UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

                             WASHINGTON, D.C. 20460
JUN  I  I  1986  .
 MEMORANDUM
 FROM:
 TO:
                                                        OFFICE OF
                                               PESTICIDES AND TOXIC SUBSTANCE?
  SUBJECT:    Data Needs Paper  for  the  Aery Iate/MethacryI ate
               Chemical  Category
Wi I I iam Far land,  Ph.D.
Ac t i ng  Di rector
Health  and Environmental
  Rev i ew Di v i s i on   (TS-796)
David Dul I
Ac t i ng  Di rec tor
Chemical  Control
                                    Division   (TS-794)
       Attached  is HERD'S proposal  for the health and environmental effects section of
 the  Testing  Recommendations/Data Needs for the  Acrylate/Methacrylate  chemical
 category.  We view this proposal as the basis for beginning negotiations with industry and
 other groups interested in testing chemicals in this category.  Clearly many of the details
 of the testing plan still need to be determined.   We expect that these testing details will
 be discussed  further  and  resolved once negotiations with the various interested parties
 begin.  We  also believe that the data needs  discussions and negotiations should be
 undertaken in conjunction with discussions  on  our  evaluation of the available toxicity
 data on this category as presented in our earlier Position Paper.

       In preparing our  data needs proposal  we have made several  assumptions  and
 identified  several considerations  that  should  be  made  clear  as  our  proposal is
 incorporated  into the regulatory  strategy for the  acrylate/methacrylate  chemical
 category.   First, and perhaps most importantly, our  testing proposal  is designed to
 provide  a  better understanding  of  the  health and  environmental  effects  of  the
 acrylate/methacrylate category as a whole. Our testing proposal may not necessarily
 provide the basis for conducting quantitative risk assessments on specific members of the
 category.  We are viewing this proposal not in relation to a particular section of TSCA,
 but as a means of qualitatively prioritizing OTS concerns for the spectrum of chemicals
 within this broad category for use under all Sections of TSCA. This proposal  must be
 viewed in the context of answering some basic, broad questions on the hazards identified
 with the category which will significantly improve our ability to assess these chemicals
 in the various regulatory  processes of TSCA.  The data from this testing will focus our
 regulatory emphasis on those chemicals that  are likely to present the greatest hazard.

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       The second  major consideration in our testing proposal is the general  lack of risk
 and economic considerations in our proposal.  Our proposal reflects primarily a hazard-
 based perspective  for identifying needed testing.  We have not attempted to prioritize
 the testing in our proposal with other types of testing that may be deemed desirable for
 the category (e.g. epidemiology, fate, and exposure).  These types of priorities need to be
 considered as an Office-level decision.

       Also,  in our proposal we have generally not considered the relative risk from the
 identified hazards of these chemicals because neither the exposure nor the dose-response
 information  is available  at this time to quantitatively  evaluate  these risks.  Without a
 good measure of the relative hazard posed by members of the category, it is not possible
 now for us to explicitly  consider relative risk when determining the general nature or
 scope of our testing proposal.  Higher risk chemicals (or categories) might, for example,
 warrent more extensive or rigourous testing than lower risk chemicals (or categories).  It
 may  be best to address this issue as an Office-level policy decision  where a more
 comprehensive view of exposure and  relative  risk can be considered.   In  this forum,
 additional  information  (e.g., exposure  and economics) may be available  to help balance
 our hazard-based testing proposal against other types of testing needed for the category
 and against the relative risk of these chemicals.  These Office-level policy decisions may
 require modifications to our attached testing proposal.

       The third  major  consideration in our proposal is related to  the sequence of testing
 for  the four areas  of testing  that we  have  identified  (absorption, carcinogenicity,
 neurotoxicity, and  ecotoxicity).  We suggest that the  four  areas  not be combined into a
 tiered scheme. Each area can be pursued as a separate line of investigation.  However, it
 may be logical to do the absorption  testing early in the program, since this testing should
 provide better insights into the limits of  our health concerns  for the larger molecular
 weight category members.

       We  have also proposed  a general approach for the  other  health  effects testing.
 For the neurotoxicity testing we expect that repeating the existing tests should be done
 first to confirm these results before a broader range of chemicals is tested to answer our
 basic category questions. In the carcinogenicity  testing  area we have identified the need
 for genotoxicity  data, modified bioassay data, and data from complete bioassays. Work
 on  expanding the genotoxicity data base is currently underway at the EPA lab at RTF.
 We believe that work  to develop data in  both  an acceptable  rrwdified  and a standard
 bioassay should be  started together.,  We are  recommending that OTS use the data,
 accepting the validity  of both positive and negative results, developed  in the modified
 bioassay as  it becomes  available  for regulatory decision-making and  for  identifying
 additional chemicals to be tested in the complete bioassay. This  modified bioassay data
 should only be accepted, however,  if  data are  simultaneously developed in a standard
 bioassay.   The standard  bioassay results,  that  we expect will take  longer  to  develop,
 would then be used to validate the modifed bioassay design and the genotoxicity tests  in
 addition to providing a  more scientifically acceptable way of evaluating the carcinogenic
 potential of the category members.


 Attachment

cc:    W. Farland          J. Du                 J. DeSantis         S. Irene
       M. May              J. Gilford             D. Klauder         A. Blaschka
       D. Beal              G. Timm              P. Hayes           J. Merenda
       B. Means            V. Nabholz            E. Falke           K. Dearf ield
       V. Turner            M. Townsend         . D. Gould           T. Jones
       A. Auletta          M. Argus             R. Brink           C. Auer

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               TESTING RECOMMENDATIONS/DATA NEEDS FOR THE

               ACRYLATE/METHACRYLATE CHEMICAL CATEGORY
 I.    Introduction

       The HERD Position Paper, The Health and Environmental Effects of Acrylate and

 Methacrylate Chemicals and the Acrylate/Methacrylate Category, presents an evaluation

 of  the  available toxicity information on this category of chemicals  and attempts  to

 identify those  areas where the data are limited  or  nonexistent.   Questions  about the

 nature  of the existing toxicity information should be directed to the "Position Paper",

 since the present paper does not reexamine  all this information.   The purpose of the

 "Data Needs Paper" is to  more clearly  identify the  important  areas  ef uncertainty  or

 data gaps encountered during toxicity assessments of chemicals in  this category and  to

 propose a testing strategy that will reduce the uncertainty of these assessments.  It is

 expected that this testing proposal will serve as an initial basis to begin negotiations with
                                                                    •
 interested parties.  Further discussion with these parties will clarify and possibly modify

 this proposal.

      Based on the available toxicity data, there is a clear need for additional testing of

 members of the acrylate/methacrylate category. The current dSta base, while providing

 the basis  for identifying several toxic effects  of concern to the Agency, is  relatively

 limited with respect  to  predicting  the relative  hazard  for the  entire spectrum  of

 chemicals that  fall  within this category.  Because  of the relatively limited nature of the

 database, decisions  on  chemicals in the category are often  made based on extrapolations

 and generalizations from the  available data.  These  extrapolations  and generalizations

 lead to  large uncertainties in our decisions.

      HERD  believes that  the  proposed  testing will  significantly   improve our

understanding of the relative toxicity of  chemicals in this category  and more accurately

define the scope of the category  for which  toxicity concerns exist.  Specifically we

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expect the test results to reduce the uncertainty  of  our assessments  in several areas.



These areas include: (I) a better basis for determining  the likelihood of human absorption



of these chemicals  (i.e., defining  the  limits of our  health  concerns), (2)  providing a



measure  of the relative  hazard for various subsets  of  the  category, and (3)  helping



prioritize our concerns  for these  chemicals for  more detailed testing and regulatory



activity.   To  reduce the uncertainty of our assessments in these areas we expect the



testing  results  to  answer some  fundamental questions  about  the  toxicity  of  this



category. These questions include:








     I.     What toxic effects are generally identified with chemicals in this category?








     2.     What  is the  relative hazard of acrylates  vs. methacrylates for these toxic



           effects?








     3.     What is  the relative hazard of  mono vs. multifunctional members for these



           toxic effects?








     4.     What  is the  relative hazard  of the  larger  motecular  weight vs.  smaller



           molecular weight members?








     5.     What  physico-chemical factors have  the greatest affect on  the dermal



           absorption ->?  these chemicals  and  what  is the relationship between these



           factors and •  ,e dermal  absorption rate for  these chemicals?








     6.     What is  the importance of  the exposure route in eliciting the health effects



           of these chemicals?

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      While the answers  to these questions will significantly improve our understanding

of the toxicity of this category of chemicals, they may not necessarily provide the basis

for conducting quantitative risk assessments on specific category members. Different or

supplementary testing  may  also  be  needed  to support  quantitative  risk assessment


decisions.

      Based on the identified data gaps and uncertainties in our assessments, we  are

proposing testing in four basic areas. These areas include:




      I.      Bioavailability/Absorption <- Because our understanding of the bioavailability

            of acrylates/methacrylates is  limited,  OTS  has been forced to rely  on  the

            qualitatively observed absorption potential of specific category members as

            an approximation of the general bioavailability of all category members.  In

            practice, this  has resulted in  our  using  the  molecular weight (MW) of  a

            category member as the measure of its absorption potential.  To do this we
                                                                     ğ
            have assumed  an  inverse relationship between  MW and absorption potential

            for category members. Empirical evidence is very limited for establishing  a

            particular  molecular weight above which absorption does not occur or is not

            biologically significant and for understanding the influence of other physico-

            chemical factors (e.g., water solubility) on the absorption potential of these

            chemicals.  Systematically testing  acrylates and methacrylates in a manner

            which  provides for careful  control of physico-chemical  properties would

            immediately  help  to  identify  the  most   important  factors   and   the

            relationships between these factors  and  the absorption potential of category

            members.  This would be a large step toward more empirically defining the

            extent or limits of our health concerns for category members.

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2.     Carcinogenic  Hazard  Potential  - Some  members of  this category  have



       produced a carcinogenic  response  in  laboratory  animals.   However, the



       relationship  between  chemical  structure and  this  response is  unknown



       because of the relatively few category members actually tested.  Also, it  is
                                                         f


       difficult to compare the available test results because few of the tests were



       conducted using the same protocol.  Additional testing would help define the


       relationship  between  chemical  structure and  the  inherent carcinogenic


       activity of  category  members  and  assist in  validating  screening  tests



       designed  to  measure  this  carcinogenic  activity  more  quickly  and  more


       economically.  Concurrent  testing in a standard 2-year  bioassay and in an



       appropriate experimental  modified  bioassay  would be  critical to  meeting



       these objectives.






3.     Neurotoxic Hazard Potential - The neurotoxicity concern for this category is


       based  on a very  limited data set.  Therefore, the basis  for identifying this"
                                                                •

       hazard with  this  category  is weak.  As  a first step,  HERD believes the


       existing neurotoxic effect data should  be confirmed by  repeating the tests



       that showed this effect by both the previously used routes of exposure and by

                                                      -Ğ•
       the route of expected  human exposure. Depending on the results, a broader


       range  of category  members might need  to  be tested to  determine the



       relative neurotoxic potential of chemicals in the category.






4.     Ecotoxic  Hazard  Potential  - The  available  ecotoxicity  hazard  data on


       category members is limited to acute tests.  Some category members have



       L.C5Q  values around I  mg/L and show  signs of  chronicity,  suggesting that



       chronic exposures would produce toxic effects at concentrations much lower



       than acute exposures.  Additional testing on  a broader range of category

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            members  would focus  our concerns  on  particular  subsets  or  individual


            category members by providing data needed for establishing a quantitative
           •%

            structure  activity  relationship  (QSAR) and by determining the relationship


            between acute and chronic toxicity values for this category of chemicals.





II.   Proposed Testing Plans





     A.     Bioavailability/Absorption





            I.     Data Gaps


                                                                   •


       HERD  has  identified  three  basic  data  gaps  in  our  understanding  of  the


bioavailability/absorption potential of fluid  acrylate/methacrylate esters. The existence


of  these  data  gaps  has  forced   us  to  make   certain  assumptions  about  the

                                                                      •
bioavailability/absorption of these chemicals that should be evaluated  with  additional


testing.  This is an important area for testing because absorption potential is usually the


first area  examined during  the evaluation of category  members in the new chemical


process.    If,  based on  a member's physical  form  and physic-chemical  parameters,


absorption  is not  considered likely, then the various  health hazards  are not expected to


be associated with that chemical.


       The   acrylate/methacrylate generic  SNUR   incorporates  an absorption-based,


molecular  weight definition  of the category which places limits on  the Agency's health


concerns for  the category.   In  establishing this category definition and  in assessing  the


bioavailability/absorption potential of individual category members, the following assumptions


have been made:

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            a)     MW is inversely  related  to the  absorption  potential of  category
                  members   and   can be  used  as  an approximation  of  absorption
                  potential.  Other physico-chemical factors  such  as water solubility
                  and octanol/water partition   coefficient  may   also affect  this
                  relationship and should be evaluated.


            b)     Absorption by the dermal or oral routes is expected to decrease with
                  increasing molecular weight in a  manner such that at a molecular
                  weight  of 1000  or  greater the absorption potential  of any  category
                  member can be considered negligible.

                                                                     •
            c)     Acrylate/Methacrylate esters with a MW of 500 or less are  expected
                  to be absorbed  to a significant degree when present at concentrations
                  of 2%  or  greater  in fluid acrylate/methacrylate substances having a
                  number average molecular weight of greater  than 1000.  •


     2.     Testing Proposal

                                                             -Ğr
       Our testing proposal is designed to determine  the relationship between physico-
chemical  factors  and  bioavailability/absorption  potential   of  these  chemicals.   It is
focused on  providing information   to evaluate the assumptions stated above that  have
been part of our decision-making approach  to assessing  chemicals in this category. The
test  plan is also  focused on dermal absorption because  this is the  most  frequently
identified exposure  route during  new  chemical  assessments.  Our testing  proposal
includes three components:

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a)     To test the effect of molecular weight on the absorption of acrylates

       and  methacrylates,   a  homologous   series  of   acrylates   and
 •ğ
       methacrylates could be synthesized where only the size and  MW are

       varied with a  repeating unit.  For example, a series of radiolabeled

       polypropylene  glycol diacrylates (PGDA) could be synthesized with a

       range of propylene glycol units (=n). The smaller size members of the

       series would be expected to  be absorbed more readily than the larger

       members of the series.  The chemicals should be dermally tested neat

       with a closed patch.  Measurements of radioactivity should be made in

       urine samples and  samples of  subcutaneous tissues at  the  site of

       application.  A sufficient number of members in thieveries should be

       tested to define the relationship  between MW and absorption.   Ideally,

       enough larger  MW  members should be  tested to identify a plateau or

       asymptote where further increases in MW do not significantly reduce

       absorption.  Selected methacrylate esters should  then'be tested to

       determine  any differences  in  absorption  between  acrylates  and

       methacrylates.

                                                 -Ğ•

b)     Once the general  relationship between MW and absorption has  been

       established for acrylates and methacrylates, the effect of  varying

       water solubility  and octanol/water partition coefficient at  a given

       MW  siioijld be evaluated.   This might  be done by comparing the

       absor  •  >n of  PGDA and a more water soluble polyethylene glycol

       diacr/l ;te of similar MW.

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       c)     We also propose testing to evaluate the importance of concentration


             in assessing absorption potential of  low MW acrylates/methacrylates


             from a fluid high acrylate/methacrylate material. For example, radio-


             labeled  neopentyl  glycol  diacrylate  (NPGDA,  MW=2I2)  could  be


             synthesized and  tested neat in the same protocol  as above to establish


             its  relative absorption in this test.  A large PGDA-n could also  be


             synthesized with n such  that the chemical will  have only  negligible


             absorption using the protocol stated above. The labeled NPGDA could


             then be mixed with the PGDA-n at  concentrations above, below, and


             at 2% and the absorption of labeled  NPGDA measured in the protocol


             listed above.

                                                                •
             A determination of a reasonable cutoff  for the percent of low MW


             species  in  high  MW acrylate/methacrylate substances could  then  be


             based on this absorption data.


                                                                 *

3.      Data Use




 The results of these  tests will provide a better basis for:




       (a)   .Understanding the  relationship between MW and absorption.




       (b)    Identifying other  physico-chemical  factors that significantly affect


             the absorption of these chemicals.




       (c)    Understanding the  absorption potential  of lower MW constituents in a


            , higher MW  mixture.
                                    8

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            (d)    Defining the range of physico-chemical factors for category members

                  beyond  which  we expect that aerylate/methacrylate chemicals will

                  not be absorbed to a significant degree and thus will not pose a health
                                                             r
                  risk to humans.



       These data will be used to provide  an  empirical basis for defining the range of

category members that  should be  expected to be  absorbed by humans and that may

present a health  risk to humans.  Acrylates or  methacrylates with physico-chemical

properties outside the category limit will not be expected to be absorbed to a significant

extent by humans and,  therefore, should not be expected  to present  a health  risk to

humans.  When combined with more detailed information on the potential health effects,

an  improved understanding of the absorption  of  these chemicals will eventually also

improve our ability to assess the relative risk of specific category members.


                                                                    *
     B.     Carcinogenic Hazard  Potential



            I.     Data Gaps



       Based on our  review of the  available data  on  the  carcinogenicity  of category

members, there are two  basic data gaps associated  with a category-wide understanding

of the carcinogenicity of acrylates/methacrylates.  First, the available test data were

generated from a chemical specific perspective and do little to help answer our basic

questions  about the  category  as a whole.   For example a measure  of  the relative

carcinogenic hazard of acrylates vs. methacrylates, mono vs. multifunctional,  and the

larger  vs. smaller MW category members cannot  be generated  from the existing data.

Second, the available data were  derived from significantly different protocols,  making

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comparisons of the results difficult.  We are currently unable to determine how reliable

the  available modified  bioassay studies are in  detecting  the inherent carcinogenic
           •*
potential  of these chemicals.  Therefore, one of the objectives of a testing program for

this category should  be the validation  of a modified bioassay  which could be used to

economically screen  chemicals containing the aerylate/methacrylate functional groups

for  their  potential carcinogenic!ty.   To most  effectively  accomplish this  objective,

results generated in a standard 2-year bioassay on a carefully selected series of category

members  should be compared with the results from an appropriate modified bioassay on a

more extensive  set of category members.   The  data generated in both assays will be

useful in describing the relative carcinogenic hazard of chemicals within the category.


                                                                   •

     2.      Testing Proposal



      Currently there are no validated in vitro or in vivo carcinogenicity screening tests

for this category  of  chemicals.   Therefore, the  most scientifically  acceptable way to

evaluate the inherent carcinogenic potential of category members is to  test them  in a

standard two-year bioassay.  A validated screening tool would be a valuable tool to help

answer  questions  about  the relative  carcinogenic  hazard ^of  the  category  and for

screening  the carcinogenic potential of "new" category members.  As a result, there is a

need for developing data from both a standard bioassay and a screening  assay.  EPA  is

currently  developing  data from  genotoxicity assays for  this category,  so our testing

proposal focuses on data development  from both the standard bioassay and a modified,

screening  bioassay.
                                         10

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       Because of the category approach to evaluating these chemicals, HERD proposes


the concurrent development of data in an acceptable modified bioassay protocol and ine
           •Ğ

a standard bioassay.  The results of the modified bioassay would provide a cost-effective


basis for evaluating and screening a range of category members', whereas the results of


the standard bioassay would be used to validate the design of the modified bioassay.


       The specific protocol  design for both the modified and standard bioassays for this


testing should be developed in  consultation with interested parties.  We believe the main


uncertainty  in the  design of  these tests is the route of administration  for the test


substance.   Inhalation does not appear appropriate  because only  low doses can  be


administered, and drinking water studies would be complicated by hydrolysis of the test


substance.  For human risk  assessment  purposes, the primary route of expected human


exposure (dermal for this category) should be used.  However, because of the irritating


properties of category members it may be difficult to reach an appropriate MTD by this


route or to generate a dose-response curve by testing over a range of doses. The dermal


route has, however,  yielded several positive results in single dose, limited bioassays. The


gavage route, while not the  route of human  exposure does have certain advantages over


the dermal  route in  this case.   First,  the gavage  route  allows higher  doses to  be


administered in a more precise  manner.  Second, dosing by^javage can be done more


frequently.  Third, irritation  appears to be less of a problem with the gavage route, but it


is still a major difficulty.  However, the gavage route is clearly not the expected route of


human exposure.


       In  addition to determining the route of exposure for both a  modified  and  the


standard bioassays, several other important aspects of the modified bioassay need to be


defined to ensure  it  is an  acceptable  test.   These factors include:   the  amount  of


histopathology, the study  duration, number  of animals, etc.   The major consideration in


defining these details will be the trade-off  between the sensitivity of the test and  the


test  cost.  The  use of statistical analyses may help in evaluating the effect of  the


various test options on the power of the modified bioassay protocol.

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       The  selection of specific  chemicals  for testing will  also  need to be  resolved

following further discussions with the interested parties. Tables I  and 2 present a list of
             •Ğ
category  members  from which  those to be tested  could be selected.   The specific

chemicals selected should  be designed to answer our  basic questions about the category

and to maximize the use of the available data and resources.



     3.     Data Use



       The most important use of this data will be to  provide the Agency with a data set

that accurately represents the inherent  carcinogenic potential of the tested category

members.  These data will provide the basis  for distinguishing the  relative carcinogenic

activity of subsets of this category by providing a reasonable degree of confidence that

negative  results indicate a  true  lack of carcinogenic activity.   These  data will also

provide an acceptable basis or baseline for validating  modified bioassay and genotoxicity

test  results that  may  be  useful to  screen a wider range of  "existing"  and "new"

acrylate/methacrylate chemicals.  These results will enable us to focus our attention on

those members or subsets of  the category that present the greatest carcinogenic hazard.

                                                              -Ğr

     C.     Neurotoxic Hazard Potential and  Other Chronic Effects



            I.     Data Gaps



       The available neur  toxicity hazard  data for this category  of  chemicals is very

limited.  It consists  primarily of one study on  2-hycfroxyethyl acrylate (2-HEA), one study

on a  methacrylate  mixture, and  several  case reports of methacrylate exposures  to

humans.   Neurotoxicity effects have been observed in so few studies  that extrapolation

to the entire category is not possible with a  reasonable degree of  certainty.  Two basic
                                         12

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data gaps are apparent from our evaluation of the available data.


           *       a)     Because  it  is possible that  the positive neurotoxicity results
                         reported are  false  positives,  there is a  need to retest the
                         chemicals  previously  studied  with a standard  protocol to
                         confirm the existence of the neurotoxic effect.


                  b)     Given  the  confirmation of  the  neurotoxic  effects  for the
                         previously   tested  chemicals,  a  wider   range  of  category
                         members would then be tested.  These additional tests  will help
                         answer questions about  the  relative neurotoxic hazard  within
                         the  various  subsets  of  the  category  (e.g.  acrylates  vs.
                         methacrylates,  mono  vs.   multifunctional,  larger   MW  vs.
                         smaller MW members).
                                                                       •

       In addition to evaluating neurotoxic effects in these studies,  it would be  valuable
to also look  for  any other chronic  effects (non-carcinogenic).  The available data that
specifically included observations for other  effects are very  limited for this category,
although no other specific effects have been noted in the available studies.


            2.    Testing Proposal


       The neurotoxicity testing should be a tiered approach designed to  first confirm the
available results, and then to develop additional data if the first tier  is positive.


                  a)     As the first proposed tier of testing, 2-HEA should be retested
                         in a  90-day subchronic study using the OTS text guidelines on
                                          13

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                         the functional observational battery and neuropathology.  Also,



                         methyl methacrylate,  penfaerythritol triacrylate, trimethylol

             •ğ

                         propane trimethyacrylate, trimethylol propane triacrylate, and



                         tripropylene  glycol diacrylate should  be  tested in  a 90-day



                         subchronic  study to confirm  the  reported  neurotoxic effects



                         for these  chemicals.    The  route  of  exposure  should  be



                         identified based on many of the same considerations identified



                         in  the carcinogenicity discussion.






                  b)     If a neurotoxic effect can be confirmed in at  least some of the



                         studies listed above,  additional studies should be performed.
                                                                     •


                         These additional studies  should involve  a  90-day subchronic



                         protocol   using  OTS   test   guidelines  on   the  functional



                         observational  battery  and  neuropathology.    Chemicals  for



                         testing should be selected from Tables I  and 2 to help answer



                         questions of the relative hazard of acrylates vs. methacrylates,



                         mono  vs. multifunctional, and the larger MW vs.  smaller MW



                         category  members  and to maximize the use of the available



                         data on this effect. Signs of other chronic (non-carcinogenic)



                         effects should be assessed in all the neurotoxicity studies.






            3.     Data Use






       The results of the testing proposal will  be used by the Agency in several  ways.



First,  it will allow us to confirm or reject  the  identification of a neurotoxicity hazard



with this category of chemicals. Second, if this hazard identification  is confirmed it will



allow us to prioritize our concerns  for a wider range of category members by identifying

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those that present the greatest hazard. Third, it will help identify other chronic effects,

if any, that should be associated with this category of chemicals.

            •Ğ


     D.     Ecotoxic Hazard Potential



            I.     Data Gaps



       The available  ecotoxicity data on this category of chemicals are primarily  from

acute toxicity  tests.   These results indicated acute LC5Q values as  low as I mg/L and

indicated signs of chronicity, which suggests that  chronic effect concentrations may be

much lower (one-twentieth or less) than acute effect concentrations.  These data, which
                                                                   •
identify  an ecotoxicity hazard concern, require further evaluation to answer some  basic

questions about the nature of the effect for a wider range of category  members. These

questions  include  the  relative  hazard  of  acrylates  vs.  methacrylates,  mono  vs.

multifunctionals, smaller  MW vs.  larger MW members, the effect of acr^late equivalent

weight (i.e., total MW divided  by the number of acrylate functional  groups),  and the

effect of other  functional groups.  Testing on fish, daphnia, and algae  is also needed to

evaluate the relative  sensitivity  among the basic groups of aquatic organisms.



            2.     Testing Proposal



      Our ecotoxicity testing proposal involves the selection of acrylate chemicals from

Table 2  and methacrylate  chemicals  from Table 3  in addition to larger prepolymers

(MW ^ 1000) that will  answer our basic questions identified above.  It is proposed that

each chemical  selected be  tested in an acute fish,  acute daphnid, and algal  toxicity

tests.  If the 96-hour EC$Q value for fish or the 48-hour ECjQ  value for daphnids is less

than I  mg/L then the appropriate chronic toxicity testing should be done.  However, if

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the acute  EC^Q  values are greater than  I mg/L but less than 100  mg/L  and there is



evidence of  cumulative toxicity (i.e.,  the fish 24-hour EC^Q/96-hr  EC$Q  ratio or  the



daphnid 24-hour ECjQAB-hour EC^Q ratio is greater than two), then the proposed chronic



toxicity testing should  also be done.  The proposed chronic toxicity testing is the fish



early life stage toxicity test and the daphnid chronic toxicity test.








           3.     Data Use








       These  data will allow  the Agency to develop a QSAR between acute toxicity  and



physico-chemical  properties,  to determine  whether certain functional groups or category



subsets present a  greater or lesser aquatic  toxicity hazard,  and to determine the limits of



our aquatic toxicity concern  for the category based on MW, acrylate equivalent weight,



and water solubility. This will allow us to focus our attention on those category members



that appear to present the greatest  ecotoxcity hazard.
                                         16

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Table  1.  Acrylate candidates  for  health  and  ecotoxicity  testing
ACID

acrylic acid
            •ğ

MONOACRYLATES

methyl acrylate
allyl acrylate
propyl acrylate
_rv-butyl acrylate
pentyl acrylate
jv-octyl acrylate
2-ethylhexyl acrylate
decyl acrylate
dodecyl acrylate

CYCLIC MONOACRYLATES

phenyl acrylate
benzyl acrylate
isobornyl acrylate

HYDP.OXY-SUBSTITUTED MONOACRYLATES

Hydroxypropyl acrylate

ALKOXIDE-SUBSTITUTED MONOACRYLATES

methoxy acrylate
butoxyethyl acrylate

PHENOXIDE-SUBSTITUTED MONOACRYLATES

phenoxyethyl acrylate

EPOXY-SUBSTITUTED MONOACRYLATES

glycidyl acrylate

NITRO-SUBSTITUTED MONOACRYLATES

2, 2-dinitropropyl acr.'.ate

AMINO-SUBSTITUTED MO'. 'CRYLATES

dimethylaminoethyl ae:vlates

CYANO-SUBSTITUTED MOr" -\CRYLATES

2-cyanoethyl acrylate
                              17

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Table 1.  (continued)
HALOGENATED MONOACRYLATES

2,3-Dichloropropyl acrylate
tribromophenyl acrylate
2,2,2-trifluoroethyl acrylate
3 r 3,4,4,4-pentafluorobutyl acrylate
nonafluorohexyl acrylate
tridecylfluorooctyl acrylate
heptadecylfluorodecyl acrylate
pentacosafluorotetradecyl acrylate

POLYACRYLATES
ethyleneglycol diacrylate
1,4-butanediol diacrylate
diethyleneglycol diacrylate
1,6-hexanediol diacrylate
tetraethyleneglycol diacrylate

trimethylolpropane triacrylate

pentaerythritol tetraacrylate

dipentaerythritol pentaacrylate
                            18

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Table 2.  Methacrylate candidates for health and ecotoxicity
          testing.
ACID

methacrylic 4acid


MONOMETHACRYLATES

methyl methacrylate
allyl methacrylate
propyl methacrylate
butyl methacrylate
2-ethylbutyl methacrylate
octyl methacrylate
ethylhexyl methacrylate
jv-decyl methacrylate
lauryl methacrylate

CYCLIC MONOMETHACRYLATES

phenyl methacrylate
benzyl methacrylate

HYDROXY-SUBSTITUTED MONOMETHACRYLATES

Hydroxypropyl methacrylate

ALKOXIDE-SUBSTITUTED MONOMETHACRYLATES

methoxyethyl methacrylate
2-(vinyloxy)ethyl methacrylate

PHENOXIDE-SUBSTITUTEP MONOMETHACRYLATES

2-phenoxyethyl methacrylate

EPOXY-SUBSTITUTED MONOMETHACRYLATES  '

glycidyl methacrylate

NITRO-SUBSTITUTED MONOMETHACRYLATES

2,2-dinitropropyl methacrylate

AMINO-SUBSTITUTED MONOMETHACRYLATES

NfN-dimethylaminoethvl methacrylates

CYANO-SUBSTITUTED MONOMETHACRYLATES

2-isocyanotomethyl methacrylate
                               19

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 Table 2.   (continued)
HALOGENATED MONOMETHACRYLATES

2-chloroethyl methacrylate
trifluoroethyl methacrylate
2,2,3,3,3-pentafluoropropyl raethacrylate
3,3,4,4,5,5,6,6-nonafluorohexyl methacrylate
lH,lH-pentadecafluorooctyl methacrylate

POLYMETHACRYLATES
ethyleneglycol dimethacrylate
1,3-butanediol dimethacrylate
diethyleneglycol dimethacrylate

aluminum trimethacrylate

ADDITIONAL METHACRYLATES

tributyltin methacrylate
3-(trimethoxysilyl) propyl methacrylate
thioglycidyl methacrylate
vinyl methacrylate
                              20

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