### 43346 Federal Register / Vol. 52, No. 218 

## '1Thursday, 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 .topresent 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 Ofinformation regarding-the hazards associated with ionizing radiation and the appropriateness ofregulation 'toprotect miners.exposed to much'hazards. In addition, major reports on-radiation

were expected from the National Academy ofSciences.(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 ofthe 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 ,foraRecommended-Standard * * * Occupational Exposure to Radon Progeny inUnderground Mines",,was received by MSHA on October 30, 1987. The NAS,report on'the Biological Effects ofIonizing Radiation (BEIRJIV) is expected to be published before the end ofthe year. The NAS-document-will specifically address the.effects of
exposure to intermllydeposited alphaemitting radionuclides such as radon daughters.

Various-members .ofthe mining community, -includingrepresentatives of both labor and industry, haveindicated in theirpost-hearing submissions the need toreviewthe supplemental material, and have,requestedan additional extension ofthepublic comment'pefiod. MSHA acknowledges the merit oftheserequests 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 ofthe permissible ;exposureievdl 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 ofI working level (WL) (or0.083 WL). NIOSH further:recommends that respirators be required when entering an

area where engineering controls have
not achieved V12 WLaverage 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 ofhazard information; .respiratory protection; worker education and-notfication;and prohibition ofsmoking.

Under section 101(a)(1) of the Federal Mine Safety and Health Act of1977, the Secretary is obligated to make a public
response to the NIOSH recommendations. Although MSHAis
not publishing the criteria document as

a proposedrule, MSHA ismaking the document available .forpublic comment

as part ofits ongoing rulemaking-to

assure the fullest input .ofthe mining community. Copies ofthe 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 -inthe Agency's final rule.

MSHA is 'alsoextending'the comment period for 'thepurpose offurthering 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 ofmining operations.

A plan approach would-address both work'practices',and feasible engineering controls -asa means to reduce radiation
exposure. It would seek'to incorporate the internationally accepted principles ofALARA.(redudtion ofexposures "as low.as reasonably achieveable"). The concept ofALARA wasraised in the proposal,.and was 'the'subject of discussions during'the public hearing. This approach'would allow tailoring ofa control strategy to the unique characteristics ofa'mine, the mine workforce, and'the particular-mining methodbeing utilized.'Sudh-a 'regulatory alternative might establish he:best feasible prdtection on a mineby-mine basis while maintaining a baseline exposure limit forall exposed'miners. Under such.an approach, operators would be encouraged to'improve protection whereverpossible. MSHA solicits commenton themerits.ofthis alternative approach, and:its appropriateness forinclusion in the Agency's regulatory.strategy for protection.miners from 'ionizing radiation. The Agency 'isparticularly intereStedin suggestions'concerning the possible contents:of a control plan, together with ideas related'to implementation, including plan review, adoption and revisionprocedures.

Date:Noveniber 6,1987. Patricia W. Silvey, ActingAssociate AssistantSecretary for MineSafetyandHealth. [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 ,EPAisspropoding

### that manufacturers and processors-oftribtityl 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.'Thisrdle is proposed in response to the-Interagency Testing Committee's (ITC's) designation ofTBP'for priority-consideration for chemical fte, health effects, and environmental.effects testing. DATES: Submitwritten comments on or betoreJanuary I1, 1988. Ifpersons 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), 'intriplicate to: TSCA Pdblic.Information :Office-(TS793), 'Office ofPestidides and Toxic Substances, Environmental'Protetion Agenqy, RoomNE-GO04, 401 M St., SW., Washington, DC20460.

Apublic\version dfthe 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) ofTSCA in response to the ITC's designation ofTBP for chemical fate, health effects, and environmental effects testing consideration.

I. Introduction

A. ITCRecommendation

TSCA (Pub. L. 94-469, 90 Stat. 2003 et seq.15 U.S.C. 2601 etseq.) established the ITCunder section 4(e) to recommend to EPA a list ofchemical substances and mixtures (chemicals) to be considered for testing under TSCA section 4(a).

The ITCrecommended 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 ofMay 19, 1986 (51 FR 18368). The ITC designated TBP forpriority consideration in its 19th Report, published in the Federal Register of November 14, 1986 (51 FR 41417). The ITCrecommended thatTBP be considered forhealth effects testing, consisting ofchronic 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 ofdata on health effects.

The ITC's rationale for chemical fate testing was based on: (1)The large production volume; (2) detection ofTgP in municipal and industrial effluents, sediments, and in river,estuarine, ground, and drinking waters; and (3) detection ofTBP in human and fish lipid tissue.

The ITC's rationale forenvironmental effects testing was based on: (1)TBP's presence in various surface and groundwaters; (2) available information showing thatTBP has acute effects on a variety of aquatic organisms at moderately low concentrations and on terrestrial plants; and (3) the appearance ofcontinual exposure ofnearly all types ofbiota to low concentrations ofTBP.

B. Opportunity forNegotiating A ConsentOrder

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 testingunder section 4of the Act. EPA intends to use such consent orders where a consensus exists among the Agency, affected manufacturers and/or processors, and interested members ofthe 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 oftest data without the necessity ofEPA using the lengthy rulemaking process.

Where EPA concludes that the Agency the affected industry and interested parties cannot reach a
consensus on the testingrequirements 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 testrules appears in detail in the Federal Register ofJune 30, 1986 (51 FR 23706).

The first step in determining the feasibility ofdeveloping a consent order fora specific compound is the identification ofinterested parties who may wish toparticipate in negotiations withEPA. In the Federal Register ofJuly 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 isproceeding with rulemaking under section 4(a) of TSCA.
C. TestRuleDevelopmeht UnderTSCA

This document is part ofthe overall implementation ofsection 4 ofTSCA (Pub. L. 94-469, 90 Stat. 2003 et seq., 15 U.S.C. 2601 etseq.), which contains authority for EPA to require development ofdata relevant to assessing the risks to health and the environment posed by exposure to a particular chemical.

Under section 4 ofTSCA, EPA must require testing of a chemical to develop 

### health or environmental data ifthe Administrator makes certain findings as described in TSCA under section 4(a)(1) (A) or (B). Detailed discussions ofthe statutory section 4 findings are provided in the Agency's first and second proposed test rules which were published in the Federal Register ofJuly 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 theITC's recommendations; production volume, use, exposure, and release information reported by manufacturers ofTBPunder the TSCA section 8(a) Preliminary Assessment Information Rule (40 CFR Part 712);health and safety studies submitted under theTSCA section 8(d)Health and Safety Data Reporting Rule (40 CFR Part716); and published and unpublished data available to theAgency. From its evaluation, as described in this proposed rule, EPA is proposing health effects testingunder section 4(a)(1) (A) and (B)and environmental effects testing under section 4(a)(1}(B). By this action,EPA is responding to theITC's designation ofTBPfor priority testing consideration.

II.Review ofAvailable Data

A. Profile

TBP is a colorless, odorless liquid (Ref.1). It has a molecularweight of 266.32 daltons (Ref.7), measured water solubility of280-:36 mg/L at 25 °C, a measured vaporpressure of127mm Hg at 177 'C, a measured boiling pointof 289 °C at 760mm Hg, and a measured log K.. of4.0 (Ref.8). Muir (1984) estimated a Henry's law constant (Hc) forTBP to be 2.48X10 -2

### atm m3/mol (Ref.54).The Agency believes this estimate ofHc is 2to 3orders 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 of1985. The estimated 1985 combined production capacity ofTBP is 6 to 9 million pounds peryear (Ref.45). The actual production and import volumes for 1985have 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 closedprocess 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 amountproduced, the triester is then pumped into tank cars, tankwagons, 55-gallon drums, or smaller containers for shipment to customers (Ref.1).

C. Uses

Some 40 to 60 percent ofall TBP consumed is used as a base stock in the formulation offire-resistant aircraft hydraulic fluids.Formulation concentrations are typically 50 to 60 percent ofthe hydraulic fluid. These hydraulic fluids are usually prepared by metering and pumping the individual components into a mixing tank where the components areblended. 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 ofthe system may result in small amounts of overflow (Ref. 1).
Some 10 to 20 percent ofthe production volume ofTBP is used for extraction and separation processes in the PUREX (PlutoniumUranium Reduction Extraction] process for the separation of plutonium and uranium from spent nuclear fuel elements. It is also used to purify 232LJ produced from the bombardment ofprotactinium-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 inniobium

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) formetals, 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 ofTBP is used as a defoamer in the paper industry and in textile sizers, inks, lacquers, and as a plasticizer (Ref. 1).

Minor uses ofTBP as a chemical reagent include the following: Use in 

### combination with other chemicals to split viruses forthe 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 ofoxalic acid in a highperformance liquid chromatographicmethod to determine oxalic acid in urine; and as a pigment-grinding assistant, a very minoruse (Ref. 1).
D.EnvironmentalRelease

TBP is expected to enter the environment as a result ofwastewater 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 washingprocedures. Small amounts ofTBP could also occur in distillation bottoms and would subsequently be incinerated or landfilled (Ref. 2).

During processing anduse ofTBP, release to water may resultfrom such activities as the cleaning ofequipment 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 ofTBP in industrial effluents, as discussed in the following paragraph, suggests that many uses of thecompound result in eventual release into the aquatic environment. There are usually no direct releases ofphosphate esters fromthe solid materials into which they are incorporated (Ref.2].

TBP was found in municipal and industrial effluents at concentrations ranging from 6.9jAg/L to 13,517jig/L (Ref. 1). Although the names and locations of theplants are confidential, the industries represented include paint and ink,printing andpublishing, organics andplastics, 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 ofTBP in groundwater underlying a landfill in Norman, Oklahoma and Hutchins etal (Ref. 5) identified traces ofTBP in groundwater in FortPolk, 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 from0.8 ng/L to 29.5ng/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 ofcompiling a list ofall 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

EPAbelieves 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 ofa 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 ofthese 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 ofthree basic types.

a.Actual.The surveyor observed the

use of the specific agent.

b. Tradename.The surveyor observed the use ofa tradename product known
to contain the specific agent.

c. Generic,The surveyor observed a product in some type ofgeneral 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 ofthe SICcodes and consists solely ofactually observed uses ofTBP in the work place.

EPA estimates 12 to 16 workers to be potentially exposed to TBP at each ofits two manufacturing sites for 25 days per year (Ref. 2). Because of the corrosive
nature ofTBP and its phosphorus oxychloride precursor (see Unit II.B.1.), workers manufacturing TBP operate processes which are closed and usually conducted under a blanket ofnitrogen. Further, because ofthe hazardous character ofphosphorus oxychloride, workers normally are protected through the use of local ventilation, appropriate respiratory equipment, and suitable protective clothing. Thus, little or no routine exposure ofworkers is expected during the synthesis ofTBP (Ref.2).

On completion of the manufacturing operation, the finishedmaterials are drummed or packaged fdt shipment. Incidental dermal contact may be encountered duringroutine connection oftransfer 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 ifboth hands were exposed and from 1 to 3 mg ofmaterial/cm2 adhered
to the skin. Similardermal contact would occur when equipment is cleaned and maintained (Ref.2).

The processing ofTBP primarily involves mechanical transfer ofpure material as itis received fora blending operation. In the processing ofTBP for aircraft hydraulic fluid, EPA estimates the involvement ofless than 70 site-days
per year and 2to 4 workers per site with

a dermal contact potential of650 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 ofTBP during industrial production, processing, oruse would be very unusual because it breaks down at high temperatures. Forthis reason it is generally used at ambient temperature (Ref. 27 and 33). This would reduce the possibility ofinhalation contact except, forexample, here aerosol formation may

occur as a result of spraying operations.

The largest potentially exposed worker population isin aircraft maintenance because manual operations could result in exposure to TBP-containing hydraulic fluid (Unit II.C.). The Bureau ofLabor Statistics (BLS) ofthe U.S. Department ofLabor 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 ofequipment.

In the case ofore extraction (primarily uranium orebenefaction), 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 ofother products as described earlier in this Unit: transfer ofstock material, drumming orpackaging, and cleaning and maintenance ofequipment.

Exposure in plastics production is assumed to be limited because ofthe frequent use ofmechanical transfers and automated processes (Ref. 2). However, possibilities ofexposure exist which are similar to those found in TBP's manufacture and the processing ofother products as described earlier in this Unit transfer of stock material, drumming or packaging, and cleaning and maintenance ofequipment.

"The identification ofTPB in releases from the spectrum ofindustries 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 ofrelevant 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 ofgeneral 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. TBPhas also been found in the drinking water of several Canadian municipalities that obtain their water from the Great Lakes (see Unit II.D). Tens ofthousands 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 ofhuman adipose tissue samples for the detection ofchemical 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 ofTBP 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 ofTBP exposure is difficult to evaluate.

F.HealthEffects

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 ofair 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 ofTBP (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 ofTBP.

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 oftest material was'placed on each patch, and

a series of15 alternate-day applications (weeks Ito 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 toolow to have elicited.

a reaction. For this reason, EPA concludes that these data are not sufficient toreasonably determine or predict the sensitization effects ofTBP. 

### 43349

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### 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 ofTBP.

3. Subchronic Toxicity

Groups of Sprague-Dawley rats consisting of 12 males and 12 females pergroup were given 0.20 or0.30 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 oftoxicity were observed,
rats in both dose groups showed diffuse hyperplasia ofthe urinary bladder epithelium on histopathological examination (see Unit II.F.8. for discussion). Numerous other organs
were examined histopathologically but showedno 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 ofSpragueDawley rats for at least 90 days at concentrations of0, 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 ofTBP was 200 ppm.

Treatment-related histopathological effects included generalized transitional-cell hyperplasia inthe urinary bladders ofthe males receiving 1,000 ppm and 5,000 ppm ofTBPand 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 ofthe study, a significant decrease in platelets in the males receiving 1,000 ppm, and a significant elevation ofthe mean activated partial thromboplastin time in the males receiving 5,000ppm. These studies are sufficient to reasonably

.;w

iQQQ Aol i(o(n( InlN V-R7- 14:,7!471 

### determine or predict the subchronic effects ofTBP.

4. Neurotoxicity



### TBP (80 mg/kg)was one ofseveral organic phosphates tested by injection into the tail vein ofrats (number in test groups not given and no mention of controls) (Ref.16). Uncoordination and mild anesthesia occurred in about 1hour and pronounced weakness in about 4 hours. With a dose of100 mg/kg, anesthesia and pronounced dyspnea occurred in 8 to 10 minutes followed by respiratory failure. There were no cholinergic symptoms. Thepaper 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 dosegroups often male and ten female Sprague-Dawley rats pergroup
were given 0.28 and 0.42 ml/kg/day of a 

### mixture of98.4percent TBPand 1.3 percent tributoxyethyl phosphate (an occasional contaminant ofTBP, Ref.44) by gavage for 14 days (Ref. 17). A control group was force-fed tap water.A significant reduction in conduction velocity ofthe caudal nerve was observed in high dosemale rats (four rats/group) 24 hours after administration ofthe last dose. Electron microscope examination of the sciatic

nerve showed morphological changes such as retraction ofSchwann cell processes surrounding fibers in both

sexes ofthe high dose group.

A study wasperformed to test TBP (purity'not given)for delayed neurotoxicity in 18-month old leghorn hens (Ref.18). The oral LD50 forTBP in hens without atropine protection against acute cholinergic effects was determined to be 1,500 mg/kg. Agroup of20 hens received a single oral dose of 1,500 mg/kg ofTBP, in gelatin capsules,

on day 0. Hens that survived were dosed again on day 21 with atropine sulfate protection. Anothergroup of10 hens

weregiven two dermal doses of1,500 mg/kg ofTBP on day 0 and day 21. On both days atropine sulfate was administered. Controls consisted ofa positive control group fordelayed neurotoxicity treated with a single oral dose of750mg/kg oftri-o-cresyl phosphate; another group was given gelatin capsules. Although a total ofsix hens died following the oral administration ofTBP,none ofthe surviving hens developed delayed neurotoxicity throughout the 42-day experiment. All ofthehens treated with dermal doses ofTBP survived the 42-day experiment and none ofthem 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 orpredict the acute and chronic neurotoxic potential ofTBP.

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 often 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. Acontrol groupwas force-fed tap water. One out offour ofthe male rats in the high-dose group showed microscopic degenerative changes in approximately 50 percent ofthe 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 toTBP (98.4 percent) levels up to 0.35 gm/kg/day 5 days/week (Ref. 22).

The negative results ofthe 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 tohave occurred in 50percent of tubules examined rather than in one out offour 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 ofTBP on gonadal function, conception, parturition, and the growth and development ofthe offspring. Therefore, EPA concludes that existing data are not sufficient to reasonably determine or predict the reproductive effects ofTBP.

7. Mutagenicity

An Ames test was conducted by the FMC Corporation with TBP (100 percent) using five strains oftest bacteria (strains TA 1535, TA 1538, TA 1537, TA 98, TA 100) both with and without the addition of an exogenous source ofliver enzyme for metabolic activation ofthe test agent. No evidence ofmutagenic activity

was found by thismethod (Ref.29). EPA concludes that thisis a valid negative
test. 

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A test using the Cy/Bly method was conducted with Drosophila to measure the accumulation ofrecessive lethals on the second chromosome of flies exposed

over a number ofgenerations for 18 months to increasing levels ofTBP (Ref. 46). TBP was not found to be mutagenic inDrosophila. 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 offlies sampled was low. Because ofthe lack of historical data and the unusual nature of the experiment it is impossible to calculate the power ofthe test. In addition, this test has not been validated in terms oftest repeatability, and sensitivity. Given these uncertainties, the study is not sufficient
to reasonably determine or predict the mutagenic effects ofTBP on Drosophila.

Although there are valid negative data for the Ames test,no further data are available to reasonably determine or predict gene mutation orchromosomal aberration effects ofTBP.

8. Oncogenicity

Urinary bladder hyperplasia was reported in both of the subchronic studies discussed earlier (UnitII.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 ofthe 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 ofthe 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 tobe associated with tumor development with many chemicals. The development of hyperplasia and ofneoplasia 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 ofhyperplasia 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 ofTBP.

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 ofmetabolism 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 ofhuman stratum

corneum conjunctur in diffusion cells. From in vitromeasurements ofsteady
state rates ofpenetration, 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 of250 mg/kg of TBP (Ref. 37). The major metabolites included dibutyl hydrogen phosphate, butyl dihydrogen phosphate, and butyl bis(3-hydroxybutyl) phosphate. Small
amounts ofderivatives hydroxylated at other carbons ofthe 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 ofTBP. In this study, the major urinary metabolites following a single intraperitoneal injection ofTBP were (3-oxobutyl)- and (3-hydroxybutyl)mercapturic acid. Traces of2-oxobutyl- and (2- hydroxybutyl)mercapturic acids were also detected.

Sasaki et al. (Ref.39) determined the in vitrometabolic pathway ofTBP 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 vitropathway.

Following a single oral dose of 

### 14CTBP (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 24hours.

Although available data give some, information about human in vitro and in vivo skin penetration, intraperitoneal rat metabolism and excretion ofTBP, comparative oral/dermal or intravenous pharmacokinetics studies are not available. None ofthe studies include comparative guinea pig/rat bioavailability, skin absorption, or tissue distribution ofTBP. EPA believes that available data are not sufficient to reasonably determine or predict the comparative oral/dermal pharmacokinetics ofTBP.

G. Environmental Effects
1.Acute Toxicity

Several studies were performed to estimate the toxicity and bioconcentration ofTBP 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 ofthe studies:

TABLE 1-AOUATIC TOXICITY AND BIOCONCENTRATION OF 

### TBP

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

Chlorellaemersoni

................................. 2 Daphniamagna
............................................................................. 1 2 '1
2 3 Fathead minnow

........................................ .................................. 4 EC50=5-10 mg/L

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

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

............................................................................. ,LC50=12.8 mg/L

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

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

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

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## I Vol. 52, No. 218 / Thursday, November 12, 1987 / Proposed Rules

TABLE 1-AQUATIC 

### Toxic'rv AND BIOCONCENTRATION OF 

### TBP-Continued

Organism estTest 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 Goldfish

............................................................................................. 4 LC 50=8.8 mg/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 Goldfish

............................................................................................. 4 BC F=7

............................................................................................. 50 Killifish

............................................................................................... 4 BC F=30

................................................................................. ......... 50 38 BCF=21-35

.................................................................................... 29



### EPA carefully analyzed the available percent ofTBP wasbiodegraded (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)Chlorellais a relatively biodegradation and TBP's relative EPA concludes that the above data are insensitive species ofalga compared to hydrophobicity indicate that flow- not sufficient to reasonably determine or Selenastrumand testingin Selenastrum through testing would better provide for predict plant uptake and translocation will provide more useful data; (2) continuous exposure toa relatively ofTBP. available data withD.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 timedependent acute compounds may underestimate toxicity. No information was found on the toxicity that may indicate cumulative EPA concludes that most ofthe acute chronic toxicity ofTBP to aquatic or toxicity,toxicity ofa byproduct that toxicity data listed in Table 1are not terrestrial organisms. would not be removed from static test sufficient toreasonably determine or systems, orpotential chronic toxicity; (3) predict the acute toxicity ofTBP to H.ChemicalFate while all ofthe 4-day fish LC50 values, daphnids, gammarids, rainbow trout,or including those conducted under flow- algae. TBP isexpected to partition to the through conditions, are very similar TBP'sherbicidal properties for aquatic and sediment environments. (within a factor of3), it is reasonable to terrestrial plants were tested with Available data suggest thatTBP 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 ofTBP. and tomato).The seedlings were dipped considers these data adequate to

The logic forrequiring flow-through in 0.5 and 5.0 percent water solutions of determine orpredict aerobic and testsforTBP is based on biodegradation TBP (frequency ofdipping notgiven), anaerobic biodegradation. An adequate potential and hydrophobicity ofTBP. Within 1week, allTBP-treated plants measurement oflog Kow is also Available data show that after 4 days' were severely injured ordead (Ref.25). available (Ref. 13). The following Table incubation in river water containing a This study makes noprovision for the 2shows the biodegradability data of relatively low concentration ofTBP- determination of concentration offree TBP. unacclimated bacteria, at least 10 TBP, metabolites, and soluble and

TABLE 2.-BIODEGRADABILITY OF TRIBUTYL PHOSPHATE

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

OECD 301C (TBP loss)

.................................................................. 28 77%

................................................................................................... 47 OECD 3010 (B D)

.......................................................................... 28 92%

................................................................................................... 54 OECD 301E (DOC Loss)

................................................................ 28 89%

....... ;

........................................................................................... 54 SCAS I

.............................................................................................. 91 96% @ 3 mg/L/day

....................................................................... 8 SCAS

................................................................................................. 147 56-- 21% @ 13 mg/L/day

............................................................ 8 Rliver die-away

...................................................................... 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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## / Proposed Rules

As noted by the ITC, the ubiquitous environmental appearance ofTPB at various concentrations (see Unit II.D.)
may mean that it is not effectively degraded below some threshold concentration or that the continuous release ofTBP 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 forTBP on the authority ofsections 4(a)(1) (A) and (B) and environmental effects testing on the authority ofsection 4(a)(1)(B) ofTSCA.

A. FindingsUnderTSCA Section 4(a)(1)(A)

1. Health Effects

EPA finds that the manufacture, processing, use, and disposal ofTBP 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 ofpotential oncogenicity risk is based on two reports of hyperplasia ofthe urinary bladder epithelium in rats after oral administration ofTBP (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 (UnitII.F.8.) (Ref.34). The data suggest thatTBP may be oncogenic, but are derived from studies that are too briefto adequately characterize this effect.

The finding ofpotential neurotoxicity risk is based on uncoordination, anesthesia, weakness, and respiratory failure in rats after injection ofTBP (Ref. 16), and reduction in caudal nerve velocity and retraction ofSchwann cell
processes surrounding sciatic nerve fibers in rats after the administration of 98.4percent TBPby gavage (Ref. 17).

The finding ofpotential dermal sensitization risk is based on the sensitization of6 out of 14 guinea pigs exposed to TBP (Ref. 32).

For the reasons stated in UnitII., 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 isnecessary 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 ofTBP does or doesnot present
an unreasonable risk ofinjuryto human health.
2.Environmntal Effects

EPA finds that the manufacturing, processing,use, and disposal ofTBP maypresent an unreasonable risk of injury to the environment because ofits release to the environment and its potential to cause lethality in terrestrial plants. The concern forpotential plant uptake effects is based on a study in which TBPwas lethal to various seedlings forwhich soluble and bound residues in the plants were not measured (Ref.25). Available data are insufficient to reasonably determine or predict theplant uptake and translocation ofTBP 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 willbe relevant to a determination that the manufacturing, processing, use, and disposal ofTBP do

ordo not present an unreasonable risk ofinjury to the environment.
B.FindingsUnderTSCA Section 4(a)(l(B)
1.Health Effects

EPA finds thatTBP is produced in substantial quantities, and that there is

ormay be significant occupational and general population exposure from its manufacture, processing, use, and disposal (see Unit II.E.). From 6 to9 million pounds ofTBPwas 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 (largestpotential exposure group) (UnitII.E.). Although themajor exposure route is thought to be dermal, the detection ofTBP 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 oralroute (Unit I1.D.) to substantial numbers ofpeople in the general population.

TBP's majoruse as an ingredient in aircraft hydraulic fluid creates the possibility ofdermal exposure of15,000 aircraft mechanics (Unit II.E.1.) at significant levels. TBP is alsoused 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 ofviruses (UnitII.C.).Although

some of these uses are highly automated, the other uses may result in exposure ofa 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 ofTBP resulting from exposure during its manufacture, processing, use, and disposal. The Agency finds that testingis necessary to develop health effects data. EPA believes that the data resulting from these test requirements willbe relevant to a determination that the manufacturing, processing, use, and disposal ofTBP do or do not present an unreasonable risk ofinjury to human health.
2.Environmental Effects

EPA finds that TBP is produced in substantial quantities (6 to9 million pounds in1985 (Ref.45)). It enters or may reasonably be anticipated to enter theenvironment in substantial quantities during manufacture, processing, use, and disposal, as evidenced byits detection in surface water,sediment, and groundwater (see UnitII.D.). EPA believes that thelow concentration ofTBP 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.).EPAbelieves that for chemicals with substantial production and ubiquitous environmental distribution, reliable data shouldbe 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). TheAgency 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 themanufacturing, processing, use, and disposal ofTBP does or doesnot present
anunreasonable risk of injury to the environment.

The ITC recommended terrestrial' invertebrate testing forTBP.EPA is considering possible test species and methods for such testing but has not yet IRI III 

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determined thebest 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 atthis time.

3.Chemical Fate

EPA finds that TBP is produced in substantial quantitites (6to 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 byits 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, andhydrolysis rate. Vapor pressure data at 25 *Care needed to estimate a reliable Hc forTBP. Data on log Koc are needed to estimate the sorption ofTBP to soil and sediments. Finally,hydrolysis rate data, which complement the biodegradation data,

are needed to estimate the persistence ofTBP 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 ofTBP doesor does notpresent an unreasonable risk ofinjury to the environment.
IV.Proposed Rule
A. ProposedTestingandTestStandards

On the basis oftheinformation presented in Unit Ifand the findings set forth in Unit III ofthis preamble, EPAis proposing health and environmental effects testingfor TBP.The tests are proposed to be conducted in accordance with EPA's TSCAGood Laboratory Practice Standards in 40 CFR Part792 and specific TSCA testguidelines in 40 CFR Parts795, 796,797, and 798, and other published testmethods as specified in the proposed rule forTBP.

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 testrule, these guidelines are being proposed as the test standards thatmust be met bythe test sponsors. The route of administration ofTBP 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 forTBP.

Finalrevisions to the TSCA test guidelines were published in the Federal Register ofMay 20, 1987 (52 FR 19056); the Agency is proposing that these revised testguidelines be adopted as the test standards forTBP.

The TSCAtest guidelines, proposed modifications, and other cited test guidelines discussed below specify generally accepted minimal conditions fordetermining toxicities and properties ofsubstances such as TBP to which ' human, aquatic, and terrestrial life are expected to be exposed. Conducting the required studies in accordance with these TSCAguidelines will help ensure that the test results are reliable and adequate.

The Agency's review ofthe TSCA Test Guidelines, which occurs on a yearlybasis according to the process described at47 FR41857 (September 22, 1982), has found no reason to conclude that theseprotocols need tobe modified significantly.
1.Health Effects

The acute neurotoxicity testingand neurobehavioral toxicity evaluation would consist ofthe 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 40CFR 798.6200, as modified in proposed §799.4360(c)(1)(i)(B)(2). To assess the effects ofrepeated long-term exposures toTBP, theAgency is proposing a subchronic (90-day) neurotoxicity and neurobehavioral toxicity evaluation consisting ofa neuropathologic evaluation oftissues perfused in situas specified in 40 CFR 798.6400, as modified in proposed §799.4360(c)(1)(i)(C)(2).

To assess the developmental effects of TBP, theAgency 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 ofTBP, theAgency is proposing that testing beconducted according to the guidelines at 40CFR 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 testingbe conducted in tiers. First-tier testing would consist ofthe detection of gene mutation in somatic cells in culture usingthe testguidelines at 40 CFR 798.5300, an in vitromammalian cytogenetics testusing the test guidelines at 40 CFR 798.5375, and an in vivo mammalian bone marrow cytogenetics chromosomal analysis test using thetest 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 inDrosophila 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 at40 CFR 798.5200 and rodent heritable translocation test using the
test guidelines at40 CFR 798.5460, and

as modified in proposed §799.4360 

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

Unless the results ofthe gene mutation in somatic cells in culture are negative, a sex-linked recessive lethal
testin Drosophila melonogasterwould 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 ofeliciting 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 -thatthe MVSL was still appropriate, EPA would notify the test sponsors by letter orFederal Register notice that they must conduct the test. If EPA determined that the test was no longernecessary, EPA would propose to amend the rule to delete the test requirement.

Other testrules 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 ofconducting the test and the availability of laboratories capable ofperforming the test.The information and assumptions have since proven to be incorrect. Accordingly, EPA is in the process ofreexamining 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 ofsuch 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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## / 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 forTBP and other substances subject to proposed and final TSCA section 4 test rules. This notice will provide up-to-date information on the cost ofMVSL 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 berequired. If the sex-linked recessive lethal test is negative, no further gene-mutation tests would be required ofTBP.

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 ofthis 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 testis negative, no further chromosomal effects testing would be required for TBP.

Under this proposed rule, ifthe result of the second-tier rodent dominant lethal testwas 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 ofa public meeting would be published in the Federal Register. Should EPA-determine, from the available weight ofevidence, that proceeding to the heritable translocation test was no longer warranted, the Agency would propose to repeal this testingrequirement 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, ifthe heritable translocation test must beperformed. EPA would also conduct internal program reviews of the reports of the gene mutations in somatic cells inculture assay, the in vitro mammalian bone marrow cytogenetics test, and the in vivo mammalian bone

marrow cytogenetics testand 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 ofMay 17, 1985 (50 FR 20662).

In order to assess the oncogenic effects ofTBP, 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 ofadministration and as modified in 40 CFR (c)(6).

To assess the dermal sensitization effects ofTBP, 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 ofadministration ofTBP in the
tests described above and the dermal route, which is thought to be a primary
route ofhuman 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 ofTBP 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 ofthe corrosive TBP could
stress the test animals, which may -distorttestresults. TBP is well tolerated by the oral route (UnitII.F.).

EPA isnot 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 of90 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 ofTBP on kidney tubules.

2.Environmental Effects

EPA is proposing environmental effects testing to determine the toxicity ofTBP to an alga, a fish, aquatic invertebrates, and terrestrial plants: (1) Selenastrumcapricornutum, in accordance with the test guidelines at 40 CFR 797,1050 as modified inproposed § 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 at40 CFR 797.1310, andas 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, isproposed for the fish acute toxicity test because

an acute testfor the fathead minnow is available and adequate in combination with the testing required forthe rainbow
trout forpurposes ofassessing the acute toxicity ofTBP to fish (see Unit II.G.). All the acute aquatic toxicity data from these tests will beused to determine whether chronic aquatic testing is
necessary according to the testing scheme presented in the following figure:

BILLING CODE 6460-50-&M 

### 43355