters will

persist. Because there is a potential for

substantial human exposure to TBP,

developmental toxicity testing is

required.

6. Reproductive toxicity. TBPTF

comments that reproductive testing

should be triggered by more general

indications of reproductive toxicity such

as in vivo genotoxicity tests (Drosophila

and in vivo cytogenetics) because there

are very low levels of exposure of both

males and females to TBP. In addition.

two long-term studies, an 18-week study

by Laham et al. and a 13-week study by

FMC, showed no effect on gonadal

tissues.

While EPA recognizes that there are

situations where short-term tests may be

appropriate to screen for reproductive

effects, EPA does not agree that in the

present situation the in vivo

genotoxicity tests are adequate to

screen for the reproductive toxicity of

TBP. And although the two studies

mentioned by TBPTF do not show

reproductive effects, they are not

acequate by themselves to determine

whether TBP has reproductive toxicity.

It is well documented that there are

effects on reproduction that are not

detectable by simple histopathological

analysis, i.e. effects on reproductive

performance, hormones, outcomes of

pregnancy, growth and maturation of

offspring postnatally. Therefore testing

specific for reproductive toxicity is

required.

7. Neurotoxicity. The TBPTF

suggested a tiered approach consisting

of an acute functional observational

battery and motor activity screen to be

followed by a subchronic behavioral

evaluation if required after program

reveiw. The TBPTF commented that

neurotoxicity testing should be by the

dermal route if this route proves feasible

from the results of the 28-day study. The

TBPTF believes that because available

studies conclusively show that TBP is

not a delayed neurotoxicant

(organophosphorus induced delayed

neurotoxicity (OPIDNJ is the primary

mechanism by which organophosphates

act directly on the nerves) a further

concern for neuropathy is unwarranted

33401
33402 Federal Register / Vol. 54, No. 155 / Monday, August 14, 1989 / Rules and Regulations

and requirements for in situ perfusion

should be removed from the test rule.

EPA does not agree with TBPTF's

tiered approach. Both acute and

subchronic tests are necessary because

EPA is concerned about acute effects as

well as the potential effects following

repeated exposure. EPA encourages use

of the relevant route of administration

when possible. Although the dermal

route of administration is theoretically

acceptable, there are a number of

practical problems which must be

addressed before a dermal study would

be acceptable. First, there must be a

demonstration that a sufficient dose of

the compound can be absorbed to

produce neurobehavioral changes.

Without such a high dose level effect,

negative results would not be

conclusive. Second, dermal application

may interefere with satisfactory

interpretation of neurobehavioral

information. Dermal application can

serve as a stress inducer and produce

alterations in various neurobehavioral

parameters. To account for this possible

confounding effect it would be

necessary to use a positive control

which can also be applied dermally (e.g.,

acrylamide). Because these problems

have not been addressed, neurotoxicity

testing by the oral route is required.

EPA believes that, although available

studies indicate that under the

conditions tested, TBP does not produce

organophosphorus-induced delayed

neuropathy (OPIDN), other available

literature provides evidence of

neurobehavioral changes following

exposure to TBP, and a standard battery

of tests is still indicated (Refs. 10

through 13).

8. Environmental effects. The TBPTF

commented that EPA's proposed

environmental effects testing is

generally reasonable and supportable.

TBPTF raised the following points. First,

TBP argued that the chronicity ratio of

24- to 96-hour LC50 for fish and certain

aquatic invertebrates (e.g., Gammorus)

or the ratio of the 24- to 48-hour LC50 for

daphnid of 2 or greater is extremely

stringent and should be modified.

Second, TBPTF believes there is no clear

need for plant translocation tests

because there is no or low level

exposure for this environment, as TBP is

shown to be readily biodegradable in

the OECD screening test, by semicontinuous activated sludge, in a river

die-away test and in ultimate

biodegradation. Third, with respect to

specific guidelines, the TBPTF believes

that ascertaining whether the test

material is in solution does not require

analysis of both the total and filtered

concentrations of the test material. The

concentration in only a filtered sample

should be required except in the algal

test, where measurements of the amount

of test material associated with the algal

cells is required. Centrifuging the

samples is better because filtration may

trap TBP in the filter medium. Requiring

analysis of both total and filtered or

centrifuged test medium will double

analysis costs without any real need.

Fourth; the time allotted (9 months) for

the completion of the flow-through acute

tests may not be adequate. Flow-through

tests with analytical measurement of

test solutions tend to experience more

problems than simple static tests; 12

months from official notification to final

report would be a more reasonable

estimate.

EPA does, not agree with the TBPTF

that the chronicity ratio for fish and

invertebrates is too stringent because

historical data confirm the predictive

capability of this decision criterion. EPA

agrees with TBPTF that the plant

translocation test is unnecessary and

EPA is not requiring this test because

human exposure from plant dietary

uptake does not appear to be of concern.

EPA-is considering whether it should

propose the early seedling growth test to

determine the toxicity of TBP to plants.

EPA does not agree that only the filtered

sample should require analysis and

supports the testing guidelines which

require analysis of both total and

filtered samples. Testing both the total

and filtered samples is necessary to

know how much dissolved test

substance is available during aquatic

toxicity tests. EPA is not requiring that

both the total and dissolved chemical be

measured for every sample. If the

dissolved test substance being measured

is consistently greater than or equal to

80 percent of total measured test

substance, for all test substance

concentrations, then it is necessary to

measure only the dissolved or total test

substance not both. EPA does not agree

with TBPTF that 9 months is inadequate

to conduct acute flow-though testing

because the TBPTF does not provide

adequate evidence to the contrary.

C. Economic Issues

1. Comment: The TBPTF has

estimated the cost of the tisting program

at about $2.4 million. The information to

be developed by the testing program is

not a capital asset; and therefore the

cost involved must be treated as current

expenses. Using the EPA estimated

production volume range of 6 to 9

million pounds during an approximate 2-

year test program, the cost of the testing

proposed per pound would be $0.15 and

$0.20 per pound of TBP produced. TBPTF

does not believe this is an

inconsequential amount.

Response: EPA's estimate of the test

cost is between $1.3 million and $1.7

million. TBPTF's estimate of the

oncogenicity test is roughly double

EPA's estimate, and accounts for the

largest portion of the difference. Some of

the other estimates submitted by the

TBPTF range from 2 to almost 10 times

greater than EPA's estimates.

EPA has developed detailed test cost

information for each test included in the

rule. TBPTF has provided no such

information nor any documentation

regarding their test cost estimates. In

addition, TBPTF has not addressed the

method used by EPA to estimate test,

cost or any of the detailed estimates.

Without any such information, EPA

cannot address the estimates provided

by TBPTF.

Also, TBPTF confuses the procedures

used to determine reimbursement for

testing costs under section 4 of'TSCA

with the analysis used to determine

economic impacts of the rule. TBPTF

looks at the accounting method used to

pay for the costs associated with testing,

while EPA's economic analysis employs

cost recovery analysis to estimate the

likelihood of adverse economic impact.

In the economic analysis, test costs are

annualized over the assumed market life

of the product to estimate the amount

which firms will have to increase price

of the product to recover the costs

associated with testing. This estimate of

product price increase, as explained in

the economic analysis, is used as an

indicator of the potential for adverse

economic impact. EPA's analysis

method is fully explained in the

economic analysis document

accompanying the proposed rule'

2. Comment: Domestic TBP, and TBPbased end-use products, effectively

compete in the international market.

Aircraft hydraulic fluids containing TBP

are used by every major airline in the

free world, and more than one-half of

the fluid produced domestically is

exported. While these fluids are

currently only available from domestic

sources, excessive testing requirements

and associated costs can only encourage

the entry of non-domestic suppliers, thus

placing an unfair competitive burden on

domestic manufacturers and processors

of TBP.

Response: As the TBPTF has

indicated, fluids containing TBP are

used by every-major commercial airline

in the free world and there are only U.S.

sources of these fluids. TBPTF has not

demonstrated that a price increase of 1.4

percent to 2.0 percent to cover the costs

of testing will be a great enough
Federal Register / Vol. 54, No. 155 1 Monday, August 14, 1989 / Rules and Regulations

incentive for companies outside of the

U.S. to begin production of TBP. In

addition, any person who begins to

import TBP from the effective date of the

rule through the reimbursement period

would also be subject to the test rule

and therefore would be subject to

reimbursement of the test costs.

3. Comnient" TBPTF comments further

that conclusions regarding the burden of

testing, which are based on fixed

assumptions in the inexact field of

economic theory, must be seriously and

thoroughly evaluated. The ability to

pass through costs under conditions of

inelastic demand and stable market

conditions may be true but dramatically

increased costs at only some producers

or processors creates unstable

conditions from both supply and

consumption dynamics. In a world-wide

market, domestic producers and

processors of TBP could be placed at an

unfair disadvantage. Even if domestic

suppliers were able to pass through

costs to domestic customers, it is less

likely that such pass-through could be

successful in foreign markets, putting a

double burden on the domestic

marketplace. It is economically more

prudent and more realistic to assume

demand for TBP to be elastic with little

probability of increasing price enough to

cover costs of testing in a reasonable

time. These increased costs, under such

assumptions, will directly impact the

profitability of TBP production and may

ultimately eliminate one or more

producers, or even the product, from the

market.

Response: TBPTF has not

demonstrated that an increase in price

of 1.4 percent to .0 percent qualifies as

"dramatically increased costs".

Moreover, as the TBPTF has indicated,

there are no, foreign sources of TBPcontaining fluids. As a result, all

producers of TBP would incur these

increased costs. EPA has not been able

to identify any viable substitutes for

TBP in its largest use. Producers of TBP

* should be able to pass along the cost of

testing to all of these customers and not

just to domestic customers.

III. Final, Test Rule

EPA is basing its final health and

environmental effects testing for TBP on

the authority of sections 4(a)[1) (A) and

(B) of TSCA.

A. Fidings

Under section 4(a)}f)(A), EPA finds

that the manufacturing, processing,

distribution, use, and disposal of TBP in

aircraft hydraulic fluid and other uses

may present an unreasonable risk of

adverse oncogenic effects, neurotoxic

effects, and dermal sensitization. These

findings are based on the available

toxicity data discussed in Unit II of this

preamble and in Unit II.F. of the

preamble to the proposed rule (52 FR

43346).

Under section 4(a)l})(B), EPA finds

that TBP is produced in substantial

quantities and that there is or may be

substantial human exposure to TBP in

its manufacture, processing, distribution.

use, and disposal. The estimated 1985

production capacity of TBP is 6 to 9

million pounds per year (Ref. 14).

Potentially 43,000 aircraft mechanics

and another roughly 3000 aircraft

industry employees at some time could

be exposed to aircraft hydraulic fluid

containing TSP (Ref. 3). The exposure of

mechanics is mainly dermal exposure

from removing and repairing

components, venting pressurized

systems at service sites, and the testing

and visual and manual inspection of

components. There is also potential of

mainly dermal exposure to TBP of

approximately 500 TBP manufacturing,

processing, and distribution workers

from such operations as handling,

transfer and packaging of products,

equipment repair, cleaning equipment

and spill cleanups. There is also

potential limited dermal exposure to

users of other TBP-containing products

(less than 10 percent concentration

representing in total 28 percent of TBP

volume) including use in original

equipment, paints and coatings, inks.

leather finishing, liquid fluorescent * penetrant, sewage treatment, vinyl floor

finish for commercial and industrial

applications, and stripping agents.

Under section 4[a)B1)fB. EPA finds

that TBP is produced in substantial

quantities, and that it enters or may

reasonably be anticipated to enter the

environment in substantial quantities as

a result of its manufacture, processing,

distribution, use, and disposal as

indicated by its presence in surface'

water, sediment and groundwater. As

stated in the proposed rule, TBP is

expected to enter the environment as a

result of wastewater release from sites

where it is made or used and from

leachate releases from landfills (see.

Unit H.D. of the proposed rule). EPA

believes that the low concentrations of

TBP detected in or released to the

environment at numerous and widely

dispersed locations suggest that the total.

releaseis, substantial under section

4(a)(1)(Bk of TSCA.

1. Health effects. EPA finds that the

available data for insufficient to

reasonably determine or predict the

oncogenicity, neurotoxicity, dermal

sensitization, developmental toxicity,

reproductive and fertility effects,

mutagenicity, and oral/dermal

pharmacokinetics of TBP resulting from

exposure during manufacturing,

processing, distribution, use, and

disposal. EPA finds that testing is

necessary to develop these data. EPA

believes that the data resulting from this

testing will be relevant to a

determination as to whether the

manufacturing, processing, distribution,

use, or disposal of TBP does or does not

present an unreasonable risk of injury to

human health.

2. Environmental effects and chemical

fate. EPA believes that, for chemicals

that have substantial production and

substantial environmental release,

reliable data should be developed to

assess their toxicity and persistence.

Available data are insufficient to

reasonably determine or predict TBP's

acute toxicity to algae, fish, and aquatic

invertebrates, and chronic toxicity to

fish and aquatic invertebrates (free

swimming and in sediment). Available

data are insufficient to reasonably

determine or predict TBP's vapor

pressure data at 250C, Koc, and

hydrolysis rate. Vapor pressure data at

25"C are needed to estimate a reliable

Henry's Law Constant (Hc) for TBP.

Data on Koc are needed to estimate the

sorption of TBP to soil and sediments.

-Finally, hydrolysis. rate data, which

complement the available

biodegradation data, are needed to

estimate the persistence of TPB in

aquatic systems. EPA finds that testing

is necessary to develop environmental

effects data and chemical fate data, and

believes that the data resulting from

these test requirements will be relevant

to a determination that the

manufacturing, processing, use and

disposal of TBP does or does not present

an unreasonable risk of injury to the

environment.

B. Required Testing, Test Standards and

Reporting Requirements

On the basis of these findings EPA is

requiring that chemical fate,

environmental effects and health effects

testing be conducted for TBP in

accordance with specific test guidelines

set forth in 40 CFR parts 796, 797 and

798, or other published test methods as

specified in this test rule as listed in the

following table.

33403
33404 Federal Register / Vol. 54, No. 155 / Monday, August 14, 1989 / Rules and Regulations

REQUIRED TESTING, TEST STANDARDS, AND REPORTING REQUIREMENTS FOR TRIBUTYL PHOSPHATE

Reporting iNueri (- Test Test standard 40 CFR citation deadline for n er

final rule1 mo) reports required

Chemical fate:

Vapor pressure ....................................................................................................... § 796.1950 .........................................................................6 0

Hydrolysis rate at 25 °C ........................................................................................ § 796.3500 ................................................................6 0

Sedim ent and soil adsorption Isotherm ............................................................... § 796.2750 ........... ...................................... ................. 9 0

Environmental effects:

Gam m arid acute toxity ........................................................................................... § 795.120 ................. ........................................................

9 0

Selenastrum acute toxicity .................................................................................... § 797.1050 ................................................................

. 9 0

Rainbow trout acute toxicity .................................................................................. § 797.1400 ................................................................

9 0 Daphnid acute toxicity ....................... ...................................................... ............. § 797.1300 ............................................... ........................ : ..... 9 0

Daphnid chronic toxicity ......................................................................................... § 797.1330 ................................................................

21 1

Fish early life stage ................................................................................................ § 797.1600 ................................................................21 1

Sediment invertebrate bioassay ............................................................................ Adam s et al. (Ref. 15) .........................................................21 1

Health effects:

Oral/derm al pharm acokinetics .............................................................................. § 798.228 .................................................................

12 1

Oncogenicity ............................................................................................................ § 798.3300 ....................................... ........................................ 53 8

Reproduction and fertility effects (oral) ............................................................... § 798.4700 ................................................................

29 4

Developm ental toxicity (oral) ................................................................................. § 798.4900 ................................................................

12 1

Dermal sensitization ............................................................................................... 798.4100 ................................................................6 0§ 

Functional observation battery (acute and subchronic) .................................... § 798.6050 ................................................................

18 2 M otor activity (acute and subchronic) ................................................................. § 798.6200 ................................................................

18 2

Neuropathology .............................................................................................. § 798.6400 ................................................................

18 2

Mam malian cells in culture .................................................................................... § 798.5300 ................................................................

10 1

Drosophila sex-linked recessive lethal ................................................................ § 798.5275 ................................................................22 1

In vitro cytogenetics ............................................................................................... § 798.5375 ................................................................10 1 In vivo cytogenetics ................................................................................................ § 798.5385 ................................................................

24 1

Dom inant lethalssay ........................................................................................... § 798.5450 ................................................................

36 5

Heritable translocation assay ................................................................................ § 798.5460: ................................................................225 3

'Number of months after effective date, except as indicated.

2 Figure indicates the reporting deadline, in months, calculated from the date of notification of the test sponsor by certified letter or FEDERAL REGISTER notice that

following public review of all the existing data for TBP, the Agency has determined that required testing must be performed.

Although the major occupational

exposure route for TBP is dermal, EPA is

requiring that testing for oncogenicity,

neurotoxicity, development toxicity,

reproductive and fertility effects shall'be

by the oral route because (1) the skin

irritating effects of TBP could confound

the results of dermal testing, (2) existing

supporting studies have been done by

the oral route, and (3) there are technical

problems conducting dermal tests. EPA

is also requiring oral/dermal

pharmacokinetics. EPA is specifying

that the Sprague-Dawley rat be used for

both oncogenicity and pharmacokinetics

testing because existing data presented

in the proposed rule show this species to

be sensitive to TBP.

EPA requires that all data developed

under this rule be reported in

accordance with its TSCA Good

Laboratory Practice (GLP] Standards, in

40 CFR part 792.

In accordance with 40 CFR part 790,

under single-phase rulemaking

procedures, test sponsors are required to

submit individual study plans at least 45

days before initiation of each test.

EPA is required by TSCA section

4(b)(1)(C) to specify the time period

during which persons subject to a test

rule must submit test data. Final testing

requirements, test standards and

reporting requirements for this TBP test

rule are summarized in the preceding

table. Interim progress reports for the

tests shall be provided to EPA at 6-

month intervals after the effective date

of this rule until the final report is

submitted to EPA.

TSCA section 14(b) governs EPA

disclosure of all test data submitted

pursuant to section 4 of TSCA. Upon

receipt of data required by this rule,

EPA will publish a notice of receipt in

the Federal Register as required by

section 4(d).

Persons who export a chemical which

is subject to a section 4 test rule are

subject to the export reporting

requirements of section 12(b) of TSCA.

Final regulations interpreting the

requirements of section 12(b) are in 40

CFR part 707. In brief, as of the effective

date of this test rule, an exporter of TBP

must report to EPA the first annual

export or intended export of TBP to each

country. EPA will notify the foreign

country concerning the test rule for TPB.

For the purpose of this test rule, these

guidelines are the test standards that

must be met by the test sponsors. The

route of administration of TBP for all

tests shall be oral unless otherwise

specified. Data resulting from these tests

will assist EPA in conducting health and

environmental risk assessments for TBP.

The TSCA test guidelines, proposed

modifications, and other .cited test

guidelines discussed in the following

paragraphs in III.B. specify generally

accepted minimal conditions for

determining toxicities and properties of

substances such as TBP to which human

and aquatic life are expected to be

exposed. Conducting the required

studies in accordance with these TSCA

guidelines will help ensure that the test

results are reliable and adequate.

The oral/dermal pharmacokinetics

test guideline in the proposed rule has

been revised based upon public

comments and is promulgated as

§ 795.228 Oral/dermal pharmacokinetics test.

EPA periodically reviews the TSCA

Test Guidelines, according to the

process described at 47 FR 41857

(September 22, 1982).

1. Health effects. The neurotoxicity

testing required will consist of an acute

and'subchronic functional observation

battery specified in § 798.6050, as

modified in § 799.4360(c)(1)(i)(A)(2), an

acute and subchronic motor activity test

specified in § 798.6200, as modified in

§ 799.4360(c)(1)(i)(B)(2), and a

subchronic neuropathologic evaluation

of tissues perfused in situ specified in

§ 798.6400, as modified in

§ 799.4360(c)(1)(i)(C)(2).

To assess the developmental effects of

TBP, EPA is requiring'that testing be

conducted by gavage according to

§ 798.4900, as modified in

§ 799.4360(c)(2)(i)(B).
Federal Register / Vol. 54, No. 155 / Monday, August 14, 1989 / Rules and Regulations

To assess the reproductive and

fertility effects of TBP, EPA is requiring

that testing be conducted according to

§ 798.4700, as modified in

§ 799.4360(c)(3)(i){B) (i)(B).

To assess the mutagenic effects of

TBP, EPA is requring that testing be

conducted in tiers. First-tier testing will

consist of the detection of gene mutation

in somatic cells in culture using the test

guideline § 798.5300, an in vitro

mammalian cytogenetics test using the

test guideline in § 798.5375, and an in

vivo mammalian bone marrow

cytogenetics chromosomal analysis test

using the test guideline in § 798.5385, as

modified in § 799.4360(c)(5)(i)(B)(2).

Unless the results of the gene mutation

in somatic cells in culture are negative, a

sex-linked recessive lethal test in

Drosophila melanogaster will be

required. Second-tier testing will consist

of a sex-linked recessive lethal assay in

Drosophila melanogaster using the test

guideline in § 798.5275, as modified in

§ 799.4360(c)(4)(i)(B)(2), and a rodent

dominant lethal test using the test

guideline in § 798.5450; third-tier testing will consist of a rodent heritable

translocation test using the test

guidelines in § 798.5460, and as modified

in § 799.4360(c)(5)(i)(D)(2).

In the proposed rule, EPA would have

required third-tier testing consisting of a

mouse visible specific locus test using

the test guideline in § 798.5200 as

modified. Positive results in the sexlinked recessive lethal test may have

triggered the requirement for conducting

a mouse visible specific locus (MVSL)

test. EPA believes that the MVSL may

be necessary, when these lower-tier

tests are positive, to establish

definitively whether a substance is

capable of eliciting heritable gene

mutations. Under the approach

proposed, EPA would have considered

the positive results in the lower-tier

tests in a public program review,

together with other relevant information,

during which interested persons would

be able to give their views to EPA. If,

after the review, EPA had determined

that the MVSL was still appropriate, EPA would have notified the test

sponsors by letter or Federal Register

notice that they must conduct the test. If

EPA had determined that the test was

no longer necessary, EPA would have

amended the rule to delete the test

requirement.

The final test rule for TBP includes

requirements to conduct the lower-tier

tests for gene mutation. However, EPA

is not promulgating the requirement for

the MVSL for TBP at this time. EPA has

based its proposal to require the MVSL,

in part, on information and assumptions

about the cost of conducting the test and

the availability of laboratories capable

of performing the test. The information

and assumptions have since proven to

be incorrect. Accordingly, EPA is in the

process of reexamining the MVSL

requirement for all those chemical

substances for which the MVSL has

been required or proposed to be

required. In particular, EPA is reviewing

whether any laboratories are available

to perform the MVSL for industry in

accordance with the TSCA Good

Laboratory Practice Standards at 40

CFR part 792 and the cost of such

testing, EPA is also reviewing possible

alternative tests to the MVSL for which

costs may be lower or laboratory

availability may be more certain.

EPA has published a notice in the

Federal Register concerning the MVSL

for TBP and other substances subject to

proposed and final TSCA section 4 test

rules (53 FR 51897). This notice provides

up-to-date information on the cost of

MVSL testing, availability of

laboratories to perform the MVSL, and

possible alternative tests to the MVSL

together with their costs and laboratory

availability. The notice also addresses

EPA's intentions about any changes to

the MVSL requirements in the various

test rules and provides an opportunity

for public comment. If, after this

proposed rule is finalized and if after

lower tier mutagenicity testing of TBP,

EPA concludes that the MVSL is

appropriate for TBP, EPA will amend

this rule to include the MVSL

requirements with any appropriate

modifications.

Should the gene mutation in somatic

cells test prove negative, no further

gene-mutation tests will be required. If

the sex-linked recessive lethal test is

negative, no further gene-mutation test

will be required of TAP.

If the results of the in vitro

mammalian cytogenetics test are

negative, an in vivo mammalian bone

marrow cytogenetics, chromosomal

analysis test will be required. Unless the

results of the in vivo test are negative, a

rodent dominant lethal test will be

required. A positive result in the rodent

dominant lethal test will tr'igger the

requirement that a heritable

translocation test be conducted. Should

the in vivo mammalian cytogenetics test

results prove negative, no further

chromosomal effects testing will be

required. If the dominant lethal test is

negative, no further chromosomal effects

testing will be required for TBP.

Under this final rule, if the result of

the second-tier rodent dominant lethal

test is positive, EPA will hold a public

program review before industry will be

required to initiate the third-tier

heritable translocation test. The public

will participate in this program review

either by submitting written comments

or commenting during a public meeting.

A request for public comment or

notification of public meeting will be

published in the Federal Register.

Should EPA determine, from the

available weight of evidence, that

proceeding to the heritable translocation

test is no longer warranted, EPA will

propose to repeal this testing

requirement and, after public comment,

issue a final amendment to rescind this

requirement. EPA will notify the test

sponsors by certified letter or Federal

Register notice, following the public

program review of all the then-existing

data for TBP, if the heritable

translocation test must be performed.

EPA will also conduct internal program

reviews of the reports of the gene

mutations in somatic cells in culture

assay, the in vitro mammalian bone

marrow cytogenetics test, and the in

vivo mammalian bone marrow

cytogenetics test and other available

mutagenicity data to evaluate whether

the sex-linked recessive lethal and the

rodent dominant lethal tests have been

triggered.

For a more detailed discussion of

mutagenicity tiered testing and public

program review procedures, see EPA's

final test rule for the C9 aromatic

hydrocarbon fraction published in the

Federal Register of May 17, 1985 (50 FR

20662).

To assess the oncogenic effects of

TBP, EPA is requiring that testing be

conducted according to § 798.3300 in

Sprague-Dawley rats and in mice via the

oral route of administration.

To assess the dermal sensitization

effects of TBP, EPA is requiring that

testing be conducted according to

§ 798.4100.

To compare the oral route of

administration of TBP in § 798.3300 and

the dermal route, in § 798.4100 which is

thought to be a primary route of human

exposure, EPA is requiring an oral/

dermal pharmacokinetic test with TBP

to examine absorption, distribution,

metabolism, and excretion. EPA is

requiring that testing be conducted

according to § 798.7485. The decision to

require most testing of TBP by the oral

route is based on the results of dermal

irritation tests showing TBP effects to

range from irritating to corrosive (Unit

II.F.1. of preamble to proposed rule).

Moreover, dermal application of the

corrosive TBP could stress the test

animals, which may distort test results.

TBP is well tolerated by the oral route

(Unit II.F. of preamble to proposed rule).

33405
33406 Federal Register / Vol. 54, No.. 155 / Monday,. August 14, 1989 / Rules and Regulations

EPA is not requiring the renal effects

test recommended by the ITC. Acute

and subacute oral studies by Mitomo et

al. (Ref. 16) showed kidney tubule

damage in rats and mice. However, two

oral subchronic rats studies of g0 days

and 126 days showed no kidney damage

even at dosages higher than the Mitomo

studies (Refs. 17 and 18). EPA believes

that there are adequate data available

to assess the effects of TBP on kidney

tubules.

2. Environmental effects. EPA is

requiring the following environmental

effects testing to determine the toxicity

of TBP to an alga, a fish, and aquatic

invertebrates: (1) Selenastrum

capricornutum, in accordance with

§ 797.1050 as modified in

§ 799.4360(d)(1)(i)(B); (2) rainbow trout

in accordance with § 797.1400, as

modified in § 799.4360(d](2)(i](B); (3)

daphnids in accordance with § 797.1300,

and as modified in § 799.4360(d)(3)i)(B);

and (4) gammarids in accordance with

§ 795.120, as modified in

§ 799.4360(d)(4)(i)(B. Only one test

species, rainbow trout, is required for

the fish acute toxicity test because an

acute test for the fathead minnow is

available and adequate in combination

with the testing required for the rainbow

trout for purposes of assessing the acute

toxicity of TBP of fish (see Unit 1.G.].

All the acute aquatic toxicity data from

these tests will be used to determine

whether chronic aquatic testing is

necessary according to the testing

scheme presented in the following

figure:

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