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 cells  in  vitro  (Agrelo and  Amos,  1981; Martin  and McDermld, 1981).   Gene
 mutations  were  observed  1n  Salmonella  (Wade  et  al..   1981;  Anderson  and
 Styles.  1978;  HerboId  and  Buselmaler,  1976; Rowland  and Severn,  1981),  E..
 coll  and  yeasts  (Noda  et   al.,  1986;  Von Wright,  1981;  Lemontt,  1978;
 NcDougall  and  Lemontt,  1979).   Hydrazlne  Induced  somatic  mutations  In
 Drosophlla (Shukla,  1972;  Vljaykumar  and Oa1n,  1979) and  mouse L5178Y cells
 hi  vitro (Rogers and  Back,  1981).   No  effect  of hydrazlne was  observed in
 the  In  vivo  mlcronucleus  test  or  the  dominant  lethal  assay  In  mice
 (Tsuchlmoto and Hatter,  1981; Epstein et al., 1972).
    Hydrazlne-lnduced   systemic   toxklty   after   Inhalation  exposure   1s
 observed  primarily  In   the  liver,  lungs  and  blood.   Dogs  exposed  to  6.6
mg/m*  Intermittently  or  1.3  mg/m'  continuously  for   6  months  suffered
 decreased  red  blood cell  counts,  hemoglobin concentration  and hematocrlts,
and  increased  erythrocyte  fragility (Haun  and  Klnkead,  1973).   Under  the
 same exposure protocol,  fatty  liver changes  In  mice and  moderate fat accumu-
 lation In  the "liver  of  rhesus monkeys were  observed.  Similarly,  Cornstock et
al.  (1954)  found  fatty  liver  changes  1n  beagle  dogs  exposed  to 18  mg
hydrazlne/m9 for  <6 months.   Cornstock  et al. (1952) reported  emphysema  and
 Interstitial  pneumonltls  1n  rats  and  emphysema  and atelectasls  1n  dogs
exposed  to  6 mg  hydrazlne/m* for 31 weeks.  Chronic Inflammation,  atelec-
 tasls and  lymphold  hyperplasla were observed 1n  guinea pigs  exposed to 3-6
mg/m»  for  2 weeks  followed  by  8 weeks  at  4-8  mg/m* (Weatherby  and Yard,
1955).   In  the   sane   study,  pathological   changes  noted  In  mongrel  dogs
exposed  to  3-6 ing/a*  Included central-zone fatty degeneration  and necrosis
of  the  livers and  accumulation of  bile pigment.   Capillary damage  In  the
kidney and lung atelectasls were also observed (Weatherby and Yard, 1955).
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     MacEwen  et  al.  (1981)  reported that hydrazlne exposure caused aspermato-
 genests  or  hypospermatogenesls  in Syrian  golden hamsters.  MacEwen  et  al.
 (1981) also  found  that  female rats suffered lesions Including ovary atrophy,
 salplngHls  and  endometrltis when  exposed  to  6.6  mg  hydrazlne/m3  for  1
 year.
     Systemic  toxlclty after  oral  exposure  to hydrazlne 1s similar to Inhala-
 tion  exposure.   B1anc1f1or1  (1970a)   administered  hydrazlne  by gavage  to
 Syrian golden hamsters  (2.8-3.0  mg/hamster  for 15-20  weeks;  assuming  a  body
 weight  of 0.14  kg,  this  Is equivalent  to -20  mg/kg)  and  observed  severe
 liver  lesions Including cirrhosis, bile duct proliferation, pressure atrophy
 and  hepatocyte degeneration.   In contrast, male albino rats  that  received
 between  15 and 25 mg  hydrazlne/kg/day for  3  or  4 weeks  suffered  no  patho-
 logical  changes of  heart,  lung,  liver,  spleen, stomach,  small  Vnte$t1n<,
 kidney, adrenal, pancreas or  testes (Weatherby and Yard, 1955).
    Occupational  exposures   to   hydrazlne  In  gold-plating  (Wrarvgsjo   and
 Martensson,  1986)  and  soldering  work   (Frost  and HJorth,  1959)  resulted  In
 contact  dermatitis  and  eczema,  respectively.   Workers  recovered completely
 after exposure was discontinued.
    Hydrazlne  does  not  appear  to be  teratogenlc,  although  U 1s  clearly
 embryo- and  fetotoxlc at levels  associated  with  maternal  toxlclty.   Lee  and
 Aleyasslne (1970) Injected  pregnant rats with  8 mg hydraz1ne/kg/day subcuta-
 neously  on gestation days  11-21.   None of  the  hydrazlne-treated  rats  gave
 birth  to  newborns  that survived  the  first 24  hours,  while  newborns  from
 untreated  control  rats  survived.  Keller  et al.  (1982)  determined  that  the
 most  susceptible  prenatal  period regarding   embryolethality   1n  rats  was
 gestation  days  7-9.    Lyng  et  al.   (1980)   administered  IntraperHoneal
0327d
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 Injections  of 4, 12.  20,  30 or  40  mg hydrazlne/kg and  found  that maternal
 toxldty  was  also Indicated by reduced weight  gain (at  12 and 20 mg/lcg) and
maternal  death (4/21 rats died  1n the 40 rag/kg group).
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                     7.   EXISTING GUIDELINES AND STANDARDS
7.1.   HUNAN
    The  ACGIH  (1989)  has  set  a TLV-TWA  for  hydrazlne at  0.1  ppm (0.13
mg/m3}  for  occupational  exposure  during   an  8-hour  workday   and  40-hour
workweek.  ACGIH  has  not recommended a TLV-STEL  for  hydrazlne (ACGIH, 1989)
but has  designated  hydrazlne as a "suspected  human  carcinogen"  and given It
a  "skin"  notation,  Indicating  that  cutaneous   absorption  may  contribute
significantly  to  total  absorption.  ACGIH  (1989)  Is  considering  a reduction
In  the TLV-THA  to  0.01  ppm.   NIOSH  (1978)  recommended that  occupational
exposure  to hydrazlne be limited to  a 2-hour celling level of 0.03 ppm (0.04
mg/m3).   OSHA (1989) has  directed that  the  final-rule PEL  for  exposure to
hydrazlne  be  set  at a  TWA  concentration of 0.1  ppm  (0.13 mg/m3).  Further-
more,  OSHA (1989)  has  given hydrazlne  a  "skin designation,"  Indicating that
dermal  absorption   of   hydrazlne may   contribute  significantly  to  total
exposure.
7.2.   AQUATIC
    Guidelines  and  standards  to protect   aquatic   life  from   exposure  to
hydrazlne were not located In the available literature cited In Appendix A.
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                              8.  RISK ASSESSMENT
 8.1.    CARCINOGENICITY
 8.1.1.    Inhalation.   MacEwen  et  al.   (1981)  Investigated  the  oncogen1c
 effects  of  a  12-roonth  Inhalation exposure  to hydrazlne  sulfate  In  mice,
 rats,  hamsters  and  dogs.   Statistically  significant   Increases   In  tumor
 Incidence  were observed  In female mice exposed to 1 ppm (lung adenoma), male
 and  female rats  exposed  to 1  or 5 ppm (nasal cavity adenoma/adenocardnoma),
 male  rats  exposed  to   5  ppm  (thyroid  adenocardnoma)  and  Syrian  Golden
 hamsters   exposed  to  5   ppm   (nasal  cavity  polyp)  (see  Table  6-1).   The
 Increases  In tumor  Incidence  and polyp  formation  were dose-related  In  all
 cases.  No Increase  In tumor Incidence was observed In dogs.
    This  study  was  well  designed and  comprehensive;  several  species  were
 exposed  to hydrazlne sulfate  at  <4 dose  levels,  hlstopathologUal  examina-
 tion of  the animals  Included 44  tissues  and  organs,  the  exposure period was
 long,  the  follow-up observation  period was  24-50 months,  and  appropriate
 controls and statistics were reported.
 8.1.2.   Oral.   B1anc1f1or1   (1970a)   administered  hydrazlne   sulfate   by
 gavage  to mice for  76-98  weeks and observed a  dose-related Increase  In  the
 Incidence  of liver  carcinomas  (see  Table 6-7).   An  adequate exposure  and
 observation  period was  used  In this study, several dose  levels  of hydrazlne
 sulfate  were administered, a  dose-related Increase  In tumor Incidence  was
 demonstrated and both male and  female  mice were tested.   The only weaknesses
 of  the  study were   that  a  single  species   was   examined  and  statistical
 analysis was not reported.
    Bosan  et al. (1987)  reported  a dose-related Increase  In  hepatocarclnomas
 after  oral exposure  of  Syrian Golden  hamsters to  hydrazlne  sulfate  for  2
 years (see  Table 6-8).   An Increase  In  DNA methylatlon 1n the liver was also
0329d
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 observed.   This was  a  well  conducted chronic  study;  however,  statistical
 analysis was not reported, and only one species was examined.
    Several  other  studies  of oral  exposure  to  hydrazlne  sulfate  In  mice
 demonstrated an  Increase  In  tumor  Incidence,  primarily  lung  or  liver  adenoma
 or  carcinoma.   Although these studies  Indicate  that,  at least  In mice,  the
 lung  Is  equally  sensitive as the liver to  the carclnogenlclty  of hydrazlne,
 they  are of  limited  value for quantitative risk  assessment  because  only one
 dose  level  was  tested and  statistical  analysis  of  the   results  was  not
 reported (Toth  1969,  1972; Roe  et  al.. 1967; Seven and B1anc1f1or1,  1966}
 (see Tables 6-2 to 6-6).
 8.1.3.   Other  Routes.   No  Indication of  carclnogenlclty   was   found  after
 administration of  hydrazlne  by subcutaneous Injection  In rats  once/week  for
 2.5 years  (Stelnhoff  and Nohr,  1988).  Negative  results were  also  reported
 for  rats  given  hydrazlne  by  Intratracheal  Instillation  for  2.5  years
 (Stelnhoff and Nohr,  1988).
8.1.4.   Height  of  Evidence.  Hydrazlne  caused  a  dose-related  Increase  1n
 the   incidence   of   tumor  formation   1n   mice  (lung  adenoma)  and   rats
 (alveolalgenlc carcinoma,  lymphosarcoma of  spleen)  after  Inhalation  exposure
 (NacEwen et  al., 1981).   Oral  exposure to  hydrazlne  caused a  dose-related
 Increase In the  Incidence  of  hepatic  carcinomas  In mice (B1anc1f1or1,  1970d;
 Bosan et al., 1987).  Other  studies also documented Increased lung and liver
 tumor Incidence after oral exposure In  mice (Blandflorl, 1970c; Toth,  1969,
 1972; Roe  et  al.,  1967; Seven and B1anc1f1or1.  1968).   Bosan  et al.  (1987)
observed an  Increased  Incidence of liver  tumors  1n hamsters  treated  orally
with hydrazlne.
    Toth  (1969)  reported  an  Increased Incidence  of  pulmonary adenoma  or
adenocarclnoma In mice  exposed orally to hydrazlne, but  observed a  decrease
 In  the   Incidence  of  mammary gland  carcinomas   In  hydrazlne-treated  female
0329d                               8-2                              07/26/90

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 mice.   Toth  (1972)  and BlandfloM  (1970c)  reported  that oral  exposure  to
 hydrazlne  did not  significantly Increase tumor formation In hamsters.
     Hydrazlne 1s genotoxlc 1n prokaryotes,  lower  eukaryotes,  Insects  and  1n
 animal  and human  cells  jhn vitro,  although no effect was  observed  1n  the  In
 vivo mlcronucleus  test  or  the dominant lethal assay In mice (see Table 6-9).
     Data   regarding  the   cardnogenlcUy   of   hydrazlne  1n   humans   were
 Inadequate.    On  the  basis   of   these  data   and   the   U.S.   EPA  (1986c)
 classification   scheme,  hydrazlne  has  been classified   In  EPA  we1ght-of-
 evldence Group B2:  probable human carcinogen (U.S. EPA,  1988,  1989).
 8.1.5.   Quantitative Risk Estimates.
     8.1.5.1.   INHALATION  — The    Inhalation   q^   for    hydrazlne,    17.1
 (mg/kg/day T1. was calculated  from data  reported  1n  MacEwen et  al.  (1981),
 which  documented a  dose-related  Increase 1n the  Incidence of  nasal  cavity
 adenoma or adenocardnoma  1n male  F344 rats.  The corresponding unit risk  Is
 4.9xlQ~3    Ug/mT1.     The    Inhalation    q^   and    unit   risk   for
 hydrazlne  has been reviewed and  verified  by the U.S. EPA  (1989).   The  dose
 associated with  a  risk level of   IxltT5  1s  5.9xlO"7 mg/kg/day.   Multiply-
 ing  this value by the reference human body weight  (70 kg)  and  then dividing
 It  by  the  reference human  Inhalation rate (20 m'/day) yields  a correspond-
 ing  air   concentration  of  2xlO~*  mg/m3.   Air  concentrations  associated
 with  risk  levels   of   lx!0~«  and  lxlO~7   are  2xlO"7   mg/m"  and  2x10~«
 mg/ma, respectively.
    8.1.5.2.   ORAL — The  oral   q^  for  hydrazlne,   3.0   (mg/kg/day)"1,
 was  calculated  from data  reported  by Blanclfforl  (1970a) that  documented a
 dose-related  Increase  1n  the  Incidence  of hepatoma  formation  1n  male  mice
 exposed  to  hydrazlne  sulfate.   The  corresponding  unit  risk  1s  8.5x10~s
0329d
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08/02/90

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        4.    The  q-j*   based  on   the   data   for   hydrazlne  sulfate   was
adopted  for hydrazlne  without  adjustment  for  differences  In the  molecular
weights  of the  two compounds.   The  oral  q  *  and  unit  risk for  hydrazlne
have been  reviewed  and  verified  by  the  U.S. EPA (1989).   The dose associated
with  a  risk  level  of  IxltT'   Is  3.3xlO~«  mg/kg/day.   Multiplying  this
value by the reference  human body weight  (70  kg)  and then dividing It by the
reference  human water  consumption  rate   (2  i/day)  yields  a  corresponding
water  concentration  of  l.ZxlCT4  mg/l.    Water   concentrations   associated
with   risk  levels  of   lxlO'«   and   lx!0~7   are  1.2xlO~5  and   1.2x10"*
mg/l, respectively.
8.2.   SYSTEMIC TOXICITY
8.2.1.   Inhalation Exposure.
    8.2.1.1.   LESS     THAN    LIFETIME    (SUBCHRONIC)  — Hydrazlne-lnduced
systemic  tox1c1ty   after  Inhalation exposure  1s   observed  primarily  In  the
liver,  lungs  and  blood.   Dogs  exposed  to 6.6  mg/m»  Intermittently  (Rec.
#3,  Appendix  C.2.1.)   or 1.3   mg/m9   continuously  for  6  months  suffered
decreased  red  blood cell  counts, hemoglobin concentration  and  hematocrlts.
and  Increased   erythrocyte  fragility   (Haun  and   Klnkead,   1973}.   Under  a
similar  exposure  protocol,  death and  fatty  liver  changes  In  mice  at  0.26
mg/m3  (Rec. #1,  Appendix   C.2.1.)  and  moderate  fat accumulation  1n  the
liver  of  rhesus  monkeys  at 1.3 mg/m»  Intermittently   (Rec.  #5,  Appendix
C.2.1.) were observed.  Similarly,  Comstock et al.  (1954) found  fatty liver
changes and death  1n  beagle  dogs exposed  Intermittently  to  18  mg hydrazlne/
                                               3
m3  for  <6 nonths  (Rec. #11. Appendix  C.2.1.).  Comstock and  Oberst (1952)
reported  death,  emphysema and   interstitial  pneumonHls  In  rats  (Rec.  #7,
Appendix C.2.1.),  and  emphysema   and atelectasls  1n dogs  (Rec. #6,  Appendix
C.2.1.)  exposed  to 6 mg  hydrazlne/m1  for  31 weeks.  Chronic  Inflammation,
0329d
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03/28/90

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 atelectasls  and lymphold hyperplasla were observed In guinea pigs exposed to
 3-6  mg/m3  for  2  weeks  followed  by  8  weeks  at  4-8  mg/m»  (Weatherby and
 Yard,  1955)  (Rec.  #12,  Appendix C.2.I.).   In the  same  study, pathological
 changes  noted  1n  mongrel dogs  exposed  to  3-6 mg/m3  Included central-zone
 fatty  degeneration  and  necrosis   of   the  liver  and  accumulation   of  bile
 pigment  (Rec.   #13,  Appendix  C.2.I.).   Capillary  damage  In the  kidney and
 lung atelectasls were also observed  (Weatherby and  Yard, 1955).
    The  subchronlc Inhalation  data,  however,  cannot be used  for derivation
 of  an  RfD.  Haun  and  Klnkead (1973)  reported  significant  mortality 1n mice
 exposed  continuously  at 0.2  ppm  (HEC  =  0.26 mg/m*),  which  represents  a
 PEL.   Calculation  of HECs for all  NOAEL and  LOAEL  values  from the  exposure
 concentrations  used  In  other  subchronlc  Inhalation  studies  (Comstock and
 Oberst,  1952;   Heatherby and  Yard,  1955)  were not  lower   than  0.26 mg/m*,
 the HEC for  the PEL In mice.
    8.2.1.2.    CHRONIC — Chronic  Inhalation  data  regarding   hydrazlne are
 also not appropriate  for derivation of a chronic Inhalation RfD.  NacEwen et
 al.  (1981)  observed  respiratory  tract  Inflammation  and  nasal/lung hyper-
 plasla  In  rats  exposed  to  0.05  ppm  (0.06 mg/m*)  hydrazlne 6  hours/day,  5
 days/week  for  1 year  (Rec.  #15, Appendix  C.2.I.).  The HEC at  which  these
 effects  appeared  (0.02  mg/m*)  Is   a   LOAEL  and  Is an  order of  magnitude
 lower  than  the  HEC (0.26 mg/m*)  associated  with significant mortality  In
 mice (Haun and Klnkead,  1973) In a  subchronlc  Inhalation  study.   Therefore,
 U Is not appropriate to derive a chronic Inhalation RfD from this LOAEL.
    Hamsters  exposed to 0.25  ppm   (0.32  mg/m*)  hydrazlne,  6 hours/day,  5
 days/week  (HEC  >   0.057 mg/m*)  for  1  year  had  widespread   toxic  effects
 (amyloldosls  1n the livers,  spleens,  kidneys, thyroids and adrenals,  liver
0329d
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01/22/90

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 hemoslderosls,   kidney   mineralization,   senile   atrophy   and  hypospermato-
 genesls)  at  the 2-year  sacrifice  (MacEwen  et al. 1981)  (Rec.  #14,  Appendix
 C.2.I.).  The NEC for  these  effects 1n  hamsters  Is  higher than the  HEC  for
 respiratory  hyperplasla  In  rats.   No  other chronic  Inhalation  studies  were
 located that would be suitable for derivation of an RfD.
8.2.2.   Oral Exposure.
    8.2.2.1.   LESS  THAN LIFETIME  (SUBCHRONIC) - Data regarding  subchronlc
oral  exposure  to hydrazlne  are  Inadequate for  derivation  of  a  subchronlc
oral  RfD.   Blandflorl  (1970a) reported only serious  liver  effects  (cirrho-
 sis,  atrophy and necrosis) after  oral exposure  to hydrazlne  1n hamsters that
received  2.8 mg hydrazlne 5  days/week  for  20 weeks,  or  3.0 mg hydrazlne  4
days/week  for  IS weeks  (Recs. #2 and 3, Appendix C.2.2.).   No other  doses
were  tested; therefore,  these data are not suitable  for  use as LOAEL values
for RfD  determinations.   Sever 1  and  Blandflorl  (1968)  treated mice orally
with  37.7  mg hydrazlne/kg/day but reported only  Increased  tumor  Incidences
and decreased  llfespan.   Weatherby and  Yard  (1955)  administered  hydrazlne
orally at  various  doses;  however,  3/10 rats  died  at  100  mg/i  (Rec.  #1,
Appendix C.2.2.), the lowest concentration tested.
    8.2.2.2.   CHRONIC — Pertinent data  regarding nonneoplastU effects  of
chronic oral exposure  of humans  or animals to  hydrazlne  were not  located 1n
the  available   literature  cited   In  Appendix  A.   Therefore,   no  data  are
available for derivation of a chronic oral RfD.
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                           9.   REPORTABLE  QUANTITIES
9.1.   BASED ON SYSTEMIC TOXICITY
    The  toxlclty  of hydrazlne  was  discussed  In  Chapter  6.  A chronic  non-
cancer toxlclty RQ  has  been derived  for  hydrazlne {U.S.  EPA,  1985),  based  on
mortality  In  mice  exposed Intermittently  to  1.3 mg/m*  for  6 months  (Haun
and Klnkead,  1973), and 1s summarized  1n Table 9-1.  More recent data  were
not  located;  hence, there  has  been no  reconsideration  of this  derivation.
The RQ of  10  derived by U.S.  EPA (1985)  Is adopted  for the purposes of  this
document.
9.2.   BASED ON CARCINOGENICITY
    Data regarding  the  cardnogenldty of  hydrazlne  are discussed  1n Chapter
6 and presented 1n  Tables  6-1  through  6-8.   Several  studies have  reported  an
Increase 1n tumor Incidence after Inhalation and  oral  exposure  to  hydrazlne.
NacEwen  et  al. (1981)  observed significantly  Increased  Incidences  of  lung
adenomas  In  mice,  nasal  cavity adenomas  and  adenocarclnomas  In  rats, and
nasal  cavity  polyps  1n hamsters,  after   Inhalation  exposure to  hydrazlne.
B1anc1f1or1 (1970a)  observed  a  dose-related  Increase In hepatic  carcinomas
after oral  exposure to hydrazlne.   Other studies also documented Increased
lung and  liver tumor  Incidences  after oral exposure  1n  mice  (Blandf 1or1,
1970c; Toth.  1969,  1972;  Roe  et al., 1967;  Seven  and  BlandfloM,  1968).
An  increase  in liver  tumor incidence was also  reported 1n  hamsters after
oral exposure to hydrazlne (Bosan et al.,  1987).
    The  genotoxldty  of   hydrazlne  has   been  demonstrated  1n prokaryotes,
lower eukaryotes,  Insects  and  1n human  and animal  cells jn vitro (Table 6-9).
0330d                               9-1                               08/01/90

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                                   TABLE  9-1
                                   Hydrazlne
                                  (302-01-2)
           Minimum Effective  Dose  (MED) and Reportable Quantity  (RQ)
Route:
Species/sex:
Oose*:
Duration:
Effect:
RVd:
RVe:
CS:
RQ:
Reference:
Inhalation
mouse/female
1.6 rag/day
6 months
mortality
5.2
10
52
10
Haun and Klnkead, 1973
'Equivalent human dose
0330d
            9-2
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     On  the basis of  the  available data, hydrazlne has  been  assigned to EPA
 we1ght-of-evidence  group  82 as a  probable  human  carcinogen  (U.S.  EPA, 1988,
 1989).
     A  human potency  factor  has been  derived  (U.S.  EPA, 1988)  based on the
 incidence  of  nasal  tumors  In rats  (MacEwen et a!., 1981) and Is presented 1n
 Table  9-2.  On  the basis of  this potency factor, hydrazlne  1s assigned to
 the  "high"  potency  group,  which,   for   EPA  we1ght-of-evidence  Group  82
 chemicals,  results  In a cancer-based RQ of  1.
0330d                               9-3                              01/22/90

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                                   TABLE  9-2

                Derivation of Potency Factor (F) for Hydrazlne
Reference:
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight3:
Duration of treatment:
Duration of study:
Llfespan of animal:
Target organ:
Tumor type:
Experimental doses/exposures:
Transformed dosesb:
(mg/kg/day)
Tumor Incidence:
Animal Potency (mg/kg/day)"1:
Human Potency0:
{ mg/kg/day T1
MacEwen et al. ,
Inhalation
rat
F344
M
air
0.35 kg
365 days
910 days
910 days
nasal cavity
1981



M
air
365 days
910 days
910 days





N
air
NA
910 days
910 days

adenoma/adenocarclnoma
5.0 ppm
0.30
72/99
19.33

1.0 ppm
0.06
11/98


0.0 ppm
0.0
0/149


Estimated
bTo derive  the transformed  doses  from the  experimental  dose data,  convert
 experimental dose  1n  (ppm) to  (mg/m>):  0.041  x mol wt  hydrazlne  x  concen-
 tration  (ppm); calculate  preliminary transformed dose (mg/kg/day) based  on
 breathing  rate  and animal  weight:  concentration  (mg/m*)  x breathing  rate
 for  rats  (0.22  m»/day)/an1mal  weight   (0.35  kg);  determine  final  trans-
 formed dose by adjusting for  duration of study,  and discontinuous  exposure:
 transformed  dose  (mg/kg/day)  x  duration of  treatment  (days)/durat1on  of
 study  (days) x 5 (treatment days/week)/? (days/week) x  6  (treatment hours/
 day)/24 (hours/day).                          :

cHuman potency « animal potency x (70 kg/0.35 kg)1/3

NA - Not available
0330d
9-4
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 Qu1ntero-Ru1z,  A.,  L.L.   Paz-Ner1  and  S.   V1lla-Trev1no.   1981.   Indirect
 alkylatlon of CBA  mouse liver DMA and RNA  by  hydrazlne in  vivo.   A possible
mechanism of action as a carcinogen.   3.  Natl. Cancer  Inst.   67(3): 613-618.

Reid, F.J.   1965.  Hydrazlne poisoning.  Br. Ned. J.  5472:  1246.

Roe. F.J.C., 6.A.  Grant and  D.N.  Mllllcan.   1967.   CarclnogenlcUy of hydra-
 zlne and 1,l-d1methylhydraz1ne for mouse lung.  Nature (London).   216: 37S.

Rogers, A.M.  and  K.C.  Back.  1981.   Comparative  mutagenldty of  hydrazlne
and  3  methylated  derivatives  In  L5178Y mouse  lymphoma  cells.   Mutat.  Res.
89(4): 321-328.
Rowland,  L.  and  B. Severn.   1981.   MutagenlcUy  of  carcinogens  and  non-
carcinogens  In  the Salmonella/mlcrosome test.  In.: Evaluation  of  Short-term
Tests  for  Carcinogens:  Report  of  the International  Collaborative  Program.
Prog. Mutat. Res.  1: 323-332.
0331d
10-14
08/09/90

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 Ruth,  J.H.   1986.   Odor thresholds and Irritation levels of several chemical
 substances:  A  review.   Am.  Ind. Hyg. Assoc. J.  47: A-142 to A-151.

 Schlessl,  H.M.   I960.   Hydrazlne  and  Its   derivatives.   1^:  K1rk-0thmer
 Encyclopedia  of Chemical  Technology,   3rd  ed.,  Vol.  12,  M.A.  Grayson,  Ed.
 John Wiley and  Sons, New York.  p. 734-771.

 Schiller, C.M.,  R.  Maiden  and I.E. Kee, Jr.  1979.  Effects of hydrazlne and
 Its  derivatives  on  the   development   of  Intestinal   brush border  enzymes.
 Toxlcol. Appl.  Pharmacol.  49(2):  305-311.

 Seller,  J.P.   1977.    Inhibition  of  testlcular  DMA  synthesis  by  chemical
 mutagens and  carcinogens.   Preliminary results 1n the validation  of  a  novel
 short-term test.  Mutat. Res.  46: 305-310.

 Sever 1,  1.  and  C.  B1anc1Hor1.    1967.   Cancerogenesl   epatlca  ne1  topi
 CBA/Cb/Se/  e   ne1  rattl  Cb/Se   da   Idrazlna  solfato.    Epatologlca.    13:
 199-208.  (Hal.)

 Sever 1,  L.  and  C.  B1anc1f1or1.   1966.  Hepatic carclnogenesls  1n CBA/Cb/Se
 mice and Cb/Se  rats  by 1son1cot1n1c  add  hydrazlde  and hydrazlne  sulfate.
 J. Natl. Cancer  Inst.  41: 331-349.

 Shukla,  P.T.   1972.  Analysis of  mutagen specificity In Orosophlla  melano-
 gaster.  Mutat.  Res.  16: 363-371.
033Id                               10-15                            08/09/90

-------
 Slna,  J.F.,  C.L.  Bean, G.R.  Dysart.  V.I. Taylor  and H.O. Bradley.   1983.
 Evaluation  of the  alkaline  elutlon/rat  hepatocyte assay  as  a predictor  of
 cardnogen1c/mutagen1c  potential.  Mutat. Res.  113(5): 357-391.
Slonlm,  A.R.  1977.   Acute toxlclty  of  selected  hydrazlnes  to the  common
guppy.  Water Res.  11(10): 689-895.

Slonlm,  A.R.  1966.   Acute toxldty  of  some  hydrazlne  compounds  to  sala-
mander larvae, Ambvstoma spp.  Bull. Environ. Contain. Toxlcol.   37:  739-746.

Slonlm,  A.R.,  and  J.B.  Glsclard.   1976.   Hydrazlne degradation 1n  aquatic
systems.  Bull. Environ. Contam. Toxlcol.   16: 301-309.

Smith, E.B.  and  D.A.   Clark.   1972.   Absorption of  hydrazlne  through  canine
skin.  Toxlcol. Appl.  Pharmacol.  21: 186-193.

Sobel, M.,  G.G.  Bond, B.J.  Skowronskl, P.J. Brownson and  R.R.  Cook.   1987.
A soft tissue  sarcoma case control  study In  a  large multl-chemical  manufac-
turing facility.   Chemosphere.  16(8/9): 2095-2099.

Sotanleml,  E.,  J.  Hlrvonen,  H.  Isomakl,  J. Takkunen  and  J.  Kalla.   1971.
Hydrazlne toxldty  1n the  human —  Report of a  fatal case.  Ann. Clln.  Res.
3: 30-33.
Sotomayor,  R.E.,  P.S.   Chauhan   and   U.K.   Ehllng.    1982.    Induction  of
unscheduled DNA  synthesis  1n  the  germ cells of  male mice after  treatment
with hydrazlne or procarbazlne.  Toxicology.  25(2-3): 201-211.
0331 d
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08/09/90

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 Southgate,  B.A.   1950.  Polluting effects  of  sewage  and Industrial wastes -
 Toxlclty of substances to  fish.   Ann.  Report  Water Pollut. Res. Bd.  (Cited
 1n  McKee and Wolf,  1963)

 Springer.  D.L.,  B.M.  Krlvak,  O.J. BrodeMck, O.J. Reed and F.N. Dost.  1981.
 Metabolic  fate of hydrazlne.   J.  ToxHol. Environ.  Health.  8(1-2): 21-29.

 SRI   (Stanford   Research   Institute).   1989.   1989  Directory  of  Chemical
 Producers:  United  States   of  America.   SRI  International, Menlo  Park,  CA.
 p.  577,  688.

 Stauffer,  T.B.   1977.   Hydrazlne evaporation.   In:  Proc. Conf.  Env.  Chem.
 Hydrazlne Fuels, Tyndall AFB.  NTIS AD-A054194.  p. 25-38.

 Stelnhoff,  0.  and U.  Mohr.  1988.  The question  of  carcinogenic  effects of
 hydrazlne.  Exp. Pathol.   33(3):  133-143.

 Stone.  D.A,  F.L. Wiseman,  J.E.  Kllduff,  S.L.  Koontz and  D.D.  Davis.   1989.
 The  disappearance  of fuel  hydrazlne  vapors  1n  fluorocarbon-fllin environ-
 mental  chambers.   Experimental observations and  kinetic  modeling.   Environ.
 Sc1. Techno!.  23: 328-333.

 Toth,  B.   1969.   Lung tumor  Induction  and  Inhibition  of  breast adenocarcl-
 nomas  by hydrazlne sulfate  1n mice.  J. Natl. Cancer Inst.  42: 469-475.

 Toth,  B.   1971.   Investigations  on the relationship  between  chemical  struc-
 ture and  carcinogenic activity of substituted hydrazlnes.  Proc.  Am.  Assoc.
 Cancer Res.  12: 55.

0331d                               10-17                            08/09/90

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 Toth,  8.   1972a.   Hydrazlne.  methylhydrazlne  and  methylhydrazlne  sulfate
 cardnogenesls  In Swiss  mice.   Failure  of  ammonium hydroxide  to Interfere  In
 the development of tumors.  Int. J. Cancer.  9: 109-118.

 Toth,   B.    1972b.    Tumour 1genes 1s   studies  with   1,2-dlmethylhydrazlne
 dlchloMde,  hydrazlne  sulfate   and   1son1cot1n1c  acid  1n  golden  hamsters.
 Cancer Res.  32:  804-807.

 Tsuchlmoto, T.  and B.E. Matter.   1981.   Activity  of coded compounds  In the
 mlcronucleus test.  Prog. Hut. Res.  1:  705-711.

 Tuazon, E.C.. W.P.L.  Carter, A.M.  Miner  and  J.N.  Pitts, Jr.   1981.  Reaction
 of hydrazlnes  with ozone  under simulated atmospheric  conditions.   Environ.
 Scl.  Techno1.  15: 823-828.

 U.S.   EPA.  1980.   Guidelines   and Methodology  Used  In  the  Preparation  of
 Health  Effect  Assessment   Chapters  of  the  Consent   Decree  Water  Criteria
 Documents.  Federal Register.  45(231):  79347-79357.

 U.S.  EPA.  1984a.  Methodology  and Guidelines  for  Ranking Chemicals  Based  on
 Chronic Tox1c1ty  Data.   Prepared  by  the Office of Health and  Environmental
 Assessment, Environmental  Criteria and  Assessment  Office, Cincinnati.  OH for
 the Office of Emergency and Remedial  Response, Washington, DC.
U.S.  EPA.   1984b.   Health  and  Environmental  Effects Profile  for  Hydrazlne
and Hydrazlne  Sulfate.   Prepared by  the  Office of Health  and  Environmental
Assessment, Environmental Criteria  and  Assessment  Office,  Cincinnati,  OH for
the Office of Solid Haste, Washington. DC.
0331 d
10-18
08/09/90

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U.S.  EPA.   1985.   Reportable  Quantity Document for  Hydrazlne  and Hydrazlne
Sulfate.   Prepared by  the  Office  of  Health  and  Environmental  Assessment,
Environmental  Criteria  and Assessment Office,  Cincinnati,  OH  for  the Office
of Emergency and Remedial Response, Washington, DC.

U.S.  EPA.   1986a.  Methodology for  Evaluating Reportable  Quantity  Adjust-
ments Pursuant  to  CERCLA  Section  102.   Prepared by the Carcinogen Assessment
Group,  Office  of   Health  and  Environmental  Assessment  for  the  Office  of
Emergency and Remedial Response, Washington. DC.

U.S.  EPA.   1986b.  Reference  Values  for  Risk  Assessment.   Prepared  by  the
Office  of  Health  and Environmental  Assessment,  Environmental Criteria  and
Assessment Office,  Cincinnati,  OH for  the  Office  of Solid Waste,  Washington,
DC.

U.S.  EPA.    1986c.   Guidelines  for   Carcinogen   Risk  Assessment.   Federal
Register.  51(185): 33992-34003.

U.S.  EPA.   1988.   Evaluation  of  the Potential CareInogenlcity of Hydrazlne
In  Support  of  Reportable  Quantity Adjustments  Pursuant to  CERCLA  Section
102.   Prepared  by the Carcinogen  Assessment  Group, Office  of   Health  and
Environmental  Assessment  for the Office of Emergency and Remedial Response,
Washington, DC.

U.S.  EPA.    1989.   Integrated  Risk  Information  System  (IRIS).   Online.
Office  of  Health  and Environmental  Assessment.  Environmental Criteria  and
Assessment Office,  Cincinnati, OH.

0331 d                               10-19                            08/09/90

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 U.S.  EPA/OWRS (U.S. Environmental Protection Agency/Office  of  Water  Regula-
 tions  and  Standards).   1986.   Guidelines  for  Deriving Numerical  National
 Water  Quality Criteria  for the  Protection  of  Aquatic  Organisms and  Their
 Uses.  U.S. EPA, Washington, DC.  p. 22-58, 98.  NTIS PB85-2270049/XAB.

 Vernot, E.H.,  J.D.  MacEwen,  R.H.  Bruner,  et  al.   1985.   Long-term Inhalation
 tox1c1ty of hydrazlne.  Fund. Appl. Toxlcol.   5:  1050-1064.

 Vljaykumar,  N.K.  and H.K.  Jain.   1979.   Comparative   studies  on  Induced
 mutations  with physical and chemical  mutagens  In  Drosophlla  roelanogaster:
 Part  1.  Specificity  and  spectrum  of  mutations.   Ind.   J.  Exp.  Blol.   17:
 61-65.

 Von  Wright,  A.   1981.   Hydrazlne and  methylhydrazlne  as  recA*  Independent
mutagens In EscheMchla  coll.   In:  Chromosome Damage and Repair,  E.  Seeberg
and  K.  Kleppe, Ed.   Plenum Press, NY.   p.  517-520.  NATO  Adv.  Study  Inst.
 Sen. A, 40.

Wade, D.R., P.H.  Lohman, E.I.  Mattern  and F. Berends.   1981.   MutagenlcHy
of  isonlazld  in Salmonella  and Us effects  on  DNA repair   and synthesis  In
human flbroblasts.  Nutat.  Res.  89: 9-20.

Hakabayashl.  T.,  H.  Hor1uch1. M.  Sokaguchl. et  al.   1983.   Induction  of
megamltochondria  1n  the mouse and  rat  livers  by hydrazlne.   Exp.   Nol.
Pathol.  39(2): 139-153.
0331 d
10-20
08/09/90

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 Hakabayashl,  T.,  K. Yamashlta, K. Adachl, et al.  1987.  Changes In physico-
 chemical  properties of mitochondria!  membranes  during the formation process
 of  megamltochondrla Induced by hydrazlne.  Toxlcol. Appl. Pharmacol.  67(2):
 235-248.

 Maid,  N.J.   1985.  Hydrazlne:  Ep1dem1olog1cal   evidence.   IARC  Sc1.  Publ.
 Iss. 65.   p.  75-80.

 Weast,  R.C.,   Ed.   1985.    CRC  Handbook of  Chemistry  and Physics,  66th  ed.
 CRC  Press,  Boca Raton, PL.  p. B-99, C-313.

 Weatherby,  J.H. and A.S.  Yard.   1955.   Observations on the subacute toxldty
 of hydrazlne.  Arch. Ind. Health.  11:  413-419.

 Wheeler,  C.E.,  S.R. Penn  and E.P. Cawley.   1965.   Dermatitis  from hydrazlne
 hydrobromlde  solder  flux.   Arch.  Dermatol.  91: 235-239.

 Wlndholz,  M.. Ed.   1983.   The  Merck   Index:  An  Encyclopedia  of  Chemicals,
 Drugs, and  B1olog1ca1s, 10th  ed.   Merck and Co.,  Inc., Rahway, NJ.  p.  473.
 691, 872.

 Hrangsjo,  K.  and  A. Martensson.  1986.   Hydrazlne contact dermatitis  from
 gold plating.  Contact Derm.  15(4):  244-245.  (Taken from NIOSH/00166309)

 Wryobek,  A.,   L.  Gordon and  G.  Watchmaker.   1981.   Effect  of 17  chemical
 agents Including  6 carclnogen/noncardnogen pairs  on  sperm  shape  abnormali-
 ties In  mice.  Prog. Mutat.  Res.  1(Eva1. Short-Term  Tests Carclnog.:  Rep.
 Int. Collab. Program): 712-717.
0331d                               10-21                            08/09/90

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 Yamamoto,  R.S.  and  J.H.  Uelsburger.   1970.   failure  of  arglnlne  glutamate  to
 Inhibit  lung  tumour  formation  by 1son1az1d  and  hydrazlne  1n mice.   Life Scl.
 9: 285-289.

 Yaws,  C.L.,  J.R.  Hooper  and  M.G.   Rojas.   1974.   Ammonia  and  hydrazlne.
 Chem. Eng.  81: 91-100.

 Yoon, J.S.,  J.H.  Mason,  R. Valencia, R.C.  Woodruff  and S.  Z1mmer1ng.   1985.
 Chemical  mutagenesls  testing  1n  DrosophHa.   IV. Results  of 45  coded com-
 pounds  tested for the  National  Toxicology Program.  Environ. Nol.  Mutagen.
 7: 349-367.
0331 d
10-22
08/09/90

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                                  APPENDIX A

                              LITERATURE SEARCHED



    This   HEED   Is  based  on  data   Identified  by  computerized  literature

 searches of  the  following:


              CHEHLINE
              TSCATS
              CASR online  (U.S. EPA Chemical Activities Status Report)
              TOXLINE
              TOXLIT
              TOXLIT 65
              RTECS
              OHM TADS
              STORET
              SRC Environmental Fate  Data Bases
              SANSS
              AQUIRE
              TSCAPP
              NTIS
              Federal Register
              CAS ONLINE (Chemistry and Aquatic)
              HSDB
              SCISEARCH
              Federal Research In Progress


These  searches  were  conducted 1n  July,  1989,  and  the  following  secondary

sources were reviewed:
    ACGIH  (American  Conference of  Governmental  Industrial  Hyglenlsts).
    1986.   Documentation  of  the  Threshold Limit  Values  and Biological
    Exposure Indices, 5th ed.  Cincinnati, OH.

    ACGIH  (American  Conference of  Governmental  Industrial  Hyglenlsts).
    1987.   TLVs:  Threshold Limit Values  for  Chemical  Substances  In the
    Work   Environment   adopted  by   ACGIH  with  Intended  Changes  for
    1987-1988.  Cincinnati, OH.  114 p.

    Clayton.  6.0.  and F.E.   Clayton,  Ed.   1981.   Patty's  Industrial
    Hygiene  and  Toxicology,  3rd rev.  ed.,  Vol.  2A.   John Wiley and
    Sons, NY.  2878 p.

    Clayton,  G.D.  and F.E.   Clayton,  Ed.   1981.   Patty's  Industrial
    Hygiene  and  Toxicology,  3rd rev.  ed..  Vol.  28.   John Wiley and
    Sons, NY.  p. 2879-3816.
0332d                               A-l                              01/22/90

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     Clayton,  G.D.  and  F.E.   Clayton,  Ed.   1982.   Patty's  Industrial
     Hygiene  and  Toxicology,  3rd  rev,  ed.,  Vol.  2C.   John Wiley  and
     Sons,  NY.   p.  3817-5112.

     Grayson,  N. and  D.  Eckroth, Ed.   1978-1984.   Klrk-Othmer  Encyclo-
     pedia  of  Chemical  Technology,  3rd  ed.   John Wiley and Sons, NY.  23
     Volumes.

     Hamilton, A.  and  H.L.  Hardy.  1974.  Industrial  Toxicology, 3rd ed.
     Publishing  Sciences Group, Inc., Littleton, MA.  575 p.

     IARC  (International  Agency  for  Research  on  Cancer).   IARC  Mono-
     graphs  on  the Evaluation  of  Carcinogenic  Risk  of Chemicals  to
     Humans.  IARC, WHO, Lyons, France.

     Jaber,  H.M.,  W.R.  Mabey,  A.T.  L1eu,  T.W.  Chou  and  H.L.  Johnson.
     1984.   Data   acquisition   for   environmental   transport  and  fate
     screening for  compounds of  Interest  to  the Office  of Solid  Waste.
     EPA  600/6-84-010.   NTIS  PB84-243906.   SRI  International,   MenTo
     Park, CA.

     NTP  (National  Toxicology  Program).  1987.   Toxicology Research and
     Testing  Program.   Chemicals   on   Standard  Protocol.   Management
     Status.

     Ouellette,  R.P.   and   J.A.   King.   1977.   Chemical Week  Pesticide
     Register.  McGraw-Hill Book Co., NY.

     Sax, I.N.   1984.   Dangerous  Properties of Industrial Materials, 6th
     ed.  Van Nostrand Relnhold Co., NY.

     SRI  (Stanford Research  Institute).   1987.   Directory  of  Chemical
     Producers.  Menlo Park, CA.

     U.S. EPA.   1986.    Report  on  Status  Report  In  the  Special  Review
     Program,  Registration  Standards  Program  and  the  Data  Call  In
     Programs.   Registration Standards  and the  Data  Call  In Programs.
     Office of Pesticide Programs, Washington, DC.

     USITC  (U.S.  International  Trade  Commission).    1986.   Synthetic
     Organic Chemicals.   U.S.   Production  and  Sales,  1985,  USITC  Publ.
     1892, Washington.  DC.

     Verschueren,  K.   1983.  Handbook  of  Environmental  Data  on Organic
     Chemicals, 2nd ed.  Van Nostrand Relnhold Co., NY.

    Wlndholz. M.t Ed.  1983.   The Merck Index,'10th  ed.  Merck and Co.,
     Inc., Rahway, NJ.

    Worthing, C.R.  and S.B. Walker,  Ed.   1983.  The  Pesticide Manual.
    British Crop Protection Council.  695 p.
0332d
A-2
01/22/90

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     In  addition, approximately  30 compendia  of  aquatic  toxicity  data were

 reviewed,  Including  the  following:


     Battelle's  Columbus  Laboratories.    1971.   Water  Quality Criteria
     Data   Book.   Volume  3.  Effects  of  Chemicals  on   Aquatic  Life.
     Selected  Data from  the  Literature  through 1968.   Prepared for the
     U.S. EPA under Contract No. 68-01-0007.  Washington, DC.

     Johnson,  W.W.  and M.T.  Flnley.   1980.  Handbook  of  Acute Toxicity
     of  Chemicals  to  Fish  and  Aquatic   Invertebrates.   Summaries  of
     Toxicity  Tests   Conducted  at  Columbia National  Fisheries Research
     Laboratory.   1965-1978.   U.S. Dept.  Interior,  Fish and Wildlife
     Serv.  Res. Publ. 137, Washington, DC.

     HcKee,  J.E.  and  H.W. Wolf.  1963.  Water  Quality  Criteria, 2nd ed.
     Prepared  for  the  Resources  Agency  of  California,  State  Water
     Quality Control  Board.  Publ.  No. 3-A.

     Plmental, D.  1971.   Ecological  Effects  of Pesticides on Non-Target
     Species.  Prepared for the U.S. EPA, Washington, DC.  PB-269605.

     Schneider, 8.A.   1979.   Toxicology  Handbook.   Mammalian  and Aquatic
     Data.   Book  1: Toxicology  Data.   Office  of Pesticide Programs, U.S.
     EPA, Washington, DC.  EPA 540/9-79-003.  NTIS PB 80-196876.
0332d                               A-3                              01/22/90

-------

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-------
                                  APPENDIX C
        DOSE/DURATION RESPONSE GRAPHS FOR EXPOSURE TO BROHOCHLOROMETHANE
C.I.    DISCUSSION
    Dose/duration-response   graphs   for   Inhalation  exposure  to  hydrazlne
generated  by the method  of  Crockett et al.  (1985)  using the computer soft-
ware  by Durkln  and  Meylan (1989) developed under contract to ECAO-C1nc1nnat1
are  presented  1n   Figures  C-l   through  C-5.   Data used  to generate  these
graphs  are presented  In  Section C.2.   In the  generation of  these figures,
all responses  were classified as  adverse  (FEL, AEL or  LOAEL)  or nonadverse
(NOEL or NOAEL)  for plotting.   The ordlnate expresses  Inhalation exposure In
either  of  two ways.  In Figures  C-l and C-2, the experimental concentration,
expressed  as mg/m3, was  multiplied by  the  time parameters  of  the exposure
protocol  (e.g.,  hours/day and days/week),  and  Is presented  as  the expanded
experimental  concentration  [expanded  exp  cone  (mg/m3)].   In  Figures  C-3
and  C-4,  the  expanded  experimental  concentration  was  multiplied  by  the
animal  Inhalation  rate  In  mVday and divided  by the animal body  weight in
kg  to calculate a  dally  dose  In mg/kg/day.  The dally  dose  was  then multi-
plied  by  the  cube  root  of  the ratio  of the  animal:human  body  weight to
adjust  for species differences  In metabolic rate  (Mantel and  Schneiderman,
1975).   The result  was multiplied  by  an  absorption  coefficient of  0.5 to
adjust  to  an  equivalent  absorbed  dose  and  then multiplied by  70  kg,  the
reference  human  body  weight, to express the  human  equivalent dose as rag/day
for a 70 kg human [human equivalent dose (mg/day)].
                                              j.
    The  adverse  effects  boundary  (solid line)  Is  drawn by  Identifying  the
lowest  adverse  effect  dose or  concentration  at the  shortest  duration of
exposure at  which  an adverse effect occurred.   From this starting point, an
Infinite line  1s extended upward,  parallel  to  the  dose axis.   The starting

0333d                                C-l                              01/22/90

-------
           1000
      C!

      \
     u
     ft
     a-
     x
     Q
     Z
    HVDINH.D2
    fInhalation Exposure)
     0.01                   0.1
HUHRN EQUIU MIMTION (fraction lifespan)

          ENVELOP NETHOO
 Key:    F « PEL
        I «= LOAEl
        N - NOEL
        Solid line - Adverse Effects Boundary
        Dashed line * No Adverse Effects Boundary
                                   FIGURE C-l

      Dose/Duration-Response Graph for Inhalation  Exposure to Hydrazlne:
             Envelope Method (Expanded Experimental Concentration)
0333d
       C-2
                                                                       01/22/90

-------

  I
  \

  :
  V

  L'

  M
  g
  «
  m
  x
 r
       e.ei
          e.eei
 (Inhalation Exposure)
     e.ei                  e.i
HUHflN EOU1U DURATION (fraction lifespan)

     CENSORED DftTfl METHOD
  Key:   F « PEL
         L - LOAEL
         N • NOEL
         Solid  line - Adverse Effects Boundary
         Dashed line • No Adverse Effects Boundary
                                   FIGURE  C-2

      Dose/Duration-Response Graph for  Inhalation Exposure to Hydrazlne:
          Censored Data Method (Expanded  Experimental Concentration)
0333d
          C-3
01/22/90

-------
         18068
     I
     J

     f
    c
    £

    :
   HYDINH.D2
   < Inhalation Exposure)
     e.ei                   0.1
HUHflN EQUIU DURRTION (fraction lifespan)
          EMUELOP ffilHOD
   Key:   F - FEl
          L « LOAEL
          N « NOEL
          Solid  line  *  Adverse Effects Boundary
          Dashed Hne • No Adverse Effects Boundary
                                   FIGURE C-3

      Dose/Ouratlon-Response Graph for Inhalation  Exposure to Hydrazlne:
                    Envelope Method  (Human Equivalent Dose)
0333d
        C-4
01/22/90

-------
       It
       it
      I

      *
            teeee F
            teee-r
               e.eei
      KMIH.'illft'

      < Inhalation Exposure)
HUKffl EOUIU DUJWIION (Fraction lifcspan)

     CENSORED DflTfl METHOD
  Key:    F = FEL
         L - LOAEL
         N * NOEL
         Solid line  •  Adverse Effects Boundary
         Dashed line * No Adverse Effects  Boundary
                                    FIGURE C-4

       Dose/Duration-Response  Graph for Inhalation Exposure to Hydrazlne
                  Censored  Data Method (Human  Equivalent Dose)
0333d
       C-5
01/22/90

-------
       e
       t
       \
       9
            IBM-:
               F3
                                                 F2
                                                            Ft
                i
       HVDORRL 02
    0.001
    I
Exposure)
     0.01                 0.1
HUHRN EQUHJ DUHIIION (fraction lifespan)

         ENUEOP HETHOD
 Key:   F -  PEL
        A -  ACl
        Solid  line « Adverse Effects Boundary
        Dashed line - No Adverse Effects  Boundary
0333d
                                   FIGURE  C-5

         Dose/Duration-Response Graph  for Oral  Exposure to Hydrazlne:
                    Envelope Method (Human Equivalent  Dose)
      C-6                               01/22/90

-------
 point  Is then  connected  to the lowest  adverse  effect dose or concentration
 at  the next  longer  duration of exposure that has  an  adverse effect dose or
 concentration equal  to or  lower   than  the  previous  one.  This  process Is
 continued  to  the  lowest  adverse  effect dose  or  concentration.   From  this
 point,  a line  parallel to  the  duration axis Is  extended Infinitely to the
 right.   The  adverse  effects  region  lies  above the  adverse  effects boundary.
    Using the envelope method,  the  no adverse effects boundary (dashed line)
 Is  drawn,  starting  with  the   point  representing  the  highest  no  adverse
 effects  dose  or  concentration.   From  this  point, a  line parallel  to  the
 duration  axis Is extended  to  the  dose  or  concentration  axis.  The starting
 point  Is  then connected to the next equal or lower no adverse effect dose or
 concentration at  a  longer  duration of  exposure.   When this  process  can no
 longer  be continued,  a line parallel  to  the dose or  concentration  axis 1s
 dropped  to  the duration axis.   The  no adverse  effects region lies below the
 no  adverse  effects  boundary.   At  either  ends  of  the  graph between  the
 adverse  effects  and no adverse  effects  boundaries  are regions of ambiguity.
 The area  (If any)  resulting from Intersections  of the adverse effects and no
 adverse effects boundaries  1s defined  as the region of contradiction.
    In  the censored  data  method, all no adverse effect points located In the
 region  of  contradiction are dropped from consideration,   and  the  no adverse
 effects  boundary  Is  redrawn   so  that  It  does  not  Intersect the  adverse
 effects  boundary  and no  region  of  contradiction  1s generated.   This method
 results  In the most  conservative definition of the no adverse effects region.
 In  Figures   C-1  through C-4,  the  adverse  effects boundary  (solid  line) Is
 defined  by  data  points  corresponding  to  LC5Q  values  In rats  (Rec.  |19),
 and mice (Rec.  #18) and  LOAELs for  lung  and  liver  effects  1n  dogs  (Rec.
 #13),  for  fatty  liver degeneration  In monkeys  (Rec.  #5), for  growth rate
0333d                               C-7                              01/22/90

-------
 depression  In  rats  (Rec.  #4),  for  amyloldosls  and  testlcular  effects  In
 hamsters  (Rec.  114), and  for  lung effects  In  rats  (Rec.  #15).  Rec.  #1,  a
 PEL  for mortality  In  mice, Is  not  displayed  because It would  obscure Rec.
 #4.   The  no adverse effects boundaries  (dashed line)  In Figures  C-1  and C-3
 are  defined by NOELs  In  dogs  examined  for  changes  1n  body weight, clinical
 chemistry,  hematology,  organ weight  and histology  (Recs.  #2  and  17).  and a
 NOEL  In female mice  examined  for effects  on  body weight  and pulmonary and
 liver   toxlcity  (MacEwen  et  al.,   1981)  (Rec.  #16).    A   small   region  of
 ambiguity  Is  evident   1n   graphs  produced  by  the  envelope  method  and  Is
 primarily  the result of  the NOEL In  mice (Rec.  #16),  suggesting  that mice
 may  be  less  sensitive  than  hamsters   and  rats  to  Inhalation exposure  to
 hydrazlne.
    Figures  C-2 and C-4  were generated with  the  censored data  method and
 show the most conservative definition of the no adverse effects region.
    Oral  nonneoplastlc  toxlclty  data  for  hydrazlne were  used  to generate
 Figure  C-5.  Two  oral  studies  were available  for  presentation 1n  dose/
 duration-response graphs:  Heatherby  and  Yard (1955)  and Blanclflorl (1970d).
 Neither  study  reported a NOEL  or   NOAEL,  and  only  serious effects  were
 observed, Including mortality  or shortened llfespan.  Lack  of NOEL or NOAEL
 data points precludes the generation of  a no adverse effects boundary.
 C.2.   DATA USED TO GENERATE DOSE/DURATION-RESPOUSE GRAPHS
C.2.1.   Inhalation.
Chemical Na*e:    Hydrazlne
CAS Number:       302-01-2
 Document Title:   Health and Environmental Effects Document on Hydrazlne
 Document Number:  pending
 Document Date:    pending
 Document Type:    HEED
0333d
C-8
01/22/90

-------
 RECORD  #1:
Comment:
 Species:
 Sex:
 Effect:
 Route:
Mice
Female
FEL
Inhalation
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
0.03 kg
0.2 ppm
0.262 mg/m"
6 months
6 months
32.00
24.00
7.00
180.00
Citation:
Number Exposed:     40
Number Responses:   1
Type of Effect:     DEATH
Site of Effect:     BODY
Severity Effect:    10

Exposed to  0,  0.2,  1  ppm continuously  or  1  or 5  ppm 6 hours/
day,  5 days/week  for  6  months.   Mortality was  dose-related,
none   In  controls;   no  statistical   analysis.   Death  due  to
hepatotoxlclty.

Haun and Klnkead, 1973
RECORD #2: Species:
Sex:
Effect:
Route:





Dogs
Hale
NOEL
Inhalation





Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
12.7 kg
1 ppm
0.234 mg/m*
6 months
6 months
32.00
6.00
5.00
130.00
Comment:


Citation:
Number Exposed:     8
Number Responses:   0
Type of Effect:
Site of Effect:
Severity Effect:    2

Exposed  to  0.2  or  1  ppm continuously  or  1 or  5  ppm  Inter
mlttently (see previous record).

Haun and Klnkead, 1973
0333d
                     C-9
                                           01/22/90

-------
 RECORD #3:
Comment:


Citation:
Species:
Sex:
Effect:
Route:
Dogs
Hale
LOAEL
Inhalation
               Number Exposed:
               Number Responses:
               Type of Effect:
               Site of Effect:
               Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
                    8      8
                    NR     NR
                    WGTDC  HEMAT
                    BODY   BLOOD
                    4      3
12.7 kg
5 ppm
1.17 mg/m»
6 months
6 months
32.00
6.00
5.00
180.00
See  previous   records;   effects  were   reported   at  1  ppm
continuous and 5 ppm Intermittent.

Haun and Klnkead, 1973
RECORD #4: Species:
Sex:
Effect:
Route:





Rats
Male
LOAEL
Inhalation





Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
f Inhal. Exp. days:
0.35 kg
1 ppm
0.234 mg/rn"
6 months
6 months
32.00
6.00
5.00
180.00
Comment:

Citation:
Number Exposed:     50
Number Responses:   NR
Type of Effect:     WGTDC
Site of Effect:     BODY
Severity Effect:    4

See record 11; dose-related growth rate depression.

Haun and Klnkead, 1973
0333d
                     C-10
                                           01/22/90

-------
 RECORD #5;
Comment:

Citation:
Species:
Sex:
Effect:
Route:
Honkeys
Female
LOAEL
Inhalation
Number Exposed:     4
Number Responses:   NR
Type of Effect:     PATHO
Site of Effect:     LIVER
Severity Effect:    5

See record #1.

Haun and Klnkead, 1973
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day;
Inhalation days/week:
# Inhal. Exp. days:
8 kg
1 ppm
0.234 mg/m3
6 months
6 months
32.00
6.00
5.00
180.00
RECORD #6: Species:
Sex:
Effect:
Route:





Dogs
NR
LOAEL
Inhalation





Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
12.7 kg
4.6 ppm
1.08 mg/m3
31 Weeks
31 Weeks
32.00
6.00
5.00
217.00
Comment:
Citation:
Number Exposed:     2      2
Number Responses:   2      2
Type of Effect:     WGTDC  DEGEN
SHe of Effect:     BODY   LUNG
Severity Effect:    4      7

Exposed  0,  4.6  ppm;  one  dog  served  as a  control.   Muscle
tremors, weakness,  vomiting after  11  weeks.  Lung:  emphysema
and atalectasls.

Corns lock et al., 1952
0333d
                     C-ll
                                           01/22/90

-------
 RECORD #7:
Comment:


Citation:
Species:
Sex:
Effect:
Route:
Rats
NR
PEL
Inhalation
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
I Inhal. Exp. days:
0.35 kg
4.6 ppm
1.08 mg/m3
31 weeks
31 weeks
32.00
6.00
5.00
217.00
Number Exposed:     20
Number Responses:   2
Type of Effect:     DEATH
Site of Effect:     BODY
Severity Effect:    1

Exposed 0,  4.6 ppm.   Ten  rats served  as  controls.
died during week 28; emphysema 1n lungs of  survivors.

Comstock et al., 1952
                                           Two  rats
RECORD #8: Species:
Sex:
Effect:
Route:





Rats
Male
PEL
Inhalation





Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
I Inhal. Exp. days:
0.35 kg
13.7 ppm
3.2 mg/m3
6 months
6 months
32.00
6.00
5.00
180.00
Comment:


Citation:
Number Exposed:     30
Number Responses:   23
Type of Effect:     DEATH
SHe of Effect:     BODY
Severity Effect:    10

Only one  exposure  level; controls not  reported.   See Section
6.1.1.1 for description of results.

Comstock et al., 1954
0333d
                     C-12
                                           01/22/90

-------
 RECORD  #9:
Comment:


Citation:
Species:
Sex:
Effect:
Route:
Mice
Female
PEL
Inhalation
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week;
# Inhal. Exp. days:
Number Exposed:     20
Number Responses:   15
Type of Effect:     DEATH
Site of Effect:     BODY
Severity Effect:    10

Only one  exposure level; controls not  reported
those surviving to term had no abnormalities.

Comstock et al.f 1954
0.03 kg
13.7 ppm
3.2 mg/m3
6 months
6 months
32.00
6.00
5.00
180.00
                                        Necropsy  on
RECORD #10: Species:
Sex:
Effect:
Route:





Guinea pigs
NR
PEL
Inhalation





Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
0.84 kg
13.7 ppm
3.2 mg/m'
6 months
6 months
32.00
6.00
5.00
180.00
Comment:

Citation:
Number Exposed:     10
Number Responses:   8
Type of Effect:     DEATH
SHe of Effect:     BODY
Severity Effect:    10

Only one exposure; controls not reported.

Comstock et al., 1954
0333d
                     C-13
                                           01/22/90

-------
 RECORD #11
Comment:


Citation:
Species:   Dogs            Body Weight:           12.7 kg
Sex:       Male            Reported Dose:         13.7 ppm
Effect:    PEL             Converted Dose:        3.2 mg/ma
Route:     Inhalation      Exposure Period:       6 months
                           Duration Observation:  6 months
                           Molecular Weight:      32.00
                           Inhalation hours/day:  6.00
                           Inhalation days/week:  5.00
                           # Inhal. Exp. days:    180.00

Number Exposed:     4
Number Responses:   2
Type of Effect:     DEATH
Site of Effect:     BODY
Severity Effect:    10

Only one  exposure;  controls not  reported.   Dogs surviving  to
term had fatty changes 1n liver, spleen.

Cornstock et al., 1954
RECORD #12: Species:
Sex:
Effect:
Route:





Guinea pigs
Male
LOAEL
Inhalation




•
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
f Inhal. Exp. days:
0.84 kg
5.7 mg/m«
1.02 mg/ra*
10 weeks
10 weeks
32.00
6.00
5.00
70.00
Comment:


Citation:
Number Exposed:     8
Number Responses:   8
Type of Effect:     HYPRP
Site of Effect:     LUNG
Severity Effect:    7

0  or  3-6  mg/m»  for   2  weeks  and  4-8  mg/m9  additional  8
weeks (TWA 5.7 mg/m').

Ueatherby and Yard, 1955
0333d
                     C-14
01/22/90

-------
 RECORD  #13:
Comment:

Citation:
Species:
Sex:
Effect:
Route:
Dogs
NR
LOAEL
Inhalation
               Number Exposed:
               Number Responses:
               Type of Effect:
               SHe of Effect:
               Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
                    2      2
                    2      2
                    PATHO  PATHO
                    LUNG   LIVER
                    7      5
Exposed to 3-6 (average 4.5 mg/m3).

Weatherby and Yard, 1955
 12.7 kg
 4.5 mg/m3
 1.07 mg/m3
 7 days
 7 days
 32.00
 6.00
 5.00
 7.00
RECORD #14:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Hamsters
Male
LOAEL
Inhalation
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day;
Inhalation days/week:
# Inhal. Exp. days:
0.13 kg
0.25 ppm
0.0584 mg/m»
365 days
730 days
32.00
6.00
5.00
730.00
160
67
PATHO
LIVER
5
159
55
ATROP
TESTE
7
164
53
PATHO
KIDNY
5
117
20
PATHO
THYRD
5
155
49
PATHO
AORNL
5
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:

Exposed  0,  0.25,  1.0,  5.0  ppm   In  well   conducted,   well
controlled  study.   Increased  amalo1dos1s  of  liver,  kidney,
spleen, thyroid, adrenal; testlcular atrophy.

MacEwen et al., 1981
0333d
                     C-15
                                           01/22/90

-------
 RECORD #15;
Comment:
Species:
Sex:
Effect:
Route:
Rats
Hale
LOAEL
Inhalation
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day;
Inhalation days/week;
# Inhal. Exp. days:
0.2 kg
0.05 ppm
0.0117 mg/m3
365 days
730 days
32.00
6.00
5.00
730.00
96
9
HYPRP
NASAL
3
95
42
HYPRP
PULMN
3
97
17
IRRIT
PULMN
3
100
NR
WGTDC
BODY
4
Citation:
               Number Exposed:
               Number Responses:
               Type of Effect:
               Site of Effect:
               Severity Effect:
Exposed 0, 0.05,  0.25,  1.0,  5.0 ppm.  Myocardlal degeneration
at 1.0  ppm in males, at  5.0 ppm 1n females.  Females  at  0.05
ppm  also  had   avarlan   atrophy,   salplngltls,   endometrltls,
reduced body weight.

MacEwen et al., 1981
RECORD #16: Species:
Sex:
Effect:
Route:





Nice
Female
NOEL
Inhalation





Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
0.024 kg
1 ppm
0.234 mg/m*
365 days
730 days
32.00
6.00
5.00
730.00
Comment:
Citation:
Number Exposed:     400
Number Responses:   0
Type of Effect:
SUe of Effect:
Severity Effect:    4

0,  0.05,  0.25,  1.0  ppm;  slight  dose-related
mortality,   but   probably  not  significant   (no
analysis).  No nonneoplastlc pathological lesions.

MacEwen «t al.. 1981
                                        Increase  In
                                         statistical
0333d
                     C-16
                                           01/22/90

-------
RECORD #17:
Comment:


Citation:
Species:
Sex:
Effect:
Route:
Oogs
Both
NOEL
Inhalation
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
Number Exposed:     8
Number Responses:   0
Type of Effect:
SHe of Effect:
Severity Effect:    2

Exposed 0,  0.25,  1.0  ppm; no  effects
chemistry, BSP retention,  pathology.

MacEwen et al., 1981
12.7 kg
1  ppm
0.234 mg/tn3
365 days
730 days
32.00
6.00
5.00
730.00
                             on  survival,  clinical
RECORD #18: Species:
Sex:
Effect:
Route:





Mice
NR
PEL
Inhalation





Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
0.03 kg
252 ppm
330 mg/m3
1 days
1 days
32.00
4.00
1.00
1.00
Comment:
Citation:
Number Exposed:     NR
Number Responses:   NR
Type of Effect:     DEATH
Site of Effect:     BODY
Severity Effect:    10

Acute  Inhalation  LCso for mice was  determined.   Not adjusted
to  equivalent  continuous exposure.   Pulmonary hemorrhage  and
edema, CNS hemorrhages due to convulsions.

Jacobson et al., 1955
0333d
                     C-17
                                           01/22/90

-------
 RECORD  #19:
Comment:
Citation:
 Species:   Rats            Body Weight:           0.35 kg
 Sex:       NR              Reported Dose:         570 ppm
 Effect:    PEL             Converted Dose:        747 mg/m3
 Route:     Inhalation      Exposure Period:       1 day
                           Duration Observation:  1 day
                           Molecular Weight:      32.00
                           Inhalation hours/day:  4.00
                           Inhalation days/week:  1.00
                           Jt Inhal. Exp. days:    1.00

 Number Exposed:     NR
 Number Responses:   NR
 Type of Effect:     DEATH
 Site of Effect:     BODY
 Severity Effect:    10

 Acute  Inhalation LC5Q  In rats  determined.   Not adjusted  to
 equivalent   continuous    exposure   concentration.    Pulmonary
 hemorrhage and edema, CNS hemorrhage due to convulsions.

 Jacobson et al., 1955
C.2.2.  Oral.

Chemical Name:
CAS Number:
Document Title:
Document Number:
Document Date  :
Document Type  :
   Hydrazlne
   302-01-2
   Health and Environmental Effects Document for Hydrazlne
   pending
   pending
   HEED
RECORD |1
Comment:
Citation:
Species:
Sex:
Effect:
Route:

Rats
Male
FEL
Water

Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
0.35 kg
100 mg/i


14.2 mg/kg/day
14 weeks
14 weeks


Number Exposed:     10
Number Responses:   3
Type of Effect:     DEATH
Site of Effect:     BODY
Severity Effect:    10

0, 0.1, 0.2,  0.5,  1 or 2 mg/mi  for  up to  14  weeks.   One rat
died after  5 weeks  exposure,  two died  after  6  weeks;  study
continued with survivors until 14 weeks.

Weatherby and Yard, 1955
0333d
                     C-18
01/22/90

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 RECORD  #2:
Comment:
Citation:
Comment:
Citation:
Comment:


Citation:
 Species:
 Sex:
 Effect:
 Route:
Rats
Male
FEL
Water
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
0.35 kg
500 mg/a
70.8 mg/kg/day
4 weeks
                                        Duration Observation: 14 weeks
Number Exposed:     10
Number Responses:   4
Type of Effect:     DEATH
Site of Effect:
Severity Effect:    10

See  record #1.   Dose  levels may  be  Inaccurate because  rats
did  not  tolerate drinking water hydrazlne concentrations well
at >500 mg/i.

Weatherby  and Yard, 1955
RECORD #3:




Species:
Sex:
Effect:
Route:

Rats
Male
FEL
Water

Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
0.35 kg
1000 mg/l
142 mg/kg/day
3 weeks
14 weeks
Number Exposed:     10
Number Responses:   1
Type of Effect:     DEATH
Site of Effect:
Severity Effect:    10

See record  #1.   Dose level  may  not be accurate  because rats
did not  tolerate drinking water  hydrazlne concentrations >500
mg/i.

Weatherby and Yard, 1955
RECORD #4:




Species:
Sex:
Effect:
Route:

Rats
Hale
FEL
Gavage

Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
0.35 kg
60 mg/kg/day
60 mg/kg/day
1 days
1 days
Number Exposed:     NR
Number Responses:   NR
Type of Effect:     DEATH
Site of Effect:
Severity Effect:    10

Acute  oral  1059 determination for  hydrazlne  In  young  rats
was ~60 mg/kg.

Weatherby and Yard. 1955
0333d
                     C-19
                                           01/22/90

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 RECORD  |5:
Comment:
Species:   Hamsters      Body Weight:
Sex:       Both          Reported Dose:
Effect:    FEL           Converted Dose:
Route:     Gavage        Exposure Period:
                         Duration Observation:

                            23
                            NR
                            SURVI
                            NR
                            10
0.14 kg
3 mg/kg/day
3 mg/kg/day
15 weeks
125 weeks
               Number Exposed:     23
               Number Responses:   14
               Type Of Effect:     DEGEN
               Site of Effect:     LIVER
               Severity Effect:    7
Citation:
Hamsters  received  0,  3 mg  hydrazlne  sulfate/day for 60  days
1n 15 weeks,  which Is equivalent to 0.42 mg  hydraz1ne/day  or
3.0   mg  hydrazlne/kg/day.   Liver   lesions   and   shortened
llfespan.

81anc1f1or1, 1970d
RECORD #6:



Species:
Sex:
Effect:
Route:
Hamsters
Both
FEL
Gavage
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
0.14 kg
3.5 mg/kg/day
3.5 mg/kg/day
20 weeks
Comment:
               Number Exposed:     35
               Number Responses:   29
               Type of Effect:     DEGEN
               Site of Effect:     LIVER
               Severity Effect:    7
                         Duration Observation: 125 weeks

                            35
                            NR
                            SURVI
                            BODY
                            10
Citation:
Hamsters  received  0,  2.8 mg  hydrazlne  sulfate/day  for  100
days In  20  weeks,  which  Is  equivalent  to 0.49 mg  hydrazlne/
day or  3.5  mg hydrazlne/kg/day.  Liver  lesions and shortened
Hfespan.

B1anc1MoM, 19700
NR = Not reported
0333d
                     C-20
       03/28/90

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            UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                     OFFICE OF RESEARCH AND DEVELOPMENT
                  ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
                               CINCINNATI. OHIO 45268
                                  AUG 25 1990
Health and Environmental Effects Document
                                   . o
W. Bruce Peirano
Acting Chief
Chemical Mixtures Assessment Branch

Matthew Straus
Chief, Waste Characterization Branch
Office of Solid Waste (OS-330)
SUBJECT:
FROM:
TO:
THRU:  fa Chris DeRosa, Ph.D.
         V  Acting Director
            Environmental Criteria and Assessment Office-Cin
                                  /, ///>/-"V
                                M/**«- V  ^-^
            William H. Farland, Ph.D.
            Director
            Office of Health and Environmental
               Assessment (RD-689)

      Attached  please  find  two  unbound  ccp'es  of  the  following  Health  and
Environmental Effects  Document (HEED) for:

      Hydrazine  (ECAO-Cin-G105)

      This document represents scientific summaries of the pertinent available data on
the environmental  fate and  mammalian and aquatic toxicity of the chemical  at an
extramural effort of about 14K. This document received internal OHEA, OPP and OTS
reviews as well  as review by two external  scientists.  Any pan of this document's  files
(e.g., drafts, references, reviews) are available to you upon request.

Attachments

cc:    K. Bruneske (OS-305) (w/attachments)
      M. Callahan (RD-689)
      P.  Durkin, Syracuse Research Corporation (w/attachments)
      S. Griffin (OS-330) (w/attachments)
      R. Hardesty (RD-689)
      M. Holland (RD-689)
      B. Hostage (OS-210) (w/attachments)
      A. McBride (OS-331)
      E. McNamara (PM-211A) (w/attachments)
                                                                            •

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1
         cc:   J. Moore (RD-689)
               M Pfaff (RD-689) (w/attachmems)
               C Ris (RD-689)
               R. Scarberry (OS-330)

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