Document ID: EPA-HQ-OW-2002-0043-0193
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2003-08-11T04:00Z

Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
EPA/
OW/
OST/
HECD
Final
draft
VIII­
50
Table
VIII­
1.
Summary
of
Toxicity
Studies
for
Cyanogen
Chloride.

Strain,
Species,

Sex
Reference
Dose
Route/
Volume
Duration
Response
at
LOAEL
NOAEL
LOAEL
Comments
One­
Day
HA
Human,

number
NS
Prentiss,

1937
Not
reported
Inhalation
Few
minutes
Copious
lacrimation
None
2.5
mg/
m3
Incomplete
reporting;

not
suitable
for
risk
assessment.

Human,

number
NS
Michigan
Department
of
Public
Health,

1977,
as
cited
by
ACGIH,

1991
Not
reported
Inhalation
Few
minutes
Severe
eye
and
nose
irritation
None
1.8
mg
/
m3
Incomplete
reporting;

not
suitable
for
risk
assessment
Dog
(
strain
not
specified,

11)
Haymaker
et
al.,
1952
2000
to
3800
mg/
m3
Inhalation
2
minutes
Mortality,
coma
apnea,

rigidity/
weakness
in
limbs,
incoordination,

pulmonary
edema,

necrosis
in
brain
None
2000
mg/
m3
Incomplete
reporting;

not
suitable
for
risk
assessment.

Various
species,
including
dogs
and
cats
Aldridge
and
Evans,

1946
50
to
120
mg/
m3
Inhalation
NS
Respiratory
irritation
and
lung
edema,
lachrymation,

Symptoms
dec
after
1­
2
min,
indicating
adaptation
Vomiting
and
loss
of
consciousness
at
high
exposures
None
50
mg/
m3
Incomplete
reporting;

not
suitable
for
risk
assessment.
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
1.
Summary
of
Toxicity
Studies
for
Cyanogen
Chloride.

Strain,
Species,

Sex
Reference
Dose
Route/
Volume
Duration
Response
at
LOAEL
NOAEL
LOAEL
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
46
Cat,
(
strain,

number
not
specified)
Aldridge
and
Evans,

1946
3000
mg/
m3
Inhalation
1­
2
minutes
Transitory
rise,
then
dec
arterial
pressure;
brief
inc,
then
dec
in
heart
rate
None
3000
mg/
m3
Incomplete
reporting;

not
suitable
for
risk
assessment.

Rabbit,

(
strain,
number
not
specified)
Aldridge
and
Evans,

1946
2000
mg/
m3
Inhalation
1­
2
minutes
Transitory
rise,
then
dec
arterial
pressure;
brief
increase,
then
decrease
in
heart
rate
None
2000
mg/
m3
Incomplete
reporting;

not
suitable
for
risk
assessment.

Ten­
Day
HA
Dog
(
strain
not
specified,

6/
group)
Reed,
1920
Not
reported
Injection
10­
12
days
Weight
loss,
depressed
reflexes,
cardiac
irregularity,
conjunctivitis,
rhinitis,

pulmonary
congestion
N/
A
N/
A
Incomplete
reporting;

not
suitable
for
risk
assessment.

Dog
(
5),
goat
(
1)
(
strain
and
sex
not
reported)
Reed,
1920
Not
reported
Inhalation
30
minutes
to
2
hours/
day
for
2
weeks
Weight
loss,
convulsions,

nausea,
vomiting,
muscle
tremors,
depressed
reflexes,
cardiac
irregularities,
pulmonary
congestion
N/
A
N/
A
Incomplete
reporting;

not
suitable
for
risk
assessment.

Subchronic
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
1.
Summary
of
Toxicity
Studies
for
Cyanogen
Chloride.

Strain,
Species,

Sex
Reference
Dose
Route/
Volume
Duration
Response
at
LOAEL
NOAEL
LOAEL
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
47
Human
Reed,
1920
Not
reported
Primarily
inhalation
­
occupational
8
months
Muscular
weakness;

lassitude;
lung
congestion;
irritation
of
eyes,
skin,
and
throat;
dec
appetite
and
severe
weight
loss
N/
A
N/
A
Incomplete
reporting;

not
suitable
for
risk
assessment.

Chronic:
None
located
N/
A
=
not
applicable;
NS
=
Not
specified
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
EPA/
OW/
OST/
HECD
Final
draft
VIII­
48
Table
VIII­
2.
Summary
of
Oral
Toxicity
Studies
for
Cyanide.

Strain,
Species,

Sex
Reference
Dose
Route
Duration
Response
at
LOAEL
NOAEL
mg
CN/

kg­
day
LOAEL
mg
CN/

kg­
day
Comments
One­
Day
HA
Human
Liebowitz
and
Schwartz,

1948
15­
25
mg
CN/
kg
Ingestion
Single
dose
Comatose,
muscular
rigidity,
inc
heart
rate,

enlarged
heart,
dec
respiratory
rate,
dilated
pupils,
weakness,
nausea,

vomiting.
None
15
mg/
kg
(
FEL)
Suicide
attempt
with
KCN.
Patient
was
a
chemist
with
daily
exposure
to
thiosulfate,

which
may
have
functioned
as
an
antidote.

Human
Lasch
and
El
Shawa,
1981
Not
reported
Ingestion
Single
dose
Vomiting,
nausea,

weakness,
confusion,

lethargy
with
hypotonia,

comatose
with
respiratory
depression,
cyanosis
N/
A
N/
A
24
children
exposed
to
cyanide
present
in
a
sweet
made
from
apricot
kernels.
Four
of
the
children
died.

Human
Uitti
et
al.,

1985;
Carella
et
al.,
1988;

Rosenberg
et
al.,
1989;

Grandas
et
al.,
1989
5.6­
8.6
mg
CN/
kg
Ingestion
Single
dose
Symptoms
of
parkinsonism
withing
3
weeks
to
1
year
following
recovery
from
cyanide
poisoning
None
5.6
mg/
kg
Four
separate
case
reports
of
patients
with
either
intentional
or
accidental
poisoning
with
either
KCN
or
NaCN
Human
Saincher
et
al.,
1994
0.56
mg
CN/
kg
Ingestion
Single
dose
Unconsciousness,

numbness,
shortness
of
breath,
weakness
of
hip
flexors
and
hamstrings.
None
0.56
mg/
kg
(
FEL)
Suicide
attempt
with
KCN.
Patient
recovered
without
antidote
therapy.
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
2.
Summary
of
Oral
Toxicity
Studies
for
Cyanide.

Strain,
Species,

Sex
Reference
Dose
Route
Duration
Response
at
LOAEL
NOAEL
mg
CN/

kg­
day
LOAEL
mg
CN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
49
Rat,
Sprague­

Dawley
(
20/
group,

sex
not
specified)
Ferguson,

1962
4
mg
CN/

kgday
Gavage
in
water
Single
dose
Mortality
(
19/
20
died)
None
4
mg
CN/
kg
(
FEL)
KCN
Mouse,

Swiss
Webster
(
20/
group,

sex
not
specified)
Ferguson,

1962
6
mg
CN/

kgday
Gavage
in
water
Single
dose
Mortality
(
19/
20
died)
None
6
mg/
kg
(
FEL)
KCN
Rat
(
strain,

sex,
and
number
not
specified)
Smyth
et
al.,

1969
Not
available
Gavage
in
water
Single
dose
Mortality
LD50
None
8,
22
mg/
kg
LD50
LD50
study.
Doses
for
KCN
and
Ca(
CN)
2,

respectively.

Ten­
Day
HA
Rat
(
strain
not
specified,

10­
24
males/
group)
Kreutler
et
al.,
1978
0,
0.2%

(
equivalent
to
87
mg
CN/
kgday
Diet,
either
2%

or
20%

casein
2
weeks
Inc
plasma
TSH,
inc
thyroid
weight
in
2%

casein
group
only
None
(
BMDL
of
2.1)
87
KCN.
This
is
a
LOAEL
in
a
sensitive
population,
protein
and
iodine
deficient.

Effects
were
not
observed
in
groups
with
sufficient
protein
and/
or
iodine
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
2.
Summary
of
Oral
Toxicity
Studies
for
Cyanide.

Strain,
Species,

Sex
Reference
Dose
Route
Duration
Response
at
LOAEL
NOAEL
mg
CN/

kg­
day
LOAEL
mg
CN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
50
Rat,
Sprague­

Dawley
(
7
males/

group)
Palmer
and
Olson,
1979
0,
200
ppm
KCN
(
8
mg
CN/
kgday
Diet
21
days
None
8,
corrected
to
<
1.6
based
on
assay
of
feed,
dose
uncertain
None
KCN
Only
endpoints
evaluated
were
weight
gain
and
liver
weight.

Analysis
of
feed
resulted
in
<
20%

recovery
of
CN,

compared
to
95%

recovery
for
CN
added
immediately
before
analysis.
Dose
calculated
based
on
an
average
body
weight
of
0.12
kg,
and
food
consumption
of
0.10
kg/
day,
using
allometric
equation
in
U.
S.
EPA,
1988.
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
2.
Summary
of
Oral
Toxicity
Studies
for
Cyanide.

Strain,
Species,

Sex
Reference
Dose
Route
Duration
Response
at
LOAEL
NOAEL
mg
CN/

kg­
day
LOAEL
mg
CN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
51
Rat,
Sprague­

Dawley
(
7
males/

group)
Palmer
and
Olson,
1979
0,
200
mg/
L
KCN
(
14
mg
CN/
kgday
Drinking
water
21
days
Statistically
significant
17%
inc
in
liver
weight
None
14
KCN
Only
endpoints
evaluated
were
weight
gain
and
liver
weight.

Dose
calculated
based
on
an
average
body
weight
of
0.12
kg,
and
water
consumption
of
0.17
L/
day,
using
allometric
equation
in
U.
S.
EPA,
1988
Basis
of
10­
day
HA
in
this
Criteria
Document
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
2.
Summary
of
Oral
Toxicity
Studies
for
Cyanide.

Strain,
Species,

Sex
Reference
Dose
Route
Duration
Response
at
LOAEL
NOAEL
mg
CN/

kg­
day
LOAEL
mg
CN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
52
Subchronic
Rat,
F344
(
10/
sex/

group)
NTP,
1993
0,
3,
10,

30,
100,

or
300
mg/
L
(
0,
0.16,

0.48,
1.4,

4.5,
and
12.5
­
males;
0,

0.16,
0.53,
1.7,

4.9,
and
12.5
females
mg
CN/
kgday
Drinking
water
13
weeks
Dec
in:
left
epididymis
weight,
left
testis
weight,

number
of
spermatid
heads
per
testis,
spermatid
count
per
mL
suspension
4.5
(
BMDL
of
0.79)
12.5
NaCN.
Basis
of
ATSDR
intermediate
MRL
of
0.05
mg/

kgday
Basis
of
longerterm
HA
and
RfD
in
this
Criteria
Document.
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
2.
Summary
of
Oral
Toxicity
Studies
for
Cyanide.

Strain,
Species,

Sex
Reference
Dose
Route
Duration
Response
at
LOAEL
NOAEL
mg
CN/

kg­
day
LOAEL
mg
CN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
53
Mouse,
B6C3F1
(
10/
sex/

group)
NTP,
1993
0,
3,
10,

30,
100,

or
300
mg/
L
,
(
0,

0.26,
0.96,
2.7,

8.6,
24.4
­

males;
0,

0.32,
1.1,

3.3,
10.1,

28.8
­
females
mg
CN/
kgday
Drinking
water
13
weeks
Dec
left
cauda
epididymis
and
left
epididymis
weight
8.6
(
BMDL
of
12)
24.4
NaCN
Dog
(
6
males/

group,

strain
not
specified)
Kamalu,

1993
0,
1.04
mg
CN/

kgday
Diet
14
weeks
Histopathological
changes
in
kidney,
testis,
adrenal
gland
None
1.04
NaCN
Dogs
are
not
a
suitable
model
for
the
toxicity
of
cyanide
in
humans,

because
their
levels
of
rhodanese
are
much
lower
than
the
levels
in
humans
(
ATSDR,

1997).
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
2.
Summary
of
Oral
Toxicity
Studies
for
Cyanide.

Strain,
Species,

Sex
Reference
Dose
Route
Duration
Response
at
LOAEL
NOAEL
mg
CN/

kg­
day
LOAEL
mg
CN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
54
Miniature
Pig,
Pittman­

Moore
(
5
females,
7
males)
Jackson,

1988
0,
0.4,

0.7,
1.2
mg
CN/

kgday
Water
24
weeks
Dec
T3
and
T4;

Behavioral
changes
0.7
1.2
KCN.
No
other
endpoints
evaluated.

NOAEL
and
LOAEL
unreliable,
because
the
observed
differences
could
have
been
due
to
variability.
Dose
groups
had
unequal
numbers
of
males
and
females,
and
the
observed
endpoints
tend
to
differ
between
the
two
sexes.

Rat
(
strain,

number,

sex
not
specified)
Philbrick
et
al.,
1979
0,
44
mg
CN/

kgday
Diet
11.5
months
Myelin
degeneration;
dec
T4
at
4
months
and
inc
thyroid
weight
at
11.5
months
None
(
BMDL
of
19
in
rats
receiving
normal
diet
and
12
in
rats
receiving
deficient
diet
44
Dose
estimated
based
on
average
food
intake/
kg
body
weight
across
rat
strains
(
U.
S.

EPA,
1988).
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
2.
Summary
of
Oral
Toxicity
Studies
for
Cyanide.

Strain,
Species,

Sex
Reference
Dose
Route
Duration
Response
at
LOAEL
NOAEL
mg
CN/

kg­
day
LOAEL
mg
CN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
55
Chronic
Rat
(
10/
sex/

group,

strain
not
specified)
Howard
and
Hanzal,
1955
0,
73,
183
ppm
(
0,
4.3,

10.8
mg
CN/
kgday
Diet
2
years
None
10.8
None
This
is
the
current
cocritical
study
for
the
current
RfD
on
IRIS(
www.
epa.
gov/
iris
)
for
cyanide
of
0.02
mg/
kg­
day.
Thyroid
hormone
levels
apparently
not
evaluated.
Doses
calculated
based
on
reported
food
consumption
and
body
weight
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
2.
Summary
of
Oral
Toxicity
Studies
for
Cyanide.

Strain,
Species,

Sex
Reference
Dose
Route
Duration
Response
at
LOAEL
NOAEL
mg
CN/

kg­
day
LOAEL
mg
CN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
56
Reproductive
and
Developmental
Rat
(
20
females/

group,

strain
not
specified)
Tewe
and
Maner,
1981
1.2,
21.6
mg
CN/

kgday
(
adults)

1.9,
34.3
mg
CN/

kgday
(
weanlings
Diet
Throughout
mating,
gestation,

and
lactation
Dec
food
consumption,

growth
rate,
liver
weight
in
weanlings
1.9
(
BMDL
of
15
mg
CN/
kgday
34.3
Control
animals
fed
basal
diet
containing
low­
HCN
cassava;

treated
animals
fed
basal
diet
supplemented
with
500
ppm
KCN.
Doses
calculated
using
average
food
factor
for
adult
female
rats
in
a
subchronic
study
of
0.102
kg/
kg
body
weight,
and
average
food
factor
of
0.162
for
female
weanling
rats
(
U.
S.
EPA,
1988)

ATSDR
=
Agency
for
Toxic
Substances
and
Disease
Registry;
BMDL
=
95%
lower
confidence
limit
on
the
benchmark
dose;
CN
=
cyanide;
F
=
female;
FEL
=
frank
effect
level;
KCN
=
potassium
cyanide;
M
=
male;
MRL
=
minimum
risk
level;
NaCN
=
sodium
cyanide;
T3=
triiodothyronine;
T4=
thyroxine;
TSH
=

thyroid
stimulating
hormone
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
EPA/
OW/
OST/
HECD
Final
draft
VIII­
57
Table
VIII­
3.
Summary
of
Inhalation
Toxicity
Studies
for
Cyanide.

Strain
Species,

Sex
Reference
Exposure
mg
CN/
m3
Duration
Duration­

Adjusted
mg/
m3
Response/
Region
NOAEL
mg
CN/

m3
LOAEL
mg
CN/

m3
Comments
One­
Day
HA
Human,
male
Singh
et
al.,

1989
213
(
200
ppm
HCN)
Single
exposure
N/
A
No
respiration
or
blood
pressure,
increased
heartbeat,
pupils
fixed
and
dilated,
no
response
to
pain.
Fatal
within
3
days
despite
treatment
None
213
(
FEL)
Case
study
of
worker
accidentally
exposed
to
hydrogen
cyanide
in
silver
plating
industry.

Human,
male
Potter,
1950
Not
reported
Single
exposure
N/
A
Unconscious,
rapid
pulse,

stertorous
respiration,

pupils
fixed
and
unreactive,

absent
reflexes,

convulsions
N/
A
N/
A
Case
report
of
worker
accidentally
exposed
to
hydrogen
cyanide.
The
subject
was
treated
and
survived.

Monkey,
Cynomolgus
(
4
males)
Purser
et
al.,

1984
106,
108,

131,
156,

166
via
face
mask
(
100,
102,

123,
147,

156
ppm
HCN)
Up
to
30
minutes
N/
A
Loss
of
consciousness,

hyperventilation,
decreased
heart
rate,
loss
of
muscle
tone
and
reflexes,

convulsions
None
106
(
FEL)
Blood
cyanide
levels
reached
steady
state
within
10
minutes.
No
correlation
between
air
concentration
and
blood
cyanide
levels.
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
3.
Summary
of
Inhalation
Toxicity
Studies
for
Cyanide.

Strain
Species,

Sex
Reference
Exposure
mg
CN/
m3
Duration
Duration­

Adjusted
mg/
m3
Response/
Region
NOAEL
mg
CN/

m3
LOAEL
mg
CN/

m3
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
58
Rat,
Wistar
(
6
males/

group)
Bhattacharya
et
al.,
1994
58
(
55
ppm
HCN)
30
minutes
N/
A
Inc
in
transthoracic
pressure,
flow,
tidal
volume;
dec
in
resp.
rate,

compliance,
minute
volume
and
pulmonary
phospholipids
None
58
No
other
endpoints
evaluated.

Ten­
Day
HA
None
located
Subchronic
Human,
male
Blanc
et
al.,

1985
16
TWA
(
15
ppm
HCN)
Mean
employment
11
±
10.4
months
N/
A
Headache,
dizziness,

nausea,
vomiting,
syncope,

slightly
inc
TSH
None
5.7
(
HEC)

(
Effect
was
sig
in
highexposure
workers,

but
only
overall
average
exposure
available)
Occupational
study
of
36
workers
in
a
silverreclaiming
facility.
No
effect
on
T3
or
T4.
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
3.
Summary
of
Inhalation
Toxicity
Studies
for
Cyanide.

Strain
Species,

Sex
Reference
Exposure
mg
CN/
m3
Duration
Duration­

Adjusted
mg/
m3
Response/
Region
NOAEL
mg
CN/

m3
LOAEL
mg
CN/

m3
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
59
Chronic
Human,
male
El
Ghawabi
et
al.,
1975
7.2,
9.3,

11.7
(
6.4,
8.3,

and
10.4
ppm)
5­
15
years
N/
A
CNS
and
thyroid
effects
None
2.6
(
HEC)
Occupational
study
of
36
workers
exposed
in
electroplating
factory.
Urinary
thiocyanate
correlated
with
CN
air
concentration
Basis
of
EPA's
RfC
for
HCN
of
0.003
mg/
m3.

CN
=
cyanide;
dec
=
decreased;
FEL
=
frank
effect
level;
HCN
=
hydrogen
cyanide;
HEC
=
human
equivalent
concentration
(
includes
adjustment
for
intermittent
exposure
and
occupational
minute
volume);
inc
=
increased;
N/
A
=
not
applicable;
T3=
triiodothyronine;
T4=
thyroxine;
TSH
=
thyroid
stimulating
hormone
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
EPA/
OW/
OST/
HECD
Final
draft
VIII­
60
Table
VIII­
4.
Summary
of
Oral
Toxicity
Studies
for
Thiocyanate
Strain,
Species,

Sex
Reference
Dose
of
Thiocyanate
Route
Duration
Response
at
LOAEL
NOAEL
mg
SCN/

kg­
day
LOAEL
mg
SCN/

kg­
day
Comments
One­
Day
HA
Guinea
pig
(
15,
Strain
and
sex
NS)
Taubman
and
Heilborn,

1930
(
as
cited
in
Lindberg
et
al.,
1941;

study
in
German)
200
mg/
kg
KSCN;

120
mg
SCN/
kg­
dose
Oral,

(
regimen
NS)
2
doses
25%
dec
in
hemoglobin
and
erythrocytes
None
120
mg/
kgdose
Smaller
doses
given
over
longer
periods
resulted
in
larger
decreases,
but
specifics
were
not
available.
Thyroid
was
apparently
not
evaluated.

Ten­
Day
HA
Healthy
adult
humans
(
6,
Sex
NS)
Smith
and
Rudolf,

1928
5
grains
NaSCN/
dose
325
mg
NaSCN/
dose
10
mg
SCN/

kgday
Oral,
Aqueous
solution
3x/
day
1
week
15­
30
mm
Hg
dec
in
systolic
blood
pressure.

No
symptoms
reported.
None
10
Normotensive
subjects
Decreased
blood
pressure
can
be
beneficial
or
adverse,

depending
on
the
subject's
baseline
blood
pressure;
shown
as
LOAEL,
based
on
potentially
adverse
effect
in
normotensives.
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
4.
Summary
of
Oral
Toxicity
Studies
for
Thiocyanate
Strain,
Species,

Sex
Reference
Dose
of
Thiocyanate
Route
Duration
Response
at
LOAEL
NOAEL
mg
SCN/

kg­
day
LOAEL
mg
SCN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
61
Normotensive
humans
(
9
M,
28
F
Age
16­
54
years)
Dahlberg
et
al.,
1984
8
mg
SCN/
day
0.11
mg
SCN/
kg­
day,
as
NaSCN
In
milk
12
weeks
No
significant
changes
from
pretest
levels
on
serum
thyroxine,
triiodothyronine,

thyrotropic
hormone,

or
on
ratio
of
T3:
T4
Serum
SCN
peaked
at
4
weeks,
at
0.78
mg/
100
mL
in
nonsmokers,
1.07
mg/
100
mL
in
smokers
0.11
None
Only
effects
on
thyroid
evaluated;
blood
pressure
not
assessed
Baseline
serum
thiocyanate
was
0.4
mg/
100
mL
in
nonsmokers,
0.84
mg/
100
mL
in
smokers
Dose
estimate
assumes
70
kg
body
weight
Co­
basis
of
longer­
term
HA
and
RfD
in
this
Criteria
Document.

Hypertensive
humans
(
21
M,
38
F
Age
21­

80,
most
age
41­

60)
Palmer
et
al.,
1929;

Palmer
and
Sprague,

1929
1.5
grains
KSCN/
dose
58
mg
SCN/
dose
TWA
1.5­
1.7
mg
SCN/

kgday
Oral
3x/
day
for
1
wk,

2x/
day
for
1
wk,

1x/
day
for
1­
2
wk
Weakness,
angina,

precordial
distress
observed
in
6
subjects
None
1.5­
1.7
Hypertensive
subjects.

42.4%
of
subjects
had
a
decrease
in
systolic
blood
pressure
of
30
mm
Hg
or
more
Effects
may
have
been
secondary
to
rapid
decrease
in
blood
pressure
No
control
group
Basis
for
10­
day
HA
in
this
Criteria
Document
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
4.
Summary
of
Oral
Toxicity
Studies
for
Thiocyanate
Strain,
Species,

Sex
Reference
Dose
of
Thiocyanate
Route
Duration
Response
at
LOAEL
NOAEL
mg
SCN/

kg­
day
LOAEL
mg
SCN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
62
Reviews
of
human
studies
Andersen
and
Chen
1940;
Ayman,

1931
Varies
Oral
See
comments
See
comments
N/
A
N/
A
Magnitude
and
time
of
onset
of
decreased
blood
pressure
are
dose­
related,
but
large
interindividual
differences
in
baseline
blood
pressure
make
evaluation
of
dose­
dependency
difficult.

Review
of
human
studies
Gorman
et
al.,
1949
Varies
Oral
Not
reported;

As
short
as
9
days
NOAEL
is
dose
considered
optimal
for
reduction
of
blood
pressure
At
LOAEL:

muscular
fatigue,

nausea
and
vomiting,

dermatitis,
disorientation,

aphasia,
hallucinations,

convulsions
5­
14
mg/
100
mL
in
blood
>
14­
20
mg/
100
mL
in
blood
Blood
levels
of
thiocyanate
used
to
account
for
interindividual
variation
in
thiocyanate
excretion.

Normal
blood
thiocyanate
reported
as
0.2­
0.7
mg/
100
mL
(
Wood,
1975).

Deaths
also
reported
in
cases
with
blood
levels
of
3.3,
4.2,

and
7.0
mg/
100
mL
blood
(
outliers).
Unclear
whether
more
rapid
administration
related
to
deaths.

Rat
(
4­

6/
group;

Sex,
strain
NS)
Wolff
et
al.,

1946
0,
0.5%
KSCN
0,
287
mg
SCN/
kg­
day
Diet
18,
24
days
Inc
thyroid
weight,

dec
protein­
bound
iodine
in
plasma,
dec
T4
iodine
and
total
iodine
in
thyroid
None
287
Based
on
a
food
factor
of
0.096
kg
diet/
kg
body
weight/
day
(
average
across
strains
and
sexes,
U.
S.
EPA,

1988)
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
4.
Summary
of
Oral
Toxicity
Studies
for
Thiocyanate
Strain,
Species,

Sex
Reference
Dose
of
Thiocyanate
Route
Duration
Response
at
LOAEL
NOAEL
mg
SCN/

kg­
day
LOAEL
mg
SCN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
63
Sherman
Rat
(
25
M/
group)
Rawson
et
al.,
1944
0,
0.25%

KSCN
0,
217
mg
SCN/
kg­
day
Drinking
water
28
days
Inc
thyroid
weight,

enlarged
thyroids
with
marked
hyperplasia
and
loss
of
colloid.
None
217
Diet
and
drinking
water
supplements
provided
a
borderline­
deficient
intake
of
iodine.
Average
consumption
factor
of
0.145
L/
kg/
day,
calculated
from
U.
S.
EPA,
1988).

F344
Rat
(
10
males/

group)
De
Groot
et
al.,
1991
0,
0.2%
KSCN
0,
123
mg
SCN/
kg­
day
Diet
4
weeks
Dec
T4,
inc
TSH
and
thyroid
weight;

moderate
thyroid
follicular
activation
None
123
Dose
calculated
based
on
reported
body
weight
and
food
intake
Subchronic
Normotensive
Indian
women
(
35)
Banerjee
et
al.,
1997
0.19
mg
SCN/
kg/
day
In
milk
>
5
years
Dec
T4
and
inc
TSH
None
0.19
(
1.3
mg/
100
mL
in
blood)
Thiocyanate
ingested
with
lactoperoxidase­
hydrogen
peroxide
system,
resulting
in
ingestion
of
OSCN.

Assumed
a
body
weight
of
60
kg.
Co­
basis
of
longer­
term
HA
and
RfD
in
this
Criteria
Document.
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
4.
Summary
of
Oral
Toxicity
Studies
for
Thiocyanate
Strain,
Species,

Sex
Reference
Dose
of
Thiocyanate
Route
Duration
Response
at
LOAEL
NOAEL
mg
SCN/

kg­
day
LOAEL
mg
SCN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
64
Hypertensive
humans
(
246,
Sex
NS)
Barker
et
al.,
1941
300
mg
KSCN/
day
180
mg
SCN/
day
2.6
mg
SCN/
kg­
day
as
KSCN
Liquid
or
tablet
daily
2­
10
yr
Neurological
effects
in
4
(
depression,

aphasia,
slurring
speech,
disorientation,
hallucinations,

unsteady
gait);

enlarged
thyroid
(
11/
246)
and
dec
metabolic
rate
in
some
subjects.

Overall
incidence
of
adverse
effects
requiring
discontinuation
of
treatment
18/
246
None
2.6
Decreased
systolic
blood
pressure
in
67%
of
subjects
(
magnitude
not
reported)

May
have
been
interruptions
in
dosing
schedule
­
not
clearly
reported
Dose
was
increased
or
decreased
as
needed;
the
doses
at
which
symptoms
were
observed
was
not
reported.

No
control
group.
Most
severe
effects
at

20
mg
thiocyanate/
100
mL
blood
Hypertensive
humans
(
5,
Sex
N)
Beamish
et
al.,
1954
2­
6
grains
KSCN/
day
1.1­
3.3
mg
SCN/
kg­
day
Oral
~
1
year
Dec
protein­
bound
plasma
iodine,
dec
thyroid
uptake
of
iodine
None
1.3­
5
mg/
100
mL
in
plasma
Note
that
effects
occurred
at
blood
concentrations
below
the
therapeutic
range
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
4.
Summary
of
Oral
Toxicity
Studies
for
Thiocyanate
Strain,
Species,

Sex
Reference
Dose
of
Thiocyanate
Route
Duration
Response
at
LOAEL
NOAEL
mg
SCN/

kg­
day
LOAEL
mg
SCN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
65
Hypertensive
humans
(
50,
sex
NS)
Goldring
and
Chasis,

1931
326
mg/
day
KSCN
or
NaSCN
2.8
mg
SCN/
kg­
day,

assuming
all
in
form
of
KSCN
Oral
daily
14­
78
days
Neurological
effects
(
depression,
aphasia,

slurring
speech,

disorientation,
hallucinations,

unsteady
gait)

Overall
incidence
of
adverse
effects
13/
50
Two
subjects
died
None
2.8
Review
of
literature
of
50
patients
in
74
trials
with
SCN
treatment.

32.4%
of
subjects
had
at
least
45
mm
Hg
systolic
and
31
mm
Hg
diastolic
decrease
in
blood
pressure
No
control
group
Hypertensive
humans
(
26,
sex
NS)
Ayman,

1931
100­
400
mg
KSCN/
dose
200­
1200
mg
KSCN/
day
1.7­
10
mg
SCN/
kg/
day
Oral
Lower
doses
up
to
4x/
day
42­

109
days
Higher
doses
up
to
3x/
day
4­
89
days
Weakness,
fatigue,

and/
or
diarrhea
in
5
subjects
at
the
lower
doses
Weakness,
fatigue,

diarrhea,
tremors,

numbness
in
upper
body
in
12
subjects
at
higher
doses.

Marked
toxicity
precluded
continued
treatment.
None
2.6
(
approximate
The
lowest
dose
at
which
toxic
effects
were
seen
was
not
clear,
but
was
near
the
bottom
of
the
dosing
range.
Decreased
blood
pressure
seen
in
only
3/
13
subjects
at
low
dose.
The
listed
LOAEL
is
based
on
a
"
widely
recommended
dosage,"
at
which
weakness
and
other
symptoms
were
observed
with
minimal
effect
on
blood
pressure.
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
4.
Summary
of
Oral
Toxicity
Studies
for
Thiocyanate
Strain,
Species,

Sex
Reference
Dose
of
Thiocyanate
Route
Duration
Response
at
LOAEL
NOAEL
mg
SCN/

kg­
day
LOAEL
mg
SCN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
66
SHN
Mouse
(
18
F/
group)
Nagasawa
et
al.,
1980
0,
0.1%,
0.3%

KSCN
0,
163,
488
mg
SCN/
kg­
day
Drinking
water
12
weeks
Significantly
dec
plasma
T4
at
both
doses.
Plasma
T3
and
mammary
development
significantly
dec
at
0.3%
None
163
SHN
strain
has
a
high
incidence
of
mammary
tumors;

preneoplastic
and
neoplastic
mammary
development
also
inhibited.
Doses
calcualted
using
the
average
water
consumption
across
strains
of
0.2718
L/
kg­
day
(
Calculated
from
U.
S.
EPA,
1988)

Wistar
Rat
3­

week­
old
(
17­
19
F/
group)
Pyska,
1977
0,
0.1%
KSCN
100
mg
SCN/
kg­
day
Drinking
water
~
10
weeks
(
until
rats
3
months
old)
Significantly
dec
plasma
proteinbound
iodine.
None
100
Mortality
reported
at
unspecified
higher
doses
Dose
calculated
based
on
allometric
equation
of
U.
S.

EPA,
1988
and
body
weight
of
0.14
kg
Weanling
Rat,
strain
NS
(
10
M/
group)
Philbrick
et
al.,
1979
0,
2240
ppm
KSCN
0,
98
mg
SCN/
kg­
day
Diet
11.5
months
Significantly
dec
plasma
T4
and
in
T4
secretion
rate
at
4
months;
at
11
months,
significantly
inc
thyroid
weight
and
dec
plasma
T4.

Histopath
showed
no
effect
on
thyroid,

optic
nerve,
sciatic
nerve,
or
other
neural
tissues
None
98
Control
&
exposed
groups
received
diet
+/­
supplementation
with
potassium
iodide.
Effects
on
thyroid
seen
+/­
KI.

In
unsupplemented
groups,

myelin
degeneration
compared
to
corresponding
control.

Dose
calculated
using
a
food
factor
of
0.073
(
average
across
strains,
U.
S.
EPA,
1988),
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
4.
Summary
of
Oral
Toxicity
Studies
for
Thiocyanate
Strain,
Species,

Sex
Reference
Dose
of
Thiocyanate
Route
Duration
Response
at
LOAEL
NOAEL
mg
SCN/

kg­
day
LOAEL
mg
SCN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
67
Fisher
344/
DuCrj
Rat
(
28­
30
M/
group)
Kanno
et
al.,
1990
0,
0.5%
KSCN
465
mg
SCN/
kg­
day
Drinking
water
25
weeks
Significantly
inc
thyroid
weight,

serum
TSH,
T3,
dec
thyroxine;
diffuse
thyroid
hyperplasia,

inc
colloid.

No
neoplasia
in
thyroids
of
control
or
treated
animals
None
465
Dose
calculated
assuming
a
body
weight
of
0.18
kg
and
water
consumption
of
.028
L/
day
(
U.
S.
EPA,
1988)
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
4.
Summary
of
Oral
Toxicity
Studies
for
Thiocyanate
Strain,
Species,

Sex
Reference
Dose
of
Thiocyanate
Route
Duration
Response
at
LOAEL
NOAEL
mg
SCN/

kg­
day
LOAEL
mg
SCN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
68
Chronic
Fischer
344
Rat
(
20
M/
dose)
Lijinsky
and
Reuber,

1982
0,
800
ppm
NaSCN
(
45
mg
SCN/
kg/
day)
Diet
130
weeks
No
inc
in
mortality.

Inc
in
liver
tumors
(
5/
20
vs.
0/
20
N/
A
N/
A
Study
limited
by
small
sample
size,
lack
of
evaluation
of
nonneoplastic
endpoints,
potential
for
age­
related
tumors.
MTD
not
reached.
Doses
calculated
Using
a
food
factor
of
0.079
for
a
chronic
study
in
male
Fischer
rats
(
U.
S.
EPA,
1988)

Fisher
344
Rat
(
20­

24/
sex/

dose)
Lijinsky
and
Kovatch,

1989
0,
0.32%

NaSCN
Authors
estimated
250
mg/
kg­
day
NaSCN
thiocyanate
in
F
(
147mg/
kg
in
M)

75
mg
SCN/

kgday
for
males
128
mg
SCN/
kg­
day
for
females
Drinking
water
5
days/
wk
112
weeks,

with
survivors
killed
at
week
130
No
incr
in
mortality,

noticeably
adverse
effects,
or
tumors
75
M
128
F
None
Thyroid­
specific
endpoints
not
evaluated;
unclear
from
the
report
whether
the
incidence
of
nonneoplastic
lesions
was
inc.
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
4.
Summary
of
Oral
Toxicity
Studies
for
Thiocyanate
Strain,
Species,

Sex
Reference
Dose
of
Thiocyanate
Route
Duration
Response
at
LOAEL
NOAEL
mg
SCN/

kg­
day
LOAEL
mg
SCN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
69
Dog
Breed
(
12,

sex
NS)
Lindberg
et
al.,
1941
325
mg
KSCN/

dose
194
mg
SCN/
dose
Oral,
regimen
NS
4­
27
weeks
estimated
Dec
serum
cholesterol,
total
protein,
erythrocyte
count,
and
hematocrit.
Histopathological
analyses
showed
bone
marrow
acellularity
and
fatty
vacuolation
of
the
liver.
N/
A
N/
A
Thyroid
endpoints
not
evaluated.

Dose
calculated
based
on
reported
dose
of
5
grains.

Study
limited
by
incomplete
reporting
of
methods.
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
4.
Summary
of
Oral
Toxicity
Studies
for
Thiocyanate
Strain,
Species,

Sex
Reference
Dose
of
Thiocyanate
Route
Duration
Response
at
LOAEL
NOAEL
mg
SCN/

kg­
day
LOAEL
mg
SCN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
70
Reproductive
and
Developmental
GR/
A
Mouse
(
18
F/
group)
Nagasawa
et
al.,
1980
0,
0.1%,
0.3%

KSCN
0,
163,
488
mg
SCN/
kg­
day
Drinking
water
5
weeks
before
mating
and
4
weeks
of
gestation
No
effect
on
fertility,

litter
size,
fetal
viability,
pup
weight,

or
maternal
pituitary
levels
of
prolactin
and
growth
hormone.
488
None
Developmental
toxicity
endpoints
not
evaluated.

Thyroid
endpoints
apparently
not
measured.
Mammary
tumor
development
inhibited.

Water
consumption
factor
of
0.27
L/
kg­
day
(
average
across
strains)

Wistar/

NIN
Rat
(
6
F/
group)
Bala
et
al.,

1996
0,
25
mg/
rat
KSCN
0,
108
mg
SCN/
kg/
day
Feed
8
weeks
before
mating,
and
during
gestation
and
lactation
Inc
maternal
thyroid
weight
and
urinary
excretion
of
iodine,

dec
serum
T4.
Pups
also
had
dec
serum
T4.
None
108
maternal
108
developmental
T3
unaffected.
Dose
calculated
based
on
amount
per
rat
and
final
body
weight
Wistar/

NIN
Rat
(
F,
Number
NS)
Raghunath
and
Bala,

1998
0,
25
mg/
rat
KSCN
0,
108
mg
SCN/
kg/
day
Feed
8
weeks
before
mating,
and
during
gestation
and
lactation
for
2
gen
Dec
serum
T4
in
F1
and
F2
pups,
with
dec
compared
to
control
somewhat
stronger
in
F2
gen.
None
108
reproductive
Other
reproductive
and
developmental
endpoints
were
not
evaluated.
Dose
calculated
based
on
amount
per
rat
and
body
weight
in
Bala
et
al.,

1996
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
Table
VIII­
4.
Summary
of
Oral
Toxicity
Studies
for
Thiocyanate
Strain,
Species,

Sex
Reference
Dose
of
Thiocyanate
Route
Duration
Response
at
LOAEL
NOAEL
mg
SCN/

kg­
day
LOAEL
mg
SCN/

kg­
day
Comments
EPA/
OW/
OST/
HECD
Final
draft
VIII­
71
Rat
(
4­
7
pregnant
F,
Strain
NS)
Kreutler
et
al.,
1978
0,
6.3,
12.6,

25.3
(
0,
40,
80,
or
160
mg
SCN/
L)

NaSCN
Drinking
water
During
gestation,

through
lactation
day
10
Inc
relative
thyroid
weight
­
at
5.6
in
dams
and
in
pups
None
6.3
maternal
equivocal
6.3
developmental
equivocal
Other
developmental
endpoints
not
evaluated.
The
LOAEL
is
equivocal,
in
the
absence
of
supporting
data
on
thyroid
hormones
or
histopathology.

In
the
absence
of
body
weight
data,
used
the
average
female
rat
water
consumption
of
0.158
L/
kg/
day
(
U.
S.
EPA,
1988)

Pregnant
Wistar
Rat
(
12­
27
F/
group)
Pyska,
1977
0,
0.1%,
0.3%,

0.5%
KSCN
thiocyanate
0,
52,
156,
260
mg
SCN/

kgday
Drinking
water
During
pregnancy
and
14
days
of
lactation
Maternal:
Significantly
dec
plasma
proteinbound
iodine,
dec
mammary
gland
weight,
DNA,
and
RNA
content
Significantly
dec
pup
litter
weight
at
14
days
None
52
Developmental
52
maternal
156
Developmental
Thyroid
effects
and
other
indicators
of
developmental
toxicity
not
evaluated
in
pups.

Consumption
factor
of
20
mL/
day
x
1/
0.23
kg
[
actual
maternal
weight]

Unclear
whether
the
effects
on
litter
weight
were
due
to
preor
postnatal
exposure
Dose
conversions:
Unless
otherwise
specified,
70
kg
was
used
as
the
default
human
body
weight
dec
=
decreased;
F
=
female;
gen
=
generation;
inc
=
increased;
KSCN
=
potassium
thiocyanate;
M
=
male;
NaSCN
=
sodium
thiocyanate;
N/
A
=
not
applicable;
NS
=
not
specified;
SCN
=
thiocyanate;
T3=
triiodothyronine;
T4=
thyroxine;
TSH
=
thyroid
stimulating
hormone;
TWA
=
time­
weighted
average
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
EPA/
OW/
OST/
HECD
Final
draft
VIII­
72
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
EPA/
OW/
OST/
HECD
Final
draft
VIII­
73
Table
VIII­
5.
Summary
of
Development
of
the
Health
Advisories
for
Cyanide
Principal
Study
Critical
Effect
NOAEL/

BMDL
LOAEL
Uncertainty
Factorsa
RfD
(
mg/
kg/
day)
Health
Advisory
(
mg/
L)

Ten­
day
Palmer
and
Olsen,
1979
Increased
liver
weight
None
14
(
drinking
water)
1000
(
10A,
10H,
10L)
N/
Ab
0.1
Longer­
term
NTP
(
1993)
Male
reproductive
(
decreased
epididymis
and
testis
weights
and
decreased
sperm
count)
4.5
(
NOAEL)
12.5
1000
(
10A,
10H,
10D)
N/
A
Child:
0.05
Adult:
0.2
NTP
(
1993)
Male
reproductive
(
decreased
epididymis
weight,
supported
by
decreased
sperm
count)
0.79
(
BMDL)
N/
A
(
BMDL)
1000
(
10A,
10H,
10D)
N/
A
Child:
0.008
Adult:
0.03
Lifetime
NTP
(
1993)
Male
reproductive
(
decreased
epididymis
and
testis
weights
and
decreased
sperm
count)
4.5
(
NOAEL)
12.5
1000
(
10A,
10H,
10D)
0.005
0.03
NTP
(
1993)
Male
reproductive
(
decreased
epididymis
weight,
supported
by
decreased
sperm
count)
0.79
(
BMDL)
N/
A
(
BMDL)
1000
(
10A,
10H,
10D)
0.0008
0.006
a.
Areas
of
uncertainty
addressed
by
uncertainty
factors
are:
animal
to
human
extrapolation
(
A);
intrahuman
variability
and
protection
of
sensitive
subpopulations
(
H);

extrapolation
from
a
LOAEL
to
a
NOAEL(
L);
extrapolation
from
a
subchronic
to
chronic
exposure
(
S);
and
lack
of
a
complete
database
(
D)

b.
N/
A
=
Not
applicable
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
EPA/
OW/
OST/
HECD
Final
draft
VIII­
74
Table
VIII­
6.
Summary
of
Development
of
the
Health
Advisories
for
Thiocyanate
Principal
Study
Critical
Effect
NOAEL/

BMDL
LOAEL
Uncertainty
Factorsa
RfD
(
mg/
kg/
day)
Health
Advisory
(
mg/
L)

Ten­
day
Palmer
et
al.,

1929;
Palmer
and
Sprague,

1929
Weakness,
angina,
precordial
distress
in
hypertensive
subjects
None
1.5
100
(
10H,
10L)
N/
Ab
0.2
Longer­
term
Dahlberg
et
al.,

1984,
Banerjee
et
al.,
1997
Thyroid
hormone
effects
(
decreased
T4,
elevated
TSH)
0.11
0.19
100
(
10H,
10D)
N/
A
Child:
0.01
Adult:
0.04
Lifetime
Dahlberg
et
al.,

1984,
Banerjee
et
al.,
1997
Thyroid
hormone
effects
(
decreased
T4,
elevated
TSH)
0.11
0.19
100
(
10H,
10D)
0.001
0.008
a.
Areas
of
uncertainty
addressed
by
uncertainty
factors
are:
animal
to
human
extrapolation
(
A);
intrahuman
variability
and
protection
of
sensitive
subpopulations
(
H);

extrapolation
from
a
LOAEL
to
a
NOAEL(
L);
extrapolation
from
a
subchronic
to
chronic
exposure
(
S);
and
lack
of
a
complete
database
(
D)

b.
N/
A
=
Not
available
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
EPA/
OW/
OST/
HECD
Final
draft
VIII­
75
Table
VIII­
7.
Summary
of
Development
of
the
Health
Advisories
for
Cyanogen
Chloride
Principal
Study
Effects
Observed
NOAEL/

BMDL
LOAEL
Uncertainty
Factorsa
RfD
(
mg/
kg/
day)
Health
Advisory
(
mg/
L)

Ten­
day
N/
Ab
CNS
(
demyelination),
cardiac
irregularities,
severe
weight
loss,
pulmonary
congestion
and
edema
N/
A
N/
A
N/
A
N/
A
0.3c
Longer­
term
N/
A
Muscular
weakness;
lung
congestion;
irritation
of
eyes,

skin,
and
throat;
decreased
appetite;
severe
weight
loss
N/
A
N/
A
N/
A
N/
A
Child:
0.1c
Adult:
0.4c
(
based
on
NOAEL)

N/
A
No
data
available
N/
A
N/
A
N/
A
N/
A
Child:
0.02c
Adult:
0.07c
(
based
on
BMDL)

Lifetime
N/
A
No
data
available
N/
A
N/
A
N/
A
0.01c
(
based
on
NOAEL)
0.08c
(
based
on
NOAEL)

N/
A
No
data
available
N/
A
N/
A
N/
A
0.002c
(
based
on
BMDL)
0.01c
(
based
on
BMDL)

a.
Areas
of
uncertainty
addressed
by
uncertainty
factors
are:
animal
to
human
extrapolation
(
A);
intrahuman
variability
and
protection
of
sensitive
subpopulations
(
H);
extrapolation
from
a
LOAEL
to
a
NOAEL(
L);
extrapolation
from
a
subchronic
to
chronic
exposure
(
S);
and
lack
of
a
complete
database
(
D)

b.
NA
=
Not
applicable
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
EPA/
OW/
OST/
HECD
Final
draft
VIII­
76
c.
Derived
using
the
cyanide
value
as
a
surrogate,
and
multiplying
by
the
ratio
of
the
molecular
weights
of
cyanogen
chloride
and
cyanide
(
64.5/
26).