TOXICITY OF NEODOL<"> SURFACTANTS
                      by

                Anna S. Mammons
                C. Donald Powers

      Science Applications International Corporation
               Oak Ridge, TN 37831

                   May 1987
                  Prepared for

             Office of Toxic Substances
         U.S. Environmental Protection Agency
              Washington, DC  20460
                  Task Officer
                 Terry O'Bryan

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                              TABLE OF CONTENTS

1.0  INTRODUCTION 	     1
2.0  DESCRIPTION OF NEODOlW PRODUCTS	     2
     2.1  NEODOL Alcohols 	     2
     2.2  NEODOL Ethoxylates  	     2
     2.3  NEODOL Sulfates 	     3
     2.4  NEODOL Ethoxysulfates 	     4
3.0  EFFECTS ON NON-MAMMALIAN ORGANISMS 	     5
     3.1  Acute Effects LCcn	     5
          3.1.1  Alcohols	     5
          3.1.2  Alcohol Ethoxylates  	     7
          3.1.3  Alcohol Sulfates 	     7
          3.1.4  Alcohol Ethoxysulfates 	     8
     3.2  Sublethal Effects  	     9
          3.2.1  Aquatic Animals  	     9
          3.2.2  Plants	    10
     3.3  Chronic Effects	    12
4.0  ENVIRONMENTAL FACTORS INFLUENCING AQUATIC TOXICITY 	    13
     4.1  Water Hardness	    13
     4.2  Biodegradablllty   	    13
     4.3  Exposure	    14
5.0  MAMMALIAN TOXICITY 	    15
     5.1  Acute Effects	    15
     5.2  Subchronic  Effects  	    16
     5.3  Chronic Effects	    17
     5.4  Carclnogenlcity	    17
     5.5  Mutagenldty	    18
     5.6  Teratogenlcity/Reproduction  	    18
     5.7  Studies In  Humans	    19
                                      11

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                              TABLE OF CONTENTS
     5.8  Metabolism	   jg
6.0  CONCLUSIONS	   20
     6.1  Toxicity to  Non-Mammalian Organisms 	   20
     6.2  Mammalian Toxicity  	   21
     6.3  1,4-Dioxane  Contamination 	   25
7.0  REFERENCES	   26
APPENDIX A - Acute Toxicity (LC50) of Alcohol
             Surfactants to Aquatic Animals 	   38
                                     iii

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                                LIST OF  TABLES
Table 1        General direction of toxicity and rate of bio-
               degradation of linear primary alcohols and deriva-
               tive surfactants in an aquatic environment as a
               function of alkyl or ethoxylate (EO) chain length  ...     6

Table 2        Effects of NEODOl products in laboratory mammals ....    22
                                     iv

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                      TOXICITY OF NEODOL(R) SURFACTANTS

1.0  INTRODUCTION

     This  report  is  the  result  of Work  Assignment #3  of  IAG #DW-89930405.
Toxicity  data from  a voluntary  submission (FYI-AX-0685-0410  Sequence  A) by
Shell  Chemical  Company   to  EPA's  TSCA Existing  Chemicals  Program  and  two
published  reports  by Arthur D. Little,  Inc.  ("Human Safety and Environmental
Aspects  of  Major  Surfactants,"  May,  1977;   "Supplement,"  by  Goyer et  al.
February,  1981)  were reviewed  to  evaluate  the toxicity and structure-activity
relationships  of  NEODOlW  chemicals  for which  data are  available and to
identify gaps  in the toxicity database.   TSCA 8(e)  submission 8EHQ-0580-0326
Sequence C was also  reviewed for its applicability to NEODOL toxicity.

     Today's dishwashing  and laundry  agents are superior to those of the  past
because  they  thoroughly  clean  man-made  fibers,  tolerate  hard  water,   form
little foam, and are readily  biodegraded.   These improvements are due largely
to  the extensive  use of three  classes of surfactants  (NEODOL  products) in
cleaning  formulations.    Derived  from  primary alcohols,  these  compounds  are
classified  according to  the  chemical  group(s)  attached  to the  alkyl  chain:
alkyl sulfates,  if sulfated; alkyl  or  alcohol  ethoxylates,  if ethylene oxides
are  present;  and  alkyl   or  alcohol  ethoxysulfates, if  ethylene  oxides  are
sulfated.

     In  addition  to the widespread  use  of  NEODOL  products  as  household
cleaning agents  (primarily the ethoxysulfates), they are extensively used in
personal care products such as shampoos, bubble baths, and cosmetics, and also
have many  industrial  applications.    NEODOL  ethoxylates  are  also used  as
analgesic.s and anesthetics.  While recent product/consumption figures have not
been provided,  a  review of the  values reported by Arthur D.  Little  (1977,
Goyer  et  al.  1981)  indicates the  considerable use of  these surface-active
agents.  Comparing data  from 1973 and  1978, annual  use of  ethoxylates in  the
United States increased from 188,000 tons to 238,000 tons during the five-year
period.  Similarly,  the  use of ethoxysulfates  rose  from 53,000 tons to 64,000
tons during  those  same years.  As  for alkyl   sul fates, 90,000 tons were used

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worldwide  in  1976.   Shell  Chemical  Company is the world's largest producer of
linear  primary alcohols and  alcohol-based  surfactants,  exceeding 450 million
pounds  per year in  the United States.   In England and Japan  certain NEODOL
products are  produced under the name DOBONOl(R).

2.0  DESCRIPTION OF NEODOl(R) PRODUCTS

     NEODOL products include:

     o     NEODOL alcohols  (ROH)
     o     NEODOL ethoxylates  [RO(CH2CH20)XH]
     o     NEODOL sulfates  (ROS03-Na+ or NH4+)
     o     NEODOL ethoxysulfates [RO(CH2CH20)xS03-Na+ or NH4+]

2.1  NEODOL Alcohols

     Linear   primary  alcohols  (ROH)  included  in  NEODOL  products  consist
essentially of two groups:  chains of Cg to GU carbon atoms and chains of q2
to C15  carbon atoms.  Nomenclature  is  based on the length of the alkyl chain.
For example,  NEODOL  91  indicates that this  product  is  a mixture of mostly Cg
to Cn  alcohols; NEODOL 25 is a mixture of mostly C12 - Ci5 alcohols (Shell b,
P. 1).

2.2  NEODOL Ethoxvlates

     NEODOL ethoxylates are  mainly produced  from the  reaction of  ethylene
oxide (CH2CH20  or  EO)  with linear  primary alcohols, although  some  branched-
chain alcohols  are  used   (Satkowski et  al.  1967,  as reported  in Arthur  D.
Little,  Inc. 1977,  p. 240).

     Examples:
          Primary
               CH3-(CH2)X CH2-0-(CH2-CH2-0)yH

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          Secondary
               CH3-(CH2)z-CH-(CH2)ziCH3
                           0-(CH2-CH2-0)yH
          x - usually 05 to Cje
          y - usually 63 to E02Q
          z + zj - usually 5 to
     NEODOL 25-3 or Cj2-l5  ^03  indicates  that  the product is comprised mostly
of Cj2 to Cj5  alcohols  reacted  with an average of 3 molecules of EO to form a
3-unit EO chain (Shell b, p. 2).

2.3  NEODOL Sul fates

     NEODOL  sul fates  (alcohol   or   alkyl  sul fates  or  AS)   are  produced  by
sulfation of the parent  alcohol  with either sulfur trioxide or chlorosulfonic
acid and subsequent neutralization  of the product with an appropriate base as
follows:

               S03 or               NaOH
          R-OH ....... >  R-OS03-H+ ...... > R-OS03'Na+
               C1S03H
     (R usually averages between 12 and 18 carbons).

     To produce secondary AS, the parent  alkene is reacted with sulfuric acid.
                       H2S04
     C-C-C-C-C-C-C-C=C  ...... >C-C-C-C-C-C-C-C-C
                                          OS03-H+
A complex mixture of  isomers can occur because the sulfate ester group can add
at any  position  along the chain,  except at the terminal carbon atoms (Higgins
and Burns  1975;  Kerfoot and Flammer 1975; Swisher 1970, p. 36; as reported in
Arthur  D. Little, Inc.  1977, p. 171).

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     NEODOL  91 -S  Indicates  that  the  alkyl  chain is  Cg  to  Cu  carbons  in

length,  and  that  the  sulfated  alcohol  has  been neutralized  with NaOH  to

produce a sodium (S)  salt  of the sulfate.   NEODOL 23-A specifies the ammonium
(A) salt of the  sulfate (Shell b, p. 1).


     AS  are  used  in many specialty  products such  as  shampoos,  cosmetics,

dentifrices,  antacids,  and depilatories (Gleason  et  al.  1969 as  reported  in

Arthur D. Little,  Inc.  1977, p.  170),  and  are extensively  used  in heavy duty

laundry products (Kerfoot  and Flammer 1975, as reported  in Arthur D. Little,
Inc. 1977, p.  170).


2.4  NEODOL Ethoxvsulfates


     Walker et al. (1973,  as  reported  in Arthur D. Little,  Inc.  1977, p. 346)

described the following procedures for production  of NEOOOL  ethoxysulfates
(EOS).


          "(1) ethoxylation of a fatty alcohol (prepared from either
               vegetable oil or petroleum hydrocarbons)

                      /       \       KOH
               R-OH + / CH2-CH2      	>      R-0-(CH2CH20)X H
                      I  \  /   J     catalyst
                      \    0  J x                  (usually x = 2-4)

          (2)  sulfation of  the  product with either sulfur trioxide
               (S03) or chlorosulfonic acid (C1S03H),

                                  S03
               R-0-(CH2CH20)X H  	>   R-0-(CH2CH20)X S03 H

          (3)  and  neutralization  to  form  either  the  sodium  or
               ammonium salt

                                OH-
          R-0-(CH2CH20)X S03 H	>  R-0-(CH2CH20)X S03'Na+(or NH4+)B
     EOS  can  be designated  as,  for example,  NEODOL  25-3A or  Ci2.15E03A,
signifying  a mixture of  12  to  15 carbon alcohols, an  average  of three mole-
cules  of EO  to form  a three-unit  chain,  sulfation  of the ethoxylate,  and
neutralization to form the ammonium salt (Shell b, p. 1).

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       EOS,  high foaming anionic surfactants,  are  principally used  in  light-duty
  dishwashing  products and laundry detergent formations.  They are  also  used  in
  shampoos  and other household specialty products (Arthur D.  Little   Inc   1977
  p. 345).
 3.0  EFFECTS ON NON-MAMMALIAN ORGANISMS

 3 . 1  Acute Effects
      Anionic surfactants  are  less  acutely  toxic  to aquatic organisms than are
 nonionic  surfactants.   However, anionics  cause  more permanent  damage  to the
 gill structure  of fish than do nonionics  (Shell  a,  p.  4).  Aquatic organisms
 are better  able to recover after exposure to  nonionic  surfactants than after
 exposure  to anionic  surfactants.    For  example,  50%  of  the  barnacle  larvae
 exposed  for 30  minutes  to the LC50 concentration  of a  nonionic surfactant
 completely  recovered within  20 minutes  after  removal  to clean  water.   By
 contrast,  barnacle  larvae  tested  under  similar  conditions  recovered  no
 swimming ability  within 48 hours  after exposure to  anionic  surfactants ended
 (Wright 1976,  as reported in Shell  a, p.  16).

      Acute toxicities, expressed as  LC50s, of  NEODOL surfactants are compared
 in Appendix A  for  those aquatic  organisms   for  which  sufficient  data  are
 available.   Chemicals are  arranged  in order of decreasing toxicity.  Results
 are discussed  in the following subsections.
3.1.1  Alcohols
     Alcohols  are  the  NEODOL  products  least  toxic  to  aquatic organisms
Toxicity decreases  with increases in the length of the carbon chain  (Table 1)
because water  solubility eventually  decreases  so that the  alcohol  floats on
the  water  surface  (Shell  a, p.  11).  This  is demonstrated  by studies with
rainbow trout  (Salmp.  gairdneri)  showing an  increase  in 96  hour LC50 values
from 6  to 10  mg/L for  Dobanol  91  (Shell  Internal  Report  TLGR.  0166.78,  as
reported in Shell a,  p.  11)  to a non-toxic  response at saturation for Dobanol
45 (Shell  Internal Report TLGR. 0162.78, as  reported in Shell a,  p. 11).

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  TABLE 1.   General  direction of toxicity and rate of biodegradation of linear primary alcohols and derivative
            surfactants  in  an aquatic environment as a function of alkyl or ethSiyfate (EO) chain" length
Chain Lenatfi
Alkyl EO
Class (No. of carbon atoms) (No. of units)
Alcohols | up
Alkyl sul fates . up
(AS) f
10
Alkyl ethoxylates I
(EO) t or . 	
I
19
1C
12
/o -
20
	 2
t
Alkyl ethoxy- 16
sul fates (EOS) 	
16
t
1 6
2
6
2
^^^^^^^^^^B^^^^=a^^B1^^^^^^^^^^^Bwa^^^^s^^B^a^MB^^^^^^-^^^a5^

Rate of
Toxicity Biodegradation
I 
t  A.
.
v Reports range from "no
effect" to "very
slight decrease" as
complexity of the
molecule increases.
1

1
1
T
xLess
toxic Same as for EO com-
Ithan pounds.
parent
r
t
Key:    | = increase

        I  = decrease
	 -no change

 NP =  not prese
= moderate or
  gradual decrease

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 3.1.2  Alcohol Ethoxylates

      The toxicity of  alcohol  ethoxylates  varies according to  both  the length
 of the  alkyl  chain  and the number of  EO  units present.  Generally,  when  the
 length  of  the alkyl  chain  remains the same,  increases  in  the number  of  EO
 units decrease the toxicity (Table 1), as  shown  in  Appendix  A by the one-hour
 LC50  studies  with goldfish  (Carassius auratus)  (Gloxhuber  et  al.   1968,  as
 reported in Shell a,  p. 14)  and  the  96-hour LC50 studies with  rainbow  trout
 (summarized by  Shell  a,  p.   13,  Figure  5)  and Daohnia  (U.S.  Food  and  Drug
 Administration,  as reported  in Shell  a, p.  15).   Shell  (a, p.  4)  suggests that
 the toxicity  is decreased because the  molecule becomes less  fat-soluble and,
 therefore,  penetrates  the gill membrane less  readily.   If, however,  the number
 of EO  units  is  unchanged and  the length of  the  alkyl  chain  is  increased,
 toxicity increases (Shell  a,  p.  13).

      Invertebrates  (except   Daohnia)  are  relatively  tolerant to   alcohol
 ethoxylates, with  most LC50 values ranging  from  500  to  5,000  mg/L (Shell  a,  p.
 13)  compared  to  bluegill  sunfish  (Laoomis  macrochirus).  with LC50 values
 ranging  from  1.8  mg/L  (C12-i5E03) to  11.0 mg/L  (C12.i5E09,  98% linear pri-
 mary),  and  rainbow trout, with  LC50  values ranging  from  0.8 mg/L (C14.15E07)
 to  8-9  mg/L  (C9.10E05)  (Appendix A).   Less  active species  are perhaps more
 tolerant to surfactants  than the more active species because  lower respiratory
 rates  cause less surfactant to pass over their gills (Shell a,  p. 4).

 3.1.3  Alcohol Sulfates

     Alcohol   sulfates  do  not  appear  to  be  as acutely toxic to   aquatic
 organisms as are the ethoxylates.  According to Kikuchi et al.  (as reported  in
 Goyer  et al.  1981, p.  100), 24-hour  LC50  values reported  for Japanese killi-
 fish  (Oryzias  latipes)  ranged  from  0.78  mg/L  for  NaC16AS   to  70  mg/L for
NaC12aveAS-   The  variation was attributed  to the  difference  in the  length of
the  alkyl  chain (Table  I).    However,  close  examination of  the  limited  LC50
data presented in Appendix A  does not clarify whether chain  length affects
toxicity.

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3.1.4  Alcohol Ethoxysulfates

     Sulfation of ethoxylates appears to reduce  their  toxicity by a factor of
21 to 23 compared to  the  parent products  (Shell  a 1985, p. 16).  According to
studies using fathead minnows (Pimeohales  promelas). the most important factor
influencing  the toxicity of  these surfactants  is the  number  of EO  units
present  rather  than  the  number  of carbon atoms  present (Monsanto Co.,  un-
published data,  as reported  in Arthur D.  Little,  Inc.  1977,  p.  363).   In-
creasing the number  of  EO  units when the  number of carbon atoms was  kept
constant and less  than  16  decreased  toxicity  (Table 1); however, when  the
number of carbon atoms  was  equal  to or  more than 16,   increasing the number of
EO  units drastically  increased toxicity   (see  Appendix  A).   The  most  toxic
surfactant  tested  was  CjsEOsS,  producing  a 24-hour  LC$Q value  of 0.8  mg/L.
The peak toxicity at  Cie  changed  very  little with EO  units decreasing  to 03.
The  least   toxic  ethoxysulfate tested  was CisE02S at  an LC$Q  of 80  mg/L.
Contrary to Monsanto's  results with minnows, Gafa (1974, as reported in Arthur
D.  Little*  Inc.  1977,  p. 363)  found CjeEOa^S to  be  one of  the least  toxic
surfactants  to goldfish.   Shell d  (unpublished data,  as  reported in Goyer et
al. 1981, p.  199) demonstrated  substantial  differences in 96-hour LC$Q values
for  rainbow  trout  when  the  numbers of  carbon  atoms were  changed  and  the
numbers of  EO units were  only slightly different.  The LC50 for C^-isEOsS was
8.9 mg/L compared  to  an  LC5Q of  400-450 mg/L for Cg.ioE02.5S.   These  results
indicate that data are  insufficient   to  generalize  about  the  factors  in-
fluencing the toxicities  of various alcohol ethoxysulfates.
              /

     The  few data  available   for  invertebrates  suggest that   they  may  be
slightly less susceptible to EOS  than are  fish.   LC$Q  values (24-hour) ranged
from 5 mg/L (C12E03S)  to 37 mg/L  (C12E03S, Ziegler or natural  fatty alcohol-
derived) in Daohnia  (Lundahl  et  al. 1972, as  reported in Arthur  D.  Little,
Inc. 1977,   p. 364).
                                      8

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3.2  Sublethal Effects

3.2.1  Aquatic Animals

     Surfactants have  been  shown  to cause a  variety of sublethal effects In
aquatic organisms, such as changes In ventilation rates, Inhibition of larval
development,  and  Immobilization.    Alcohol  ethoxylates  and  ethoxysulfates
affect the  ventilation rates of blueglll sunfish.   For example,  forty-eight
hour tests  by Makl  (1979a,  as reported  In Goyer  et  al.  1981, p.  158} demon-
strated that  concentrations ranging  from 0.26 mg/L to 1.2  mg/L of C^.sEO
suppress ventilation rates In bluegills  by 30  to 50%  compared  to controls.  To
a  lesser  extent, similar effects  were  also caused  by  C^^EO.   However, 48
hours of exposure to 0.39 mg/L ^03$ significantly  increased the ventilation
rate of  bluegills (Maki  1979a,  as reported  in  Goyer et  al. 1981,  p. 198).
Larval development was inhibited in the  Eastern oyster (Crassostrea viralnical
after 48  hours  exposure to  a 0.11 mg/L  concentration of Ci^EO (Maki 1979b,
as reported in  Goyer  et  al.  1981,  p.  159),  in the Pacific  oyster (Crassostrea
ojflas)  after  48 hours  exposure  to a  0.84 mg/L  (average)   concentration of
NaC^AS (Cardwell et  al.  1977, as  reported  in  Goyer  et  al.  1981, p.  104),  and
in  the horse clam  (Tresus cajjax)  after 48  hours  exposure to  a  0.4   mg/L
concentration of NaC^AS (Cardwell et al.  1978,  as  reported in  Goyer et  al.
1981, p.  104).   Immobilization of barnacle nauplii  occurred  after 30 minutes
exposure  to 580 mg/L  of a concentration of CjoEt^o  (Wright  1976,  as reported
in Goyer  et al.  1981,  p.  159).   Daohnia  were  immobilized by concentrations of
sulfates  ranging from 42 mg/L  for C^AS to 8200 mg/L  for CsAS  indicating  a
trend  of  increasing   AS  toxicity with  increasing  numbers   of  carbon atoms
(Lundahl  and  Cabridenc  1978,  as reported  in Goyer et  al.  1981,  p.   97).
Similarly, Wright (1976, as  reported in  Goyer  et  al. 1981,  p. 97) found CjnAS
to be  approximately ten times as toxic  as CsAS in barnacle  larvae (Elininius
modestus).  However,  Bode et al.   (1978, as reported in Goyer et al. 1981, p.
101) found toxicity decreased with increasing  chain  length when  budding Hvdra
attenuata were  exposed to CJQ,  C^,  C^, and  C^AS.   The decrease was attri-
buted to reduced water solubility at the assay temperature  of 20C.

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     Most  data  indicate  that  increasing  the  length  of  the  alkyl  chain  of
alcohol sulfates  tends  to increase toxicity  (Table 1).   Insufficient data are
available on sublethal  effects to make such generalizations about ethoxylates.

     Another type of effect was detected in whitefish fCareaonus clupeaformisl
by Hara  and  Thompson (1978, as reported in  Goyer et al.  1981,  p.  103).   The
olfactory bulbar  electric response  was  suppressed with  0.1 mg/L Ci2aveAS, the
lowest concentration  at which sublethal effects  were observed.   The authors
considered this an adverse effect because feeding and migrating behavior could
be impaired by reduced  olfactory sensitivity.

     Feather  oils of  ducks were  dissolved  after 30 minutes  exposure  to  a
solution of 19 mg/L C12AS in distilled water (Choules et al. 1978, as reported
in Goyer  et  al.  1981,   p.  110).  Such an effect could   obviously place water-
fowl at increased risk  of hypothermia in waters polluted with detergents.

3.2.2  Plants

     Surfactants  are toxic  to  aquatic plants.  Alcohol  ethoxylates  have  been
shown to inhibit the growth of algae.  C^.^AEs was algistatic to populations
of the diatom  (Navicula seminuluml at concentrations of 5-10 mg/L and to the
green  algae  (Selenastrum capricornutuml at  concentrations of  50 mg/L.   The
same surfactant was algicidal to the diatom at 100 mg/L  and to the green algae
at 1000 mg/L (Payne and Hall 1979,  as reported in Goyer  et al.  1981,  p. 156).

     The  growth  of  12 species  of marine  phytoplankton  (chlorophyceae)  was
completely inhibited  by MgC12aveAS  at  concentrations  of  100  and 1000 mg/L.
Nannochloris  sp.   and   Stichococcus  sp. were  completely  inhibited  by  this
surfactant at  10 mg/L  (Ukeles 1965, as reported in Arthur  D.  Little,  Inc.
1977, p.  194).   Rockstroh (1967,  as reported  in  Arthur  D.  Little,  Inc.  1977,
p. 196) demonstrated the  toxicity  of  Na-C12aveAS  to  ciliates  fCvrtolophosisl.
Exposures of 4  and 15  minutes to  concentrations  of 0.1 and 0.2  mg/ml  caused
autolysis  of  the cytoplasm,  fissures  in  the  mitochondrial  membrane,   and
formation of a diffuse mitochondrial edema.
                                     10

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     An  unusual  relationship  between toxicity  of a  coconut-alcohol-derived
ethoxysulfate and  a red tide dinoflagellate (Gvmnodinium breve)  was  reported
by Kutt  and Martin  (1974,  as  reported in Goyer  et  al .  1981, p.  201).   Mor-
tality decreased  with  increasing concentrations  of  the surfactant  (87%  with
2.5 ug/L, 63% with  12.5 mg/L, and 44% with 50 ug/L).   No explanation was given
for these abnormal  results.

     Surfactants  also  affect  the  growth and  developmnt  of higher  plants.
Aquatic duckweed (Lemna minor) was adversely affected by exposures to C^^AE.
On the basis  of frond count, the 7-day  650 was 21  mg/L and  on the basis of
root length,  it  was 1.9 mg/L (Bishop  and  Perry  1979,  as  reported in Goyer et
al. 1981, p.  166).   Of ten AE surfactants tested on  rye and barley grasses by
Valores and Letez  (1978, as reported in Goyer et al .  1981, p. 166), n-pri-Ci2-
15AE3 and n-pri-Cj2-i5AE3  were  the  most  toxic  to both grasses.  Barley growth
was reduced 25% and 20%, respectively, and rye growth was reduced 50% and 80%,
respectively.   All  surfactants tested  inhibited growth in both  grasses at
concentrations of  100 mg/L.   The least phytotoxic compounds  were n-pri
15AE20 n-pri Cg.nAEe, and n-
     Grain  yield was  reduced  in paddy rice  plants  watered with  50  mg/L AS.
Water  absorption  by  the  roots  was markedly  inhibited,  photosynthesis was
inhibited,  and  considerable  yellowing  of  the  leaf  blade  also  occurred
(Taniyama  and  Nomura  1978,   as  reported  in  Goyer et  al.  1981,   p.   109).
However,  a  stimulatory effect was  demonstrated with corn  seeds  watered with
0.01,  0.1,  or 1 g/L Cj2aveAS (Nadasy et  al.  1972,  as reported  in  Arthur D.
Little,  Inc.  1977,  p.  197).   Seeds weighed 97%,  130%, and 136% of controls,
respectively.  Similar increases  also occurred  in length and dry weight of the
corn plants.   Treatment of barley seeds (Hordeum vulaare L.) with 100% active
NaCi2aveAS  (10~3M)  for 24 hours  before  germination resulted  in significant
growth  inhibition  as  determined  by shoot  length  (Antonielli  and   Lupatteli
1977,  as  reported  in Goyer et  al. 1981).
                                      11

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 3.3   Chronic  Effects

      Few  data are available on  the  chronic effects of NEODOL products.  Much
 of the  data that are available are "no observed effect concentrations"  (NOEC)
 for ethoxylates  derived by  Maki  from  studies with fathead minnows and Daohnia.
 For example,  a chronic  toxicity  test emphasizing  egg production and spawning
 rate  in minnows  resulted in  a  NOEC  of 0.32 mg/L,  the highest concentration
 tested  for C12-5EO  (Maki  1979c,  as  reported in  Goyer et  al.  1981,  p. 160).
 For Daphnia,  a similar  NOEC,  0.27 mg/L,  was obtained with a chronic exposure
 to  C13.67E02.25S  (Mak1  1979d,  as  reported in  Goyer et  al. 1981,  p. 200).
 Growth was  inhibited, however, in the fathead minnow after  a  one-year exposure
 to 0.22 mg/L  concentration  of  Cj3.7E02.2sS  (Maki, 1979d, as reported in Arthur
 D. Little,  Inc.  p.  200).   Maki  (1979a, as  reported in Shell  a,  p. 18) demon-
 strated that  chronic exposure to low levels of  alcohol  ethoxylates decrease
 respiratory rates  in  fathead minnows,  whereas  the  rates are  increased  by
 exposures to  ethoxysulfates.   The mode of action is unknown.

     Other  studies  have shown  that  egg  fertilization can  be  inhibited  in
 crustaceans by  exposure to  surfactants.   Grammo and  Jorgensen  (1975,  as
 reported  in  Goyer  et  al.  1981, p.  160  and Shell a,  p.  19)  caused  almost
 complete  inhibition  of  egg  fertilization  by exposing mussels fMvtilus edulisl
 to 2 mg/L TAE10  (ethoxylated tallow alcohol) for five months.  Some inhibition
 occurred at concentrations  as  low as  0.1  mg/L.   Arthur D.  Little, Inc. (1977)
 reviewed  the results   of   a  chronic toxicity  test  on  clam  (Mercenaria
 mercenaria) and  oyster  (Crassostrea  virainical  larvae.  At 1 mg/L AS,  ferti-
 lized egg  development was significantly retarded compared  to controls, while
 complete  inhibition of development  occurred  at 2.5  mg/L.   After a  10-day
 exposure to 5 mg/L,  clam mortality was 68%; oyster mortality was 82% after 12
days exposure.

     More studies are needed before conclusions  can be reached about the long-
term toxicity of surfactants  to  aquatic systems.   The limited  data available
 indicate that, generally, concentrations exceeding  0.2 mg/L can  cause  adverse
effects in aquatic organisms when exposures last for several months.
                                     12

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4.0  ENVIRONMENTAL FACTORS INFLUENCING AQUATIC TOXICITY

4.1  Water Hardness

     Water hardness  appears  to play  a  role in the  toxicity of at  least  the
alcohol  sulfates.    WUh  an  Increase  In  water hardness,  the toxicity  (and
uptake)  of AS increases  (Arthur  D.  Little, Inc.  1977,  p.  165; Goyer  et  al.
1981, p. 85 and  106).   The effect of water hardness on ethoxylate and ethoxy-
sulfate toxicity is less  certain,  however.   Studies  by Maki  and Bishop (1979)
and Maki et al. (1979) using  Daohnia and Cj^EOy suggest a slight decrease in
EO toxicity with  increased water hardness  (as reported  in Goyer  et  al. 1981,
p. 161).  However, no  such trends were  apparent  in similar studies by Procter
and Gamble Company  (unpublished  data, as reported in  Goyer  et  al.  1981).   No
intra-species, water hardness data were available for EOS.

4.2  Biodearadabilitv

     It is generally agreed in all  reports  reviewed  (Shell  a and b;  Arthur D.
Little,  Inc.  1977,  Goyer  et  al.  1981)  that" the linear  primary alcohol-based
surfactants  do  not  persist  in   laboratory or field  tests.   Even  slightly
branched or  secondary structures  are easily degraded,  albeit at a  somewhat
slower  rate  (Table  1).   Concentrations  of EO as  high as 1000 mg/L  in shake
flask tests simulating  spills, were 70 to 80% degraded in three days (Kravetz
et al.  1979,  as  reported in Shell  a,  p.  5).   Goyer et al.  (1981,  p.  143)
suggests, however, that  a study using an atmosphere containing 70% oxygen to
enable  "complete  surfactant  oxidation  to  C02n  may  not   be  indicative  of
degradation rates occurring in the  same  time period  under natural  conditions.
Ethoxysulfates added to activated sludge were completely metabolized to carbon
dioxide and water within five to ten days  (Mlura  et al.  1979 and  Itoh et  al.
1979, as reported in Goyer et al. 1981,  p. 195).   Numerous other studies using
sludge  or river,  estuarine  or  ocean  waters  have   demonstrated  the  rapid
breakdown of these compounds.   Degradation of ethoxylates has been shown to be
generally faster in saltwater than  in freshwater,  and  faster in freshwater at
high  temperatures  than  at lower  temperatures  (Schoberl and Mann,   1976,  as
reported in Goyer et  al.  1981, p.  142).  The degradation rate of ethoxylates
                                      13

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 is  also influenced  by the length  of the  EO  chain; increased  length  of the
 chain  caused  degradation  to  be   slower,  especially  in  freshwater  at  low
 temperature.    Ethoxylates having  100  EO units/mole  of  alcohol  biodegrade
 considerably slower  (20% ultimate biodegradation in 21 days) than those having
 up  to  30 EO units/mole  of alcohol  (90%  or more in 21 days)  (Kravetz  et al.
 1979, as reported  in Shell  p. 5;  Goyer et al.  1981, p. 144).  Shell claims to
 market  only products  having  a maximum  of 13  EO units/mole  (NEODOL 45-13).
 Biodegradation was essentially complete 10 days after DOBONOL 45-7,  simulating
 a spill  condition,  was  added to an  activated  sludge  medium (Cook  1979,  as
 reported in Shell a, p. 5).

      Degradation results In a rapid  loss  of toxicity of surfactants  to aquatic
 organisms.   Products resulting from EO biodegradation were  much  less  toxic to
 rainbow trout  and goldfish  than  were the parent  compounds (Reiff  1976  and
 Kurata  et al.  1977,  as reported in  Goyer  et al.  1981,  p. 153).  Maki  et  al.
 (1979,  as  reported  in  Goyer et  al.  1981, pp.  151 and  152) concluded  that
 initial  concentrations of 3 mg/L or  less  of C14.5 E07 in stream water  effluent
 was  non-toxic  to  fathead  minnows  within  24 hours.  At 10 mg/L, toxicity  was
 observed for five days in stream water and  for two  to  three days in secondary
 effluent.   NEODOL-type surfactants  are readily  utilized as a carbon  (energy)
 source  by bacteria  present  in  activated sludge and natural waters (Shell a  p
 5).

 4.3   Exposure

      By  comparing  an  organism's  sensitivity to  a chemical  with the  concentra-
 tion  of that chemical likely  to be  present in  the environment, one can often
 predict with reasonable accuracy the potential threat posed by the chemical to
 the  organism.    Modeling  techniques have  been   used  to  estimate   surfactant
 concentrations  in 20  estuarine locations  (Maki  1979b, as reported in Goyer et
 al.  1981, pp.  163 and 164).   Estimated maximum  EO concentrations ranged from
0.2  ug/L in Penobscot  Bay,   Maine  to 19.8 ug/L  in the  Hudson River;  the
geometric mean  for  all  estuaries was 3.2  ug/L.   It should be noted that these
values are probably high because the  model was provided with an elevated
                                     14

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estimate of inflow from sewage treatment plants.  Further, degradation was not
factored in.

     Comparing these  estimated  concentrations  with  the acute sensitivities of
test species,  it appears unlikely  that,  short of  a  direct  spill,  concentra-
tions of  surfactants  acutely dangerous to aquatic  organisms  will  be attained
in the environment.

5.0  MAMMALIAN TOXICITY

5.1  Acute Effects
     All LDso data  reviewed  indicate that,  at their worst, NEODOL surfactants
are moderately  toxic (0.5 to 5 g/kg)  when  rated according to Gosselin et al .
(1976,  as  reported  in  Shell  b,  p.  10).   LDsgs for  all  types of surfactants
generally exceed  1.0 g/kg.   Alcohols appear to be the least toxic (oral 1050$
>5 g/kg), becoming  more so with  either sulfation or ethoxylation.  Sulfation,
however, decreases  the  toxicity of alcohol ethoxylates (Shell  b, pp. 9-11).

     Acute  oral  toxicity  studies  with  rats  indicate  that  the degree  of
ethoxylation  has  some  influence  on  toxicity.    For example,  NEODOL 91-2.5
produced  LDsgs  ranging  from 2.7 to 10 g/kg  (Shell  Internal  Reports HSE-78-
0156,  TLGR.124.79,  and  TLGR. 088.80,  as  reported  in Shell b, p.  11), whereas
NEODOL  91-8  was more  toxic,  exhibiting  LDsgs  of  1.0  or   2.7  g/kg (Shell
Internal Reports  TLGR. 088. 80 and  TLGR. 0024. 76, as reported in Shell b, p. 4).
The length  of the alkyl chain does  not appear to  influence the  acute  toxicity
of alcohol  ethoxylates  (Shell b, Table V, p.  12).

     Skin and eye irritation tests with rabbits have demonstrated that NEODOL
surfactants,  except the  alcohols,  are generally severe  irritants at high or
undiluted concentrations  (Shell  b,  pp. 17 and 20).  Shell b  (p. 21),  however,
reports  that when  directions  are  followed,  actual  use  concentrations  for
NEODOL  products are <0.04%.   At 0.1% dilutions, NEODOL products tested ranged
from  non-irritating  for  alcohols and alcohol sul fates  to  non-irritating to
mildly  irritating for alcohol ethoxylates (Shell b,  p. 21).
                                      15

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      Most  NEODOL  products produced  negative results  in  skin  sensitization
 tests  (Shell  b,  p.  25,  Table XIV).   Most  exceptions  showed some,  weak or
 moderate,  sensitivity  in one  type of  test  but  none  in other  tests.    By
 contrast, NEODOL  25-3 was found  to  be  a  very weak sensitizer in the Maximiza-
 tion Test (Shell  b,  p.  25).   Results of  repeated-insult patch tests of NEODOL
 products in  human volunteers  agree  with  most observations in  animal  studies
 that NEODOL products are not skin sensitizers (Shell  b,  pp. 25 and 27).
 5.2  Subchronic Effects
      Available data  indicate  that  effects of subchronic exposures  to surfac-
 tants mainly involve changes in organ and body weights.   Studies exposing rats
 for 16 weeks to a diet containing  C12  sulfate (4% of the total  diet)  resulted
 in  reduced body weights (Arthur D.  Little,  Inc.  1977 and 1981  and Fitzhugh and
 Nelson 1948, as  reported  in Shell  b,  p.  29).  Compared to controls,  ethoxy-
 lates (C13E06 and C14E07) produced elevated.liver weights in rats  exposed  to
 concentrations  equivalent  to  1%  of  the total  diet (Brown  and Benke  1977,
 Arthur D.  Little,  Inc.  1977,  and Goyer et al.  1981,  as reported  in Shell  b,  p!
 29).    Lower  body weight  was  also  observed  with exposure .to C13E06.   Other
 subchronic  feeding   studies  exposing  rats  to  sulfates  and  ethoxysulfates
 produced no major biological  effects  at concentrations up to  0.1% of  the diet
 for 13 weeks  (Shell Internal  Report R(T)-12-66  and Walker  et  al. 1967,  as
 reported  in Shell b, p.  29).    Increases  in  serum urea  or protein  concentra-
 tions  and  increases  in some organ  weights  occurred at concentrations of 0.5%
 of  the  diet.  Because histopathology  was  normal,  these effects were  considered
 minor.

     Another type  of effect  observed  was  slight inhibition of the progression
 of  cholesterol-induced  atherosclerosis  in  rabbits  (Kivak  et  al.  1975 as
 reported  in  Goyer et  al.  1981).    The  mechanism  of  action is not known,
 although a reduction in accumulation of  cholesterol esters in  aortic tissue
was suggested as a possibility  (Morin et al. 1974, as reported in Goyer et al
 1981).
                                     16

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5.3  Chronic  Effects

     The  few  data available  on the  chronic  effects  of surfactants do  not
demonstrate any  alarming  effects.   One or two  year studies using 1.0% alcohol
sulfate  (Goyer et al. 1981, p.  118)  or 0.5% alcohol  ethoxysulfate (Arthur D.
Little,  Inc.  1977, p. 377), respectively,  in  the  diets of rats have produced
no  adverse  effects.   However,  1% alcohol ethoxylate,  C^-is  05.5,  added to
the  diets of rats for two years resulted  in reduced body weight,  elevated
organ to  body weight  ratios for  liver,  kidney,  brain,  and heart in females and
for  liver in males  and  increased  incidence  of  focal myocarditis,  a  common
spontaneous  lesion found  in  aging  populations of rats  (Procter  and Gamble,
unpublished data,  as  reported in Goyer  et al.  1981, p. 174).  Food consumption
was also  reduced in groups having reduced body weights, and was attributed to
poor palatability of the  diet.   Reduced body weights  and  increased  organ to
body weight  ratios also  occurred in  females  at the 0.5% treatment level.   A
second feeding study  using as much as 1.0% Ci4_15 EO;  in the diets of rats for
two years resulted in reduced  body  weight gains for females and males,  and in
decreased  absolute  organ  weights  for liver,  kidney,  heart,  and  thyroid/
parathyroid glands in females and  for  brain and  adrenals in males in the 1%
treatment  groups.    Gross incidences  of  focal   myocarditis  increased  with
increasing treatment  levels for  all groups  of  rats at 12  months,  but  severity
of lesions was not treatment-related (Proctor and Gamble,  unpublished  data, as
reported  in Goyer et  al.  1981,  p. 175).  Eighteen  months  exposure to  repeated
dermal  applications  of up to 5.0% C^-iaEOe^ produced no  notable results in
ICR Swiss mice (Procter and Gamble  Company, unpublished  data,  as  reported in
Goyer et al.   1981, p. 176).

5.4  Carcinoaenicitv

     No  evidence  for  carcinogenic  potential   of NEODOL products  has emerged
from the limited data available from long-term  oral or dermal  studies  exposing
rats or  mice to  C12_i3  E06<5  or  C14.15  E07 (Proctor  and  Gamble  Company,
unpublished data,  as  reported in Goyer  et al.  1981, pp.  174-176);  C^S  (Goyer
et al.  1981,  p. 119); or C12E03S (Tusing et al. 1962,  as reported  in Arthur D.
Little,  Inc.   1977, p. 378).
                                     17

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 5.5   Mutaqenicltv

      Mutagenicity has not been demonstrated  for  any  NEODOL  product  tested with
 in  vitro or jn  vivo  mammalian systems or in bacterial or yeast systems.  The
 following  NEODOL products have been tested for mutagenicity:  C12ave AS  (Hope
 1977,  as  reported  in Goyer  et  al.  1981,  p.  120);  n-pri-C12_13E03   (Shell
 Toxicology Laboratory unpublished data, as  reported in Goyer et al. 1981,  p.
 177);  CJ2-15EOS  (Hope  1977,  as reported in Goyer et  al.  1981,  p. 209); C12_
 13E02.5S (53:43)  (Inoue  et al.  1980,  as reported  in Goyer  et  al.  1981,   p.
 210);  and  n-pri-C12-i5E03S  (Shell  Research  Limited,  unpublished  data,   as
 reported in Goyer et  al.  1981,  p.  210).

 5.6   Teratooeni ci tv/Reproducti on

      Few teratogenesis/reproduction  studies  have  been  performed  with  NEODOL
 products;  no  teratogenesis studies have  been  performed with AES administered
 alone.   However,  formulations  containing AES  administered  orally  to mice,
 rats,  or rabbits  have produced no  teratogenie  effects (limori  et al. 1973,
 Iseki  1972, Nolan  et  al.  1975,  and  Palmer et al. 1975  as reported in Arthur  D.
 Little,  Inc. 1977, p.  379).  Results  from testing the  following chemicals have
 shown  no  cause  for  concern:   C14.15  E07  and C12E06  (Proctor  and  Gamble
 unpublished data, as  reported in  Arthur  D. Little,  Inc.  1977, p.  322)  and
 C12E03S  (Tusing et al. 1962,  as  reported in Arthur D.  Little,  Inc.  1977,   p.
 378).

     An  alcohol  sulfate whose  chain  length  was not  identified  has also been
 tested .(Nomura et  al.  1980, as reported in Goyer et al. 1981, p.  119).  Dermal
 applications of 10 to  20% concentrations  of the alcohol  sulfate  to pregnant
mice on days 1 to  10 of gestation interfered with embryonic development  at the
cleavage stage.    Applications  of 2%  on  days 1 through  17  also  reduced  the
number of pregnancies,  but the number of animals compared  was too small to  be
statistically significant.  Dermal applications of 10% alcohol sulfate twice a
day prior to implantation  (days 0 to 3) resulted in an elevated incidence of
deformed embryos, compared to controls (29.1% vs 4.9 of 0 in controls) (Nomura
                                      18

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et al. 1980, as reported in Goyer et al. 1981, p. 120).  Dermal application of
the alcohol sulfate during late pregnancy did not interfere with gestation.

     More  tests,  especially with AES  products,  are necessary before conclu-
sions can  be  reached about the teratogenic  potential  or reproductive effects
of surfactants.

5.7  Studies in Humans

     Studies  using  human  volunteers  have demonstrated  the  skin  irritation
properties  of  NEODOL products  (Shell b, p.  27).   In most cases, 1% dilutions
caused  very  slight  to  mild  Irritation  with  repeated  exposures.    Alcohol
ethoxylates appear to  be the least  irritating,  with only non-to-mild irrita-
tions caused  by repeated  exposures  to dilutions up to 25%.   Use  of certain
alcohol  ethoxylates   as  analgesics  and  anesthetics   have  caused no adverse
reactions  in humans  (Goyer et al. 1981, p. 130).

5.8  Metabolism

     Alcohol  sulfates,  short-chain  ethoxylates, and ethoxysulfates   (Goyer et
al.  1981,  pp.  121,   178,  and  211,  respectively)  are readily  absorbed when
administered orally  to rats,  and are primarily excreted in urine.  Increasing
the  alkyl  chain length of an  ethoxylate  decreases  its excretion in  urine and
feces,  and increases the  amount  in  expired air (Goyer et  al. 1981,  p. 178).
Increasing the length  of the  EO unit  of  an  ethoxysul fate causes  it  to be
poorly  absorbed  and excreted  primarily unchanged  in  the feces  (Arthur D.
Little,  Inc.  1977, p. 381).

      Cutaneous  absorption  of  alcohol  ethoxylates  (about  50%)  is  somewhat
slower  than  absorption  after oral  administration  (>75%)  (Drotmann  1977 and
1980,  as  reported in  Shell  b, p. 33).   Dermal  absorption of similar alcohol
ethoxylates is greater than dermal  absorption  of  alcohol sulfates or ethoxy-
sul fates   (Black  and Howes  1979,  as  reported  in  Shell  b, p.  33).   Maximum
absorption of  alcohol  sulfates on human callus occurred with a chain  length of
12 carbons (Dominguez  et al. 1977,  as reported  in Goyer  et  al.  1981, p. 123).
                                      19

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 After application of  100  mg of an alcohol  ethoxylate  (C12E06)  to human skin,
 most  (81% average)  was  recovered from  swabbing  the  skin  after 144  hours
 (Drotman 1980, as reported in Goyer et al. 1981, p.  180).

 6.0  CONCLUSIONS

 6.1  Toxicitv to Non-Mammalian Organisms

      Certain   structure-activity  relationships  have been  delineated  for  the
 alcohol-derived surfactants in aquatic  systems  (see Table 1).  As  the  number
 of carbon atoms  in  the  alkyl  chain of  straight-chain alcohols  increases,  the
 toxicity  of  the  alcohol  decreases.    When  the  (EO)  chain  length of  alkyl
 ethoxylates remains  the same, an increase in the  alkyl chain  length increases
 toxicity.   Conversely, when the  alkyl  chain remains the same,  an  increase  in
 the EO chain  length  decreases toxicity  (as opposed  to the  response  of labora-
 tory rodents).  The sulfation  of the  end EO group  reduces the  acute toxicity
 of these compounds by a factor of more  than 20  compared to the  parent ethoxy-
 late compound.   Alcohol  sulfates  also  appear  to  be  less acutely toxic  to
 aquatic  organisms than are the alcohol ethoxylates.   Although anionic surfac-
 tants  are less  acutely  toxic  than nonionic surfactants,  fish have a greater
 ability  to recover  after exposure  to  nonionic  surfactants  than  to  anionic
 surfactants.

     Surfactants  have  been shown to cause a variety of  sublethal effects  in
 aquatic  organisms, such  as changes  in  ventilation rates,  inhibition of larval
 development and  immobilization.

     The limited  data  available on  the chronic effects  of surfactants  (mainly
 the ethoxylates)  indicate that growth inhibition and altered respiratory rates
 in crustaceans can be caused by long-term exposures.   In general, exposure for
 several months to  concentrations  exceeding 0.2 mg/L  can cause  adverse  effects
 in aquatic animals.

     Surfactants  have  been  shown  to  inhibit  the growth  and  development  of
aquatic microflora and higher plants such as  barley and  rye.
                                     20

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     Due to dissolution of the waterproofing oils on their feathers,  waterfowl
may be at increased risk of hyperthermia if exposed to surfactants.

     NEODOLs and the other alcohol-based surfactants do not persist in aquatic
environments,  and  are  readily  biodegraded  to  apparently  non-toxic  inter-
mediates, then to  carbon dioxide  and  water.   Short of a direct spill, concen-
trations of  surfactants reaching waterways would  be  substantially  lower than
those that are acutely toxic to aquatic organisms.

     Effects of  repetitive exposures  to surfactants  have  not  been  adequately
studied.  Additional toxicity  tests should  focus on the effects of continuous
exposure  of early life stages  of test  organisms to  low  concentrations  of
surfactant, a situation such as might exist near a sewage outfall or drainage/
overflow conduit.

     The  effects  of  1,4-dioxane contamination  of ethoxysulfates on aquatic
organisms cannot be determined from available data.

6.2  Mammalian Toxicitv

     In general, NEODOL products exhibit a low order of toxicity to mammals in
toxicity  tests  (see Table  2).   At worst,  acute  toxicity  can  only  be labeled
moderate,  except  in  the  cases  of skin or eye  irritations which  are  often
severe  for  undiluted derivitized NEODOL products.  However,  dilutions of 0.1%
are  generally  non-irritating, and according to  Shell,  use concentrations are
only <0.04%.

     NEODOL  alcohols,  which are  the  least  acutely toxic to mammalian systems,
become  more toxic with either  sulfation  or  ethoxylation.    Sulfation  of an
ethoxylate,  however,  decreases toxicity.   Length  of  the alkyl chain does not
appear  to play a significant role  in  acute toxicity of alcohol ethoxylates.

     Subchronic  and chronic dietary tests resulted  in reduced  body weights and
increased organ  to body weight ratios for some organs.  There was no evidence
of carcinogenicity or  mutagenicity for  any NEODOL product  tested.
                                      21

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                            TABLE 2.   Effects  of NEODOl(R)  products  In  laboratory mammals
                            Alcohol Sulfates
                                  Alcohol Ethoxylates
                                  Alcohol Ethoxysulfates
ro
ro
    Acute  LOcn
    (g/kg)
    Skin irrita-
    tion (rabbits)
    Eye irritation
    (rabbits)
    Subchronic
 Oral  or dermal,  rats,  or
 rabbits,  >1;  commercial
 use dilutions between  5
 and 15.
0.1% dilution, non-
irritating; >10% dilution,
severe.

Undiluted, severe to
extreme.
4% given in diet for 16
weeks reduced body weight
of rats; cumulative skin
irritation; daily inges-
tion of 250 mg/kg for two
months slightly inhibited
progression of choles-
terol-induced athero-
sclerosis in rabbits.
Oral,  rats,  0.87  to  >10;
dermal,  rats or rabbits,
>2;  inhalation (4 hrs.
exposure) rats, between
1.5  and  3 mg/L.

0.1%,  non-irritating to
mild;  >10%,  mild  to
severe.

>10%,  practically non-
irritating to extreme;
0.1% non-irritating.

1% given in diet for 13
weeks reduced body weight,
increased liver weight of
rats.
Oral, rats, 1.7 to 5;
dermal, rabbits, 4.7 to
12.9.
0.1%, non-irritating to
minimal; undiluted, mild
to severe.

Undiluted, severe; 0.1%
non-irritating.
                                                                                      0.5% given in diet for 13
                                                                                      weeks increased kidney,
                                                                                      liver,  and heart weights
                                                                                      in female and kidney
                                                                                      weights in male rats;
                                                                                      repeated skin (guinea pigs
                                                                                      and rabbits)  exposure to
                                                                                      10% dilutions,  severe
                                                                                      irritation;  1% no reac-
                                                                                      tion.

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                     TABLE 2.   Effects of NEODOlW products In laboratory mammals (Continued)
                           Alcohol Sulfates
                                  Alcohol Ethoxylates
                                  Alcohol  Ethoxysulfates
    Chronic
    Carcinogenic
ro
   Mutagenic
 1% in diet, rats, one
year, no adverse effects.
No evidence from long-term
feeding studies in rats or
skin-painting tests in
mice.
No effects on chromosomes
of rat bone marrow cells
from 90 day diet of
maximum tolerated dose
(1.13% active ingredient).
1% in diet, rats, two
years, reduced body
weight, elevated organ to
body weight ratios,
increased incidence of
focal myocarditis.  5%
dermal application to mice
for 1.5 years, no notable
results.

No evidence from long-term
feeding tests in rats or
from long-term percu-
taneous administration to
mice.

No evidence from in vitro
and host-mediated mutagen-
icity tests.
0.5%  in diet, rats, two
years, no adverse effects.
No evidence from two-year
feeding (0.5%), drinking
water (0.1%), or skin-
painting (5.0%) studies.
No effects on choromosomes
of rat bone marrow cells
from 90 day diet of
maximum tolerated dose
(1.13% active ingredient).
No evidence from hamster
embryo cell culture or
yeast or bacteria studies.

-------
                 TABLE 2.  Effects of NEODOlW products In laboratory mammals (Continued)
Teratogenic/
Reproductive
                        Alcohol  Sulfates
 No  evidence  from ingestion
 of  up  to 300 mg/kg during
 gestation.   Daily skin
 application  of 20% to
 pregnant mice on  days 1 to
 10  interfered with
 embryonic development; 10%
 2 times/day, pregnant
mice, days 0 to 3,
elevated incidence of
deformed embryos.  Doses
severely toxic to dams
reduced litter size and
caused fetal  loss in mice
but not in rats or
rabbits.
                                  Alcohol Ethoxylates
No evidence from feeding
(up to 0.5%) studies in
rats or rabbits.
                                                                                   Alcohol Ethoxysulfates
No data on AES admini-
stered alone.  No evidence
from oral administration
of formulations containing
AES to mice, rats, or
rabbits.  No adverse
reproductive effects from
0.1% in the diets of rats
for two generations.

-------
     Data  are  generally  lacking  on  teratogenic/reproductive  effects.   Data
available from a limited  number of  feeding  studies  indicate no teratogenicity
for any of the NEODOL products tested.   However,  repeated dermal  exposure of
mice  to  high  concentrations  of  an  alcohol  sulfate  during  early  gestation
interrupted cleavage  of eggs  and  retarded fetal  development.  Further studies
should be  performed to clarify the  teratogenic  potential  and/or reproductive
effects of NEODOL products.

     Animal studies show  that, in general, NEODOL products administered orally
are  readily  absorbed, metabolized,  and  primarily  excreted  in  the  urine.
Cutaneous  exposure,  the  usual route of exposure to  most surfactants, results
in slower  absorption  of alcohol ethoxylates.

6.3  1.4-Dioxane Contamination

     There  is  concern  because 1,4-dioxane  is  a  contaminant of  some NEODOL
products.   Shell  (May 7,  1980 memorandum to G.T. Youngblood) claims that 1,4-
dioxane (OCH2CH20CH2CH2)  is present only  in their EOS products, and postulates
that  it  is  formed during  sulfation of  the EO and that  the presence  of a
polyoxyethylene chain and a  highly  acidic agent, such as sulfur trioxide, are
required.   The typical  potential  exposure for an adult female is estimated to
be 1.65 x  10'8g/kg/d  from hair shampoo and 7.56 x 10"10 g/kg/d from light duty
liquid  (Shell  c  1980,  Appendix  B-3).   Worst case  estimates are  1.12  x 10"
7g/kg/d for shampoo and 6.68  x 10~9g/kg/d for light  duty liquids.

      It  is impossible to determine  from the  data provided  whether dioxane
contributes to the  observed EOS toxicity.  However,  dioxane  contamination does
not  alter  the  significance of the toxicity of NEODOL products, for it appears
that  it  is  often the dioxane-contaminated  products (EOS)  to which  environ-
mental species are exposed.   It  would  be useful to compare the toxicities of
contaminated samples  with purified  samples.
                                      25

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-------
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                                      27

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                                     28

-------
Granmo A.,  Jorgensen G.   1975.   Effects on fertilization  and  development  of
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Kerfoot O.C.,  Flammer H.R.  1975.  Synthetic  detergents:   Basics Hydrocarbon
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                                      29

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Kikuchi  M.,  Wakabayashi M.,  Kohima  H.,  Yoshida T.   1978.   Uptake, distribu-
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Kravetz  L.H., et  al.   1979.  Ultimate biodegradation of alcohol ethoxylates 2.
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Kutt E.G.,  Martin D.F.   1974.   Effect of selected  surfactants on  the growth
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                                     30

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 Maki  A.W.  1979b.   An environmental  safety evaluation of  detergent  chemicals
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 Maki  A.W.,  Rubin A.J., Sykes  R.M., Shank R.L.    1979.   Reduction  of nonionic
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 Miura K., Yamanaka K., Sangai T., Yoshimura K.,  Hayashi  N.  1979.  Application
 of biological  oxygen consumption measurement technique to  the biodegradation
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Monsanto  Company,  unpublished  data.   (As  reported in  Arthur  D.  Little, Inc.
 1977).
                                     31

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 Morin R.J.,  Edralin G.G., Woo  J.M.   1974.   Esterification  of cholesterol  by
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 Nadasy M., Dobozy O.K.,  Bartha  B.,  Palfi D.,  Kolesei  M.  1972.  Anwendung von
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                                     32

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Reiff B.  1976.  The effect of biodegradation of three nonionic surfactants on
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Reiff  B.,  Lloyd  R., How M.J.,  Brown D., Alabaster  J.S.   1979.   The  acute
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Shell c.   Shell  Chemical Company.   1980.    (8EHQ-0580-0326 Sequence C).   1,4
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Shell d.   Shell  Chemical Company,  unpublished data  (as reported in Goyer et
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                                     33

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Shell Chemical Company.  1980.  Interoffice Memorandum from J.J. Coyle to G.T.
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Shell Internal  Report R(T)-12-66.   The  comparative toxicity  of  some  biode-
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Shell  Internal   Report  TLGR.0052.77.   The  acute toxicity  of Dobanol  25  to
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Shell Internal  Report TLGR.0064.77.   The acute toxicity of Dobanol  45-18  to
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Shell Internal  Report TLGR.0066.77.   The acute  toxicity of Dobanol  91-5  to
rainbow trout.   (As  reported in Shell a).
                                      34

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Shell Internal Report  TLGR.0079.068.   The  acute toxicity of Dobanol 91-2.5 to
rainbow trout.  (As reported in Shell a).

Shell  Internal  Report  TLGR.0088.80.    Toxicology  of  detergents:    The acute
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Shell  Internal  Report  TLGR.0124.79.   Toxicology  of  detergent intermediates:
acute mammalian toxicity,  skin and eye  irritancy  and  skin sensitizing poten-
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Shell  Internal  Report  TLGR.0161.78.   The acute  toxicity  of Dobanol  23 to
rainbow trout.  (As reported in Shell a).

Shell  Internal  Report.   TLGR.0162.78.  .The  acute toxicity of Dobanol  45 to
rainbow trout (as reported in  Shell a).

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Shell Research Limited, unpublished data (as reported  in Goyer et al. 1981).

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                                      35

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 spending  surfactants  derived from  synthetic  alcohols.    Fd  Cosmet  Toxicol
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 U.S.  Department of  the Interior.   Letter to Shell Development  Co.  Subject:
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            i

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 Valoras N.,  Letez J.   1978.   Screening of Neodal chemicals for  potential  use
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 Walker  A.P.,  Ashforth, 6.K.,  Davies, R.E., Newman, E.A. and Ritz,  H.L.  1973.
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 Walker  A.I.T.,   Brown  V.K.H.,  Ferrigan L.W.,  Pickering R.G.,  Williams  D.A.
 1967.   Toxicity of  sodium lauryl  sulfate,  sodium lauryl  ethoxysulfate,   and
 corresponding  surfactants  derived  from  synthetic  alcohols.    Food  Cosmet
Toxicol 5:763-769.   (As reported in Shell b).

Wright  A.   1976.   The use  of recovery  as  a  criterion  for  toxicity.   Bull
Environ Contam Toxicol 15(6):747-749.  (As reported in Goyer et al. 1981).
                                     36

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APPENDIX A.  Acute toxlclty
                                                      of alcohol surfactants to aquatic animals
Exposure
(hours)
Surfactant
LC50 (mg/L)
Reference
    Daphnia maqna
      24          C12_13E06.5
CO
C12-15E09
C14E08
C12-14E07.4
C12-14E06.3
                               (39%)
                  C12-14E011
                  NaC12-14AS
                  NaC^aveAS  (Ziegler derivative)
                  C12-14E03S  (Ammonium  salt)
                  C12-14E03S  (Sodium salt)
                                  0.57

                                  1.1
                                  1.71

                                  2.0
                                  2.3
                                  2.5
                                  3.3

                                  5.0
                                  5.1
                                  6.3
                                 13.5
                                 16.3
                                 18.9
Shell Internal Report  1974.  ECO 1
Program
Arthur D. Little, Inc.  1978
Shell Internal Report  1974.  ECO 1
Program
Arthur 0. Little, Inc.  1978
Arthur D. Little, Inc.  1978
Arthur 0. Little, Inc.  1978
Shell Internal Report  1974.  ECO 1
Program
Lundahl et al.  1972
Arthur D. Little, Inc.  1978
Arthur D. Little, Inc.  1978
Lundahl et al.  1972
Continental Oil Co., unpublished data
Continental Oil Co., unpublished data

-------
              APPENDIX A.  Acute toxldty (LC50) of alcohol surfactants to aquatic animals (continued)
     Exposure
     (hours)
      Surfactant
 LC5o (mg/L)
                                                                 Reference
to
00
    Daohnia maana
     24           Cn.16E03S
     48
     96
C14.15E07
C12-14E02.2S (Natural alcohol
              derived)
Ci2E03S (Ziegler derived)
C14E03
                  C14E02
                  C14E04
                  C14EOg
    Blueaill  sunflsh  (Leooomis macrochirusl
     24
 19.6  (average)

 0.36  (average)
 21

 37
 0.73
 0.83
 1.53
 1.76
 4.17
10.07

 0.3

 1.8
 Unilever Research Laboratories,  unpub-
 lished  data
 Goyer et al.   1981
 Lundahl  et  al.   1972
 Lundahl  et  al.   1972
 U.S. Food and Drug Administration
 U.S. Food and Drug Administration
 U.S. Food and Drug Administration
 U.S. Food and Drug Administration
U.S. Food and Drug Administration
U.S. Food and Drug Administration
                                                                       Procter and Gamble Company, unpublished
                                                                       data
                                                                       U.S. Dept. of Interior  1968

-------
              APPENDIX A.  Acute toxlclty (LC50) of alcohol surfactants to aquatic animals (continued)
    Exposure
    (hours)
Surfactant
LC50 (mg/L)
Reference
    Blueaill sunfish (Leooomis macrochirus)

                  C12-15E09
CO
vo
                  C12-13E6.5
                  Ci4E03S


                  C12-15E09 (75% linear primary)

                  C14-18E09
                              1.87


                              2.4 (average)

                              1.9


                             <2.1; <2.4


                              2.45; 2.36


                              4.3


                             <5.7; <7.5


                              7.1


                              8.0

                             10
                   Shell Internal Report  1974.   ECO 1
                   Program

                   U.S. Dept. of Interior.  1968

                   Procter and Gamble Co., unpublished
                   data

                   Procter and Gamble Co., unpublished
                   data

                   Shell Internal Report.   1974.  ECO 1
                   Program

                   Procter and Gamble Co., unpublished
                   data

                   Procter and Gamble Co., unpublished
                   data

                   Procter and Gamble Co., unpublished
                   data

                   Cook Research Laboratories  1966

                   Cook Research Laboratories  1966

-------
APPENDIX A.   Acute toxldty  (LC50) of alcohol surfactants  to  aquatic animals (continued)
Exposure
(hours)
Blued ill


24







Surfactant
sunflsh (Leopomls macrochlrus)
C17.9E1.9S
C12-15E09 (98% linear primary)
C19.6E01.1S
Ci3E03S
C12-15E03A
Cl2-15E03S
C12E03S
C12E03S
C12E02.iS
C8E03S
LC50 (mg/L)

10.8
11.0
15
24
32
32
37
73
87
>250
Reference

Procter and Gamble Co., unpublished
data
Cook Research Laboratories 1966
Procter and Gamble Co., unpublished
data
Procter and Gamble Co., unpublished
data
Shell Internal Report 1971
Shell Internal Report 1971
Procter and Gamble Co., unpublished
data
Procter and Gamble Co., unpublished
data
Procter and Gamble Co., unpublished
data
Procter and Gamble Co., unpublished
                                                         data

-------
APPENDIX A.  Acute toxlclty (1X50) of alcohol surfactants to aquatic animals (continued)
Exposure
(hours) Surfactant
Blueaill sunfish (Leopomis macrochirus)
C10E02tlS
96 NH4C15AS, branched
NH4C12.i4AS
NH4C15AS
NaC12AS
NaC12AS
NH4C15AS
NH^nAS, branched
NH4Ci3AS, branched
NH4C12AS
"50

375
2
3
3
4
4
5
16
18
20


.13
.2
.39
.5
.83
.19
.5
.4
.3
(ng/L)


(1
(2.
(2


.37-3.
8-3.7)
.59-4.


3D

43)

Procter
data
Procter
data
Procter
data
Procter
data

Reference

and Gamble
and
and
and
Bishop and
(4
(3
(13
(15
(16
.06-5.
.97-6.
.1-21.
.2-22.
.0-25.
75)
77)
0)
2)
7)
Procter
data
Procter
data
Procter
data
Procter
data
Procter
and
and
and
and
and
Gamble
Gamble
Gamble
Perry
Gamble
Gamble
Gamble
Gamble
Gamble

Co.,
Co.,
Co.,
Co.,
1979
Co.,
Co.,
Co.,
Co.,
Co.,


unpublished
unpubl
ished
unpublished
unpubl

unpubl
unpubl
unpubl
ished

ished
ished
ished
unpublished
unpubl
ished
                                                          data

-------
              APPENDIX A.  Acute toxlclty (LC50) of alcohol surfactants to aquatic animals (continued)
     Exposure
     (hours)
                     Surfactant
ro
 Blueaill  sgnfi^  (LeoDomis  macrochirus)
               NH4C16AS

               NH4CHAS

               C16-18AS
              NaCjAS

Rainbow trout (Salmo qalrdneri)
 96           C14_15E07

              C12-15E9
              C12-14E10.5
              C12.i5E03
              C12-13E2
              C14-15E11
LC50 (mg/L)
                                                                                   Reference
                                                     21.7 (16.7-28.1)   Procter and Gamble Co.,  unpublished
                                                                        data
                                                     26.0 (19.0-35.4)   Procter and Gamble Co.,  unpublished
                                                                        data.
                                                     76.0 (50-116)       Procter and Gamble Co.,  unpublished
                                                                        data.
                                                   1000
                                                      0.8
                                                      0.9
                                                      1.2
                                                  1.8 and 0.8
                                                  1.3 and 1.7
                                                     1 - 2
                                                   1.8 - 2.5
                  Procter and Gamble Co., unpublished
                  data.
                  Abram et al.   1977
                  Reiff  1976
                  U.S.  Dept.  of Interior.   1968
                  Reiff et al.   1979
                  Shell  Internal  Report, TLGR  113.78
                  Shell  Internal  Report, TLGR  0115.78
                  Reiff   1976

-------
         APPENDIX A.   Acute toxldty
                                             of alcohol  surfactants  to  aquatic animals  (continued)
Exposure
(hours)
                   Surfactant
  LC50 (mg/L)
           Reference
Rainbow trout I Sal mo oairdneri)
              C14-15E011
96
              C12-i3
              C14-15E018
              C9-10E02.5
              Cg-io
              C9-10E05
              C12-15
              C9-10E02.5S
Fathead, minnow fPimeohales oromelasl
 24           C16E06S
              C16E04S
   1.1
   2.7
   4 - 10
   5 - 6.3
   5 - 7
   6 - 10
   8 - 9
   8.9 (7.3-10.3)
  28 (23-35)
  45
400 - 450

   0.8
   0.9
Abram et al.  1977
Arthur 0. Little, Inc.  1978
Shell Internal Report, TLGR 0161.78
Shell Internal Report, TLGR 0064.77
Shell Internal Report, TLGR 79.068
Shell Internal Report, TLGR 0166.78
Shell Internal Report, TLGR 0066.77
Shell Chemical Co., unpublished data
Shell Chemical Co., unpublished data
Shell Internal Report, TLGR 0052.77
Shell Chemical Co., unpublished data

Monsanto Co., unpublished data
Monsanto Co., unpublished data

-------
           APPENDIX A.  Acute toxlclty (LC50) of alcohol  surfactants to aquatic animals (continued)
 Exposure
 (hours)
Surfactant
                                                                                Reference
 Fathead minnow (Plmeohales promelas)
               Ci6E02S
               C12E02S
               C14E02S
  24           C12_14E06.3
               C12-14E7.4
               Ci8E06S
               C14E04S
               C14E06S
               Ci8E04S
              CnE04S
              C18E02S
Goldfish (Carasslus auratus)
  6           C12.14E08
              C15E03.2S  branched
                              1.0
                              1.5
                              1.8
                              1.8
                              1.8
                             2.1
                             4.0
                             9.3
                            15
                            17
                            80

                             1.8
                            3.7
 Monsanto
 Monsanto
 Monsanto
 Arthur D
 Arthur D,
 Monsanto
 Monsanto
 Monsanto
 Monsanto
 Monsanto
 Monsanto
 Co., unpublished data
 Co., unpublished data
 Co., unpublished data
.  Little,  Inc.   1978
.  Little,  Inc.   1978
Co.,  unpublished data
Co.,  unpublished data
Co.,  unpublished data
Co.,  unpublished data
Co.,  unpublished data
Co.,  unpublished data
Reiff et al.  1979
Gafa  1974

-------
              APPENDIX A.  Acute toxlclty (LC50) of alcohol  surfactants  to aquatic animals  (continued)
    Exposure
    (hours)
                    Surfactant
 LC50  (mg/L)
            Reference
U1
Goldfish fCarassius auratus)
              C12-14E010.5
              nC14AS (92.4% AI)
              C12E04
              C14E03S
              nC14AS (94.3% AI)
              C14AS (94% AI, branched)
              nC12-15AS (95.8% AI)
              C12-15AS
              Cn.15AS
              C14E03S (5% branched)
              C13E05
              nC12-16AS (94-3
              nC13AS (94.8% AI)
              C16E03.4S
 4.3
 5.0
 5.2
 6.0
 6.3
 7.8
 7.8
 7.8
 8.1
 8.1
 8.5
12.0
18.3
41.0
Reiff et al.   1979
Gafa  1974
Marchetti   1964
Gafa  1974
Gafa  1974
Gafa  1974
Gafa  1974
Gafa and Lattanzi  1974
Gafa and Lattanzi  1974
Gafa  1974
Shell Internal Report, TLGR 79.068
Gafa  1974
Gafa  1974
Gafa  1974

-------
              APPENDIX A.  Acute toxlclty (LC50) of alcohol surfactants to aquatic animals (continued)
o
Exposure
(hours) Surfactant
Goldfish I Carassius auratus)
C14AS (98% AI, branched)
Cl2E02.eS
nC12AS (93% AI)
C12E02.6S (5* branched)
nC16AS (95.3% AI)
1 C12E02
C12E04
Ci2E06
C12E08
C12E010
C12E012
C12E014
Cl2>i6
C12E018
-C50 (mg/L)

49.1
55.0
60.0
66.5
>300
2
4
5
7
10
20
30
40
100
Reference

Gafa 1974
Gafa 1974
Gafa 1974
Gafa 1974
Gafa 1974
Gloxhuber et al.
Gloxhuber et al.
Gloxhuber et al.
Gloxhuber et al.
Gloxhuber et al.
Gloxhuber et al.
Gloxhuber et al.
Gloxhuber et al.
Gloxhuber et al.






1968
1968
1968
1968
1968
1968
1968
1968
1968

-------
APPENDIX A.  Acute toxlclty (LC50) of alcohol surfactants to aquatic animals (continued)
Exposure
(hours)
^^^^^^^^M
Goldfish
48




Surfactant LC50 (mg/L)
fCarasslus auratus)
. C12-15E09 (oxo-9) 1.4
Cl2-15E<>9 (LA-9) 1.9
C12-14E07 3.3
C12-14E09 5.1
C12-14E012 12.0
Reference

Kurata et al. 1977
Kurata et al. 1977
Kurata et al. 1977
Kurata et al . 1977
Kurata et al. 1977







Hermit crab
48




C12-15E03 (30%, kerosene 85
solution)
C12E01 (30%, Isopropanol 1000
solution)
C12E03 (30%, Isopropanol <1000
solution)
C12E09 (30%, Isopropanol 1000
solution)
C14-15E03 (30%, Isopropanol <1000
Shell Internal Report,
U.S. Dept. of Interior
Shell Internal Report,
Shell Internal Report,
Shell Internal Reoort.
EMGR 0150.71
1968
EMGR 0162.71
EMGR 0162.71
EMGR 0162.71
              solution)

-------
              APPENDIX A.   Acute toxlclty (1.650) of alcohol  surfactants to aquatic animals (continued)
    Exposure
    (hours)
      Surfactant
    LC50 (mg/L)
           Reference
    Hermit crab
00
    Brown shrimp

     48
                            (30%, kerosene
                             solution)
C14E03 (30* isopropanol
        solution)

C16E09 (30* isopropanol
        solution)

C14EOg (30% ?)
                         (30%, isopropanol
                          solution)
                  C14-15E01 (30% isopropanol
                             solution)


                  C16-18E06 (30% isopropanol
                             solution)

                  Cl6-18E09 (30%, isopropanol
                             solution)
C14-15E03 (30%t kerosene
           solution)
 <2000



  1500



  2000



  2500

  3500



3000-6000



  4000



  4000
    50
Shell Internal Report, EMGR 0162.71



Shell Internal Report, EMGR 0162.71



Shell Internal Report, EMGR 0162.71



Shell Internal Report, EMGR 0162.71

Shell Internal Report, EMGR 0162.71



Shell Internal Report, EMGR 0162.71



Shell Internal Report, EMGR 0162.71



Shell Internal Report, EMGR 0162.71
Shell Internal Report, EMGR 0162.71

-------
          APPENDIX A.  Acute toxldty (LC50) of alcohol  surfactants to aquatic animals (continued)
Exposure
(hours)
        Surfactant
Brown shrimp
  C12-15E03 (30%, kerosene
             solution)
  C12-15E03 (30%. Isopropanol
             solution)

  C14-15E03 (30%, Isopropanol
             solution)

  C14-15E01 (30%, Isopropanol
             solution)

  C12-15E09 (30%, Isopropanol
             solution)
LC50 (mg/L)
                                                20-30


                                                200


                                                200


                                                500


                                              >3300
                                                                   Reference
                   Shell  Internal  Report,  EMGR 0150.71
                   Shell  Internal  Report,  EMGR  0162.71
                   Shell  Internal Report,  EMGR 0162.71
                  Shell  Internal Report, EMGR 0162.71
                  Shell Internal Report, EMGR 0138.71

-------