ACROLEIN
Ambient Water Quality Criteria
              Criteria and Standards Division
              Office of Water Planning and Standards
              U.S. Environmental Protection Agency
              Washington, D.C.

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                              CRITERION DOCUMENT



                                   ACROLEIN



CRITERIA




                                 Aquatic Life



     For acrolein the criterion to protect freshwater aquatic



life as derived using the Guidelines is 1.2 ug/1 as a 24-hour



average and the concentration whould not exceed 2.7 ug/1 at any



time.



     The data base for saltwater aquatic life is insufficient to



allow use of the Guidelines.  The following recommendation is



inferred from toxicity data for freshwater organisms.



     For acrolein the criterion to protect saltwater aquatic life




as derived using procedures other than the Guidelines is 0.88



ug/1 as a 24-hour average and the concentration should not exceed



2.0 ug/1 at any time.




                                 Human Health




     For the protection of human health from the adverse effects



of acroelin ingested through the consumption of water and contaminated



aquatic organisms a criterion of 6.5 ug/1 is suggested.

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Introduction



     Acrolein has a wide variety of applications.  It  is directly



used as a biocide for aquatic weed control; for algae, weed and



mollusk control in re-circulating process water systems; for



slime control in the paper industry; and to protect liquid fuels



against microorganisms.  Acrolein is also used directly for



crosslinking protein collagen in leather tanning and for tissue



fixation in histological samples.  It is widely used as an inter-



mediate in the chemical industry.  Its dimer, which is prepared



by a thermal, uncatalyzed reaction, has several applications,  in-



cluding use as an intermediate for crosslinking agents, humec-



tants, plasticizers, polyurethane intermediates, copolymers and



homopolymers, and Greaseproofing cotton.  The monomer  is utilized



in synthesis via the Diels-Alder reaction as a dienophile or a



diene.  Acrolein is widely used in copolymerization but its



homopolymers do not appear commercially important.  The



copolymers of acrolein are used in photography, for textile



treatment, in the paper industry, as builders in laundry and



dishwasher detergents, as coatings for aluminum and steel panels,



as well as other applications.  Hess, et al. (1978) described



marketing aspects of acrolein.  In 1975 worldwide production was



about 59 kilotons.  Its largest market was for methionine



manufacture.  Worldwide capacity was estimated at 102



kilotons/year of which U.S. capacity was 47.6 kilotons/year.



     Acrolein (2-propenal) is a liquid with a structural formula



of CH2=CHCHO and a molecular weight of 56.07.  It melts at



-86.95C, boils at 52.5 to 53.5C, and has a density of 0.8410



at 20C (Weast, 1975).  The vapor pressure at 20C is  215 mm Hg
                             A-l

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and its water solubility  is 20.8 percent  by weight  at  20C

(Standen, 1967).

     A flammable liquid with a pungent odor,  acrolein  is  an  un-

stable compound that undergoes polymerization to  the plastic

solid disacryl, especially under light or  in  the  presence of

alkali or strong acid  (Windholz, 1976).   It is  the  simplest

member of the class of unsaturated aldehydes,  and the  extreme

reactivity of acrolein is due to the presence of  a  vinyl  group
     H                           0
     C-) and an aldehyde  group (-C-H) on  such a small  molecule
(Standen, 1967).  Additions to the carbon-carbon double  bond  of

acrolein are catalyzed by acids and bases.  The addition of

halogens to this carbon-carbon double bond proceeds  readily

(Standen, 1967).

    .Freshwater acute toxicity values as  low  as 61 ug/1  have  been

reported.  A chronic fish value of 21.8 ug/1  has been demonstrat-

ed.  Acrolein has been found to bioconcentrate 344 times in a

freshwater fish.  Saltwater acute toxicity in one fish species

was found to be 240 ug/1.  No bioconcentration or chronic data

are available for marine species.

     Acrolein has been shown to produce a great variety  of dis-

orders in mammalian animals and man.  However, it has not been

shown to be a teratogen and only a mild to weak mutagen,  if one

at all, depending on the test system employed.  Though it has

been suspected as a carcinogen or cytotoxigen, information does

not definitively produce evidence of confirmation.

     Acrolein can enter the aquatic environment by its use as an

aquatic herbicide, from industrial discharge, and from the chlor-
                              A-2

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ination of organic compounds in waste water and  drinking  water



treatment.  It is often present in trace amounts  in  foods and  is



a component of smog, fuel combustion, wood and possibly other



fires, and cigarette smoke.  An evaluation of available data  in-



dicates that, while industrial exposure to manufactured acrolein



is unlikely, acrolein is pervasive from nonmanufactured sources.



Acrolein exposure will occur through food ingestion  and inhala-



tion.  Exposure through the water or dermal route  is  less likely.



However, analysis of municipal effluents of Dayton,  Ohio  showed



the presence of acrolein in 6 of 11 samples, with  concentrations



ranging from 20 to 200 yg/1 (UoS. EPA, 1977).



     Bowmer, et al. (1974) described the loss of  acrolein by



volatilization and degradation in sealed bottles  and  tanks of



water.  The amounts of acrolein dissipated after  eight days were



34 percent from the tank and 16 percent from the  bottles.  The



rate of disappearance of acrolein in the tank was  0.83 day"-1-



at a pH of 7.2.  The lack of turbulence in the tank  reduced acro-



lein loss by volatilization to 1/20 of what would  be  expected  if



volatilization was controlled only by resistance  in  the gas phase



and any discrete surface layers.  The authors agree  with  Geyer



(1962), who states that the primary degradation  reaction  is re-



versible hydrolysis to ^-hydroxypropionaldehyde,  which is less



volatile than acrolein.



     The fate of acrolein in water was observed  in buffered solu-



tions and in natural channel waters (Bowmer and  Higgins,  1976).



An equilibrium between dissipating acrolein and  degradation pro-



ducts was reached in the buffered solution following  dissipation



of 92 percent of the acrolein, but in natural waters  there was  no
                             A-3

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indication of an equilibrium, with the dissipating  reaction, ap-
parently being continued to completion.  In natural waters/  the
accumulation of a reaction  (degradation) product was  greater at
higher initial acrolein-concentration, and decay was  rapid when
acrolein concentration fell below 2 to 3 mg/1.  The initial
period of slow decline preceding the rapid dissipation  period is
thought to be the result of microbiological processes.   Unlike
earlier works (Bowmer, et al.  1974), there was an  eight- to ten-
fold increase in the observed dissipation rate as compared  to the
expected rate in two of four flowing water channels,  suggesting
major losses in volatilization and absorption.
                             A-4

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                           REFERENCES




Bowmer, K.H., and M.L.  Higgins. 1976.  Some aspects of the per-



sistence and fate of acrolein herbicide in water. Arch. Environ.




Contain. 5: 87








Bowmer, K.H., et al. 1974.  Loss of acrolein from water by vola-



tilization and degradation. Weed Res. 14: 325.








Geyer, B.P. 1962.  Reaction with water. In C.W. Smith, ed.  Acro-



lein. John Wiley and Sons, Inc., New York.








Hess, L.B., et al. 1978. Acrolein and derivatives. In  Kirk-



Othmer Encyclopedia of Chemical Technology. 3rd ed. Interscience



Publishers, New York.








Standen, A., ed. 1967.  Kirk-Othmer Encyclopedia of Chemical



Technology. Interscience Publishers, New York.








U.S. EPA. 1977. Survey of two municipal wastewater treatment



plants for toxic substances.  Wastewater Res.  Div. Municipal



Environ. Res. Lab., Cincinnati, Ohio.








Weast, R.C., ed. 1975.  Handbook of chemistry  and physics. 56th



ed.  CRC Press, Cleveland, Ohio.








Windholz, M., ed. 1976.  The Merck Index. 9th  ed. Merck and Co.,



Inc., Rahway, N.J.
                             A-5

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AQUATIC LIFE TOXICOLOGY*



                      FRESHWATER ORGANISMS



Introduction



     Much of the data concerning the effects of acrolein on



freshwater aquatic organisms has been determined using  static  test



conditions with unmeasured concentrations.  Consequently,  these



data may underestimate the toxicity of this volatile, unstable



chemical.  The study of Bond, et al. (1960) shows acrolein to  have



a substantially greater acute toxicity to fish than  the 14 other



herbicides tested.  This relationship is also seen in a toxicity



bibliography of five herbicides (Folmar, 1976).



Acute Toxicity



     Seven LC50 values for 24-, 48-, and 96-hour exposures are



available for six fish species (Table 1).  All values were deter-



mined under static conditions.  The adjusted values  for the  six



species tested showed a narrow range of toxicity (23 to 87 ug/D-



In the study of Bond,  et al. (1960), the 24-hour LC50 of  80 ug/1
*The reader is referred to the Guidelines for Deriving Water



Quality Criteria for the Protection of Aquatic Life  [43  FR  21506



(May 18, 1978) and 43 FR 29028 (July 5, 1978)] in order  to  better



understand the following discussion and recommendation.   The



following tables contain the appropriate data that were  found  in



the literature, and at the bottom of each table are  the  calcula-



tions for deriving various measures of toxicity as described  in



the Guidelines.
                              B-l

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for chinook salmon  is only 1.2 times  the LC50 of  65  ug/1  for  rain-



bow trout.  Among the adjusted LC50 values for  four  species tested



by Louder and McCoy  (1962),  the highest, 87 ug/1  for largemouth



bass, is only 3.2 times higher than the lowest, 27 ug/1 for mos-



quitofish.  The geometric mean LC50,  40 ug/1? divided by  the  sen-



sitivity factor (3.9), results in the Final Fish  Acute Value  for



acrolein of 10 ug/1-



     The data base  for invertebrate species is  limited to two



static tests with Daphnia magna (Table 2)? therefore,  no  compari-



son of relative species sensitivity can be made.  The adjusted



LC50 values of 48 ug/1 and 68 ug/1 show that Daphnia magna has



about the same sensitivity to acrolein as fish.   The geometric



mean divided by the  Guideline species sensitivity factor  (21)



results in the Final Invertebrate Acute Value of  2.7 ug/1 which



becomes the Final Acute Value since it is lower than the  compar-



able value (10 ug/1) for fish.



Chronic Toxicity



     The chronic toxicity data base consists of one  value for fish



and one for invertebrate species.  A  life cycle test with fathead



minnows (Macek, et  al. 1976) resulted in a chronic value  of 21.8



ug/1 (Table 3).  Survival of newly hatched second generation  (F^)



fathead minnow fry was significantly  reduced at 42 ug/1 but was



not significantly different  from control survival at 11 ug/1.  A



dilutor malfunction  killed or severely stressed the  fish  at an



intermediate concentration?  21 ug/lf  so no second generation  fish



were produced.  The  chronic  value is  about half the  adjusted  mean
                             B-2

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LC50 value for fish and the adjusted LC50 value for  fathead



minnows (Table 1).  The Final Fish Chronic Value  is  3.3  ug/1



     Macek, et al. (1976) also conducted the only  freshwater



invertebrate chronic test.  Based on the cumulatively  reduced



survival of Daphnia magna through three generations, a chronic



value of 24 ug/1 is obtained (Table 4).  The unadjusted  acute



values for this species are 57 ug/1 and 80 ug/1-   These  data show



that there is little difference in concentrations  between  the



acute and chronic effects of acrolein on Daphnia magna.  The



chronic value divided by the sensitivity factor (5.1)  is the Final



Invertebrate Chronic Value of 4.7 ug/1.  As with  the acute data,



estimated chronic values show no appreciable difference  in



sensitivity between freshwater fish and invertebrate species.   The



slightly lower Final Fish Chronic Value of 3.3 ug/1  is the Final



Chronic Value.



     It is interesting to note that the Final Invertebrate Chronic



Value is higher than the Final Invertebrate Acute  Value  when both



are derived from data for Daphnia magna..  This is  the  result of



the small difference in the acute and chronic toxicity of  this



species as discussed above and the fact that the  species sensi-



tivity factor (21) for acute data is larger than  that  (5.1)  for



chronic data.  There are insufficient species tested to  evaluate



the accuracy of these factors and, therefore, they are not used



for acrolein.



Plant Effects



     No usable plant data were available.
                             B-3

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Residues



     Bluegills exposed for 28 days to 13 ug/1 of 14C-acrolein



bioconcentrated acrolein 344 times (Table 5).  The half-life was



greater than 7 days.  Thin layer chromatography was used  to verify



concentrations.



Miscellaneous



     The additional information on short-term exposures of fish



agree with previously described acute data.  Hartley and  Hattrup



(1975) observed 32 percent mortality of rainbow trout exposed  for



48 hours to 48 ug/1.  The 24-hour mean time to death concentra-



tions for brown trout and bluegill were calculated to be  46 ug/1



and 79 ug/1, respectively (Burdick, et al. 1964).  Macek, et al.



(1976) reported a 6-day incipient LC50 of 84 ug/1 for fathead



minnows.  The avoidance response seen in rainbow trout at 100  ug/1



(Folmar, 1976) is above reported acute levels.  Ninety-eight per-



cent of adult snails and 100 percent of snail eggs died after  a



24-hour exposure to 10,000 ug/1 (Ferguson, et al. 1961).
                             B-4

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CRITERION FORMULATION



                     Freshwater-Aquatic Life



Summary of Available Data



     The concentrations below have been rounded  to  two  significant



figures.



     Final Fish Acute Value = 10 ug/1



     Final Invertebrate Acute Value = 2.7 ug/1



          Final Acute Value = 2.7 ug/1



     Final Fish Chronic Value =3.3 ug/1



     Final Invertebrate Chronic Value = 4.7 ug/1



Final Plant Value = not available



     Residue Limited Toxicant Concentration = not available



          Final Chronic Value = 3.3 ug/1



          0.44 x Final Acute Value = 1.2 ug/1



     The maximum concentration of acrolein is the Final Acute



Value of 2.7 ug/1 and the 24-hour average concentration is 0.44



times the Final Acute Value.  No important adverse  effects on



freshwater aquatic organisms have been reported  to  be caused by



concentrations lower than the 24-hour average concentration.



     CRITERION:  For acrolein the criterion to protect  freshwater



aquatic life as derived using the Guidelines is  1.2 ug/1  as a



24-hour average and the concentration should not exceed 2.7 ug/1



at any time.
                             B-5

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              Table   1.   Freshwater fish acute values  for acrolein
                                                                Adjusted













ro
i
en



Bioaeeay Test Time
prganjsp Method-- Cone .** (hrs)
Chinook salmon S U 24
(fingerling).
Oncorhynchus tshawytscha
Rainbow trout S U 24
(fingerling) ,
Salmo gairdneri
Fathead minnow, S U 48
Pimephales promelas
Mosquitofish. S U 48
Gambusla affinls
Bluegill. S U 96
Lepomis macrochirua

Bluegill, S U 96
Lepomis macrochirus
Largemouth bass, S U 96
Micropterus salmoides

LC50 LC50
juq/1) (uq/ll heference
80 29 Bond, et al.


65 23 Bond, et al.


115 51 Louder & McCoy

61 27 Louder & McCoy

100 55 Louder & McCoy

90 49 U.S. EPA. 1978

160 87 Louder & McCoy



1960


1960


, 1962

. 1962

. 1962



. 1962

*  S = static
 U = unmeasured
                                                     40.2
   Geometric mean of adjusted  values = 40.2 Mg/1     A'A = 10   Mg/1

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              Table  2.   Freshwater invertebrate acute values for acrolein
                                                                Adjusted

Organism
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Bicassay Test Time LC50 I.CliO
Mctnou* Cor.c.** ((IKS) (uci/ll (uq/l| Kcterence
S U 48 57 48 Macek, et al. 1976

S U 48 80 68 U.S. EPA. 19.78

*  S = static



** U = unmeasured



   Geometric mean of adjusted  value  57.2 wg/1
= 2.7

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                    Table  3.    Freshwater fish chronic values for acrolein


                                                        Chronic
                                              Limits     Value
      Organism                     Test*      (ug/i)     (ug/l)          fieferenct


      Fathead minnow.               LC      11.4-41.7    21.8           Macek,  et al.   1976
      Pimephales promelas
       * LC = life  cycle or partial life cycle


                                                        21 fl
         Geometric mean of chronic value * 21.8 (jg/1     67 = 3.3   Mg/1

         Lowest chronic value = 21.8

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                   Table  4. Freshwater invertebrate chronic  values  for acrolein
Organism
Cladoceran,
Daphnia magna

* LC = life cycle
Geometric mean
Teat*
LC
or partial life
of chronic value
Limits
fuq/1)
16.9-33.6
cycle
- 24 vg/l
Chronic
Value
(uq/l> Reference
24 Macek. et al. 1976
24
-57T- 4.7 KB/1
             Lowest chronic value = 24   iJg/1
00
I

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0)
I
                         Table  5.    Freshwater residues for acrolein (U.S. EPA, 1978)
           Organism
                                             Bioconcentration Factor
                                                                          Time
                                                                          (days)
           Bluegill.
           Lepomis macrochlrus
344
28

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                          Table  6.   Other freshwater data for acrolein
                               Teat
                                                                  Result
DO
I
       Organism
       Snail (adult),            24 hra   98% mortality
       Australorbls glabratus

       Snail (egg).              24 hrs   100% mortality
       Australorbts glabratus
Rainbow trout (fry),
Salmo galrdneri

Rainbow trout,
Salmo galrdnerl

Brown trout
(fIngerllng).
Salmo trutta

Fathead minnow,
Pimephales promelas
 1 hr    Avoidance


48 hrs   32% mortality


24 hrs   Hean time to death



 6 days  Incipient LC50
       Blueglll (flngerling),    24 hrs   Mean time to death
       Lepomts macrochlrus
10,000    Ferguson, et al.  1961


10,000    Ferguson, et al.  1961


   100    Folmar, 1976


    48    Hartley & Hattrup, 1975


    46    Burdick, et al.  1964



    84    Macek, et al.  1976


    79    Burdick. et al.  1964
       Lowest value = 46 Mg/1

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                       SALTWATER ORGANISMS



Introduction



     Acrolein is used as a fungicide and a herbicide.   It  has  been



applied directly to the'saltwater environment  to control fouling



organisms in cooling water systems of coastal  power plants.  The



data base for toxicity of acrolein is limited  to the  results of



acute exposures of one fish and three invertebrate species,



performed with unmeasured test concentrations.



Acute Toxicity



     The longnose killifish was exposed for  48 hours  to acrolein



in a flow-through test (Butler, 1965).  The  adjusted  LC50  is 150



ug/1 (Table 7).  Adjusted LC50 values for six  species of fresh-



water fish ranged from 23 to  87 ug/1  (Table  1).  The  Final Fish



Acute Value for saltwater fish, obtained using the species



sensitivity factor  (3.7), is  41 ug/1.



     The adjusted LC50 values for three invertebrate  species



ranged from 33.1 to 764.8 ug/1 (Butler, 1975;  Dahlbergl; 1971). -



Brown shrimp and the eastern  oyster were the most sensitive



species tested  (Table 8).  The Final  Invertebrate Acute Value,



obtained using  the  species sensitivity factor  (49) is 2.0  ug/1/



and was an order of magnitude less than the  lowest LC50 value  of



tested species.



Chronic Toxicity



     No chronic effects of acrolein on saltwater fish and  inverte-



brate species have  been reported.
                              B-12

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Plant Effects
     The effects of acrolein on saltwater and freshwater plants
have not been studied.  Because acrolein is a herbicide, phyto-
toxicity to aquatic species might be expected.
                             B-13

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CRITERION FORMULATION             -    -  .
                       Saltwater-Aquatic Life
Summary of Available Data
     The concentrations  below have been rounded  to  two  significant
figures.
     Final Fish Acute  Value = 41 ug/1
     Final Invertebrate  Acute Value = 2.0 ug/1
          Final Acute  Value = 2.0 ug/1
     Final Fish Chronic  Value = not available
     Final Invertebrate  Chronic Value = not available
     Final Plant Value = not available
     Residue Limited Toxicant Concentration = not available
          Final Chronic  Value = not available
          0.44 x Final Acute Value = 0.88 ug/1
     No saltwater criterion can be derived for acrolein using  the
Guidelines because no  Final Chronic Value for either fish or
invertebrate species or  a good substitute for either value is
available.
     Results obtained  with acrolein and freshwater  organisms
indicate how a criterion may be estimated.
     For acrolein and  freshwater organisms 0.44  times the Final
Acute Value is less than the Final Chronic Value which  is derived
from results of a life cycle test with the fathead  minnow.  There-
fore, it seems reasonable to estimate a criterion for acrolein and
saltwater organisms using 0.44 times the Final Acute Value.
                             B-14

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     The maximum concentration of acrolein  is  the  Final  Acute



Value of 2.0 ug/1 and the estimated 24-hour average  concentration



is 0.44 times the Final Acute Value.  No  important adverse  effects



on saltwater aquatic organisms have been  reported  to be  caused  by



concentrations lower than the 24-hour average  concentration.



     CRITERION:  For acrolein the criterion to protect  saltwater



aquatic life as derived using procedures  other than  the  Guidelines



is 0.88 ug/1 as a 24-hour average and the concentration  should  not



exceed 2.0 ug/1 at any time.
                             B-15

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CD
I
                     Table   7.   Marine fish acute values for acrolein  (Butler,  1965)


                                                                        Adjusted
                               Bioaseay  Test      Time      LC50       LCbO
       Oygapism                Method*   Cone.**    (Era)      (ug/11
       Longnose killifish         FT       U        48         240        150
       (juvenile),
       Fundulus similis
       *  FT - flow-through

       ** U = unmeasured

          Geometric mean of adjusted  values " 150 pg/1    r-j = 41  pg/1

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Tdbie 8.  Marine invertebrate acute values for acrolein
03
1
H"
Organism
Eastern oyster,
Crassostrea virginica
Barnacles (adult),
Balanus eburneus
Barnacles (adult) ,
Balanus eburneus
Brown shrimp (adult),
Penaeus aztecus

biodssay
Metnoa*
FT
S
S
FT
Test
Cone .**
U
U
U
U
* S  static; FT = flow- through
** U = unmeasured
***EC50: 50% decrease in shell growth of
Time
(nts)
96
48
48
48
oyster;
i' a ..n / 1
LC50
55***
2,100
1,600
100***
or loss of
97.9 
Adjusted
LCbO
(uq/1) hereience
42.4 Butler, 1965
764.8 Dahlberg, 1971
582.7 Dahlberg, 1971
33.1 Butler, 1965
equilibrium of brown shrimp.
n ..,. 1 1
                                       49

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                           ACROLEIN



                          REFERENCES







Hartley, T.R., and A.R. Hattrup.  1975.  Acrolein residues



in irrigation water and effects on rainbow trout.  Bur.



Reclam. Rep. REC-ERC-75-8.







Bond, C.E., et al.  1960.  Toxicity to various herbicidal



materials to fishes.  Biol. problems in water pollut., Trans.



1959 seminar. Public Health Service.  Tech. Rep. W60-3;



96-101. U.S. Dep. Health Educ. Welfare.







Burdick, G.E., et al.  1964.  Toxicity of aqualin to finger-



ling brown trout and bluegills.  N.Y. Fish Game Jour.  11:



106.







Butler, P.A.  1965.  Commercial fisheries investigations.



Effects of pesticides on fish and wildlife, 1964 research



findings Fish Wildl. Serv.  U.S. Fish Wildl. Serv. Circ.







Dahlberg, M.D.  1971.  Toxicity of acrolein to barnacles,



Balanus eburneus.  Chesapeake Sci.  12: 282.







Ferguson, F.F., et al.  1961.  Control of Australorbis glabratus



by acrolein in Puerto Rico.  Pub. Health Rep.  76: 461.
                               B-18

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Folmar, L.C.  1976.  Overt avoidance reaction of rainbow

trout fry to nine herbicides.  Bull. Environ. Contain. Toxicol.
                     t
15: 509.




Louder, D.E., and E.G. McCoy.  1962.  Preliminary  investiga-

tions of the use of aqualin for collecting fishes.  Proc.

16th Annu. Conf. S.E. Assoc. Game Fish Comm.  240.




Macek, K.J., et al.  1976.  Toxicity of four pesticides

to water fleas and fathead minnows: Acute and chronic toxicity

of acrolein, heptachlor, endosulfan, and trifluralin to

the water flea  (Daphnia magna) and the fathead minnow  (Pime-

phales promelas).  EPA 600/3-76-099. U.S. Environ.  Prot. Agency,




U.S. EPA. 1978.  In-depth studies on health and environmental


impacts of selected water pollutants.  Contract No. 68-01-4646.
                             B-19

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                          ACROLEIN



Mammalian Toxicology and Human Health Effects



                          EXPOSURE



Introduction



     Acrolein is the simplest unsaturated aldehyde:



          CH2=CHCHO



It is a colorless volatile liquid.  Table 1 describes its



salient physical properties.  Since it is a highly reactive



organic chemical and capable of self-polymerization, the



marketed product contains an inhibitor (0.1 percent hydro-



quinone) to prevent its degradation.  It is extremely reactive



at high pHs (Hess, 1978; Smith, 1962).  Methods for acrolein



analysis are summarized in Table 1A.



     Acrolein has a wide variety of applications.  It is



directly used as a biocide for aquatic weed control; for



algae, weed and mollusk control in re-circulating process



water systems; for slime control in the paper industry; and



to protect liquid fuels against microorganisms.  Acrolein



is also used directly for crosslinking protein collagen



in leather tanning and for tissue fixation in histological



samples.  It is widely used as an intermediate in the chemical



industry.  Its dimer, which is prepared by a thermal, uncat-



alyzed reaction, has several applications, including use



as an intermediate for crosslinking agents, humectants,



plasticizers, polyurethane intermediates, copolymers and



homopolymers and Greaseproofing cotton.  The monomer is



utilized in synthesis via the Diels-Alder reaction as a



dienophile or a diene.  Acrolein is widely used in copolymeri-



zation but its homopolymers do not appear commercially important,





                              C-l

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                           TABLE 1
               Physical Properties of Acrolein
                   (Smith, 1962; Hess, 1978)
Empirical formula

Molecular Weight

Melting Point, C

Boiling Point, C

Vapor pressure at 20C, KPa  (mmHg)

Refractive Index nQ  (20C)

Viscosity at 20C, cS

Solubility in Water  (weight  %)

Critical Properties:

     Temperature,  K
     Pressure,atm.
     Volume, cc/g-mole
C3H40

56.06

-86.95

52.69

29.3  (220)

  1.4017

  0.393

20.6
 510
 51.58
 189
                              C-2

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                           Table  1A

    Methods for Acrolein Measurement (Brady et al., 1977;
          Kissel  et  al.,  1978;  Bellar and Sigsby,  1970).
     Analytical Method
Detection Limit
Interferences
NMR (Aldehydic proton)

Colorimetry
  2,4-D
  4-hexylresourcinol

Fluorimetry
  Direct
  J-Acid
  m-aminophenol derivative

Differential pulse
  polarography

Gas chromatography
  Flame-ionization
  Mass Spectral
   100 mg/1
    80 jug/1
   700 jug/1
    20 mg/1
    20 ng/1
    30 jug/1
   500 /ig/1
    50 fig/I
     few
    many
    many
  very few
  very few
  very few

     few
  very few
  very few
                              C-3

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The copolymers of acrolein are used in photography, for
textile treatment, in the paper industry, as builders in
laundry and dishwasher detergents, as coatings for aluminum
and steel panels, as well as other applications  (Smith,
1962; Hess, 1978).  Hess  (1978) described marketing aspects
of acrolein.  In 1975 worldwide production was about 59
kilotons.  Its largest market was for methionine manufacture.
Worldwide capacity was estimated at 102 kilotons/year of
which U.S. capacity was 47.6 kilotons/year.
     The present technology for acrolein preparation employs
catalytic oxidation of propene in the vapor phase.  Typical
reaction conditions consist of feeding propylene and air
at 300 to 400C and 30 to 45 psi over the catalyst (usually
of the bismuth-molybdenum or the antimony family)  (Hess,
1978).
     Acrolein inadvertently enters the environment from
natural and anthropogenic sources.  It is often present
in trace amounts in foods and is a component of smog, fuel
combustion, wood and possibly other fires, and cigarette
smoke.  An evaluation of  available data indicates  that,
while industrial exposure to manufactured acrolein is unlikely,
acrolein is pervasive from non-manufactured sources.  Acrolein
exposure will occur through food ingestion and through inhala-
tion.  Exposure through the water or dermal route  is unlikely.
                               C-4

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Ingestion from Water
     There is no evidence that acrolein is a contaminant
of potable water or water supplies.  No available monitoring
study has noted .its presence, and acrolein is not listed
in compendia on water monitoring (Junk and Stanley, 1975;
Shackelford and Keith, 1976; Abrams, et al. 1975). Investiga-
tions on the fate of acrolein in water suggest that it dissi-
pates with a half-life on the order of four to five hours.
Based on these studies and the half-life in water  (see Table
2), it can be assumed that negligible acrolein is present
in water supplies.
     Acrolein is applied to the canals as a biocide for
the control of harmful organisms and aquatic weeds (Van
Overbeek, et al. 1959).  This application has prompted studies
to delineate the amount of acrolein required to maintain
effective pest control (Bowmer and Sainty, 1977; Hopkins
and Hattrup, 1974).  The studies have examined dilution
problems and pathways for loss.  Degradation and evaporation
appear to be the major pathways for loss, while a smaller
amount is lost through absorption and uptake in aquatic
organisms and sediments.  In a review of the Russian litera-
ture, Melnikov  (1971) indicates that acrolein is used as
a biocide in water reservoirs.
     Analytical difficulties complicate the measurement
of aqueous acrolein.  This problem has been demonstrated
in studies on the degradation of aqueous acrolein.  Some
of these analytical problems could exist in measurements
of acrolein  in other media.
                              C-5

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                           TABLE 2

     First Order  Rate  Constants  of Acrolein  Degradation
     in Laboratory Experiments  (Bowmer  and Higgins,  1976)
Water3
Supply
Supply
Drainage
Supply
Supply
Supply
Distilled
EH
7
7
7
7
7
7

.3
.3
.8
.2
.2
.2

Initial
acrolein
ppm

8.
6.
6.
6.
17
50
6.

0
8
4
1
.5
.5
4
10
hi

23
15
45
13
14
11
3k

.7
.9
.1
.3
.2
.4
2.7
SE
2
2
7
1
2
1
0
.4
.0
.5
.9
.5
.0
.3
aWater from canal supply, canal drainage, or distilled water
                            C-6

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     Kissel, et al. (1978) have demonstrated the analytical
problems in a study of the effect of pH on the rate of degra-
dation of aqueous acrolein.  Their study compared acrolein
measurement by ten analytical techniques on six pH buffer
systems  (pH 5,7 and 9).  The analytical methods were:
     (a)  bioassay with an ATPase enzyme system,
     (b)  bioassay by a plate count method,
     (c)  bioassay by fish kill (bluegill sunfish),
     (d)  chemical titration with bromide-bromate solution-
          iodide- thiosulf ate,
     (e)  colorimetric by the 2,4-dinitrophenylhydrazone  (DNP),
     (f)  fluorometric analysis (m-aminophenol) with excita-
          tion at 372 nm and emission at 506 nm,
     (g)  gas-liquid chromatography (on 6' Poropaks Q with
          injection temperature of 250C and column at 200C),
     (h)  nuclear magnetic resonance using aldehyde proton
          at 9.44 ppm vs. tetramethylsilane,
     (i)  polarographic analysis,
     (j)  fluorometric analysis directly on acrolein with
          excitation at 276 nm and emission at 370 nm.
Kissel, et al. (1978)  separated the analytical techniques into
three groups: bioassay, derivatization, and direct measure-
ment.  Differences between bioassay methods were less than for
any other group.  They considered bioassay a ^good measure
of true acrolein concentration.  Some titrimetric methods
were satisfactory but others were poor.  Among the direct
methods, they considered that GLC and direct fluorimetry
were poor but that NMR and polarographic analyses were better.
                             C-7

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Kissel, et al.  (1978) did not identify reasons for the large



discrepancies.  Also, they noted that acrolein rapidly degraded



at pH 9.



     Bowmer and coworkers (Bowmer and Higgins, 1976; Bowmer



and Sainty, 1977; Bowmer, et al. 1974; O'Loughlin and Bowmer,



1975) have measured  acrolein degradation rate in laboratory



and field.studies.   They evaluated the possible degradation



pathway in buffered, distilled water.  At pH 5, the acrolein



reacted by a reversible hydrolysis and yielded an equilibrium



mixture containing^8-hydroxypropionaldehyde: acrolein in 92:8



ratio.

          H20 + CH2  = CHCHO	^HOCH2CH2CHO



In alkali the primary reaction was consistent with a polycon-



densation.  In  natural waters they observed no evidence



for an equilibrium.  They considered the initial product
                           \


as chemical degradation and suggested, but did not demonstrate,



that  it further degraded to carboxylic acid via microbial



pathway.  Acrolein was analyzed by colorimetry using the



2,4-DNP method  and by bioassay.  Results were conflicting,



and they  concluded that the analytic complication  (as described



by Kissel, et al. 1978) resulted from the ability of the



hydroxypropionaldehyde to form a 2,4-DNP derivative, but



that  it was not a biocide.  They resolved the analysis problem



by flushing the volatile acrolein from a sample by means



of an air stream, which left the non-volatile hydroxypropionaldehyde



ifr-solution.  Acrolein concentration was measured as the



difference between acrolein-2,4-DNP absorbance in samples



before  and after  the flush  (Bowmer, et al. 1974).  Their



laboratory studies utilized samples sealed in bottles and
                              C-8

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maintained at 20.6C.  Table 2 summarizes their results.
The authors also examined acrolein loss in field studies,
using actual irrigation channels.  The apparent dissipation
rate, k, was estimated at 0.16 hr~ , which is about an order
of magnitude faster than measured in laboratory experiments.
They suggested that the difference could result in part
from volatization and absorption.
     Hopkins and Hattrup (1974) examined acrolein loss in
field studies in canals of the Columbia River basin.  Their
analytical technique was fluorometric analysis of the m-
aminophenol derivative.  The work of Kissel, et al. (1978),
which is discussed above, suggested that this analytical
method could yield higher acrolein concentrations than were
actually present.  Table 3 describes the acrolein concentration
in a flow-plug measured during a 48-hour study period in
two canals.  Hopkins and Hattrup (1974) suggested that dissi-
pation resulted from acrolein degradation, volatilization,
and absorption to weed tissue.
     Potable water is normally treated with a chemical oxidant,
usually chlorine or less often ozone.  These oxidants will
react with olefins and are very likely to react with the
olefinic portion of acrolein.  Ozone will likely initially
yield a malonozonide.  Aqueous chlorine (which exists as
HOC1) will probably degrade acrolein as follows (Hess, et
al. 1978): CH2 = CH-CHO + HOC1	HOCH2 CHC1CHO + C1CH2CH(OH)CHO.
The relative amounts of these two possible initial acrolein
derivatives and their degradation products are not .known
 (Morris, 1975).
                             C-9

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                                 TABLE  3

        Acrolein Dissipation in Two Canals of the Columbia River
            Basin Over  48  Hours  (Hopkins  and  Hattrup,  1974)
Canal
  Intended
Application
    ppm
   Sampling  Point     Acrolein
Miles Below Initial      ppm
     Appl. Point
Potholes
    0.14
              Booster  application  at
                     12.6 miles
East Low
    0.11
        1.0
        10.0
        12.5

        13.5

        15.0
        20.0
        30.0
        35.0

        1.0
        5.0
        10.0
        20.0
        30.0
        40.0
        64.5
0.14
0.10
0.09

0.20

0.18
0.15
0.08
0.05

0.09
0.10
0.10
0.08
0.06
0.02
0.03
                                  C-10

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Ingestion from Foods



     Acrolein is a common component of food at ug/g concentra-



tions.  It is commonly generated during cooking or other



processing, and is sometimes produced as an unwanted by-product



in the fermentation of alcoholic beverages.  The information



on acrolein in foods has been generated primarily to identify



organoleptic properties, so its relevance to exposure levels



is limited.



     Acrolein can be produced by cooking potatoes in water.



El'Ode, et al. (1966)  investigated acrolein production in



potato extract (Katahdin variety)  and synthetic mixtures



of the extract.  The synthetic mixture contained amino acids



(glycine, glutamic acid, lysine, methionine, and phenylalanine)



and sugar (glucose, fructose, maltose, and sucrose). Acrolein



was identified (by GC) as a product of heating some but



not all mixtures of amino acid and sugar.  They did not



identify acrolein as a product of heating the actual potato



extract  (30 minutes at 180C) or of heating the synthetic



potato mixture (60 minutes at 100C).



     As reviewed by Izard and Libermann  (1978) , acrolein



is generated when animal or vegetable fats are subjected



to high temperatures.   In these cases, acrolein is formed



primarily from the dehydration of glycerol.



     Kishi, et al. (1975) identified acrolein production



from cooking potatoes or onions in edible oil.  They detected



2.5 to 30 mg/m  acrolein in the vapors 15 cm above the surface



of the heated oil.  Cooking about 20 g of potatoes or onions



in the oil yielded 200 to 400 ug of acrolein.  The authors



did not determine whether the acrolein came from the oil,



                              C-ll

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the potatoes, the onions, or from all three sources.



     Hrdlicka and Kuca  (1965) examined aldehydes and  ketones



in turkey before cooking and in volatiles produced by either



boiling  (3 kg in 6 liters of distilled water for three hours)



or roasting  (3 kg at 170 to 190C for three hours).   Raw



turkey was extracted at 2C with 75 percent ethanol for



72 hours and volatiles were collected by vacuum distillation.



The carbonyl fraction was derivatized with 2,4-DNP and the



derivatives were identified by paper chromatography.   Acrolein



was identified in raw turkey and in the volatile products



from both cooking methods.



     Love and Bratzler  (1966) identified acrolein  in  wood



smoke.  Samples  (whole smoke and vapor phase) were collected



from hardwood sawdust (mainly maple) burned on a hot  plate



(490 to 500C) and from commercial smokehouses  (operated



at 48 to 49.5C).  The carbonyl compounds were trapped in



2,4-DNP solution and the derivatives were identified  by



GC.  Acrolein was identified in all smoke samples  but was



not quantified.



     Levaggi and Feldstein  (1970) examined acrolein concentra-



tions in the emissions from a commercial coffee roaster.



Acrolein was trapped in Greenberg-Smith impingers  containing



o.ne percent  sodium bisulfite solution and was quantified



by colorimetric  4-hexylresorcinol method.  At the  emission



outlet  (after burner abatement device) they measured  0.60



mg/m  acrolein,  while no acrolein was detected in  the inlet



air.
                             C-12

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     Boyde, et al. (1965)  measured the unsaturated aldehyde



fraction in raw cocoa beans and chocolate liquor.  The 2-



enols were measured by absorbance (at 373 nm) of its 2,4-



DNP derivative.  Samples were extracted with hexane and



cleaned on Celite prior to the derivatization.  The 2,4-



DNP derivatives were separated into fractions prior to mea-



surement.  They measured 2-enol concentrations of 0.6 to



2.0 jumoles/100 g fat in raw cocoa beans and 1.3 to 5.3 jumoles/



100 g in the chocolate liquor.



     Alcoholic beverages often contain trace amounts of



acrolein (Rosenthaler and Vegezzi, 1955).  It sometimes



is a problem since it causes an organoleptic condition called



"pepper" by the alcohol fermentation industry.  As a means



of controlling the "pepper" character, acrolein production



has been investigated.  According to Serjak, et al. (1954)



acrolein is detectable in low-proof whiskey at concentrations



as low as 10 mg/1.  This value probably represents the upper



limit for acrolein, since industry adapts corrective procedures



to reduce "pepper" by reducing acrolein concentration.



     The chief pathway for acrolein entry to the alcohol



has been delineated as mash fermentation  (Serjak, et al.



1954; Sobolov and Smiley, 1960; Hirano, et al. 1962).  When



glucose levels in the mash are low, some bacterial strains



convert glycerol to acrolein.



     Avent  (1961) investigated the contamination of a wine



with 14 pg/g of acrolein, which was initially acrolein-free.



The possible source was a glycerol-impregnated oak cask.



     Hrdlicka, et al.  (1968) identified acrolein in the



volatile fraction of a hops sample.  No quantitative data
                             C-13

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were available.
     Alarcon  (1976a) has demonstrated the formation of acrolein
from methionine, homoserine, homocysteine, cystathionine,
spermine, and spermidine under conditions similar to those
used in food processing  (neutral pH, 100C).
     The information reviewed herein is insufficient to
develop a conclusive measure of acrolein exposure in food,
but it indicates that acrolein is a component of many foods.
Processing can increase the acrolein content. Volatile frac-
tions collected during cooking suggest that some acrolein
would remain  in the food.  Based upon organoleptic factors,
it is probably reasonable to assume that acrolein would
seldom exceed 10 mg/1, if it were present.
     A bioconcentration factor (BCF) relates the concentration
of a chemical in water to the concentration in aquatic organ-
isms, but BCF's are not available for the edible portions
of all four major groups of aquatic organisms consumed in
the United States.  Since data indicate that the BCF for
lipid-soluble compounds is proportional to percent lipids,
BCF's can be  adjusted to edible portions using data on per-
cent lipids and the amounts of various species consumed
by Americans.  A recent survey on fish and shellfish comsump-
tion in the United States (Cordle, et al. 1978) found that
the per capita consumption is 18.7 g/day.  From the data
on the 19 major species identified in the survey and data
on the fat content of the edible portion of these species
(Sidwell, et  al. 1974) , the/relative consumption of the
four major groups and the weighted average percent lipids
for each group can be calculated:

                             C-14

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                          Consumption       Weighted Average
          Group            (Percent)          Percent Lipids
Freshwater fishes             12                  4.8
Saltwater fishes              61                  2.3
Saltwater molluscs             9                  1.2
Saltwater decapods            18                  1.2
Using the percentages for consumption and lipids for each
of these groups, the weighted average percent lipids is
2.3 for consumed fish and shellfish.
     A measured steady-state bioconcentration factor of
344 was obtained for acrolein using bluegills containing
about one percent lipids (U.S. EPA, 1978).  An adjustment
factor of 2.3/1.0 = 2.3 can be used to adjust the measured
BCF from the 1.0 percent lipids of the bluegill to the 2.3
percent lipids that is the weighted average for consumed
fish and shellfish.  Thus, the weighted average bioconcentra-
tion factor for acrolein and the edible portion of all aquatic
organisms consumed by Americans is calculated to be 344
x 2.3 = 790.
Inhalation
     Acrolein inhalation occurs through many exposure routes.
Acrolein is generated during oxidation of a variety of organic
substrates.  It has been noted as a combustion product of
fuels and of cellulosic materials  (e.g., wood and cigarettes),
as an intermediate product in atmospheric oxidation of propy-
lene, and as a component of the volatiles produced by heating
organic substrates.  Actual exposure will depend on general
environmental conditions and specific behavior patterns.
Total inspiration is the sum of acrolein inhalations from
                             C-15

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the ambient air, from local air (e.g., occupational considera-



tions, vehicular considerations, side-stream smoke from



cigarettes) and from cigarette smoke.



     Acrolein is a component of the urban smog; its concentra-



tion has been measured in Los Angeles atmosphere  (Renzetti



and Bryan, 1961; Altshuller and McPherson, 1963).  Renzetti



and Bryan collected ambient air in 1960 using a series of



vapor traps containing SD-3A alcohol and quantified acrolein



by absorbance of the 4-hexylresorcinol-mercuric chloridetri-



chloroacetic acid derivative (605 nm). Altshuller and McPherson



(1963) also examined the atmosphere in 1961, but collected



samples in bubblers containing the 4-hexylresorcinbl reagent.



Similar results were obtained with both studies.  For ten



days during a September-October-November period acrolein



averaged 0.012 mg/m  with a peak concentration of 0.025 mg/m  .



Acrolein concentration for seven days of this period in



1961 averaged 0.018 mg/m  and peaked at 0.030 mg/m .  For



all 1961 acrolein averaged 0.016 mg/m  and peaked at 0.032 mg/m .



     Graedel, et al. (1976) developed a mathematical model



for photochemical processes in the troposphere.  They combined



chemical kinetic measurements and assumed values, time-varying



sources of trace contaminants, solar flux variations, bulk



air flow, and a geographical matrix of "reaction volumes"



for Hudson County, N.J.  Their computed peak acrolein concen-



tration was 0.03 mg/m  .  They did not account for other



sources of acrolein or for any degradation pathway (McAfee



and Gnanadesikan, 1977).  That their calculated value favorab-



ly compared with the peak values measured in Los Angeles



(0.025 to  0.032 mg/m3) could be an artifact.
                             C-16

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     Trattner, et al. (1977) suggested that enols are present
in the air of a subway system.  They were measuring airborne
particulates by an infrared technique.  Samples were collected
on a cascade impactor system containing a 0.313 u back-up
filter.  Potassium bromide pellets were prepared from each
sample fraction.  Evidence for the unsaturated aldehyde
assignment were weak maxima observed at 1,695 cm    (6.90 u)
in the pellets prepared from final inpactor and backup filter
samples.  They made no quantitative assessment.
     Acrolein is a common constituent of vehicle exhaust
(Natl. Acad. Sci. 1976; Tanimoto and Uehara, 1975).  The
exact concentration depends upon the type of gasoline, eng-
ine, and operating conditions.  Acrolein concentrations
have been measured' by a variety of methods and the  consensus
of the studies suggests that the acrolein concentration
usually does not exceed 23 mg/m .  It has been measured
in diesel engines at 6.7 mg/m  and in internal combustion
engines at 6.0, 22.5,  16.1,  14.7, and about 11.5  mg/m
(Natl. Acad. Sci. 1976).  Day, et al. (1971) reported acro-
lein in emissions from a 1969 Chevrolet truck operated on
a dynamometer.  Acrolein was measured (by the colorimetric
2,4-DNP method) as 0.05 mg/m3 for hot idle, 6.4 mg/m3 at
30 mph, and 4.4 mg/m  at 50 mph.
     Bellar and Sigsby  (1970) developed a GC unit which
trapped organic substrates from air directly onto a GC cutter
column  (ten percent sucrose octaacetate on Gas-Chrorn Z)
at -55C and then injected the sample onto the analytical
column.  Their unit was capable of measuring acrolein in
the subpart per million range.  The unit was applied in

                             C-17

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measuring diesel exhaust, ambient air  in an area of  traffic
and ambient air in open  field.  Diesel exhaust contained
12.4 mg/m  acrolein.  No acrolein was  detected in  the open
field sample and, at most, a  trace was present in  the sample
from the area of traffic.
     Cigarette smoking produces acrolein.  While a cigarette
smoker directly inspires acrolein, some questions  exist
on passive exposure of non-smokers to  acrolein, from side-
stream smoke (Kusama, et al.  1978; Horton and Guerin, 1974;
Jermini, et al. 1976; Weber-Tschopp, et al. 1976a).
     Horton and Guerin  (1974) measured acrolein content
of cigarettes by cryogenic trapping smoke onto a gas chromato-
graphy column.  A six-part smoking machine was used  with
puff set at one-minute intervals, two-second durations,
and 35 ml volume.  Measured acrolein content for the tested
cigarettes is described  in Table 4.
     Hoffman, et al.  (1975) measured acrolein in marijuana
and tobacco cigarettes using  gas chromatography. Cigarettes
were rolled to 85 nun  length using standard cigarette paper.
Experimental details  were incomplete.  Hoffman, et al.  (1975)
stated that smoking machines  (1 or 20  channel) were  employed
and contained ten or  fewer cigarettes.  Error was  placed
at +4 to 6 percent.   They reported acrolein delivery from
mainstream smoke was  92  ug from marijuana cigarettes and
85 ug from tobacco cigarettes.
     The potential exposure of non-smokers to side-stream
and exhaled cigarette smoke is an unresolved question.
Holzer, et al.  (1976) suggested that passive exposure to
cigarette smoke is not  important, while Swiss workers  (Weber-
                             C-18

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                                TABLE 4

           Acrolein Delivery from some Experimental and some
            Commercial Cigarettes (Horton and Guerin, 1974)
Cigarette
                                       Acrolein Delivery
jjg/cig. ug/puff jug/g tobacco burned
Kentucky Reference (IRI)
Commercial 85 mm, filtered
Commercial 85 mm, non-filtered
Experimental 85 mm, charcoal
filtered
Experimental 85 mm (same as
above) , no-charcoal
Commercial 85 mm, little cigar
Experimental 85 mm, marijuana
128
102
111
62
103
70
145
12
10
12
7
12
8
14
159
153
135
97
155
107
199
                                 C-19

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Tschopp, et al. 1976b; Jermini, et al. 1976) have offered
evidence that passive exposure is an important inhalation
route.
     Holzer, et al.  (1976) developed an absorption tube
sampling method to collect organic materials (volatiles
and "particulate matter associated").  The tubes  (88 mm
x 2.5 mm ID) were packed with Tenax GC or Carbopack BHT.
These tubes had an uncertain capacity for substances of
lower retention than benzene, including acrolein, so their
results were only qualitative for acrolein.  The sample
tubes were directly desorbed and analyzed by GC-MS (mass
spectral detection) using a glass capillary column.  They
compared the GC chromatograms of a sample of urban air  (3.5
liter samples at 220 ml/min), a standard cigarette (IRI,
University of Kentucky) (3 ml of smoke taken during a puff
of two-second duration and 35 ml volume), and air where
a cigarette had been smoked under standard conditions  (same
sampling conditions as for urban air).  They suggested that
the volatiles in both air samples were associated with gasoline
vapors and that cigarette smoking did not appreciably add
to these volatiles.  The journal editor disagreed and in
a footnote stated that the chromatograms suggested "a person
breathing in a room where one cigarette was smoked inspires
the equivalent of a 3.5 ml puff of cigarette smoke."
     The Swiss team  (Jermini, et al. 1976; Weber-Tschopp,
et al. 1976b) measured acrolein concentration from cigarettes
 (U.S.) in side-stream smoke within a nearly air-tight, 30-
m  climatic room and in a 272-liter plexiglass chamber.
Acrolein was measured by gas chromatography. They reported
acrolein concentrations as follows:  in the 30-m  room,
                             C-20

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0.11 mg/m  and 0.87 mg/m  with 5 and 30 cigarettes, respect-
ively; and in the chamber, 0.85 mg/m  for one cigarette.
These results suggested that inhalation of significant quanti-
ties of acrolein can result from passive exposure to side-
stream smoke.
     Acrolein has been identified as a component in smoke
from wood burning.  Its detection in wood smoke at commercial
smoke houses  (Love and Bratzler, 1966) was discussed in
the "Ingestion from Food" section.  Bellar and Sigsby  (1970)
studied volatile organics by GC  (see above) in emissions
from a trench incinerator burning wood.  They published
chromatograms for the wood smoke emissions but did not present
quantitative data.  The acrolein peak was present in the
chromatogram for wood smoke from the incinerator without
forced air.  With forced air, the chromatogram did not contain
a peak for acrolein and the peaks for carbonyl compounds
were lower than those for alcohols.
     Hartstein and Forshey (1974) measured combustion products
from burning four classes of materials:  polyvinyl chloride,
neoprene, rigid urethane foams, and treated wood.  The materi-
als were burned by two techniques:  a sealed system  (approxi-
mately 370C) and a stagnation burner  (approximately 400C).
Condensible products were collected in a liquid nitrogen
trap and analyzed by GC  (thermal conductivity detection).
They noted that the acrolein concentrations measured were
less than the actual amount present, since the tars and
condensed water will retain some acrolein.  They never observed
acrolein in emissions from the PV, neoprene, and urethane
foam samples.  Acrolein was in emissions from all wood samples.
                             C-21

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Table 5 summarizes  their  results.
Dermal
     Based upon the physical properties and known distribution
of acrolein in the  environment, dermal exposure  is  judged
negligible.
                       PHARMACOKINETICS
Absorption
     Egle  (1972) has measured  the retention of inhaled acrolein
as well as formaldehyde and propionaldehyde in mongrel dogs
anesthetized with sodium  pentobarbital.  In this study,
dogs were exposed to acrolein  concentrations of  0.4 mg to
0.6 mg/1 for one to three minutes, and retention was calculated
using the amount inhaled  and the amount recovered.  In mea-
surements of total  respiratory tract rentention  at  ventilatory
rates between 6 and 20, 81 to  84 percent of acrolein was
retained.  An increase  in tidal volume  (from 100 ml to 160
ml) resulted in a significant  (p  0.001) decrease in acrolein
retention  (from 86  to 77  percent).  This was consistent
with finding that acrolein was taken up more readily by
the upper  than the  lower  respiratory tract.
Distribution
     No studies were found that were directly relevant to
the distribution of acrolein upon oral administration.
Munsch, et al.  (1974b)  have examined the incorporation of
tritiated  acrolein  in rats.  Rats were injected  (i.p.) with
acrolein at 3.36 mg/kg  70 hours after partial hepatectomy.
At 24 hours after injection, 88.66, 3.13,  1.72,  0.94, and
0.36 percent of the recovered  radioactivity was  found in
the acid-soluble, lipid,  protein, RNA, and DNA fractions
                             C-.22

-------
                           TABLE 5

     Acrolein Produced by Burning Standard Southern Pine
                (Hartstein and Forshey, 1974)
  Wood

Treatment
Acrolein Produced (mg/g wood burned)
               Sealed     Stagnation
                Tube        Burner
None

None

Pentachlorophenol

Creosote

Koppers fire retardent Type C

Koppers waterborne preservative
     CCA
                0.67

                0.62

                1.21

                0.43

              unknown


                0.47
0.21



0.70

0.59

0.22


0.68
                             C-23

-------
of the liver.  Based on measurements taken ten minutes  to
24 hours after dosing, the extent of RNA and DNA binding
remained relatively constant, while protein binding  increased
by about 70 percent.  In vitro studies on the binding of
acrolein to nucleic acids are discussed in the "Acute Effects
on Experimental System" section.
Metabolism
     In terms of the potential toxicologic effects of acrolein
in drinking water, the instability of acrolein at acid  pH's
(see "Ingestion from Water" section) may be highly significant.
As discussed by Izard and Libermann  (1978) and detailed
in the "Effects" section of this report, several of  the
toxic effects of acrolein are related to the high reactivity
of the carbon-carbon double bond.  However, the low  pH's
encountered in the upper portions of the gastrointestinal
tract would probably rapidly convert acrolein to saturated
alcohol compounds.  The primary breakdown product would
probably be beta propionaldehyde (see "Ingestion from Water"
section).  If this is the case, the  toxic effects of acrolein
given by oral administration would differ markedly from
the effects observed following other routes of administration.
No information is available on the toxic effects of  the
acrolein breakdown products.  However, an analysis of subchro-
nic and chronic studies suggest that acrolein is markedly
less toxic when given by oral administration than when  in-
haled  (see the "Basis and Derivation of Criterion" section).
     Relatively little direct information is available  on
the metabolism of acrolein.  Smith and Packer  (1972) found
that preparations of rat liver mitochrondria were capable
                             C-24

-------
of oxidizing several saturated aldehydes but not unsaturated
aldehydes such as acrolein, crotonaldehyde, and cinnamaldehyde.
Iri vitro, acrolein can serve as a substrate for alcohol
dehydrogenases from human liver, horse liver, and yeast
with equilibrium constants of 6.5 x 10~  , 8.3 x 10~   ,
and 16.7 x 10   M, respectively (Pietruszko, et al. 1973).
As cited above, jji vivo studies in rats indicate that  a
portion of subcutaneously administered acrolein is converted
to 3-hydroxypropylmercapturic acid (Kaye and Young, 1972;
Kaye, 1973).  Acrolein has also been shown to undergo  both
spontaneous and enzymatically catalyzed conjugation with
glutathione  (Boyland and Chasseaud, 1967; Esterbauer,  et
al. 1975).
     Alarcon  (1964, 1970) has demonstrated that acrolein
is formed during the degradation of oxidized spermine  and
spermidine.  Serafini-Cessi  (1972) has shown that acrolein
is a probable metabolite of allyl alcohol.  Several investiga-
tors have demonstrated that acrolein is a metabolite of
the anti-tumor agent cyclophosphamide  (Alarcon, 1976b; Alarcon
and Meienhofer, 1971; Alarcon and Melendez, 1974; Alarcon,
et al. 1972; Conners, et al. 1974; Cox, et al. 1976a,b;
Farmer and Cox, 1975; Gurtoo, et al. 1978; Hohorst, et al.
1976; and Thomson and Colvin, 1974.)
Excretion
     In rats given single subcutaneous injections of acrolein,
10.5 percent of the administered dose was recovered in the
urine as 3-hydroxypropylmercapturic acid after 24 hours
(Kaye and Young, 1972; Kaye, 1973) .
                               C-25

-------
                           EFFECTS



Acute, Sub-acute, and Chronic Toxicity



     Acute Effects on Experimental Systems:  Several  investi-



gators have described the gross toxic effects of acute lethal



exposure to acrolein on  experimental mammals  (Boyland, 1940;



Carl, et al. 1939; Carpenter, et al. 1949; Skog, 1950; Smyth,



et al. 1951; Pattle and  Cullumbine, 1956; Philippin,  et



al. 1969; Salem and Cullumbine, 1960).  Albin  (1962)  has



summarized some of these earlier studies as well as unpub-



lished reports  (Table 6).  Skog (1950) compared the patho-



logical effects of acute lethal subcutaneous and inhalation



exposures to acrolein in rats.  After inhalation exposures,



the rats evidenced pathological changes only in the lungs.



These changes included edema, hyperemia, hemorrhages, and



possible degenerative changes in the bronchial epithelium.



Similar changes have been noted in mice, guinea pigs, and



rabbits  (Pattle and Cullumbine, 1956; Salem and Cullumbine,



1960).  After administering lethal subcutaneous doses of



acrolein to rats, Skog  (1950) noted less severe lung  damage



(edema without significant hemorrhaging) but also  found



pathological changes in  the liver  (hyperemia and fatty degen-



eration) and kidneys  (focal inflammatory changes).



     Given the probable  instability of acrolein on oral



administration, a quantitative comparison of oral  exposure



with other routes would  be of particular interest.  In a



study by Carl, et al.  (1939), rats given intraperitoneal



injections of acrolein at 2.5 mg/kg/day died on the second



day.  Single doses of 10 mg/kg given to two rats by stomach



tube killed both within  24 hours.  However, six rats  tolerated
                             C-25

-------
                    TABLE 6



Acute Lethal Toxicity of Acrolein  (Albin, 1962)
Species
Mouse
Mouse
Dog
Rat
Rat
n Rat
^j Mouse
Rabbit
Rabbit
Rabbit
Rabbit
Rabbit
Rabbit
Route
Inhalation
Inhalation
Inhalation
Inhalation
Oral
Oral
Oral
Percutaneous
Percutaneous .
Percutaneous
Percutaneous
Percutaneous
Percutaneous
Ex?:r
LCcQ-875 ppm 1 min
LC50-175 ppm 10 min
LC5Q-150 ppm 30 min
LCcQ-8 ppm 4 hr
LD5Q-46 mg/kg
LD5Q-42 mg/kg
LD5Q-28 mg/kg
LD5Q-200 mg/kg
LDcQ-562 mg/kg " " *
LD5Q-335 mg/kg
LD5Q-1022 mg/kg
LD5Q-164 mg/kg
LD5Q-238 mg/kg
Remarks
Approximate value
Approximate value
Approximate value
Approximate value
Approximate value



Undiluted acrolein
20% acrolein in water
10% acrolein in water
20% acrolein in mineral
10% acrolein in mineral












spirits
spirits

-------
doses of 5 mg/kg/day given by stomach tube for nine days.
Although firm conclusions cannot be made from this limited
data/ these results suggest that acrolein has a greater
acute lethal potency when administered intraperitoneally
than when given orally.
     The sublethal effects of acute acrolein exposure on
the liver have received considerable investigation.  In adult
male rats, inhalation exposures to acrolein or intraperitoneal
injections of acrolein cause increases in hepatic alkaline
phosphatase activity as well as increases in liver and adrenal
weights.  These effects, however, occurred only in exposures
causing dyspnea and nasal irritation (e.g., 4.8 mg/m  x
40 hours).  Other hepatic enzyme activities - acetylcholine
esterase and glutamic-oxalacetic transaminase - were not
affected.  Since similar patterns were seen with other res-
piratory irritants, the alkaline phosphatase response was
attributed to an alarm reaction rather than specific acrolein-
induced liver damage  (Murphy, et al. 1964).  In subsequent
studies  (Murphy, 1965; Murphy and Porter, 1966) , the effect
of acrolein on liver enzymes was linked to stimulation of
the pituitary-adrenal system resulting in hypersecretion
of glucocorticoids and increased liver enzyme synthesis.
Although these results do not suggest that acrolein is a
direct liver toxin, Butterworth, et al.  (1978) have shown
that intravenous infusions of acrolein at doses of 0.85
and 1.70 mg/kg induce periportal necrosis in rats.  In
further studies on the adrenocortical response of rats to
acrolein, Szot and Murphy  (1970) demonstrated increased
plasma and adrenal corticosterone levels in rats given
                            C-28

-------
intraperitoneal injections of acrolein.  Unlike similar effects
caused by DDT and parathion, the effect of acrolein was
not blocked by subanesthetic doses of phenobarbital and
was blocked by dexamethasone only at lower doses of acrolein.
The degree of increased corticosterone levels is dependent
on the state of the adrenocortical secretory cycle in which
acrolein as well as other toxins are administered (Szot
and Murphy, 1971).
     Since acrolein is a component of cigarette smoke, the
sublethal effects of acrolein on the respiratory system
have been examined in some detail.  Murphy, et al. (1963)
found that inhalation of acrolein at concentrations of 0.92
to 2.3 mg/m  for periods of up to 12 hours caused dose-related
increases in respiratory resistance, along with prolonged
and deepened respiratory cycles in guinea pigs.  In tests
on guinea pigs exposed to whole cigarette smoke from various
types of cigarettes, Rylander (1973) associated concentra-
tions of acrolein and acetaldehyde with decreases in the
number of free macrophages.  Mice exposed to acrolein in
air at concentrations of 2.3 to 4.6 mg/m  for 24 hours evi-
denced decreased pulmonary killing of Staphylococcus aureus
and Proteus mirabilis.  This decrease in intrapulmonary
bacterial killing was aggravated in mice with viral pneumonia
(Jakab, 1977).  Kilburn and McKenzie  (1978) have shown that
inhalation of acrolein  (13.8 mg/m  x 4 hours) is cytotoxic
to the airway cells of hamsters, causing both immediate
and delayed exfoliation.  When administered with or adsorbed
onto carbon particles, acrolein induced leukocyte recruitment
to the airways, mimicking the effect of whole cigarette
                              C-29

-------
smoke.  In single ten-minute inhalation exposure to mice,



acrolein caused dose-related decreases in respiration attri-



buted to sensory irritation, with an EC5Q of 3.9 mg/m   (Kane



and Alarie, 1977).  Formaldehyde causes the same effect



and exhibits competitive agonism in combination with acrolein



(Kane and Alarie, 1978).



     Acrolein has been shown to exert pronounced ciliastatic



activity in a variety of aquatic invertebrates  (see review



by Izard and Libermann, 1978).  As discussed by Wynder,



et al.  (1965) , impairment of ciliary function in the respira-



tory tract of mammals may be involved in the pathogenesis



of several respiratory diseases, including cancer.  Of several



respiratory irritants examined by Carson, et al. (1966),



acrolein was the most effective in reducing mucus flow rates



in cats after short-term inhalation exposures.  In in vivo



assays of chicken trachea ciliary activity, acrolein and



hydrogen cyanide were found to be among the most potent



ciliatoxic components of cigarette smoke (Battista and Kensler,



1970).  Similarly, in tests on various types of cigarette



smoke, Dalhamn (1972) associated ciliastasis in cats with



variations in the concentrations of acrolein and tar.



     In in vitro studies on the effects of cigarette smoke



components on rabbit lung alveolar macrophages, acrolein



has been shown to inhibit phagocytosis, adhesiveness, and



calcium-dependent ATP-ase activity  (Low, et al. 1977) and



to inhibit the uptake of cycloleucine and  -aminoisobutyrate



but not 3-0-methyglucose (Low and Bulman, 1977).  However,



acrolein has been shown to inhibit the uptake of glucose



by rabbit erythocytes  (Riddick, et al. 1968).



     Egle and Hudgins  (1974) noted that low doses (0.05 mg/kg)





-.   . .                 J       030

-------
of acrolein administered by intravenous injection to the
rat caused an increase in blood pressure but that higher
doses (0.5 to 5.0 mg/kg) caused marked decreases in blood
pressure and bradycardia..  The pressor response was attributed
to increased catecholamine release from sympathetic nerve
endings and the adrenal medulla, while the depressor response
was attributed to vagal stimulation.  Similar effects were
noted- in one-minute inhalation exposures to acrolein in
which concentrations of 2.5 and 5.0 mg/1 induced depressor
effects.  Acrolein elicited significant cardiovascular effects
at concentrations below those encountered in cigarette smoke.
Basu, et al. (1971) have also examined the effects of acrolein
on heart rate in rats.  Tachycardia was induced in animals
under general (sodium pentobarbital) anesthesia, while brady-
cardia was induced in animals receiving both general anesthesia
and local ocular anesthesia (2 percent tetracain hydrochloride)
prior to acrolein exposure.  Pretreatment with atropine
(0.5 mg/kg i.v.) along with local and general anesthesia
blocked the bradycardic response.  Tachycardia was attributed
to increased sympathetic discharge caused by eye irritation.
Since the bradycardic response was blocked by atropine,
parasympathetic involvement was suggested.
     Several groups of investigators have examined the gen-
eral cytotoxic effects of acrolein.  Alarcon  (1964) determined
the inhibitory activities of spermine, spermidine, and acro-
lein to S-180 cell cultures.  The concentrations of these
compounds causing 50 percent inhibition were 1.4 to 1.5
x 10"  m moles/ml for spermine, 2.8 to 3.1 x 10~  m moles/ml
for spermidine, and 2.6 to 3.5 x 10~  m moles/ml for acrolein.
                             C-31

-------
Since the inhibitory potencies of these compounds were similar
and since only the two amines required amine oxidase in
                          /"
exerting the inhibitory effect, Alarcon (1964) proposed
that the inhibitory activity of the two amines was due to
the in vitro formation of acrolein.  Two groups of investi-
gators have examined the role of acrolein in the virucidal
effects of oxidized spermine (Bachrach, et al. 1971; Bachrach
and Rosenkovitch, 1972; Nishimura, et al. 1971, 1972).
Both groups determined that the antiviral potency of acrolein
was substantially less than that of oxidized spermine and
that the antiviral effects of oxidized spermine are not
attributable to the generation of acrolein.
     Koerker, et al. (1976) have examined the cytotoxicity
of acrolein and related short-chain aldehydes and alcohols
to cultured neuroblastoma cells.  Aldehydes were consistantly
more toxic than the corresponding alcohols.  Based on viabil-
ity of harvested cells and increase in the number of sloughed
cells after exposure, acrolein was more potent than formalde-
hyde, and much more potent than acetaldehyde, or propionalde-
hyde.  Based on decreases in neurite formation and viability
of sloughed cells, formaldehyde was somewhat more potent
than acrolein and substantially more potent than either
acetaldehyde or propionaldehyde.  In j.n vitro tests on Ehrlich-
Landschutz diploid ascites tumor cells, Holmberg and Malmfors
(1974) found acrolein to be substantially more toxic than
formaldehyde over incubation periods of one to five hours.
Both of these aldehydes, however, were among the more toxic
organic solvents assayed in this study.  Similarly, in J.TI
vitro tests of tobacco smoke constituents on mice ascites
                              C-32"

-------
sarcoma BP8 cells  (48-hour exposure periods)/ Pilotti,  et
al. (1975) found aldehydes to be among the most  toxic group
of compounds studied.  At a concentration of 100 juM, acrolein
caused substantially greater inhibition  (94 percent) than
formaldehyde (15 percent).
     Several of the cytotoxicity studies on acrolein have
addressed the role of acrolein in the antineoplastic effects
of cyclophosphamide.  Sladek (1973) determined  the  cytotoxic
activities of cyclophosphamide and various cyclophosphamide
metabolities, including acrolein, to Walker 256  ascites
cells.  In this study, ascites cells were exposed to the
various compounds  in vitro for one hour, then injected  into
host rats.  The proportion of viable ascites cells  was  esti-
mated from survival times of the rats.  Based on this assay,
acrolein was found to be only marginally cytotoxic  (LCgQ
of 8.75 juM) and did not account for a substantial proportion
of the cytotoxicity of cyclophosphamide metabolites generated
iH ZJLZ2*  Cyclophosphamide itself was virtually  non-toxic
 (LCg0 of  > 100 /iM).  Similar results on the cytotoxicity
of acrolein to Walker ascites cells was obtained by Phillips
 (1974) using an in vitro test system in which cells were
exposed to cytotoxic agents for one hour, then  transfered
to fresh culture medium.  Cytotoxicity was expressed as
a 72-hour ICcQ - the exposure concentration causing a 50
percent decrease in cell number compared to untreated cells
72 hours after treatment.  The ICcn for acrolein was 1.0
>ug/ml  (approximately 18 uM) and the IC5Q for cyclophosphamide
was 6,000 /ig/ml.   Lelieveld and Van Putten  (1976) measured
the cytotoxic effects of cyclophosphamide and six possible
metabolites, including acrolein, to normal hematopoietic
                             C-33

-------
stem cells of mice, osteosarcoma cells, and L1210 leukemia
cells.  Acrolein was inactive against normal hematopoietic
stem cells and osteosarcoma cells, and less active than
cyclophosphamide against leukemia cells.  Similarly, Brock
(1976) has found that acrolein is less active than cyclophos-
phamide against Yoshida ascitic sarcoma of the rat.
     The cytotoxic effects of acrolein may be attributed,
at least in part, to direct damage of nucleic acids or im-
paired nucleic acid or protein synthesis.  Using primary
cultures of mouse-kidney tissue exposed to a total of 70
ug acrolein, Leuchtenberger, et al.  (1968) noted a progres-
sive decrease in the uptake of tritiated  uridine, decreased
RNA, and pycnosis of cell nuclei.  Similarly, in cultures
of polyoma-transformed cells from cell lines of Chinese
hamsters exposed to acrolein at concentrations of 0.8 to
2.5 x 10~  M for one hour, Alarcon (1972) found concentra-
tion-related decreases in the uptake of tritiated uridine,
tritiated thymidine, and tritiated leucine.  Using similar
methods, Kimes and Morris (1971) have also demonstrated
inhibition of DNA, RNA, and protein synthesis by acrolein
in Escherichia coli.
     In in vitro studies on the kinetics  of acrolein inhibi-
tion of rat liver and E. coli RNA polymerases, Moule, et
al.   (1971) found that inhibition was unaffected by the
amount of DNA in the medium but was partially offset by
increased levels of RNA polymerase, suggesting that acrolein
acts on RNA polymerase rather than DNA.   In parallel studies
on rat liver and E. coli DNA polymerase,  Munsch, et al.
(1973) noted that acrolein inhibited rat  liver DNA polymerase
but stimulated E. coli DNA polymerase.  Since the active

                             C-34

-------
site of rat liver DNA polymerase is associated with a functional
sulfhydryl group but E. coli DNA polymerase is not; and
since acrolein's inhibitory effect on rat liver DNA polymerase
could be antagonized by 2-mercaptoethanol (see the "Synergism
and/or Antagonism" section), these investigators concluded
that acrolein acts on rat liver DNA polymerase by reacting
with the sulfhydryl group.  Subsequently, Munsch, et al.
(1974a) demonstrated that tritiated acrolein binds 20 to
30 times more to rat liver DNA polymerase than to E. coli
DNA polymerase.  In partially hepatectomized rats given
intraperitoneal injections of acrolein at doses of 0.1 to
2.7 mg/kg, DNA and RNA synthesis was inhibited in both the
liver and lungs (Munsch and Frayssinet, 1971).
     Subacute Toxicity to Experimental Mammals:  Most studies
on the subacute toxicity of acrolein have involved inhala-
tion exposures.  In one-month inhalation exposures of rats
to acrolein at a concentration of 1.2 mg/m , Bouley  (1973)
noted decreases in growth rates and in the levels of oxida-
tion-reduction coenzymes in the liver  (additional details
not given).  Rats continously exposed to acrolein in the
air at a concentration of 1.27 mg/m  for up to 77 days evi-
denced decreased food intake accompanied by decreased body
weight gain.  Between days 7 and 21 of exposure, animals
evidenced nasal irritation.  Changes in relative lung and
liver weights, as well as serum acid phosphatase activity,
are summarized in Table 7.  Respiratory tract irritation,
a decrease in the number of alveolar macrophages, and in-
creased susceptibility to respiratory infection by Salmonella
enteritidis were noted only during the first three weeks
                            C-35

-------
of exposure  (Bouley, et al. 1975, 1976).  Philippin, et
al. (1969) also noted decreased body weight in mice exposed
to acrolein  in the air at concentrations of 13.8 mg/m  and
34.5 mg/m ,  six hours per day, five days per week, for six
weeks.  Although the decreased body weight was significant
(p  0.01), the extent of the decrease was neither substantial
(approximately six percent) nor dose-related.
     Lyon, et al.  (1970) exposed rats, guinea pigs, monkeys,
and dogs  to  acrolein concentrations of 1.6 and 8.5 mg/m
in the air for eight hours per day, five days per week,
for six weeks.  In addition, continuous exposures were con-
ducted at 0.48, 0.53, 2.3, and 4.1 mg/m  for 90 days.  The
following biological end points were used to assess the
effects of exposure:  mortality, toxic signs, whole body
weight changes, hematologic changes (hemoglobin concentration,
hematocrit,  and total leukocytes), biochemical changes (blood
urea nitrogen, alanine and aspartate aminotransferase activi-
ties) , and pathological changes in heart, lung, liver, spleen,
and kidney.  No gross effects were noted in the continuous
exposures to 0.48 and 0.53 mg/m  or in the repeated exposures
to 1.6 mg/m  acrolein.  In continuous exposures to 2.3 and
4.1 mg/m  and in repeated exposures to 8.5 mg/m , dogs and
monkeys displayed signs of eye and respiratory tract irritation
and rats  evidenced decreased weight gain.  All animals exposed
repeatedly to 1.6 mg/m  acrolein developed chronic inflammatory
changes of the lung.  These changes were more pronounced
in dogs and monkeys than in rats and guinea pigs.  At 8.5
mg/m  squamous metaplasia and basal cell hyperplasia of
the trachea from dogs and monkeys were attributed to acrolein
                             C-36

-------
                                             TABLE 7

                   Relative Weights  of  Lungs  and Liver, and Serum Level of Acid
                        Phosphatases (n = number of rats, m = mean value,
                         s.d.  =  standard  deviation)  (Bouley,  et al.  1976)
       Parameters
                                    Time
Control rats
Test rats  Statistical analysis
lungs weight x 100

body weight
                             15th and 32nd days  no significant difference between 2 x 10 control
                                                                and 2 x 10 test rats
                                   77th day
                                                        n = 10
                                                        m = 0.489
                     n = 15
                     m = 0.588
                  t  =  2.67
                0.02>P>0.01
n .
i
u>
liver weight x 100
body weight
s.d. =
15th day n =
m =
s.d. =
0.087
10
5.00
0.14
s.d.
n
m
s.d.
= 0.111
= 10
= 4.55
= 0.14

t
0

= 7.12
.001>P
                                32nd and 77 days  no significant difference between 10 and 15
                                                         control, and 10 and  15 test  rats
mU of acid phosphatases
per ml of serum
                                   15th day
    n = 10
    m = 77.87
 s.d. = 10.59
   n =  10
   m =  62.11
s.d. =  6.72
t = 3.91
P = 0.001
                              32nd and 77th days  no significant differences between 10 and 11
                                                         control, and 10 and 11 test rats

-------
.  exposure.  In addition,  this exposure induced necrotizing
  bronchitis and bronchiolitis with squamous metaplasia  in
  the lungs of seven of nine monkeys.  Similar pathological
  results were noted in continuous exposures to 2.3 and  4.1
  rag/m .
       Feron, et al. (1978) exposed hamsters, rats, and  rabbits
  to acrolein vapor at concentrations of 0.4, 3.2, and 11.3
  mg/m  six hours per day, five days per week, for 13 weeks.
  At the highest concentration, all animals displayed signs
  of eye irritation, decreased food consumption, and decreased
  weight gain.  In rats and rabbits, no abnormal hematological
  changes were noted.  Female guinea pigs at the highest dose,
  however, showed statistically significant increases in the
  number of erythrocytes,  pack cell volume, hemoglobin concen-
  tration, and the number  of lymphocytes and a decrease  in
  the number of neutrophilic leukocytes.  Additional changes
  noted in this study are  summarized in Table 8.
       Watanabe and Aviado (1974) have demonstrated that re-
  peated inhalation exposures of mice to acrolein  (100 mg/m
  for 30 minutes, twice a  day for five weeks) cause a reduc-
  tion in pulmonary compliance.
       The subacute oral toxicity of acrolein has been examined
  in less detail.  Albin  (1962) indicates that rats exposed
  to acrolein in drinking  water at concentrations up to  200
  mg/1 for 90 days evidenced only slight weight reduction
  at the highest level tested.  This was attributed to unpala-
  bility of the drinking water.  Similar results have been
  reported by Newell (1958)  (summarized in Natl. Acad. Sci.
  1977).  In one study, acrolein was added to the drinking
  water of male and female rats at concentrations of 5,  13,
                               C-38

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                                                TABLE 8

                   Summary of Treatment-Related Effects  in Hamsters, Rats and Rabbits
                    Repeatedly Exposed to Acrolein for  13 Weeks (Feron, et al. 1978)
o
i
OJ
vo
          Criteria
          affected
    Effects'
                                  Hamsters
                                  Acrolein  (ppm)
Rats
Acrolein (ppm)
Rabbits
Acrolein (ppm)

.Symptomatology
Mortality
Growth
Pood intake
Haematology
Urinary amorphous
material
Urinary crystals
Organ weights
Lungs
Heart
Kidneys
Adrenals
Gross pathology
Lungs
Histopathology
Nasal cavity
Larynx
Trachea
Bronchi + lungs
0.4
0
0
0
NE
0

0
0

0
0
0
0

0

0
0
0
0
1.4
X
0
0
NE
0

0
0

0
0
0
0

0

X
0
0
0
4.9
XXX
0

NE
X

+
-

++
+
+
0

0

XXX
X
XX
0
0.4
0
0
-
0
0

0
0

0
0
0
0

0

X
0
0
0
1.4 4.9
X XX
0 +++
	 	
_ 
0 0

0 +
0

0 ++
0 +
0 +
0 +++

0 x

XX XXX
0 xx
0 xxx
0 xxx
0.4.
0
0
0
0
0

0
0

0
0
0
0

0

0
NE
0
0
1.4
X
0
-

0

0
0

0
0
0
0

0

0
NE
0
0
4.9
xxx
0


0

+
0

++
0
0
0

0

XX
NE
X
XX
                  aO = not affected; x = slightly affected; xx = moderately  affected;
              xxx = severely affected; + = slightly increased; ++ = moderately  increased;
              +++ = markedly increased; - = slightly decreased; = moderately  decreased;
                              	 = markedly  decreased;  NE = not examined.

-------
32, 80, and 200 mg/1 for 90 days.  No hematologic, organ-
weight, or pathologic changes could be attributed to acrolein
ingestion.  At the highest concentration, water consumption
was reduced by one-third for the first three weeks.  By
the 12th week, the rats had apparently adapted to the odor
and taste of acrolein.  In a subsequent study, acrolein
was added to the drinking water of male rats at concentrations
of 600, 1,200, and 1,800 mg/1 for 60 days.  All animals
died at the two higher concentrations, and one of five animals
died at 600 mg/1 concentration.  Death was apparently due
to lack of water intake.  Tissues from the animals surviving
600 mg/1 did not show any gross or micropathologic abnor-
malities.
     Chronic Toxicity to Experimental Mammals:  The only
published chronic toxicity study on acrolein is that pre-
sented by Feron and Kruysse  (1977).  In this study, male
and female Syrian golden hamsters were exposed to acrolein
at 9.2 mg/m  in the air, seven hours per day, five days
per week, for 52 weeks.  During the first week of exposure,
animals evidenced signs of eye irritation, salivated, had
nasal discharge, and were very restless.  These signs disap-
peared during the second week of exposure.  During the expo-
sure period, males and females had reduced body weight gains
compared  to the control animals but the survival rate was
unaffected.  Hematological changes - slight, but statistically
significant increased hemoglobin content and packed cell
volume - occurred only in females.  Similarly, significant
(p  0.05) decreases  in relative liver weights  (-16 percent)
and increases in lung weights  (+32 percent) occurred only
                               C-40

-------
in females.  In both sexes, pathologic effects included
inflammation and epithelial metaplasia in the nasal cavity.
No other pathological changes in the respiratory tract were
attributable to acrolein.
     Effects on Humans:  As summarized in Table 9, consider-
able information is available on the irritant properties
of acrolein to humans.  In studies on photochemical smog,
Altshuller (1978)  has estimated that acrolein could cause
35 to 75 percent as much irritation as formaldehyde,  Schuck
and Renzetti (1960) indicated that acrolein and formaldehyde
account for most of the eye irritation caused by the photooxi-
dation of various hydrocarbons.  Acrolein is also involved
in the irritant effect of cigarette smoke (Weber-Tschopp,
et al. 1976a,b, 1977).
     Relatively little information, however, is available
on the toxic effects of acrolein in humans.  Henderson and
Haggard (1943) state that vapor concentrations of 23 mg/m
are lethal in a short time.
     In a study on irritant dermatitis induced by diallyl-
glycol carbonate monomer, Lacroix, et al. (1976) conducted
patch tests on humans with acrolein.  In these tests, acrolein
solutions in ethanol caused no irritation at concentrations
(v/v) of 0.01 to 0.1 percent.  At a concentration of one
percent, six of 48 subjects evidenced a positive response
(two erythemas and four serious edemas with bullae).  At
a concentration of ten percent, all eight subjects evidenced
a positive response.  Histological findings of a second
series of tests with ten percent acrolein are summarized
in Table 10.

                             C-41

-------
                                                 TABLE 9

                                Irritant Properties of Acrolein to Humans
      Exposure
                                   Effect
                                              Reference
n
i
^
M
      0.58 mg/m  x 5 min.
      2.3 mg/m3 x 1 min.
      2.3 mg/m  x 2 to 3 min.

      2.3 mg/m  x 4 to 5 min.
4.1 mg/m3 x 30 sec.
4.1 mg/nu x 1.0 min.
4.1 mg/m  x 3 to 4 min.
      12.7 mg/m  x 5 sec.

      12.7 mg/nu x 20 sec,
      12.7 mg/m  x 1 min.
      50.1 mg/m  x  1 sec,

      0.48 mg/m3

      2.3  mg/m
      9.2  mg/m

      1.8  mg/m  x 10 min.
      2.8  mg/m  x 5 min.
moderate irritation of sensory
  organs

slight nasal irritation
slight nasal and moderate eye
  irritation
moderate nasal irritation and
  practically intolerable eye
  irritation

odor detectable
slight eye irritation
profuse lachrymation; practically
  intolerable

slight odor; moderate nasal and
  eye irritation
painful eye and nasal irritation
marked lachrymation; vapor prac-
  tically intolerable

intolerable

odor threshold

highly irritation
lacrimation

lacrimation within 20 seconds,
  irritation to exposed mucosal
  surfaces
lacrimation within 5 seconds,
  irritating to exposed mucosal
  surfaces
                                                                         Albin, 1962
                                                                         Reist and Rex, 1977

                                                                         Pattle and
                                                                           Cullumbine, 1956

                                                                         Sim and Pattle,
                                                                           1957

-------
                           TABLE 10

      Patch  Tests  with ten percent  Acrolein in Ethanol on
Control Subjects  (Biopsied at 48 Hours)  (Lacroix,  et  al.  1976)

CM
CM
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
No of Polymorph. Papillary
biopsy infiltrate edema
375 +++ ++
376 + ++
74 ++ ++
88 ++ ++
89 + +
90 + +
91 ++ +
178 . + +
179 + +
346 0 +
347 +++ +
348 ++ ++
Epidermis
0
necrosis
0
necrosis
0
necrosis
0
necrosis
necrosis
bullae
0
bullae
Result
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
                             C-43

-------
     Kaye and Young  (1974) have detected 3-hydroxypropylmer-
capturic in the urine of patients receiving cyclophospharaide
orally  (50 mg twice  or thrice daily) but not in the urine
of untreated humans.  Based on analogies to the metabolic
patterns of cyclophosphamide in rats, these investigators
concluded that acrolein is probably a metabolite of cyclophos-
phamide in man.
     In studies on human polymorphonuclear leukocytes  (PMN's),
Bridges, et al.  (1977) found that acrolein was a potent
in vitro inhibitor of PMN chemotaxis (EC5Q of 15 jam) but
had no significant effect on PMN integrity (measured by
beta-glucuronidase release, lactic acid dehydrogenase  release,
and cell viability)  or glucose metabolism  (measured by glucose
utilization, lactic  acid production, and hexose monophosphate
activity).  Cysteine, at a concentration of 10 mM, completely
blocked the inhibitory effect of 160 /am acrolein on PMN
chemotaxis.  These results are consistent with the assumption
that acrolein inhibits chemotaxis by reacting with one or
more essential thiol groups on cellular proteins involved
in chemotaxis.  These proteins, however, do not appear to
be involved in glucose metabolism.
     Schabort (1967) demonstrated that acrolein inhibits
human lung lactate dehydrogenase.  Inhibition appeared to
be non-competitive with respect to NADH and uncompetitive
with respect to pyruvate.
     Little information is available on the chronic effects
of acrolein on humans.  An abstract of a Russian study indi-
cates that occupational exposure to acrolein  (0.8 to 8.2
mg/m ), methylmercaptan  (0.003 to 5.6 mg/m ), methylmercaptor-

-------
propionaldehyde (0.1 to 6.0 mg/m ), formaldehyde  (0.05  to
8.1 mg/m ), and acetaldehyde (0.48 to 22 mg/m ) was associated
with irritation of the mucous membranes.  This effect was
most frequent in women working for less than one  and greater
than seven years (Kantemirova, 1975).
Synergism and/or Antagonism
     Acrolein is highly reactive with thiol groups.  Acrolein
rapidly conjugates with both glutathiohe and cysteine  (Ester-
bauer, et al. 1975, 1976).  Cysteine has been shown to  antago-
nize the cytotoxic effects of acrolein on ascites tumor
cells of mice (Tillian, et al. 1976).  Cysteine also antago-
nizes the inhibition of acrolein on rabbit alveolar macrophage
calcium-dependent ATPase, phagocytosis, adhesiveness  (Low,
et al. 1977).  Both cysteine and ascorbic acid have been
shown to antagonize the acute lethal effects of orally  admin-
istered acrolein in male rats (Sprince, et al. 1978).  Munsch,
et al. (1973, 1974a) have demonstrated that 2 mercaptoetha-
nol antagonizes the inhibitory effect of acrolein on rat
liver DNA polymerase.  The irritant effects of. acrolein
injected into the footpad of rats was blocked by  N-acetyl-
cysteine, penicillamide, glutathione,  2P-mercaptopropioriyl-
glycine,  2-mercaptoethanol, and ,^,^-dimethylcysteamine  (White-
house and Beck, 1975).
     The effects of acrolein, unlike those of DDT and para-
thion, on the adrenocortical response of rats is  not inhibited
by pretreatment with phenobarbital and is only partially
inhibited by dexamethasone (Szot and Murphy, 1970).
     Pretreatment of rats with acrolein (3 mg/kg  i.p.)
significantly prolongs hexobarbital and pentobarbital sleeping
time  (Jaeger and Murphy, 1973).
                             C-45

-------
Teratogenicity
     No reports have been encountered on the potential terato-
genicity of acrolein.
     Bouley, et al.  (1976) exposed male and female rats       ;
to 1.3 mg/m  acrolein vapor for 26 days and found no signifi-
cant differences  in  the  number of pregnant animals as well
as the number and mean weight of fetuses.
Mutagenicity
     In the dominant-lethal assay for mutagenicity in ICR/Ha
Swiss mice, acrolein did not cause a significant increase
in early fetal deaths or pre-implantation losses at doses
of 1.5 and 2.2 mg/kg given in single intraperitoneal injec-
tions to male mice prior to an eight-week mating period
(Epstein, et al.  1972).
     As summarized by Izard and Libermann  (1978), Rapoport
(1948) assayed several olefinic aldehydes for  their ability
to induce sex-linked mutations in Drosophila melanogaster.
Acrolein had the  highest activity, causing 2.23 percent
mutations  (15 mutations  among 671 chromosomes).
     Using a strain  of DNA polymerase deficient Escherichia
coli, Bilimoria  (1975) detected mutagenic activity in acrolein
as well as cigar, cigarette, and pipe smoke.   In a strain
of E. coli used for  detecting forward mutations  (from gal
Rs to gal  and from  5-methyltryptophan sensitivity to 5-
methyltryptophan  resistance) and reverse mutations  (from
arg" to arg ), acrolein  demonstrated no mutagenic activity
with or without activation by mouse liver homogenates  (Ellen-
berger and Mohn,  1976, 1977).
                             C~46

-------
     Bignami, et al. (1977) found that acrolein induced



mutagenic effects in Salmonella typhimurium strains TA1538



and TA98 (insertions and deletions), but showed no activity



in strains TA1535 or TAlOO (base-pair substitutions).  Anderson,



et al.  (1972) were unable to induce point mutations in eight



histidine requiring mutants of S. typhimurium.  This system



also gave negative results of 109 other herbicides but was



positive for three known mutagens:  diethyl sulfate, N-methyl-



N1-nitro-N-nitrosoguanidine, and ICR-191.



     Izard  (1973) determined the mutagenic effects of acrolein



on three strains of Saccharomyces cerevisiae.  In strain



N123, a histidine auxotroph, acrolein at 320 mg/1 induced



twice the control incidence of respiratory-deficient mutants.



In two methionine auxotroph haploid strains used to assay



for frameshift mutations and base-pair substitutions, acrolein



was inactive.  As discussed by Izard and Libermann  (1978),



these results suggest that acrolein is not a strong inducer



of respiratory deficient mutants and does not appear to



induce  frameshift mutations or base pair substitutions in



S. cerevisiae.  However, this lack of activity could be



due to  the high toxicity or instability of acrolein or to



the inability of these strains to convert acrolein to some



other active molecule.



Carcinogenicity



     Ellenberger and Mohn  (1976) indicated that acrolein



is "known as  (a) cytotoxic and carcinogenic compound."



The carcinogenicity of acrolein has not been confirmed in



our review of the literature.  In the chronic inhalation



study by Feron and Kruysse  (1977), summarized in the "Chronic
                             C-47

-------
Toxicity to Experimental Animals" section, acrolein gave
no indication of carcinogenic activity, had no effect on
the carcinogenic activity of diethylnitrosamine, and had
a minimal effect on the carcinogenic activity of benzo(o^)
pyrene.  Detailed tumor pathology from this study is pre-
sented in Table 11..  Based on these results, Feron and Kruysse
(1977) concluded that "...the study produced insufficient
evidence to enable acrolein to be regarded as an evident
cofactor in respiratory tract carcinogenesis."  Similar
results have been obtained in a not yet published bioassay
sponsored by the National Cancer Institute  (1979).  In this
study, hamsters were exposed to 11.5 mg/m  acrolein vapor,
six hours per day, five days per week, throughout their
lifespan.  No evidence was found that acrolein was a carcin-
ogen or a cocarcinogen with either benzo(o.)pyrene or ferric
oxide.  DiMacco (1955) summarizes a study by Savoretti (1954)
indicating that acrolein resulted in an increase in the
incidence of benzopyrene-induced neoplasms.  This summary
does not provide information on the species tested, doses,
routes of administration, or the significance of the observed
increase.
     Boyland  (1940) found that acrolein, at daily oral doses
of 0.25 mg/mouse, had a marginal (p<0.1) inhibitory effect
on the growth of spontaneous skin carcinomas and a signifi-
cant  (p<0.05)  inhibitory effect on the growth of grafted
sarcomas.
                             C-48

-------
                                    TABLE 11
Site, Type, and Incidence of Respiratory Tract Tumors in Hamsters Exposed  to Air
               or Acrolein Vapor and Treated Intratracheally with
                         BP or Subcutaneously with DENA
                            (Feron  and  Kruysse,  1977)
Incidence of tumors
Inhalation of
Site and type
of
tumors
No of animals
examined
o Larynx
',. Papilloma
o Trachea
Polyp
Papilloma
Squamous cell
carcinoma
Bronchi
Polyp
Papilloma
Adenocarc inoma
Squamous cell
carcinoma
Lungs
Papillary
adenoma
Acinar adenoma
Adenosquamous
adenoma
Squamous cell
carcinoma
Oat cell-like
carcinoma

-a 0.9%
NaClb
14 14
\/
28

0

0
0

0

0
0
0

0


0
0

0

0

0
BPC
(18.2
mg)

27

1

0
0

0

0
1
0

0


0
0

1

0

0
air
BPd
(36.
mg)

24

0

0
1

2

0
0
1

0


3
2

0

0

0
Inhalation of acrolein

4
DENA6
Females
27

3

0
8

0

0
2
0

0


0
0

0

0

0

_a 0.9%
NaClb
14 13
V
27

0

0
1

0

0
0
0

0


0
0

0

0

0
BPC
(18.2
mg)

29

0

1
3

0

0
0
0

0


2
2

0

0

0
BPd
(36.4
mg)

30

0

0
6

2

0
0
0

1


4
5

2

1

1


DENA6

28

5

0
8

0

1
1
0

0


0
0

0

0

0

-------
                                                  TABLE  11 (Cont.)
i-n
O
Incidence of tumors
Inhalation of
Site and type
of
tumors

No of animals
examined
Nasal cavity
Polyp
Papilloma
Adenocarc inoma
Larynx
Papilloma
Trachea
Polyp
Papilloma
Squamous cell
carcinoma
Anaplastic
carcinoma
Sarcoma
Bronchi
Polyp
Papilloma
Adenoma
Adenocarcinoma
Lungs
Papillary adenoma
Acinar adenoma
Adenosquamous
adenoma
Adenocarcinoma

-a 0.9%
NaClb
15 15
V
30

0
0
0

0

0
0

0

0
0

0
0
0
0

0
0

0
0
BPC
(18.2
mg)


29

0
0
0

0

0
2

0

0
0

0
1
0
0

0
1

1
0
air
BPd
(36.4
mg)
Males

30

0
0
0

1

0
5

1

1
1

0
2
0
1

6
3

2
2
Inhalation of acrolein


DENAe


29

1
0
1

7

2
1

0

0
0

1
2
0
0

0
0

0
0

a 0.9%
NaClb
15 15
V
30

0
0
0

0

0
0

0

0
0

0
0
0
0

0
0

0
0
BPC
(18.2
mg)


30

0
0
0

0

1
1

0

0
1

0
1
0
0

0
1

1
0
BPd
(36.4
mg)


29

0
0
0

1

2
3

3

2
1

2
0
1
2

4
3

1
0


DENA6


30

0
1
0

4

1
5

0

0
0

0
0
0
0

0
0

0
0

-------
TABLE 11  (Cont.)


Site and type
of
tumors
Adenosquamous
carcinoma
Squamous cell
o carcinoma
^ Oat cell-like
^ carcinoma
Anaplastic
carcinoma
.No further treatment.
Given intratracheally
oGiven intratracheally
Given intratracheally
^Given subcutaneously
Incidence of tumors
Inhalation of air Inhalation of acrolein
BPC BPd BPC BPd
-a 0.9% (18.2 (36.4 _a 0.9% (18.2 (36.4
NaClb mg) mg) DENAe NaClb mg) mg) DENAe
Males
00000010

0 0 1 00 1 1 0

00000010

0 0 10 0 0 0 0

(0.2 ml) weekly during 52 wk.
in 52 weekly doses of 0.35 mg.
in 52 weekly doses of 0.70 mg.
in 17 three-weekly doses of 0.125 ul.
.n.*** 4 A. WL v> s^.t i x"f V% ^i  * VN w ^ Vv -* 1 ^ e-*m *~i *- * i ^ 4- XN T   r* ^ r*

-------
                     CRITERION  FORMULATION



Existing Guidelines  and  Standards



     The current  time-weighted average TLV  for  acrolein



established by  the American Conference of Governmental Indus-



trial Hygienists  (ACGIH, 1977) is 0.1 ppm  (  0.25 mg/m3).



The same value  is recommended  by the Occupational  Safety



and Health Administration  (39  FR 23540).  The ACGIH standard



was designed to "minimize, but not entirely  prevent,  irrita-



tion to all exposed  individuals" (ACGIH, 1974).  Kane and



Alarie  (1977) have reviewed the basis for this  TLV in terms



of both additional data  on human irritation  and their own



work on the irritant effects of acrolein to  mice  (summarized



in the  "Acute, Subacute, and Chronic Toxicity"  section).



These investigators  concluded  that "the 0.1  ppm TLV for



acrolein is acceptable but is  close to the highest value



of the acceptable 0.02 to 0.2  ppm range predicted  by this



animal model" (Kane  and  Alarie, 1977).



     The Food and Drug Administration permits the  use of



acrolein as a slime-control substance in the manufacture



of paper and paperboard  for use in food packaging  (27 FR



46) and in the treatment of food starch at not  more than



0.6 percent acrolein (28 FR 2676).



     In the Soviet Union, the  maximum permissible  daily



concentration of acrolein in the atmosphere  is  0.1 mg/m



(Gusev, et al. 1966).  This study did not specify  whether



this level is intended as an occupational or ambient air



quality standard.



Current Levels of Exposure



     As detailed in  the  "Exposure"  section, quantitative
                             c-52

-------
estimates of current levels of human exposure cannot be
made based on the available data.  Acrolein has not been
monitored in ambient raw or finished waters.
Special Groups at Risk
     Since acrolein is a component of tobacco and marijuana
smoke, people exposed to cigarette smoke are a group at
increased risk from inhaled acrolein.  In addition, acrolein
is generated by the thermal decomposition of fat, so cooks
are probably also at additional risk (see "Exposure" section)
Since acrolein has been shown to suppress pulmonary antibac-
terial defenses, individuals with or prone to pulmonary
infections may also be at greater risk (Jakab, 1977).
Basis and Derivation of Criterion
     Although acrolein is mutagenic in some test systems
(see "Mutagenicity" section) and can bind to mammalian DNA
(see "Acute Effects on Experimental Systems" section), cur-
rent information indicates that acrolein is not a carcinogen
or cocarcinogen ("Carcinogenicity" section).  Water quality
criteria for acrolein could be derived from the TLV, chronic
inhalation studies, and subacute oral studies using non-
carcinogenic biological responses.
     Stokinger and Woodward (1958) have described a method
for calculating water quality criteria from TLV's.  Essen-
tially, this method consists of deriving an acceptable daily
intake (ADI) for man from the TLV by making assumptions
on breathing rate and absorption.  The ADI is then parti-
tioned into permissible amounts from drinking water and
other sources.  However, because the TLV is based on the
prevention of the irritant effects of acrolein on inhalation
                             C-53

-------
exposures,  such  a  criterion would have little, if any, validity.
     A criterion could  also be estimated based on chronic
inhalation  data.   As  summarized  in the "Chronic Toxicity
to Experimental  Animals" section, female hamsters exposed
to acrolein at 9.2 mg/m in the  air, seven hours per day,
five days per week, for 52 weeks evidenced slight hemato-
logic changes, significant decreases in liver weight, and
significant increases in lung weights  (Feron and Kruysse,
1977) .  By  making  assumptions of respiratory volume and
retention,  the exposure data from this study can be converted
to a mg/kg  dose  and an  "equivalent" water exposure level
can be calculated.  The average  body weight for the hamsters
at the end  of the  exposure was about 100 g.  Assuming a
mean minute volume of 33 ml for  a 100 g hamster  (Robinson,
1968) and a retention of 0.75, the average daily dose is
estimated at 68.3 jug/animal  (9.2 mg acrolein/m  x 0.033
1/min x 1 m /1000  liters x 60 min/hour x 7 hours/day x 5
days/7 days x 0.75) or  683 pg/kg.  Using an uncertainty
factor of 1,000  (Natl.  Acad. Sci. 1977), an estimated
"unacceptable" daily  dose for man is 0.683 jug/kg or 47.8
/jg/man, assuming a 70 kg body weight.
     A criterion based  on this daily dose level would be
unsatisfactory for two  reasons.  First, the dose data used
to derive the standard  are not based on a NOEL.  In this
respect, the derived  criterion could represent an undesirably
high level  in water.   Secondly,  the estimation is based
on an inhalation study. Given the probable instability
of acrolein in the gastrointestinal tract, the use of inhala-
tion data may not  be  suitable for deriving a criterion.
                              C-54

-------
     In Drinking Water and Human Health, the National Academy



of Sciences (NAS, 1977)  summarized the study by Newell (1958)



in which acrolein was added to the drinking water of rats



at concentrations of 5,  13, 32, 80, and 200 mg/1 for 90



days without apparent adverse effects (see "Subacute Toxicity



to Experimental Animals" section).  Because this study did



not involve a chronic exposure, the National Academy of



Sciences (1977) declined to derive an acceptable daily intake



for man based on this study.  However, McNamara  (1976) has



suggested that subacute  exposures can be used to estimate



chronic no-effect levels.  Based on an extensive review



of the literature comparing subacute and chronic toxicity



tests, McNamara  (1976) noted that "for 95 percent of chemical



compounds...(on which data were available)...a three-month



no-effect dose divided by a factor of ten will produce no



effects in a lifetime."   Using this approximation for acrolein,



the no-observable-effect level for acrolein on rats can



be estimated at 20 mg/1  of water.   Assuming a daily water



consumption of 35 ml/day and a body weight of 450 g (ARS



Sprague-Dawley, 1974), the chronic no-effect dose for rats



is estimated at 1.56 mg/kg.  This value may be converted



into an ADI for man by applying an uncertainty factor.



Since the chronic no-effect dose is merely an estimate based



on observed relation-ships between subacute and chronic



toxicity, an uncertainty factor of 1,000 is recommended



(Natl. Acad. Sci.  1977). Thus, the estimated ADI for man



is 1.56/ag/kg or 109 jug/man, assuming a 70 kg body weight.



Therefore,  consumption of 2 liters of water daily and 18.7



grams of contaminated fish having a bioconcentration factor
                              C-55

-------
of 790, would result in, assuming 100 percent gastrointestinal
absorption of acrolein, a maximum permissible concentration
of 6.50^ug/1 for the ingested water:
               109 jag
                                  = 6.50 jug/1
(2 liters + (790 x 0.0187) x 1.0
This calculation assumes that 100 percent of man's exposure
is assigned to the ambient water pathways of ingesting water
and contaminated fish/shellfish products.  Although it is
desirable to develop a criterion based on total exposure
analysis, the data for other exposure is not sufficient
to support a factoring of the ADI level.
     In summary, based on the use of acute toxicologic data
for rats, and an uncertainty factor of 1000, the criterion
level corresponding to the calculated acceptable daily intake
of  1.56 jug/kg, is 6.50 jug/1.  Drinking water contributes
12 percent of the assumed exposure while eating contaminated
fish products accounts for 88 percent.  The criterion level
for acrolein can alternatively be expressed as 7.38 jug/1
if exposure is assumed to be from the consumption of fish
and shellfish products alone.
                              C-56

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                          REFERENCES



Abrams, E.F., et al. 1975.  Identification or organic com-



pounds in effluents from industrial sources. EPA-560/3-75-



002. PB-241-641. Natl. Tech. Inf. Serv., Springfield, Va.







Alarcon, R.A. 1964.  Isolation of acrolein from incubated



mixtures of spermine with calf serum and its effects on



mammalian cells.  Arch. Biochem. Biophys. 106: 240.







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