Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
EPA/
OW/
OST/
HECD
i
Final
draft
TABLE
OF
CONTENTS
Table
of
Contents
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i
Chapter
I.
Executive
Summary
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I­
1
Chapter
II.
Physical
and
Chemical
Properties
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II­
1
Chapter
III.
Toxicokinetics
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III­
1
A.
Absorption
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III­
1
B.
Distribution
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III­
2
C.
Metabolism
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III­
5
D.
Excretion
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III­
26
E.
Bioaccumulation,
Retention
and
Body
Burden
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III­
31
F.
Summary
of
Toxicokinetics
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III­
34
Chapter
IV.
Human
Exposure
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IV­
1
A.
Drinking
Water
Exposure
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IV­
1
A.
1
National
Occurrence
Data
for
Cyanogen
Chloride
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IV­
2
A.
1.1
Quarterly
Finished
Water
and
Distribution
Maximum
for
Cyanogen
Chloride
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IV­
3
A.
2
National
Occurrence
Data
for
Cyanide
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IV­
5
A.
2.1
National
Drinking
Water
Contaminant
Occurrence
Database
Data
on
Cyanide
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IV­
6
B.
Exposure
to
Sources
Other
Than
Drinking
Water
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IV­
12
B.
1
Dietary
Intake
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IV­
15
B.
2
Air
Intake
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IV­
19
B.
3
Dermal
Exposure
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IV­
20
C.
Overall
Exposure
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IV­
20
D.
Summary
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IV­
26
Chapter
V.
Health
Effects
in
Animals
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V­
1
A.
Short­
Term
Exposures
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V­
1
B.
Long­
Term
Exposures
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V­
14
C.
Reproductive/
Developmental
Toxicity
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V­
28
D.
Mutagenicity
and
Genotoxicity
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V­
36
E.
Carcinogenicity
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V­
39
Chapter
VI.
Health
Effects
in
Humans
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VI­
1
A.
Case
Reports
and
Clinical
Studies
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VI­
1
B.
Epidemiological
Studies
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VI­
13
C.
Summary
of
Human
Studies
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VI­
18
Chapter
VII.
Mechanism
of
Toxicity
and
Sensitive
Populations
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VII­
1
A.
Biochemical
Basis
of
Toxicity
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VII­
1
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
EPA/
OW/
OST/
HECD
ii
Final
draft
B.
Mechanism
of
Carcinogenesis
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VII­
15
C.
Interactions
and
Suceptibilities
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VII­
18
D.
Summary
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VII­
31
Chapter
VIII.
Quantification
of
Toxicological
Effects
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VIII­
1
A.
Introduction
to
Methods
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VIII­
1
A.
1
Quantification
of
Noncarcinogenic
Effects
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VIII­
1
A.
1.1
Drinking
Water
Equivalent
Level
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VIII­
4
A.
1.2
Health
Advisory
Values
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VIII­
4
A.
2
Quantification
of
Carcinogenic
Effects
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VIII­
6
B.
Noncarcinogenic
Effects
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VIII­
9
B.
1
Cyanide
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VIII­
9
B.
1.1
One
day
Health
Advisory
for
Cyanide
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VIII­
9
B.
1.2
Ten
day
Health
Advisory
for
Cyanide
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VIII­
10
B.
1.3
Longer­
term
Health
Advisory
for
Cyanide
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VIII­
13
B.
1.4
Reference
Dose,
Drinking
Water
Equivalant
Level
And
Lifetime
Health
Advisory
for
Cyanide
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VIII­
17
B.
2
Thiocyanate
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VIII­
23
B.
2.1
One­
day
Health
Advisory
for
Thiocyanate
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VIII­
23
B.
2.2
Ten­
day
Health
Advisory
for
Thiocyanate
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VIII­
23
B.
2.3
Longer­
term
Health
Advisory
for
Thiocyanate
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VIII­
25
B.
2.4
Reference
Dose,
Drinking
Water
Equivalent
Level,
and
Lifetime
Health
Advisory
for
Thiocyanate
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VIII­
29
B.
3
Cyanogen
Chloride
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VIII­
31
B.
3.1
One­
day
Health
Advisory
for
Cyanogen
Chloride
.
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VIII­
37
B.
3.2
Ten­
day
Health
Advisory
for
Cyanogen
Chloride
.
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VIII­
37
B.
3.3
Longer­
term
Health
Advisory
for
Cyanogen
Chloride
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VIII­
38
B.
3.4
Reference
Dose,
Drinking
Water
Equivalent
Level,
and
Lifetime
Health
Advisory
for
Cyanogen
Chloride
.
VIII­
40
C.
Carcinogenic
Effects
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VIII­
42
D.
Characterization
of
Uncertainties
and
Data
Gaps
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VIII­
44
Chapter
IX.
Risk
Characterization
Summary
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IX­
1
A.
Hazard
Characterization
and
Mode
of
Action
Implications
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IX­
1
B.
Dose­
Response
Characterization
and
Implications
in
Risk
Assessment
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IX­
9
C.
Weight
of
Evidence
and
Implications
in
Risk
Conclusions
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IX­
17
D.
Exposure
Characterization
and
Implication
in
Relative
Source
Contribution
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IX­
19
E.
Risk
Characterization
for
Drinking
Water
Exposure
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IX­
26
F.
Comparison
With
Other
Standards
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IX­
30
Chapter
X.
References
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.
X­
1
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
EPA/
OW/
OST/
HECD
iii
Final
draft
Appendix
A.
Benchmark
Dose
Modeling
Results
.
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A­
1
Appendix
B.
Benchmark
Dose
Modeling
Output,
Available
electronically
only
.
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B­
1
Appendix
C.
CYANATE
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C­
1
Appendix
D.
CYANAMIDE
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D­
1
Appendix
E.
HYDROGEN
CHLORIDE
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E­
1
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
EPA/
OW/
OST/
HECD
iv
Final
draft
TABLES
I­
1
Summary
of
Health
Advisory
Values
for
Cyanogen
Chloride
.
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I­
1
II­
1
Physical
and
Chemical
Properties
of
Cyanogen
Chloride
and
its
Potential
Metabolites
.
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II­
1
III­
1
HCN
and
HSCN
Levels
Following
Inhalation
of
CNCl
or
HCN1
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III­
8
IV­
1
Cyanogen
Chloride
Quarterly
Distribution
System
Finish
and
Maximum
.
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IV­
4
IV­
2.
National
Drinking
Water
Contaminant
Occurrence
Database
Public
Water
Supply
­
National
Drinking
Water
Data
for
Cyanide
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.
IV­
8
V­
1.
Reproductive
Effects
in
Rats
and
Mice
Administered
Sodium
Cyanide
in
Drinking
Water
for
13
Week.
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.
V­
16
VI­
1
Serum
Thiocyanate
and
Thyroid
Hormone
Levels
in
Women
Exposed
for
>
5
Years
to
Thiocyanate
in
Milk
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VI­
7
VIII­
1
Summary
of
Toxicity
Studies
for
Cyanogen
Chloride
.
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.
VIII­
45
VIII­
2
Summary
of
Oral
Toxicity
Studies
for
Cyanide
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VIII­
47
VIII­
3
Summary
of
Inhalation
Toxicity
Studies
for
Cyanide
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.
VIII­
56
VIII­
4
Summary
of
Oral
Toxicity
Studies
for
Thiocyante
.
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VIII­
69
VIII­
5.
Summary
of
Development
of
the
Health
Advisories
for
Cyanide
.
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.
VIII­
70
VIII­
6
Summary
of
Development
of
the
Health
Advisories
for
Thiocyanate
.
.
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.
VIII­
71
VIII­
7
Summary
of
Development
of
the
Health
Advisories
for
Cyanogen
Chloride
.
.
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.
VIII­
72
FIGURES
III­
1
Reactions
of
cyanogen
chloride
.
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.
III­
13
III­
2
Cyanide
Primary
Metabolic
Pathways
.
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.
III­
21
Drinking
Water
Criteria
Document
for
Cyanogen
Chloride
and
Potential
Metabolites
EPA/
OW/
OST/
HECD
v
Final
draft
Acknowledgements
Acknowledgements
This
document
is
an
update
and
expansion
of
the
Rough
Final
Draft
for
the
Drinking
Water
Criteria
Document
on
Haloacetonitriles,
Chloropicrin
and
Cyanogen
Chloride
(
U.
S.
EPA,
1987).
The
section
on
cyanide
is
an
update
and
extension
of
Drinking
Water
Criteria
Document
for
Cyanide
(
U.
S.
EPA,
1992),
and
the
section
on
thiocyanate
is
an
update
and
extension
of
an
Issue
Paper
prepared
by
U.
S.
EPA's
Superfund
Health
Risk
Technical
Support
Center
(
U.
S.
EPA,
1997a).
Full
literature
searches
were
conducted
in
December
1999
on
the
toxicity
of
cyanogen
chloride,
cyanide,
thiocyanate,
cyanate,
cyanamide,
and
HCl,
and
on
exposure
to
cyanogen
chloride
and
cyanide.
These
searches
were
supplemented
by
selected
key
references
identified
after
the
search.

Contributor
and
Chemical
Manager
Nancy
Chiu,
Ph.
D.,
U.
S.
EPA
Office
of
Water
Contractor
Authors:

Lynne
T.
Haber,
Ph.
D.
(
TERA)
Joan
S.
Dollarhide,
M.
S.,
M.
T.
S.
C.,
J.
D.
(
TERA)
Claudine
Kasunic,
M.
S.
(
GRAM,
Inc.)
Bruce
Allen,
M.
S.
(
ENVIRON)

Peer
Reviewers
Patricia
McGinnis,
Ph.
D.,
DABT,
Syracuse
Research
Corporation
John
Reif,
M.
Sc.
(
Med),
D.
V.
M.,
Colorado
State
University
Alan
Stern,
Dr.
P.
H.,
DABT,
New
Jersey
Department
of
Environmental
Protection
