FINAL DRAFT
United States ECAO-CIN-G070
Env^ronmema. Protecnon February, 1990
Research and
Development
HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT FOR
MOLYBDENUM AND SELECTED MOLYBDENUM COMPOUNDS
Prepared for
OFFICE OF SOLID WASTE AND
EMERGENCY RESPONSE
Prepared by
Environmental Criteria and Assessment Office
Office of Health and Environmental Assessment
U.S. Environmental Protection Agency
Cincinnati, OH 45268
DRAFT: DO NOT CITE OR QUOTE
NOTICE
This document 1s a preliminary draft. It has not been formally released
by the U.S. Environmental Protection Agency and should not at this stage be
construed to represent Agency policy. It 1s being circulated for comments
on Its technical accuracy and policy Implications.
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DISCLAIMER
This report 1s an external draft for review purposes only and does not
constitute Agency policy. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
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PREFACE
Health and Environmental Effects Documents (HEEDs) are prepared for the
Office of Solid Waste and Emergency Response (OSWER). This document series
Is Intended to support listings under the Resource Conservation and Recovery
Act (RCRA) as well as to provide health-related limits and goals for emer-
gency and remedial actions under the Comprehensive Environmental Response,
Compensation and Liability Act (CERCLA). Both published literature and
Information obtained for Agency Program Office files are evaluated as they
pertain to potential human health, aquatic life and environmental effects of
hazardous waste constituents. The literature searched for In this document
and the dates searched are Included 1n "Appendix: Literature Searched."
Literature search material Is current up to 8 months previous to the final
draft date listed on the front cover. Final draft document dates (front
cover) reflect the date the document 1s sent to the Program Officer (OSWER).
Several quantitative estimates are presented provided sufficient data
are available. For systemic toxicants, these Include Reference doses (RfDs)
for chronic and subchronlc exposures for both the Inhalation and oral
exposures. The subchronlc or partial lifetime RfO 1s an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time Interval I.e., for an Interval that
does not constitute a significant portion of the Hfespan. This type of
exposure estimate has not been extensively used, or rigorously defined as
previous risk assessment efforts have Focused primarily on lifetime exposure
scenarios. Animal data used for subchronlc estimates generally reflect
exposure durations of 30-90 days. The general methodology for estimating
subchronlc RfDs Is the same as traditionally employed for chronic estimates,
except that subchronlc data are utilized when available.
In the case of suspected carcinogens, a carcinogenic potency factor, or
q-j* (U.S. EPA, 1980), 1s provided. These potency estimates are derived
for both oral and Inhalation exposures where possible. In addition, unit
risk estimates for air and drinking water are presented based on Inhalation
and oral data, respectively. An RfD may also be derived for the
noncardnogenlc health effects of compounds which are also carcinogenic.
Reportable quantities (RQs) based on both chronic toxlclty and carclno-
genldty are derived. The RQ 1s used to determine the quantity of a hazard-
ous substance for which notification Is required In the event of a release
as specified under the Comprehensive Environmental Response, Compensation
and Liability Act (CERCLA). These two RQs (chronic toxldty and carclno-
genldty) represent two of six scores developed (the remaining four reflect
IgnltabUHy, reactivity, aquatic toxlclty, and acute mammalian toxlclty).
Chemical-specific RQs-Teflect the lowest of these six primary criteria. The
methodology for chronic toxlclty and cancer based RQs are defined In U.S.
EPA, 1984 and 1986a, respectively.
111
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EXECUTIVE SUMMARY
*
Molybdenum Is a silvery-gray metal that belongs to group VIB of the
periodic table of elements. It can have valence states of +6, *5, +4, f3,
+2 and 0, although valence state +6 Is the most stable. Host of the world's
molybdenum comes from mined ores, although It Is also recovered as a
by-product of copper mining. The only commercially Important molybdenum
mineral 1s molybdenite (molybdenum dlsulflde). Molybdenum producers
concentrate the molybdenite ore by crushing, grinding and using flotation
processes to yield a molybdenite concentrate which 1s then roasted to
convert the sulflde to the oxide. The converted oxide, known as technical
molybdlc oxide (chemically, molybdenum trloxlde), can be added to steel In
this form (Barr, 1981) and Is the primary end-use commercial molybdenum
material. In 1987, U.S. molybdenum producers produced -75 million pounds of
contained molybdenum In molybdenite concentrate. United States consumption
of molybdenum In 1987 was -33 million pounds of contained molybdenum. The
end-use pattern for molybdenum In 1987 was as follows: steel (56%), cast
Iron (4%), superalloys (8.8%), alloys (excluding steel and superalloys)
(2%), mill products made from metal powder (11.5%), chemicals and ceramics
(8.9%) and miscellaneous (8.8%) (USDI, 1988).
Molybdenum Is a natural element that cannot be degraded by environmental
processes. Although environmental processes may transform one molybdenum
compound Into another, the molybdenum Is still present. The major source of
molybdenum release to the atmosphere Is the combustion of coal, which
releases participate ash containing molybdenum Into the atmosphere (Section,
3.3.). The primary processes that remove atmospheric molybdenum are wet and
dry deposition. One of the most "Important factors that determines the
1v
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degree of molybdenum transport In water and soil 1s pH. In general,
Increases 1n solubility enhance molybdenum availability to plants and
transport 1n water and soil. As the pH of the media Increases, molybdenum
mobility in soil and water and uptake In plants Increase (Lindsay, 1979;
Bohn et al., 1985; Davles, 1980). Dissolved molybdenum In soil and water
usually occurs as the molybdate Ion. The mobility of molybdenum In soil and
water may decrease by sorptlon onto Fe_0. and humlc materials In these
& 0
media. Molybdenum leaching from fly ash Increases as pH Increases and
because the leaching molybdenum Is In the form of the molybdate Ion (Goetz,
1983). Therefore, fly ash deposited on alkaline soils 1s more likely to
leach molybdenum Into the underlying soil than Is fly ash deposited on
acidic soils.
Molybdenum occurs naturally In soils at levels that commonly range from
0.2-5 ppm, although an accepted average soil content 1s 2 ppm (Lindsay,
1979). Molybdenum does not occur naturally In elemental form, but primarily
as sulfldes or oxides. The concentration of molybdenum In surface waters Is
generally <5 yg/l, although concentrations <500 yg/l were reported
In some drinking waters. Concentrations >20 yg/l In water are probably
due to an anthropogenic Influence (Chappell et al., 1979). The average
human dally Intake of molybdenum In drinking water 1s reportedly <5 vg,
which represents only 1.5% of the total dally Intake (Wlersema et al., 1984;
Chappell et al., 1979). The average amount of molybdenum In the American
diet Is 288 ng/g of food (M1ller-Ihl1 and Wolf, 1986). Assuming the average
American adult consumes 1600 g of food/day, the average dally Intake of
molybdenum Is 460 yg. A similar food Intake of 335 yg/day was reported
and thought to represent 98.5% of the total dally Intake (Wlersema et al.,
1984). Available ambient air monitoring data for molybdenum (Wlersema et
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a!., 1984; Evans et al., 1984} Indicate that dally Intake from Inhalation.
represents only <0.1154 of total dally Intake. The major source of molyb-
denum emissions to the atmosphere Is the combustion of coal by electric
power generation stations and Industry (U.S. EPA, 1973; Nrlagu and Pacyna,
1988). The molybdenum Is emitted In the coal fly ash, which eventually
settles to terrestrial surfaces and surface waters.
Data currently available Indicate that molybdenum can be acutely toxic
to freshwater vertebrates at concentrations >0.73 ppm (B1rge, 1978; B1rgo et
al., 1979). Molybdenum can be acutely toxic to saltwater fauna at concen-
trations >147 mg/t (Morgan et al., 1986).
BCF values for molybdenum In aquatic fauna did not exceed 100, although
values In algae could be >2000 and <10,000 In aquatic plants (Brooks and
Rumsby, 1965; Suloway et al.. 1983; Sakaguchl et al., 1981; Kovacs et al.,
1984). The highest concentrations of molybdenum In aquatic macrophytes were
from samples collected from the Tejo River, Portugal (8.2 ppm dry weight)
(Freltas et al., 1988). The highest levels of molybdenum In tissues of
Invertebrates were reported for Molna rectlrostrls (605 mg/kg dry weight)
and ollgocheates (60.3 mg/kg dry weight) from a sewage treatment basin In
•• • '
Hungary (Czegeny and Deval, 1985). No single sample of fish exceeded 3.6
yg/g dry weight (carp; Sa1k1 and May, 1988). Levels In wildlife were <0
to -58 wg/g wet weight (Wren et al., 1983).
Excretion studies using pigs suggest that ~80-86% of an orally admin-
istered dose of Mo was fairly rapidly absorbed from the gastrointestinal
tract (Bell et al., 1964). In 6- to 10-year-old girls, a positive balance
was observed when the diet provided 40-80 jig Mo/day (Engel et al., 1967).
Molybdenum appears to be rapidly absorbed from the gastrointestinal tract of
guinea pigs. Studies using rats suggest that absorption of molybdenum from
vl
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molybdenum trloxlde Is more rapid than from molybdenite, because the former
1s more soluble In digestive juices (Falrhall et al., 1945). Molybdenum was
widely distributed throughout the body after oral dosing of steers (Comar et
al., 1949) and guinea pigs (Falrhall et al., 1945). Qualitatively similar
results were obtained In mice after Intravenous Injections and In rats after
oral administration of radlolabeled molybdenum (Nellands et al., 1948;
Rosoff and Spencer, 1973). In mice, rats and steers, liver and kidneys
accumulated a considerable percentage of the administered dose. In humans,
molybdenum 1s found mainly 1n the liver, kidneys, fat and blood (Goyer,
1986).
Molybdenum 1s apparently eliminated primarily by excretion. There was
no evidence found for metabolism of Mo. In swine, urinary excretion
accounted for 80-86% of an oral dose and fecal excretion accounted for
8.6-14.6% (Bell et al., 1964). In humans treated Intravenously, urinary
excretion accounted for 16.6-27.2% of the dose and fecal excretion for
1.0-6.8%. Substantial amounts of Mo may be lost through profuse sweating
(Consolazlo et al., 1964). Following Intravenous treatment, mice excreted
35.6% of the dose 1n the urine and 2.6% In the feces over a 24-hour period
(Rosoff and Spencer, 1973). Lener and B1br (1979) demonstrated
qualitatively that biliary excretion 1s Involved 1n Mo elimination, but the
extent of excretion by this route was not determined.
Reported oral LD^.s for Mo In rats exposed through diet for 40 days
were 101 mg/kg for calcium molybdate, 125 mg/kg for molybdenum trloxlde and
333 mg/kg for ammonium molybdate (Falrhall et al., 1945). L0,_ data for
DU
other species were not available. Short-term oral studies with various
species Indicate that molybdenum depresses body weight gain and affects the
gastrointestinal tract, the liver and kidneys. The doses associated with
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these, effects vary with different molybdenum compounds. In rats,, sodium
molybdate caused death 1n <2 weeks at doses of 250 mg Ho/kg (Ne1lands et
al., 1948), whereas 571 mg Ho/kg/day from ammonium molybdate was not lethal
(Rana et al., 1980). Ammonium tetrathlomolybdate 1s apparently considerably
more toxic than other molybdenum compounds, since dietary doses of 0.3 mg
Ho/kg for 21 days had gastrointestinal and skeletal effects In rats (Fell et
al., 1979; Spence et al., 1980). Inhalation of dusts of molybdenum trloxlde
and calcium molybdate killed guinea pigs In <5 weeks at levels of 200 and
155 mg Ho/m3, respectively; however, these experiments were not well
designed and the results not clearly reported (Falrhall et al., 1945).
Molybdenum added to the diet of male rats -as the trloxlde, calcium
molybdate, or as ammonium molybdate In doses between 85 and 6757 mg Ho/kg
for 8-232 days caused weight loss and mortality (Falrhall et al., 1945).
In rabbits, dietary doses of >91 mg Ho/kg as sodium molybdate In the
diet caused anemia and, eventually, death In "40 days, but doses of <25 mg
Mo/kg had no noticeable adverse effects (ArMngton and Davis, 1953; Robinson
et al., 1969). In rats, doses of -20 mg Ho/kg/day from sodium molybdenum
for 42 days 1n the diet or drinking water significantly decreased body
weight gain (Lallch et al., 1965; Nellands et al., 1948).
In rats, sodium molybdate added to the drinking water at levels that
provided doses of 0.28-2.8 6 mg Mo/kg/day decreased the Incidence of tumors
Induced by known carcinogens (Luo et al., 1983; Wei et al., 1985). However,
Intraperltoneal Injections of molybdenum trloxlde In mice for a total dose
of 31(>7 mg Mo/kg over a 30-day period Increased the Incidence of lung tumors
(not statistically significant) and significantly Increased the number of
lung tumors/mouse (Stoner et al., 1976). The overall evidence Indicates
that some molybdenum compounds are weak mutagens In bacterial assays
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(Kanematsu et al., 1980; Rosmann et al., 1984). In the only assay using
mammalian cells, molybdate anlons gave a 'positive mutagenlc response
(Zellkoff et al., 1986). Sodium molybdate did not produce developmental
toxldty when Injected Intravenously to pregnant hamsters (Perm, 1972).
In a 3-generat1on study by Schroeder and MHchener (1971), a dose of 1.9
mg Ho/kg In drinking water was associated with early death In offspring,
Increased number of dead Utters, maternal mortality and the birth of runts.
In rats, 20 ppm Mo In the diet (1 mg/kg/day) was associated with reduced
body weight gain In male rats and reduced lactation Index In female rats; 80
-ppm (4 mg/kg/day) was associated with male Infertility (Jeter and Davis,
1954).
An RfD of 1 yg Mo/kg/day was derived for subchronlc oral exposure to
sodium molybdate based on the LOAEL of 1 mg Mo/kg/day In rats In the
reproductive study by Jeter and Davis (1954). Because Mo Is a nutritionally
essential element, and because the subchronlc oral RfD Is somehow below the
recommended dally allowance for Mo, the subchronlc oral RfD was also adopted
as the RfD for chronic exposure. The RfD values are well below the line for
adverse effects 1n a dose/duration-response plot of the oral toxlclty data.
An RQ of 100 pounds was derived based on reproductive effects In mice 1n a
3-generat1on study (Schroeder and MUchener, 1971). Molybdenum was assigned
to EPA Group D: not classifiable as to human cardnogenlclty. A cancer-
based RQ was not derived.
1x
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TABLE OF CONTENTS
Page
1. INTRODUCTION 1
1.1. STRUCTURE AND CAS NUMBER 1
1.2. PHYSICAL AND CHEMICAL PROPERTIES 1
1.3. PRODUCTION DATA 1
1.4. USE DATA 4
1.5. SUMMARY 8
2. ENVIRONMENTAL FATE AND TRANSPORT 9
2.1. AIR 9
2.2. WATER 10
2.3. SOIL 10
2.4. SUMMARY 11
3. EXPOSURE 13
3.1. WATER 13
3.2. FOOD 14
3.3. INHALATION 14
3.4. DERMAL '. . 15
3.5. SUMMARY 16
4. ENVIRONMENTAL TOXICOLOGY 17
4.1. AQUATIC TOXICOLOGY 17
4.1.1. Acute Toxic Effects on Fauna 17
4.1.2. Chronic Effects on Fauna . 18
4.1.3. Effects on Flora 19
4.1.4. Effects on Bacteria "... 20
4.2. TERRESTRIAL TOXICOLOGY 20
4.2.1. Effects on Fauna 20
4.2.2. Effects on Flora 20
4.3. FIELD STUDIES 20
4.4. AQUATIC RISK ASSESSMENT 27
4.5. SUMMARY 30
!• ' f
5. PHARMACOK1NETCS ,- 31
5.1. ABSORPTION 31
5.2. DISTRIBUTION 32
5.3. METABOLISM 35
5.4. EXCRE1ION 35
5.5. SUMMARY 36
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TABLE OF CONTENTS (cent.)
Page
6. EFFECTS 38
6.1. SYSTEMIC TOXICITY 38
6.1.1. Inhalation Exposure 38
6.1.2. Oral Exposure 40
6.1.3. Other Relevant Information 47
6.2. CARCINOGENICITY 50
6.2.1. Inhalation 50
6.2.2. Oral 50
6.2.3. Other Relevant Information 50
6.3. MUTAGENICITY 52
6.4. DEVELOPMENTAL TOXICITY 54
6.5. OTHER REPRODUCTIVE EFFECTS 54
6.6. SUMMARY 56
7. EXISTING GUIDELINES AND STANDARDS 58
7.1. HUMAN : 58
7.2. AQUATIC 58
8. RISK ASSESSMENT 59
.8.1. CARCINOGENICITY 59
8.1.1. Inhalation 59
8.1.2. Oral 59
8.1.3. Other Routes'. 59
8.1.4. Weight of Evidence 59
8.1.5. Quantitative Risk Estimates 60
8.2. SYSTEMIC TOXICITY. . . 60
8.2.1. Inhalation Exposure 60
8.2.2. Oral Exposure 60
9. REPORTABLE QUANTITIES 65
9.1. BASED ON SYSTEMIC 10XICITY 65
9.2. BASED ON CARCINOGENICI1Y 69
10. REFERENCES. . . 72
i *. —
APPENDIX A: LITERATURE SEARCHED 88
APPENDIX B: SUMMARY TABLE FOR MOLYBDENUM 91
APPENDIX C: DOSE/DURATION RESPONSE GRAPH(S) FOR EXPOSURE TO
MOLYBDENUM " 92
x1
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LIST OF TABLES
No. Title Page
1-1 Synonyms, CAS Numbers, Molecular Weights, Empirical
Formulas and Structures of Molybdenum and Compounds 2
1-2 Physical Properties of Molybdenum and Compounds 3
1-3 U.S. Manufacturers of Selected Molybdenum Compounds 5
1-4 Salient Molybdenum Statistics 7
4-1 Molybdenum Concentrations 1n Field Collected Flora and
Fauna 22
5-1 The Distribution of Molybdenum Following Oral Adminis-
tration of.Molybdenum Tr1ox1de to Guinea P1gs 33
6-1 Ingestlon of Molybdenum by Groups of Male White Rats Fed
Diets Containing Various Molybdenum Compounds 41
6-2 Mutagenldty Testing of Molybdenum 53
9-1 Toxldty Summary for Molybdenum Compounds 66
9-2 Composite Scores for Molybdenum Compounds 68
9-3 Molybdenum: Minimum Effective Dose (MED) and Reportable
Quantity (RQ) 70
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LIST OF ABBREVIATIONS
ADI Acceptable dally intake
BCF Bloconcentratlon factor
CAS Chemical Abstract Service
CS Composite score
OFF 011sopropy1 phosphorofluorldate
ECso Concentration effective to 50% of recipients
(and all other subscripted dose levels)
GMAV Genus mean acute values
GMCV ~ Genus mean chronic values
LC5Q Concentration lethal to 50% of recipients
(and all other subscripted dose levels)
1050 Dose lethal to 50% of recipients
MBN • Methylbenzyln1trosam1ne
MED Minimum effective dose
NMU N-N1troso-n-methylurea
NOAEL No-observed-adverse-effect level
NOEL No-observed-effect level
NSEE N-NHrososarcos1ne
PEL Permissible exposure limit
ppm Parts per million
RQ Reportable quantity
RVd Dose-rating value
RVe Effect-rating value
TLm -Median tolerance unit
TLV Threshold limit value
TWA Time-weighted average
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1. INTRODUCTION
1.1. STRUCTURE AND CAS NUMBER
The structure, CAS registry numbers, molecular weights and empirical
formulas of molybdenum and selected molybdenum compounds are presented In
Table 1-1. The selection of molybdenum compounds for discussion was based
upon the ability of the molybdenum Ion to dissociate under physiological
conditions, the presumption that the molybdenum 1on would be the most toxic
moiety and the availability of toxlcologlcal and physlcochemlcal data.
1.2. PHYSICAL AND CHEMICAL PROPERTIES
Molybdenum 1s a silvery-gray metal that belongs to group VIB of the
periodic table of elements (Barr, 1981). -It can have valence states of *6,
+5, -t-4, +3, +2 and 0, although valence state +6 1s the most stable.
Physical properties of molybdenum and selected molybdenum compounds are
listed In Table 1-2.
Molybdenum metal has an extremely high melting point (2626°C) that
permits high-temperature applications such as furnace parts, rocket nozzles,
welding tips, thermocouples, glass-melting electrodes, dies and molds (Barr,
1981). It resists corrosion by mineral acids and some liquid metals.
1.3. PRODUCTION DATA
Most of the world's molybdenum supply comes from mined molybdenum ores,
although H Is also recovered as a by-product of copper mining. The only
commercially Important molybdenum mineral Is molybdenite (molybdenum
dlsulflde). Primary ore bodies In the Western Hemisphere contain -0.2-0.4%
molybdenum and give a recovery of 2-4 kg/metric ton of ore (Barr, 1981).
Molybdenite ore Is concentrated by crushing and grinding the ore and
then subjecting H to a series of flotation operations. Molybdenite concen-
trate contains -90X molybdenum dlsulflde; the remainder 1s primarily silica.
0186d -1- 02/05/90
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TABLE 1-1
2 Synonyms.
a.
Compound (Synonyms)
Molybdenum
Ammonium molybdate
(ammonium orthomolybdate)
(ammonium normal molybdate)
Amonlum dlmolybdate .-;
iv> Ammonium hep tamo Tybdate
(ammonium paramolybdate)
Molybdenum dlsulflde
(molybdenum sulflde)
(molybdenite)
Molybdenum trloxlde
(molybdenum anhydride)
(molybdlc acid anhydride)
(molybdlc oxide)
Sodium molybdate
CAS Numbers, Molecular Heights, Empirical Formulas and
Structures of Molybdenum and Compounds
CAS Number
7439-98-7
13106-76-8
27546-07-2
i
12027-67-7
1317-33-5
1313-27-5
7631-965-0
10102-40-6
(dlhydrate)
Molecular Empirical
Weight Formula
95.94 Mo
196.01 H6MoN204
339.96 HeMo2N207
11,163.89 H24Mo7Ne024
160.06 HoS2
143.94 Mo03
205.92 MoNa204
Structure
Mo
(NH4)?Mo04
(NH4)2Mo207
(NH4)6Mo7024
MoS2
Mo03
Na2Mo04
o
in
oo
us
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00
en
Q.
TABU 1-2
Physical Properties of Molybdenum and Compounds
Chemical
Molybdenum
Ammonium
molybdate
Ammonium
heptamolybdate
(tetrahydrate)
i Molybdenum
dtsulftde
Molybdenum
trloxlde
Sodium molybdate
aBarr, 1981
°Weast, 1985
NO . No data
Description Melting Point Boiling Point
CC) CC)
silver -gray metal3 2626a 5560*
r
colorless solid0 decomposes0 decomposes0
colorless to yellowish -^0 at 90° decomposes 190°
solid0
black luster solid0 1185° ND
colorless or white- 795° sublimes 1155°
yellow solid0
white solid0 687° NO
Density
(g/cm»)
10.223
(20*C)
2.276b
(25'C)
2.498°
4.80°
(14-C)
4.692°
(21'C)
3.2Bb
Vapor
Water Solubility Pressure
(mm Hg|
Insoluble6 2.96xlO"«a
(1725*C)
soluble with NO
decomposition0
43 g/100 ccb ND
(cold water)
Insoluble0 ND
0.1066 g/100 cc 1.0
(18*C)° (734-C)0
44.3 g/100 cc NO
(cold water)0
in
CO
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The concentrate 1s then roasted to convert the sulflde to the oxide. The
converted oxide, known as technical molybdlc oxide (chemically, molybdenum
trloxlde), can be added to steel 1n this form (Barr, 1981) and Is the
primary end-use commercial molybdenum material (USDI, 1988).
Aqueous solutions of purified molybdlc oxide can be converted to
ammonium molybdate or sodium molybdate by reaction with ammonia or sodium
hydroxide, respectively (Barry, 1981).
U.S. manufacturers of ammonium molybdate, molybdenum trloxlde, molyb-
denum dlsulflde and sodium molybdate are given In Table 1-3. Salient
statistics for molybdenum for 1983-1987 are presented 1n Table 1-4. The
decreased production of molybdenite concentrate In 1987 was due to a cutback
by domestic producers to correct an over-supply situation. The two largest
U.S. producers of molybdenum are AH AX Inc., and Cyprus Minerals Co. (USDI,
1988).
1.4. USE DATA
The apparent U.S. consumption of contained molybdenum 1n 1987 was -33
million pounds. Apparent consumption 1s defined as U.S. primary plus
secondary production, plus Imports, minus exports, plus adjustments for
government and Industry stock changes. The end-use pattern for molybdenum
In 1987 was as follows: steel (56%), cast Iron (4%), superalloys (8.8%),
alloys (excluding steel and superalloys) (2%), mill products made from metal
powder (11.5%), chemicals and ceramics (8.9%) and miscellaneous (8.8%).
Based upon the various commercial molybdenum chemicals, consumption of
molybdenum In 1987 was as follows: molybdlc oxide (58%), ferromolybdenum
(15.5%), ammonium and sodium molybdate (5.0%), other materials (21.4%)
(USDI, 1988). Ferromolybdenum Is formed by reducing technical molybdlc
oxide with Iron oxide (Barr, 1981).
0186d -4- 02/05/90
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TABLE 1-3
U.S. Manufacturers of Selected Molybdenum Compounds*
Manufacturer
Location
Ammonium molybdate (basic molybdate)
Gulf Chemical & Metallurgical Co.
The Procter & Gamble Co.
R1chardson-V1cks, Inc., subsidiary
J.T. Baker Inc., subsidiary
Molybdenum trloxlde (molybdenum anhydride,
molybdlc acid anhydride, molybdlc oxide)
AMAX Inc.
AMAX Metal Products division
BP America, Inc.
BP Minerals America
Kennecott division
Utah Copper division
Cyprus Minerals Co.
Cyprus Metec Corp.
Freeport, Texas
PhllUpsburg, New Jersey
Fort Madison, Iowa
Langeloth, Pennsylvania
Salt Lake City, Utah
Wlnslow, New Jersey
Molybdenum dlsulflde (molybdenum sulflde)
AMAX Inc.
AMAX Metal Products division
BP America, Inc.
BP Minerals America
Kennecott division
Utah Copper division
Cyprus Minerals Co.
Cyprus Metals Co. division
Dow Corning Corp.
Phelps Dodge Corp.
Chlno Mines Co., subsidiary
Unocol Corp.
Molycorp, Inc., subsidiary
Langeloth, Pennsylvania
Salt Lake City, Utah
Chains, Idaho
Trumbull, Connecticut
Hurley, New Mexico
Questa, New Mexico
0186d
-5-
05/31/89
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TABLE 1-3 (cont.)
Manufacturer Location
Sodium molybdate
AMAX, Inc.
AMAX Metal Products division Fort Madison, Iowa
Cyprus Minerals Co.
Cyprus Metec Corp. Wlnslow, New Jersey
North Metal and Chemical Co. York, Pennsylvania
The Procter & Gamble Co.
R1chardson-V1cks, Inc., subsidiary
J.T. Baker Inc., subsidiary PhllUpsburg, New Jersey
*Source: SRI, 1988
0186d -6- 05/31/89
-------
o
CO
o.
T/toefi-4
Salient Molybdenum Statistics3
(In thousands of pounds of contained molybdenum and thousands of dollars)
'
United States:
Concentrate:
' i
Production '
Shipments
Value
Reported consumption
Imports for consumption
Stocks, Dec. 31: mine and plant
Primary products:
Production
Shipments
Reported consumption
Stocks, Dec. 31: producers'
World: Mine production
1983
i
33,593
48.805
$166,612
27,014
1.673
11.637
37,533
50,562
27,225
28,352
. 140,616°
1984
103,664
102,405
$326.780
54,843
28
12,450
79.689
65,527
34,792
22,155
214,275°
1985
108,409
111,936
$347,812
Confidential
112
9,332
87,436
73,861
33,451
21,014
216,364
1986
93,976
95,006
$240,484
53,061
1.120
8,715
41,490
57.855
31,898
20,699
203,466°
1987
75,117
69.868
$179,286
37,442
1.264
15,082
34,659
40.668
32,629
22.168
186,405d
aSource: USOI, 1988
°Rev1sed
cPre!1m1nary
^Estimated
CO
CO
-------
The ammonium molybdates are used as specialty catalysts and as
h1gh-pur1ty sources for producing molybdenum metal (Barry, 1981). Sodium
molybdate 1s used In the pigment and metal-f 1n1sh1ng Industries, as a soil
additive and for aqueous corrosion-Inhibition applications (Barry, 1981).
1.5. SUMMARY
Molybdenum 1s a silvery-gray metal that belongs to group VIB of the
periodic table of elements. It can have valence states of +6, *5, +4, +3,
4-2 and 0, although valence state +6 1s the most stable. Most of the world's
molybdenum comes from mined ores, although 1t 1s also recovered as a
by-product of copper mining. The only commercially Important molybdenum
mineral 1s molybdenite (molybdenum dlsulflde). Molybdenum producers
concentrate the molybdenite ore by crushing, grinding and using flotation
processes to yield a molybdenite concentrate, which 1s then roasted to
convert the sulflde to the oxide. The converted oxide, known as technical
molybdlc oxide (chemically, molybdenum trloxlde), can be added to steel 1n
this form (Barr, 1981) and Is the primary end-use commercial molybdenum
material. In 1987, U.S. molybdenum producers produced -75 million pounds of
contained molybdenum 1n molybdenite concentrate. U.S. consumption of molyb-
denum In 1987 was -33 million pounds of contained molybdenum. The end-use
pattern for molybdenum In 1987 was as follows: steel (56%), cast Iron (4%),
superalloys (8.8%), alloys (excluding steel and superalloys) (2%), mill
products made from metal powder (11.5%), chemicals and ceramics (8.9%) and
miscellaneous (8.8%) (USDI, 1988).
0186d -8- 02/05/90
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2. ENVIRONMENTAL FATE AND TRANSPORT
Molybdenum 1s a natural element that cannot be degraded by environmental
processes. Although environmental processes may transform one molybdenum
compound Into another, the molybdenum will still be present. Therefore, the
environmental fate and transport of molybdenum Involves Us transport In and
between environmental media (air, water and soil) and conversion from one
compound Into another. Molybdenum reactions are described as some of the
most complex of any chemical element (Lindsay, 1979), and a detailed discus-
sion of chemical equilibria 1n soil and water Is beyond the scope of this
document. Therefore, this section will discuss only the more Important.
aspects that Influence the fate and transport of molybdenum.
2.1. AIR
The major source of molybdenum release to the atmosphere 1s the combus-
tion of coal, which releases partlculates containing molybdenum Into the
atmosphere (Section 3.3.). Molybdenum released to the atmosphere from
combustion processes will probably exist as an oxide (U.S. EPA, 1973).
Molybdenum partlculates released from mining operations, which generally
Involve molybdenum sulflde ores, will contain molybdenum In a sulflde form.
It Is unlikely that molybdenum 1n these partlculates undergoes any chemical
transformation In air. Molybdenum partlculates In air will eventually
settle to the earth's surface by dry and wet deposition. The rate of depo-
sition depends on the size, density and water solubility of the particles.
The residence time of the particles ranges from a few days to 60 days
(Lantzy and MacKenzle. 1979).
0186d -9- 05/31/89
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2.2. WATER
The fate of molybdenum 1n aquatic systems Is expected to depend partly
on the pH of the media (Section 2.3.)- In general, molybdenum solubility
Increases as pH Increases In the environmental range (Lindsay, 1979; Bohn et
a!., 1985; Davles, 1980), suggesting that the dissolved molybdenum content
In water will Increase as the water becomes more alkaline. In acidic
waters, the molybdenum content In sediments and suspended material 1s likely
to be higher (In general) than In alkaline waters because of precipitation
from solution. Dissolved molybdenum 1n environmental waters exists as the
molybdate 1on. This 1on can react with cations In water to form Insoluble
compounds, or the soluble compounds may be readily bloavallable to plants
and animals • for uptake. Soluble molybdenum compounds may be sorbed by
Fe.O. and humlc materials 1n water (Bysshe, 1988).
Molybdenum 1n aquatic systems Is unlikely to be transported by volatili-
zation. Pertinent data regarding blodegradatlon of molybdenum In water were
not located In the available literature dted 1n Appendix A.
2.3. SOIL
Molybdenum occurs 1n soil naturally or from anthropogenic sources such
•'•' f t * ' ^ _ '„ _ .
as atmospheric fallout of partlculate matter from coal combustion or land-
filling of coal combustion ash (Section 3.1.). One of the most Important
factors that determines the degree of molybdenum transport or conversion
from one form to another Is pH (Lindsay, 1979; Bohn et a!., 1985; Davles,
1980). In general, solubility and molybdenum availability to plants or
leaching Increases as- pH Increases 1n the environmental range (Lindsay,
1979; Bohn et al.. 1985; Davles, 1980). Soil may be limed to raise Us pH
and Increase molybdenum availability to plants In molybdenum-deficient areas
0186d -10- 01/30/90
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(Davles, 1980), Intentional soil applications of soluble sodium and
ammonium molybdates Is used to Increase molybdenum availability 1n
molybdenum-deficient soils (Barry, 1981).
Partlculate and ash material from coal combustion contains molybdenum
mostly 1n the form of molybdenum oxides (U.S. EPA, 1973). The fate of this
material 1s of prime Importance, since 1t occurs In soil from human Input
rather than naturally. Goetz (1983) examined the leaching of molybdenum
from coal fly ash and found a strong dependence on pH. Adsorption of molyb-
denum to the fly ash decreased with Increases 1n pH, thereby permitting more
leaching from the fly ash as pH Increased. The form of the leaching molyb-
denum was the molybdate 1on. Molybdenum oxide (HoO«) Is an add oxide and
can combine with cations In soil to form molybdates (Davles, 1980). There-
fore, fly ash deposited on alkaline soils Is more likely to leach molybdenum
Into the underlying soil than Is fly ash deposited on acidic soils. Soluble
molybdenum 1n soil usually occurs as the molybdate Ion (Lindsay, 1979; Bonn
et al., 1985; Davles, 1980). This 1on Is affected by Iron oxides 1n soil,
which can adsorb or react with the molybdate 1on, thereby controlling
transport (Davles, 1980). Molybdenum may also form chelates with organic
matter In soil. Mlcroblal breakdown would keep the element In a continual
state of circulation and Increase Us availability to plants (Davles, 1980).
2.4. SUMMARY
Molybdenum 1s a natural element that cannot be degraded by environmental
processes. Although environmental processes may transform one molybdenum
compound Into another, the molybdenum 1s still present. The major source of
molybdenum release to the atmosphere Is the combustion of coal, which
releases partlculate ash containing molybdenum Into the atmosphere (Section
i*
3.3.). The primary processes that remove atmospheric molybdenum are wet and
0186d -11- 01/30/90
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dry deposition. One of the most Important factors that determines the
degree of molybdenum transport In water and soil 1s pH. In general,
Increases In solubility enhance molybdenum availability to plants and
transport In water and soil. As the pH of the media Increases, molybdenum
mobility In soil and water and uptake 1n plants Increases (Lindsay, 1979;
Bohn et al., 1985; Davles, 1980). Dissolved molybdenum 1n soil and water
usually occurs as the molybdate 1on. The mobility of molybdenum In soil and
water may decrease by sorptlon onto Fe n and humlc materials 1n these
media. Molybdenum leaching from fly ash Increases as pH Increases; the
leaching molybdenum 1s In the form of the molybdate Ion (Goetz, 1983).
Therefore, fly ash deposited on alkaline soils Is more likely to leach
molybdenum Into the underlying soil than 1s fly ash deposited on addle
soils. Since natural soil 1s likely to contain predominantly the same
chemical forms of molybdenum as fly ash, leaching characteristics 1n soil
will be similar.
0186d -12- 01/30/90
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3. EXPOSURE
Molybdenum occurs naturally In soils at levels commonly ranging from
0.2-5 ppm, although an accepted average soil content Is 2 ppm (Lindsay,
1979). Molybdenum does not occur naturally 1n elemental form, but primarily
as sulfldes or oxides.
3.1. WATER
The presence of molybdenum 1n surface, ground and drinking waters Is
expected, since molybdenum occurs naturally In soil. The concentration of
molybdenum In surface waters 1s generally~<5 vg/l, although concentra-
tions <500 vg/s, were reported for some drinking waters. Concentrations
>20 pg/l 1n water are probably due to an anthropogenic Influence
(Chappell et a!., 1979).
The average human dally Intake of molybdenum In drinking water Is
reportedly <5 vg (VHersema et al., 1984; Chappell et a!., 1979). Accord-
Ing to Wlersema et al. (1984), Intake of molybdenum In drinking water repre-
sents only 1.554 of the total dally Intake. Intake of food Is the major
route of molybdenum exposure (Section 3.2.).
Anthropogenic Inputs of molybdenum Into aquatic ecosystems can result
from a variety of wastewater sources Including domestic, electric power
generation, mining, smelting and refining wastewaters as well as wastewaters
from manufacturing processes such as those of metals and chemicals. A major
source of molybdenum release to soil and water Is atmospheric fallout from
coal fly ash and landfllllng of bottom ash from coal combustion. Dumping of
sewage sludge Is a major source of molybdenum release to aquatic ecosystems
(Nrlagu and Pacyna, 1988).
0186d -13- 07/26/89
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3.2. FOOD
Molybdenum 1s common In foods. The average amount of molybdenum In the
American diet 1s 288 ng/g of food. This was determined by selecting a
variety of commonly consumed, everyday foods and blending them Into a
homogeneous reference material; this was followed by elemental analysis.
The diet material used for this analysis was accepted by the National Bureau
of Standards as a Reference Material (M1ller-Ihl1 and Wolf, 1986). Assuming
the average American adult consumes 1600 g of food/day, the AOI of
molybdenum Is 460 yg. This value 1s reasonably close to a value of 335
yg/day reported by Wlersema et ^V. (1984). According to Wlersema et al.
(1984), Intake of molybdenum through food represents 98.5% of the total
dally Intake of molybdenum.
3.3. INHALATION
The major source of molybdenum emissions to the atmosphere Is the
combustion of coal by electric power generation stations and Industry (U.S.
EPA, 1973; Nrlagu and Pacyna, 1988). Worldwide emissions of molybdenum from
coal combustion In 1983 were estimated to range from 628-4800 thousand kg
(Nrlagu and Pacyna, 1988). The vehicle by which molybdenum Is released from
coal combustion 1s fly ash, which reportedly contains average molybdenum
concentrations ranging from 12-100 mg/kg (U.S. EPA, 1973; Hjelmar, 1983).
The amount of molybdenum In fly ash depends on the amount In the source
coal. Molybdenum 1s also released 1n oil ash partlculates from oil combus-
tion (U.S. EPA, 1973; Nrlagu and Pacyna, 1988). Worldwide emissions of
1 • • " r< ".'
molybdenum from oil combustion 1n 1983 were -165-943 thousand kg (Nrlagu and
'»
Pacyna, 1988). Molybdenum Is also released to air from open-pit mining of
molybdenum and copper ore, ferromolybdenum production, steel production
0186d -14- 07/26/89
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using molybdenum and roasting of molybdenum ore (U.S. EPA, 1973). A molyb-
denum concentration of 160 ppm was detected 1n partlculate material released
from a Philadelphia municipal Incinerator (Olmez et a!., 1988). The
chemical forms of molybdenum released to the atmosphere are believed to be
primarily oxides and sulfldes (U.S. EPA, 1973).
A1r-mon1tor1ng data for molybdenum from the National A1r Surveillance
Network and various EPA regional offices were compiled for 1977-1979. The
compilation Is divided Into urban and nonurban frequency distributions. In
urban atmospheres, 70% of the 10,769 air samples were below molybdenum
detection limits (analytic detection limit not reported). The maximum con-
centration 1n a single sample for each of the 3 years was 120-275 ng/m3,
while the arithmetic mean concentration for each of the 3 years was 2.2-1.5
ng/m3 In urban air. In nonurban air, 90% of 1402 samples were below
detection limits. The maximum concentration In a single sample for each of
the 3 years was 16-4 ng/ma, while the arithmetic mean concentration for
each of the 3 years was 1.1-0.8 ng/m3 In nonurban air (Evans et a!.,
1984). W1tz et al. (1986) found molybdenum levels of 20.6-61.2" ng/m3 In
Indoor air of cars traveling on Los Angeles freeways.
Wlersema et al. (1984) monitored ambient air for molybdenum and other
compounds at various locations 1n Texas between 1978 and 1982 and found the
highest annual molybdenum concentration to be 19 ng/m3 In Fort Worth.
Based upon this value, Wlersema et al. (1984) estimated that only 0.11% of
the total dally human Intake of molybdenum results from Inhalation.
3.4. DERMAL
Pertinent monitoring data regarding the dermal exposure of molybdenum
were not located 1n the available literature cited In Appendix A.
0186d -15- 05/31/89
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3.5. SUMMARY
Molybdenum occurs naturally In soils at levels that commonly range from
0.2-5 ppm, although an accepted average soil content Is 2 ppm (Lindsay,
1979). Molybdenum does not occur naturally In elemental form, but primarily
as sulfldes or oxides. The concentration of molybdenum In surface waters Is
generally <5 yg/l, although concentrations <500 yg/l were reported
In some drinking waters. Concentrations >20 yg/l In water are probably
due to an anthropogenic Influence (Chappell et al., 1979). The average
human dally Intake of molybdenum In drinking water Is reportedly <5 vg,
which represents only 1.5% of the total dally Intake (Wlersema et al., 1984;
Chappell et al., 1979). The average amount of molybdenum In the American
diet Is 288 ng/g of food (MUler-IhH and Wolf, 1986). Assuming the average
American adult consumes 1600 g of food/day, the average dally Intake of
molybdenum 1s 460 v9- A similar food Intake of 335 yg/day was reported
and thought to represent 98.5% of the total dally Intake (Wlersema et al..
1984). Available ambient air-monitoring data for molybdenum (Wlersema et
al., 1984; Evans et al., 1984) Indicate that dally Intake by Inhalation
represents only <0.11% of total dally Intake. The major source of molyb-
denum emissions to the atmosphere 1s the combustion of coal by electric
power generation stations and Industry (U.S. EPA, 1973; Nrlagu and Pacyna,
1988). Molybdenum 1s emitted In the coal fly ash, which eventually settles
to terrestrial surfaces and surface waters.
0186d -16- 07/26/89
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4.. ENVIRONMENTAL TOXICOLOGY
4.1. AQUATIC TOXICOLOGY
4.1.1. Acute Toxic Effects on Fauna. Abbott (1977) assessed the acute
toxlclty of molybdenum (as ammonium molybdate) to hermit crab, Eupagurus
bernhardus. shore crab, Cardnus maenas. pullet-shell, Venerupls pullastra.
and starfish, Asterlas rubens. Specimens of each species were exposed to
molybdenum for <48 hours and monitored over a 5-day recovery period. The
48-hour TL values for shore and hermit crab were 1108 and >191 <254
m
mg/l, respectively. The 24-hour TL values for starfish and pullet-
shell were >127 <254 and >254 <509 mg/l, respectively.
Dorfman (1977) assessed the acute toxlclty of molybdenum (as molybdenum
oxide) to the mummlchog, Fundulus heteroclltus. Fish were collected from
marine waters with a salinity >17 o/oo and acclimated to laboratory condi-
tions for 3 days before the test. Tests were conducted at salinities of 7.9
and 18.8 o/oo and at 20°C. Nine fish were exposed to each concentration of
molybdenum 1n groups of three. The 96-hour TL values for fish exposed to
molybdenum In the low- and h1gh-sal1n1ty test solutions were 230 and 315 .
mg/l, respectively.
B1rge (1978) and Blrge et al. (1979) assessed the acute toxlclty of
molybdenum to rainbow trout. Salmo galrdnerl. goldfish, Carraslus auratus.
and the narrow-mouthed toad, Gastrophryne carollnensls. In semi-static
embryolarval assays. Fertilized eggs of each species were exposed to
molybdenum from fertilization to 4 days posthatch. Total exposure times for
goldfish and toad were 7 days but 28 days for trout. Test solutions were
renewed twice dally. Test temperatures were 13°C for trout and 22.0°C for
the other two species. The LCrQ values obtained for trout, goldfish and
toad were 0.73, 60.0 and 0.96 ppm, respectively.
0186d -17- 07/26/89
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Horgan et al. (1986) assessed the acute toxIcHy of molybdenum (as
ammonium molybdate) to larvae of the mussel, MytHus edulls. Gametes were
obtained from mussels chilled to 4°C for 22 hours before being transferred
to 22°C water. Gametes released from Isolated male and female mussels over
a 1-hour period were combined In a 1 JL beaker to achieve fertilization.
Exposure to molybdenum was begun within 2 hours of fertilization. Test
solutions were maintained at the fertilization temperature of 19°C. Molyb-
denum concentrations were analytically verified. Investigators reported a
48-hour ECgg of 147 mg/i based on mortality and abnormal development.
4.1.2. Chronic Effects on Fauna.
4.1.2.1. TOXICITY — Abbott (1977) reported that exposure of hermit
crab, Eupaqarus bernhardus. to 100 mg/i molybdenum (as ammonium moybdate)
for 50 days resulted 1n no mortalities among test animals.
4.1.2.2. BIOACCUNULATION/BIOCONCENTRATION — Brooks and Rumsby (1965)
determined the level of molybdenum In three species of New Zealand bivalves
from Tasman Bay. They reported enrichment factors for the scallop, Pecten
novaezelandlae. oyster, Ostrea slnuata. and mussel, Hytllus edulls. of ^0,
30 and 60, respectively.
Suloway et al. (1983) assessed the uptake of molybdenum from fly ash
extracts by fathead minnows, Plmephales promelas. and green sunflsh, Lepomls
cyanellus. Tests were conducted In 60 8. aquaria containing 40 I of
diluted extract at 23°C. Fish were fed frozen brine shrimp dally over the
30-day exposure period. F1sh were freeze-drled whole, homogenized and
* ( — . —
digested to provide samples for analysis of molybdenum. Molybdenum concen-
> *'.
tratlons In minnows exposed to extracts of five separate fly ash samples
ranged from 0.062-1.06 mg/kg compared with <0.05 mg/kg 1n controls.
0186d -18- 07/26/89
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Molybdenum concentrations 1n sunfIsh exposed to extracts of the same fly ash
samples ranged from 0.08-2.38 mg/kg compared with <0.064 mg/kg 1n -controls.
The BCFs for molybdenum In both species ranged from -1-100.
4.1.3. Effects on Flora.
4.1.3.1. TOXICITY — Colmano (1973) assessed the effects of molyb-
denum on cultures of Euglena gradlls. Cells were grown normally under 300
foot-candles of fluorescent light at 24-26°C 1n a medium containing 5.44 ppm
molybdenum. No abnormal cells were observed In cultures grown 1n the
presence of 96 ppm molybdenum. At concentrations between 96 and 960 ppm
molybdenum, the Euqlena cells clustered In groups of three to nine and
divided abnormally. Cultures exposed to >960 ppm molybdenum did not grow.
4.1.3.2. BIOCONCENTRATION — Sakaguchl et al. (1981) assessed the
accumulation of molybdenum (as ammonium molybdate) from test solutions by
green mlcroalgae, Chlorella regularls. two species of Chlamydomonas and
three species of Scenedesmus. Tests were conducted 1n 500 mj. Erlenmeyer
flasks for 20 hours at a pH of 5.0 and a temperature of 30°C. Cell cultures
were constantly stirred while being exposed to 10 mg/s. molybdenum.
Preliminary studies demonstrated that growth of C_. regulaMs was not
affected at 20 mg/a molybdenum but was markedly Inhibited at 50 mg/a.
C_. regulaMs. Chlamydomonas spp. and Scenedesmus spp. absorbed 13,200,
9445-21,167 and 7567-23,214 yg/g molybdenum for dry cells, respectively,
to produce BCFs of 1320, 944-2116 and 756-2321, respectively.
Kovacs et al. (1984) measured molybdenum 1n water and aquatic plants
from Lake Balaton, Hungary. They reported concentration factors for
Ceratophyllum submersum. HydrochaMs morsus.. Lemna trlscula. Hyrlophyllum
sj) lea turn. Potamogeton sp. and Stralotes aloldes ranging from 100-10,000.'"
They also reported a concentration fa'ctor of 100 for Cladophora glomerata.
0186d -19- 05/31/89
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4.1.4. Effects on Bacteria. Pertinent data regarding the effects of
exposure of aquatic bacteria to molybdenum were not located 1n the available
•
literature dted 1n Appendix A.
4.2. TERRESTRIAL TOXICOLOGY
4.2.1. Effects on Fauna. Pertinent data regarding the effects of expo-
sure of terrestrial fauna to molybdenum were not located In the available
literature dted 1n Appendix A.
4.2.2. Effects on Flora. Molybdenum 1s an essential plant mlcronutrlent
believed to be Important In nitrogen fixation and protein synthesis.
Molybdenum has been applied as a fertilizer to crops such as clover, lettuce
and spinach 1n molybdenum-deficient soils. Liming of add soils has been
necessary In many cases to release tightly bound molybdenum and Increase Us
b1oava1labH1ty (Davles, 1980). Dreesen and Cokal (1984) assessed the b1o-
avallabllUy of molybdenum to alfalfa, clover, barley, saltbush and summer
cypress grown on soils covering uranium mine tailings. Species were
selected on the basis of their use In reclamation efforts. Plants were
grown from seeds 1n a media without soil until a root mass developed (-4
weeks). The plants were then grown on the test material for an additional
4-6 weeks before harvesting. Concentrations of molybdenum 1n the harvested
plant materials did not exceed 5.4 yg/g but since these species - were
selected because of their use 1n reclamation efforts, they might be expected
to tolerate higher molybdenum levels than other plants.
4.3. FIELD STUDIES
Colborn (1982a,b) assessed the ability of aquatic Insects to serve as
biological monitors for molybdenum'. Aquatic Insects, Prunella sp., Clnyq-
mula sp. and Brachycentrus brachycentrus were collected from an unpolluted
stream (Coal Creek) and transplanted to sites on the Slate River receiving
0186d -20- 02/05/90
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discharges from a mining operation. Despite the lack of measurable levels
of molybdenum In water from either the control or transplant site, body
burden levels of molybdenum In caddlsfHes Increased (0.86-2.3 and 1.25-1.55
ppm) after 65-70 hours 1n separate trials. Molybdenum levels In mayflies
rose from 1.75-2.93 ppm after 65 hours 1n one experiment but declined from
2.75-1.57 ppm after 70.5 hours 1n a second trial. Fluctuations 1n molyb-
denum levels were negatively associated with changes In the body burden
level of cadmium.
Levels of molybdenum In tissues of flora and fauna from the field are
presented 1n Table 4-1. The highest concentrations of molybdenum In aquatic
macrophytes were reported for samples collected from Kesterson Reservoir,
California (5.25 ppm dry weight), hydroelectric storage lakes In New Zealand
(<5.6 yg/g dry weight). Lake Balaton, Hungary (<6.88 ppm dry weight), and
the Tejo River, Portugal (8.2 ppm dry weight) (Rawlence and UhUton, 1976;
Ohlendorf et a!., 1985; Frletas et a!., 1988). Levels of molybdenum In
grasses exceeded that reported for aquatic macrophytes. Cherry and Guthrle
(1979) reported levels of 6.2 and 10.7 ppm In nutgrass and sedgegrass,
respectively.
The highest levels of molybdenum In tissues of Invertebrates were
reported for Holna rectlrostrls (605 mg/kg dry weight), ollgocheates (60.3
mg/kg dry weight), Slqara lateralls (30.9 mg/kg dry weight) and Chlronomus
annularls (17 mg/kg dry weight) collected from a sewage treatment basin
(Czegeny and Deval, 1985). Generally, however, molybdenum levels In aquatic
Invertebrates were <5'ppm. No single sample of carp exceeded 3.6 ^g/g dry
weight (Salkl and Hay, 1988). Levels In wildlife were <0.58 vg/g wet
weight (Wren et al., 1983).
0186d -21- - 02/05/90
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o
CD
O.
TABIE 4-1
Molybdenum Concentrations In Field-Collected flora and fauna
Species
Tissue
Molybdenum Concentration
Sampling Site
Reference
i
ro
o
in
Plankton
Freshwater anglosperms
Plants
Aquatic plant
Caulerpa sp.
. *• i
• ;
Duckweed
Lcmna pcrpusllla
Aquatic vascular plants
Nophar advena
Pontederla cordata
Hymphaea odorata
Oecodon vertlclllatus
Aquatic macrophytes
Ceratophyllum
Elodea
Lagaroslphon
Potamoqeton
tgurla
Hymphaea
Plants
duckweed, Lemna
cattail, Typha
algae. Osclllatorla
hydrodlctyon
Aquatic plants
Ceratophyllum submersum
Hydrocharlj morsus
Lemna trlscula
Hyrlophyllum splcatum
Potamogeton pectlnatus
Potamoqeton perflolatus
Stratlotes aloldes
Cladophora glomerata
.whole samples
whole body
•whole body
whole body
whole body
whole body
whole body
whole body
.whole body
leaf and stem
whole body
0.13-1.5 |ig/g dry weight
0.26-4.6 mg/kg dry weight
5.25 ppm dry weight
0.27-0.46 ppm dry weight
0.34 ppm
0.01-1.8 ppm
0.4-5.6 yg/g dry weight
0.5 ppm
5.15. 5.23 ppm dry weight
5.35. 5.62 ppm dry weight
2.22 ppm dry weight
2.18, 6.88 ppn dry weight
1.60. 3.73 ppn dry weight
0.73-31.21 ppm dry weight
2.33-6.05 ppra dry weight
0.6-2.86 ppm dry weight
series of lakes In New Zealand
Japan
Kesterson Reservoir, California
Red Sea Coast. Saudi Arabia
damp ash sediment
Llnsley Pond, Cedar Lake.
North Branford. CT
hydroelectric strorage lakes.
New Zealand
fly ash basin drainage system.
Savannah River Project
Lake Balaton, Hungary
Rawlence and Whttlon, 1976
Yamamoto et at.. 1985
Ohlendorf et al.. 1986
Al-Amoudl and EI-Naggar.
1987
Cherry and Guthrle. 1979
Cowglll. 1974
Rawlence and Whltton. 1979
Cherry and Guthrle, 1978
Kovacs et at.. 1984
CO
-------
(cont.)
GO
sr
a.
Species
Tissue
Molybdenum Concentration
Sampling Site
Reference
ro
co
i
Aquatic macrophytes
Hyrlophyllum
Vertlcllatum
Potacnogetum crlspus
Ranunculus sp.
Potamoqetum sp.
Japanese seaweeds
Nut grass
Cyperus retrofractus
Sedge grass
Andropoqon vlrqlnkus
Invertebrates
midges, Chlronorolnal
adonates Llbellula
Hacromla
Ischnura;
crayfish, Cambarus
snails, Physa
Invertebrates
Holna rectlrostrls
Daphnla maqna
Slqara latelalls
Chlronomus annularlus
ollgochaetes
Crayfish
Procambarus clarkll
Golden King Crab
Uthodes aequlsplna
whole body
whole body
whole body
whole body
whole body
' whole body
whole body
abdominal regions
whole body
whole body
whole body
whole body
whole body
thoracic fatty
material
gills
hepatopancreas
muscle
13 ppm dry weight
8.? ppm dry weight
0.14 ppm dry weight
6.5 ppm dry weight
6.2 ppm
10.7 ppm
3.7 ppm
27.3. 60S mg/kg dry weight
1.2, 2.2 mg/kg dry weight
<30.9 mg/kg dry weight
<17.0 mg/kg dry weight
60.3 mg/kg dry weight
<0.1-4.0 ppm (weight)
0.7-4.0 mg/kg dry weight
0.45-2.15 mg/kg dry weight
0.2-0.85 mg/kg dry weight
Fradel Dam, lejo River, Portugal
0.06-1.16 mg/kg dry weight Japan
ash deposit
ash deposit
fly ash basin drainage system,
Savannah River Project
sewage treatment
sewage treatment
sewage treatment
sewage treatment
sewage treatment
South Louisiana
basin, Hungary
basin, Hungary
basin, Hungary
basin, Hungary
basin, Hungary
Alice and Hastings Arms,
British Columbia
Alice and Hastings Arms,
British Columbia
Alice and Hastings Arms.
British Columbia
frletas et al., 1988
Yamamoto et al.. 1985
Cherry and Guthrle. 1979
Cherry and Guthrle. 1979
Cherry and Guthrle. 1978
Ciegeny and Deval, 1985
Czegeny and Deval. 1985
Czegeny and Oeval, 1985
Czegeny and Oeval, 1985
Czegeny and Devat. 1985
Bernard and Roy, 1977
Thompson et al.. 1986
Thompson et al.. 1986
Thompson et al.. 1986
o
tn
CD
u>
-------
IABIF 4-1 (cont.)
0
CD
Q.
1
r\i
1
o
O
Species
Insects, aquatic
Megarcys slgnata
Prunella
Hydropsyche
llnyqmula
'teronarcella bad la
Aquatic Insects
water boatmen
midge larvae
dragonfly nymphs
Aquatic Insects • •'
water boatmen
midge larvae
dragonfly nymphs
damsel fly nymphs
Asiatic clam
Corblcula flumlnla
Asiatic* lam
Clam
Elliptic dllatata
Cockle
Katalysla scalar Ina
Musset
Mytllus edulls
Oyster
Ostrea slnuata
Rock oyster
Saccostrea cuccullata
Scallop
Pec ten novae-ielandlae
Tissue
whole body
whole body
whole body
valve
viscera
whole soft tissue
soft tissues
whole soft tissue
kidney
gill
mantle
soft tissue
whole soft tissue
soft tissue
whole soft tissue
Molybdenum Concentration
0.09-1.65 ppm dry weight
<2.1 ppm dry weight
<1.6 ppm dry weight
0.30. 0.40 ppm
2.1. 16.3 ppm
0.73 iig/g wet weight
<2 mg/kg dry weight
<1.0 ppm dry weight
-38 ppm dry weight
-IS ppm dry weight
-7 ppm dry weight
-0.6 mg/kg dry weight
0.1-0.4 ppm dry weight
<1-3 mg/kg dry weight
0.1-2.3 ppm dry weight
Sampling Site
East River/Upper Gunnlson River.
Colorado
Kesterson Reservoir. California
Volta Wildlife Area. California
New River. Glen Lyn. Virginia
New River. Glen Lyn. Virginia
Tadenac Lake. Ontario
Princess Royal Harbour, Albany,
Australia
Taiman Bay. Nelson, New Zealand
Ml. Desert Island, Lamolne, Maine
Four sites In New Zealand
Tasman Bay. Nelson. New Zealand
Oampter Archipelago, Gldley Island,
Western Australia
Tasman Bay, Nelson. New Zealand
Reference
Colborn. 19B2b
Ohlendorf et al.. 1986
Ohlendorf et al.. 1986
Rodgers et al.. 1980
Rodgers et al.. 1980
Wren et al.. 1983
Talbot and Chang. 1987
Brooks and Rumsby. 196S
Sutherland and Major, 19B1
Kennedy, 1986
Brooks and Rumsby, 196S
Talbot and Chang. 1987
Brooks and Rumbsy, 1965
10
o
-------
TABtt^l
(cont.)
CO
Cf>
a.
i
ro
tn
i
07/26/8'
Species
Freshwater fish
Angullla
Salmo sp.
Levclscus sp.
fish
Chondrostema
Smallmoulh bass
Hlcropterus dolomleu -
Common carp
Cyprlnus carplo
Lake charr
Salvellnus namaycush
Bluntnose minnow
Plmepha-les notatus
Hosqultof Ish
Gambusla offlnls
Northern pike
tiox luclus
Dover sole
Hlcrostomus paclf Icus
Blueglll sunflsh
Lepomls macrochlrus
Lake trout
S. namaycush
Rainbow smelt
Osmerus mordox
Herring gull
Larus argentatus
Tissue
muscle
whole body
, fish muscle
t
i
whole body
fish muscle
fish muscle
muscle tissue
whole body
fish muscle
liver
whole body
muscle
fish muscle
muscle
Molybdenum Concentration
<0.18 ppm dry weight
0.46 ppm fresh weight
0.63 pg/g wet weight
<3.6 pg/g dry weight
0.41 pg/g wet weight
O.SS pg/g wet weight
0.4 ppm
0.36-0.67 ppm
O.S2 pg/g wet weight
0.081-0.13 pg/g wet weight
<2.8 pg/g dry weight
2.2-8.5 ppb fresh weight
O.SO pg/g wet weight
0.58 pg/g wet weight
Sampling Site
Turin region, Italy
Fradel Dam. Tejo River, Portugal
ladenac Lake, Ontario
Lower San Joaquln River. California
ladenac Lake, Ontario
ladenac Lake, Ontario
fly ash basin drainage system.
Savannag River Project
Grassland Water District.
Merced County, California
ladenac Lake, Ontario
south California coast
lower San Joaquln River,
California
Cayuga Lake. New York
Tadenac Lake, Ontario
ladenac Lake, Ontario
Reference
Parlsl et al.. 1986
Freltas et al.. 1988
Wren et al.. 1983
Salkl and Hay. 1988
Wren et al.. 1983
Wren et al.. 1983
Cherry and Guthrle. 1978
Ohlendorf et al., 1987
Wren et al.. 1983
Oe GoetJ et al., 1973
Salkl and Hay, 1988
Tong et al.. 1974
Wren, et al.. 1983
Wren et al., 1983
-------
TABIE 4-1 (cont.)
0
£ Species
en
Q.
Common loon
Cavla Immer
American coot
tul lea amerlcana
Beaver
Castor canadensls
Raccoon
Procyn lotor
Otter
Lutra canadensls
llssue
' muscle
muscle
muscle
, muscle
muscle
Molybdenum Concentration Sampling Site
0.59 vg/g wet weight ladenac Lake. Ontario
0.58 vg/g vet weight ladenac Lake. Ontario
0.46 v9/g wet weight ladenac Lake. Ontario
0.56 v9/g wet weight ladenac Lake. Ontario
0.54 vg/g wet weight ladenac Lake. Ontario
Reference
Wren et al.. 1983
Wren et al.. 1983
Wren et al.. 1983
Wren et al.. 1983
Wren et al.. 1983
0*
1
in
•*x
o)
CD
-------
4.4. AQUATIC RISK ASSESSMENT
The lack of pertinent data regarding effects of exposure of aquatic
fauna and flora to molybdenum precluded the development of a freshwater
criterion by the method of U.S. EPA/OWRS (1986) (Figure 4-1). Additional
data required for the development of a freshwater criterion Include the
results of acute assays with planktonlc and benthlc crustaceans, an Insect,
a nonarthropod and nonchordate species and an Insect or species from a
phylum not previously represented. The development of a freshwater
criterion also requires data from chronic toxIcHy tests with two species of
fauna and one species of algae or vascular plant and at least one bloconcen-
tratlon study.
The lack of pertinent data regarding the effects of exposure of aquatic
fauna and flora to molybdenum precluded the development of a saltwater
criterion by the method of U.S. EPA/OWRS (1986) (Figure 4-2). Additional
data required for the development of a saltwater criterion Include the
results of acute assays with a second chordate species, a nonarthropod and
nonchordate species, a mysld or panaeld crustacean, three ' additional
nonchordate species and one other species of marine fauna. The development
of a saltwater criterion also requires data from chronic toxlclty tests wlth-
two species of fauna and one species of algae or vascular plant and at least
one bloconcentratlon study.
Data currently available Indicate that molybdenum can be acutely toxic
to freshwater vertebrates at concentrations >0.73 ppm. Molybdenum can be
acutely toxic to saltwater fauna at concentrations >147 mg/i.
0186cl -27- 01/30/90
-------
TEST TYPE
Farm ly Gl*lAva
Chordate (Salmonid-f i»h> 0.73*
•c-
Chordate (Marmwater fifth) 60. O"
• 2
Chordat* (fifth or amphibian) 0. 9£*
Crustacean (planPtonic) NA
Crufttacean ( bent hi c) NA
Insect an NA
non-Art hrc-pc-dX-Chc-rdate NA
GMCV
NA
NA
NA
NA
NA
NP
NA
&CF-
NA
NA
NA
NA
NA
NA
NA
New Insect ar. c>>* phylum
ive
NA
NA
NA
xxxxxxxxxxxx
xxxxxxxxxxxx
NA
NA
«uc»
l*'- pl«r,t
xxxxxxxxxxxx
xxxxxxxxxxxx
NA
NA
•NA=N:t Av*il*tle •c.'S-day LC(» ir< ppw fo»* ambry*-larval
trc-'jt, Sc>lf'r-»si us aur-at us • 7-day LC«* in pprn for »tnbryc--larval
riarrc-w.-inc'uthec tc-ao, 6*st rc-pht-vne care-1 1 rigrisa *
FIGURE 4-1
Organization Chart for Listing GMAVs, GMVCs and BCFs Required to Derive
Numerical Water Quality Criteria by the Method of U.S. EPA/OHRS (1986)
to Protect Freshwater Aquatic Life From Exposure to Molybdenum
0186d
-28-
01/30/90
-------
Farm 1 y
Chordate
Chordate
*3
non-Art hropod /-Chord at e
#4
Crustacean (Mysid/Panaeid)
rion-Chordat e
#6
non-Chordate
#7
rion— Chordate
#6
other
algae
#10
Vascular plant
GMAV*
££9»
NA
147-
NA
NA
NA
NA
NA
XXXXXXXXXXXX
XXXXXXXXXXXX
XXXXXXXXXXXX
XXXXXXXXXXXX
TEST TYPE
GMCV-
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
BCF«
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
•NA=Not Available »9£-hour TL, in mg/L for the mummichog,
FundM1 us heteroclit us •46-hour EC*• in mg/L for larvae of the
mussel, Wyti1 us edulis
FIGURE 4-2
Organization Chart for Listing GMAVs, GMVCs and BCFs Required to Derive
Numerical Water Quality Criteria by the Method of U.S. EPA/OHRS (1986)
to Protect Saltwater Aquatic Life From Exposure to Molybdenum
0186d
-29-
05/31/89
-------
4.5. SUMMARY
Data currently available Indicate that molybdenum can be acutely toxic
to freshwater vertebrates at concentrations >0.73 ppm (B1rge, 1978; B1rge et
al., 1979). Molybdenum can be acutely toxic to saltwater fauna at concen-
trations >147 mg/i (Morgan et al., 1986).
BCF values for molybdenum In aquatic fauna did not exceed 100, although
values In algae could be >2000 and <10,000 1n aquatic plants (Brooks and
Rumsby, 1965; Suloway et al., 1983; Sakaguchl et al., 1981; Kovacs et al.,
1984). The highest concentrations of molybdenum 1n aquatic macrophytes were
from samples collected from the Tejo River, Portugal (8.2 ppm dry weight)
(Freltas et al., 1988). The highest levels of molybdenum In tissues of
Invertebrates were reported for Molna rectlrostrls (605 mg/kg dry weight)
and ollgocheates (60.3 mg/kg dry weight) from a sewage treatment basin 1n
Hungary (Czegeny and Deval, 1985). No single sample of carp exceeded 3.6
yg/g dry weight (Salkl and May. 1988). Levels In wildlife were <0.58
vg/g wet weight (Wren et al., 1983).
0186d -30- 01/30/90
-------
5. PHARMACOKINETICS
5.1. ABSORPTION
Engel et al. (1967) conducted a dietary study with 36 pre-adolescent
girls aged 6-10 years to collect balance data on some trace elements, molyb-
denum. The subjects, divided Into three groups of 12 each, received three
different controlled diet patterns. Group 1 received the controlled diet
during 14 consecutive 4-day periods, group 2 during five consecutive 6-day
periods and group 3 during an unspecified number of 6-day periods. Between
94 and 189 ppb molybdenum was present In the diets. Molybdenum was measured
1n urine and feces collected throughout the experiment. For dally Intakes
between 40 and 80 yg of molybdenum, net retention varied between 3.4 and
32.6 yg. No clear relationship could be established between amount of
Intake and net retention, but all diets resulted In positive balances,
Indicating that storage occurred when the Intake was -100 yg/day.
Van Campen and Mitchell (1965) Injected Jji situ llgated segments of the
gastrointestinal tract of female Sprague-Dawley rats with radioactive
ammonium molybdate In saline. Within 2 hours, 9.5% of the administered dose
(2.7 yM Mo/rat) was taken up 1n the duodenum, 8.354 In the 1leum, 6.8% 1n
the mldgut and 3.6% 1n the stomach.
Bell et al. (1964) administered a single oral (gavage) or Intravenous
dose of radioactive molybdenum (as ammonium molybdate In aqueous solution)
to 20 castrated male pigs of mixed breeding (39 kg bw). Based on data
provided by the Investigators, the doses were -0.06 mg/kg or 0.5 mg/kg. Two
hours after dosing by either route and with either dose, 6% of the adminis-
tered dose was detected In whole blood; this declined to 0.07% at 48 hours.
0186d -31- 07/26/89
-------
Urinary excretion accounted for 80-86% of the dose during 5 posttreatment
days, with very little additional excretion after the first 24-hour collec-
tion period. Fecal excretion accounted for 8.6-14.6% of the dose over the
5-day collection period. These data suggest that Mo Is rapidly and
efficiently absorbed from the gastrointestinal tracts of swine.
Falrhall et al. (1945) administered oral doses (presumably by gavage) of
-30 mg Ho/kg/day from molybdenum trloxlde for 10 days to guinea pigs and
measured the urinary and fecal excretion of molybdenum before and during
exposure, as well as for 8 days after exposure. The Investigators concluded
that molybdenum was rapidly absorbed, since fecal excretion Increased
greatly after dosing started.
5.2. DISTRIBUTION
Without providing documentation, Goyer (1986) stated that, 1n humans, -9
mg of molybdenum Is located primarily In the liver, kidneys, adrenals and
omentum.
Comar et al. (1949) reported that an oral dose of 41 mg/kg of radio-
labeled molybdenum trloxlde In aqueous solution given to 14-month-old steers
was widely distributed after 12 days, with high selective accumulations In
the adrenals, bone, liver, eye. Intestinal lymph glands and kidney. The
authors also reported that 0.26, 0.51 and 0.42% of the Ingested dose was
found In the liver at 16, 41 and 64 hours after dosing, respectively. A
similar pattern of distribution was observed after a single Intravenous
Injection of 11 mg/kg.
Falrhall et al. (1945) administered a'single 50 mg oral dose of Mo as'*'
molybdenum trloxlde In gum arable solution to young adult male guinea pigs
and measured the content of Mo In several tissues at 4, 16 and 48 hours
after treatment (Table 5-1). Similar levels of Mo were located 1n the major
rf
0186d -32- 07/26/89
-------
TABLE 5-1
The Distribution of Molybdenum Following Oral
Administration of Molybdenum Trloxlde to Guinea P1gs*
Tissue
Kidneys
Spleen
Blood
B1le
Liver
Lungs
Muscle
Interval
After Dosage
4 Hours - 16 Hours
Molybdenum Content (mg Mo/10
'0.46
0.26
0.26
0.28
0.20
0.31
NR
0.20
0.12
0.05
0.20
0.08
0.10
0.02
48 Hours
g tissue)
0.07
0.18
0.50
0.30
0.03
0.09 . .
0.01
'Source: Falrhall et al., 1945
NR = Not reported
0186d -33- 05/31/89
-------
tissues at 4 hours after treatment, but levels 1n the kidneys exceeded those
1n the liver. No tissue appeared to preferentially retain Mo, but the
highest tissue levels at the end of the 48-hour test period were In the
blood. In other oral studies, Falrhall et al. (1945) reported levels of Mo
In bone between those for the liver and kidneys.
In a study by Falrhall et al. (1945) molybdenum was highly concentrated
In lungs, kidneys and bone after repeated (1 hour/day, 5 days/week for 5
weeks) Inhalation exposures of guinea pigs to molybdenum trloxlde dust (155
mg Mo/m3) and molybdlc oxide fumes (52 or 186 mg Mo/m3).
In a study by Rosoff and Spencer (1973), Swiss-Webster mice (3/sex/
group) received an Intravenous Injection of an unspecified amount of molyb-
denum-99 (as ammonium molybdate In aqueous solution) and were sacrificed 1
or 24 hours after the Injection. Organs, tissues and blood were assayed for
radioactivity. Liver, kidney and pancreas had the highest uptake (18.1,
11.6 and 4.7X of the dose, respectively, after 1 .hour). Uptake In other
organs varied between 0.8 and 2.3 X of the dose. In the group sacrificed 24
hours after treatment, the percentage of the dose found In the liver and
testes was similar to that found In those sacrificed 1 hour after Injection.
The greatest decline In molybdenum concentration was seen In blood. When
the results were expressed as percentage of the dose/organ, the liver had
the highest concentration of molybdenum (25.6 and 20.9% of dose at 1 and 24
hours, respectively). Other organs had much smaller amounts.
Nellands et al. (1948) gave six male Sprague-Dawley rats oral doses of a
solution containing 13.34 mg of radlolabeled molybdenum. Radlolabel was
measured In several tissues 2.5. 26.1 and 51.0 hours after treatment. On a
per-gram-of-t1ssue basis, the highest levels were located In the stomach.
0186d -34- 05/31/89
-------
blood and kidneys at 2.1 hours after treatment and In the kidneys, Intes-
tines and bones at 51 hours after treatment. In rats similarly treated at
26.68 mg Ho/kg, the highest levels 25.8 hours after treatment were In the
stomach, Intestines and bones.
5.3. METABOLISM
Data were not located regarding the metabolism of molybdenum; appar-
ently, elimination of molybdenum Involves excretion rather than metabolism.
5.4. EXCRETION
In the 10-day oral study using guinea pigs (see Section 5.1.), Falrhall
et al. (1945) concluded that elimination from the body was rapid, since
fecal and urinary Mo levels returned to pre-exposure levels shortly after
exposure ceased.
In a study by Lener and B1br (1979), male Ulstar rats with cannulated
bile ducts were anesthetized with urethane and given an Intravenous Injec-
tion of radioactive pentavalent or hexavalent molybdenum In solution at
doses of 0.08 or 4.6 mg Mo/kg. The biliary excretion of penta- and hexava-
lent molybdenum peaked 1 hour after the Intravenous Injection of 0.08 mg/kg
and slowly declined over the next 3 hours- A similar result was obtained
with the 4.6 mg/kg dose of hexavalent molybdenum. However, the biliary
concentration of pentavalent molybdenum after the 4.6 mg/kg dose reached
only one-fourth that of the hexavalent form. The whole-body excretion of
molybdenum after a subcutaneous dose of 4.6 mg Mo/kg was faster for the
hexavalent than for the pentavalent form, but no difference between the two
forms was seen with a dose of 0.08 mg Mo/kg. Also, after an Intravenous
dose of 4.6 mg Mo/kg, hexavalent molybdenum decreased faster In blood, liver
and jejunolleocecum than did the pentavalent form.
0186d -35- 07/26/89
-------
In mice given a single Intravenous dose of radlolabeled molybdenum (see
Section 5.2.), 35.6% of the dose was excreted In the urine and only 2.6% 1n
the feces In 24 hours (Rosoff and Spencer, 1973).
In four patients receiving single 50-100 yd Intravenous doses of
radioactive molybdenum, 16.6-27.2% of the dose was excreted In the urine In
a 5-day period, the highest percentage being excreted on day 1 and declining
thereafter. In contrast, excretion In the feces totaled 6.8 and 1.0% of the
dose In two patients tested over a 10-day period (Rosoff and Spencer, 1964).
Engel et al. (1967) also reported that, In'humans, the urinary excretion of
molybdenum exceeded that In the feces by a factor of -2 after oral dally
Intakes between 40 and 80 yg.
In swine, the cumulative urinary excretion of molybdenum peaked at
-75-80% of an oral dose 24 hours after dosing and Increased only to 80-86%
during a 5-day period (Bell et al., 1964) (see Section 5.1.). In contrast*
fecal excretion reached only 8.6-14.6% of the administered dose In the same
observation period.
Consolazlo et al. (1964) studied the excretion of molybdenum In the
sweat of throe male volunteers exposed to 37.8°C and 50% relative humidity
during four 4-day periods. The average dally Intake of molybdenum was 172
yg. Molybdenum 1n the sweat was reported only In one of the exposure
periods and amounted to 61 yg. In the same period, the urinary and fecal
excretions of molybdenum were 188 and 82 yg, respectively. The authors
concluded that, under conditions of profuse sweating,'the loss of molybdenum
should not be disregarded.
5.5. SUMMARY
Excretion studies using pigs suggest that -80-86% of an orally admin-
istered dose of Mo was fairly rapidly absorbed from the gastrointestinal
i*
0186d -36- 07/26/89
-------
tract (Bell et a!., 1964). In 6- to 10-year-old girls, a positive balance
_x
was observed when the diet provided 40-80 yg Ho/day (Engel et a!., 1967).
Molybdenum appears to be rapidly absorbed from the gastrointestinal tract of
guinea pigs. Studies using rats suggest that absorption of molybdenum from
molybdenum trloxlde Is more rapid than from molybdenite, because the former
Is more soluble In digestive juices (Falrhall et a!., 1945). Molybdenum was
widely distributed throughout the body after oral dosing of steers (Comar et
a!., 1949) and guinea pigs (Falrhall et al., 1945). Qualitatively similar
results were obtained In mice after Intravenous Injections and In rats after
oral administration of radlolabeled molybdenum (Nellands et al., 1948;
Rosoff and Spencer, 1973). In mice, rats and steers, liver and kidneys
accumulated a considerable percentage of the administered dose. In humans,
molybdenum Is found mainly In the liver, kidneys, fat and blood (Goyer,
1986).
Molybdenum Is apparently eliminated primarily by excretion, as no
evidence was found for metabolism of Mo. In swine, urinary excretion
accounted for 80-86% of an oral dose and fecal excretion accounted for
8.6-14.6% (Bell et al., 1964). In humans treated Intravenously, urinary
excretion accounted for 16.6-27.2% of the dose and fecal excretion for
1.0-6.8%. Substantial amounts of Mo may be lost through profuse sweating
(Consolazlo et al., 1964). Following Intravenous treatment, mice excreted
35.6% of the dose In the urine and 2.6% In the feces over a 24-hour period
(Rosoff and Spencer, 1973). Lener and B1br (1979) demonstrated qualita-
tively that biliary excretion Is Involved In Mo elimination, but the extent
of excretion by this route was not determined.
0186d -37- 07/26/89
-------
6. EFFECTS
6.1. SYSTEMIC TOXICITY
6.1.1. Inhalation Exposure.
6.1.1.1. SUBCHRONIC — Falrhall et al. (1945) exposed male guinea
pigs to dusts of molybdenite, calcium molybdate and molybdenum trloxlde at
estimated concentrations of 279, 155 and 200 mg of molybdenum/m3 air,
respectively, for 1 hour/day, 5 days/week for 5 weeks. Data regarding
control (unexposed) animals were not given. Mean particle size was 1.63
vm, but size distribution data were not reported. Exposure to molybdenite
dust had no noticeable effects on a group of 25 guinea pigs other "Than
Increased respiratory rate during exposure. One animal died after three
exposures, but the cause of death was not Indicated. Molybdenum trloxlde
was.a respiratory Irritant 1n 51 exposed guinea pigs. In addition, loss of
appetite, weight loss, diarrhea, hair loss and muscle Incoordlnatlon were
observed. Twenty-six of the 51 guinea pigs died during the testing period.
Hlstologlcal examination of animals 1n this group revealed slight to
moderate swelling of hepatocytes with occasional necrosis and fatty Infil-
tration. Traces of fatty deposits were seen In the kidneys. Most of the
animals examined showed mild to moderate amounts of alveolar and bronchial
exudate. Exposure of 24 guinea pigs to calcium molybdate dusts (neutralized
with calcium hydroxide) Induced no clinical signs of toxlclty; however,
Falrhall et al. (1945) mentioned that 5/24 animals died during the
experiments.
Falrhall et al. .(1945) also exposed male guinea pigs (number not
V
specified) to fumes of molybdenum trloxlde. Fumes were produced by arcing
across a 110-volt d.c. circuit with molybdenum metal electrodes. The
animals were exposed to the trapped fumes 1 hour/day, 5 days/week for 5
0186d -38- 05/31/89
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weeks. The estimated concentrations were 52 or 186 mg Mo/ma of air. No
clinical signs of toxlclty were noticed with the low molybdenum dose, and no
deaths occurred In this group. An 8.3% mortality was observed In the high-
dose group, but the authors do not mention the number of exposures or the
cause of death.
6.1.1.2. CHRONIC — Walravens et al. (1979) studied the effect of
molybdenum dust on a group of 25 male workers aged 19-59 (mean 30.8) from a
molybdenite roasting plant. A control group of 24 unexposed subjects of
comparable age (sex not specified) was used. Oust particles had a diameter
of <10 ym and were composed mainly of molybdenum trloxlde and other
soluble oxides. Duration of employment In the factory by the experimental
subjects ranged from 0.5-20 years. Based on different levels of exposure In
the different areas of the factory, the authors calculated that each subject
was exposed to an 8-hour TWA of 9.47 mg Ho/m3. Biochemical variables
monitored Included urinary and plasma molybdenum, serum ceruloplasmln and
uric add, and urinary uric add/creat1n1ne ratios. The mean serum levels
of ceruloplasmln and uric acid were significantly greater In exposed
subjects than In control Individuals. Plasma molybdenum levels In unexposed
subjects varied from undetectable to 34 ng/ml, whereas In those exposed to
w
molybdenum dust, the range was 9-365 ng/mi. The urinary levels of molyb-
denum In 14 exposed subjects fell between 120 and 11,000 yg/mn, compared
with 20-230 pg/ms. In 18 unexposed Individuals. It could not be deter-
mined whether molybdenum was absorbed through the lungs or In the gastro-
intestinal tract. In addition, the Investigators Indicated that the wide
range of plasma molybdenum levels may reflect "that the blood samples were
collected when some workers were starting their 8-hour shift, others were In
the middle of the work day, and some had Just completed the shift."
0186d -39- 07/26/89
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6.1.2. Oral Exposure. In most oral exposure studies, the basal diet fed
to animals, which was generally used as the control diet, contained trace
amounts of molybdenum. These trace amounts are not mentioned In the
descriptions of the studies, since they represent a very small percentage of
the total molybdenum administered; therefore, their contribution to the
development of toxic effects Is considered negligible.
6.1.2.1. SUBCHRONIC — Falrhall et al. (1945) fed rats diets (not
described) to which one of several Ho compounds were added, as presented In
Table 6-1. The Investigators stated that molybdenite. In which the Mo Is
present In a valence of «4, was poorly-soluble In digestive juices. Tissue
concentration studies suggest that this compound was poorly absorbed. The
other Mo compounds are all hexavalent and readily soluble In gastrointes-
tinal tract contents. Tissue concentration studies suggest that they were
more readily absorbed. No adverse effects were observed regarding clinical
appearance, food consumption, body weight gain or hlstologlcal appearance of
(unspecified) organs and tissues In rats fed diets containing molybdenite.
Thus, from this study, the dose of 4310 mg Mo/kg/day can be Identified as a
NOAEL for rats fed diets containing molybdenite.
Diets that provided estimated doses of 111, 203, 350. 1471 or 6757 mg
Mo/kg/day (from molybdenum trloxlde) for <137 days caused 50% mortality In
the lowest dose group 1n 120 days. All animals In the two highest dose
groups died In the first 2 weeks of the study. In rats fed a diet contain-
ing calcium molybdate at levels that provided doses of 70, 181, 326, 573 or
J . „ ~ - - . I ,-,....' t - •- ll'K Q1" ' * C T*,' ' , ".
2986 mg Mo/kg/day for .£137 days, 50% mortality occurred In the lowest dose
group In 137 days, whereas all the rats In the highest dose group died
within 17 days. When the diet contained ammonium molybdate at a level that
t
provided a dose of 100 mg Mo/kg/day, 25% of the rats died In 232 days, but
0186d -40- 07/26/89
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TABLE 6-1
oo
cr>
CL
Ingestlon of Molybdenum by Groups of Hale White Rats Fed Diets Containing Various Molybdenum Compounds3
o
in
oo
Compound >
Control . ;
Molybdenite
Molybdenum trloxlde
.
Calcium molybdate
Ammonium molybdate
,
'
Number of
Rats/Group
48
8
8
8
8
10
10
8
8
10
10
10
10
10
8
8
8
Exposure
(days)
137
44
44
44
120
137
137
14
8
137
128
137
57
17
232
13
9
Estimated
Mo Intake^ •
(mg/day)
0
10
100
500
10
25
50
100
500
9
21
43
86
430
10
100
500
Average
Body Ue1ghtc
(kg)
0.137
0.117
0.113
0.116
0.09
0.123
0.143
0.068
0.074
0.129
0.116
0.132
0.15
0.144
0.1
0.068
0.077
Estimated
Dosage of Mod
(mg/kg/day)
0
85
885
4310
111
203
350
1471
6757
70
181
326
573
2986
100
1470
6494
aAdopted from Falrhall et al. (1945)
Data provided by Investigators
Calculated from Initial and terminal body weight data provided by Investigators
Estimated dally Intake of Mo divided by average body weight
-------
all died before 2 weeks when the dose was 1470 or 6494 mg/kg/day. Toxldty
signs attributable to molybdenum 1n all three forms were diminished food
Intake, weight loss, llstlessness and rough hair coat. Results of hlsto-
pathologlcal examination, 1f performed, were not reported.
Gavage doses of 25, 100 or 200 mg/day of Mo from calcium molybdate In
gum arable (53, 218 and 410 mg Mo/kg/d based on body weight data) given to
groups of eight male guinea pigs for 95 days caused 12.5, 25 and 25% mortal-
ity, respectively. Similar administration of 25 mg Mo/day from molybdenum
trloxlde (85 mg Ho/kg/day) caused 75X mortality 1n 99 days. Doses of 100
and 200 mg Mo/day from molybdenum trloxlde (303 and 583 mg/kg/day) caused
100X mortality 1n 27 and 9 days, respectively (Falrhall et al., 1945). No
controls were given the vehicle alone, and the nutritional adequacy of the
diet was not reported.
Arrlngton and Davis (1953) fed groups of two to five weanling Dutch
rabbits of both sexes commercial diets containing added sodium molybdate
(purity not reported) at 0.014, 0.05, 0.1, 0.2 or 0.4X. Dosages of 6.9,
24.5, 49, 98 or 196 mg Mo/kg/day can be estimated by applying a reference
food factor of 0.049 (U.S. EPA, 1986b). Diets containing 0, 0.014, 0.1, 0.2
or 0.4% Ho were also fed to groups of two to four mature rabbits. The exact
duration of the treatment Is not stated, but was presumably <17 weeks
according to data presented 1n one of the tables. The animals were examined
dally for signs of toxlclty, and body weight gain was monitored weekly from
24 six-week-old rabbits. The hematocrlt was measured periodically and the
hemoglobin concentration, every 2 weeks. The frequency of the analyses
Increased upon manifestation of toxic signs. Doses <49 mg/kg/day Induced
anorexia, weight loss, alopecia and anemia 1n young rabbits after 4 weeks of
treatment. Mature rabbits at this dosage developed these signs after longer
0186d -42- 07/26/89
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periods of treatment. A total of 10 deaths occurred 1n the groups given the
two highest doses of molybdenum within 30 and 54 days of treatment. Seven
young rabbits given doses <49 mg/kg/day developed deformities In the front
legs progressing to the point where they could not maintain their weight.
Hemoglobin concentration and the number of red blood cells were markedly
reduced starting at week 3 In rabbits given doses of 49 mg/kg/day. Two
young rabbits at 49 mg Mo/kg/day gradually recovered after Initially showing
signs of toxldty, suggesting that young rabbits may be more sensitive than
adults to Mo toxldty. Since no effects were observed with doses of <24.5
mg Ho/kg/day, this value represents a NOEL. Addition of copper to the
experimental diet relieved the signs of toxldty Induced by molybdenum.
Robinson et al. (1969) studied the effects of two diets supplemented
with sodium molybdate (purity not reported) on the life span of rabbit
erythrocytes. Sodium molybdate was added to basic diets at 0.4%. By
adjusting for content of Ho and application of a reference food factor, a
dose of 91 mg Mo/kg/day can be estimated. The erythrocytes were labeled U»
vivo with 32-P DFP Injected Intravenously. Four different groups were
formed. In group 1, eight control and 12 test rabbits previously mantalned
on a commercial pelleted diet were Injected with DFP the day molybdate
feeding was begun. In group 2 (eight controls, 11 test rabbits previously
maintained on the pelleted diet) were fed the test diet for 52 days before
the OFP Injection. Group 3 (eight controls, 11 test rabbits) was fed an
oats-alfalfa (nutritionally deficient) diet, and= the DFP was Injected 27
days before molybdate.-feeding began. Group 4 (seven controls, 12 test
rabbits), also fed the oats-alfalfa diet, was Injected with DFP 7 days
before the test feeding started. Total Mo exposure time was not clear, but
0186d -43- 05/31/89
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the total experimental period was apparently 60 days. There were no statis-
tically significant differences 1n red blood cell survival time between
treated rabbUs and controls In groups 1 and 2 (pellet-fed rabbits), but
body weight gain was reduced In test animals. The erythrocyte survival time
of controls In group 3 (oat-alfalfa-fed) did not differ from that of the
test animals from group 3. However, 1n group 4, a significant difference
was seen In erythrocyte survival time between control and test animals. No
deaths attributable to molybdenum Ingestlon occurred 1n pellet-fed rabbits.
Seven of eleven and 11/12 rabbits died after 12-35 days on the test diet 1n
groups 3 and 4, respectively. The mean survival time of the molybdenum-fed
rabbits In group 4 was 24.2 days. Although the authors Indicate that
hemoglobin concentration and packed cell volume were measured throughout the
experiment, no values are given. The authors stated, however, that a severe
anemia developed In test rabbits on the oats-alfalfa diet.
An early study by Franke and Hoxon (1937) provides data regarding the
effects of oral Ingestlon of molybdenum In rats. In this study, groups of
10 Wlstar rats of both sexes were fed a wheat diet (nutritional adequacy not
described) containing 25 or 50 ppm of molybdenum as ammonium molybdate
(purity not reported) for 100 days. The authors calculated that the
low-dose diet provided 1.75 and 1.87 mg Ho/kg/day to male and female rats,
respectively, and that the high-dose diet provided 3.35 and 3.68 mg
Mo/kg/day to males and females, respectively. Two groups of 10 rats each
were fed the wheat diet only and served as controls. Body weight, food
consumption and hemoglobin concentration were monitored regularly throughout
the experiment. Molybdenum, at either level, caused no deaths and had no
noticeable effects on hemoglobin concentration In male or female rats.
0186d -44- 07/26/89
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Although the authors concluded that treatment had no effect on body weights,
rats In the 50 ppm group had body weights slightly but consistently below
those of controls at <20 days (females) or 40 days (males) of exposure.
Food consumption was apparently not affected. Accepting the author's
conclusion that body weight was not affected, this study defines NOAELs of
3.35 and 3.68 mg Ho/kg/day for male and female rats, respectively.
Lallch et al. (1965) studied the effect of dietary molybdenum on
abnormal skeletal growth In weanling male Sprague-Dawley rats (39-45 g bw).
Sodium molybdate (purity not reported) was added to a basic diet (1.6 ppm
Cu) at concentrations of 1.0, 1.5 or 2.0 g/kg of food. By adjusting for
content of Ho and applying a reference food factor of 0.05 (U.S. EPA, 1980),
doses of 23, 35 or 47 mg Ho/kg/day can be estimated. There were seven rats
1n the low-dose group, four In the Intermediate and 11 In the high-dose
group. After 6 weeks on the diet, the rats were sacrificed and autopsies
performed. Ten rats fed a molybdenum-free diet served as controls. All
three dietary levels of molybdenum greatly decreased weight gain (35%
decrease for the low- and Intermediate- and 60X decrease for the high-dose
diet) and transient diarrhea was common during the first 2 weeks of feeding.
Other toxic signs observed were mandlbular nodulatlons and gross deformities
of the knee Joint. Test rats also developed malformations of the long
bones. The three long bones examined (femur, tibia and humerus) were
shorter with Increased shaft diameters. Malformations of the sternum and
vertebral column were noticed only In rats of the high-dose group. Hlsto-
loglcal examination of the major organs did not reveal any significant
alterations. Skin and bone of rats In the high-dose group (93 mg/kg/day)
showed a great Increase In molybdenum content over control rats. Combining
molybdenum with copper 1n the diet prevented the development of bone
malformations, but not the loss of weight.
0186d -45- 07/26/89
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Winston et al. (1973) conducted a toxlclty study using rats mantalned on
a commercial diet to determine the effect of molybdenum on the response to
cold stress. Hale and female Sprague-Dawley rats were given 0 or 10 ppm of
molybdenum (from sodium molybdate, purity not reported) in the drinking
water from birth. Assuming rats weigh 0.35 kg and drink 0.049 s. of
water/day (U.S. EPA, 1986b), these levels of molybdenum provided estimated
doses of 0 and 1.4 mg Ho/kg/day. At 5-12 months old. the rats were tested.
The response to cold stress was examined by keeping groups of rats for 4
days In a chamber at room temperature or 3°C and determining the weight
changes. A group of rats given molybdenum-free water was divided Into
subgroups, one of which was tested at 3°C and the other maintained at ?5°C.
A similar subdivision was made In the group administered molybdenum. In
each of the four subgroups, there were two to five females and 11-12 males.
All rats subjected to the low-temperature test had depressed body weight
gain; however, this depression was significantly greater (p<0.01) In those
receiving molybdenum than In those given molybdenum-free water. Hales and
females showed the same pattern of response.
Nellands et al. (1948) fed a group of four 21-day-old male Sprague-
Dawley rats a purified diet (virtually free of Cu) containing 40 mgX (400
' • r , ' "
ppm) molybdenum (from sodium molybdate) for 6 weeks. A control group was
fed a molybdenum-free purified diet. Rats fed the test diet, which provided
20 mg Ho/kg/day (assuming a food factor of 0.05), gained weight signifi-
cantly more slowly than rats on the control diet. Rats fed a diet contaln-
r - , - ..;*,-., , .'- '•- • •-•".'. -
Ing 400 ppm Mo supplemented with 5X whole liver substance (rich in trace
* * r
elements Including Cu) outgalned control rats fed the purified diet.
6.1.2.2. CHRONIC — Pertinent data regarding chronic oral exposure to
•,,. - - •><;' - .'•."•'
molybdenum compounds were not located In the available literature cited In
i*
Appendix A.
0186d -46- 07/26/89
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6.1.3. Other Relevant Information. Molybdenum 1s a basic component of
the prosthetic group of flavoproteln enzymes such as xanthlne oxldase,
nitrate reductase, aldehyde oxldase, nltrogenase and xanthlne dehydrogenase.
In addition, molybdenum Is essential for the utilization of Inorganic
nitrogen In the synthesis of proteins, nucleic adds and other nitrogenous
cell constituents (Lener and Blbr, 1984). Xanthlne oxldase plays a crucial
role In the end stage of purlne catabollsm, by catalyzing the aerobic
dehydrogenatlon of hypoxanthlne to xanthlne and of xanthlne to uric acid.
Therefore, a reduction 1n the molybdenum content In body tissues may
decrease the activity of xanthlne oxldase, which may be reflected as hypo-
urlcemla, hypourkosurla and elevated urinary xanthlne. This can result In
calculus formation In the kidney collecting tubules (Lener and B1br, 1984;
Solomons, 1984).
The Impact of Cu nutrition on the toxlclty of Mo has been reviewed by
Underwood (1977). An antagonism occurs between Cu and Mo such that animals
fed diets deficient In Cu are likely to experience unusually severe conse-
quence of Increased Mo Intake. For example, Robinson et al. (1969) reported
severe anemia and mortality In rabbits fed a nutritionally Inadequate diet
that also provided Mo at 91 mg/kg/day for <60 days. The same dosage of Mo
In rabbits fed a commercial (presumably adequate) diet only reduced the rate
of body weight gain.
Nellands et al. (1948) fed groups of 21-day-old male Sprague-Dawley rats
purified diets virtually devoid of Cu containing 0, 50, 100 or 500 mg% (0,.
500, 1000 or 5000 ppm) Mo from sodium molybdate for <4 weeks to Investigate
effects on body weight gain. Assuming a food factor for rats of 0.05 (U.S.
EPA, 1980), these dietary concentrations corresponded to doses of 0, 25, 50
and 250 mg/kg/day, respectively. Ra'ts on the 5000 ppm diet lost weight and
0186d -47- 07/26/89
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died shortly after 1 week of treatment. Gross pathological examination
revealed extreme emaciation. There were no effects on hematologlcal
parameters. A dose-related depres- slon of body weight gain was reported at
the lower dosage levels.
Oral LDcnS of 101, 125 and 333 mg Mo/kg were reported In rats for
calcium molybdate, molybdenum trloxlde and ammonium molybdate, respectively,
In a dietary study In which rats were fed Ho for 40 days (Falrhall et a "I.,
1945). Intragastrk Intubation of neonatal rats on days 4-15 with a neutral
solution of ammonium molybdate that provided doses of 200 mg Mo/kg/day had
no adverse effects on body weight, hemoglobin, hematocrH or hlstopathology
(Hunt and Navla, 1973). However, the same doses given In acidic solutions
Induced fatty liver and death.
In a study by Rana et al. (1980), 10 male albino rats fed a diet that
provided 1.0 g/kg bw of ammonium molybdate (571 mg Ho/kg/day) for 20 days
lost considerable weight, from 103 g at the start of the experiment to 60 g
after 20 days of the test diet. Concurrent controls fed a standard labora-
tory diet went from an Initial body weight of 105-140 g In the same period
of time. Information regarding food consumption was not given. In addi-
tion, molybdenum enhanced the rate of Upld accumulation In the liver and
kidneys, compared with control rats. The same group of Investigators, using
the same protocol, reported that molybdenum decreased the activities of the
enzymes alkaline and acid phosphatase and llpase, but did not alter glucose-
6-phosphatase and chollnesterase In rat liver (Rana and Kumar, 1980a). Rana
and Kumar (1980b) also reported that the percentage of total proteins
significantly decreased In the kidneys, but not 1n the liver, of rats
treated as described above.
0186d -48- 07/26/89
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Molybdenum caused thyroldal hypofunctlon In male New Zealand rabbUs fed
diets containing 0.3% molybdate Ions for 25 and 31 days, as Indicated by a
50% decrease In thyroldal hormone synthesis and secretion, compared with
controls (Wldjajakusuma et al., 1973). Also, body weights, hemoglobin
concentrations and packed cell volumes were significantly reduced. By
adjusting for content of Mo and assuming a food factor for rabbits of 0.049
(U.S. EPA, 1986b), a dose of 98 mg Mo/kg/day can be estimated.
Bandyopadhyay et al. (1981) reported that oral administration of
ammonium molybdate In water at doses of 500 mg/kg bw (289 mg Ho/kg/day) to
male Wlstar rats for 28 days Induced moderate to severe hlstologlcal changes
In the liver and kidneys and caused marked growth retardation, compared with
basal diet-fed controls. A high-protein diet could partially prevent these
changes. Molybdenum also altered the activities of several glycolytlc
enzymes In the liver and kidneys as well as the serum levels of prolactln,
cortlsol and lutelnlzlng and follicle-stimulating hormones.
Rats fed a basal diet supplemented with 6 mg/kg (6 ppm) of Mo from
ammonium tetrathlomolybdate (0.3 mg/kg/day, assuming a food factor of 0.05)
for 21 days developed hlstologlcal alterations In the gastrointestinal tract
Including cell fragmentation and necrosis In the caecum and colon, compared
with controls fed a basal diet alone (Fell et al., 1979). Also, mltochon-
drlal abnormalities 1n the duodenum and jejunum were noticed. A dietary
concentration of 6 ppm Mo (0.3 mg Mo/kg/day) for 21 days also caused severe
skeletal abnormalities In rats (Spence et al., 1980). Alterations were most
prominent In long-bone growth plates, muscle Insertions and beneath the
periosteum. . , , .
Falrhall et al. (1945) administered molybdenum trloxlde to guinea pigs
by dally stomach Intubation at 25, "50, 75, 100 or 200 mg/kg/day for <25
0186d -49- 07/26/89
-------
days. The estimated doses adjusted for content of Mo were 17, 33, 50, 67
and 133 mg Mo/kg/day. All animals exposed to the two higher doses died by
the 9th day. Hlstologlcal examination of the tissues revealed fatty changes
In the liver and swollen hepatocytes and epithelial cells In the convoluted
tubules of the kidney, as well as dose-related Increases 1n the Incidence
and Intensity of fatty Inclusions In the cortical epithelium. Mild to
moderate congestion was observed 1n the lungs, and pulp retlculum cells In
the spleen Increased. No changes were noticed In the heart. There was no
mention of a control group.
6.2. CARCINOGENICITY
6.2.1. Inhalation. Pertinent data regarding the Inhalation carclnogen-
Iclty of molybdenum compounds were not located 1n the available literature
cited In Appendix A.
6.2.2. Oral. The only Information regarding oral carclnogenlclty of
molybdenum can be found In Luo et al. (1983), described 1n Section 6.2.3.
In this study, no tumors or pretumorous lesions were found In the esophagus
and forestomach of male Sprague-Dawley rats receiving 2.8 mg Mo/kg/day for
<30 weeks.
6.2.3. Other Relevant Information. The co-carcinogenic properties of
molybdenum were studied by Luo et al. (1983). In this study, weanling male
Sprague-Dawley rats (10-15/group) were given sodium molybdate In the
drinking water at levels of 0, 2 or 20 ppm Mo (0. 0.28 or 2.8 mg Mo/kg/day
assuming rats drink 0.049 I/day and weigh 0.35 kg) for 19 or 30 weeks.
_,,,., i . r ~ •
Treated groups also received twice weekly Intubations of a solution of the
carcinogen NSEE for 8 consecutive weeks beginning at the 4th week. Three
, :
additional groups were treated with either NSCE or saline Intragastrlcally,
or with 20 ppm Mo In the drinking water. Addition of molybdenum, at either
0186d -50- 07/26/89
-------
dose level, significantly Inhibited the formation of tumors In the esophagus
and forestomach Induced by administration of NSEE. Molybdenum by Hself did
not Induce tumors In either organ.
Bogdcn et al. (1986) studied the co-carcinogenic properties of molyb-
denum 1n male Sprague-Dawley rats administered the esophageal carcinogen
HBN. Groups of rats (nine/group) received sodium molybdate In the drinking
water at concentrations that provided Ho at 0, 15 or 45 ppm. Before expo-
sure to Mo, the rats were pretreated with 2.5 rag/kg of MBN Intragastrlcally
In 10% ethanol twice/week for 5 weeks. A third group received only MBN for
5 weeks. After a subsequent 12-week period of exposure to Mo, the rats were
killed and their esophagi prepared for gross and hlstologlcal examination.
No significant differences were noticed among the three treatment groups
regarding the number of rats bearing precancerous lesions, gross papHlomas
or carcinomas or the number of esophageal lesions/rat.
Stoner et al. (1976) examined the carcinogenic properties of Intraperl-
toneal Injections of molybdenum trloxlde In the Strain A mice lung tumor
assay. Groups of 20 mice (10/sex/group) received Injections of molybdenum
trloxlde In 0.85% saline three times/week for a total of 19 Injections.. The
cumulative dose received by each mouse In each of the three test groups was
633, 1823 or 3167 mg Mo/kg. Two additional groups either remained untreated
or received the solvent alone. Positive controls received a single Intra-
perHoneal Injection of 20 mg urethane/mouse. The average number of lung
tumors/mouse In the highest dose group was 1.13, compared with 0.42 and 0.28
In solvent controls and untreated mice, respectively. This difference was
significant (p<0.05). In addition, the number of mice bearing tumors was
higher in the high group (10/15) than In the control groups (7/19), although
the difference was not statistically significant (p>0.08; Fisher Exact Test
performed at SRC). The number of mice with lung tumors and the average
0186d -51- 07/26/89
-------
number of lung tumors/mouse In the low and Intermediate dose groups was not
significantly different than In controls. The authors concluded that molyb-
denum was "weakly positive" 1n this assay. In view of the small Increase In
the number of lung tumors/mouse and the Insignificant Increase 1n the number
of mice bearing tumors, the evidence for cardnogen1c1ty In this test 1s
Inconclusive.
We1 et al. (1985) administered molybdenum (unspecified form) to female
Sprague-Dawley rats maintained on a low (0.026 ppm) Ho diet at a level of 10
ppm In the drinking water for 125 or 198 days. This level of molybdenum In
the water corresponds to a dose of 1.4 mg Ho/kg/day, assuming rats weigh
0.35 kg and consume 0.049 I of water/day (U.S. EPA, 1986b). The rats also
received a single Intravenous Injection of the carcinogen NMD. The positive
control group received only NMU, whereas a negative control group was given
molybdenum-free demlneraHzed water and no NMU. After 125 days, the Inci-
dence of mammary tumors In the positive controls and NMU-molybdenum group
did not differ significantly. However, after 198 days, positive controls
had a tumor Incidence of 90.5%, compared with 50% 1n those receiving
NMU-molybdenum.
6.3. MUTAGENICITY
Several molybdenum compounds have been tested for mutagenldty In
bacteria (Table 6-2). Negative or weakly positive mutagenlc responses were
seen In Bacillus subtills as Judged by a DNA repair assay (Kanematsu et al.,
1980). When tested In Escherlchla coll. sodium molybdate Induced lambda
prophages (Rossman et al., 1984) and enhanced the mutagenldty of ultra-
violet light (Rossman and Molina, 1986). In the only available report
regarding mutagenldty of molybdenum In mammalian cells, molybdate Ions
caused forward mutations 1n Chinese hamster lung cells (Zellkoff et al..
1986).
0186d -52- 07/26/89
-------
o
CO
o.
TABLf 6-2
Mutagenlclty Testing of Molybdenum
Assay Indicator Organism Purity
(X)
i
Microbiological Assays
Rec assay (DNA repair) Bacillus subtllts NR
H17, H«5
Rec assay (DNA repair) B. subtllls NR
H17. M«5
Ul
*j° xProphage Induction Escherlchla coll technical
WP2S (x) grade
ONA repair -- C. coll ' technical
1 WP2 (trpE) grade
F
Mammalian cells
forward mutation * Chinese hamster NR
lung cells (V79)
Application Concentration
or Dose
plate 0.005-0.5 M
Incorporation (0.05 ml)
plate . 0.7 M
Incorporation (0.05 ml)
plate 0.05 N
Incorporation
plate 0-30.000 nM
Incorporation
cell culture NR
Response Comment
Compounds tested
were MoS?, MoOi and
H2M00«.
-/» Compound tested was
(NH4)( Moy024.
» Compound tested was
Na?Mo04.
t NajHoO^ enhanced
the mutagentclty of
UV light.
• (HoOi)'* was tested;
relatively nontoxlc
doses were used.
Reference
Kanematsu
et al.. 1980
Kanematsu
et al.. 1980
Rossman
et al.. 1984
Rossman and
Molina. 1986
Zellkoff
et al.. 1986
NR * Not reported; -/» * weakly mutagenlc
o
Ul
CD
VD
-------
6.4. DEVELOPMENTAL TOXICITY
The only report available regarding developmental effects of molybdenum
1s that of Perm (1972). In that study, Intravenous Injections of sodium
molybdate \n doses <100 mg Mo/kg to pregnant hamsters on day 8 of gestation
were neither embryoddal nor developmentally toxic.
6.5. OTHER REPRODUCTIVE EFFECTS
In a 3-generat1on reproductive study (Schroeder and Kitchener, 1971),
Charles River CD mice (five/sex) mantalned on a diet containing 1.95 ppm Cu
and 0.045 ppm Ho were administered molybdenum In the drinking water at <6
months of age at a concentration of 10 ppm (from an unspecified soluble
salt), which provided a dose of 1.9 mg Ho/kg/day, assuming mice consume
0.0057 i of water/day and weigh 0.03 kg (U.S. EPA, 1986b). Randomly
selected pairs (unspecified number) from the first (F,.), second (F,B),
or third Utter (F,-) were allowed to breed at will to produce the second
generation (F.). The same procedure was followed to produce the third
generation (F3). Control animals received plain delonlzed water. Molyb-
denum caused 15 early deaths out of 238 offspring 1n the F. generation but
none In controls (p<0.001); It caused five dead Utters In the F_ genera-
tion but none In controls (not statistically significant). In the F,
generation, there were 4 maternal deaths (none In controls; p<0.05), 4 dead
Utters (none In controls; p<0.05), 34 young deaths (1 1n controls;
p<0.0001), 11 runts (none In controls; p<0.0001), and 3 failures to breed
(none In controls; not statistically significant). The F_ generation
" J r - — W
totaled 123 mice, compared with 230 for the control group. Ihe total number
\ .
of Utters/generation, as well as the average Utter size/generation, were
not affected by Ingestlon of molybdenum.
0186d -54- 01/30/90
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Intravenous Injection of molybdenum (0.1 ml of a 100 mH solution of
( . _ _ > " .j. . ,,.j j - c *, . -1., .* 4>- t-f ._...- - .....
sodium molybdate, -30 mg Ho/kg) Into pregnant mice on day 3 of pregnancy did
not Interfere with Implantation or subsequent development of the fetuses.
When mice were Injected on day 8 of gestation, molybdenum Induced signifi-
cant decreases In the weight of the fetuses and In the degree of skeletal
ossification; the number of resorptlons was not affected (Wide, 1984).
In a study by Jeter and Davis (1954), groups of 8-16 Long-Evans rats
(4-8/sex) were fed a basal diet supplemented with sodium molybdate at 20, 80
or 140 ppm Ho for ~90 days. The control (basal) diet was analyzed, found to
contain Ho at <1 ppm and supplemented with copper sulfate to contain Cu at 5
or 20 ppm. In addition, a group of four male and four female rats was fed a
diet containing 80 ppm Ho and 20 ppm Cu. Assuming a food factor for rats of
0.05, the 20, 80 and 140 ppm Ho diets correspond to dosages of 1, 4 and 7 mg
Ho/kg/day, respectively. Reduced rate of body weight gain was reported In
all Mo-treated groups of males and In females treated with Ho at 80 or 140
ppm \n diets containing 5 ppm Cu. No effect on body weight gain was
observed In rats treated with 80 ppm Ho on the 20 ppm Cu-conta1n1ng d1»t,
and no effect on blood hemoglobin concentration was reported In any
Ho-treated groups. AchromotMchla and alopecia were observed In some rats -
• •*
1n the 80 and 140 ppm Ho groups and occasionally 1n the 20 ppm Ho groups on
diets containing 5 ppm Cu. When the rats were allowed to breed, male
Infertility was observed In 80 and 140 ppm Ho groups on diets containing 5
ppm Cu. Hales that received molybdenum at 80 and 140 ppm produced only one -
litter (out of four matlngs), as compared with four Utters (out of four
mat Ings) produced by males not receiving molybdenum. The 20 ppm Ho 5 ppm Cu
and 80 ppm Ho 20 ppm Cu diets did not affect fertility. Control animals
produced eight Utters out of eight'matlngs. Examination of the testes of
0186d -55- 07/26/89
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the males from the 80 and 140 ppm Mo (5 ppm Cu) diets producing only one
IHter showed various degrees of seminiferous tubule degeneration. Testes
from control rats were normal. Molybdenum did not affect female fertility
or gestation, but did Interfere with normal lactation, as Indicated by
reduced weaning weight of offspring of dams exposed to >20 ppm Mo, 5 ppm Cu.
6.6. SUMMARY
Reported oral LD^nS for Mo exposed to rats In the diet for 40 days
were 101 mg/kg for calcium molybdate, 125 mg/kg for molybdenum trloxlde and
333 mg/kg for ammonium molybdate (Falrhall et al., 1945). LD5Q data for
other species were not available. Short-term oral studies with various
species Indicate that molybdenum depresses body weight gain and affects the
gastrointestinal tract, the liver and kidneys. The doses associated with
these effects vary with different molybdenum compounds. In rats, sodium
molybdate caused death In <2 weeks at doses of 250 mg Mo/kg (Nellands et
al., 1948), whereas 571 mg Mo/kg/day from ammonium molybdate was not lethal
(Rana et al., 1980). Ammonium tetrathlomolybdate Is apparently considerably
more toxic than other molybdenum compounds, since dietary doses of 0.3 mg
Mo/kg for 21 days had gastrointestinal and skeletal effects In rats (Fell et
al., 1979; Spence et al., 1980). Inhalation of dusts of molybdenum trloxlde
and calcium molybdate killed guinea pigs 1n <5 weeks at levels of 200 and
155 mg Mo/m3, respectively; however, these experiments were not well
designed and the results not clearly reported (Falrhall et al., 1945).
Molybdenum added to the diet of male rats as the trloxlde, calcium
ft ' _ i • * >•
molybdate, or as ammonium molybdate In doses between 85 and 6757 mg Mo/kg
for 8-232 days caused weight loss and mortality (Falrhall et al., 1945).
In rabbits, dietary doses of >91 mg Mo/kg as sodium molybdate In the
> ' , • i
diet caused anemia and, eventually, death In -40 days, but doses of <25 mg
» «*
0186d -56- 07/26/89
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Ho/kg had no no-tlceable adverse effects (Arrlngton and Davis, 1953; Robinson
et a!., 1969). In rats, doses of -20 mg Ho/kg/day from sodium molybdenum
for 42 days 1n the diet or drinking water significantly decreased body
weight gain (Lallch et al., 1965; Nellands et al., 1948).
In rats, sodium molybdate added to the drinking water at levels that
provided doses of 0.28-2.8 6 mg Ho/kg/day decreased the Incidence of tumors
Induced by known carcinogens (Luo et al., 1983; He1 et al., 1985). However,
IntraperUoneal Injections of molybdenum trloxlde In mice for -a total dose
of 3167 mg Mo/kg over a 30-day period Increased the Incidence of lung tumors
(not statistically significant) and significantly Increased the number of
lung tumors/mouse (Stoner et al., 1976). The overall evidence Indicates
that some molybdenum compounds are weak mutagens In bacterial assays
(Kanematsu et al., 1980; Rosmann et al., 1984). In the only assay using
mammalian cells, molybdate anlons caused a positive mutagenlc response
(Zellkoff et al., 1986). Sodium molybdate was not developmentally toxic
when Injected Intravenously to pregnant hamsters (Perm, 1972).
In a 3-generat1on study by Schroeder and Kitchener (1971), a dose of 1.9
mg Mo/kg In drinking water was associated with early death 1n offspring,
Increased number of dead litters, maternal mortality and the birth of runts.
In rats, 20 ppm Mo In the diet (1 mg/kg/day) was associated with reduced
body weight gain In male rats and reduced lactation Index In female rats; 80
ppm (4 mg/kg/day) was associated with male Infertility (Jeter and Davis,
1954).
0186d -57- 01/30/90
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7. EXISTING GUIDELINES AND STANDARDS
7.1. HUMAN
ACGIH (1988) recommended a TLV-TWA of 5 mg Mo/m3 and 10 mg Mo/m3 for
soluble and Insoluble molybdenum compounds, respectively. This recommenda-
tion 1s based largely on the conclusions of Falrhall et al. (1945) and
Mogllvskaya (1950) that Industrial exposure results In a low order of
toxlclty (ACGIH, 1986). OSHA (1989) established a PEL for soluble compounds
of molybdenum 1n air of 5 mg/m3 TWA. The OSHA PEL 1n air for Insoluble
compounds, based on physical Irritation of Mo03 (ACGIH, 1986), 1s 10 mg
Mo/m3 for total dust, and 5 mg Mo/m3 for the resplrable fraction, based
on limited Industrial experience with these compounds, to protect against
eye, nose and skin Irritation and chronic respiratory effects (OSHA, 1989).
7.2. AQUATIC
Guidelines and standards for the protection of aquatic life from
exposure to molybdenum were not located In the available literature cited In
Appendix A.
0186d -58- 05/31/89
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8. RISK ASSESSMENT
8.1. CARCINOGENICITY
8.1.1. Inhalation. Pertinent data regarding the Inhalation carclnogen-
1cUy of molybdenum compounds were not located In the available literature
cited In Appendix A.
8.1.2. Oral. As part of the study by Luo et al. (1983) In which the
Investigators examined the co-carcinogenic properties of molybdenum and
NSEE, one group of female Sprague-Dawley rats was given 20 ppm of molybdenum
(from sodium molybdate) In the drinking water for <30 weeks. This concen-
tration of molybdenum, equivalent to a dose of 2.8 mg Mo/kg/day, did not
Induce tumors In the esophagus or forestomach, the only two organs examined
at the end of the dosing period.
8.1.3. Other Routes. Stoner et al. (1976) gave groups of male and female
Strain A mice Intraperltoneal Injections of molybdenum trloxlde, for a total
dose of 633, 1823 or 3167 mg Mo/kg. Mice were Injected throe times/week for
a total of 19 Injections 1n a 30-week period. In the group given the
highest dose, the number of lung tumors/mouse was significantly higher
(p<0.05) than In those receiving the vehicle alone or those untreated. An
Insignificant Increase was reported In the number of mice bearing lung
tumors. Ihe Incidence In the low and Intermediate dose groups did not
differ significantly from that In controls. In the study by Luo et al.
(1983), molybdenum Inhibited the formation of esophageal and forestomach
tumors Induced by N-n1trososarcos1ne. Molybdenum did not alter the carclno--
genie potency of methylbenzylnltrosamine (Bogden et al., 1986).
8.1.4. Weight of Evidence. No data were available regarding the carclno-
genlclty of molybdenum compounds In humans. The limited negative carclno-
genldty results from the study using rats by Luo et al. (1983), the
0186d -59- 07/26/89
-------
Inconclusive results of the Strain A mouse lung tumor assay (Stoner et al.,
1976} and the co-cardnogen1cHy studies (Bogden et al., 1986; Luo et al.,
1983) constitute Inadequate evidence to evaluate the carcinogenic potency of
sodium molybdate. According to U.S. EPA (1986a) guidelines, molybdenum can
be placed 1n EPA Group D: not classifiable as to cardnogenldty to humans.
8.1.5. Quantitative Risk Estimates. The lack of suitable positive Inha-
lation and oral carcinogenic data precludes the derivation of carcinogenic
potency factors for molybdenum.
8.2. SYSTEMIC TOXICITY
8.2.1. Inhalation Exposure. Inhalation studies conducted by Falrhall et
al. (1945), In which guinea pigs were exposed to dusts or fumes of several
molybdenum compounds 1 hour/day, 5 days/week for 5 weeks, are considered
Inadequate as the basis for deriving a chronic or subchronlc Inhalation RfD.
The study's exposure schedule can be better described as Intermittent acute
exposures, and adjustments for continuous exposure may result In misleading
figures. Furthermore, molybdenum dusts caused deaths at <4. weeks of
exposure, which Is considered acute. Relevant human data were not located
1n the available literature.
8.2.2. Oral Exposure.
8.2.2.1. LESS THAN LIFETIME EXPOSURES (SUBCHRONIC) — Several
subchronlc oral studies were performed with different molybdenum compounds
In animals. Falrhall et al. (1945) reported high mortality In rats given
molybdenum trloxlde. calcium molybdate or ammonium molybdate In the diet at
doses >111, 70 and 100 mg Mo/kg/day, respectively, for 120-232 days (Rec. '
#5, 6 and 7). Similar results were reported for guinea pigs receiving
calcium molybdate (Rec. #8) or molybdenum trloxlde (Rec. #9) by gavage at
0186d -60- 07/26/89
-------
doses >53 and 303 mg Ho/kg/day, respectively, for 95 days (Falrhall et al.,
1945). In general, the studies of FaUhall et al. (1945) were not clearly
reported.
In rabbits, anemia and mortality occurred with doses of 91 mg Mo/kg/day
(Rec. #12} for <60 days (Robinson et al., 1969), or 49 mg Mo/kg/day {Rec.
#11) for 120 days (Arrlngton and Davis, 1953). Nevertheless, a dose of 24.5
mg Ho/kg/day was Identified as a NOAEL for rabbits from Arrlngton and Davis
(1953) (Rec. #10).
From the study by Franke and Moxon (1937), In which rats were fed a diet
supplemented with molybdenum for 100 days, NOAELs of 3.35 (Rec. #13) and
3.68 mg Ho/kg/day (Rec. #14) were Identified for males and females, respec-
tively. Body weight gain, food consumption and hemoglobin concentration
were monitored.
Two reproductive studies were located 1n the literature, and both
reported adverse reproductive effects at rather low doses, compared to other
endpolnts studied (Jeter and Davis, 1954; Schroeder and Mltchener, 1971).
In the study by Jeter and Davis (1954), male rats fed a diet supplemented
with sodium molybdate to provide doses of 4 (Rec. #2) or 7 mg Mo/kg/day for
-90 days produced fewer Utters than those given a lower dose of 1 mg
Mo/kg/day (Rec. #1) or control rats (no statistical analysis was provided).
Males that received molybdenum produced only one litter (out of four
matlngs), compared with four Utters (out of four ma tings) produced by males
not receiving molybdenum.'' The low-dose and control groups had 100% mating
success. Hlstologlcal examination of the testes of the affected males from
the 4 and 7 mg Mo/kg/day groups showed various degrees of seminiferous
tubule degeneration. Growth retardation was significant (5% level) In all
treated groups of males and In females of the 2 highest dosage levels on
0186d -61- 07/26/89
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diets containing 5 ppm Cu. Hemoglobin levels, measured throughout the
experimental period, were not affected. Molybdenum did not affect female
fertility or gestation but Interfered with normal lactation, as Indicated by
reduced weaning weights of offspring In all treated groups {5 ppm Cu). The
dosage of 1 mg Mo/kg/day 1s considered a LOAEL for weight gain In males and
Impaired lactation In females.
In a 3-generatlon study, molybdenum given In the drinking water to mice
for <6 months at a level to provide a dose of 1.9 mg Mo/kg/day (Rec. #3)
caused significant (p<0.001) early mortality In the offspring of the F..
generatloa fSchroeder and MHchener, 1971). In addition, 1n the test groups
of the F- generation, there were 4 maternal deaths (p<0.05), 4 dead
o
Utters (p<0.05), 34 young deaths (p<0.0001) and 11 runts (p<0.0001). For
this study, the dose of 1.9 mg Mo/kg/day represents a LOAEL.
The LOAEL of 1 mg Mo/kg/day (Rec. #1) In the rat study by Jeter and
Davis (1954) and the LOAEL of 1.9 mg Ho/kg/day In the mouse study (Rec. #3)
by Schroeder and Mltchener (1971) are similar. Either could serve as the
basis for risk assessment. Schroeder and MHchener (1971) evaluated repro-
ductive performance over three generations but In only five pairs of mice In
each generation. Jeter and Davis (1954) only evaluated reproduction 1n one
generation but used slightly larger group sizes and evaluated other end-
points of toxlclty, as well. Most Importantly, Jeter and Davis (1954)
provided diets containing 5 ppm Cu, which Is the NRC (1978) recommendation
for this species. Schroeder and Mltchener (1971) on the other hand,
provided a diet containing only 1.95 ppm Cu, somewhat below the NRC (1978)
recommendation of 4.5 ppm for this species. . - ,.
Because of the Impact of Cu nutrition on the toxlclty of Mo (see Section
6.1.3.) and the uncertainties associated with possibly suboptlmal Cu levels
-> i*
0186d -62- 07/26/89
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In Schroeder and MHchener (1971), the LOAEL of 1 mg Mo/kg/day from Jeter
and Davis (1954) Is chosen as the basis for risk assessment. Therefore,
applying an uncertainty factor of 1000 (10 each for Inter- and Intraspecles
extrapolation and 10 to reflect the use of a LOAEL Instead of NOAEL) to the
dose of 1 mg, a subchronlc oral RfD of 1 yg Ho/kg/day Is derived. This
subchronlc RfD Is somewhat below the recommended dietary allowance for
molybdenum of 150-500 yg/day (NAS, 1980) and supports the notion that
long-term Intake of these levels of molybdenum are not only safe, but essen-
tial. The RfO of 1 vg Mo/kg/day, derived from data obtained from sodium
molybdate, should be protective for soluble salts and compounds containing
hexavalent Ho, provided that toxlclty of the nonmolybdenum moiety does not
become a factor 1n the toxldty of the molybdenum compound. Acute and
subchronlc data In rats by Falrhall et al. (1945) suggest that the toxlclty
of calcium molybdenum trloxlde and ammonium molybdate Is similar. The RfD,
however, does not apply to Mo obtained from ammonium tetrathlomolybdate.
Confidence In the data base Is low, largely because chronic data were
not available and because the data do not clearly define a target organ or a
critical effect In humans or laboratory animals. None of the longer-term
studies provided an adequate hlstopathologlcal evaluation. Confidence In
the key study Is medium, because several endpolnts of toxlclty were
evaluated In rats maintained on a diet that was adequate In Cu nutrition.
Confidence In the RfD Is medium. The RfD should be sufficiently conserva-
tive, because 1t 1s below the NAS (1980) recommended dally allowance for Ho.
8.2.2.2. CHRONIC^EXPOSURE --Pertinent data regarding the toxlclty of
chronic oral exposure to Ho were not located In the available literature
cited In Appendix A. In the absence of chronic data, an RfD for chronic
oral exposure can be derived from' the subchronlc data. Ordinarily, an
0186d -63- 07/26/89
-------
uncertainty factor of 10 would be applied to the subchronlc RfD or to the
subchronlc benchmark dose that was the basis for the subchronlc RfD, to
expand from subchronlc to chronic exposure. This manipulation Is not neces-
sary for Ho, however, because Ho Is a nutritionally essential trace element,
and the RfD for subchronlc exposure Is somewhat below the recommended dally
allowance. Therefore, the subchronlc oral RfD of 1 yg Ho/kg/day 1s
considered sufficiently protective for chronic oral exposure, as well.
Confidence In the data base Is low, and confidence 1n the key study and RfD
Is medium, as discussed above.
0186d -64- 07/26/89
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9. REPORTABLE QUANTITIES
9.1. BASED ON SYSTEMIC TOXICITY
The toxlclty of molybdenum compounds was discussed In Chapter 6 and
dose-response data considered for CS derivation are summarized 1n Table 9-1.
Since no chronic data were available, subchronlc data were considered. In
Table 9-1, the dosage of molybdenum compounds Is expressed 1n terms of
molybdenum element In mg/kg/day, and the equivalent human dose 1s expressed
1n mg of molybdenum/kg/day. Table 9-1 also shows that the different molyb-
denum compounds used Induced similar adverse effects at similar doses
expressed as molybdenum element.
Effects attributed to subchronlc Inhalation and oral exposure to
molybdenum are mortality and reduced survival (RV =10), weight loss or
depressed body weight gain (RV =4), anemia (RV -5) and skeletal deformi-
ties In ttie young (RV =9) (ArMngton and Davles, 1953; Lallch et al.,
1965; Nellands et al., 1948; Robinson et al., 1969). However, the Impair-
ment of reproductive performance 1n mice and rats (see Table 9-1) provided
what proved to be the most sensitive endpolnt, based on estimated human
equivalent. doses calculated for these effects (Jeter and Davis, 1954;
Schroeder and MHchener, 1971).
Composite scores and their corresponding RQs are calculated In Table 9-2
for the effects Identified 1n Table 9-1. Data selected for Inclusion 1n
Table 9-2 Include the lowest human equivalent dose associated with mortality
as well as lower human equivalent doses associated with less severe effects.
Accordingly, mortality In the guinea pig Inhalation study by Falrhall et al.
(1945) and mortality In offspring of mice In a 3-generat1on drinking water
study In rats (Schroeder and MHchener, 1971) were selected for Inclusion In
Table 9-2. Because the Falrhall et al. (1945) Inhalation study has several
0186d -65- 05/31/89
-------
TABU 9-1
0
CO
Q-
Route
Inhalation
Inhalation
Inhalation
i
Cf
i
Inhalation
Oral
Oral
Oral
Oral
(gavage)
Oral
(gavage)
o
v! Oral
Species/
Strain
human
guinea
plg/NR
guinea
plg/NR
mice/
B6C3F1
rat/NR
rat/NR
rat/NR
guinea
plg/NR
guinea
plg/NR
rabbit/
Dutch
Sex/Number
H/25
M/51
M/24
both sexes/
20 total
M/B
M/10
M/B
M/B
M/B
both sexes/
7 total
Average
Body
Weight
70b
0.84°
0.84°
0.03°
0.09d
0.129d
O.ld
0.46d
0.29d
1.1-
Compound/Purity/
Vehicle
Mo oxIdes/NR/dust
Mo03/NR/dust
CaMo04/NR/dust
Mo03/NR/dust
Mo03/NR/food
CaHo04/NR/food
(NH4)?Mo04/
NR/food
CaMo04/NR/ 10X
gum arable
Mo03/NR/10X gum
arable
Na 3X004 -2H20/NR/
diet
Exposure
occupational.
9.47 mg Mo/m*
200 mg mo/m*.
1 hour/day,
5 days/week
for 5 weeks
155 mg Mo/m>.
1 hour/day,
S days/week
for 5 weeks
67 mg Ho/m».
6 hours/day.
S days/week
for 13 weeks
111 mg/kg/day
for 120 days
70 mg/kg/day
for 137 days
100 mg/kg/day
for 232 days
53 mg/kg/day
for 95 days
85 mg/kg/day
for 99 days
0.1JC Mo In diet
for 13 weeks
Transformed
Animal Dose
(mg/kg/day)
NA
2.83C
15. 5<
IIId
70d
100d
53
85
49*
Equivalent
Human Dose9
(mg/kg/day)
0.64C
0.65
0.5
0.12
12.1
8.6
11.3
9.9
13.7
12.3
Response
Altered serum
ceruloplasmln.
uric acid and
urinary uric acid/
creatlnlne ratios
Respiratory Irri-
tation, weight
loss, diarrhea,
liver and kidney
changes, mortality
Mortality
No effects observed
Mortality
Mortality
Mortality
Mortality
Mortality
Anemia; weight
loss; alopecia;
Reference
Ualravens
et al.. 1979
Falrhall
et al.. 1945
Falrhall
et al.. 1945
NTP. 1983
Falrhall
et al.. 1945
Falrhall
et al., 1945
Falrhall
et al.. 1945
Falrhall
et al.. 1945
Falrhall
et al.. 1945
Arrlngton and
Davis. 1953
CD
ID
front leg abnor-
malities
-------
TABlf
(cont.)
o
03
o.
Route
Oral
Oral
Oral
Oral
Oral
i
T* Oral
Oral
Species/
Strain
rabbit/
Dutch
rabbit/
NR
rat/
Sprague-
Oawley
rat/
Sprague-
Dawley
rat/
Sprague-
Daw'ley
mice/CD
rat/long-
Evans
Sex/Number
both sexes/
B total
NR/12
M/7 |
both sexes/
14 total
H/4
both sexes/
5 pairs
both sexes/ .
4 pairs
Average
Body
Weight
3.8°
O.ld
0.35°
0.1d
0.03°
0.35°
Compound/Purity/
Vehicle
Na?Mo04-2H20/NR/
diet
NapMo04/NR/d1et
Na?Mo04/NR/d1et
Na2Mo04/NR/
drinking water
Na2Mo04>2H20/NR/
diet
unspecified
soluble salt/NR/
drinking water
Na2Ho04*2H20/NR
) '
Transformed
Exposure Animal Dose
(mg/kg/day)
0.2X Ho In diet 9B«
for 17 weeks
0.4X Na?Ho04 91e
In diet for 42
days
0.1X Na2Mo04 23e
In diet for 6
weeks
10 ppm Ho In 1.4'
water for 5-12
months
400 ppm Ho In 20*
diet for 6
weeks
10 ppm Ho In 1.9'
water for 6
months
20 ppm Ho In le
food for -90
days
Equivalent
Human Dose8
(mg/kg/day)
24.5
34.5
2.6
0.24
2.3
0.14
0.17
Response
Mortality
Anemia; mortality
Eecreased weight
gain; skeletal
deformities
Reduced adapta-
bility to cold
temperature
Decreased weight
gain
Early death of
offspring In Fj
generation
Decreased weight
gain; Impaired
lactation (reduced
weaning weight)
Reference
Arrlngton and
Davis. 1953
Robinson
et al.. 1969
lallch et al..
1965
Winston et al..
1973
Nellands
et at.. 1948
Schroeder and
HUchener, 1971
Jeter and
Davis. 1954
'Calculated by multiplying the animal dose expressed as mg/kg/day molybdenum by the cube root of the ratio of the animal body weight to the reference body
weight for a 70 kg human
••Reference body weight from U.S. EPA (1980, 1986b)
'Calculated by expanding to continuous exposure, multiplying by the reference Inhalation rate and dividing by the reference body weight for the species
dEst1mated from data provided by the Investigators
0 'Based on reference food factors from U.S. EPA (I960, 19B6b)
-~j
J^J 'Calculated by assuming a dally water consumption of 0.049 t for rats and 0.0057 i for mice (U.S. EPA, 19B6b)
C7»
x,
CD
IO
-------
o
CO
CD
I
TABLE 9-2
Compos tie Scores for Molybdenum Compounds
Route
Inhalation
.
Oral/water
Oral/diet
Species Compound Animal Dose
(mg/kg/day)
guinea pig CaMoO^ 2.2
mice ' unspecified 1.9
soluble salt
rat Na2Mo04.2H20 ,
Chronic
Human HEO* RV,j Effect RVe CS
(rng/day)
35 3.2 Mortality 10 32
9.8 4 Mortality In offspring 10 40
11.9 3.9 Impaired lactation In 8 31.2
females (reduced wean-
Ing weight of offspring)
RQ Reference
t
100 Falrhall
et al., 1945
100 Schroeder and
Mltchener. 1971
100 Jeter and
Davis. 1954
'Calculated by multiplying the human equivalent dose by TO kg to present the MEO In terms of mg/day for a 70 kg human
o
in
CD
U)
-------
deficiencies, the results must be Interpreted with caution. The guinea pigs
were exposed to the test chemical 1 hour/day, 5 days/week for 5 weeks. This
exposure schedule models Intermittent acute exposure rather than a truly
subchronic exposure protocol. Furthermore, the Investigators provided no
Information regarding the number of exposures that caused death.
In the derivation of the CSs for these effects, an uncertainty factor
was not applied to expand from subchronic to chronic exposure. As discussed
In Section 8.2.2.2., H does not appear to be necessary to expand from
subchronic to chronic exposure because Mo 1s a nutritionally essential trace
element.
From the three studies presented In Table 9-2. -the higher CS of 40.
which corresponds to an RQ of 100, 1s chosen to represent the hazard
associated with chronic exposure to molybdenum compounds (Table 9-3).
9.2. BASED ON CARCINOGENICITY
Limited cardnogenlcHy data, summarized In Section 6.2., consist of the
study by Luo et al. (1983) In which the Investigators examined the
co-carcinogenic properties of molybdenum and N-n1trososarcos1ne. As part of
the experimental series, one group of Sprague-Dawley rats was given 20 ppm
of molybdenum (2.8 mg Mo/kg/day) In the drinking water for <30 weeks. In
this group, no tumors were found 1n the esophagus or forestomach, the only
organs examined. Moreover, molybdenum Inhibited the formation of esophageal
and forestomach tumors Induced by NSEE. Molybdenum did not alter the
carcinogenic potency of MBO (Bogden et al., 1986), but repeated Intraperl-
toneal Injections of 3167 mg Mo/kg In mice Increased the number of lung
tumors/mouse In the Strain A mouse lung tumor assay (Stoner et al., 1976).
Data regarding cardnogenlcHy In humans were lacking, and molybdenum was
classified In EPA Group D: not classifiable as to human cardnogenlcHy.
0186d -69- 07/26/89
-------
TABLE 9-3
Molybdenum
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route: oral/drinking water
Species/Sex: rats/both
Dose*: 11.9 mg/day
Duration: 90 days
Effect: decreased weight gain; Impaired lactation 1n females
(reduced weaning weight)
RVd: 3.9
RVe: 8
/
CS: 31.2
RQ: 100
Reference: Jeter and Davis, 1954
*Equ1valent human dose
0186d -70- 05/31/89
-------
Hazard ranking Js not possible for EPA Group D chemicals, hence a cancer-
based RQ cannot be derived.
0186d -71- 05/31/89
-------
10. REFERENCES
Abbott, O.J. 1977. The toxUHy of ammonium molybdate to marine Inverte-
brates. Mar. Pollut. Bull. 8(9): 204-205.
ACGIH (American Conference of Governmental Industral Hyg1en1sts). 1986.
Documentation of the Threshold Limit Values and Biological Exposure Indices,
5th ed. Cincinnati, OH. p. 415.
ACGIH (American Conference of Governmental Industral Hyglenlsts). 1988.
Threshold Limit Values and Biological Exposure Indices for 1988-1989, 5th
ed. Cincinnati. OH. p. 28-29.
Al-Amoud1, O.A. and M.E. El-Naggar. 1987. Distribution of heavy metals In
a species of Caulerpa from Shauba, Saudi Arabia. Mlcroblos. 52(211): 81-86.
Arrlngton, L.R. and G.K. Davis. 1953. Molybdenum toxlclty In the rabbH.
J. Nutr. 51: 295-304.
Bandyopadhyay, S.K., K. Chatterjee, R.K. T1war1, et al. 1981. Biochemical
studies on molybdenum toxlclty In rats: Effects of high protein feeding.
Int. J. V1tam. Nutr. Res. 51(4): 401-409.
Barr, R.Q. 1981. Molybdenum and molybdenum alloy. I_n: Klrk-Othmer
Encyclopedia of Chemical Technology, Vol. 15, 3rd ed., M. Grayson and D.
Eckroth, Ed. John Wiley and Sons, Inc., New York. p. 670-682.
0186d -72- 07/26/89
-------
Barry,, H.F. 198,1. Molybdenum compounds. In: Klrk-Othmer Encyclopedia of
Chemical Technology, Vol. 13, 3rd ed., H. Grayson and D. Eckroth, Ed. John
Wiley and Sons, Inc., New York. p. 683-697.
Bell, M.C., E.G. Dlggs, R.S. Lowrey and P.L. Wright. 1964. Comparison of
Ho" metabolism In swine and cattle as affected by stable molybdenum. J.
Nutr. 84: 367-372.
Bernard, O.L. and K.W. Roy. 1977. Heavy metals In Louisiana crayfish
Procambarus clarkll determined by x-ray fluorescence analysis. In.: Fresh-
water Crayfish, Vol. 3, O.V. Llndqulst, Ed. p. 357-361.
Blrge, W.3. 1978. Aquatic toxicology of trace elements of coal and fly
ash. Doe Symp. Ser. 48: 219-240.
Blrge, W.J., J.A. Black and A.G. Westerman. 1979. Evaluation of aquatic
pollutants using fish and amphibian eggs as bloassay organisms. Anlm.
Monlt. Environ. Pollut. p. 108-118.
Bogden, J.D., H.R. Chung, F.W. Kemp, K. Holding, K.S. Bruenlng and Y. Naveh.
1986. Effect of selenium and molybdenum on methylbenzylnltrosamlne-lnduced
esophageal lesions and tissue trace metals In the rat. J. Nutr. 116(12):
2432-2442. . . --
Bohn, H.L., B.L. McNeal and G.A. O'Connor. 1985. Soil Chemistry, 2nd ed.
John Wiley and Sons, New York. p. 308.
0186d -73- 07/26/89
-------
Brooks, R.R. and M.G. Rumsby. 1965. The blogeochemlstry of trace element
uptake by some New Zealand bivalves. Llmnol. Oceanogr. 10(4): 521-527.
Bysshe, S.E. 1988. Uptake by biota. IJK Environmental Inorganic Chemistry
Properties, Processes and Estimation Methods, I. Bodek, et a!., Ed.
Pergamon Press, New York. p. 4.3-10.
Chappell, W.R., R.R. Heglen, R. Houre-Eraso, C.C. Solomons and T.A. Tsongas.
1979. Human Health Effects of Molybdenum 1n Drinking Water. Health Effects
Research Laboratory, Cincinnati, OH._ p. 116.
Cherry, D.S. and R.K. Guthrle. 1978. Mode of elemental dissipation from
ash basin effluent. Hater A1r Soil Pollut. 9(4): 403-412.
Cherry, D.S. and R.K. Guthrle. 1979. The uptake of chemical elements from
coal ash and settling basin effluent by primary producers: 2. Relation
between concentrations In ash deposits and tissues of grasses growing on the
ash. Scl. Total Environ. 13(1): 27-32.
Colborn, T. 1982a. Aquatic Insects as measures of trace element presence
In water: Cadmium and molybdenum. AS1M Spec. Tech. Publ. 766. Aquat.
Toxlcol. Hazard Assess. 61(2): 316-325.
Colborn, T. 1982b. Measurement of low levels of molybdenum In the environ-
ment by using aquatic' Insects. Bull. Environ. Contam. Toxlcol. 29(4):
422-428.
0186d -74- 07/26/89
-------
Colmano, G. 1973. Molybdenum toxldty: Abnormal cellular division of
teratogenlc appearance In Euqlena gradHs. Bull. Environ. Contam. Toxlcol.
9(6): 361-364.
Comar, C.L., L. Singer and G.K. Davis. 1949. Molybdenum metabolism and
Interrelationships with copper and phosphorus. 3. B1ol. Chem. 180: 913-922.
Consolazlo, C.F., R.A. Nelson, L.O. Matoush, R.C. Hughes and P. Urone.
1964. The trace mineral losses 1n sweat. U.S. Army Med. Res. Nutr. Lab.
Report No.~284. 15 p.
Cowglll, U.M. 1974. The hydrogeochemlstry of Llnsley Pond, North Branford,
Connecticut. II. The chemical composition of the aquatic macrophytes.
Arch. Hydroblol. Suppl. 45(1): 1-119.
Crockett, P.W., B. Klllan, K.S. Crump and R.B. Howe. 1985. Descriptive
methods for using data from dissimilar experiments to locate a no-adverse-
toxlc-effects region In the dose-duration plane. Prepared by K.S. Crump and
Co., Inc., under Contract No. 68-01-6807 for Environmental Criteria and
Assessment Office, U.S. EPA, Cincinnati, OH.
Czegeny, I. and I. Daval. 1985. Accumulation of heavy metals In aquatic
organisms of sewage water treatment plants. In: Symposia Blologlca.
Hungarlca, 3. Salankl/'Ed.. Vol. 29. 0{0): 105-110.
Davids, B.E. 1980. Applied Soil Trace Elements. John Wiley and Sons, New
York. p. 176-192.
0186d -75- 07/26/89
-------
De GoelJ, 3.M., V.P. Gulnn, D.R. Young and A.J. Hearns. 1973. Neutron
activation analysis trace element studies of dover sole liver and marine
sediments. 1%: Int. Atomic Energy Agency Proceedings Series. Comparative
Studies of Food and Environmental Contaminations, Otan1em1, Finland, August,
1973. 623 p.
Dorfman, D. 1977. Tolerance of Fundulus heteroclltus to different metals
In salt waters. Bull. NO Acad. Scl. 22(2): 21-23.
Dreesen, D.R. and E.J. Cokal. 1984r Plant uptake assay to determine b1o-
avallablllty of Inorganic contaminants. Water Air Soil Pollut. 22(1):
85-94.
Ourkln, P. and W. Heylan. 1988. User's guide for D2PLOT: A program for
dose/duration graphs. Prepared by Chemical Hazard Assessment Division,
Syracuse Research Corp. under Contract No. 68-C8-0004 for Environmental
Criteria and Assessment Office, U.S. EPA. Cincinnati. OH.
/
Ellis. B.G., B.D. Knezek and L.U. Jacobs. 1983. Leaching of micro-
nutrients. lt±: Soil Science Society of America. Chemical Mobility and
Reactivity In Soil Systems. SSSA Special Publ. No. 11. American Society of
Agronomy and Soil Science Society of America, HAdlson, WI.
Engel, R.W., N.O. Price and R.F. Miller. 1967. Copper, maganese, cobolt
and molybdenum balance 1n pre-adolescent girls. J. Nutr. 92: 197-204.
0186d -76- 02/05/90
-------
Evans, E.G., G.F. Evans, O.B. Ray et al. 1984. A1r quality data for metals
1977-1979 from the National Air Surveillance Networks. EPA-600/S4-83-053.
Off. Res. Devel. Environ. Honlt. Systems Lab., Research Triangle Park, NC.
p. 3.
Falrhall, L.T., R.C. Dunn, N.E. Sharpless and E.A. Prltchard. 1945. The
toxUHy of molybdenum. Pub. Health Bull. No. 293. 36 p.
Fell, B.F., 0. Dlnsdale and T.T. El-Gallad. 1979. Gut pathology of rats
dosed with tetrathlomolybdate. 3. Comp. Pathol. 89(4): 495-514.
Ferm, V.H. 1972. The teratogenlc effects of metals on mammalian embryos.
Adv. Teratol. 5: 51-75.
Franke, K.W. and A.L. Moxon. 1937. The toxlclty of orally Ingested
arsenic, selenium, tellurium, vanadium and molybdenum. J. Pharmacol. Exp.
Ther. 61: 89-102.
Freltas, M.C., M.C. Vaz Carrelro, M.F. Rels and E. Mar\1nho. 1988. Deter-
mination of the level of some heavy metals In an aquatic ecosystem by
Instrumental neutron activation analysis. Environ. Technol Lett. 9(9):
969-976.
Goetz, L. 1983. Radlochemlcal techniques applied to laboratory studies of
water leaching of heavy metals from coal fly ash. Water Scl. Technol.
15(11): 25-47.
0186d -77- 02/05/90
-------
Goyer, R.A.. 1986. Toxic effects of metals. In: Casarett and Douglas,
Toxicology, 3rd ed. p. 582, 615-616.
HJelmar, 0. 1983. Marine disposal of fly ash from coal-fired power plants.
Water Scl. Techno!. 15(11): 109-131.
Hunt, C.E. and 3.M. Navla. 1973. Effects of Sr, Mo, L1 and B on developing
teeth and other tissues of neonatal rats. Trace Substances In Environmental
Health VI. p. 159-168.
Jeter, M.A. and G.K. Davis. 1954. The effect of dietary molybdenum upon
growth, hemoglobin, reproduction and lactation of rats. J. Nutr. 54:
215-220.
Kanematsu, N., M. Hara and T. Kada. 1980. Rec assay and mutagenlclty
studies on metal compounds. Mutat. Res. 77(2): 109-116.
Kennedy, P.C. 1986. The use of mollusks for monitoring trace elements 1n
the marine environment In New Zealand 1. The contribution of Ingested
sediments to the trace element concentrations In New Zealand mollusks. New
Zealand 3. Mar. Freshwater Res. 20(4): 627-640.
Kovacs, M., 1. Nyary and L. Toth. 1984. The microelement content of some
submerged and floatlng..aquatic plants. Acta Bot. Hung. 30(1-2): 173-185.
«..» . •
Lallch, J.J., K. Groupner and J. Jolln. 1965. The Influence of copper and
molybdate salts on the production of bony deformities In rats. Lab. Invest.
> r*
14(8): 1482-1493.
0186d -78- 02/05/90
-------
Lantzy, R.J. and F.T. Mackenzie. 1979. Atmospheric trace metals: Global
cycles and assessments of man's Impact. Geochlm. Cosmochlm. Acta. 43:
511-525.
Lener, J. and B. Blbr. 1979. Biliary excretion and tissue distribution of
penta- and hexavalent molybdenum 1n rats. Toxlcol. Appl. Pharmacol. 51(2):
259-263.
Lener, J. and B. Blbr. 1984. Effects of molybdenum on the organism (a
review). J. Hyg. Epidemic!. Mlcroblol. Immunol. 28(4): 405-419.
Lindsay, W.I. 1979. Chemical Equilibria In Soils. John Wiley and Sons,
New York. p. 365-372.
Luo, X.H., H.3. We1 and S.P. Yang. 1983. Inhibitory effects of molybdenum
on esophageal and forestomach cardnogenesls 1n rats. 0. Natl. Cancer Inst.
71(1): 75-80.
Mantel, N. and M.A. Schnelderman. 1975. Estimating "safe" levels, a
hazardous undertaking. Cancer Res. 35: 1379-1386.
M1ller-Ihl1, N.J. and W.R. Wolf. 1986. Characterization of a diet
reference material for 17 elements! Anal. Chem. 58: 3225-3230.
Mogllvskaya, O.Y. 1950. No title given. Gig. SanH. 12: 18. (Cited 1n
ACGIH, 1986)
0186d -79- 02/05/90
-------
Morgan, J.D., D.G. Mitchell and P.M. Chapman. 1986. Individual and
combined toxldty of manganese and molybdenum to mussel, Mytllus edulls.
larvae. Bull. Environ. Contam. Toxlcol. 37: 303-307.
NAS (National Academy of Sciences). 1980. Recommended Dally Allowances,
9th ed. Food and Nutrition Board, National Academy of Sciences, Washington,
DC. (Cited 1n Solomons, 1984}
Nellands, 3.B., F.M. Strong and C.A. Elvehjen. 1948. Molybdenum In the
nutrition of the rat. J. B1ol. Chem. 172: 431-439.
NRC (National Research Council). 1978. Nutrient requirements of domestic
animals. Nutrient Requirements of Laboratory Animals, 3rd ed. National
Academy of Science,'Washington, DC. p. 17, 41, 45.
NMagu, J.O. and J.M. Pacyna. 1988. Quantitative assessment of worldwide
contamination of air, water and soils by trace metals. Nature. 333:
134-139.
NTP (National Toxicology Program). 1983. Subchronlc Inhalation toxldty
studies of molybdenum trloxlde. Unpublished. Research Triangle Park, NC.
Ohlendorf, H.M., D.J. Hoffman, M.K. Salkl and T.W. Aldrlch. 1986.
Embryonic mortality and abnormalities of aquatic birds: Apparent Impacts of
selenium from Irrigation dralnwater. Sd. Total Environ. 52(1-2): 49-63.
0186d -80- 02/05/90
-------
Ohlendorf, H.M., R.L. Hothem, T.W. Aldrlch and A.J. Krynltsky. 1987.
Selenium contamination of the grasslands, a major California waterfowl area.
Sc1. Total Environ. 66: 169-183.
Olmez, I., A.E. Sheffield, G.E. Gordon et al. 1988. Compositions of
particles from selected sources In Philadelphia for receptor modeling appli-
cations. J. Air Pollut. Control Assoc. 38: 1392-1402.
OSHA (Occupational Safety and Health Administration). 1989. Occupational
Standards. Permissible Exposure Limits. 29CFR 1910.1000. Federal
Register. 54(12): 1596, 1945.
Parlsl, E., G. Fornerls and V. Glaccone. 1986. Freshwater fish as biologi-
cal Indicators of heavy metal pollution. Ind. Aliment. (Plnerolo, Italy).
25(3): 214-218.
Rana, S.V.S. and A. Kumar. 1980a. Enzymologlcal studies on the liver of
rats fed with molybdenum and copper. Toxlcol. Lett. 6: 163-166.
Rana, S.V.S. and A. Kumar. 1980b. Proteins, I1p1ds, and carbohydrates In
the liver and kidney of rats after molybdenum and copper treatment. Bull.
Environ. Contam. Toxlcol. 25(1): 146-152.
' , i"
Rana, S.V.S., A. Kumar, N.G. Bhardwaj and A. Kumar. 1980. Llplds In the
liver and kidney of rats fed various heavy metals. Acta. Anat. 108(3):
402-412.
0186d -81- 02/05/90
-------
Rawlence, D.3. and 3.S. WhUton. 1976. An element survey of the aquatic
macrophytes, water and plankton from the Walkato River, North Island, New
•
Zealand. Mauri Ora. 4: 121-131.
Robinson, G.A., V.E. ValU, B.J. McSherry and A.M. Peplno. 1969. The
survival of DF32 P-labelled erythrocytes In molybdate-fed rabbits. Can. J.
Physio!. Pharmacol. 47(4): 343-347.
Rodgers, J.H., Jr., D.S. Cherry, R.L. Graney, K.L. Dlckson and J. Cairns,
Jr. 1980. Comparison of heavy metal Interactions In acute and artificial
stream bloassy techniques for the Asiatic clam (Corblcula flumlnea).
Aquatic Toxlcol. ZSTM STP. 707. p. 266-280.
Rosoff, B. and H. Spencer. 1964. Fate of molybdenum-99 In man. Nature.
202: 410-411.
Rosoff, B. and H. Spencer. 1973. The distribution and excretion of
molybdenum-99 1n mice. Health Physics. 25(2): 173-175.
Rossman, T.G. and M. Molina. 1986. The genetic toxicology of metal
compounds: II. Enhancement of ultraviolet light-Induced mutagenesls In
Escherlchla coll WP2. Environ. Mutagen. 8(2): 263-271.
Rossman, T.G., M. Molina and L.W. Meyer. 1984. The genetic toxicology of
metal compounds: I. Induction of lambda prophage 1n E_. coll WP2S (Lambda).
Environ. Mutag. 6(1): 59-69.
0186d -82- 02/05/90
-------
Salkl, U.K. and. T.W. May. 1988. Trace element residues 1n bluegllls and
common carp from the lower San Joaquln River, California (USA) and Us
tributaries. Scl. Total Environ. 74(0): 199-218.
Sakaguchl, 7., A. NakaJIma and T. Horlkoshl. 1981. Studies on the accumu-
lation of heavy metal elements In biological systems. XVIII. Accumulation
of molybdenum by green mlcroalgae. Eur. 0. Appl. M1crob1ol. Blotechnol.
12(2): 84-89.
Schroeder, H.A. and M. HUchener. 1971. Toxic effects of trace elements on
the reproduction of mice and rats. Arch. Environ. Health. 23: 102-106.
Solomons, N.W. 1984. The other trace minerals manganese, molybdenum,
vanadium, nickel silicon and arsenic. In: Current Topics 1n Nutrition and
Disease. Absorption and Malabsorptlon of Mineral Nutrients, Vol. 12, N.W.
Solomons and I.H. Rosenberg, Ed. Alan R. L1ss, Inc., New York. 314 p.
Spence, J.A., N.F. Suttle, G. Wenham, T. El-Gallad and I. Bremner. 1980. A
sequential study of the skeletal abnormalities which develop In rats given a
small dietary supplement of ammonium tetrathlomolybdate. 3. Comp. Pathol.
90(1): 139-153.
SRI (Stanford Research Institute). 1988. 1987 Directory of Chemical
Producers: United States of America. SRI International, Menlo Park, CA.
p. 460, 789-790, 950.
0186d -83- 02/05/90
-------
Stoner, G.D., H.B. Shlmkln, M.C. Troxell, T.L. Thompson and L.S. Terry.
1976. Test for cardnogenlclty of metallic compounds by the pulmonary tumor
response 1n strain A mice. Cancer Res. 36(5): 1744-1747.
Suloway, J.J., W.R. Roy, l.H. Skelly, D.R. Dlckerson and R.H. Schuller.
1983. Chemical and lexicological properties of coal fly ash. Report
IL/SGS/EGN-105. NTIS PB84-116110. 77 p.
Sutherland, J. and C.W. Major. 1981. Internal heavy metal changes as a
consequence of exposure of Hytllus edulls. the blue mussel, to elevated-
external copper(II) levels. Comp. Blochem. Physlol. C. Comp. Pharmacol.
68(1): 63-68.
Talbot, V. and H.J. Chang. 1987. Rapid multielement analysis of oyster and
cockle tissue using x-ray fluorescene spectrometry, with application to
reconnaissance marine pollution Investigations. Sc1. Total Environ. 66:
213-223.
Thompson, J.A.J., M.D. Nasslchuk, D.U. Paton. B.J. Rein and H.A Farrell.
1986. Examination of tissue metal burdens and metal-binding protein In the
golden king carb (LUhodes aequlsplna Benedict) from AUc Arm and Hastings
Arm, British Columbia, Canada. Can. Tech. Rep. F1sh Aquat. Sc1. 0(1440):
1-44.
Tong, S.C., W.D. Youngs, W.H. Gutenmann and 0.3. L1sk. 1974. Trace metals
In Lake Cayuga lake trout (Salvenllnus namaycush) In relation to age. J.
Fish Res. Board Can. 31(2): 238-239.
0186d -84- 02/05/90
-------
Underwood, E.J. 1977. 4V Molybdenum toxldty. ITK Trace Elements In Human
and Animal Nutrition, 4th ed. Academic Press, New York, NY. p. 120-131.
USDI (U.S. Department of Interior). 1988. Molybdenum. Reprint From the
1987 Bureau of Mines Minerals Yearbook. U.S. Department of the Interior,
Bureau of Mines, Washington, DC.
U.S. EPA. 1973. National Emissions Inventory of Sources and Emissions of
Molybdenum. GCA Technology D1v., GCA Corp., Bedford, Mass. 36 p.
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. 1984. Methodology and Guidelines for Ranking Chemicals Based on
Chronic Toxldty 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. 1986a. Guidelines for Carcinogenic Risk Assessment. Federal
Register. 51(185): 33992-34003.
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.
0186d -85- 02/05/90
-------
U.S. EPA/OWRS (Office of Water Regulations and Standards). 1986. Guide-
lines for Deriving Numerical National Water Quality Criteria for the Protec-
tion of Aquatic Organisms and Their Uses. U.S. EPA, Washington, DC.
p. 22-58, 98. NTIS PB85-227049/XAB.
Van Campen, D.R. and E.A. Mitchell. 1965. Absorption of Cr64, Zn«s,
Mo" and Fes» from Ugated segments of rat gastrointestinal tract. J.
Nutr. 86: 120-124.
Walravens, P.A., R. Moure-Eraso, C.C. Solomons, W.R. Chappell and G.
Bentley. 1979. Biochemical abnormalities 1n workers exposed to molybdenum
dust. Arch. Environ. Health. 34(5): 302-308.
Weast, R.C., Ed. 1985. CRC Handbook of Chemistry and Physics, 66th ed.
CRC Press, Inc., Boca Raton, FL. p. B-72, B-116-117, B-144, D-194.
Mel. H.J., X.M. Luo and S.P. Yang. 1985. Effects of molybdenum and
tungsten on mammary cardnogenesls In SD rats. J. Natl. Cancer Inst.
74(2): 469-473.
Wide, M. 1984. Effect of short-term exposure to five Industrial metals on
the embryonic and fetal development of the mouse. Environ. Res. 33(1):
47-53.
i, * . *
Hldjajakusuma, M.C., P.K. Basrur and G.A. Robinson. 1973. Thyroid function
In molybdenotlc rabbits. J. Endocrlnol. 57(3): 419-424.
0186d -86- 02/05/90
-------
Wlersema, 3.M., L. Wright, B. Rogers, R. Barta, L. Haeuser and 3.H. Price.
1984. Human exposure to potentially toxic elements through ambient air 1n
Texas. .In.: Proc. 77th APCA Annual Meeting, Austin, TX, January, 1984.
p. 15.
Winston, P.W., L. Hoffman and W. Smith. 1973. Increased weight loss In
molybdenum-treated rats 1n the cold. Trace Sub. Environ. Health. 7:
241-244.
W1tz, S., J.A. Wood and M.W. Wadley. 1986. Toxic metal and hydrocarbon
concentrations 1n automobile Interiors during freeway transit. J.TK Proc.
192nd National Meeting ACS Dlv. Environ. Chem. 26: 302-305.
Wren, C.O., H.R. Maccrlommon and B.R. Loescher. 1983. Examination of bio-
accumulation and blomagnlflcatlon of metals In a Precambrlan Shield lake.
Water Air Soil Pollut. 19(3): 277-291.
Yamamoto, T., Y. Otsuka, K. Aoyama, H. Tabata and K. Okamoto. 1985. The
distribution of chemical elements In selected marine organisms: Comparative
blogeochemlcal data. In: Proc. Symp. Mar. Estauarlne Geochem, Chelsea, MI,
1984. p. 315-327.
Zellkoff, J.T., N. Atkins and T.G. Rossman.-. 1986. Mutagenldty of soluble
metal salts using the V-79 hypoxanthlne-guanlne phosphorlbosyltransferase
mutation assay. Environ. Mutagen. 8(6): 95. - ,•=.:.
0186d -87- 02/05/90
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APPENDIX A
LITERATURE SEARCHED
This HEED 1s based on data Identified by computerized literature
searches of the following:
CHEMLINE
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 In Hay, 1988, 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, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxlco.logy, 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. 2B. Oohn WHey and
Sons, NY. p. 2879-3816.
0186d -88- 05/31/89
-------
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, M. 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, Menlo
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 1n 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, NO.
Worthing, C.R. and S.B. Walker, Ed. 1983. The Pesticide Manual.
British Crop Protection Council. 695 p.
0186d -89- 05/31/89
-------
In addition, approximately 30 compendia of aquatic toxldty 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 H.T. Flnley. 1980. Handbook of Acute Toxldty
of Chemicals to Fish and Aquatic Invertebrates. Summaries of
Toxldty Tests Conducted at Columbia National Fisheries Research
Laboratory. 1965-1978. U.S. Dept. Interior, F1sh and Wildlife
Serv. Res. Publ. 137, Washington, DC.
McKee. J.E. and H.W. Wolf. 1963. Water Quality Criteria, 2nd ed.
Prepared for the Resources Agency of California, SJate Water
Quality Control Board. Publ. No. 3-A.
Plmental, D. 1971. Ecological Effects of Pesticides on Non-Target
Spedes. Prepared for the U.S. EPA, Washington. DC. PB-269605.
Schneider, B.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.
0186d -90- 05/31/89
-------
APPENDIX B
o
CO
O.
r
05/31 /8<
Species
Inhalation Exposure
Subchronlc ; ID
Chronic ID
Carclnogenlclty ID
Oral Exposure
Subchronlc rat
Chronic rat
Carclnogenlclty ID
REPORTABLE QUANTITIES
Based on chronic toxlclty:
Based on Carclnogenlclty:
in - Incnfftrtont Hat*- NA .
Summary
Exposure
ID
ID
ID
1.0 mg/kg/day
1n the diet
for -90 days
1.0 mg/kg/day
In the diet
for -90 days
ID
100 pounds
ID
nnt annllrahlp
Table for Molybdenum
Effect
ID
ID
ID
Decreased weight gain;
Impaired lactation
(reduced weaning weight)
Decreased weight gain;
Impaired lactation
(reduced weaning weight)
ID
RfD or qj* Reference
ID NA
ID NA
ID NA
1x10"* mg/kg/day Jeter
Davis
1x10"" mg/kg/day Jeter
Davis
ID NA
Jeter
Davis
NA
and
, 1954
and
, 1954
.
and
, 1954
-------
APPENDIX C
DOSE/DURATION RESPONSE GRAPHS FOR EXPOSURE TO MOLYBDENUM
C.I. DISCUSSION
Dose/duration-response graph(s) for Inhalation and oral exposure to
molybdenum generated by the method of Crockett et al. (1985) using the
computer software by Durkln and Meylan (1988) developed under contract to
ECAO-C1nc1nnat1 are presented 1n Figures C-l through C-4. Data used to
generate these graphs are presented 1n Section C.2. In the generation of
these figures, all responses are classified as adverse (PEL, AEL or LOAEL)
or nonadverse (NOEL or NOAEL) for plotting. For Inhalation exposure, the
ordlnate expresses concentration In either of two ways. In Figure C-l, 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 expanded experimental concentration [expanded exp. cone.
(mg/m3)]. In Figure C-2, the expanded experimental concentration was
multiplied by the cube root of the ratio of the animalchuman body weight to
adjust for species differences 1n basal metabolic rate (Mantel and
Schnelderman, 1975) to estimate an equivalent human or scaled concentration
[scaled cone. (mg/m3)].
For oral exposure, the ordlnate expresses dosage as human equivalent
dose. The animal dosage In mg/kg/day Is multiplied by the cube root of the
ratio of the animal:human body weight to adjust for species differences In
basal metabolic rate (Mantel and Schnelderman, 1975). The result Is then
_ • C~ ("*
multiplied by 70 kg, the reference human body weight, to express the human
equivalent dose as mg/day for a 70 kg human.
0186d -92- 05/31/89
-------
iwe
I II
1
Z
S
199 •-
--M4
j
J
-I
.81
1 r>ihalM*)or>
NUMN EOUIU BUMATION (f>>««tien
MT« KtTNOV
0.1
Key:
N . NOAEL
F » PEL
Solid line - Adverse Effects Boundary
Dashed line « No Adverse Effects Boundary
FIGURE C-l
Dose/Duration - Response Graph for Inhalation Exposure to Molybdenum:
Censored 'Data Method
0186d
-93-
07/26/89
-------
1M
r.
\
I
6
V
III
12
; 5
-M4
16 4
0.01
0.1
NUMN taUlU BUMTION
CXNSOR£» MT« NCTNO»
Key: N . NOAEL
F . FEL
Solid line - Adverse Effects Boundary
Dashed line - No Adverse Effects Boundary
FIGURE C-2
Dose/Duration - Response Graph for Inhalation Exposure to Molybdenum:
Censored Data Method
0186d
-94-
07/26/89
-------
188888
\
f
V
I
9
a
h.
z
a
ieee T
188 '-
18 -r
8.881
(Oral Exposuw)
•4M
*22
•*.
"
-
LI
»a»-
4-
n
8.81 8.1
HUNAN EQUIU BUXATION (fy>«ctien lif»«>«n)
ENVELOP NTTMOP
Key:
A « AEL
L - LOAEL
N « NOAEu
Solid line « Adverse Effects Boundary
Dashed line « No Adverse Effects Boundary
FIGURE C-3
Dose/Duration - Response Graph for Oral Exposure to Molybdenum:
Envelope Method
0186d
-95-
05/31/89
-------
1HMMH
» imee -
•
T
\
?
t
V
u 18*9-
, M
«
B
»
31 BO *
* vc
»
K
z
1 «•
I •
1 ' . 1 I .... | , .1 | , .,.,,,,;
Insufficient Data fop Ctntor Lin* :
.
! A22
i 1 Fl&3 F21 F12 *"4 ' "
ij, i»ttl » n
: '^^^^ " u. g '*
' \ •
-*.«' eu
; \ :
: \ 3
X «
r ' \ u " -
= \a« =
.091
(Oral Exposui"*)
0.81 t.l
HUNAN X9UIU »UR«TION
CDttOXEV MI* NXTHO»
Key:
A « AEL
L - LOAEL
N . NOAEu
Solid line - Adverse Effects Boundary
Dashed line - No Adverse Effects Boundary
FIGURE C-4
Dose/Duration - Response Graph for Oral Exposure to Molybdenum:
Censored Data Method
0186d
-96-
05/31/89
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The boundary for adverse effects (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 point, an Infinite
line Is extended upward, parallel to the dose axis. The starting 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 concen-
tration equal to or lower than the previous one. This process 1s continued
to the lowest adverse effect dose or concentration. From this point, a line
1s extended to the right, parallel to the duration axis. The region of
adverse effects lies above the adverse effects boundary.
Using the envelope method, the boundary for no adverse effects (dashed
line) 1s drawn by Identifying the highest no adverse effects dose or concen-
tration. 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 lower or equal no adverse effect dose or concentration at a longer
duration of exposure. When this process can no longer be continued, a line
1s dropped parallel to the dose or concentration axis to the duration ax'is.
The no adverse effects region lies below the no adverse effects boundary.
At either end of the graph between the adverse effects and no adverse
effects boundaries are regions of ambiguity. The area (1f any) resulting
from Intersection 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
effect boundary 1s redrawn so that 1t does not Intersect the adverse effects
boundary and no region of contradiction Is generated. This method results 1n
the most conservative definition of the no adverse effects region.
0186d -97- 05/31/89
-------
Figures C-l and C-2 reflect the paucity of the data regarding Inhalation
exposure to molybdenum. The data, composed of only five records, were
extracted from Falrhall et al. (1945). This study suffers from serious
deficiencies In design and In the manner in which the results are described.
The data point N, (NOAEL), derived from exposure to molybdenite, seems to
conflict with lower experimental concentrations of other molybdenum
compounds that Induce lethality (F., F. and F,.}. It may be that
molybdenite has a lower deposition rate than other molybdenum compounds or a
lower absorption rate; however, there are no data to support this assump-
tion. The data point N., the concentration that caused no adverse
effects, represents Inhalation of fumes of molybdenum trloxlde at a concen-
tration level considerably lower than the other points 1n the graph.
Another significant feature of these graphs 1s the large region of
ambiguity, which reflects the limited size of the data base.
Figures C-3 and C-4 show the dose/duration-effect graphs generated by
the envelop and censored data methods for oral exposure to molybdenum,
respectively. The boundary for adverse effects 1s defined by an AEL (A27)
from Falrhall et al. (1945) from a gavage study 1n guinea pigs, a FEL (F28)
from the same experimental series (Falrhall et al., 1945) and two reports of
AELs In rats (A26 superimposed onto A25) from short-term studies (Fell et
al., 1979; Spence et al., 1980). In the two latter studies, ammonium
tetrathlomolybdate was used; therefore, It appears that this compound 1s
considerably more toxic than other molybdenum compounds. Another signifi-
cant feature 1s the data point N. from Falrhall et al. (1945), In which
molybdenite was administered to guinea pigs. The fact that the dose used
was without effects agrees with the lack of toxlclty of molybdenite by
Inhalation. The fact that reproductive effects (L,) are manifested at
0186d -98- 05/31/89
-------
doses much Tower than those causing other systemic effects 1s highly
significant, and this finding was used as the basis of the oral RfD.
C.2. DATA USED TO GENERATE DOSE/DURATION-RESPONSE GRAPHS
C.2.1. Inhalation Exposure
Chemical Name: Molybdenum
CAS Number: 439-98-7
Document Title: Health and Environmental Effects Document on Molybdenum
Document Number:
Document Date:
Document Type: HEED
RECORD #1
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Guinea pigs
Male
NOEL
Inhalation
Dose: 279.000
Duration Exposure: 5.0 weeks
Duration Observation: 5.0 weeks
Number Exposed: 25
Number Responses: 25
Type of Effect:
Site of Effect: SENSR
Severity Effect:
Animals were exposed to molybdenite dust 1 hour/day, 5 days/
week for 5 weeks. The only reported effect 1s an Increase In
respiratory rate.
Falrhall et al., 1945
RECORD #2: Species: Guinea
Sex: Male
Effect: FEL
Route: Inhalat
Number Exposed:
Number Responses:
Type of Effect:
SHe of Effect:
Severity Effect:
pigs
Ion
26
51
DEATH
LIVER'
10
Dose: . 200.000
Duration Exposure: 5.0 weeks
Duration Observation: 5.0 weeks
26
' 51
DEATH
KIDNY
10
Comment:
Citation:
Animals were exposed to molybdenum trloxlde 1 hour/day, 5.
days/week for 5 weeks. Weight loss and diarrhea occurred.
Necrosis and fatty changes In the liver and kidneys were
observed.
Falrhall et al., 1945 "
0186d
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05/31/89
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RECORD #3:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Guinea pigs
Hale
PEL
Inhalation
Dose: 155.000
Duration Exposure: 5.0 weeks
Duration Observation: 5.0 weeks
Number Exposed: 5
Number Responses: 24
Type of Effect: DEATH
SHe of Effect: NR
Severity Effect: 10
Calcium molybdate dust neutralized with calcium hydroxide was
used. No signs of clinical toxldty were observed, but the
authors report that 5/24 animals died during exposure.
Falrhall et al., 1945
RECORD #4:
Species:
Sex:
Effect:
Route:
Guinea pigs
Male
NOEL
Inhalation
Dose:
Duration
Duration
Exposure:
Observation:
52.000
5.0 weeks
5.0 weeks
Comment:
Citation:
Number Exposed:
Number Responses:
Type of Effect:
SHe of Effect:
Severity Effect:
Animals were exposed to fumes of molybdenum trloxlde 1 hour/
day, 5 days/week for 5 weeks. No signs of toxldty were
noticed.
Falrhall et al., 1945
RECORD #5:
Species:
Sex:
Effect:
Route:
Guinea pigs
Hale
PEL
Inhalation
Dose:
Duration
Duration
Exposure:
Observation:
186.000
5.0 weeks
5.0 weeks
Comment:
Citation:
Number Exposed: NR
Number Responses: NR
Type of Effect: DEATH
SHe of Effect: NR
Severity Effect: 10
Animals were exposed to fumes of molybdenum trloxlde 1 hour/
day, 5 days/week for 5 weeks. The only Information given 1s
that 8.3X mortality occurred.
Falrhall et al., 1945 "
0186d
-100-
05/31/89
-------
RECORD #18:
Comment:
CUatlon:
Species:
Sex:
Effect:
Route:
Rats
Hale
PEL
Food
Dose: 101.000
Duration Exposure: 40.0 days
Duration Observation: 40.0 days
Number Exposed: 10
Number Responses: 5
Type of Effect: DEATH
SHe of Effect: NR
Severity Effect: 10
Comment:
CUatlon:
RECORD #19:
The dose corresponds
additional Information
Falrhall et al., 1945
Species: Rats
Sex: Male
Effect: PEL
Route: Food
to an 1050 for calcium
was provided.
molybdate. No
Dose: 125.000
Duration Exposure: 40.0 days
Duration Observation: 40.0 days
Number Exposed: 10
Number Responses: 5
Type of Effect: DEATH
SHe of Effect: NR
Severity Effect: 10
Comment:
Citation:
RECORD #20:
The dose corresponds to an 1059 for molybdenum trloxlde.
No additional Information was provided.
Falrhall et al.. 1945
Species:
Sex:
Effect:
Route:
Rats
Male
PEL
Food
Dose: 333.000
Duration Exposure: 40.0 days
Duration Observation: 40.0 days
Number Exposed: 10
Number Responses: 5
Type of Effeci: DEATH
SHe of Effect: NR
Severity Effect: 10
The dose corresponds to an 1059 for ammonium molybdate,
additional Information was provided.
Fairhall et al., 1945
No
0186d
-107-
05/31/89
-------
Sex:
Effect:
Route:
rtdiS
«R
i-EL
Gavage
uose: 200.000
Duration Exposure: 13.0 days
Duration Observation: 13.0 days
Number Exposed: NR
Number Responses: NR
Type of Effect: DEATH
Site of Effect: LIVER
Severity Effect: 10
Comment: Neonatal rats received sodium molybdate In an acidic solution.
Fatty liver and death occurred. If administered In a neutral
solution no adverse effects were reported.
Citation: Hunt and Navla, 1973
RECORD #22:
Species: Rats
Sex: Hale
Effect: AEL
Route: Food
Number Exposed:
Number Responses:
Type of Effect:
SHe of Effect:
Severity Effect:
10
10
OTHER
LIVER
5
Dose:
Duration Exposure:
Duration Observation:
10
10
HGTDC
BODY
571.000
20.0 days
20.0 days
Comment: Ammonium molybdate was given to albtao rats,
developed In liver and kidneys.
Citation: Rana et al., 1980
Fatty changes
RECORD #23:
Species:
Sex:
Effect:
Route:
Rabbits
Hale
AEL
Food
Dose:
Duration
Duration
Exposure:
Observation:
98.000
25.0 days
25.0 days
Comment:
Citation:
Number Exposed: 7
Number Responses: 7
Type of Effect: FUND
SHe of Effect: ENDOC
Severity Effect: 8
New Zealand rabbits were administered sodium molybdate In the
diet. Holybdenum caused thyroldal hypofunctlon. Body
weight, hemoglobin and packed cell volume were reduced.
Uldjajakusuma et al., 1973
0186d
-108-
05/31/89
-------
RECORD #24:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Rats
Hale
AEL
Water
Number Exposed: 5
Number Responses: 5
Type of Effect: HISTO
Site of Effect: LIVER
Severity Effect: 5
Dose: 289.000
Duration Exposure: 28.0 days
„ Duration Observation: 28.0 days
5
5
WGTNS
BODY
Ammonium molybdate was administered to Mlstar rats. Fatty
changes In liver and kidney were noticed. Molybdenum also
caused marked growth retardation.
Bandyopadhyay et a!., 1981
RECORD #25:
"~~
Species:
Sex:
Effect:
Route:
Rats
Hale
AEL
Food
Dose:
Duration
Duration
Exposure:
Observation:
0.300
21.0 days
21.0 days
Comment:
Citation:
Number Exposed: 36
Number Responses: 36
Type of Effect: DEGEN
Site of Effect: COLON
Severity Effect: 6
Ammonium tetrathlomolybdate was used. Cell fragmentation and
necrosis In the caecum and colon were observed.
Fell et al., 1979
RECORD #26:
Species:
Sex:
Effect:
Route:
Rats
Hale
AEL
Food
Dose:
Duration
Duration
Exposure:
Observation:
0.300
21.0 days
21.0 days
Comment:
Citation:
Number Exposed: 24
Number Responses: 24
Type of Effect: ANATM
SHe of Effect: MSKEL
Severity Effect: 7
Ammonium tetrathlomolybdate was used. Severe skeletal
abnormalities were observed 1n long bones growth plates and
muscle Insertions.
Spence et al., 1980
0186d
-109-
05/31/89 '
-------
RECORD #27;
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Guinea pigs
Hale
AEL
Gavage
Dose:
Duration Exposure:
Duration Observation:
17.000
25.0 days
25.0 days
NR
NR
HISTO
LIVER
5
NR
. NR
HISTO
KIDNY
5
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Molybdenum trloxlde was administered to an unspecified number
of guinea pigs. Severity of the effects Increased with
Increasing dosages.
Falrhall et al., 1945
RECORD #28: Species: Guinea
Sex: Male
Effect: PEL
Route: Gavage
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
pigs
NR
NR
DEATH
BODY
10
Dose: 67.000
Duration Exposure: 9.0 days
Duration Observation: 9.0 days
-
•
Comment: Molybdenum trloxlde was administered to an unspecified number
of guinea pigs. All died by the 9th day. Fatty changes in
the liver and kidney were observed.
Citation: Falrhall et al., 1945
RECORD #29:
Species:
Sex:
Effect:
Route:
Rats
Male
NOCEL
Water
Dose:
Duration
Duration
Exposure:
Observation:
2.800
30.0 weeks
30.0 weeks
Number Exposed: 20
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Comment: Sprague-Dawley rats were administered sodium molybdate In the
drinking water. No evidence of tumors or pretumorous lesions
was observed In esophagus or forestomach, only organs
examined.
Citation: Luo et al., 1983
NR « Not reported
-110-
05/31/89
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