43346 Federal Register / Vol. 52, No. 218 '1 Thursday, November 12, 1987 / Proposed Rules

SUPPLEMENTARY INFORMATION: On

August 13-14, 1987,tMSHA conducted- a

public'hearirIg inDenver, Colorado to

allow-members of.the.mining community

and otheriinterestedparties .to present

testimony and-supporting:data

concerning MSHA's 'proposed revisions

to its-existing ionizing radiation

standards for underground metal and

nonmetal mines (51 FR 45678).

During the hearing and the subsequent

comment period. 'the Agency received -a

substantial.amount Of information

regarding-the hazards associated with

ionizing radiation and the

appropriateness of regulation 'to protect

miners.exposed to much'hazards. In

addition, major reports on-radiation

were expected from the National

Academy of Sciences.(NAS) and the

National Institute'for Occupational

Safety and Hedlth (NIOSH). To enable

interested parties'to fully discuss this

material and the issues raised during the

public hearing the comment period was

extended to October 30, 1987 (52 FR

33956). A prepublication copy of the

NIOSH document "Criteria for a

Recommended Standard * *

Occupational Exposure to Radon

Progeny in Underground Mines",

together with a companion:document

"Review Comments and Responses for

Criteria ,fora Recommended-Standard

* * * Occupational Exposure to Radon

Progeny in Underground Mines",,was

received by MSHA on October 30, 1987.

The NAS,report on'the Biological Effects

of Ionizing Radiation (BEIRJIV) is

expected to be published before the end

of the year. The NAS-document-will

specifically address the.effects of

exposure to intermllydeposited

alphaemitting radionuclides such as

radon daughters.

Various-members .of the mining

community, -including representatives of

both labor and industry, haveindicated

in their post-hearing submissions the

need toreviewthe supplemental

material, and have ,requestedan

additional extension of thepublic

comment'pefiod. MSHA acknowledges

the merit of theserequests and has

determined that-a further extension'is

appropriate. Accordingly,'MSHA -will

permit the rulemaking record-to remain

open until'F6bruary 29, 1988 to

accommodate -public -response.

The NIOSH criteria:document

recommendsa reduction of the

permissible ;exposure ievdl to 1-working

level month:as an upper limitwith mine

operators making every effort toireduce

and maintainmexposure to radon

daughters as lowas -possible. In

addition, :the average workshift

concentration isnot toexceed -1/12 of I

working level (WL) (or 0.083 WL).

NIOSH further:recommends that

respirators be required when entering an

area where engineering controls have

not achieved V12 WL average workshift

concentration, when entering areas

where 'concentrations are unknown, or

during emergencies. 'Respirator credit

would be allowed. Other

recommendations address analytical

methods; recordkeeping; medical

surveillance; posting of hazard

information; .respiratory protection;

worker education and -notfication; and

prohibition of smoking.

Under section 101(a)(1) of the Federal

Mine Safety and Health Act of 1977, the

Secretary is obligated to make a public

response to the NIOSH

recommendations. Although MSHA is

not publishing the criteria document as

a proposed rule, MSHA is making the

document available .for public comment

as part of its ongoing rulemaking-to

assure the fullest input .of the mining

community. Copies of the document are

available upon request'from MSHA's

Office of.Standards, Regulations, and

Variances. MSHA'will'continue to

review and evaluate the NOISH criteria

document and comments received on it

and will'respond'to the

recommendations -in the Agency's final

rule.

MSHA is 'also extending'the comment

period for 'the purpose of furthering

discussion. on the appropriateness'of

including avradidtion control'plan as

partof the -standard. This concept -was

suggested'duing the public'hearing. The

NIOSH criteria document also

recognizes the'need to adapt work

practicesand enngineefing controls to

unique 'features of mining operations.

A plan approach would-address both

work'practices',and feasible engineering

controls -as a means to reduce radiation

exposure. It would seek'to incorporate

the internationally accepted principles

of ALARA.(redudtion of exposures "as

low.as reasonably achieveable"). The

concept ofALARA was raised in the

proposal,.and was 'the'subject of

discussions during'the public hearing.

This approach'would allow tailoring of a

control strategy to the unique

characteristics ofa 'mine, the mine

workforce, and'the particular-mining

method being utilized.'Sudh-a 'regulatory

alternative might establish he :best

feasible prdtection on a mineby-mine

basis while maintaining a baseline

exposure limit for all exposed'miners.

Under such.an approach, operators

would be encouraged to 'improve

protection whereverpossible. MSHA

solicits commenton the merits .of this

alternative approach, and:its

appropriateness for inclusion in the

Agency's regulatory.strategy for

protection.miners from 'ionizing

radiation. The Agency 'is particularly

intereStedin suggestions'concerning the

possible contents :of a control plan,

together with ideas related'to

implementation, including plan review,

adoption and revision procedures.

Date: Noveniber 6, 1987.

Patricia W. Silvey,

Acting Associate Assistant Secretary for

Mine Safety and Health.

[FR Doc. 87-26121 ,Filed 11-10-87; 8:45.am]

BILLING CODE-4510-43-AM

ENVIRONMENTAL-PROTECTION

AGENCY

40 CFR Parts 795.and 799

[OPTS-42100; FRL-3289-6]

Tributyl Phosphate; Proposed Test

Rule

AGENCY:Environmental PrOtection

Agency (EPA).

ACTION: Proposed rdle.

SUMMARY ,EPA is spropoding that

manufacturers and processors -of tribtityl

phosphate (T.BP, CAS No. 126- 73-18) be

required, under section'4 df'the'Toxic

Substances Control 'Act :(TSCA), to

perform testing 'for neurotoxidity,

developmental toxicity, reproductive

toxicity, mutagenicity, oncogenicity,

dermal:sensitization,.oral/ dermal

pharmacokinetics, environmental

effects, 'and dhemical fate. 'This rdle is

proposed in response to the-Interagency

Testing Committee's (ITC's) designation

of TBP'for priority-consideration for

chemical fte, health effects, and

environmental.effects testing.

DATES: Submit written comments on or

betore January I1, 1988. If persons

request an opportunity to submit-oral

comment by December'28, 1987, EPA

will hold a-public meeting on this rule in

Washington, DC.For further information

on arranging to speakat the meeting see

Unit VII-of this-preamble.

ADDRESS: Submit written comments,

identified by the document control

nuiber'(OPTS-42100), 'in triplicate to:

TSCA Pdblic.Information :Office -(TS793), 'Office ofPestidides and Toxic

Substances, Environmental'Protetion

Agenqy, RoomNE-GO04, 401 M St.,

SW., Washington, DC 20460.

A public\version df the administrative

record supporting'this action'(with any

confidential business information

deleted) is available for inspection it

the above address from 8 aim. to 4,p.m..
Federal Register / Vol. 52, No. 218 / Thursday, November 12, 1987 / Proposed Rules

Monday through Friday except legal

holidays.

FOR FURTHER INFORMATION CONTACT:

Edward A. Klein, Director, TSCA

Assistance Office (TS-799), Office of

Toxic Substances, Room E-543, 401 M

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

554-1404.

SUPPLEMENTARY INFORMATION: EPA is

issuing a proposed test rule under

section 4(a) of TSCA in response to the

ITC's designation of TBP for chemical

fate, health effects, and environmental

effects testing consideration.

I. Introduction

A. ITC Recommendation

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

seq. 15 U.S.C. 2601 et seq.) established

the ITC under section 4(e) to recommend

to EPA a list of chemical substances and

mixtures (chemicals) to be considered

for testing under TSCA section 4(a).

The ITC recommended TBP (CAS No.

126-73-8) with intent to designate for

chemical fate, health effects, and

environmental effects testing in its 18th

Report, published in the Federal Register

of May 19, 1986 (51 FR 18368). The ITC

designated TBP for priority

consideration in its 19th Report,

published in the Federal Register of

November 14, 1986 (51 FR 41417). The

ITC recommended that TBP be

considered for health effects testing,

consisting of chronic toxicity including

oncogenic, neurotoxic, renal,

reproductive, and developmental effects;

chemical fate testing, including

persistence in anaerobic soils and

sediments; and environmental effects

testing, including chronic effects on

aquatic and terrestrial plants, daphnids

and/or other aquatic invertebrates, and

acute and chronic effects on benthic

organisms and soil invertebrates, if

found persistent under anaerobic

conditions.

The ITC's rationale for health effects

testing was based on: (1) A large

production volume; (2) a high number of

workers occupationally exposed; and (3)

the lack of data on health effects.

The ITC's rationale for chemical fate

testing was based on: (1) The large

production volume; (2) detection of TgP

in municipal and industrial effluents,

sediments, and in river, estuarine,

ground, and drinking waters; and (3)

detection of TBP in human and fish lipid

tissue.

The ITC's rationale for environmental

effects testing was based on: (1) TBP's

presence in various surface and

groundwaters; (2) available information

showing that TBP has acute effects on a

variety of aquatic organisms at

moderately low concentrations and on

terrestrial plants; and (3) the appearance

of continual exposure of nearly all types

of biota to low concentrations of TBP.

B. Opportunity for Negotiating A

Consent Order

EPA has issued an Interim Final Rule

that amends EPA's procedural

regulations in 40 CFR Part 790 for the

development and implementation of

testing requirements under section 4 of

TSCA. The amendments established

procedures for using enforceable

consent orders to require testing under

section 4 of the Act. EPA intends to use

such consent orders where a consensus

exists among the Agency, affected

manufacturers and/or processors, and

interested members of the public about

the need for and scope of testing

requirements. The consent order

provides an alternative to the test rule

development process, facilitating the

rapid development of test data without

the necessity of EPA using the lengthy

rulemaking process.

Where EPA concludes that the

Agency the affected industry and

interested parties cannot reach a

consensus on the testing requirements or

other provisions to be included in the

consent order, the Agency will proceed

with rulemaking under section 4(a) of

TSCA. A description of the procedures

governing consent orders and test rules

appears in detail in the Federal Register

of June 30, 1986 (51 FR 23706).

The first step in determining the

feasibility of developing a consent order

for a specific compound is the

identification of interested parties who

may wish to participate in negotiations

with EPA. In the Federal Register of July

2, 1986 (51 FR 24222), EPA announced

that the Agency was considering

developing a testing consent order for

TBP. This notice requested interested

parties to identify themselves. FMC

Corporation, Mobay Chemical

Corporation, and Stauffer Chemical

Company requested participation in

negotiating a consent order; however, a

final agreement was not obtained.

Consequently, the Agency is proceeding

with rulemaking under section 4(a) of

TSCA.

C. Test Rule Developmeht Under TSCA

This document 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 contains

authority for EPA to require

development of data relevant to

assessing the risks to health and the

environment posed by exposure to a

particular chemical.

Under section 4 of TSCA, EPA must

require testing of a chemical to develop

health or environmental 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 Agency's first and second

proposed test rules which were

published in the Federal Register of July

18, 1980 (45 FR 48524) and June 5, 1981

(46 FR 30300).

In evaluating the ITC's testing

recommendations for TBP, EPA

considered all available relevant

information including the following:

Information presented in the ITC's

report recommending testing

consideration and public comments on

the ITC's recommendations; production

volume, use, exposure, and release

information reported by manufacturers

of TBP under the TSCA section 8(a)

Preliminary Assessment Information

Rule (40 CFR Part 712); health and safety

studies submitted under the TSCA

section 8(d) Health and Safety Data

Reporting Rule (40 CFR Part 716); and

published and unpublished data

available to the Agency. From its

evaluation, as described in this

proposed rule, EPA is proposing health

effects testing under section 4(a)(1) (A)

and (B) and environmental effects

testing under section 4(a)(1}(B). By this

action, EPA is responding to the ITC's

designation of TBP for priority testing

consideration.

II. Review of Available Data

A. Profile

TBP is a colorless, odorless liquid

(Ref. 1). It has a molecular weight of

266.32 daltons (Ref. 7), measured water

solubility of 280-:36 mg/L at 25 °C, a

measured vapor pressure of 127 mm Hg

at 177 'C, a measured boiling point of

289 °C at 760 mm Hg, and a measured

log K.. of 4.0 (Ref. 8). Muir (1984)

estimated a Henry's law constant (Hc)

for TBP to be 2.48 X10 - 2 atm m3/mol

(Ref. 54). The Agency believes this

estimate of Hc is 2 to 3 orders of

magnitude too high.

B. Production

TBP is produced in the United States

(U.S.) by two manufacturers: FMC

Corporation and Stauffer Chemical

Company. Monsanto Company, a former

manufacturer, discontinued TBP

production at the end of 1985. The

estimated 1985 combined production

capacity of TBP is 6 to 9 million pounds

per year (Ref. 45). The actual production

and import volumes for 1985 have been

submitted as confidential business

information.

43347
43348 Federal Register / Vol. 52, No. 218 / Thursday, November 12, 1987 / Proposed Rules

Acyclic triphosphates such as TBP are

commercially prepared from phosphorus

oxychloride and the appropriate

alcohols (Ref. 1). Phosphorus

oxychloride reacts violently with water

or moisture in the air, and consequently

the reaction is usually contained in a

closed process and is run under a dry

nitrogen blanket. When the reaction is

completed, the triester may be washed

with a mild basic solution and then with

water which is subsequently removed

by decanting and vacuum distillation.

Depending on the amount produced, the

triester is then pumped into tank cars,

tank wagons, 55-gallon drums, or

smaller containers for shipment to

customers (Ref. 1).

C. Uses

Some 40 to 60 percent of all TBP

consumed is used as a base stock in the

formulation of fire-resistant aircraft

hydraulic fluids. Formulation

concentrations are typically 50 to 60

percent of the hydraulic fluid. These

hydraulic fluids are usually prepared by

metering and pumping the individual

components into a mixing tank where

the components are blended. The fluids

are then pumped into 55-gallon drums or

tank trucks which are shipped to

distributors/customers. When used, the

fire-retardant hydraulic fluids are

pumped into the system, which is bled

to ensure that no air remains in the '

system. The bleeding of the system may

result in small amounts of overflow (Ref. 1).

Some 10 to 20 percent of the

production volume of TBP is used for

extraction and separation processes in

the PUREX (Plutonium Uranium

Reduction Extraction] process for the

separation of plutonium and uranium

from spent nuclear fuel elements. It is

also used to purify 232

LJ produced from

the bombardment of protactinium-231.

Many other metals can be extracted

using TBP as the solvent. For example,

cerium(IV) is separated from trivalent

lanthanides; polonium can be separated

from lead, bismuth, and niobium, from

tantalum, or from impurities in niobium

ore. TBP is also used to extract indium,

thorium, uranyl nitrate, and, in an analytical procedure, strontium-90. It is

used as an ion-association reagent (acid

media) for metals, and also used in

liquid-liquid extraction as a modifier in

a mixture with an extractant and a

diluent (Ref. 1), and in equipment

cleaning (Ref. 2).

Approximately 5 to 10 percent of TBP

is used as a defoamer in the paper

industry and in textile sizers, inks,

lacquers, and as a plasticizer (Ref. 1).

Minor uses of TBP as a chemical

reagent include the following: Use in

combination with other chemicals to

split viruses for the preparation of

subvirion vaccines; for impregnation

into resins that remove trace metal

impurities from acid solutions; as a

coating on high-performance liquid chromatographic columns that are used

to quantify urinary porphyrins; for

extraction of oxalic acid in a highperformance liquid chromatographicmethod to determine oxalic acid in

urine; and as a pigment-grinding

assistant, a very minor use (Ref. 1).

D. Environmental Release

TBP is expected to enter the

environment as a result of wastewater

releases from sites where it is made or

used and from leachate releases from

landfills.

During production, TBP may be

released to surface waters in the

wastewater used in washing procedures.

Small amounts of TBP could also occur

in distillation bottoms and would

subsequently be incinerated or

landfilled (Ref. 2).

During processing and use of TBP,

release to water may result from such

activities as the cleaning of equipment

used in formulating aqueous-based

polishes and from spillage during the

draining and/or refilling of airplane

hydraulic systems (Ref. 2). Some release

could occur during ore extraction. The

reported presence of TBP in industrial

effluents, as discussed in the following

paragraph, suggests that many uses of

the compound result in eventual release

into the aquatic environment. There are

usually no direct releases of phosphate

esters from the solid materials into

which they are incorporated (Ref. 2].

TBP was found in municipal and

industrial effluents at concentrations

ranging from 6.9 jAg/L to 13,517 jig/L

(Ref. 1). Although the names and

locations of the plants are confidential,

the industries represented include paint

and ink, printing and publishing,

organics and plastics, pulp and paper,

pharmaceuticals, explosives, foundries,

aluminum, electronics, organic

chemicals, transportation equipment,

and publicly owned treatment works.

Dunlap et al. (Ref. 4) identified 1.7 mg/L

of TBP in groundwater underlying a

landfill in Norman, Oklahoma and

Hutchins et al (Ref. 5) identified traces

of TBP in groundwater in Fort Polk,

Louisiana. TBP (concentration not given)

was also found in Philadelphia drinking

water (Ref. 6).

In a study by Williams et al. (Ref. 40),

TBP was found in drinking water

derived from the Great Lakes or

adjacent water bodies in 12 Canadian

communities at concentrations ranging

from 0.8 ng/L to 29.5 ng/L. About half

the locations are near U.S. communities

such as Buffalo, NY and Niagara Falls,

NY that may draw water from the same

sources.

EPA conducted a study for the

purpose of compiling a list of all organic

compounds. that have been found in

water (Ref. 41). TPB was also found in

water (Cincinnati, OH and Miami, FL),

effluent from a chemical plant, effluent

from two landfill leachates, a well, and

a river. The report gave only the

locations mentioned and no TBP

concentrations (Ref. 57).

E. Human Exposure

1. Occupational

EPA believes that there are numerous

possibilities for occupational exposure

to TBP. However, the extent to which

such exposures actually occur in TBP's

production, distribution, and use is

unclear because of a lack of detailed

information about many of the specific

industries involved. According to the

National Occupational Hazard Survey

(NOHS, 1972-1974) by the National

Institute for Occupational Safety and

Health (NIOSH), 30,555 workers in 15

industries and 30 occupations were

potentially exposed to TBP.

Approximately /s of these workers fall

into the Standard Industrial

Classification (SIC) for "Transportation

by Air" (Ref. 53). This probability

sample was based upon a 1970 list of

businesses covered under the

Occupational Safety and Health Act.

Potential exposure estimates thus refer

to the year 1970. Estimates are derived

from surveyor observations of three

basic types.

a. Actual. The surveyor observed the

use of the specific agent.

b. Tradename. The surveyor observed

the use of a tradename product known

to contain the specific agent.

c. Generic, The surveyor observed a

product in some type of general use

which leads NIOSH to suspect that the

specific agent may be contained in that

product.

According to the National

Occupational Exposure Survey (NOES,

1981-1983) by NIOSH 12,111 workers in

6 industries and 13 occupations were

potentially exposed to TBP (Ref. 3).

However, this survey does not include

workers in the SIC category,

"Transportation by Air", which includes

the aircraft mechanic occupation that

EPA considers an important area of

potential exposure to TBP. Also, the

NOES, using probability sampling

techniques, selected approximately 4,500

workplaces in the U.S. for walk-through

surveys. It is abroad-scope survey, not
Federal Register / Vol. 52, No. 218 / Thursday, November 12, 1987 / Proposed Rules

designed to stand as a definitive study

or provide precise information for any

one particular hazard. The NOES data

used are preliminary. The NOES

includes only a few of the SIC codes and

consists solely of actually observed uses

of TBP in the work place.

EPA estimates 12 to 16 workers to be

potentially exposed to TBP at each of its

two manufacturing sites for 25 days per

year (Ref. 2). Because of the corrosive

nature of TBP and its phosphorus

oxychloride precursor (see Unit II.B.1.),

workers manufacturing TBP operate

processes which are closed and usually

conducted under a blanket of nitrogen.

Further, because of the hazardous

character of phosphorus oxychloride,

workers normally are protected through

the use of local ventilation, appropriate

respiratory equipment, and suitable

protective clothing. Thus, little or no

routine exposure of workers is expected

during the synthesis of TBP (Ref. 2).

On completion of the manufacturing

operation, the finishedmaterials are

drummed or packaged fdt shipment.

Incidental dermal contact may be

encountered during routine connection

of transfer lines between reactor and

drumming station and during drumming.

If no gloves were worn, this contact

could amount to some 1,300 to 3,900 mg/

contact if both hands were exposed and

from 1 to 3 mg of material/cm2 adhered

to the skin. Similar dermal contact

would occur when equipment is cleaned

and maintained (Ref. 2).

The processing of TBP primarily

involves mechanical transfer of pure

material as it is received for a blending

operation. In the processing of TBP for

aircraft hydraulic fluid, EPA estimates

the involvement of less than 70 site-days

per year and 2 to 4 workers per site with

a dermal contact potential of 650 to 1950

mg/day (Ref. 2).

An industrial hygiene report from Los

Alamos Scientific Laboratory indicated

that irritating fumes may form when TBP

is heated, necessitating ventilation of

the work area (Ref. 1). However, the

heating of TBP during industrial

production, processing, or use would be

very unusual because it breaks down at

high temperatures. For this reason it is

generally used at ambient temperature

(Ref. 27 and 33). This would reduce the

possibility of inhalation contact except,

for example, here aerosol formation may

occur as a result of spraying operations.

The largest potentially exposed

worker population is in aircraft

maintenance because manual

operations could result in exposure to

TBP-containing hydraulic fluid (Unit

II.C.). The Bureau of Labor Statistics

(BLS) of the U.S. Department of Labor

reported 99.000 aircraft engine

mechanics and 15.000 aircraft nonengine

mechanics in 1986 (Ref. 42); the latter

figure is consistent with the roughly

10,000 aircraft workers estimated to be

exposed in the NOHS. Preliminary

information indicates that mechanics

involved in large aircraft repair at one

site are, on the average, potentially

exposed to hydraulic fluid

approximately once per week for 30

minutes to 2 hours (Ref. 43); however,

EPA is uncertain whether that exposure

scenario is typical for the industry and

what the range of actual individual

exposures might be. A potential for hand

exposure to hydraulic fluid (1,300 to

3,900 mg., both hands) applies to aircraft

mechanics in the same manner as that

described earlier in this Unit for the

transfer and packaging phase of

manufacturing operation and the

cleaning and maintenance of equipment.

In the case of ore extraction (primarily

uranium ore benefaction), EPA

estimates that there are up to 25 plant

sites and 2 to 8 workers per site.

Mechanical transfers and automated

processes are typical (Ref. 2). However,

possibilities of exposure exists which

are similar to those found in TBP's

manufacture and the processing of other

products as described earlier in this

Unit: transfer of stock material,

drumming or packaging, and cleaning

and maintenance of equipment.

Exposure in plastics production is

assumed to be limited because of the

frequent use of mechanical transfers and

automated processes (Ref. 2). However,

possibilities of exposure exist which are

similar to those found in TBP's

manufacture and the processing of other

products as described earlier in this Unit

transfer of stock material, drumming or

packaging, and cleaning and

maintenance of equipment.

"The identification of TPB in releases

from the spectrum of industries cited in

Unit II.D suggests a potential for'worker

exposures in those industries,

particularly in smaller operations where

procedures are less likely to be

automated and isolated from potential

worker contact. The Agency encourages

the submission of relevant data,

especially on exposure potential and

work practices in the paper, textile, inks,

and coatings industries (see Unit B.C.).

2. General Population

A potential route of general

population exposure is through contact

with contaminated environmental

media, including drinking water (see

Unit 11. D.). TBP has been found in

numerous industrial effluents,

groundwater in Oklahoma and

Louisiana, in drinking water in

Philadelphia, PA; Cincinnati, OH; and

Miami, FL; and in river water. TBP has

also been found in the drinking water of

several Canadian municipalities that

obtain their water from the Great Lakes

(see Unit II.D). Tens of thousands of

people draw their water from these

sources. Although the concentrations of

TBP found so far in drinking water are

extremely low, EPA will examine

closely any additional evidence of such

exposure.

EPA conducted an analysis of human

adipose tissue samples for the detection

of chemical substances. The primary

focus was to document trends in human

exposures to environmentally persistent

contaminants. Forty-six composite

samples (20 adipose tissue samples per

composite sample) were analyzed. A

trace of TBP was found in one

composite sample of a 0 to 14 year old

group from the East North Central area

(Ohio, Indiana, Illinois, Michigan, and

Wisconsin) (Ref. 20). The'significance of

this evidence of TBP exposure is

difficult to evaluate.

F. Health Effects

1. Acute Toxicity

LD50 or LC50 values for TBP in rats

ranged from 1,390 to 3,200 mg/kg with

oral administration (Refs. 9 through 12),

500 to 1,600 mg/kg with intraperitoneal

administration (Refs. 13 and 51), and

less than 2,000 mg/L of air via inhalation

administration (Ref. 14). In another rat

inhalation study, one third of the

animals died after a 6-hour exposure at

3,800 ppm of TBP (Ref. 11). Two dermal

toxicity studies with rabbits produced

LD50 values ranging from equal to or

greater than 3.1 g/kg to equal:to or

greater than 10.0 g/kg (Refs. 10 and 15),

and two dermal irritation studies with

rabbits showed TBP to be a mild to

severe irritant (Refs. 14 and 55).

These studies are sufficient to

reasonably determine or predict theacute toxicity of TBP.

2. Dermal Sensitization

Skydrol ® 500B--4, an aircraft hydraulic

fluid containing less than 25 percent TBP

(Ref. 28), was patch-tested for dermal

irritation and sensitization in 53 men

and women; all completed the test [Ref.

24). Approximately 0.2 mL of test

material was'placed on each patch, and

a series of 15 alternate-day applications

(weeks I to 5) was carried out during the

induction phase. Each patch was

removed and the dermal area examined

after 24 hours for three successive days.

None of the 53 participants were

sensitized. Photosensitization was not

evaluated, and the exact TBP

concentration tested is unknown but':

may have been too low to have elicited.

a reaction. For this reason, EPA

concludes that these data are not

sufficient to reasonably determine or

predict the sensitization effects of TBP.

43349

- - • ;1
Federal Register / Vol. 52, No. 218 / Thursday, November 12, 1987 / Proposed Rules

Fourteen guinea pigs were tested for

dermal sensitization to TBP by the "drop

on" method. Six of the 14 were

sensitized (Ref. 32). The test method,

including the control procedure and the

grading system, was not described. No

photosensitization test was conducted.

Although this study suggests a skin

sensitization hazard due to TBP

exposure, it does not supply sufficient

data to fully determine or predict the

dermal sensitization potential of TBP.

3. Subchronic Toxicity

Groups of Sprague-Dawley rats

consisting of 12 males and 12 females

per group were given 0.20 or 0.30 g/kg of

TBP by gavage 5 days/week for 18

weeks in the low-dose group and for 6

weeks in the high-dose group (Ref. 22). A

control group was given water by

gavage. Because no change was seen

after 6 weeks in the high-dose group,

their dosage was increased to 0.35 g/kg

for the remaining 12 weeks. Although no overt signs of toxicity were observed,

rats in both dose groups showed diffuse

hyperplasia of the urinary bladder

epithelium on histopathological

examination (see Unit II.F.8. for

discussion). Numerous other organs

were examined histopathologically but

showed no pathological changes. The

investigators also reported decreased

body weight in high-dose males and

decreased red blood cell count in highdose females.

In another study (Ref. 23), TBP (over

99 percent purity) was administered

continuously in the diet of SpragueDawley rats for at least 90 days at

concentrations of 0, 8, 40, 200, 1,000, and

5,000 ppm. Fifteen male and fifteen

female rats were randomly assigned to

each dose group. No mortality occurred

during this study. Histopathologic

examinations were conducted on

selected tissues from all control and

high-dose animals and on livers and

urinary bladders from all animals. The

no-effect dose level of TBP was 200 ppm.

Treatment-related histopathological

effects included generalized

transitional-cell hyperplasia in the

urinary bladders of the males receiving

1,000 ppm and 5,000 ppm of TBP and the

females receiving 5,000 ppm (see Unit

II.F.8. for discussion). Clinical signs that

may have been treatment-related were

sporadic abdominogenital staining on

several males and females receiving

1,000 ppm and 5,000 ppm TBP doses

during the first 19 days of the study, a

significant decrease in platelets in the

males receiving 1,000 ppm, and a

significant elevation of the mean

activated partial thromboplastin time in

the males receiving 5,000 ppm. These

studies are sufficient to reasonably

.;w i QQQ Aol i(o(n( InlN V-R7- 14:,7!471

determine or predict the subchronic

effects of TBP.

4. Neurotoxicity

TBP (80 mg/kg) was one of several

organic phosphates tested by injection

into the tail vein of rats (number in test

groups not given and no mention of

controls) (Ref. 16). Uncoordination and

mild anesthesia occurred in about 1 hour

and pronounced weakness in about 4

hours. With a dose of 100 mg/kg,

anesthesia and pronounced dyspnea

occurred in 8 to 10 minutes followed by

respiratory failure. There were no

cholinergic symptoms. The paper states

that artificial respiration had to be given

in some cases, but does not specify for

" which chemicals. Also, chemical purity

is not stated; no-effect levels were not

determined. Apparently TPB

administered intravenously is much

more toxic to rats than administered by

other routes (II.G.).

Two dose groups of ten male and ten

female Sprague-Dawley rats per group were given 0.28 and 0.42 ml/kg/day of a

mixture of 98.4 percent TBP and 1.3

percent tributoxyethyl phosphate (an

occasional contaminant of TBP, Ref. 44)

by gavage for 14 days (Ref. 17). A

control group was force-fed tap water. A

significant reduction in conduction

velocity of the caudal nerve was

observed in high dose male rats (four

rats/group) 24 hours after

administration of the last dose. Electron

microscope examination of the sciatic

nerve showed morphological changes

such as retraction of Schwann cell

processes surrounding fibers in both

sexes of the high dose group. A study was performed to test TBP

(purity'not given) for delayed

neurotoxicity in 18-month old leghorn

hens (Ref. 18). The oral LD50 for TBP in

hens without atropine protection against

acute cholinergic effects was

determined to be 1,500 mg/kg. A group

of 20 hens received a single oral dose of

1,500 mg/kg of TBP, in gelatin capsules,

on day 0. Hens that survived were dosed

again on day 21 with atropine sulfate

protection. Another group of 10 hens

were given two dermal doses of 1,500

mg/kg of TBP on day 0 and day 21. On

both days atropine sulfate was

administered. Controls consisted of a

positive control group for delayed

neurotoxicity treated with a single oral

dose of 750 mg/kg of tri-o-cresyl

phosphate; another group was given

gelatin capsules. Although a total of six

hens died following the oral

administration of TBP, none of the

surviving hens developed delayed

neurotoxicity throughout the 42-day

experiment. All of the hens treated with

dermal doses of TBP survived the 42-day

experiment and none of them developed

signs of toxicity. These results indicate

that delayed neurotoxicity is not a

concern with TBP.

Although the first two studies cited

suggest that TBP may cause neurotoxic

effects, they are inadequate to

determine or predict the acute and

chronic neurotoxic potential of TBP.

5. Developmental Toxicity

No developmental toxicity data for

TBP have been found in the literature or

have been reported under the TSCA

section 8(d) rule (51 FR 18323; May 19,

1986).

6. Reproductive Toxicity

In a 1984 study by Laham et al. (Ref.

19) two groups of ten male and two

groups of ten female Sprague-Dawley

rats were given 0.14 and 0.42 ml/kg of

TBP (98.4 percent) by gavage daily for 14

days. A control group was force-fed tap

water. One out of four of the male rats

in the high-dose group showed

microscopic degenerative changes in

approximately 50 percent of the

seminiferous tubules.

A follow-up 18-week study which was

conducted by the same investigators

failed to identify any testicular changes

in rats of the same strain exposed by

gavage to TBP (98.4 percent) levels up to

0.35 gm/kg/day 5 days/week (Ref. 22).

The negative results of the follow-up

study contradict the previous study.

However, the high TBP dosage in the

follow-up study was less than in the

previous study. Tubular degeneration is

said to have occurred in 50 percent of

tubules examined rather than in one out

of four of the rats examined in the high

dose group. In addition to the

contradictions in these two studies,

there are no available reproductive

studies designed to provide general

information about the effects of TBP on

gonadal function, conception,

parturition, and the growth and

development of the offspring. Therefore,

EPA concludes that existing data are not

sufficient to reasonably determine or

predict the reproductive effects of TBP.

7. Mutagenicity

An Ames test was conducted by the

FMC Corporation with TBP (100 percent)

using five strains of test bacteria (strains

TA 1535, TA 1538, TA 1537, TA 98, TA

100) both with and without the addition

of an exogenous source of liver enzyme

for metabolic activation of the test

agent. No evidence of mutagenic activity

was found by this method (Ref. 29). EPA

concludes that this is a valid negative

test.

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A test using the Cy/Bly method was

conducted with Drosophila to measure

the accumulation of recessive lethals on

the second chromosome of flies exposed

over a number of generations for 18

months to increasing levels of TBP (Ref.

46). TBP was not found to be mutagenic

in Drosophila. The frequencies of

accumulated lethal mutations in the

TBP-treated flies and the controls were

11.1 and 9.3 percent. Only one

population cage was used per chemical

and control, and the number of flies

sampled was low. Because of the lack of

historical data and the unusual nature of

the experiment it is impossible to

calculate the power of the test. In

addition, this test has not been

validated in terms of test repeatability,

and sensitivity. Given these

uncertainties, the study is not sufficient

to reasonably determine or predict the

mutagenic effects of TBP on Drosophila.

Although there are valid negative data

for the Ames test, no further data are

available to reasonably determine or

predict gene mutation or chromosomal

aberration effects of TBP.

8. Oncogenicity

Urinary bladder hyperplasia was

reported in both of the subchronic

studies discussed earlier (Unit II.F.3.). In

an 18-week, two-dose gavage study with

Sprague-Dawley rats (Ref. 22), animals

in both dose groups (0.20 and 0.30-0.35

g/kg) showed diffuse hyperplasia of the

bladder epithelium. In a 90-day dietaryfeeding study with Sprague-Dawleyderived rats at TBP concentrations 0, 8,

40, 200, 1,000, and 5,000 ppm (Ref. 23),

the only treatment-related

histopathological finding was

generalized transitional-cell hyperplasia

in the urinary bladders of the 1,000 ppm

and 5,000 ppm males and the 5,000 ppm

females.

Although all hyperplasia does not

necessarily lead to neoplasia,

hyperplasia has been shown to be

associated with tumor development with

many chemicals. The development of

hyperplasia and of neoplasia is both

time and dose dependent. In a 2-year

study, it could be expected that bladder

hyperplasia would be observed at dose

levels well below those used in the

subject studies. Furthermore, in EPA's

judgement, the degree of hyperplasia

induced in the TBP subchronic studies

strongly suggests a potential for

progression to tumor formation.

The available data suggest that TBP

may have oncogenic potential, but are

not sufficient to fully determine or

predict the oncogenic effects of TBP.

9. Pharmacokinetics (Oral/Dermal

Absorption, Distribution, Metabolism,

and Excretion)

Jones (Ref. 35) concluded that TBP is

metabolized to the corresponding

dialkyl phosphate, and S-alkyl cysteine.

Jones further concluded that

monodealkylation appears to be a

common route of metabolism for trialkyl

phosphates, most likely occuring

through enzymatic hydrolysis (P-O

cleavage) and de-O-alkylation (C-0

cleavage, with reduced glutathione

acting as an alkyl receptor), Test species

were male rats and mice.

Marzulli et al. (Ref. 36) demonstrated

that 32p- and 14C-labeled TBP can

penetrate sheets of human stratum

corneum conjunctur in diffusion cells.

From in vitro measurements of steady

state rates of penetration, the

investigators were able to predict in

vivo skin penetration rates. This in vitro

model gave essentially the same results

as tests on anterior forearms of three

human subjects.

Eleven phosphorus-containing

metabolites were identified in a 24-hour

urine sample from rats following

intraperitoneal injection of 250 mg/kg of

TBP (Ref. 37). The major metabolites

included dibutyl hydrogen phosphate,

butyl dihydrogen phosphate, and butyl

bis(3-hydroxybutyl) phosphate. Small

amounts of derivatives hydroxylated at

other carbons of the butyl groups were

also detected. The major metabolic

intermediates were considered to be

dibutyl 3-hydroxybutyl phosphate and

dibutyl 3-oxobutyl phosphate.

In a follow-up study (Ref. 38) to

determine whether these metabolites

are formed by mixed-function oxidases,

by esterases, or by glutathione Stransferase, investigators identified

sulfur-containing metabolites of TBP. In

this study, the major urinary metabolites

following a single intraperitoneal

injection of TBP were (3-oxobutyl)- and

(3-hydroxybutyl)mercapturic acid.

Traces of 2-oxobutyl- and (2-

hydroxybutyl)mercapturic acids were

also detected.

Sasaki et al. (Ref. 39) determined the

in vitro metabolic pathway of TBP using

liver homogenate, forming first tributyl

hydroxy phosphate and then tributyl

dihydroxyphosphate, with dibutyl

phosphate being only a minor dead-end

point in the in vitro pathway.

Following a single oral dose of 1

4CTBP (14 mg/kg) to male rats, 50, 10, and

6 percent of the label was excreted in

the urine, exhaled air, and feces,

respectively, within 24 hours (Ref. 37).

Following a single intraperitoneal

injection (14 mg/kg), 70, 7 and 4 percent

was excreted in the urine, exhaled air,

and feces, respectively, within 24 hours.

Although available data give some,

information about human in vitro and in

vivo skin penetration, intraperitoneal rat

metabolism and excretion of TBP,

comparative oral/dermal or intravenous

pharmacokinetics studies are not

available. None of the studies include

comparative guinea pig/rat

bioavailability, skin absorption, or

tissue distribution of TBP. EPA believes

that available data are not sufficient to

reasonably determine or predict the

comparative oral/dermal

pharmacokinetics of TBP.

G. Environmental Effects

1. Acute Toxicity

Several studies were performed to

estimate the toxicity and

bioconcentration of TBP in aquatic

organisms. All these studies used

nominal TBP concentrations or static

test conditions, except the studies

conducted by Geiger et al. and the

Analytical Bio Chemistry Laboratories,

Inc. (Ref. 26 and 49) which used

measured TBP concentrations and flowthrough conditions. The following Table

1 is a summary of the studies:

TABLE 1-AOUATIC TOXICITY AND BIOCONCENTRATION OF TBP

Test e (Ref. Organism days Test value No.)

Chlorella emersoni ................................. 2

Daphnia magna ............................................................................. 1

2

'1

2

3

Fathead minnow ........................................ .................................. 4

EC50= 5-10 m g/L ...........................................................................

EC50= 5.8 m g/L .............................................................................

LC50= 9.0 m g/L .............................................................................

,LC50= 12.8 m g/L ......................................................................

LC50= 3.7 mg/L ............... ...................

LC50= 2.1 m g/L ..............................................................................

LC50= 8.0 m g/L............................................."............................

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TABLE 1-AQUATIC Toxic'rv AND BIOCONCENTRATION OF TBP-Continued

Organism est Test value (Ref.

days No.)

4 LC50=11.0 mg/L ............................................................................ 26

4 LC50=6.4 mg/L .............................................................................. 49 Killifish ............ :................................................................................... 4 LC 50 = 9.6 m g/L .............................................................................. 50

G oldfish ............................................................................................. 4 LC 50= 8.8 m g/L .............................................................................. 50

Zebrafish ........................................................................................... 4 LC 50= 11.4 m g/L ............................................................................ 56 4 LC50=10-14 mg/L ........................................................................ 47

Rainbow trout ................................................................................... 4 LC50= 5-9 m g/L ............................................................................. 51

4 LC50=8.2 mg/L ............................................................................. 30

4 LC50=11.0 mg/L ......... ...... ...... ............. 52

Zebrafish ........................................................................................... 10 Tox Threshold= 13.5 mg/L ................... ...... 56

48 Tox Threshold=8.3 mg/L ............................................................. 56

G oldfish ............................................................................................. 4 B C F = 7 ............................................................................................. 50 Killifish ............................................................................................... 4 B C F = 30 ................................................................................. ......... 50 38 BCF=21-35 .................................................................................... 29

EPA carefully analyzed the available percent of TBP was biodegraded (Unit bound residues in pooled plant organs acute toxicity data and concluded the II.H.). This susceptibility to and pooled whole plants. Therefore,

following: (1) Chlorella is a relatively biodegradation and TBP's relative EPA concludes that the above data are

insensitive species of alga compared to hydrophobicity indicate that flow- not sufficient to reasonably determine or

Selenastrum and testing in Selenastrum through testing would better provide for predict plant uptake and translocation

will provide more useful data; (2) continuous exposure toa relatively of TBP.

available data with D. magna, while constant TBP concentration than static

generated by methods unacceptable for or renewal systems. Static tests on such 2. Chronic Toxicity

TBP, suggest a time dependent acute compounds may underestimate toxicity. No information was found on the

toxicity that may indicate cumulative EPA concludes that most of the acute chronic toxicity of TBP to aquatic or

toxicity, toxicity of a byproduct that toxicity data listed in Table 1 are not terrestrial organisms. would not be removed from static test sufficient to reasonably determine or

systems, or potential chronic toxicity; (3) predict the acute toxicity of TBP to H. Chemical Fate

while all of the 4-day fish LC50 values, daphnids, gammarids, rainbow trout, or

including those conducted under flow- algae. TBP is expected to partition to the

through conditions, are very similar TBP's herbicidal properties for aquatic and sediment environments.

(within a factor of 3), it is reasonable to terrestrial plants were tested with Available data suggest that TBP is

require a flow-through test with rainbow various seedlings (sweet corn, substantially biodegraded in aerobic,

trout to provide more reliable data to cucumber, cotton, lima bean, tobacco, but not anaerobic environments. EPA

assess the potential hazard of TBP. and tomato). The seedlings were dipped considers these data adequate to

The logic for requiring flow-through in 0.5 and 5.0 percent water solutions of determine or predict aerobic and

tests for TBP is based on biodegradation TBP (frequency of dipping not given), anaerobic biodegradation. An adequate potential and hydrophobicity of TBP. Within 1 week, all TBP-treated plants measurement of log Kow is also

Available data show that after 4 days' were severely injured or dead (Ref. 25). available (Ref. 13). The following Table

incubation in river water containing a This study makes no provision for the 2 shows the biodegradability data of

relatively low concentration of TBP- determination of concentration of free TBP.

unacclimated bacteria, at least 10 TBP, metabolites, and soluble and

TABLE 2.-BIODEGRADABILITY OF TRIBUTYL PHOSPHATE

Test Test- days Test (Ref. value No.)

O EC D 301C (TBP loss) .................................................................. 28 77% ................................................................................................... 47

O EC D 3010 (B D ) .......................................................................... 28 92% ................................................................................................... 54

O EC D 301 E (DO C Loss) ................................................................ 28 89% ....... ; ........................................................................................... 54

SCAS I .............................................................................................. 91 96% @ 3 m g/L/ day ....................................................................... 8

SCAS ................................................................................................. 147 56-- 21% @ 13 m g/L/day ............................................................ 8 Rliver die-aw ay ...................................................................... 7........... 4 10%Y .................................................................................................... 8 . 7 100% ........................................................................................ ...... 8

Ultimate biodegradation .................................................................. 7 1% of theoretical C02 at 20 mg/L .............................................. 8

*28 3% of theoretical C02 at 20 mg/L ...................................... I 8

7 30% of theoretical C02 at 19.4 mg/L ......................................... 8

- 28 91% of theoretical C02 at 19.4 mg/L ......................................... 8

Anaerobic biodegradation (TBP loss) ........................................... 30 0% ...................................................................................................... 28

'Semi-Continuous Activated Sludge.

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As noted by the ITC, the ubiquitous

environmental appearance of TPB at

various concentrations (see Unit II.D.)

may mean that it is not effectively

degraded below some threshold

concentration or that the continuous

release of TBP into the environment

leads to some low-level equilibrium

concentration reflecting both input and

removal processes (51 FR 18369).

I1. Findings

EPA is basing its proposed health

effects testing for TBP on the authority

of sections 4(a)(1) (A) and (B) and

environmental effects testing on the

authority of section 4(a)(1)(B) of TSCA.

A. Findings Under TSCA Section

4(a)(1)(A)

1. Health Effects

EPA finds that the manufacture,

processing, use, and disposal of TBP

may present an unreasonable risk of

injury to human health due to

potentially significant levels of

occupational and general population

exposure as discussed in Unit II.E., and

to its potential to cause oncogenicity,

neurotoxicity, and dermal sensitization

based on available animal studies (see

Unit II.F.).

The finding of potential oncogenicity

risk is based on two reports of

hyperplasia of the urinary bladder

epithelium in rats after oral

administration of TBP (Refs. 22 and 23).

Although all hyperplasia does not

necessarily lead to neoplasia,

hyperplasia has been shown to be

associated with tumor development with

many chemicals (Unit II.F.8.) (Ref. 34).

The data suggest that TBP may be

oncogenic, but are derived from studies

that are too brief to adequately

characterize this effect.

The finding of potential neurotoxicity

risk is based on uncoordination,

anesthesia, weakness, and respiratory

failure in rats after injection of TBP (Ref.

16), and reduction in caudal nerve

velocity and retraction of Schwann cell

processes surrounding sciatic nerve

fibers in rats after the administration of

98.4 percent TBP by gavage (Ref. 17).

The finding of potential dermal

sensitization risk is based on the

sensitization of 6 out of 14 guinea pigs

exposed to TBP (Ref. 32).

For the reasons stated in Unit II., EPA

also finds that available data are

insufficient to reasonably determine or

predict the oncogenicity, neurotoxicity,

and dermal sensitization effects from

exposure during TBP's manufacturer,

processing, use, and disposal. The

Agency finds that testing is necessary to

develop health effects 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 human

health.

2. Environmntal Effects

EPA finds that the manufacturing,

processing, use, and disposal of TBP

may present an unreasonable risk of

injury to the environment because of its

release to the environment and its

potential to cause lethality in terrestrial

plants. The concern for potential plant

uptake effects is based on a study in

which TBP was lethal to various

seedlings for which soluble and bound

residues in the plants were not

measured (Ref. 25). Available data are

insufficient to reasonably determine or

predict the plant uptake and

translocation of TBP resulting from

exposure due to release during its

manufacture, processing, use, and

disposal. The Agency finds that testing

is necessary to develop these data. EPA

believes that the data resulting from this

test requirement will be relevant to a

determination that the manufacturing,

processing, use, and disposal of TBP do

or do not present an unreasonable risk

of injury to the environment.

B. Findings Under TSCA Section

4(a)(l(B)

1. Health Effects

EPA finds that TBP is produced in

substantial quantities, and that there is

or may be significant occupational and

general population exposure from its

manufacture, processing, use, and

disposal (see Unit II.E.). From 6 to 9

million pounds of TBP was produced in

the U.S. in 1985 (Ref. 45). According to

the NOHS, (1972-1974), 33,555 workers

are potentially exposed to TBP;

according to the NOES (1981-1983),

12,111 nonaircraft workers are

potentially exposed; and according to

the BLS (1986), there are 15,000

nonengine aircraft mechanics

potentially exposed (largest potential

exposure group) (Unit II.E.). Although

the major exposure route is thought to

be dermal, the detection of TBP in

drinking water in the U.S. and in

Canadian drinking water taken from the

Great Lakes indicates the possibility of

human exposure by the oral route (Unit

I1.D.) to substantial numbers of people in

the general population. TBP's major use as an ingredient in

aircraft hydraulic fluid creates the

possibility of dermal exposure of 15,000

aircraft mechanics (Unit II.E.1.) at

significant levels. TBP is also used in

extraction and separation processes for

various metals, in textile sizers, inks,

and lacquers, and as a plasticizer. It has.

several minor uses, for example, the

splitting of viruses (Unit II.C.). Although

some of these uses are highly

automated, the other uses may result in

exposure of a substantial number of

industrial workers.

Available data are insufficient to

reasonably determine or predict the

neurotoxicity, developmental toxicity,

reproductive'and fertility effects,

mutagenicity, oncogenicity, dermal

sensitization, and oral/dermal

pharmacokinetics of TBP resulting from

exposure during its manufacture,

processing, use, and disposal. The

Agency finds that testing is necessary to

develop health effects data. EPA

believes that the data resulting from

these test requirements will be relevant

to a determination that the

manufacturing, processing, use, and

disposal of TBP do or do not present an

unreasonable risk of injury to human

health.

2. Environmental Effects

EPA finds that TBP is produced in

substantial quantities (6 to 9 million

pounds in 1985 (Ref. 45)). It enters or

may reasonably be anticipated to enter

the environment in substantial

quantities during manufacture,

processing, use, and disposal, as

evidenced by its detection in surface

water, sediment, and groundwater (see

Unit II.D.). EPA believes that the low

concentration of TBP detected in or

released to the environment at

numerous, widely-dispersed locations

suggest that the total quantity released

to the environment is substantial (see

Unit II.D.). EPA believes that for

chemicals with substantial production

and ubiquitous environmental

distribution, reliable data should be

developed to assess their toxicity and

persistence. Available data are

insufficient to reasonably determine or

predict TBP's acute effects on aquatic

algae, fish, and invertebrates, and

chronic effects on fish and aquatic

invertebrates (free swimming and in

sediment). The Agency finds that testing

is necessary to develop environmental

effects 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.

The ITC recommended terrestrial'

invertebrate testing for TBP. EPA is

considering possible test species and

methods for such testing but has not yet

IRI III

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Federal Register / Vol. 52, No. 218 / Thursday, November 12, 1987 / Proposed Rules

determined the best approach to testing

for this effect under TSCA section 4. The

Agency is soliciting public comments on

this issue (see Unit V.) and is not

proposing the testing at this time.

3. Chemical Fate

EPA finds that TBP is produced in

substantial quantitites (6 to 9 million

pounds in 1985 (Ref. 45)). It enters or

may reasonably be anticipated to enter

the environment in substantial

quantities during manufacture,

processing, use, and disposal, as

evidenced by its detection in surface

water, sediment, and groundwater (see

Unit II.D.). Available data are

insufficient to reasonably determine or

predict TBP's vapor pressure at 25 *C,

log Koc, and hydrolysis rate. Vapor

pressure data at 25 *C are needed to

estimate a reliable Hc for TBP. Data on

log Koc are needed to estimate the

sorption of TBP to soil and sediments.

Finally, hydrolysis rate data, which

complement the biodegradation data,

are needed to estimate the persistence

of TBP in aquatic systems. EPA 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.

IV. Proposed Rule

A. Proposed Testing and Test Standards

On the basis of the information

presented in Unit If and the findings set

forth in Unit III of this preamble, EPA is

proposing health and environmental

effects testing for TBP. The tests are

proposed to be conducted in accordance

with EPA's TSCA Good Laboratory

Practice Standards in 40 CFR Part 792

and specific TSCA test guidelines in 40

CFR Parts 795, 796, 797, and 798, and

other published test methods as

specified in the proposed rule for TBP.

The oral/dermal pharmacokinetic test

guideline proposed in § 798.7470 is

revised and recodified in Part 795 as

section § 795.228 Oral/dermal

pharmacokinetic test. For the purpose of

this test rule, these guidelines are being

proposed as the test standards that must

be met by the test sponsors. The route of

administration of TBP for all tests would

be oral unless otherwise specified. Data

resulting from these tests will assist the

Agency in conducting health and

environmental risk assessments for TBP.

Final revisions to the TSCA test

guidelines were published in the Federal

Register of May 20, 1987 (52 FR 19056);

the Agency is proposing that these

revised test guidelines be adopted as the

test standards for TBP.

The TSCA test guidelines, proposed

modifications, and other cited test

guidelines discussed below specify

generally accepted minimal conditions

for determining toxicities and properties

of substances such as TBP to which '

human, aquatic, and terrestrial 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 Agency's review of the TSCA

Test Guidelines, which occurs on a

yearly basis according to the process

described at 47 FR 41857 (September 22,

1982), has found no reason to conclude

that these protocols need to be modified

significantly.

1. Health Effects

The acute neurotoxicity testing and

neurobehavioral toxicity evaluation

would consist of the functional

observation battery as specified in 40

CFR 798.6050, modified in proposed

§ 799.4360(c)(1)(i)(A)(2), and the motor

activity test as specified in 40 CFR

798.6200, as modified in proposed

§ 799.4360(c)(1)(i)(B)(2). To assess the

effects of repeated long-term exposures

to TBP, the Agency is proposing a

subchronic (90-day) neurotoxicity and

neurobehavioral toxicity evaluation

consisting of a neuropathologic

evaluation of tissues perfused in situ as

specified in 40 CFR 798.6400, as

modified in proposed

§ 799.4360(c)(1)(i)(C)(2).

To assess the developmental effects of

TBP, the Agency is proposing that

testing be conducted by gavage

according to the guidelines at 40 CFR

798.4900, as modified in proposed

§ 799.4360 (c)(2)(i)(B).

To assess the reproductive and

fertility effects of TBP, the Agency is

proposing that testing be conducted

according to the guidelines at 40 CFR

798.4700, as modified in proposed

§ 799.4360(c)(3)(i)(B)(i)(B).

To assess the mutagenic effects of

TBP, the Agency is proposing that

testing be conducted in tiers. First-tier

testing would consist of the detection of

gene mutation in somatic cells in culture

using the test guidelines at 40 CFR

798.5300, an in vitro mammalian

cytogenetics test using the test

guidelines at 40 CFR 798.5375, and an in

vivo mammalian bone marrow

cytogenetics chromosomal analysis test

using the test guidelines at 40 CFR

798.5385, as modified in proposed

§ 799.4360 (c)(5)(i)(B)(2); second-tier

testing would consist of a sex-linked

recessive lethal assay in Drosophila

nielanogaster using the test guidelines at

40 CFR 798.5275, as modified in

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

rodent dominant lethal test using the

test guidelines at 40 CFR 798.5450; and

third-tier testing will consist of a mouse

visible specific locus test using the test

guidelines at 40 CFR 798.5200 and rodent

heritable translocation test using the

test guidelines at 40 CFR 798.5460, and

as modified in proposed § 799.4360

(c)(5(i)(D)(2).

Unless the results of the gene

mutation in somatic cells in culture are

negative, a sex-linked recessive lethal

test in Drosophila melonogaster would

be required. Positive results in the sexlinked recessive lethal test would trigger

the requirement for conducting a mouse

visible specific locus (MVSL) test. EPA

believes that the MVSL is 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 consider

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 the

Agency. If, after the review, EPA

determined -that the MVSL was still

appropriate, EPA would notify the test

sponsors by letter or Federal Register

notice that they must conduct the test. If

EPA determined that the test was no

longer necessary, EPA would propose to

amend the rule to delete the test

requirement.

Other test rules have included the

requirement for the MVSL, including

those for the C9 aromatic hydrocarbon

fraction (50 FR 20662),

diethylenetriamine (50 FR 21398), and

four fluoroalkenes (52 FR 21516). EPA

based the requirement in those rules, 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.

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Federal Register / VoL 52. No. 21a / Thursday, November 12, 1987 1 Proposed Rules

Once EPA completes its evaluation of

this additional information, EPA will

publish a notice in the Federal Register

concerning the MVSL for TBP and other

substances subject to proposed and final

TSCA section 4 test rules. This notice

will provide 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 will also address

EPA's intentions about any changes to

the MVSL requirements in the various

test rules and will provide an

opportunity for public comment. If, after

this exercise, EPA concludes that the

MVSL is appropriate for TBP, EPA will

include the MVSL requirements with

any appropriate modifications in the

final rule.

Should the gene mutation in. somatic

cells test prove negative, no further

gene-mutation tests would be required.

If the sex-linked recessive lethal test is

negative, no further gene-mutation tests

would be required of TBP.

If the results of the in vitro

mammalian cytogenetics test are

negative, an in vivo mammalian bonemarrow cytogenetics, chromosomal

analysis test would be required. Unless,

the results of this in vivo test are

negative, a rodent dominant lethal test

would be required. A positive result in

this rodent dominant lethal test would

trigger the requirement that a heritable

translocation test be conducted. Should

the in vivo mammalian cytogenetics test

results prove negative, no further

chromosomal effects testing. would be

required. If the dominant lethal test is

negative, no further chromosomal effects

testing would be required for TBP.

Under this proposed rule, if the result

of the second-tier rodent dominant

lethal test was positive, EPA would hold

a public program review before industry

would be required to initiate the thirdtier heritable translocation test (see Unit

IV.D.). The public would participate in -

this program review either by submitting

written comments or commenting during

a public meeting. Request for public

comment or notification of a public

meeting would be published in the

Federal Register. Should EPA-determine,

from the available weight of evidence,

that proceeding to the heritable

translocation test was no longer

warranted, the Agency would propose to

repeal this testing requirement and, after

public comment, issue a final

amendment to rescind this requirement.

EPA would 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 would 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 C aromatic

hydrocarbon. fraction published in the

Federal- Register of May 17, 1985 (50 FR

20662).

In order to assess the oncogenic

effects of TBP, the Agency is proposing

that testing be conducted according to

the guidelines at 40 CFR 789.3300 in

Sprague-Dawley rats and in mice via the

oral route of administration and as

modified in 40 CFR (c)(6).

To assess the dermal sensitization

effects of TBP, the Agency is proposing

that testing be conducted according to

the guidelines at 40 CFR 798.4100.

For the Agency to extrapolate the oral

route of administration of TBP in the

tests described above and the dermal

route, which is thought to be a primary

route of human exposure, the Agency is

proposing an oral/dermal

pharmacokinetic test with TBP to

examine absorption, distribution,

metabolism, and excretion. The Agency

is proposing that testing be conducted

according to the guidelines being

proposed under § 795.228. The decision

to require most testing of TBP by the

oral routeis based on the results of

dermal irritation tests showing TBP

effects to range from irritating to

corrosive (Unit II.F.1.). 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.).

EPA is not proposing the renal effects

test recommended by the ITC. Acute

and subacute oral studies by Mitomo et

al (Ref. 9) showed kidney tubule damage

in rats and mice. However, two oral

subchronic rat studies of 90 days and

126 days showed no kidney damage

even at dosages higher than the Mitomo

studies (Ref. 22 and 23]. EPA believes

that there are adequate data available

to assess the effects of TBP on kidney

tubules.

2. Environmental Effects

EPA is proposing environmental

effects testing to determine the toxicity

of TBP to an alga, a fish, aquatic

invertebrates, and terrestrial plants: (1)

Selenastrum capricornutum, in

accordance with the test guidelines at 40

CFR 797,1050 as modified in proposed

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

in accordance with the guidelines at 40

CFR 797.1400, as modified in proposed

§ 799*4360(d(2)'fB1; (3)' daphnids in

accordance with the guidelines at 40

CFR 797.1300, and as modified in

proposed § 799.4360(d) (3)(B); (4)-

gammarids in accordance with the

guidelines at 40 CFR 797.1310, and as

modified in proposed § 799.4360(d)

(4)(B); and (5) plant uptake and

translocation in accordance with the

guidelines at 40 CFR 797.2850. Only one

test species, rainbow trout, is proposed

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 to fish (see Unit II.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:

BILLING CODE 6460-50-&M

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