‘CHAPTER 4

PHARMACOLOGY OF MERCURY

The basic pharmacological activity of mer-
cury is centered about the strong attraction
of this metal for certain sensitive ligands of
proteins located in enzymes, cell mem-
branes, and cell stroma. The total body re-
sponse to this binding is dependent upon the
cells, tissues, and enzyme systems affected
and the concentration of mercury present in
these sites. Therefore, the degree of absorp-
tion and excretion and the tissue distribution
play a major role in the final effect of mercu-
ry on the organism. The different forms of
mercury vary in their absorption, distribu-
tion, and excretion characteristics and,
therefore, vary in their effects upon man or
animal.

IV.A. Absorption

The absorption of mercury and its com-
pounds varies considerably with the chemi-
cal form of the metal and with the route of
exposure.

IV. A. 1. Oral Absorption — It is generally
considered that elemental mercury is not
absorbed from the intestinal tract. The mild
catharsis, diuresis, or intoxication resulting
from the ingestion of mercury results from
small particles of oxides or sulfides found
on the surface of mercury. These oxides and
sulfides are the result of atmospheric expo-
sure and oxidation. In water, especially in
the presence of the chloride ion, mercury
can be slowly oxidized to the mercuric ion.
So long as the state of subdivision of the
mercury is quite coarse, the rate of solution
in body fluids is too slow to give rise to cu-
mulative effects (Goodman and Gilman,
1965).

Soluble inorganic mercurials, such as mer-
curic chloride, are absorbed from the gas-

trointestinal tract but only to the extent of
about 2% (Clarkson, 1971). This is probably
because these compounds show a strong
avidity for a large number of groupings on
proteins, and after binding to SH groups, the
mercuric ion ‘still contains a free valence
capable of combining ‘with some other
properly placed group. This fixes the mer-
curic ion to the protein’ of the intestinal
mucosa preventing or delaying absorption,
and producing local irritation (Hughes,
1957). ‘

Swensson, Lundgren and Lindstrom (1959)
studied the absorption of mercuric chloride
and mercuric nitrate from subacute oral
administration in rats. The animals were
administered the compounds in water, fed
ad libitum, at a concentration of 2 mg Hgl/li-
ter of water. The animals were sacrificed at
1, 2, and 3 weeks. Absorption of both mer-
curial salts occurred as indicated by very
low levels of mercury in the blood, brain,
and liver as compared to organic mercurials.

Fitzhugh, Nelson, Laug, and Kunze (1950)
studied the absorption of mercuric acetate
and phenylmercuric acetate from chronic
oral administration in rats. The animals were
administered the compounds in their diets at
levels ranging from 0.1 to 160 ppm, ad Jibi-
tum, for up to 2 years. Feces and urine sam-
ples were analyzed for mercury at 6 months
and | year. The livers and kidneys were ana-
lyzed for mercury in animals sacrificed at 1
year and at termination. Diets containing the
same quantity of mercury but in different
forms, viz., phenylmercuric acetate and
mercuric acetate, produced a large differ-
ence in tissue concentration of mercury. For
example, at a dosage level of 0.5 ppm mer-
cury, the liver contained, on the average, 2
1/2 times and the kidneys 28 times as much

51


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with mercury compounds."*

I. “Etiology. clinical picture, renal function."”
Hl. ‘Treatment and prognosis.””
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63, 69, 75 (1965).

Vasilevskaya, A.E., and Sheherbakov. V.P. ‘*Deter-
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96 (1963).

Vasilevskaya, A.E., Sheherbakov, V.P., and Lev-
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Vickers, T.J., and Merrick, S.P. “Determination of
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atomic fluorescence flame spectrometry."’ Talan-
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Vignoli, L., and others. Comparative study of recent
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Voight, G.E. ‘‘Histochemical examination of the mer-
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sublimate poisoning."’ Acta histochem. 14: 315
(1962).

Voress. H.E., and Smeleer, N.K. “Mercury toxici-
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sion. Technical Information Service Extension.
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Wahlberg. P.. et al. (Aland Cent. Hosp., Dept. Intern.
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(1971).

Walker, K.C. ‘‘Legislative restrictions by Federal ac-
tion in the United States."’ Oikos Supp. 9: 21
(1967).

Wallace, R.A.. Fulkerson, W., Shults, W.D.. and
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(Jan, 1971).

Wands, Ralph C. Personal communication; (1970).

Wanntorp, H., ef al. “‘Mercury residues in wood pi-
geons."’ (Columba p. palumbus L.) in 1964 and
1966 Nordisk Veterinarmedicin 19 (10): 474
(1967).

Wakary, J.. and Hubbard, D.M. ‘‘Acredvnia and mer-
cury."* I. Radic. 42: 365 (1953).

Ward, F.N., and’McHugh, J.B. ‘Determination of
mercury in vegetation with dithizone. A single

extraction procedure.’’ U.S. Geol. Survey. Pro-
fessional Papers, No. 501 D: 128 (1965).

Warren, H.V., and Delavault, R.E. ‘‘Mercury content
of some British soils." Oikos 20 (2): 537 (1969).

Wassarman, P.M., Watson, H.C., and Major, J.P.
“Reaction of the sulfhydryl groups of lobster-
muscle glyceraldehyde-3-phosphate dehydrogen-
ase with organic mercurials."’ Biochem. et Bi-
physica Acta 191 (1): 1 (1969).

Wawrzyckzek, W., and Wisniewske. W. ‘‘Titrime-
trische bestimmung von quecksilber (II) -ionen
mit kaliumjodid unter verwendung van Jod-
Starke als indicator Z. Anal. Chem. 249 (6): 366
(1970).

Webb, J.L. ‘‘Enzyme and metabolic inhibitors."’ Vol.
IL. Acad. Press, New York (1966).

Weed, L.A., and Ecker, E.E. **Phenylmercuric com-
pounds.”* Their action on animals and their pre-
servative values.”* J. Inf. Dis. 52:354 (1933).

Wei, et al. “The fatal dose of methylmercury in man.””
J. Amer. Med. Assoc. 216 (8): 1347 (1971).

Weiner, I.M, Garlid. K., Sapir, D., and Mudge, G.H.
“The effect of dimercaprol on the renal excretion
of mercurials."* J. Pharmacol. exp. Ther. 127: 325
(1959).

Weiner, I.M., Levy, R.I., and Mudge. H. ‘‘Studies on
mercurial diuresis; renal excretion, acid stability
and structure-activity relationships of organic
mercurials."’ J. Pharmacol. Exp. Ther. 138: 96
(1962).

Weir, P.A.. and Hine, C.H. ‘Effects of various metals
on behavior of conditioned goldfish." Arch. of
Environ. Health 20 (1): 45 (1970).

Weissman, N., Schoenbach, E.B., and Armistead,
E.B. “The determination of sulfhydryl! groups in
serum.” J. Biol. Chem. 187: 153 (1950).

Wessel, W., Georgsson, G., and Sefscheider, I. ‘*E-
lektronemikroskopische untersuchungen uber
weg and wirking hochdosierten sublimats nach
injektion in die arteria renalis."" Virchiows Arch.
Abt. B. Zellpath 3(1): 88 (1969).

West, J.M. ‘‘Mercury."’ in U.S. Bureau of Mines
Minerals Handbook. (1968).

Westerhagen, B.V. ‘“‘Innenohrveranderungen am
meerschweinchen nach chronischer quecksilverv-
ergiftung."" Arch. Klin. Exp. Ohr. Nas. -u.
Kehik. Heilk. 193 (1): 70 (1969).

Westermark. T. ‘*Kvicksilver hos vattenlevande or-
ganismer." In Kvicksilverfragan i sverige."
Stockholm. p. 25 (1965).

Westermark. T., Berg. W.. Johnels, A., Sjostrand, B.,
and Norlindk, T. “‘Orienterande kvickselver anal-
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Anslag. 4296, Royal Inst. of Tech., Stockholm.
(1966).

117


VII. Ornamental Plants

1. Bulbs and Corms
A. Mercury compounds

(1) Cyano (methylmercuric) guanidine:
{Ref. I-C-46-00] For root, stem and bulb
rots: 5.0 ppm solution. Soak.

(2) Mercurous chloride: (alone or with
mercuric chloride) [Ref. I-M-0500.01] Gladi-
olus corms only. 0.9 Ib/5 gal. Dip.

(3) N-Methylmercuri-1, 2, 3, 6-tetrahy-
dro-3, 6-endomethano-3, 4, 5, 6, 7, 7-te-
trachlorophthalimide: [Ref. I-M-15-00.01]
Gladiolus corms only: 1 pt of 10.0% formu-
lation/50 gal. Soak.

(4) Phenylmercuric acetate: [Ref. I-P-
08-00.03] Bulbs: 2.0 fl. oz of 10% formula-
tion/2 gal. Soil soak.

(5) Phenylmercuric triethanol ammon-
ium lactate: [Ref. I-P-17-00.02] 117 to 750
ppm dip.

(6) Sodium ethylmercuri thiosalicylate:
(Ref. I-S-11-00.01] For bulbs and corms: 2 to
3 pt of 12% solution/100 gal. Soak.

B. Substitute compounds

(1) Copper chloride: [Ref. I-C-26-50.01]
Household use: For Fusarium rot only 1
tbs/gal/12 sq ft of soil. Minimal effective-
ness.

(2) p-(Dimethylamino) — benzenediazo
sodium sulfonate: [Ref. I-D-14-00.02] 1.25 to
2.8 02/50 gal/400 sq ft, or use 0.5 pt above
solution/each 6-inch pot.

(3) Methyl isothiocyanate: (Ref. I-M-
07-00.01] 25 to 50 gal/acre.

(4) Sodium o-phenylphenate: [Ref. 1-S-
16-00.07] Bulbs, Corms - rots: 514 ppm. sol-
ution as tetrahydrate. Soak.

(5) 2-(4-thiazolyl) benzimidazole (Thia-
bendazole): (Ref. I-T-09-00.01]: Bulbs,
Corms-Fusarium rot: 1080 ppm. Soak.

(6) Thiram: [Ref. I-T-10-00.08] Bulbs,
Corms- decays. Dust with 4.0 to 12.0% for-
mulation,

C. Comparative effectiveness and impact

(1) Effectiveness of substitute com-
pounds ranges from low to comparable to
mercury compounds.

(2) Impact of withdrawal of mercury
for these uses will be slight on manufacturer
but much more costly to florist and nursery-
man.

2. Cuttings
A. Mercury compounds

(1) Cyano (methylmercuric) guanidine:
[Ref. I-C-46-00.02] 2.5 ppm solution. Dip.
Soil-borne diseases.

(2) Methylmercury hydroxide: [Ref. I-
M-18-00.01] Carnation cuttings only: 2.2
ppm. Dip.

B. Substitute compounds

(1) 8-Quinolinol benzoate: [Ref. I-Q-01-
00.01] 250 to 500 ppm solution. Soak soil.
Damping-off.

(2) 8-Quinolinol sulfate: [Ref. I-Q-03-
00.01] 180 to 260 ppm solution. Dip cuttings
or soak soil. Soil-borne diseases.

(3) Thiram: [Ref. I-T-10-00.04] 15,000
ppm dust as dip for hardwoods, or 3 oz of
15% formulation/pt as softwood dip.

C. Comparative effectiveness and impact

(1) Mercury is more effective than the
substitute* compounds against a broader
range of pathogens and at lower dosages and
lower costs.

(2) Other, now unregistered products,
are available or will soon be available with
good effectiveness for these uses but at
much higher cost.

(3) The impact of withdrawal of mercu-
ry for treating cuttings will be negligible on
the manufacturer but severe on the nursery-

17


MERCURIAL PESTICIDES,

MAN, AND THE
ENVIRONMENT

ENVIRONMENTAL FROTECTION AGENCY
1971


Stanley. W.. et al. “Measurement of atmospheric lev-
els of pesticides."’ Environmental Sci. Technol.

55); 430 (1971).

Steinhausen, M., Eisenbach, J.M.. and Helmstadter,
V. “Concentrations of Lissamine Green in proxi-
ma} tubules and antidiuretic and mercury poi-
soned rats and permeability of these tubules.”*
Pfltigers Arch. 311(1): (1969).

Steinwall, O., and Olsson, Y. “Impairment of the
, blood-brain barrier in mercury poisoning.’ Acta.
Neurol. Scandinav. 45: 351 (1969).

Stejskol, J. ‘Acute renal insufficiency in intoxicants
with mercury compounds. JI} Pathological find-
ings."* Acta Medic. Scandinav. 117: 75.1965).

Stewart. D.K.R., and Ross, R.G. “‘Note on Mercury
fesidues in potatoes.”’ Can. J. Plant Sci. 42: 370
(1962).

Stock. A., and Cucel F. “Die verbreitung des queck-
,Silbers."* Naturwiss. 22: 390 (1934).

Stock, A. ‘Der quecksilbergehalt des menschlichen
jorganismus."* Z. Biochem. 304: 73 (1940).

Stone, H.M. “tA note on the mercury content of ap-

;Ples treated with phenylmercury dimethyl dithio-
carbamate."’ New Zealand J. Agr. Res. 7: 439
+ (1964).
Stone, H.M.. and Clark, P.J. ‘‘Mercury content of
» tomatoes.’’ New Zealand J. Sci. 1:373 (1958).
Stone. H.M., Clark, P.J., and Jacks, H. ‘‘Mercury
+. content of apples.” New Zealand J. Sci. Tech-
nol.. B 38: 843 (1957).

Stone. H.M., and Jacks, H. ‘Mercury residues on

‘tomatoes."’ New Zealand J. Sci. Technol. B 35:
301 (1954).

Storrs. B.. et al. “Organic mercury poisoning Ala-
mogordo, New Mexico.”” Morbidity and Mortali-
ty 19 (3): 25 (1970).

Strickland, A.H. ‘Some estimates of insecticide and
fungicide usage in agriculture and horticulture in
England and Wales. 1960-64."’ J. Applied Ecol. 3:
3 (1966).

Suciu, I., and Morenca E., “The effect of treatment
b TA in acute intoxication by mercury va-
pour."’ Arch. Mal. Prof. 29: 11-2 (41) (1968).

Sumino, K. ‘Analysis of organic mercury compounds
by gas chromatography. Part I. Aanalytical and
exttaction method of organic mercury com-
pounds.”’ Kobe J. Med. Sci. 14 (2): 115 (1968).

Sumino, K. “Analysis of organic mercury compounds
by gas chromatography. Part II]. Determination of
organic mercury compounds in various samples."’
Kobe J. Med. Sci. 14 (2): 131 (1968).

Sumner, J.B., and Myrback, K “Ober schwermetall

' _inaktiverung hockgereinigter urease.”’, Hoppe-
Seyl. 7: 189 (1930).

Sunderman, F.W., Hawthorne, M.F., and .Baker,

G.L. “Delayed sensitivity of the skin to phenyl-

U.S, GOVERNMENT PRINTING UFFICE:1973 514-154/212 1-3

mercuric acetate."” AMA Arch. Indust. Health,
13: 574 (1956).

Surtskin, A., and Yagi, K. ‘‘Distribution in renal cell
fractions of sulfhydryl groups in rats on normal
and sucrose diets and its relation to renal mercury
distribution after mercuric chloride infection.””
Amer. J. Physiol. 192: 405 (1958).

Suzuki, T. ‘Neurological symptoms from concentra-
tion of mercury in the brain in “Chemical
Fallout."’ Miller, M.W., and Berg, G.G., eds.
C.C. Thomas Publishers. Springfield, Ill. (1969).

Suzuki. T. ‘‘Advice of the International Committee on
the maximum allowable concentration of mercury
and its compounds.” Japan J. Ind. Health, 11 (2):
80 (1969).

Suzuki, T., Furukawa, K., and Tonomura, K. ‘*Stud-
ies on the removal of inorganic mercurial com-
pounds in waste by the cellreused method of mer-
cury resistant bacterium.”’ J. Fermant. Technol.
46 (12): 1048 (1968).

Suzuki, T., Keitaro, N., Kunio, K. ‘Urinary excre-
tion of mercury in workers engaged in electrolysis
of salt water in a chemical plant."’ Shikoku. Acta.
Med. 23 (2): 32 (1967).

Suzuki, T., Matsumoto, N., Miuama, R., and Katsun-
uma, H. ‘*Placental transfer of mercuric chloride,
phenylmercury acetate and methylmercury ace-
tate in mice."’ Ind. Health 5: 148 (1967). «

Suzuki, T.; Miyama, T., and Katsunuma, H. ‘‘Bodily
distribution of mercury in mice after subcuta-
neous administration of methyl-, ethyl- and pro-
pyl-mercuric acetate. Japan J. Exptl. Med., 33:
277 (1963).

Suzuki, T.. Miyama, T., and Katsunuma, H. ‘‘Com-
parative study of bodily distribution of mercury in
mice after subcutaneous administration of propyl,
cutyl- and amylmercury acetate."’ Japan J. Exptl.
Med. 34: 211 (1964).

Suzuki, T., Miyama, T., and Katsunuma, H. “Affinity
of mercury to the thyroid.’’ Ind. Health (Kawo-
saki, Japan) 4: 69 (1966).

Swensson, A. ‘Investigations on the toxicity of some
organic mercury compounds which are used as
seed disinfectants.’’ Acta Med. Scan., 143:365
(1952).

Swensson, A. ‘Comparative of toxicity of various
organic compounds.’’ Japan Med. Assoc. J., 61,
1056 (1969).

Swensson, A. “Investigations on the toxic affects of
different mercury compounds on young, white
leghorn cocks."* Poultry Sci. 48: 1567 (1969).

Swensson, A., Lundgren, K.D., and Lindstrom, O.
“Retention of various mercury compounds after
subacute administration.” Arch. Indust. Health
20: 467 (1959).

Swensson, A., Lundgren, K.D., and Lindstrom, O.
“Distribution and excretion of mercury com-

113


acetate as it does with mercuric chloride.
While the placenta takes up a large amount
of mercury, only traces are demonstrable in
the fetus. After 8 to 16 days, however, the
yolk sac epithelium and the fetal membranes
show a greater amount than the placenta.

The placenta does not constitute a barrier to
mercury after the administration of methyl-
mercuric dicyandiamide. In the fetus, the
concentration equals that in the mother, and
the distribution differs only in that there
appears to be more mercury in the fetal skin.

TV.C. Metabolism and Excretion

Inorganic mercury and phenylmercury com-
pounds may be slowly metabolized in the
liver: and kidneys, while alkyl and alkoxy-
alkylmercury compounds are relatively sta-
ble iff the body. Ulfvarson (1962) studied the
distribution and excretion of mercuric ni-
trate, phenylmercuric hydroxide, methoxy-
ethylmercuric hydroxide, methylmercuric
hydroxide, and methylmercuric dicyandia-
mide after subacute, subcutaneous adminis-
tration to rats. He found that a simple distri-
bution equilibrium between different organs
existed for the alkyl and alkoxyalkyl-
mercury compounds. This was not the case
for mercuric nitrate or phenylmercuric hy-
droxide which were continuously translocat-
ed toward the kidneys. There is no reason to
believe such a gradual accumulation should
occur with stable substances which are able
to pass permeable membranes. It is very
likely that this translocation is connected
with a chemical change of the compounds,
which results in a gradual change of the par-
tition coefficients. The chemical reactions to
the final product must also be rather slow,
since otherwise the new derivatives would
immediately distribute in the final way.
Ulfvarson estimated the half-life of the
methylmercury salts as between 15 and 20
days and the methoxyethylmercury hydrox-
ide as between 4 and 10 days. Since mercu-
ric nitrate and phenylmercuric hydroxide

60

were unstable in the body, the estimation of
their half-life was more difficult. The excre-
tion data indicate a half-life of between 4
and 10 days in the beginning of the experi-
ment.

Berlin (1963) studied the renal uptake, ex-
cretion, and retention of mercury in rabbits
during an infusion of phenylmercury acetate
or methylmercuric dicyandiamide. The renal
excretion did not exceed 10% of the amount
of mercury in the blood passing through the
kidneys in the case of either compound.
There was no correlation between the
amount of mercury accumulated in the kid-
neys and the urinary excretion of mercury,
although there was a correlation between the
urinary excretion of mercury and the blood
concentration. In the case of phenylmercu-
ric acetate, a small percentage of the infused
mercury was excreted in the urine while
about 30% was accumulated in the kidneys.
After infusion with methylmercuric dicyan-
diamide, the urinary excretion of mercury
did not exceed a few parts per thousand of
the infused dose and less than 10% accumu-
lated in the kidneys.

Miller, et al. (1960, 1961) administered phen-
ylmercuric acetate and ethylmercuric chlo-
ride intravenously, intramuscularly, and oral-
ly to chicks, rats, and dogs. Phenylmercuric
acetate appeared to be absorbed unchanged,
regardless of the route of administration. In
rats, slightly over half of the urinary mercu-
ry was in a form other than phenylmercuric
acetate. Metabolism was fairly rapid and
occurred mainly in the liver and kidney, with
accumulation of mercury in these organs.
With dogs, a greater proportion of the uri-
nary mercury was not present as phenylmer-
cury. Phenylmercuric acetate was detecta-
ble only for 96 hours. Less than 10% of the
initial dose was excreted unchanged in the
urine. In contrast, when ethylmercuric
chloride was given to chicks and rats orally,
the intact ethylmercury was detectable in
the liver and kidneys for 21 days. The excre-


Table 1. Toxicity of Various Compounds of Mercury*

. Route of Toxicity
Compound Animal Administration mg/kg

Inorganic
Mercuric chloride Rat oral 37 (LD,5)

” ” Mouse sc 230¢+""

” ” Mouse iv 716"

” ” Rabbit sc 10 (LD)
Alkylmercury
Ethylmercuric chioride Mouse ip 16 (LD,.)
Ethylmercuric dicyandiamide Mouse oral go”
Ethylmercuric phosphate Rat oral 30”
Ethylmercuric thioglycolate Rat ip 20”
Ethylmercuric thioglycolate Rabbit iv 20 (MLD)
Ethylmercuric toluenesulfonate Mouse ip 28 (LDgo)
Isopropyimercuric hydroxide Mouse ip 2”
Methylmercuric chloride Rabbit iv 15 (LD)
Methylmercuric chloride Mouse ip 20 (LD,»)
Methylmercuric dicyandiamide Rat oral 3200¢«"
Methylmercuric dicyandiamide Mouse ip 200”
Methyimercuric dimercaptopropanol Mouse ip 22 (PLD)
Methylmercuric hydroxide Mouse ip 17 (LDso)
Methylmercuric propanediolmercaptide Mouse ip 20¢~”
Arylmercury
Phenylmerouric acetate Mouse ip 13 (LD,y)
Phenylmercuric catecholate Mouse ip 50-100 (LD,,)
Phenylmercuric dinaphthylmethane-disulfonate Mouse ip 25 (LD5o)
Phenylmercuric dinaphthylmethane-disulfonate Mouse oral 7 ”
Phenylmercuric nitrate Mouse iv 270”
Alkoxyalkyl
Methoxyethylmercuric acetate Rat oral 16 (LD,,)
Methoxyethylmercuric silicate Mouse ip so.”

* Adapted from Swensson and Ulfvarson (1963) and Spector (1955)

Suzuki (1969) administered methylmercuric
acetate labeled with 203Hg dissolved in dis-
tilled water subcutaneously to mice daily for
10 successive days. The daily dose was ei-
ther 50 or 100 # g/3Hg/mouse. During the
course of the experiment, the mercury con-
centrations of the various organs and tissues
did not reach saturation. The concentrations
of mercury in the blood was constantly high-
er than that in the brain in the course of ad-
ministration and for a short period after it,
but the decrease of mercury concentration
in the blood was faster than that in the brain.
The biological half-life of mercury in the
brain was calculated to be 7.2 and 6.2 days

72

respectively and that in the blood 4.2 and 4.1
days respectively for the 50 and 100 u g Hg/
mouse.

Sebe, et al., (1962) studied the toxicity of a
series of alkylmercury compounds. Com-
pounds of alkylmercury containing R-Hg or
R-Hg-S with the methyl,’ ethyl, or n-propyl
chain administered orally to rats were toxic
to the central nervous system and induced
paralysis of the legs. Iso-propyl compounds
and other alkylmercury ¢ompounds with 4
or 5 carbon atoms were shown not to cause
these injuries.


(2) Substitute compounds

(a) Sodium pentachlorophenate
(79%): [Ref. Reg. No. 464-299] 0.1% to 0.2%
product by weight of particular substrate.

(b) 1-(3-chloroallyl)-3, 5, 7-triaza-!-
azoniaadamatane chloride (90%): [Ref. Reg.
No. 464-327]

(aa.) Aqueous paint systems: 0.1%
to 0.2% product by weight of formulation.

(bb.) Paint components: 0.05% to
0.15% product by weight of media.

(c) Sodium 2, 4, 5-trichlorophenate
(85%): [Ref. Reg. No. 464-131] For preser-
vation of polyvinyl acetate emulsions:0.4%
product by weight of media.

(d) Sodium o-phenylphenate: [Ref.
Reg. No. 464-78] Preservation of carbohy-
drate thickener solutions: 0.05% to 0.2%
product by weight of media.

(e.) 50:50 mixture o-phenylphenol
and Pentachlorophenol: (Ref. Reg. No. 464-
70 and 464-72]

0.5% of mixture based on weight of wet
formulation for preservation of protein col-
loids.

(f) Sodium 2-pyridinethiol 1-oxide
(2%): Ref. Reg. No. 1258-846] Preservation
of acrylic latex paint, 0.25% product by
weight of formulation.

(g) 2-(Thiocyanomethylthio) benzo-
thiazole (32%) and 2-Hydroxypropyl metha-
nethiosulfonate (28%): [Ref. Reg. No. 1448-
27)

Alkyl-modified emulsion paint preservative:
0.3% to 1.0% product by weight of formula-
tion.

(h) Alkyl (50%C >, 30%C 4. 17%Cy.
3%C,g) dimethyl ethylbenzyl ammonium
cyclohexylsulfamate (80%): [Ref. Reg. No.
1839-36]

(aa.) Latex paint preservative:
0.1% to 0.2% product by weight of paint.

(bb.) Carbohydrate and protein
colloid preservative: up to 0.1% product by
weight of formulation.

(i) Dehydroabjetylamine pentachlor-
phenate (50%): [Ref. Reg. No. 2829-59]
Water-based paint preservative: 0.35%

product based on finished weight of formula-
tion.

(j) Alkyl (5% caprylyl, 56% lauryl,
18% myristyl, 7% palmityl, 5% stearyl, 2%
linoleyl) hydrochlorides (25%): [Ref. Reg.
No. 8489-13] Preservation of water-contain-
ing and emulsion-type adhesives, Paints and
their components: 0.15% to 0.3% product
based on total weight of composition.

(k) 1, 2-benzisothiazolin-3-one
(23%): [Ref. Reg. No. 10182-1] Preservation
of water-based paints, emulsion paints and
components: {0.15% product based on total
weight of paint.

(3) Comparative effectiveness and im-
pact :

(a) Mercury compounds can cause
“browning’’ of certain paint formulations,
substitute compounds much less so.

(b) Some substitute compounds im-
part objectionable odor to finished paint
film.

(c) Substitute compounds appear to
be adequate.

(d) Impact on industry expected to
be negligible, price of end-product to con-
sumer expected to rise.

C. Latex vinyl! paint finish on asbestos ceil-
ing tile (bacteriostatic and self-sanitizing
against bacteria)

(1) Mercury compounds

(a) Phenylmercuric acetate (0.0034%
to 0.004% by weight of total product): [Ref.
Reg. Nos. 7816-3, 8700-2] Product is compo-
nent of tile vinyl latex paint applied at rate of
3.13 gal paint per 100 sq ft. of ceiling tiles or
panels, equal to 0.02 Ib phenylmercuric ace-
tate per 1000 sq ft.

(b) Phenylmercuric propionate

(0.0013% to 0.005% by weight of total tile):
[Ref. Reg. Nos. 7850-11, et al]
Product is component of vinyl latex paint
applied to asbestos ceiling tile. Bears bacter-
iostatic (bacterial growth inhibiting) and self
-sanitizing (reduction of bacterial numbers)’
claims; used primarily in hospitals and nurs-
ing homes.


the ionized ligands on the cell’s outer sur-
face. There is strong evidence for the exist-
ence of three types of metal-binding ligands
on the surface of the cell, namely sulfhy-
dryl, phosphoryl, and carboxyl groups. Ev-
idence indicates that ribonucleic acid is the
source of the phosphoryl! groups on the cell
membrane. The sulfhydryl group is the prin-
cipal binding site for mercury. Metal interac-
tions with SH-groups lead to a generalized
breakdown of the permeability of the barrier
of the cell (Passow, et al., 1961).

Several types of enzymes are located on the
cell’s outer surface. These include: enzymes
that digest external substrates (such as in-
vertase and phosphatases), enzymes con-
cerned in active transport phenomena, and
enzymes involved in membrane synthesis.
These enzymes are probably found in all
cells and have been verified in red blood
cells. Because of their location, the enzymes
of the cell surface are particularly suscepti-
ble to heavy metals.

Some sugars enter cells slowly by simple
diffusion. Certain other sugars enter quite
rapidly by a special mechanism. Evidence
indicates that the entry mechanism involves
a definite chemical specificity, that pairs of
sugars compete with each other, that the
kinetics of entry follow mass-law behavior,
and that the entry is susceptible to traces of
heavy metals.

Mercury often produces an all-or-none re-
sponse in which no effect is observed until a
certain threshold concentration is attained.
The response once elicited is maximal for a
given cell. The curves relating dose and
effect do not represent the parameters of the
chemical reaction of the metal and cellular
receptors, but rather the distribution of
thresholds in the population. A distribution
equation, usually the normal curve, can fit
the data, whereas a mass-law equation will
not. If mercury is added to a suspension of
yeast cells, rapid loss of potassium occurs.

66

The defect in the membrane is not specific
for potassium. It represents a general break-
down of the permeability barrier. The indi-
vidual cells respond in an ‘‘all-or-none’’
fashion. The reason for this is that mercury
is acting on sites maintaining structural in-
tegrity, possibly SH groups in the mem-
brane. No single one of these ligands plays
any measurable functional role. However,
when many of these groups are cross-linked
by reaction with mercury, the stress on the
membrane is sufficient to destroy it as a
permeability barrier. In other words, if
groups of ligands acting in unison are essen-
tial for a particular function, all-or-none re-
sponses may occur (Passow, et al., 1961).

Erythrocytes of man and rodents are readily
permeable to glycerol. Entry of glycerol into
the cells is prevented by traces of mercury.
Mercury is probably temporarily fixed to fi-
gands in the membrane that control glycerol
permeability. Subsequently, it moves into
the interior of the cell and combines with the
many complexing substances. As long as
some mercury is bound to the membrane,
inhibition of glycerol takes place. The inhibi-
tion disappears as soon as all of the mercury
has passed through the membrane. At very
high mercury concentrations, the complex-
ing ligands of the cell interior become satu-
rated. The excess mercury remains attached
to the cell membrane and a permanent re-
duction of glycerol permeability is produced
(Passow, et al., 1961). .

Mercury inhibits the uptake of glucose by
the rat diaphragm. The inhibition reaches a
concentration-dependent maximal value in
less than 20 minutes. After a lag of over 30
minutes, a second effect gradually develops:
respiration becomes progressively inhibited,
provided relatively high concentrations of
mercury are applied. Upon addition of slow-
ly penetrating complexing agents like BAL
or cysteine, the inhibition of glucose trans-
port can be reversed whereas that of respira-
tion cannot. The respiration of muscle ho-


ve

VU. 8. Turf Disease Control—Coatinued

é
s > $ y e < y
é £ é é gf / &e/ § é
é < $ 9 = &y / = é
se sg g ¥ & o F
Compounds ‘ounces actual per 1000 square feet
(19) 2-(4-Thiazoly!)
benzimidazole 6-12 6-12 6 -12
{Ref. 1-T-09-00.02]
(20) Thiram 19 to 2.0 to 19 to 2.25 to 4.5 to
{Ref. I-T-10-00.04] 45 3.25 45 3.38 6.0
(21) Zinc ion-maneb
complex 3.2 to 3.2 to 3.2 to 3.2 to 64 4.8 to
(Ref. 1-2-04-00.08} 64 64 64 64 64
(22) Zineb 1s 1.0 to
{Ref. 1-2-10-00.12} 15

*Cadmium resistant stains of this pathogen are common,


seury.’”? J. Marine Biol. Assoc. U. K. 35: 531
» (1956).

Corner, E.D.S., and Sparrow, B.W. “‘The modes of
, action of toxic agents. II. Factors influencing the
,.toxicities of mercury compounds to certain crus-

tacea.”” J. Marine Biol. Assoc. U.K. 36: 459
(1957).

Cortivo; L.A., “Weinberg, S.B., Graquinta, B.S.,
Jacobs, M.B. ‘Mercury levels. in normal human
tissue.’’ J. Forensic Sciences, 9501 (1964).

Craig, S. ‘Toxic ions in bivalves."’ J. Amer. Osteo-
pathic Assoc. 66: 1000 (May 1967}.

Cueto, C., Shaw, W.C., Lindsay, D.R., Shapiro,
R.E., Cope, O.B., and Lambour, V.W. ‘tA report
om mercury hazards in the environment.” The
Mecurial Pesticide Registration Review Panel.
U.S. Dept. HEW (January 1971).

Cummings, J.N. ‘‘Poisoning by mercury.” in Heavy
Metals and the Brain. Blackwell Scientific Publi-
cations, Ltd. Oxford 1959.

Cuppage. F.E., Cunningham, N. and Tate, A. ‘‘Nu-
cleic acid synthesis in the regnerating nephron
following injury with mercuric chloride.”” Lab.
Inv. 21 (5): 449 (1969).

Curley, A. “Suggested procedure for the analysis of
Hg and Pb in Blood and urine by atomic absorp-
tion spectrophotometry.’’ Personal Communica-
tion (1970).

Curley, A., Sedlak, V.A. Girling, E.F., Hawk, R.E.,
Barthel, W.F., Pierce, P.E., and: Likosky, W.H.
“Identification of Organic Mercury as Cause of
Poisoning of Humans and Hogs.” Science 172:65
(1971).

Currier, R.D., and Haerer, A.F. “‘Amyotrophic lateral
sclerosis.”* Arch. Environ. Health 17:712 (1968).

Curry. A.S. “Poison detection in human organs.”
Charles C. Thomas, Publisher, Springfield, Ill.
(1963).

Butterworth, T., Streax, L.P. ‘‘Mercurial pigmenta-
tion of nails.”’ Arch. Dermat. 8855 (1963).

Cafruny, E.V., and Gussin, R.Z. ‘Renal tubular ex-
cretion of mercurials in the aglomerular fish Lo-
phius americanus.”’ J. of Pharmacol. and Exptl.
Therap. 155 (1): 181 (1967).

Carpenter, K.E..“‘The lethal action of soluble metallic
salts on fishes.” Brit. J. Exptl. Biol. 4: 378 (1967).

Cassano. G., Piero. L.V., Bernardino, G., and Luigi,
U. “The distribution of inhaled mercury (Hq.
203) vapors in the brain of rats and mice.”’ J. Neu-
ropathol. Exptl. Neurol. 28(2): 308 (1969).

Celeste, A.C., and Shane, C.G. FDA Papers, p. 27
(Nov. 1970).

Cember, H. ‘A model for kinetics of mercury elimina-
tion.” Amer. Ind. Hyg. Assoc. J. 30(4): 367
(1969).

Cember, H.P., Gallagher, and Faulkner, A. ““Distribu-
tion of mercury among blood fractions and serum

proteins." Amer. Ind. Hyg. Assoc. J. 29(3) 223
(1968).

Clarkson, T. ‘Toxicological Aspects.’’ Ann. Occup.
Hyg. 8, p. 73 (1965).

Clarkson, T.W. “Isotope exchange methods in studies
of the biotransformation of organomercurial
compounds in experimental animals.’’ Rep. Univ.
Rochester A.E.P., No. UR-49-958 (1968).

Clarkson, T. W. “Isotope exchange methods in
studies of the biotransformation of organomer-
curial compounds in experimental animals.” In
Chemical Fallout Miller, M.W., and Berg, G.G.,
eds., C.C. Thomas, Publisher, Springfield, Ill.
(1969).

Clarkson, T.W. “Epidemiological and Experimental
aspects of lead and mercury contamination of
food."’ Fd. Cosmet. Toxicol. 9: 229 (1971).

Clarkson, T.W., “Epidemiological and Experimental
aspects of lead and mercury contamination of
food.”’ Fd. Cosmet. Toxicol. 9: 229 (1971).

Clarkson, T.W., and Magos, L. ‘The effect of sodium
maleate on the renal deposition and excretion of
mercury.”* Brit. J. Pharmacol. Chemotherapy, 31:
560 (1967).

Clegg, D.J. ‘‘Embryotoxic effects of contaminants.””
Unpublished paper presented at CF & DD Sym-
posium (June 1970).

Cohen, S.I., and W.J. Shibe. ‘Mercury residues in
certain fruits resulting from the use of phenylmer-
cury fungicides.” Abstr. p. 13A 119th Meeting
Amer. Chem. Soc., Boston, (1951).

Dahhan, S.S., Orfaly, H. ‘‘Electrocardiographic
changes in mercury poisoning.” Amer. J. of Car-
diology 14 (2): 178 (1964).

Dal Cortivo, L.A., Weinberg, S.B., Giaquinta, P., and
Jacobs, M.B. ‘‘Mercury levels in normal human
tissue."’ J. Forensic Sci., 9 (4): 501 (1964).

Dale, F.H. Letter of March 3, 1970 to Harry W. Hays,
USDA. (See North Dakota Press Release, Au-
gust, 1970).

Daniel, J.W., and Gage, J.C. “The metabolism of 2-
methoxy (14C)-ethylmercury chloride."’ Bioch-
em. J., [11(3), 20 (1969).

Das, H.A., van Raaphorst, J.G., Hoede. D., and Zon-
derhuis, J. ‘Determination of mercury in potato
flour." Internat. J. Appl. Rad. Isotopes 17: 252
(1966).

Delaughter, B. ‘Mercury determinations in industrial
plant atmopsheres by atomic absorption spectro-
photometry." Atomic Absorption Newsletter 9
(2): 49 (1970),

Demis, D.J. and Rothstein, A. ‘Relationships of cell
surface to metabolism XII. Effect of mercury and
copper on glucose uptake and respiration of rat
diaphragm.” Amer. J. Physiol. 180 566 (1955).

Dinman. B.D., Evans, E.E., and Linch, A.L. “Organ-
ic mercury.”* Arch. Indust. Health. 18: 248 (1958).

97


XII. Seed Treatments -
Field Crops

A. Mercury compounds:

Phenylmercuric acetate-see tables | through see tables | through 7, attached

7, attached.

‘XII, Seed Treatments

B. Substitute compounds:

1. Barley
9 ¥ fa
& ‘ 3/sx =
ef #s e /¥/8/s8/E8/ 3 3
Sef & § /§/8 fe S/28/ ¥
ss & y g/SP $/8 § v £
_ Poa S/N &
ounces actual per bushel p-p.m.
Black loose smut, 0.019
covered smut to 1200 to
0.038 0.15-2.10]0.18]2.04] 1.5 | 1.6 1600
Damping-off, seed decay, | 1?
seedling blights 0.038 |{1.2-1.9]0.75-2.10} _|2.04 1.6 |0.42-0.53
0.019
Stripe to
0.038
XH. Seed Treatments
2. Cotton
‘’
s . x
Faff x & /s
& 2 a e/ 2
£8) ¢/8/) 8/9 é
‘ff 4 O/ & /8/ F

ounces actual per 100 pounds
0.075 40 | 10
Sore shin to to to
0.338 |13.0-3.5 65 60 | 25
Surface seed-bome | 9978
anthracnose 0.338 14-21
Damping-off, Seed rot | 0.075 09 | 40| 10 [189] 084
and decay, seedling] to to | to | to | to | to
blights 0.338 |}3.0-3.5]2.7-4.0/2.9-5.7/6.5|14-2.1| 9.6 [1.3 | 60] 25 | 3.00] 294

124Thiocyanomethyithio) benzothiazole

2Used as a supplement to suitable standard seed treatments. with PCNB.

3p-(Dimethylamino) benzenediazo sodium sulfonate.

45-ethoxy-3-trichloromethyl-1,2,4-thiadiazole,

SUsed in combination with Captan,

31


chloride. ethylmercuric chloride, and n-bu-
tylmercuric chloride), there was a marked
accumulation of alkylmercury in the blood,
especially in the nonstromal fractions of the
erythocytes. Ethylmercuric chloride gave
lower concentrations in the blood than did n-
butylchloride. In a later study, Takeda
(1968b) found that more than 97% of the
mercury in the blood after the administra-
tion of 7° Hg-labeled ethylmercuric chloride
was in the form of ethylmercury. The ethyl-
mercury residues accumulated in the hemo-
globin, forming a mercaptide linkage with
SH groups of cysteine residues in the hemo-
globin molecules. He attributes the high,
long-lasting accumulation of aklylmercury in
the blood to the high affinity of alkylmercury
for hemoglobin.

Phenylmercuric acetate appears to be ab-
sorbed unchanged. regardless of the route of
administration. The transportation via the
blood appears to be as phenylmercury. The
phenylmercury present in the blood after 48
hours appears to account for the total mer-
cury in the blood (Miller, et al., 1960).

IV.B.2. Brain — The concentrations of mer-
cury found in the brain after administration
of inorganic, aryl, and alkylmercury com-
pounds are lower than the concentrations
found in other organs and tissues. While the
blood-brain barrier is a relative hindrance to
their passage, the alkylmercury compounds
reach a higher concentration in the brain
than do the arylmercury compounds. How-
ever, there is some disagreement in the liter-
ature as to these differences, especially in
the rat. In addition, there are considerable
species differences in mercury levels in the
brain. In the rat, short-chain alkylmercury
compounds reach a higher level in the brain
than do the longer chain compounds.

Swensson, et al., (1959a) administered 203
Hg-iabeled mercuric chloride, mercuric ni-
irate, phenylmercuric acetate, cyano (meth-
ylmercuri) guanidine, and methylmercuric

56

hydroxide to rats in their drinking water at 2
mg Hg per liter for 3 weeks and determined
the distribution of mercury in the various
organs. He found that the inorganic com-
pounds gave a very low mercury content in
the brain: In fact, no mercury could be dem-
onstrated after 1 week exposure and very lit-
tle after 2 or 3 weeks. The animals which
received phenylmercuric acetate had some-
what higher mercury contents in the brain,
and the animals exposed to cyano (methyl-
mercuri) guanidine had much higher levels.
The ratio between blood and brain mercury
contents seemed to be constant for each
substance and indicated a distribution equi-
librium. However, in an earlier study
(1959b) Swensson failed to demonstrate
these differences after a single intravenous
administration of 100 u g 203Hg as mercuric
nitrates, phenylmercuric acetate, or methyl-
mercuric hydroxide.

Friberg (1957) compared the tissue’ distribu-_
tion of mercury in rabbits after the single
subcutaneous administration of 2 mg 2°3Hg
per kg. of body weight as mercuric chloride
or phenylmercuric acetate. Readings were
made after 1, 6, and 40 days. The readings in
the cerebrum, cerebellum and brain stem
were less than 1% of the corresponding renal
levels. He found no significant difference in
the mercury concentration in the brain re-
sulting from the administration of mercuric
chloride or phenylmercuric acetate.

Gage (1964) studied the distribution, metab-
olism and excretion of phenylmercuric ace-
tate and methylmercuric dicyandiamide af-
ter repeated subcutaneous administration of
0.15 mg Hg per rat and after a single 0.5 mg
dose.

More mercury accumulated in the brain with
methylmercuric dicyandiamide than with
phenylmercuric acetate. Gage postulated
that the higher concentration of methylmer-
cury in the brain was due to the sustained
higher concentration in the plasma and not


(3) Phenylmercuric propionate: [Ref. I-
P-15-00.01] Fungistatic disposable bags for
garbage and other wastes: 0.02% by weight.

B. Substitute compounds

(1) Alkyl dimethyl benzyl ammonium
chloride: [Ref. I-A-08-15.02] Fungistatic
surface treatment: 5000 ppm plus 250 ppm
TBTO.

(2) Bis (tributyltin) — sulfosalicylate:
[Ref. I-B-12-00.01] 0.05% by weight or as
required.

(3) 4-Chloro-3, 5-xylenol: [Ref. I-C-21-
00.02] Use as required.

(4) 3,4’, 5-Tribromosalicylanilide: (Ref.
I-T-11-00.02]

(5) Tributyltin linoleate: [Ref. I-T-12-
50.01] 0.43%, more or less as required, by
weight of resin.

(6) Tributyltin monopropylene glycol
maleate: [Ref. I-T-12-60.01]

(a) For floor tile use 0.8% by weight
of plasticizer.

(b) For calendered film use 0.2 to 1.0%
by weight of plasticizer.

C. Comparative effectiveness and impact

(1) Higher concentrations of substitute
compounds at higher costs are needed to
secure adequate protection in place of mer-
cury.

(2) Relative spectrums of microorgan-
ism control not known.

(3) Impact on manufacturer and con-
sumer not known but probably insignificant,
since no replies were received to our De-
cember 3, 1970, Federal Register request for
comments and views.

2. Plastics (polyethylene)

A. Mercury compounds

Phenylmercuric borate: [Ref. I-P-08-10.01}
50 ppm PMB plus 31.25 ppm diisobutyl-
phenoxyethoxyethyl dimethyl benzyl am-

monium chloride by weight of pellets before
molding. Fungistat.

B. Substitute compounds

(1) Captan: [Ref. I-C-10-00.16] 0.44 to
1.74% by weight of stabilizer.

(2) Ziram: [Ref. I-Z-11-00.07] 0.225%
plus 0.0195% of zinc 2-mercaptoben-
zothiazole by weight of resins.

C. Comparative effectiveness and impact

(1) Substitute compounds require dos-
age rates of 85 to 248 times that of mercury
for effective fungal control.

(2) Relative spectrums of microorgan-
ism control are unknown.

(3) Impact on withdrawal of mercury
for this use is unknown but assumed to be
minimal.

3. Plastics (polystyrene)

A. Mercury compounds

Phenylmercuric borate: [Ref. I-P-08-10.01]
50 ppm PMB plus 31.25 ppm diisobutyl-
phenoxyethoxyethyl dimethyl benzyl am-
monium chloride by weight of pellets before
molding. Fungistat.

B. Substitute compounds

Ziram: {Ref. I-Z-11-00.07] 0.255% plus
0.0195% of zinc 2-mercaptobenzothiazole
by weight of resin.

C. Comparative effectiveness and impact

(1) Substitute compound requires dos-
age rate 85 times that of mercury for compa-
rable effectiveness.

(2) Relative spectrums of microorgan-
ism control are unknown.

(3) Impact of withdraw! of mercury use
is unknown but assumed to be minimal.

27


liver, subcellular distribution of the com-
pounds was quite similar. Takeda, et al.,
(1968), administered single subcutaneous
doses of inorganic mercury, phenylmercury,
ethylmercury, and n-butylmercury com-
pounds. With the alkylmercury compounds,
there was a gradual increase in the accumu-
lation of mercury in the kidneys. There was
a difference in the distribution of ethylmercu-
ry and n-butylmercury. With butylmercury,
there was a larger amount of mercury in the
blood than in the muscles. The opposite was
true with ethylmercury.

Friberg, et al. (1957) studied the distribution
of 3Hg-labeled mercuric chloride and
phenylmercuric acetate in rabbits after a
single subcutaneous injection. In the kid-
neys, almost all of the mercury was in the
cortex. The mercury concentrated in the
tubules and not in the glomeruli. Bergstrand,
et al. (1958), administered 20317 g-labeled
mercuric chloride and phenylmercuric ace-
tate subcutaneously to rabbits at a dose of 2
mg per kilogram of body weight. The kid-
neys were studied | and 6 days after injec-
tion. Mercury invariably accumulated in the
cortex and subcortical stratum of the kid-
neys. Much of the activity in the renal cor-
tex was derived from the regions around the
intralobular vein and the neighboring
straight tubules. In the subcortical stratum,
the activity could be traced to the tubular
epithelium between the arciform veins. No
activity was demonstrated in the glomeruli.
In sections taken 6 days after injection of
organic mercury, the activity in the subcorti-
cal stratum was even higher. Whether or not
this is specific for organic mercury could not
be definitely decided.

Organic mercurials reach a higher concen-
tration in the kidneys than do the inorganic
mercurial compounds (Swensson, et al.,
1959a, 1959b). In the kidneys, almost all of
the mercury is found in the cortex. The mer-
cury is concentrated in the tubules and not in
the glomeruli (Friberg, et al., 1957; Berg-

strand, et al., 1958). This localization of mer-
cury in the renal cortex is to be expected,
since this is the basis for the pharmacologi-
cal action of the mercurial diuretics. Two
mechanisms may contribute. In the first
place, organic mercurials are weak acids
which are secreted in the proximal region of
the renal tubule. In the second place, the
hemodynamics of the kidney are favorable
to cortical deposition. The cortex is the first
area of the kidneys with which mercury in
the arterial blood will equilibrate. Moreover,
since mercury is present in the blood as a
nonultrafilterable protein-complex, it will be
retained in the bloodstream during the glom-
erular filtration process. Consequently, the
concentration of the mercurial in the blood-
stream just distal to the glomerulus will be
increased by 20%, depending upon the frac-
tion of plasma filtered. In addition, the dis-
tribution of blood vessels in the medulla is
such as to produce a low effective blood flow
in the region of the loop of Henle and the
distal tubule (Passow, et al., 1961).

With inorganic mercury there is a marked
concentration of mercury in the liver, in the
periportal connective tissue, lymph space,
or in the bile ducts. Organic mercury pro-
duces a more even distribution pattern, ex-
cept for areas of slightly increased density
around the portal vein. There is a higher
concentration of mercury in the red pulp of
the spleen than in the white pulp (Friberg, et
al., 1957).

The placenta apparently constitutes a barrier
to mercury after the administration of mer-
curic chloride. In the 24-hour autoradi-
ograms, it appears strongly darkened; the
visceral yolk sac epithelium adjacent to the
fetus shows only traces of mercury. Locali-
zation apparently corresponds to that of the
maternal organs, as judged from the faint
pictures (Bolin 1963a).

The placenta affords a barrier to mercury
after the administration of phenylmercuric

59


Doudoroff, P. ‘*Water quality requirements of fishes
and effects of toxic substances.” In M. Brown:
The Physiology of Fishes. Acad. Press, New
York p. 403 (1957).

Doudoroff, P., and Katz, M. ‘*Critical review of litera-
ture on the toxicity of industrial wastes and their
components to fish. I]. The metals as salts.’
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Dragitjina, E.A., and Karimov, A.K. ‘‘Clinical effects
in poisoning with granosan.”’ Gig. i Sanit. 21 (4):
31 (1956).

Duggan, R.E. Private communication. (1970).

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Eades, J.F. ‘Pesticides residues in the Irish environ-
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Economic Planning Agency of Japan. ‘‘Establishment
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Edelstam, C., and others. ‘Ecological aspects of the
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50: 14 (1969).

Edwards, G.N. Two cases of poisoning by mercuric
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(1959).

Egan, H., and R. G. Lidzey. ‘‘Phenylmercury salicy-
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Ellis, W.E., and Fang, S.C. ‘‘Elimination, tissue accu-
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Enders, A. and Noetzel, Hr. “‘Spezifische Verande-
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Engleson, G., and Hernar, T. ‘‘Alkylmercury poison-
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Epps. Ernest A. ‘Colorimetric determination of mer-
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Evans, B.S. ‘A new color reagent for lead and its use
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for the determination of mercury in solution.”
Analyst 51: 224 (1926).

Eybyl. V., Sykora, J., and Mertl, F ‘Einfluss von
natriumselenit. natrium tellurit und natriumsulfit
auf retention und verteilung von quicksilber bei
mausen.”’ Arch. Toxikol. 25(3/4): 296 (1969).

Eybyl, V., Sykora, J., and Mertl, F. ‘‘The influence of
sodium sulfite, sodium tellurite and sodium selen-
ite on the retention of zinc, cadmium, and mercu-
ry in organisms.’* Experentia 25 (5): 504 (1969).

98

Farvor, M.A. and Cember, H. ‘‘Difference between In
Vitro and In Vivo distribution of mercury in blood
proteins.”’ J. Occup. Med. 11 (1): 11 (1969).

Fimreite, N. *‘Mercury uses in Canada and their possi-
ble hazards as sources of mercury contamina-
tion.’’ Canadian Wildlife Service, Pesticide Sec-
tion Manuscript Report No. 17: 19 (1969).

Finkel, A.J. ‘Mercury residue blood levels and toler-
ance limits in fish eaters."’ J. Amer. Med. Assoc..
216 (7): 1208 (1971).

Fiori, A. and Giusti, G.V. ‘*Histochemical detection
of thallium.’* Zacchia 5:121 (1969).

Fitsimmons, J.R., and Kozelka, F.L. “Effects of
BAL on tissue distribution and excretion of mer-
cury in acute mercury poisoning.”’ J. Pharmacol.
98:8 (1950).

Fitsimmons. J.R.. and Kozelka, F.L. ‘Effects of
BAL on tissue distribution and excretion of mer-
cury in acute mercury poisoning.”’ J. Pharmacol.
98: 8 (1950).

Fleischer, M., et al. In Mercury in the environ-
ment.’’ Geological Survey professional paper
713, U.S. Dept. of Interior. (1970).

Fitzhugh, O. Nelson, A., Laug, E.P., and Kunze, F.
“Chronic oral toxicities of mercuryphenyl and
mercury salts.” J. Indust. Hyg. Occup. Med. 2:
433 (1950).

Food and Agriculture Organization of the United Na-
tions. Committee on Pesticides in Agriculture.
Evaluation of the toxicity of pesticides residues in
food. FAO Meeting Report. No. PL/1963/13: 172
p (1964).

Foran, T.A. and Epstein, H.S. Brief for Secretary
Clifford M. Hardin, USDA. Nor. Am v. Hardin,
No. 18, 478, p. 34, U.S. Ct. Appeals for Seventh
District.

Ford, D.W., and Burkholder, C.L. ‘Mercury spray
residues—their estimation on apples at harvest
time.” Agri. Chemicals 7:44 (1952).

Forney, R.B., and Harger, R.N. ‘‘Mercury content of
human, tissue from routine autopsy material.””
Federation Proc. 8: 292 (1949).

Fowler, L., Mahan, J.N., and Shepard, H.H. The Pes-
ticide Review, ASCS, USDA (1969).

Freyschuss, S., Lindstrom, O., Lundgren, K.D., and
Swensson, A. ‘*Yrkeshygieniska undersékningar
i sambad med anvandande av organiska kvicksil-
verféreningar inom pappersbrunk och exportsli-
perier."’ Sv. Papperstidn. 61: 568 (1958).

Friberg, L. ‘‘Studies on the accumulation, metabo-
lism, and excretion of inorganic mercury (Hg.203)
after prolonged subcutaneous administration to
rats."’ Acta Pharmacol. et toxicol. 12: 411 (1956).

Friberg. L.T., chairman: Report of the International
Committee: “Maximum allowable concentrations
of mercury compounds.”’ Arch. Environmental
Health, 19: 891 (1969).


pounds for controlling most seed-borne
pathogens and some soil-borne organisms.

(2) The impact of withdrawal of mercu-
ry for these uses will be minimal.

(3) Note: The manufacturer has already
ceased production of this chemical. Regis-
trations are now continued in effect only to
cover merchandise in channels of trade.

PESTICIDE USES OF MERCURY

XIII.

Surfaces (fungistats)

(see also XI. Sanitizers)

1. Fungistats on Commercial, Institutional
and Household Surfaces e.g. [cabinets,
floors, walls, ceilings, garbage cans, lockers,
masonry, tile, refrigerator and other hard
surfaces; blankets, canvas goods, carpeting,
clothing, cubicle curtains, hampers, laundry
bags, leather goods, linens, mattresses, uni-
forms, upholstery and similar porous sur-
faces.]

A. Mercury compounds

20 ppm of Sodium — ethylmercurit-
hiosalicylate plus 4860 ppm alkyl dimethyl
benzyl ammonium chloride, 360 ppm tribu-
tyltin benzoate, 240 ppm tributyltin isopro-
py! succinate, 120 ppm tributyltin linoleate
and 250 ppm isopropyl! alcohol, applied as a
low-pressure bomb spray. [Ref. I-A-08-
25.04]

B. Substitute compounds

(1) Alkyl dimethyl benzyl ammonium
chlorides: [Ref. I-A-08-00.01, I-A-08-15.01,
I-A-08-20.01, I-A-08-25.04, I-A-08-35.01, I-
A-08-45.04, I-A-08-50.01] 200 to 30,000 ppm
alone or in combination with a large number
of other active ingredients as low pressure
bomb sprays or by mopping, wiping or
washing.

(2) Alkyl dimethyl benzyl ammonium
saccharinate: [Ref. I-A-11-00.01]

(a) 400 ppm plus 100 ppm sodium g-
phenylphenate by mop or spray.

(b) 10,000 ppm plus 2500 ppm sodium
o-phenylphenate and 237,000 ppm isopro-
panol by low pressure bomb.

(3) Aklyl dimethyl 3, 4-dichlorobenzyl
ammonium chloride: (Ref. I-A-14-20.01] 700
ppm plus 138 ppm tributyltin benzoate and
isopropanol by mop, sponge. brush or spray.

(4) Alkyl dimethyl ethylbenzyl ammon-
jum cyclohexyl sulfamate: [Ref. I-A-17-
00.01] 3,000 to 3,200 ppm plus 645, 000 to
675,500 ppm ethyl alcohol and 50,000 ppm
propylene glycol by low-pressure bomb
spray.

(5) Ammonium hydroxide-Cy Fatty
acid-Silver Complex: [Ref. I-A-32-00.01] 860
ppm metallic silver equivalent as a low-
pressure bomb spray.

(6) Bis (tributyltin) oxide: [Ref. I-B-09-
00.01] 420 ppm in low-pressure bomb spray.

(7) Calcium hypochlorite: (Ref. I-C-07-
00.01] 7300 ppm by brush or sponge. Note:
Not a substitute for residual properties of
mercury compounds.

(8) Captan: [Ref. I-C-10-00.15] 375 ppm
plus 240,600 ppm isopropanol as low pres-
sure bomb spray.

(9) Chlorine dioxide: [Ref. I-C-13-
60.01] 1000 ppm plus 292,000 ppm ethanol
and 3000 ppm sodium carbonate as low pres-
sure bomb spray. Note: Not a substitute for
residual properties of mercury compounds.

(10) 4-Chloro-3, 5-xylenol: [Ref. I-C-
21-00.01] 3300 ppm as a spray.

(11) Diisobutylphenoxyethoxyethyl
dimethyl benzyl ammonium chloride: [Ref.
T-D-13-00.01] 700 to 2000 ppm plus isopropyl
alcohol or other agents.

(12) 80 percent methyldodecylbenzyl
trimethyl ammonium chloride plus 20%
methyldodecylxylene bis (trimethyl ammon-
ium chloride): [Ref. I-M-09-00.02]

37


the previous century, suggesting that the
mercury contamination of water follows the
general increased industrial activity (Wal-
lace, et al., 1971).

In 1966, Westermark, et al., demonstrated
that part of the mercury content in bird’s
feathérs is metallo-organic. In 1967, Noren
and West66 demonstrated that almost all
mercury present in fish muscle appears in
the form of methylmercury (Johnels and
Westermark, 1969). Methoxyethylmercury
compounds were substituted for alkylmer-
cury compounds in seed-dressing formula-
tions after February 1966, and the relative
amount of dressed seed used for sowing
was also reduced from 80% (prior to 1966) to
12% (1967). These changes apparently had
no deleterious effect on crop yield. In 1966
and 1967, the mercury levels in the feathers
of predatory birds with a terrestrial food
chain abruptly dropped to levels about 50%
above those typical for the previous century
(Wallace, et al., 1971).

VI.C. Canada and the United States — In
1967, a limited study of mercury residues in
U.S. foods was conducted by the Food and
Drug Administration as part of the Pesticide
Total Diet Study. Six food classes were ana-
lyzed by neutron activation analysis, and the
results indicated background level of mercu-
ry in the order of 0.002 to 0.050 ppm. No fur-
ther testing was performed in this country
until 1970. In 1969, following warnings of
significant mercury pollution in the central
provinces, studies were initiated by the
Canadian Wildlife Services to define the sit-
uation. Shortly thereafter, several commer-
cial catches of fish (walleye. northern pike,
bass, and jackfish) taken from Lake Winni-
peg, Cedar Lake, Saskatchewan River, and
Red River in the Province of Manitoba were
detained by the Canadian Federal Depart-
ment of Fisheries and Forestries, because
they contained: mercury residues ranging
from 5 to 10 ppm. As a result of concurrent
testing by Ontario officials, the Canadian

Government publicly embargoed all com-
mercial fish taken from Lake Saint Clair
effective March 23, 1970.

On April 10, 1970, a formal monitoring pro-
gram was initiated by the United States
Food and Drug Administration in all 17 of its
districts. All of the 75 known, chlor-alkali
plants in the United States were visited. Ag-
ricultural run-off and other industrial
sources of pollution were also examined
during the investigation. When the industrial
process was suspected of polluting water,
samples of fish were collected and analyzed
to determine the impact of the contamina-
tion on the environment. Any fish exceeding
the interim guideline level of 0.5 ppm mercu-
ry in commercial channels were recom-
mended for seizure (Mercurial Pesticide
Review Panel Report, 1971).

The majority of the fish analyzed have been
collected from areas where investigations
have shown contamination with mercury
wastes. Of 763 composite samples of fish
examined by the Food and Drug Administra-
tion, 683 samples were below 0.5 ppm mer-
cury, while 124 were above. The highest
mercury residue thus far encountered was a
Lake Onondaga catfish composite which
was found to contain 4.3 ppm. In areas such
as the Rocky Mountains with no known pol-
lution sources, ‘‘background’’ can run as
high as 0.2 ppm mercury but averages less
than 0.1 ppm, depending upon the species
(Mercurial Pesticide Review Panel Report,
1971).

The Review Panel reached the following ten-
tative conclusions on mercury contamina-
tion of the environment:

(1.) Where there are chlor-alkali plants,
there is a great possibility of mercury escap-
ing into the environment. Since fish have a
great propensity for bioconcentration of
mercury, the fish level reflects the degree of
pollution of the water.

81


maternal tissues and may cause fetal neurol-
ogical damage. All of the compounds of
mercury are capable of causing chromoso-
mal aberrations. This effect is more marked
with the alkyl and aryl compounds than with
inorganic mercury.

A complicating feature of the mercury prob-
lem was the discovery that mercury in river
and lake bottoms can be converted into
methylmercury. This biotransformation is
responsible for the contamination of
aqueous systems and their associated biota.
Indirectly, this process may also play,
through the evaporation of dimethylmercu-
ry, a role in the atmospheric transport of
mercury. In addition, microbial systems in
the interstinal flora of birds and mammals

may be involved in the methylation of mer-
cury.

Because of its volatility, mercury normally
circulates in the environment between the
soil and water and the atmosphere. Man’s
use of mercury has added to this natural cir-
culation by increasing the concentration in
the atmosphere over the years through the
burning of fossil fuels and the smelting of
ores. Man has also produced areas of abnor-
mally high concentrations of mercury
through industrial wastes and the use of
mercurial pesticides. The pollution of rivers
and lakes with mercury from the effluents of
industrial plants has been abated. However,
the pesticidal use of mercury remains as the
largest intentional dissipative or nonrecycla-
ble use of mercury in the United States.


INTRODUCTION

The realization of the toxicity of mercury
dates back as far as recorded history. Hip-
pocrates (460-377 B.C.), Pliney the Elder
(23-79 A.D.), Galen (131-200 A.D.), Avicen-
na (980-1037 A.D.), and Paracelsus (1493-
1541 A.D.) have all written on the toxic ef-
fects of mercury (Battigelli, 1960; Goldwa-
ter, 1957). The first mention of mercury as
an industrial hazard appeared in the middle
of the 19th century in connection with hat-
ters employing mercury nitrate in the felting
process. In spite of the early realization of
the hazard involved with this use of mercu-
ry, it continued until recent times. In 1941,
the U.S. Public Health Service published the
results of a field study showing that more
than 10% of the workers examined were
suffering from chronic mercury poisoning
(Neal, 1941). The expression ‘‘mad as a hat-
ter’’ is believed to have originated as a result
of one of the toxic manifestations of mercu-
ry poisoning. The hazard in this industry as
well as in many others, e.g., mining, manu-
facture of thermometers and barometers,
testing departments, and laboratories has
been either eliminated or greatly reduced.

Although progress has been made in in-
dustrial safety, ‘‘epidemic’’ outbreaks of
chronic mercury poisonings still occur. This
is due, in part, to the extensive increase in
the industrial and agricultural uses of mercu-
ry in recent decades. In 1958, Benning de-
scribed mercury intoxication in more than 60
workers in an Ohio plant employed in the
manufacture of carbon brushes. In another
episode, inhalation of mercury vapors from
a mercury-containing paint was implicated
in an outbreak of neuromyasthenia in a Ken-
tucky electronics plant (Miller et a/., 1967).

Reports of poisonings resulting from the use
of alkylmercury seed disinfectants soon fol-
lowed their introduction. In 1940 Hunter, et
al described in detail four cases of alkylmer-

cury poisonings resulting from industrial
exposure. Ahlmark (1948) described five
cases of poisoning (two fatal) of workmen
involved in manufacture and handling of
methylmercury compounds. In 1949, Lund-
gren and Swensson reported eight cases of
occupational poisoning by alkylmercury
compounds. Between 1956 and 1960, there
were over three hundred patients suffering
from mercuric poisoning admitted to hospi-
tals in Mosul and Baghdad, Iraq. They had
consumed wheat treated with ethylmercury
toluene sulfonanilide (Jalili and Abbasi,
1961). Similar episodes occurred in Pakistan
(Haq, 1963) and Guatemala, (Ordones, et al,
1966). Numerous other cases of poisoning
with alkylmercury compounds have been
reported in the literature and by the press.
The most recent and the most publicized in
this country occurred in Alamogordo, N.
M., in 1969, when three members of one
family were poisoned from eating pork from
hogs which had been fed grain treated with
an alkylmercury pesticide.

During the past 20 years, there have been
two occurrences of human mercury poison-
ing in Japan resulting from the eating of con-
taminated fish. The first incident occurred in
Minamata in 1953. The outbreak reached
almost epidemic proportions. The source of
contamination was traced to a vinylchloride
and acetaldehyde plant which discharged
large quantities of methylmercury into Mini-
mata Bay. From 1953 to 1970, 121 persons
were reported poisoned after having eaten
fish and shellfish caught in Minimata Bay.

There were 46 deaths recorded. It was some
time before Japanese medical authorities
recognized and documented the similar clini-
cal disorder of a large number of people in
the Minamata area. A second incident oc-
curred in the riverside villages of the Agano
River in Niigata prefecture where 47 cases
and six deaths were observed through 1970.

iti


ve

XI. Seed Treatments

7. Wheat
© £ 2 2 2 2
s ; & $ = 2 s
= S & g £ < RS
£ OF x 2 = ? a $ Ss =
Sof & /gs/ ¥ £ g é & &/ S$) & é Ss / €
e* § s s S ¢ &
Go
ounces actual per bushel oz. copper/bushel | p.p.m.
Dwarf bunt, Bunt 0.019 || 0.66 0.20 | 0.75 | 0.50 0.47 1200
(stinking smut) to to to to to 1.44 0.125 1.0 1.8 16 to 0.4-0.8 | 1.0-2.0 to
Flag smut, covered smut| 0.038 || 1.20 | 0.53 | 2.10 | 0.75 [ 0.52 1600
0.019
Kernel smudge to
0.038
Seed decay, 0.019 0.66 0.75 0.50 0.47
Seedling blights to to to to 0.125 1.0 16 to
0.038 1.20 2.10 0.75 0.52

' 27.6% Sodium dimethyl dithiocarbamate + 2.4% Sodium 2-mercaptobenzothiazole.

?In combination with PCNB.
> Limited to foundation and registered seed.
“In combination with Captan.


reduction of enzyme activity is dependent
upon the accessibility and on the functional
significance of the various metal-binding
groups. Of primary importance are the inter-
actions with the ligands which are functional
in bond formation with the components of
the enzyme-substrate complex at the active
center of: the enzyme. Other changes are
brought about by metal combination with
groups linked to the active center. The metal
bindings with no functional significance play
an indirect role. By combining with mercu-
ry, they reduce the amount available for
reaction with functional ligands, thereby
affording protective action (Passow, et al.,
1961).

Summer and Myrback (1930) found that
90% inhibition of urease activity resulted
when 50 atoms of mercury were attached to
one molecule of urease: Only 15 atoms of
silver were required to yield 95% inhibition.
It was concluded that a large fraction of the
mercury atoms bound to the enzyme is asso-
ciated with ligands which play no role in ca-
talysis. Thus in urease inhibition by SH-
seeking metals chemical affinities, functional
importance of ligands, diversion to ‘‘insensi-
tive’’ sites, and accessibility of ‘‘sensitive’’
ligands all play a role (Passow, et al., 1961).

Inhibitory effects of heavy metals may also
result from interactions with ligands which
are not directly involved in the active center
of the enzyme. The binding of the mercury
cation to the side-chain residues of the pro-
tein may result in electrostatic charge and a
shift in the ionization constant of the active
center, leading to changes in the catalytic
activity (Klotz, 1959). The inhibitory effect
of relatively high concentrations of Hg++
on chymotrypsin have been attributed to
changes in the polymeric forms of the en-
zyme (Green, Glander, Cunningham, 1952).

A second type of indirect action may be a
consequence of structural changes in the
protein. In the presence of mercury, oxygen

uptake by hemoglobin increases, particular-
ly at low O, pressures (Riggs, 1952). The
author stated that the metal is not attached
to the heme-ring but probably exerts its in-
fluence by changing the structure of the
globin moiety of the hemoglobin molecule.
More recently Resnik demonstrated that the
addition of more than 10 equivalents of mer-
cury per hemoglobin molecule produced
marked changes in the absorption spectra
and the rotary dispersion curves of both
HbO, and metHb. The final product in both
instances was similar to acid-denatured pro-
tein. He postulated that mercuric chloride is
capable of reaction not only with the sulfhy-
dryl groups but also the imidazole residues
of hemoglobin (Resnik, 1964).

Cell membranes contain large quantities of
lipids, mainly phospholipids. It is well
known that very small amounts of heavy
metals produce appreciable changes of sur-
face tension and surface charge of lipid
films. Alterations of these variables may be
expected to lead to marked changes of
permeability and metabolic activities of sur-
face enzymes (Passow, 1961).

IV.D.5. Action on Cells — The cell mem-
brane is the first and most important site of
action of metals. Frequently, almost all of
the metal applied is rapidly absorbed by the
easily accessible ligands of the outer surface
of the membrane. The interior of the cell, on
the other hand, is protected by the mem-
brane as a diffusion barrier and also by the
many inert substances in the cytoplasm that
can react with and divert the metal. Many of
the metal-binding ligands are essential to the
maintenance of the membrane as a diffusion
barrier or are necessary for the functioning
of the enzyme of the membrane. The general
pharmacology of mercury, therefore, is
largely concerned with pathological changes
of functions associated with the cell mem-
brane (Rothstein, 1959).

Studies with yeast cells have revealed much
about the interaction of heavy metals with

65


days. Using the plasma clot method, the
number of cells from the two groups was
compared with normal for abnormal chromo-
somal patterns. The incidence of unstable
chromosomes characterized as polyploid,
chromatid gap, or fragmented was 19.3% on
day 5; on day 9, this incidence was 16.6%
compared to 3.2% for the control group.

Murakami, et al., (1955) investigated the ter-
atogenic properties of phenylmercuric ace-
tate, an ingredient of a vaginal contraceptive
product, in mice. One-fourth of a vaginal
contraceptive tablet containing phenylmer-
curic acetate was placed in the vaginas of
mice on the 7th day of pregnancy. In another
group of mice, an aqueous solution of the
tablet with the corresponding amount of
phenylmercuric acetate was injected subcu-
taneously on the 8th day of pregnancy. A
control group of mice was also utilized. The
rate of occurrence of abnormalities was
highest in the mice which received phenyl-
mercury vaginally (15.1%) and lowest in the
controls (2.7%). The group receiving phenyl-
mercury subcutaneously was intermediate
between the two (9.1%). Clegg (1970) report-
ed that the administration of a single dose of
14 mg/kg of body weight of methylmercuric
phosphate to pregnant rats on the 10th day
of pregnancy resulted in reduced body
weight of the offspring and an incidence of
31.6% cleft palates.

V.B. Toxicity to Humans

The symptoms resulting from poisoning with
the inorgani¢é mercurials differ in essential
points from those resulting from poisoning
with the organic mercury compounds. The
symptomology of human poisoning with
both types of compounds resembles that
seen in laboratory animals.

V.B.1. Inorganic Mercury Compounds —
Soluble inorganic compounds of mercury
are irritating to the skin and mucous mem-
branes. This effect is marked with mercuric

chloride. Concentrations of 1 to 5% cause
irritation, vesiculation, and corrosion of the
skin and mucous membranes. More dilute
solutions produce irritation to sensitive skin.
Mercuric chloride may be absorbed from the
intact skin and mucous membranes to the
extent of producing symptoms of poisoning
(Bidstrup, 1964).

V.B.1.1. Acute Poisoning — The oral inges-
tion of doses as low as 0.5 g of mercuric
chloride has produced death. The mean le-
thal dose in adults is probably between | and
4g (Gleason, Gosselin, and Hodge, 1963.)

When ionizable mercuric salts are ingested,
necrosis begins immediately in the mouth,
throat, esophagus, and stomach. Within a
few minutes, violent pain, profuse vomiting,
and severe purging is experienced. The pa-
tient may die within a few hours from peri-
pheral vascular collapse secondary to fluid
and electrolyte losses. If the patient survives
this phase, the primary gastroenteritis sub-
sides spontaneously within a few days. A
second phase, developing within 1 to 3 days
after exposure, is characterized by stomati-
tis, membranous colitis, and tubular nephri-
tis. This second phase which is seen even in
noncorrosive preparations of mercury is
independent of the portal of entry, and is
associated with a slow and prolonged excre-
tion of mercury by the salivary glands, the
gastrointestinal mucosa, and the kidneys.
Death in this phase is usually the result of
complete renal failure (Gleason, Gosselin,
and Hodge, 1963). Postmortem examination
shows inflammation and corrosion along the
alimentary canal and severe damage to the
kidneys. The glomeruli as well as the tubules
are involved (Goldwater, 1957).

V.B.1.2.Chronic Poisoning— The most fre-
quent manifestations of chronic inorganic
mercurial poisoning are (1) gingivitis and
stomatitis, often associated with loss of
teeth; (2) tremor, involving the hands and

75


MERCURIAL
PESTICIDES,

MAN, AND THE
ENVIRONMENT

Special Pesticide Review Group
Office of Pesticides Programs

UNITED STATES
ENVIRONMENTAL PROTECTION AGENCY
Washington, D.C. 20460


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Holt, G. ‘‘Mercury residues in wild birds in Norway:
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Hook, O.. Lundgren, K.D., and Swensson, A. “On
alkylmercury poisoning with a description of two
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Hopes, M. ‘‘Phenylmercuric compounds: a review of
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Hordynska, S., Legatowa, B., and Bernstein, I.
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Hordynska, S., Legatowa, B., and Bernstein, I.
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Horwitz, W. ‘‘Official methods of analysis of the As-
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Hosahara, K. ‘Mercury content of deep-sea water.””
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Howard, F.L., and Schlenker, F.S. ‘Magnitude of
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Howell. J. ‘‘Mercury residues in chicken eggs and tis-
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Hughes, W.L. Jr. **An albumin fraction isolated from
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Hughes, W.L. ‘*Protein mercaptides.*’ Cold Spring
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102

Ino, H. School of Medicine, Niigata University,
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(3): 165 (1970).

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(1969). ‘

Irukayama, K. ‘‘Mercury in Minamata district before
and after the suspension of the production of ac-
etaldehyde in Minamata factory.”’ J. Kumamoto
Med. Soc., 43 (11): 946 (1969).

Trukayama, K. ‘Removal of mercury from waste wa-
ter containing mercury compounds of the Mina-
mata factory.”’ J. Kumamoto Med. Soc. 43 (12):
987 (1969).

Irukayama, K. *‘The course of Minamata disease and
the immediate problems.’ The Journal of Public
Health Practice 33 (2): 70 (1969).

Irukayama, K., Kondo, T., and Ushikusa, S. ‘‘Metab-
olism of methylmercury sulfate and’ methylmer-
cury iodine in animals."* Jap. J. Hyg. 21: 231
(1967).

Irukagawa, K.. ef al. ‘Studies on contamination in
Minamata Bay.” Kumamoto Med: J. (Jap. edi-
tion) (supp 1) 31:57 (1957).

Irukayama, K. and others. ‘Studies ‘on the origin of
the causative agent of Minamata disease.’’ I.
Organic mercury compounds in the fish and shell-
fish from Minamata Bay.’ Kumamoto Med. J. 14
(4): 157) (1961).

Irukayama, K. and others. “Studies on the origin of
the causative agent of Minamata disease. II.
Comparison of the mercury compoundi in the
shellfish from Minamata Bay with mercury com-
pounds experimentally accumulated in the control
shellfish."" Kumamoto Med. J. 15 (1): 1 (1962).

Irukayama, K. and others. ‘*Studies on the origi
the causative agent of Minamata disease. III.
Industrial wastes containing mercury compounds
from Minamata factory." Kumamoto Med. J. 15
(2): 57 (1962),

Irukayama. K. ‘‘The pollution of Minamata Bay and
Minamata disease.’ Proceedings of the Third In-
ternational Conference, Munich, Germany, 1966.
Adv. Water Pollution Res. 3: 153 (1967).



MERCURIAL PESTICIDES, MAN,
AND THE ENVIRONMENT

CONTENTS

Page

Introduction
Foreword ...
Recommendations concerning the registrations of mercurial pesticides
Chapter 1. The Pesticide Uses of Mercury ..
Introduction ............06+
Summary and Conclusions .
I. Coatings ...
Il. Fabrics and Textiles
Il. Fibers and Cordage ...
IV. Food, Feed and Tobacco Crops
Vv. Food and Feed Containers
VI. Humans
VII. Ornamental Plants ..
VIII. Paper (mold resistant)
IX. Plastics ..
Xx. Rubber ..
XI. — Sanitizers ..
XII. Seed Treatments- Field Crops .
XIII. Surfaces (fungistats) ..........
XIV. Tanneries (bacteriostats and fungistats)
XV. WOO ons. eeececeeseeeeeeeeteeeeeeteeereseeeeenens
XVI. Dental and Surgical Instruments (disinfection)
XVII. Miscellaneous ................
Chapter 2. Analytical Methods for Mercury ..
Chapter 3. Prevalence of Mercury in the Environmen'
Chapter 4. Pharmacology of Mercury
Chapter 5. Toxicology of Mercury ...
Chapter 6. Ecologic Effects of Mercury Contamination
Chapter 7. The Hazard of Mecurial Pesticide Use
Selected Bibliography



Irving, H.M., Irving, N.H., and Kiwan, A.M. ‘‘Stud-
ies with dithizone XVII. The extraction constants
of. organomercury (II) dethizonates.’? Anal.
Chem. Acta. 45 (3): 477 (1969).

Ishii, Y. ‘‘The determination of mercury in hairs of
normal persons living in Ohita Prefecture and of
cadmium in urine of normal persons living along
the Okudake River in Ohita Prefecture.’ J. Ku-
mamoto Med. Soc. 44 (2): 150 (1970).

Isotov, B.N. “‘Isolation, detection and determination
of ethylmercurichloride in biological materials.”
Farnatsevt Zh (Kiev) 24 (5): 70 (1969). *

Ito, H. ‘‘Pathological studies on Minamata disease
experimental production on Minamata disease in
the cat.”’. Kumamoto Med. J. (Jap. edition) supp.
131: 282 (1957).

Iwasaki, Y., Ijuta, F. “‘A histochemical detection of
organic mercury in tissue - A modified Timms sil-
ver sulfate method.’’ Not Shinker 21 (4): 349
(1969). .

Jackim, E., Hamlin, J.M., and Sonis, S. ‘Effects of
metal poisoning on five liver enzymes in the killi-
fish."’ (Fundulus heteroclitus) J. Fisheries Res.
Board of Can. 27 (2): 383 (1970).

Jacobs. M.B., and Goldwater. L.J. ‘*Ultramicro-
determination of mercury in apples."’ Food Tech-
nol. 15:357 (1960).

Jalili, M.A., and Abbasi, A.H. ‘‘Poisoning by ethyl-
mercury toluene sulphonanilide.’* Brit. J. Indust,
Med. 18: 303 (1961).

Jensen, S. ‘“‘Sources of error and confirmation in the
determination of methylmercury radicals." Fish-
eries Research Board of Canada Translation Se-
ties No. 1394 from Nordisk Hygienisk Tidskrift
50 (2): 85 (1969).

Jensen, S., and Jernelov, A. ‘Biosynthesis of mono-
and dimethylmercury.”” Nature, London 223:
1453 (1969).

Jensen, S., and Jernelév, A. “Biological methylation
of mercury in aquatic organisms."’ Nature, Lon-
don 223 (5207): 753 (1969).

Jensen, S., and Jernelév, A. ‘Biological methylation
of mercury in aquatic organisms.”’ Nature, Lon-
don 223 (5207): 753 (1969).

Jernelév, A. ‘‘Laboratory experiments on the change
of mercury compounds from one into another.”
Fisheries Research Board of Canada Translation
Series No. 1352."’ From Vatten 24 (4): 360 (1968).

Jernelév, A: “*The menace of mercury.’” New Scien-
tist 40 (627); 627 (1968).

Jernelév, A. “Conversion of mercury compounds.”
Chemical Fallout, Miller, M.W., and Berg, G.G.,
eds., C.C. Thomas, Publisher, Springfield, Ill.,
pg. 68 (1969).

Jernelév, A. ‘‘Release of methyl mercury from sedi-
ments with layers containing inorganic mercury at

different depths.’’ Limnology and Oceanography
15 (6): 958 (1970).

Jervis, R.E., Debrun, Mrs. D., Lepage, W., and Tie-
fenbach, Mrs. B. ‘‘Mercury residues in Canadian
foods, fish, wildlife.’’ Summary of Progress, Na-
tional Health Grant Project No. 605-7-510. Tract
mercury in environment meterials for the period
September 1969 - May 1970.

Joensuu, O.I., ‘Fossil fuel as a source of mercury pol-
lution.” Science 172: 1027 (1971).

Johansen, O., and Steinnes, E. ‘‘A simple neutron ac-
tivation method for mercury in biological materi-
al.’ Intern. J. Appl. Rad. Isotopes 20 (11): 751
(1969).

Johnels, A.G., Personal communication; (1970). Cited
in Nelson N. et al., Environ. Res. 4(1): (1971).
Johnels, A.G., Olsson, M., and Westermark, T.
“*Esox lucius and some other organisms as indica-
tors of mercury contamination in Swedish lakes

and rivers.’’ Bull. Off. int. Epiz. 69: 1439 (1968).

Johnels, A.G., and Westermark, T. ‘‘Studier pa kvick-
silverhalten hos nagra organismer i svensk nat-
ur.”’ Viltforskningsradets nordiska konferens.
Foredrag och diskussioner, Statens veterinar
medicinska anstalt, Stockholm, 198 (1967).

Johnels, A.G., and Westermark, T. ‘Mercury con-
tamination in Sweden.”” Chemical Fallout, Miller,
M.W.; and Berg, G.G., eds. C.C. Thomas, Pub-
lisher, Springfield. IN. (1969).

Johnels, A.G., Westermark, T., Berg, W., Perrson,
P.I., and Sjéstraad, B. ‘Pike (Esox lucius L.) and
some other aquatic organisms in Sweden as indi-
cators of mercury contamination in the environ-
ment."* Oikos 18: 323 (1967).

Joint Mercury Residues Panel. ‘‘Determination of
mercury in apples and tomatoes.”* Analyst 86: 608
(1961).

Jones. J., Erichsen, R. “The metals as salts." In Fish
and River Pollution, p. 66 (1964).

Jones, L., and Schwartzman, G. “Determination of
mercury in pink wheat.’’ J. Assoc. Offic. Agr.
Chem. 46; 879 (1963).

Jonasson, I.R.. Boyle. R.W. ‘Geochemistry of mer-
cury.’’ Royal Soc. of Canada Symp.. Mercury in
Man’‘s Environment, Ottawa, February 15-16,
1971.

Jovicic, B. ‘Pertacutaneous intoxication by fungi-
cides based on mercury.”” Ann. Occup. Hyg. II:
305 (1968).

Jozsef, B., Marget, M., Maria, S., and Ferene, N. A
Wofatox-mérgezéz therapiajarol Orvosi Hetilap
110 (5): 251 (1969).

Kahrs, F.R. “Chronic mercurial poisoning in swine.”
Cornel Vet. 58: 67 (1968).

Kamps, L., and Malone, B. ‘Determination of meth-
ylmercury in fish and animal tissues by gas-liquid

103


Vil. 8. Turf Disease Control—Continued

un,
Ping
Ce

Lu,
in,

Compounds

ounces actual per 1000 square feet

do)

Phenylmercuric
monoethanol
ammonium lactate
[Ref. 1-P-12-00.01]

13

13

13

-13 to .26

any

Phenylmercutic
triethanol

ammonium lactate
(Ref. L-P-17-00.01}

AS

1S

AS

AS to .20

. Substitute compounds:

ay

Benomyl
{Ref. I-B-02-00.02]

Q)

Cadmium-calcium-
copper-zinc-chromate
complex

{Ref. -C-01-00.01]

3 -4*

8 -12

())

Cadmium carbonate
[Ref. 1C-02-00.01

23*

4)

Cadmium chloride
[Ref. 1€-03-00.01]

()

Cadmium sebacate
[Ref. 1C-04-00.01]

1.2to24

6)

‘Cadmium succinate
[Ref. I-C-05-00.01]

[)

Captan
{Ref. I-C-10-00.12]

16 — 32

16 — 32

16 — 32

(8)

Chioranil
[Ref. I-C-12-00.03]}

3.2



aquatic ecosystem. While 60 ppb ethylmer-
cury is lethal to marine phytoplankton, as lit-
tle as 0.1 to 0.6 ppb alklymercury introduced
into seawater will produce a measurable in-
hibition of photosynthesis and growth. It
appears that concentrations of mercurial
compounds well below the proposed water-
quality standards of 5 ppb'can have a detri-
mental effect on phytoplankton (Harriss and
White, 1970). The authors also conclude that
the use of organomercurial compounds in
any way that permits their discharge into
natural waters should be stopped as soon as
possible. The long-term effects of mercury
pollution below concentrations of 1 ppb
must be determined to establish adequate
water-quality standards. In another study,
half of the goldfish continuously exposed to
a concentration of 820 ppb mercuric chloride
died within 7 days, yet an exposure for only
2 days to 3 ppb mercuric chloride produced a
measurable impairment in learning behavior
(Weir and Hine, 1970).

VI.E. Mercury in Birds — Stickel, in ‘‘Haz-
ards of Mercury’’ (Nelson, et al., 1971),
gives an excellent account of the effect of
mercury on birds in Sweden.

According to Stickel, birds have been seri-
ously affected by mercury in Sweden. Treat-
ed seed had the most dramatic effect, while
aquatic contamination had less sudden and
dramatic effects. The world-wide ramifica-
tions are just beginning to be known.

The acute toxicity of methylmercury to
birds results from levels about the same as
those toxic for laboratory mammals, around
12 to 20 mg/kg of body weight. Chronic tests
with birds have been carried out largely with
seed operationally dressed with about 15 to
20 ppm methylmercury. These seed killed
pheasants in 29 to 61 days and jackdaws in
26 to 38 days.

Mercury residues in liver-kidney composites
of birds killed experimentally with treated

seed ranged from 30 to 130 ppm for pheas-
ants, 70 to 115 ppm for jackdaws, and 50 to
200 ppm for magpies. Muscle levels in
pheasants ranged from 20 to 45 ppm. Stickel
concludes that kidney-liver residues of 30
ppm or more in birds indicated critical expo-
sure and perhaps death; normal levels, by
contrast, are less than 1 ppm. Using these
criteria in judging wild birds, both those
found dead and those taken alive, more than
half the bird populations of Sweden were
carrying increased levels of mercury and
many birds had died outright. Population
declines occurred in a number of species
(Nelson, et al., 1971).

Stickel reported that Tehning demonstrated
that pheasants could readily eat enough
dressed seed to create the observed tissue
levels of mercury and to cause death. Seed
is often available on the surface, especially
at the turn-around areas at the ends of fields.
The effects of mercury were complicated by
the presence of aldrin and dieldrin in the
seed dressing, and the amount of aldrin and
dieldrin in the birds was not determined. The
use of aldrin or dieldrin is no longer legal in
Sweden.

Stickel also reports that while seed-eating
birds were declining, predatory birds that
fed on them—or on fish—were in a worse
situation. He states that all studies he has
seen support the view that free and protein-
bound methylmercury acts in the same way
and with equal force (Nelson, et al., 1971).

Hawks and owls were hard-hit. Wild
seed-eaters had liver residues ranging up to
140 ppm, but predatory birds had levels up
to 300 ppm. As predatory birds are rarely
numerous and have relatively low reproduc-
tive rates, they might have been exterminat-
ed over large areas, if the release of mercury
had not been stopped. However, since the
ban on seed dressing with methylmercury
took force in 1966, goshawks have been re-
covering, and their residues of mercury have
dropped (Nelson, et al., 1971).

83


physical defects and the mental deteriora-
tion often remain. This clinical picture has
been reproduced in animal experiments
(Lundgren and Swensson, 1949).

The clinical details of the Minamata, Japan,
and the Alamogordo, N. Mex., poisonings
have been reported by Takeuchi (1970) and
Gregg, et al., (1971), respectively.

77


2693-57, 2693-20]

(aa.) 0.5 to 6.0%, in combination
with 3.75% cuprous oxide and 1.4 to 6.5%
“mercury phenate.”*

(bb.) 0.5 to 6.0%, in combination
with 17.5% cuprous oxide.

(c) Mercury phenate:

1.4 to 6.5%, in combination with mercuric
oxide (see 4 A (a) above)

(d) Phenylmercuric acetate: [Ref.
Reg. Nos. 3073-17, 25, and 26] 4.5%, used
alone.

(e) Phenylmercuric oleate: [Ref.
Reg. Nos. 539-214, 215, 216 and 218]

(aa.) 0.95 to 1.11%, used alone, or
(bb.) 0.89% in combination with
23,88% metallic copper.
(2) Substitute compounds

(a) Copper (metallic): [Ref. Reg.
Nos. 8120-3 and 9792-1] 15.0 to 48.2% by
weight.

(b) Copper acetoarsenite: [Ref. Reg.
Nos. 390-11 and 390-38] 16 to 26.5% in com-
bination with 13.5% copper powders or 2.0%
Bis (tributyltin) oxide.

(c) Copper hydroxide: [Ref. Reg.
Nos. 3073-2 and 3073-34] 8 to 9% in combi-
nation with 48% copper oxide or 24% copper
oxide.

(d) Copper linoleate: [Ref. Reg. No.
2693-47] 9.4% in combination with 31.5%
cuprous oxide.

(e) Copper oleate: [Ref. Reg. Nos.
9461-50 and 9461-48] 3.4 to 8.0% in combina-
tion with 38.9 percent cuprous oxide or 10%
cuprous oxide.

(f) Copper resinate: [Ref. Reg. No.
2568-7] 3% in combination with 16.8% cu-
prous oxide plus 12.6% capric acetoarsenite
plus 1.4% pine oil.

(g) Cuprous oxide: [ref. Reg. Nos.
10250-1 and 3658-2] 7.5 to 74.5% alone

(h) Bis (tributyltin) oxide: [Ref. Reg.
Nos. 390-30 and 568-20] 4.6 to 10% alone.

(i) Dichlone: [Ref. Reg. No. 3658-3]
5.5 percent in combination with 51.2% cu-
prous oxide.

(j) Pentachlorophenol: [Ref. Reg.

No. 9461-52] 2.23% in combination with
24.59% cuprous oxide plus 1.86% Bis (tribu-
tyltin) oxide.

(k) Phenarsaxine chloride: [Ref. Reg.
Nos. 2693-35 and 2693-36] 4.5 to 6.4% in
combination with 19.4% cuprous oxide or
31.5% cuprous oxide.

(Il) Tributyltin fluoride: [Ref. Reg.
Nos. 3658-14 and 8019-13] 5.55 to 14.3%
alone.

(3) Comparative effectiveness and im-

pact

(a) Substitute compounds are effec-
tive replacements for mercury in marine
finishes.

(b) Impact of withdrawal of mercury
from these uses will be insignificant.

B. Paints (bacterial preservative)

(1) Mercury compounds
Phenylmercuric oleate (30%): [Ref. Reg.
Nos. 6516-10 and 8489-1]

(a) 2 ounce by weight packet to | gal
of oil based paint, application to marine
surfaces on pleasure craft.

(b) 0.5 Ib product/100 gal finished
formula.

(2) Substitute compounds

(a) 2, 3, 4, 6-Tetrachlorophenol
(74%): [Ref. Reg. No. 464-71] 1.0% to 3.0%
product by weight of formulation.

(b) 2, 3, 5, 6-Tetrachloro-4-(methyl-
sulfonyl) pyridine (82%): [Ref. Reg. No.
464-333]

(aa.) Oil-based high zinc content:
0.25% to 0.5% by weight of formulation.

(bb.) Zinc-oxide free systems: | to
3% to weight of formulation.

(cc.) Interior paints: flat finishes -
0.3%: gloss paints 0.7% by weight of formu-
lation.

(c) 2-(Thiocyanomethylthio) benzo-
thiazole (32%) and 2-Hydroxypropyl metha-
nethiosulfonate (28%): [Ref. Reg. No. 1448-
27)

(aa.) Oil paint, zine oxide: 0.1 to
0.5% by weight of formulation. ‘

(bb.) Oil paint, zinc-free alkyd: 0.3
to 1.0% by weight of formulation.


where A mercury and A silver are the iso-
topic abundances of the respective lines of
interest.

Mtusiak and coworkers (1964) described a
method for analysis of mercury in biological
substances wherein they passed wet digests
or urine over copper powder over a period
of 1 hour using suction to control the flow
rate. The copper powder was then placed in

46

the crater of the electrode of a spectrograph
and the 2537 A mercury line used for analy-
sis.

Pakter (1968) describes a method he devel-
oped for determination of mercury in or by
absorption on manganese dioxide. The mer-
cury can then be driven from the manganese
dioxide by heat and measured by conven-
tional methods such as dithizone or atomic
absorption methods.


A study was conducted by Goldwater and
Jacobs (1964) to determine the concentration
obtained in a room painted with paint con-
taining mercury and the effects on the inhab-
itants of the room. It was found that a con-
centration of 0.17 mg/m3 of mercury vapor
was reached in 90 minutes after painting.
The total mercury concentration was of the
order of 0.20 mg/m3 for about 4 1/2 hours.
After 24 hours with no exceptional attempts
at ventilation, the concentration of mercury
decreased to insignificant levels. Some mer-
cury was absorbed by the inhabitants of the
room, as measured by comparative excre-
tion concentrations of mercury in the urine.
However, the mercury concentration in the
urine of the test subjects was no greater than
found in the urine of unexposed ‘‘normals.””
No evidence was found of mercury expo-
sure or absorption in a degree that would
constitute a hazard to the painters or to the
occupants of the room.

As reported earlier, Hirschman, et al.
(1963), associated acrodynia in a S-year-old
child to the inhalation of mercury vapors ina
freshly painted room. Miller, et al. associat-
ed neuromyasthenia in 49 employees to the
exposure of organic mercury from freshly
painted walls.

(2) Exterior Paints — In their reply to the
Federal Register Notice on Mercury, the
National Paint, Varnish and Lacquer Asso-
ciation stated that mercury is lost from
painted exterior surfaces. The majority of
this is washed from the painted surface and
goes into the ground. The statement is made
that the mercury (phenylmercury) is firmly
bound to the soil and is not removed by dilu-
tion with water or saline solution. The Asso-
ciation therefore contends that the mercury
thus removed from the painted surfaces
does not enter the aquatic eco system.

The thesis that mercury thus bound will not

eventually end up in water is untenable.
Mrak (1969) stated that because of the tight

90:

binding characteristics of pesticide residues
to soil particles, the general pollution of
water by pesticides occurs through the
transport of soil particles to which the resi-
due is attached. Soil residues may, there-
fore, be a cause for concern; since they may
reach man by a number of routes; uptake
from soil by consumable crops; leaching into
water supplies; and volatilization into the
air.

The National Paint, Varnish, and Lacquer
Association states that there are no substi-
tutes now available for mercury for the pres-
ervation of paint; and without preservatives,
latex paints will spoil during manufacture.
The Association states that it will require |
year to develop a suitable substitute for
mercury in interior paint and 3. years to de-
velop a substitute for mercury for exterior
paint.

Paint manufacturers do recycle wash water
and use it in the preparation of other batches
of paint, thus the manufacture of paint does
not contribute to mercury pollution.

This is a highly significant use of mercury. It
is the largest dissipative use of mercury in
the United States today.

There are latex paints on the market which
contain preservatives other than mercury.
Therefore, there seem to be suitable substi-
tutes for mercury in the preservation of
paint.

(3) Ship bottom antifouling paints — This
use constitutes a direct contamination of
water with mercury. This contamination
may result from the slow leaching of mercu-
ry from the painted ship bottom or from dust
and chips from the ship bottom when it is
scraped and sanded prior to repainting.
Mercury may be released in acutely toxic
amounts during this sanding operation.
Schrager (1964) reported on the occurrence
of tubular necrosis in a 2-year-old child ex-


mogenates is reduced almost immediately on
addition of mercury, and the inhibition can
be rapidly reversed by the addition of cy-
steine., It appears that the metal first inter-
acts with functional groups at the cell sur-
face, therefore inhibiting the transport of
sugar. Subsequently it slowly enters the
cells, and the respiration is progressively
inhibited (Demis and Rothstein, 1955). Stud-
ies of binding of mercury by rat diaphragm
confirm this interpetation. Uptake of mercu-
ty by the excised diaphragm proceeds fairly
rapidly for about 20 minutes. Thereafter, the
rate of mercury uptake proceeds at a much
lower rate constant. The time-sequence in-
volves a rapid diffusion through the intersti-
tial spaces and immediate binding on the cell
surface, followed by a slow penetration
through the membrane to the respiratory
sites within the interior of the cell.

In epithelial tissues such as the small intes-
tine and the kidney, several populations of
cells are found in a definite geometrical ar-
rangement. The actions of mercury here are
more complicated than in a homogeneous
population of cells. Similarities are found,
however, because the absorptive and secre-
tory functions of the epithelia represent spe-
cialized use of mechanisms present in nearly
all cells. It can be stated that any observed
inhibition of mercury of the net transport of
salt solutions or of glucose across epithelia
can be explained in terms of mechanisms
similar to those active in the cells (Passow,
et al., 1961).

The action of mercury on the membrane of
the columnar epithelial cells of the jejunum
is. similar to its action on the membranes of
muscle and red blood cells. Immediately fol-
lowing the addition of mercury (as mercuric
chloride) to the mucosal side, rapid re-
sponses are observed in the electrical poten-
tial across the intestine, the loss of cellular
K+, and the cessation of glucose uptake.
Each of these responses is associated with
the action of mercury on the membrane fac-

ing the lumen. After a delay period, other
functions are inhibited. These include Na*
and glucose transfer into the serosal solution
and the production of lactic acid. Similar
disturbances in electrolyte equilibrium have
been reported for the action of mercury on
kidney slices (Kleinzeller, et al., 1957).

Mercury can produce one kind of response
when added to the mucosal side of an epi-
thelial tissue and a different response when
introduced on the serosal side. When mercu-
ry at 10-4 M is in contact with the mucosal
surface of frog skin, transport of salts and
water is reduced, because of the specific in-
hibition of the sodium transfer system.
Since the effects are noted at mercury levels
which do not produce inhibition of cellular
metabolism, it seems likely that the toxic
action of mercury is mediated through a di-
rect effect on the outward-facing membrane
of the epithelial cells. When mercury is
present on the serosal side in the same con-
centration, sodium transport is accelerated.
This response has been attributed to an in-
teraction of mercury with the inward-facing
membrane of the epithelial cells (Passow, et
al., 1961).

IV.D.6. Differences in Biological Behavior
of Various Mercury Compounds — Hughes
(1957) offered a physio-chemical explanation
for the differences in biological behavior of
metallic mercury, inorganic mercury, and
alkyl and arylmercury compounds. Hughes
states that alkylmercury halide possesses
both a stable carbon-mercury bond and the
essentially ionic mercury-halide bond. Car-
bon-mercury bonds possess a wide range of
stabilities. In general, aliphatic carbon com-
bines more stably with mercury than aro-
matic carbon; however, both would appear
to be sufficiently stable to resist usual phy-
siological processes. The pharmacology. of
methylmercury halides may be discussed in
terms of the affinity of methylmercury ion

67


4. Polyvinyl Chloride Film (bacteriostatic at
surface)

A. Mercury compounds

Phenylmercuric propionate (0.62%): [Ref.
Reg. No. 7101-2] Product is disposable plas-
tic bag impregnated with mercurial and bear-
ing bacteriostatic (bacterial growth inhibit-
ing) claim.

B. Substitute compounds

(1) Captan  (N-trichloromethylthio-4-
cyclohexene-1, 2-dicarboximide) (90%):
{Ref. Reg. No. 1965-11] 0.2 to 0.5% product
by weight of total formula.

(2) 4-chloro-3, 5-xylenol (100%): [Ref.
Reg. No. 4026-4] Recommended for ‘‘plas-
tics’’ but no dosages available.

(3) Tri-n-butyltin linoleate (75%): (Ref.
Reg. No. 5204-15] 0.15 to 0.2% product by
weight based on plastic mix weight.

(4) Diphenylstibine 2-ethylhexoate
(10%): [Ref. Reg. No. 5204-42] 1.3 to 5%
product based on weight of film.

(5) Tributyltin linoleate (98%): [Ref.
Reg. No. 8314-4] 0.43% product by weight
of plastic mix.

(6) 3, 4, 5-Tribromosalicylanilide
(97%) and 3. 5 Dibromosalicylanilide (2%):
[Ref. Reg. No. 6390-29] 2.0% product based
on total weight of media.

C. Comparative effectiveness and impact

() Substitute compounds appear to be
more than adequate.

Xx.
1. Fungistats
A. Mercury compounds
(1) Phenylmercuric acetate: [Ref. I-P-
08-00.10] Fungistat: 125-225 ppm. spray sur-
faces.
(2) Phenylmercuric borate: [Ref. I-D-
13-00.02 and I-P-08-10.01] Fungistat: 50 ppm

28

(2) Impact on industry and consumer
appears to be nil.

5. Vinyl (bacterial preservatives)
A. Mercury compounds

Phenylmercuric hydroxide (17%): [Ref. Reg.
No. 6516-3] Vinyl (otherwise unidentified)
coating for fabrics, ground together with
chlorinated paraffin: 0.5 lb product/99.5 Ib
media.

B. Substitute compounds

(1) Diphenylstibine 2-ethylhexoate
(10%): [Ref. Reg. No. 5204-42] Polyvinyl
chloride: 1.3 to 5% product by weight.

(2) Captan (N-trichloromethyIthio-4-
cyclohexene-1, 2-dicarboximide) (90%):
[Ref. Reg. No. 1965-11] Polyvinyl chloride:
0.2 to 0.5% product by weight.

(3) Bis (tri-n-butyltin) oxide (.075%)
and alkyl (61%C 9. 23%C 4, 11%C yg, S%Cg-
Cyg) dimethyl benzyl ammonium chlorides
(1.5%): [Ref. Reg. No. 3090-137] 1 part
product to 2 parts water, “‘spray surface uni-
formly.”*

C. Comparative effectiveness and impact

(1) Substitute compounds appear to be
adequate.

(2) Impact on industry expected to be
minimal. Cost to consumer expected to in-
crease.

Rubber

plus 31.25. ppm. _—_diisobutylphenox-
yethoxyethyl dimethyl benzyl] ammonium
chloride, before molding.

B. Substitute compounds: [Ref. I-Z-08-15.

01)

(1) Alkyl dimethyl benzyl ammonium
chloride and Bis (tributyltin) oxide: [Ref. I-


great on the consuming lumber industry
where federal specifications now require
such treatment or where it is required by
foreign purchasers of lumber.

2. Fence posts (rot and decay application)
A. Mercury compounds

(1) Mercuric chloride: [Ref. I-M-04-
00.01] 1 tbs of 33.2% mercuric chloride plus
33.2% arsenious oxide/0.75 inch x 2.0 hole
bored 6 inches above ground line, in green
posts. Posts over 4 inches in diameter re-
quire 2 to 3 holes. Plug holes after filling. No
access to livestock.

(2) Phenylmercuric oleate: [Ref. I-P-14-
00.01] 1.0 to 1.25% solutions - soak

B. Substitute compounds

(1) Anthracene oil: (Ref. I-A-35-00.01]
soak

(2) Coal for neutral oils: [Ref. I-C-22-
00.01] soak.

(3) Copper naphthenate: [Ref. I-C-30-
00.01] soak.

(4) Copper sulfate plus sodium fluoride
or sodium chromate: [Ref. I-C-38-00.01]
soak.

(5) Creosote (coal tar): [Ref. I-C-41-

00.01] soak.

(6) Creosote (wood): ([Ref. 1I-C-42-
00.01] soak.

(7) Pentachlorophenol: [Ref. I-P-05-

00.01] 5% solution, soak.

(8) 5.09% sodium dichromate plus
5.36% copper sulfate and 0.2% chromic acid
solution: [Ref. I-S-07-50.01] soak.

(9) Tetrachlorophenol: [Ref.
00.01] 5% solution, soak.

I-T-06-

(10) Zinc naphthenate:: (Ref. I-Z-05-
00.01] 20% solution, soak.

C. Comparative effectiveness and impact

(1) Substitute compounds are at least as
effective as mercury compounds for the con-
trol of rot and decay of fence posts.

(2) Substitute compounds frequently
provide objectionable coloration to treated
wood, mercury does not.

(3) Substitute compounds frequently
impair the paintability of treated wood, mer-
cury does not. i

(4) Impact of withdrawal of mercury
for treating fence posts will be negligible.

3. Lumber and timbers (rot and decay - con-
sumer application)

A. Mercury compounds 5

(1) Phenylmercuric oleate: [Ref. I-P-14-
00.01] 1.0 to 1.25% solution by brush, spray
or dip.

(2) 0.6% Phenylmercuric oleate plus
7.125% technical pentachlorophenol: [Ref.
I-P-14-00.01] brush, spray or dip.

B. Substitute compounds

See 2, B above. Apply by dip, spray or soak.
C. See 2, C above.

D. Addendum
(1) Mercury compounds
0.28% Phenylmercuric oleate plus 0.28%

TBTO and 12.5% zinc naphthenate - house-

hold use by brush spray or dip. [Ref. Reg.
No. 390-3]

XVI. Dental and Surgical Instruments
(disinfection)

1. Mercury compounds

A. Phenylmercuric borate (0.1%): (Ref.
Reg. No. 1293-1] Instrument disinfectant
used undiluted.

40

B. 3-(Hydroxymercuri)-4-nitro-o-cresol
(0.48%): [Ref. Reg. No. 275-3] Disinfectant,
used undiluted.


Ramel, C. ‘Genetic effects of organic mercury com-
pounds.’” Hereditas, 57: 445 (1967).

Ramel, C. Genetic effects of organic mercury com-
pounds,’’ Hereditas, 57: 445 (1967).

Ramel, C. ‘‘Methylmercury as a mitosis disturbing
agent.”’ Japan Med. Assoc. J. 61: 1072 (1069).
Ramel, C. “‘Genetics effects of organic mercury com-
pounds. I. Cytological investigations on allium

roots."* Hereditas, 61: 208 (1969).

Rathje, A.O. ‘A rapid ultraviolet absorption method
for the determination of mercury in urine.”
Amer. Ind. Hyg. Assoc. J. 30 (2): 126 (1969).

Rayudu, G.V.S., Tiefenbach, B., and Jervis, R.E.
“Neutron activation determination of trace mer-
.cury in Canadian foods."’ Trans. Amer. Nuc.
‘Soc. 14th Ann. Meeting, p. 54 (1968).

Rehfus, R.. Priddy, A.H., and Barnes, M.E. ‘‘Mercu-
‘ty contamination in the environment: A bibliogra-
ey. ”* U.S. Dept. of Interior. Office of Library

ciences. July 1970.

Rentos, P.G., and Seligman, E.J. ‘‘Relationship be-
tween environmental exposure to mercury and
clinical observation.” Arch. Environ. Health 16
(6): 794 (1968).

Report of an International Committee. ‘Maximum
allowable concentrations of mercury com-
pounds.” Arch. of Environ. Health 19 (6): 891
(1969).

Résnik, R.A. ‘‘Interaction of mercuric ion with hemo-

_ globin.” Nature, 203: 880 (1964)
‘exed, B.. et al. ‘Co-operation in research.” Oikos
Supp. 9: 42 (1967).

Riggs. A.F. ‘‘Sulfhydrylgroups and the interaction

between the hemes in hemoglobin.’ J. Gen. Phy-
___ Siol. 36, 1-16 (1952).

Rodgers, E.O., et al. ‘The toxicity of pyridylmercuric
acetate technical (PMA) to rainbow trout (Salmo
gairdnerii). Progressive Fish-Culturist 13 (2): 71
(1951).

Rokutanda, T.. et al. ‘*Bacteriological and immuno-
logical studies on Minamata disease." Kumamoto
Med. J: (Jap. ed.) (Supp. 1) 31:48 (1957)

Ross, A.F. ‘‘Mercuric polyneuropathy with albumino-
cytologic dissociation and eosinophilia.” J.
Amer. Med., 188 June (1964).

Ross, R.G,; and Stewart, D.K.R. ‘‘Mercury residues
on apple fruit and foliage.’’ Can. J. Plant Sci., 40:
117 (1960).

Ross, R.G.,’ and Stewart, D.K.R. ‘“‘Movement and
accumulation of mercury in apple trees and soil.”*
Can. J. Plant Sci. 42: 280 (1962).

Ross, R:G., and Stewart, D.K.R. ‘“‘Mercuric reisudes
in potatoes in relation to foliar sprays of phenyl-
mercury chloride.’”” Can. J. Plant Sci. 44: 123
(1964).

Rothes, G., and Havermann, H. ‘‘Versuche uber ver-
tutterungsmoghchkeit von mit ceresan gebeiztem

getreide bei Huhnern, Schweinen und Pferden.”*
Nachr. Schadlingshekampfung 14: 47 (1939).
Rothstein, A. ‘Cell membrane as site of action of
heavy metals."’ Fed. Proc. 18, 1026 (1959).
Rothstein, A., and Hayes, A.D. “The metabolism of
mercury in the rat.’’ J. Pharm. Exptl. Therap..
130: 166 (1960).

Rucker, R.R., and Amend, D.F. ‘Absorption and re-
tention of organic mercurials by rainbow trout
and chinook and sockeye salmon.’ Progressive
Fish-Culturist 31 (4): 197 (1969).

Ruckelshaus, W.D. ‘*Reasons underlying the registra-
tion decisions concerning products containing
DDT, 2.4, 5-T, Aldrin and Dieldrin. Press release
(March 18, 1971).

Ruzicka, J., and Lamm, G. “Automated determina-
tion of traces of mercury in biological materials
by substoichiometric radiosotope dilution.”’ Tal-
anta 16 (2): 157 (1969).

Saito, M., Kitayama, M., Mori, M., and Kitsutaka, T.
“Studies on prevention of poisoning by agricul-
tural chemicals (Part 13) mercury residues in pad-
dyfield regions.”” Hokkiaido Ritsu Eisei Kenky-
ashoho 19: 127 (1969).

Samsahl, K. ‘*Radiochemical method for determina-
tion of arsenic, bromind, mercury, antimony and
selenium in neutron-irradiated biological materi-
al.’* Anal. Chem. 39 (12): 1480 (1967).

Samsahl, K., Brune, D., and Wester, P.O. ‘‘Simulta-
neous determination of 30 trace elements in can-
cerous and noncancerous human tissue samples
with gamma-ray spectrometry." AE-124. Aktie-
bolaget Atomenergi. Stockholm, Sweden (1963).

Sandell, E.B. ‘‘Colorimetric Determination of Traces
of Metals.”’ 3rd ed. Interscience, New York
(1959).

Sandor, C., Fercuc, G., Mihaly, T., and Dezso, F.
““Mérgezésen vescfrtalom utani rehabilitatio.”’
Orv. Hetilap. 110: 1905 (1969).

Schacter, M.M. ‘Apparatus for cold vapor atomic
absorption of mercury.”’ J. Assoc Offic. Anal.
Chem. 49 (4):778 (1966).

Scrager, G.O. ‘‘Acute mercury poisoning in a child
following contact with marine antifouling paint.””
J. Pediatrici 65, 780 (1964).

Schopf, E. ‘“‘Mitore-induction durch organische
quecksilberverbindungen in lymphocyten-kultu-
ren.” Die Naturvissenschaften 9, 464 (1969).

Schdpf, E., Schulz, K.H., and Isensee, I. ‘‘Utersu-
chungen uber dea lymphocytentransforma-
tionstest bei quecksilber-allergie.”” Arch. Klin.
Exp. Derm. 234 (4): 420 (1969).

Schoreder, H.A. ‘Use of diuretic agents.’ J. Amer.
Med. Assoc., 147: 1109 (1951).

Science and Technology Agency of Japan. ‘‘Special
studies of microanalysis of mercury compounds

a8T


cannot be measured against the interference
background.

The method of getting around this problem
is to irradiate the sample and then add a few
milligrams of carrier mercury, generally
mercuric chloride. The sample is then di-
gested, the mercury precipitated or extract-
ed and the analysis completed by counting
the isolated portion and calculating the mer-
cury content from the radioactivity remain-
ing.

However, that is unsatisfactory with many
biological samples such as fish in which most
of the mercury is present as methylmercury
compounds. The mercury becomes radioac-
tive on irradiation, but in the isolation step,
much of the radioactive mercury is lost be-
cause of the difficulty in digestion. It simply
is not precipitated or extracted with the car-
rier. Results may reflect only 10% of the
actual level in such cases.

Sjostrand (1964) described the procedure
used in Sweden. The sample, sealed in a
quartz tube, was exposed to neutron radia-
tion in a nuclear reactor. The sample was
then transferred to a flask and 20 mg of Hg
(HgCl,) added as carrier and digested. The
mercury was distilled from a perchloric acid
solution and electrolytically plated out on a
weighed gold foil. The foil was weighed to
determine percent recovery of Hg and the
197g measured by y -spectrometry. Sensi-
tivity of the procedure is said to be about 10°

5 ppm He.

II.D. Gas-Liquid Chromatography — Since
alkylmercury compounds tend to be difficult
to analyze and yet are prevalent in many
substrates, a number of scientists have at-
tempted to devise methods suitable for sam-
ples containing such mercury derivatives.

K. Sumino (1968) used gas chromatography
to determine methylmercury in marine prod-

ucts and phenylmercury in rice to levels
lower than 0.01 ppm.

Westé6 (1967, 1968) used electron capture
GLC to determine methylmercury in fish
and other foods of animal origin. She report-
ed that most of the mercury present in fish,
eggs and meat was in the form of methyl-
mercury. 82% for ocean fish and 92% in
fresh water fish.

In contrast to the two above methods in
which the organic mercurials were chroma-
tographed as the chlorides, Tatton and
Wagstaffe (1969) extracted and chromato-
graphed these compounds as their dithizon-
ates. Apparently the intact dithizonates
chromatographed and the specific organic
mercurials could be identified by their reten-
tion time. Both these authors and Westid
also used TLC as an additional means of
identification.

II.E. Miscellaneous Methods — Tong, Gu-
tenman and Lisk (1969) applied the use of
spark source mass spectrometry to analysis
of apples for mercury. In this, a pair of in-
dium electrodes was used to make a graded
series of exposures on the same photograph-
ic plate for emulsion calibration relating
microdensitometric measurements of mass
line optical transmittance (%T) to exposure
level (E). The %T values for silver (m/e
107), mercury (m/e 198, 199, 201, and 202),
and their corresponding backgrounds were
measured. These values were converted into
E values according to the emulsion calibra-
tion curve. The ratio of mercury to silver
was then determined by the exposure (E)
ratio of mercury to silver (each element hav-
ing been corrected for the isotopic abund-

ance and background) according to Equation
1.

mercury/silver (mole ratio) =
(mercury - “mercury background) Asilver

ay

Esilver -Esitver background) Amercury

45


2. Substitute compounds

A. n-Alkyl (60%C)4, 30%Cig, 5%Cj>,
5%Cjg) dimethylbenzym ammonium chlo-
ride (total 10%): [Ref. Reg. No. 859-7] Use-
dilution: 1 fluid 0z/2 gal water.

B. Potassium o-phenylphenate, and po-
tassium o-benzyl-p-chlorophenate (and solu-
bilizing and sequestering agents) (total
19.2%): [Ref. Reg. No. 1750-32] Use-dilu-
tion: 1-100.

C. Tetradecyl dimethyl benzyl ammo-
nium chloride (1.25%), dodecyl dimethyl-
benzyl ammonium chloride (0.25%), and
isopropyl alcohol (17.5%): [Ref. Reg. No.
3625-1] Use-dilution: 4 fluid oz product/gal
water.

D. Isopropanol, and n-alkyl (50%C,,,
40%C 15, 10%Cj¢) dimethylbenzyl ammon-
ium chloride (total 29% actives): (Ref. Reg.
No. 4330-1] Use-dilution: 1-32

XV.
1. Broomcorn
A. Mercury compounds

Phenylmercuric acetate: [Ref. I-P-08-00.09]
200 ppm in dye bath by weight of solution.

B. Substitute compounds
None.
C. Impact

(1) Broomcern brooms and brushes
must have a bright color and clean appear-
ance to be saleable. A fungistatic agent with
residual qualities is necessary in broom
manufacture.

(2) Although no substitutes for mercury
are registered for this use, it would appear
that a suitable replacement compound could
be found: with little effort. Therefore, the
impact of withdrawal of mercury for this use
should be slight to moderate on the manu-
facturer and consumer.

E. Cresol, benzaldehyde, safrole, and
formaldehyde (total 30% actives): [Ref. Reg.
No. 5493-2] Use-dilution: 1-32.

F. Cresols, formaldehyde, phenylethyl,
alcohol, and benzyl alcohol (total 95%):
[Ref. Reg. No. 5493-4] Use-dilution: 2 fluid
oz/gal of water.

G. Diisobutylcresoxyethoxyethyl-dime-
thylbenzyl ammonium chloride and o-phen-
ylphenol ethoxynonyl-pheno| complex
(1.1%), and methyl-p-hydroxybenzoate
(0.3%): [Ref. Reg. No. 7150-4] Use-dilution:
1 part product to 3 parts water.

3. Comparative effectiveness and impact

A. Substitute compounds are better disin-
fectants than mercury compounds.

B. No impact on industry or the consum-
er expected.

Miscellaneous

2. Cellulose sponges
A. Mercury compounds

Phenylmercuric acetate: [Ref. I-P-08-00.09]
750 ppm solution.

B. Substitute compounds
None.
C. Impact

Unknown. Substitute compounds should not
be difficult to find once the consumers are
aware of the withdrawal of mercury for this
use.

3. Seam and bedding compounds (boat con-
struction)

A. Mercury compounds

Phenylmercuric oleate: [Ref. I-P-14-00.01]
400 ppm PMO plus 1425 ppm. Pentachloro-
phenol by volume of compound.

41


CHAPTER 5

TOXICOLOGY OF MERCURY

V.A. Toxicity to Laboratory Animals

The absorption, distribution, metabolism,
excretion, and the action of mercury at cel-
lular and subcellular levels has previously
been discussed. This section will deal with
the toxic effects of mercury on the intact
animal.

V.A.1, Acute and Subacute Toxicity — The
acute toxicity of inorganic mercury is great-
er than that of the organic mercurials, re-
gardless of the route of administration. The
arylmercury, alkylmercury, and the alkoxy-
mercury compounds seem to be equally tox-
ic. The symptoms of poisoning with alkyl-
mercury compounds may appear several
weeks after administration, but the toxicity
is still less than that of inorganic mercury
when the observation period is prolonged to
1 month (Swensson and Ulfvarson, 1963).

Swensson (1952) studied the relative acute
toxicities of mercuric chloride, methylmer-
curic chloride, and methylmercuric dicyan-
diamide, intraperitoneally, in mice. In this
study, mercuric chloride was found to be the
most toxic. Thereafter, with decreasing tox-
icity, were phenylmercuric acetate, the al-
kylmercuric chlorides, and the alkylmercu-
ric dicyandiamides. No difference in toxicity
was noted between ethyl and methylmercur-
ic chlorides. Methylmercuric chloride and
methylmercuric dicandiamide were of equal
toxicity by the intravenous route in rabbits.
With repeated intraperitoneal injections of
one-tenth to one-fourth of the Probable Le-
thal Dose (PLD), there was a gradual in-
crease in the appearance of central nervous
system effects. Histological studies revealed
diffuse injuries in the CNS with all com-
pounds tested (inorganic mercury was not

included in this study). Gage and Swan
(1961) demonstrated that only alkylmercury
compounds gave evidence of neurotoxic
effects which developed in survivors of the
median lethal dose in animals receiving sub-
lethal doses. Short term tests with methyl-
mercury (10 to 90 days) showed that a daily
intake of 0.4 to 1.0 mg Hg/kg of body weight
caused neurological symptoms in rabbits,
dogs, and cats (Lefroth, 1969). The acute
toxicities of the mercurials are summarized
in Table 1.

Methylmercuric chloride, suspended in olive
oil, was administered to mice, orally via
stomach tube, at levels of 4.6 to 100 mg Hg/
kg of body weight. The animals at the lower
levels (4.6 to 14.7 mg Hg/kg) received seven
daily injections, while the animals at the
higher dosage levels received only a single
injection. Neurological symptoms appeared
in two groups given one dose of 32 and 46
mg Hg/kg, respectively. In groups which
received a dose larger than 46 mg Hg/kg,
death occurred before any neurological
symptoms could be detected. Mice receiving
a dose less than 32 mg Hg/kg showed no
neurological symptoms up to the 30th day
after the dose was administered. Seven daily
doses of 10 and 14.7 mg Hg/kg administered
to two different groups of mice induced neu-
rological symptoms; all mice from the latter
group died within 5 days after the last dose
was administered. Only one of ten mice died
as the result of the lower dose. The domi-
nant neurological symptoms related to cere-
bellar, or vestibulocerebellar regulation of
movement of posture. A brain concentration
of mercury of 20 ug/g of wet tissue was
found only in those groups which had shown
some neurological symptoms (Suzuki, 1969).

71


(2.) The mercury content of fish is related to
the species, the size, locality, and Jength of
exposure to mercury.

(3.) Agricultural runoff from areas where
heavy use has been made of mercury-treated
seeds can result in residues in fish greater
than 0.5. ppm mercury.

A systematic survey of wildlife and animal
food products (including freshwater and
marine fish) has been underway in Canada,
and the initial results were made available in
the summer of 1970. At that time, using neu-
tron activation analysis, elevated levels of
mercury were found in several pheasants
from Alberta and in pike, pickerel, and
whitefish from the Great Lakes area. Avian
products generally contained less than 0.05
ppm, and most fish (except those from heav-
ily contaminated areas) averaged 0.2 ppm or
less. The levels of mercury found in these
fishwere omewhat lower than those found by
other laboratories, and the explanation given
was that smaller fish were sampled for anal-
ysis.

In the fall of 1970, the United States Food
and Drug Administration found that canned
tuna sold in the United States contained up
to 1.2 ppm mercury (average 0.37 ppm) and
that frozen swordfish ranged from 0.18 to
2.4 ppm (average 0.93). Surprisingly high
levels (25 170 ppm) were also found in liv-
ers of fur seals and sea lions off the western
coast of North America. A 21 member ad
hoc committee of experts reviewed the
FDA’s data on mercury contamination in
swordfish and suggested that swordfish con-
sumption be curtailed in the United States.
In May 1971, the Food and Drug Adminis-
tration issued the statement that the *‘public
stop eating this fish until and unless the situ-
ation can be remedied.””

VI.D. Mercury in Fish — In Sweden, the
pike contain two to three times more mercu-
ry than do the other fish in the same waters.
This fish is taken as the standard for black-
listing waters. A body of water is blacklisted

82

in Sweden when a sample of five pike shows
residues of 1 ppm or more of mercury in
most of the five. If one or two of the five
have a higher level, another sample may be
requested. Statisticians have advised a sam-
ple of at least 11, but costs would be prohibi-
tive. At present, the judgment is made more
or less subjectively from the sample of five.
If residues are between 0.2 and | ppm,
Swedes are advised to eat fish from these
waters no more often than once a week. The
Swedish action level of 1 ppm is considered
too high, but if 0.5 ppm were the criterion,
as in the United States and Canada, five
times as many waters would be blacklisted
and monitoring costs would be extravagant
(Nelson, et al., 1971). '

When comparing residues of mercury for

blacklisting purposes, levels in pike are ad-

justed to fit a pike weighing | kg., or about

2.2 pounds. This is done, because pike keep

growing and keep increasing in concentra-

tion of mercury. The curve of the increase in

the level of mercury tends to flatten in large, *
old pike, but it does not seem to reach a

steady state (Nelson, et al., 1971).

Fish and shellfish found dead at Minamata
contained 9 to 24 ppm mercury on a wet-
weight basis. One Swedish pike was taken
which contained 17 ppm, however, pike
have been killed experimentally at muscle
levels of mercury of 5 to 9.1 ppm. Stickel
(Nelson, et al., 1971) states that there is
clearly an overlap between the curves of res-
idue distribution in living wild pike and ex-
perimentally killed pike. He believes that
Swedish pike have died from mercury poi-

soning in the wild, and losses were gradual
and unobserved.

The lethal concentration of mercury com-
pounds found for various aquatic organisms
is listed in the appendix. While such infor-
mation indicates that mercury compounds
are remarkably toxic at low concentrations,
it does not define the maximal levels which
should be avoided to maintain a healthy


C. Comparative effectiveness and impact;

(1) Mercury as PMA is the only availa-
ble control for stripe (Helminthosporium) of
barley.

(2) Mercury compounds are broad
spectrum fungistats for a wide range of path-
ogens on field crop seeds. They control sev-
eral diseases for which label claims have
never been noted, such as certain bacterial
pathogens on cotton seed and fusarium scab

(3) Mercury as PMA is effective at 0.1
to 0.01 of the concentration of substitute
materials.

(4) The impact on withdrawal of these
uses for PMA would be severe and result in
greatly increased costs to the commercial
seed treater, the farmer and consumer of
crops grown from the treated seed.

D. An estimation of the potential use of
PMA for the preceeding seven field crops is

of cereals.

given in table 8.

Table 8. Estimated Potential Use of Phenylmercuric Acetate
Field Crop Seed Treatments — Based
On 1969 Seed Requirements

Crop Seed Seed Used — 1969 PMA Hg
X 1,000 Ib, act. X 1,000 Ib. X 1,000
Barley 16,000 bu. 246 147
Cotton
acid delinted 95, 184 Ib. 671.05 399.74
reginned 179,897 Ib. 1,902.42 1,133.27
fuzzy 11,422 Ib. 181.18 107.93
Flax 72 bu. 0.64 0.38
Oats 59,563 bu. 106.10 63.20
Rice 2,119 bu. 0.08 0.05
Sorghum 129,041 Ib. 4.10 2.45
Wheat 1,552 bu. 3.40 2.03
Totals 2,871.43 1,710.52*

*Note that the Pesticide Review — 1970 shows that only 204,364 pounds of mercury was used in 1969 for all
agricultural purposes. Assuming that all of the 204,364 pounds was used for treating seed, only about 8 per-
cent of the seed was treated with mercury.

‘A. Mercury compounds:

XIL Seed Treatments
8. Flower Seeds

Hydroxymercurichlorophenol Ornamental Seed and Bulb Treatments

[Ref. I-N-06-00.02]

Treatment Treatment
‘Avdp. oz. Kvdp. oz.

28.6% Soak time 28.6% Soak time

Name of Seed per 15 pounds in normal Name of Seed per 15 pounds in normal

seed solution seed solution

Acroclinium Loz. Aquilegia hor. 60 mi
‘Ageratum loz, Arabis alpina Loz. 60 mi
‘Agrosteman loz. Arctotis loz. 90 mi
‘Amaranthus thor. Aster Loz, 60 min
Antirrhinum Wor. Balsam oz. 30 min.
(snapdragon) Browallia Loz. 30 min

35


Magos, I., and Cernik, A. A. “‘A rapid method for esti-
mating mercury in undigested biological sam-
ples.’ Brit. J. Ind. Med. 26 (2): 144 (1969).

Magos. . and Stoytchev. T. ‘Combined effect of
sodium maleate and some thiol compounds on
mercury excretion and redistribution in rats.”
Brit. J. Pharmacol. 35: 121 (1969).

Magos. L.. Tuffery, A.A., and Clarkson. T.W. **Vola-
tilization of mercury by bacteria.” Brit. J. Ind.
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Prepared by the Special Pesticide Review Group of the Office of Pesticides
Programs, Environmental Protection Agency.

SPECIAL PESTICIDE REVIEW GROUP

O. Garth Fitzhugh, Ph.D., Chairman
Lamar B. Dale, Jr., Ph.D.

William Barthel

G. A. Reich, M.D., M.P.H.

William F. Durham, Ph.D.

Thomas E. DeVaney

Joseph G. Cummings

Cipriano Cueto, Ph.D.

SPECIAL WORKING GROUP ON MERCURY
Aram Beloian

Edward P. Carter
Lee M. Loeser

With Library Assistance of:

Mrs. Claudia Lewis

ABOUT THIS REPORT

This staff report represents a scientific and technical assessment of mercurial products regis-
tered with the U.S. Environmental Protection Agency for pest control purposes. This informa-
tion was developed to assist the Agency in evaluating the past, present, and future impact of
these pesticides on man and his environment prior to determining whether their continued use

is in the public interest.

In making this determination, the Agency also will consider data supplied by other scientific
sources, both governmental and private, as well as pertinent economic and social factors.
Therefore, any conclusions and recommendations for action contained in this preliminary
report should not be construed as the position of the EPA or necessarily indicative of the

course of action it might finally take with regard to mercurial pesticides.


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100

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Halasz, P., Mechler, F., Fehrer, O., and Demjanov-
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transmission in the superior cervical ganglion of



speculate that this may explain why pre-
vious investigators have been unable to find
deposits of mercury in the brain adequate to
explain the clinical picture; measurements
were made on the whole organ or large parts
of it and generally at relatively short times
after administration. The localization of
mercury in tissues adjacent to the cerebro-
spinal canal causes Berlin to suggest that
mercury reaches the brain through the cere-
brospinal fluid rather than the blood. There
is a relatively high concentration of mercury
in the gray matter of the cerebellum, area
postrema, the subfornical body, and the
tuber cinereum.

After phenylmercuric acetate, the picture is
quite similar to that of mercuric chloride; the
autoradiograms of the brain, brain stem,
and spinal cord in the first 24 hours after
exposure show a uniform density which is
slight in comparison with the other organs.
After 4 days, there is a more differential
accumulation of mercury which is even
greater at 16 days. As with inorganic mercu-
ty, there is an accumulation in the dorsal
part of the brain stem, especially in the area
corresponding to the area postrema, in areas
adjacent to the lateral ventricle, and in the
area corresponding to the hypothalamus and
tuber cinereum. It also accumulated in the
gray substance of the cerebellum.

After an injection of methylmercuric di-
cyandiamide, as with inorganic mercury and
phenylmercury, very little mercury is taken
up by the central nervous system in the first
few hours. Accumulation occurs gradually
over a period of several days and is not cor-
related with the level of mercury in the
blood. The distribution in the brain is quite
different from that seen after the injection of
inorganic mercury or phenylmercury. With
these compounds, the distribution was het-
erogeneous, but after methylmercury it is
more uniform. Although the gray substances
takes up more mercury than the white, as in
the case of inorganic mercury, the regions

58

which show the maximum concentration of
mercury are not the same. These are the
hippocampus and the gray matter of the cer-
ebellum.

IV.B.3. Liver, Kidney, and Other Organs
and Tissues— After absorption, the aryl and
alkylmercury compounds accumulate at
higher concentrations in the liver and kid-
neys than do the inorganic compounds of
mercury. The alkylmercurys are more even-
ly distributed throughout the body than the
other two groups of compounds. Inorganic
and phenylmercury compounds translocate
from the liver to the kidneys with time. The
spleen and muscle concentrations of mercu-
ry are lower than those found in the liver and
kidneys. Both aryl and alkylmercury com-
pounds give a high content of mercury in the
hair. With methylmercury, the concentra-
tion of mercury in the hair is greater than in
the other tissues.

Swensson, et al. (1959a, 1959b) studied the
distribution of mercury in the body of rats,
rabbits, and dogs after the administration of
inorganic, aryl, and alkylmercury com-
pounds, both by the oral and intravenous
routes. He found that administration of the
organic compounds by the oral route in rats
resulted in much higher mercury concentra-
tions in the liver and kidneys than the inor-
ganic compound.

On the other hand, after intravenous admin-
istration to rabbits, mercuric nitrate and
phenylmercuric acetate were deposited
chiefly in the kidneys, whereas methylmer-
curic hydroxide appeared to be more uni-
formly distributed throughout the body. El-
lis, et al. (1967) studied the tissue distribu-
tion of mercury after single oral doses of
203Hg-labeled mercuric acetate or phenyl-
pheny!
mercuric acetate. With both compounds, the
highest concentrations of mercury were
found in the kidneys and then the liver, lung,
and heart; accumulations in other organs
were comparatively small. In the kidney and


Kruger mercury vapor meter and deter-
mined the mercury content by its absorb-
ance. Values as low as 0.01 ppm Hg were
reported.

Pappas and Rosenberg (1966) used a Schoni-
ger combustion flask to burn samples. The
released mercury was absorbed in dilute
HCI and collected on a CdS-impregnated
asbestos pad. The pad was pyrolyzed at
650°C and the released Hg vapor swept into
a quartz-windowed cell where its absorb-
ance was measured by a photometer using a
mercury lamp as the light source. Sensitivity
of 0.01 ppm Hg was reported for wheat
samples.

Lidums and Ulfvarson (1968) burnt small
samples (20-200 mg) of biological material in
astream of oxygen, and collected the Hg on
gold foil. The gold foil was then heated, re-
leasing mercury vapor which was swept into
acell and its absorbance measured by a pho-
tocell using a mercury lamp as the light
source. As little as 0.001 w g Hg/g sample
could be determined. The procedure was
said to work well for blood, plasma, urine
and sea bottom sediments, but the authors
were not quite satisfied with it for more diffi-
cult organic samples.

A.O. Rathje (1969) determined mercury in
urine without digestion. The urine (2 ml) was
treated with 5 ml conc. HNO,, diluted to 50
ml and the mercury reduced by the addition
of stannous chloride. Air or nitrogen was
then bubbled through the solution and the
mercury vapor swept through a drying tube
into the cell of the detector. The instrument
used was a Perkin Elmer Model 303 atomic
absorption spectrophotometer with a GE
64811 mercury discharge lamp to provide the
253.7-mm line and with the burner assembly
removed and replaced by an 8-inch cell with
quartz windows. As little as 6 ng Hg could
be detected, thus for a 2-ml sample indicat-
ing a sensitivity of 0.003 ppm.

44

Uthe, Armstrong and Stainton (1970) of the
Fisheries Research Board of Canada deter-
mined mercury in fish using very small sam-
ples (0,1-0.5 g). The sample was first digested
with H,SO, at 50°-60°C and then with
KMn0O, at room temperature. The mercury
was reduced with stannous sulfate and the
mercury vapor swept by an air stream
through a drying tube and a gas cell ina Per-
kin-Elmer atomic absorption spectrophoto-
meter.

More recently the Association of Official
Analytical Chemists has accepted the pre-
scribed atomic absorption method as official.
A brief description of the method is as fol-
lows:

Five gram samples of fish are digested under
a water condenser first with H,SO,, HNO;
and NaMoO, and then with HNO, and
HC10,. The digest is made up to 100 ml, and
a 25-ml aliquot taken for atomic absorption
analysis. Using a closed system consisting
of a reaction flask, a drying flask, a gas cell
in an atomic absorption spectrophotometer
and a recirculating air pump, the mercury is
reduced with stannous chloride and the re-
sulting mercury vapors swept through the
gas cell where the absorbance is measured.

II.C. Neutron Activation — The use of neu-
tron activation analysis has excited the at-
tention of many analysts, because of certain
apparent advantages. It purports to be a
nondestructive method. Also, it can yield
definitive results with very small samples of
even such materials as skin or hair. Further,
in a reactor designed for automatic analysis,
practically the entire operation becomes
automatic including irradiation, counting
and calculations.

However, the accuracy of the method is
affected by the fact that sodium is present in
practically all biological samples. If the level
of sodium activity following irradiation is
permitted to decay to tolerable limits, often
the mercury has decayed to the point that it


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Swedish birds from the past 100 years."’ Oikos 17:
71 (1966).

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of Swedish birds from the past 100 years.’ Oikos
17(1):71 (5966).

Berg, G. Introduction: “‘A view from the podium.”
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versity of Rochester. In Chemical Fallout, Miller.
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lisher, Springfield. Ill. (1969).

Berglund, Nilsson, G. ‘Mercury in food prod-
ucts’ Methylmercury poisoning from eating
game birds."’ 19 p. Fisheries Research Board of
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artidningen 64 (37): 3621 (1969).

Berglund, F., and Wretlind, A. ‘Toxicological evalua-
tion of mercury in Swedish fish.’’ 5 p. U.S. Bu-
reau of Commercial Fisheries. Trans. from Var,
Foda 19(1):9 (1967).

Berglund, F., and Berlin, M. ‘Risk of methylmercury
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95


man or florist until suitable inexpensive re-
placements are available.

3. Flowering and Foliage Plants (Soil treat-
ments)

A. Mercury compounds

(1) Cyano (methylmercuric) guanidine
[Ref. I-C-46-00.02] 2.5 to 5.3 ppm as soil
drench for soil-borne diseases.

(2) Hydroxymercurichlorophenol:
[Ref. I-H-06-00.01] 0.0143 to 0.0214 Ib/10 sq
ft.

(3) Phenylmercuric acetate: [Ref. I-P-
08-00.04] 26 ppm solution as soil spray.

B. Substitute compounds

(1) Captan: [Ref. I-C-10-00.12] 15 gal of
1200 ppm solution/1000 sq ft.

(2) Chloropicrin: [Ref. I-C-19-00.01]

(a) 485 to 1976 Ib/acre with cultipack
or water seal.

(b) 150 to 200 Ib/acre with plastic
seal.

(c) 82 to 115 Ib plus 168 to 235 Ib
methyl bromide/acre with plastic seal.

(d) 319 Ib plus 240 Ib Dichloropro-
penes/acre with plastic seal.

(3) p-(Dimethylamino) —_ benzenediazo
sodium sulfonate: (Ref. I-D-14-00.02]: 1.25
to 2.8 02/50 gal/400 sq ft or 1 pt above solu-
tion/each 6-inch pot.

(4) Methyl bromide: [Ref. I-M-06-
00.02] 1 to 2 1b/100 sq ft with tarpaulin, 20 to
50 gal of 65% formulation/acre by chisel
application.

(5) Methyl isothiocyanate: [Ref. I-M-
07-00.01] 25 to 50 gal/acre

(6) Pentachloronitrobenzene: [Ref. I-P-
04-00.07] 27 to 232 Ib/100 gal or 65 to 232 Ib
as a dust/acre.

(7) Tetrahydro-3, 5-dimethyl-2H-1, 3,
5: thiadiazine-2-thione (Mylone): [Ref. I-T-
07-00.02]: 4.1 Ib/10 to 80 sq yd.

18

C. Comparative effectiveness and impact

(1) Highly effective substitute com-
pounds are already registered for this use
and are widely employed.

(2) Impact of withdrawal will be slight
on manufacturers and consumers alike.

4. Flowering and Foliage Plants (Foliar treat-
ments)

A. Mercury compounds

(1) Cyano (methylmercuric) guanidine:
(Ref. I-C-46-00.02] 25 ppm. Apply as neces-
sary.

(2) Phenylmercuric triethanol ammon-
ium lactate: [Ref. I-P-17-00.01] Gladiolus
only. 146 ppm. Dip flower spikes before
shipment or storage. Laurel and Rhododen-
dron: 94 ppm in 2 or 3 applications.

B. Substitute compounds

(1) Benomyl: [Ref. I-B-02-00.02] 4 0z/
100 gal, as required.

(2) Captan: [Ref. I-C-10-00.11 through
-13] 1.0 Ib/100 gal or 2.1 Ib as a dust/acre, as
required.

(3) Copper-Bordeaux: [Ref. I-C-25-
00.08] Use 2-2-50 to 4-4-50 mixtures as re-
quired.

(4) Copper oleate: [Ref. I-C-30-50.03]
Up to 4 Ib of 25% formulation/gal. Home-
owner use, as required.

(5) Copper oxychloride: [Ref. 1-C-32-
00.06 and .07] 2.1 Ib metallic copper equiva-
lent/100 gal; 0.125 to 0.25 oz of metallic cop-
per plus 0.1 to 0.2 oz of sulfur and 0.025 to
0.050 oz of zineb/gal. Household use, as
required.

(6) Copper oxychloride sulfate: [Ref. I-
C-33-00.08] 1.25 to 2.2 Ib metallic copper
equivalent/100 gal, or 1.4 to 3.5 Ib as a dust/
acre. As required.

(7) Copper 8-quinolinolate: [Ref. I-C-
34-00.01] 1.0 oz of 2.0% formulation plus
Karathane (dinocap) and petroleum distil-


terial, or 0.03% product based on finished
weight of material; apply as spray.

(2) Phenylmercuric acetate (15%): [Ref.
3090-28] 10 parts product to 90 parts water;
spray on material depositing 0.3% of total
mixture in the filling material.

B. Substitute compounds

(1) Bis (tri-n-butyltin) oxide (25%):
[Ref. 6390-7] 0.1 to 0.2% by weight of mate-
rial.

(2) n-Alkyl (60% Cy 4, 30% Cig, 5% Cy,
5% Cg) dimethylbenzyl ammonium chloride
(50%): [Ref. 6390-9] Apply to leave 0.25 to
1% product by weight.

(3) n-Alkyl (60% Cy 4, 30% Cy. 5% Cy,
5% Cyg) dimethyl benzyl ammonium 2
ethylhexoate (25%): [Ref. 6390-13] Apply to
yield 0.025% active ingredient by weight.

(4) Tributyltin neodecanoate (98%):
[Ref. 8314-5] 0.1 to 2% product by weight of
material.

(5) Alkyl (average Cj) amine salts of
tetrachlorophenol (100%): [Ref. 3090-146]
0.25 to 2% product based on dry weight of
material.

(6) Sodium pentachlorophenate (79%)
and sodium salts of other cholorophenols
(11%): [Ref. 464-125] 0.1 to 0.75% product
by weight of material treated.

(7) Zine dimethyldithiocarbamate
(46%) and zinc 2-mercaptobenzothiazole
(4%): [Ref. 1965-26] 1 to 1.5% product by
weight of material.

(8) Sodium pentachlorophenate (79%):
[Ref. 464-125] 0.1 to 0.75% product by
weight of treated material.

C. Comparative effectiveness and impact

(1) Substitute compounds appear to be
adequate.

(2) Impact on industry and consumer
expected to be minimal.

IV. Food, Feed and Tobacco Crops
(see also XI, Seed Treatments)

1. Cotton
A. Mercury compounds

Cyano (methylmercuric) guanidine: (Ref. I--
C-46-00.01} 0.016 Ib plus 0.68 to 0.72 Ib of
pentachloronitrobenzene/acre (12,400 linear
ft of row) in furrow and covering soil at time
of planting. For soil-borne seedling diseases.

B. Substitute compounds

(1) Captan: (Ref. I-C-10-00.11] 4 to 6 Ib/
acre (12,400 linear ft of row) or 1.0 Ib plus
1.0 lb pentachloronitrobenzene/12,400 linear
ft of row in furrow and covering soil at time
of planting.

(2) Chloroneb: [Ref. I-C-16-00.11] 1.0
to 2.0 Ib/12,400 linear ft of row

(3) Dichlone: [Ref. I-D-06-00.04] 0.5 Ib/
12,400 linear ft of row.

14

(4) 5-Ethoxy-3-trichloromethyl-1, 2, 4-
thiadiazole: [Ref. I-E-01-00.01] 0.25 to 0.37
Ib plus 1.0 to 1.5 Ib of pentachloroni-
trobenzene/ 12.400 linear ft or row.

(5) Monosodium salt of 2, 2-Methyle-
nebis- (3, 4, 6-trichlorophenol): (Ref. I-M-
22-00.01] 0.560 to 1.125 0z/12,400 linear ft of
row.

(6) Pentachloronitrobenzene: [Ref. I-P-
04-00.06] 1.0 to 5.0 Ib/12,400 linear ft of row.

(7) Zinc ion- maneb coordination prod-
uct: [Ref. I-Z-04-00.06]

(a) 0.45 to 1.2 Ib/12,400 linear ft of
row.

(b) 0.3 Ib plus 0.3 Ib PCNB/12,400
linear ft of row.

(8) Zineb: [Ref. 1-Z-10-00.08]

(a) 2.25 to 3.75 Ib/12,400 linear ft of
row.

(b) 1.3 Ib plus 0.75 Ib captan and 1.15
Ib PCNB/12,400 linear ft of row.


Friberg, L. ‘‘Studies on the metabolism of mercuric
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(1953).

Friberg, L., Odeblad, E., and Forssman., S. **Distribu-
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cutaneous injection."’ Arch. Industr. Health, 16:
163 (1957).

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Fry. D.S.. and Wolfson, N. ‘The binding of organic
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Fujiki, M. **Studies on the course that the causative
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Fukuhara, N. **Ultrastructural changes in the cerebel-
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Fujita, E. ‘‘Experimental studies of organic mercury
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363 (1965a).

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Goldberg, A.A., and Shapero, M. “Toxicological haz-
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99


2. Substitute compounds

A. Alkyl dimethyl benzyl ammonium
chlorides and Bis (tributyltin) oxide: {Ref. I-
A-08- 15.02]

(1) 3750 ppm quaternary alone.

(2) 5000 ppm quaternary plus 250 ppm
TBTO.

(3) 625 to 2500 ppm quaternary plus 125
to 500 ppm TBTO.

B. Captan:
0.15 to 0.96% by weight.

C. 4-Chloro-3, 5-Xylenol: [Ref. I-C-21-
00.02] Use as required.

D. Copper 8-quinolinolate: [Ref. I-C-34-
00.02] Use as required or 0.04%. metallic
copper equivalent in wax sizing.

E. Diisobutylphenoxyethoxyethyl dime-
thyl benzyl ammonium chloride: [Ref. I-D-
13-00.01] Use 0.4% of a mixture of 40.9%
quaternary plus 11.7% tributyltin salicylate
based on dry weight of solids; or use 0.5 of
above in the tub size.

F N-Dodecylguanidine hydrochloride:
[Ref. I-D-27-80.01] 0.4 to 0.8% on weight of
paper.

G. Dodine: [Ref. I-D-28-00.04] 0.8% on
weight of paper.

H. 2, 2’-Methylenebis-(3, 4, 6-trichloro-
phenol): (Ref. I-M-13-00.03] 0.02 to 0.25%
on weight of paper.

Ix.

1. Plastics (unspecified)
A. Mercury compounds

(1) Phenylmercuric acetate: [Ref. I-P-
08-00.01] Fungistatic surface treatment: 150
to 225 ppm spray.

26

I. Sodium dimethyldithiocarbamate:
[Ref. I-S-09-00.05] 0.455 to 0.911% plus 0.04
to 0.08% sodium 2-mercaptobenzothiazole
based on weight of sheet.

J. Sodium pentachlorophenate: [Ref. I-S-
15-00.03] 0.1 to 0.5% based on weight of
sheet.

K. Sodium o-phenylphenate: [Ref. I-S-
16-00.09] 0.1 to 0.3% on weight of stock.

L. Thiram: Ref. I-T-10-00.08] 0.3 to 1.2%
plus 0.3 to 1.2% of zinc pentachlorophenate
based on weight of finished paper.

M. 3,4’ 5-Tribromosalicylanilide: [Ref. I-
T-11-00.01] 0.025 to 0.25% or 200 or more
ppm based on weight of paper.

N. Ziram: (Ref. 1-Z-11-00] 0.46 to 0.86%
plus 0.02 to 0.037% zinc-2-mercaptoben-
zothiazole on weight of sheet.

3. Comparative effectiveness and impact

A. Mercury compounds are highly effec-
tive at low concentrations. Substitute mate-
rials require higher dosages.

B. Mercury compounds are colorless.
Some substitute compounds impart undesir-
able colors, others do not.

C. Substitute compounds appear to be
adequate.

D. Impact on industry will be very small,
none on consumer.

Plastics

(2) Phenylmercuric borate: [Ref. I-D-
13-00.04] Fungistatic film: 50 ppm phenyl-
mercuric borate plus 31.25 ppm diisobutyl-
phenoxy ethoxyethyl dimethyl benzyl
ammonium chloride by weight of pellets
before molding.


Mukhtarova, N.D. “‘Takayasi syndrome in chronic
granosan poisoning.’ Gig. Truda Prot. Zabol. 14
(9): 27 (1969).

Mukjacjeva, O.N. ‘On the clinical picture of non-
occupational poisoning with granosan.’’ Soviet
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mercury in fish by flameless atomic absorption: A
collaborative study.’ Unpublished manuscript.
Food and Drug Administration, Denver, Colora-
do (1970).

Muraki, K. ‘“‘Experimental studies on the cause of
Minamata disease in cats. II. Hg.-content of or-
gans chronically intoxicated with fish and Hg.-
ethy! phosphate.’’ Folia Pharmacol. Jap. 61 (4):
269 (1965).

Murakami, U., Kameyama, Y., and Kato, T. “Effects
of vaginally applied contraceptive with phenyl-
mercuric acetate upon developing embryos and
their mother animals.’* Ann. Rep. Res. Inst. En-
viron, Med., Nagoya Univ., Japan, 88 (1955).

Muto, T., and Suzuki, T. ‘‘Analytical results of resi-

* dual mercury in the Japanese storks; ciconia ci-
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and Toyooka regions.”’ Jap. J. of App!. Entomol.
and Zool. 11 (1): 15 (1967).

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in the Minamata District—with special reference
to the pediatric observation."’ Kumamota Med. J.
(Jap, ed.) (Supp. 1) 31: 10 (1957).

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etiology occurring in the Minimata District—with
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penicillamine on the brain defect of fetal rat poi-
soned transplacentally with methylmercury.”
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apples and pears.’ N.S, Wales. Dept. Agric.
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(1964),

109


coin, Wallace. et al., report on the work of
Furutani and Osajima which gave positive
results. They demonstrated that a well-
drained soil containing 0.3 ppm mercury
grew rice containing 0.3 ppm, while a poorly
drained soil containing 1.4 ppm yielded rice
containing 0.8 ppm mercury.

Evidence is in favor of the translocation of
mercury from soil to plants, including the
edible portions. In addition, evidence is also
in favor of the conclusion that mercury-
treated plants will bear fruit with a higher
mercury content than the normal back-
ground.

I.E. Animals — ‘‘Background”’ levels of
mercury for animals are difficult to assess,
since the agricultural use of mercury prod-
ucts is so widespread, and completely un-
contaminated food sources are rare. Wal-
lace, et al., (1971), give the normal value for
eggs and the flesh of birds and. animals as
generally less than 0.02 ppm. Marine fish
have mercury concentrations usually below
0.10 ppm and nearly always below 0.15 ppm,
whereas the mercury levels of 0.20 ppm or
less are assumed to be normal for fresh wa-
ter fish. The higher background levels found
for fish when compared to other animals or
fruits and vegetables is due to the marked
ability of fish to accumulate mercury.

III.F. Fossil Fuels — From the beginning of
time, the products and residues of geochem-
ical processes and the life cycles of terrestri-
al and aquatic organisms have combined to
yield very appreciable mercury contents and
distinct regional patterns in fossil fuel de-
posits. Joensuu (1971) analyzed 36 American
coals and found an average mercury content
of 3.3 ppm.

Applying a conservative estimate of | ppm
mercury in coal to the yearly world produc-
tion of coal of 3 x 10? tons per year. Joensuu
concluded that 3000 tons of mercury per
year are released into the environment. He
compares this to the calculated upper limit
of natural release of mercury due to chemi-
cal weathering of 230 tons per year.

I11.G. Other Sources — Other sources of
mercury in the environment have included
mine tailings, discharges from chlor-alkali
plants, and dissipative uses such as paints,
agricultural pesticides, pulp and paper, and
pharmaceuticals. Of the dissipative uses,
paint and agricultural pesticides are the larg-
est. Mercury losses from chlor-alkali plants
have been greatly reduced in the past year,
and the pulp and paper uses have been cur-
tailed.



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Laurent, P. ‘La pseudobranchie de Téléostéens:
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Lee. W.R. “The history of the statutory control of
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Lee, D.F., and Rongham, J.A. ‘*Mercury residues in
potatoes."’ Pest. Sci. 1: 150 (1970).

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“Mercury content determination in grains not
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14: 221 (1963).

Leger, R. ‘Mounting peril; mercury contamination in
grains not treated with mercuric fungicides.”
Roczniki Pah. 14: 221 (1963).

Leger, R. ‘Mounting peril, mercury contamination of
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Lieck, H., and Agren. G. ‘‘On the occurrence of a
thiamine-inactivating factor in some species of
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Lihnell, D.. and Stenmark, A. “Bidrag till kannedo-
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with phenyl mercuric acetate. ‘*Rice Experiment
Station, Crowley, La.. S6th Annual Report
(1964).

Lindstedt, G. ‘*A rapid method for the determination
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Lindstedt, G.. and Share, I. “*Microdetermination of
mercury in biological samples. Part I]. An appara-
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in digested samples.”” Analyst 96 (1140): 223
(1971).

Lindstrom, O. “Diffusion of mercurial in the fruit coat
of treated seed."’ J. Agri. Food Chem. 7: 562
(1959),

Lidums, V., and Ulfvarson, U. “Mercury analysis in
biological material by direct combustion in oxy-
gen and photometric determination of the mercu-

106

ry vapour."’ Acta Chemic Scandinavica 22 :
2150 (1968).

Ling. Clement. ‘*Portable atomic absorption photome-
ter for determining nanogram quantities of mercu-
ry in the presence of interfering substances.”
Anal. Chem. 40 (12): 1876 (1968).

Ljunggren, L. ‘The influence of mercury poisoning
on the reproduction and general health of wood
pigeons."* Viltrevy 5 (8): 423 (1968).

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Science Research Council. Stockholm, Sweden.
March 20, 1969.

Lofroth, G., and Duffy, M.E. ‘‘Birds give warning.””
Environment II (4): 10 (1969).

Loosmore, R.M.. Harding, J.D.J., and Lewis. G.
“*Mercury poisoning in pigs.”’ Vet. Rec. 81: 268
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“Studies in humans on the distribution of mercu-
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for biological substances. This affinity may
be described by the equation:

CH,Hg* + X= CH,HgxX
Relative affinities for various biological
substances may then be obtained by com-

paring the equilibrium constants for this re-
action.

_ CH3HeX
CH3Hgt =X

Hughes has measured some equilibrium
constants and the values are given below:

Association Constants of Methylmercury for Certain Ligands

Ligand RSTM OH” I BrCl

Log, K 7 9.7 9.0 7.0 5.7

Equilibrium Constants of CH, Hgl for several Proteins

Protein Kx 10°
Human serum albumin 25
Bovine serum albumin 1
Bovine oxyhemoglobin 20
Bovine carbonylhemoglobin 6

Hughes argues that from the magnitude of
these association constants, methylmercury
ion can exist only in infinitesimal concentra-
tions in biological solutions. Thus at pH 7,
there must be 500 times as much methylmer-
cury hydroxide as methylmercury ion. If
chloride is also present at physiological con-
centrations (0.1M), Hughes calculates that
there must be 100 times as much methylmer-
cury chloride as methylmercury hydroxide.
However, since all biological systems con-
tain thiols, the extremely large association
constant for this reaction must mean that all
but traces of the mercurial will be bound to
thiols, provided that they exceed the amount
of mercury present. This is usually the case,
since human blood plasma is 0.5 millimolar

68

thiol, and the red cells contain 60 times as
much sulfhydryl in their hemoglobin. Man's
plasma alone should be able to combine with
1 1/2 M of mercurial containing 300 mg of
mercury. Methyl mercury also has a strong
affinity for many other groupings present in
biological substances as discussed in the
previous section (Hughes. 1957).

One can modify the relative affinity of the
mercurials for various sulfhydryl com-
pounds by replacing the CH, group with
larger organic radicals and with organic radi-
cals containing other functional groups. One
may expect interference from a large group-
ing if the SH group were located in a ‘‘tight””
part of the protein molecule, or if there were
charges on groups adjoining the SH group;
and if the mercurial carried an identical
charge. If the mercurial carried the charge
opposite to that of the region surrounding
the SH group, the affinity should be in-
creased. Similarly, after binding to SH, the
mercuric ion still contains a free valence
capable of combining with some other
properly placed group. Therefore, in gener-
al, mercuric ions should bind more tightly
than simple mercurials, and considerable
variation in affinity should exist from protein
to protein (Hughes, 1957).

Most of the thiols of human plasma can be
accounted for by serum mercapto-albumin
containing | thiol group per protein mole-
cule. However, 5 to 10% of the total thiol
content of human plasma is present in the
form of small molecules. Thus a mechanism
is provided for the egress of mercury from
the blood stream in combination with one of
the small diffusible thiols. Simple mercuri-
als, such as methylmercury halides, are 100
times as soluble in lipids as water. The
amount of mercury present at any one site
must be small in the presence of thiol, a
definite infinitesimal amount is always pres-
ent, and if any leaves the system by dis-
solving in a lipoid membrane, more will dis-
sociate from the protein-mercurial complex


5. Trees and Shrubs (Foliar application for
disease control)

A. Mercury compounds

() Methylmercury — 8-hydroxyquino-
linolate: [Ref. I-M-19-00.01 and .02] For
anthracnose, leaf blights, leaf spots, twig
blights. 1 0z/100 gal (75 ppm solution).
Spray.

(2) Phenylmercuric acetate: [Ref. I-P-
08-00] For anthracnose, leaf blight, leaf
spots, twig blights. 125 ppm solution, spray.

(3) Phenylmercuric dimethyldit-
hiocarbamate: [Ref. I-P-] For twig blight on
eastern red cedar only, in nurseries. 180 ppm
solution, spray at 10- to 14-day intervals.

(4) Phenylmercuric triethanol ammon-
ium lactate: [Ref. I-P-]

(a) For elm leaf spot only: 9.4 ppm
spray at 2- to 3-week intervals.

(b) For hickory, maple, oak, etc.
anthracnose, leaf spots. Use 9.4 to 19.0 ppm
spray as required.

B. Substitute compounds

None directing use on trees specified for
mercury compounds. Maneb is used for an-
thracnose on dogwood and might be some-
what effective on other trees.

C. Comparative effectiveness and impact

(1) Adequate substitutes for mercury
are not registered.

(2) Impact of withdrawal of mercury
compounds for these uses would be slight on
the manufacturer but severe on the consum-
er and would result in loss of many trees,
particularly Sycamore severely injured by
anthracnose. Cost of tree removal on city
streets and in parks is very high.

20

6. Trees and Shrubs (Injection application)
A. Mercury compounds

Mercuric chloride: [Ref. I-M-04-00.02] For
Dutch Elm disease. Inject 0.12% solution in
methyl alcohol.

B. Substitute compounds
None
C. Comparative effectiveness and impact

Impact of withdrawal of mercury for this
will be highly important to the manufactur-
er, but product is of doubtful or marginal
value, and impact on disease control will be:
very slight to negligible.

7. Trees and Shrubs (wound dressings)
A. Mercury compounds

(1) Mercuric chloride: [Ref. I-M-04-
00.02] 1930 ppm.

(2) Phenylmercuric nitrate: [Ref. I-P-
13-00.01] 3000 ppm.

B. Substitute compounds

(1) Copper naphthenate: [Ref. I-C-30-
00.01] 3.3 to 10.0% in asphalt.

(2) Copper sulfate, basic: [Ref. I-C-36-
00.10] 1.9% as metallic copper equivalent
plus 1.2% phenol.

(3) Sodium o-phenylphenate: [Ref. I-S-
16-00.07] 2.0% tetrahydrate paste.

(4) Thiram: [Ref. I-T-10-00.05] 1.0%
paste or in asphalt.

C. Comparative effectiveness and impact

() Effectiveness of substitute com-
pounds is probably about equal to that of
mercury.

(2) Impact on withdrawal of mercury
for this use would be neglibible.


considerable risk for accumulation of alkyl-
mercury compounds on repeated exposure.

Serious poisonings and fatalities resulting
from the manufacture and handling of the
alkylmercury compounds have been de-
scribed in the literature. Hundreds of people
have been poisoned from the consumption
of wheat treated with these compounds; an
entire family was poisoned from the eating
of meat from hogs fed alkylmercury-treated
grain. The fish which caused the epidemic
poisonings in Minamata and Niigata con-
tained this compound as did the seeds which
caused the drastic reduction in the bird pop-
ulations in Sweden. It is the opinion of this
Special Group that pesticides containing
alkylmercury compounds can not be labeled
adequately to protect the safety of the pub-
fic. The Group recommends that the regis-
trations for pesticides containing alkylmer-
cury compounds be suspended, because of
the immininent hazard to human health.

VII.B.2. Pesticides Containing Metallic
Mercury, Arylmercury or Inorganic Mercu-
ry — The pesticides comprising this catego-
ry are considered on the basis of their poten-
tial for environmental contamination and on
the basis of the possible effect the particular
use may have on human health.

VII.B.2.1. Pesticidal Mercury and the envi-
ronment — Mercury resulting from pestici-
dal use may contaminate the soil, water, or
atmosphere. Because of the volatility of
mercury and its natural circulation in the
environment, mercury contamination of the
soil or atmosphere will eventually result in
water and food residues.

Pesticidal mercury may reach the soil froma
number of sources: from treated seeds or
grain: from fall-out following sprayed appli-
cations to agricultural and ornamental
plants: from the treatment of lawns and turf;
from the wash-off of painted structures; and
from the emptying of vats in which bulbs,

88

corms, textiles, fabrics, fibers, logs, or lum-
ber were treated.

Mercury may reach water either directly
from one of the above applications, e.g.,
emptying of vats in which fabrics were treat-
ed. Mercury may also reach the aquatic envi-
ronment bound to soil particles or from the
washing of the atmosphere by rain.

Mercury may become firmly bound to the
soil. This phenomenon of mercury adsorp-
tion is intimately related to the type of soil
with which the mercury comes in contact.
The nature of the colloidal soil particles,
whether they are high in organic content or
are of clay or sandy composition, affects
adsorption. The solubility of the mercury
compound and the pH of the soil also affects
soil adsorption. The temperature and the
condition of soil moisture also play an im-
portant role in adsorption (Mrak, 1969). The
affinity of certain soils for mercury is indi-
cated by the failure of mercury applied as
orchard sprays (phenylmercuric acetate)
over a period of several years to migrate
below the surface 2 inches; the soil con-
tained 500 or 1,100 ppb mercury depending
on the number of spray applications (Ross
and Stewart, 1962).

Even in those instances in which mercury is
firmly adsorbed to soil, water contamination
may result. Mercury held in the soil may be
carried by water with possible subsequent
contamination of water courses, water sup-
plies, and groundwater. Runoff after either
rainfall or irrigation may physically trans-
port particles to which mercury adheres, or
the water may leach the pesticide from the
soil particles (Mrak, 1969).

Much has been said about the natural back-
ground of mercury in the environment.
However, it is difficult, if not impossible, to
separate the naturally occurring mercury
levels from the levels created by man. The


CHAPTER I

THE PESTICIDE USES OF MERCURY

Introduction

Because of incomplete records and the fact
that specific uses for products registered
‘*For manufacturing use’* can not always be
identified, we are not certain that we have
identified all pesticide uses of mercury or all
available substitutes. It is estimated that the
following outline covers approximately 98%
of all such uses.

The classification of uses is arbitrary and is
usually based on label claims which are of-

ten so general in nature as to prohibit specif-
ic identification.

According to figures produced by the Bu-
reau of Mines, about 986,252 Ib of metallic
mercury were used in the production of pes-
ticides in 1969. This included production of
products from imported mercury and other
sources.

Summary and Conclusions

There is a serious lack of information on
nonagricultural uses of mercury-containing
pesticides, and data are not available for a
proper evaluation of the economic impact of
the withdrawal of such uses.

Mercury compounds presently registered
include alkyl, aryl and inorganic types. All
alkylmercury compounds used for seed
treatments and all mercury compounds used
as slimicides, algicides and in laundries have
previously been cancelled and are not in-
cluded in this report. The remaining uses
involve many different commercial, house-
hold, industrial and institutional applica-
tions. Uses requiring the largest amounts of
mercury include paints, seed treatments and
turf disease control.

A careful review of registrations of nonmer-
curial products indicates that no substitutes
are currently registered for the following
uses:

(1) barley - seed treatment for stripe
disease

(2) broomcorn - for mildew control
(3) cellulose sponges - preservation

(4) sacks, bins and containers for
treated seed - fungus and bacterial
plant disease organisms

(5) seam and bedding compounds used
in boat construction

(6) textures and other dry products
ultimately applied by dispersion in
water

(7) elm trees (by injection) - Dutch
Elm Disease

(8) wheat - seed treatment - seed-
borne phase of smut control.

It is also recognized that, although substitute
materials appear to be available for all other
uses, the general patterns described on
many product labels preclude an accurate
assessment of individual applications in spe-


to maintain the equilibrium. It is thus possi-
ble for all the mercury to diffuse through the
membrane: Hughes postulates that these
mechanisms would explain the rapid distri-
bution of methylmercuric halide to all tis-
sues of the body. Other compounds of mer-
cury show a different distribution pattern.

Larger compounds of mercury do not ap-
pear to be selectively soluble in lipid sol-
vents: they seem to be of such large size as
not to diffuse through pores in cell mem-
branes. The upper limit of size for ready
diffusion is not known; however, even glu-

cose, an uncharged molecule, appears to
enter cells only by active transport. In the
case of charged molecules, even smaller
molecules may be excluded.

The bivalency of inorganic mercury, despite
its small size, may act to restrict further its
diffusibility since. with both bonds clinging
to protein, the amount of time when it is free
for diffusion must be reduced still further.
This bivalency may also explain its ability to
coagulate proteins since, by bonding to adja-
cent protein molecules, it can link them to-
gether causing aggregation (Hughes, 1957).

69


later other parts of the body; and (3) person-
ality change known as erethism. This condi-
tion is characterized by irritability, bursts of
temper, and excitability, sometimes alter-
nating with depression. There are numerous
other signs and symptoms including saliva-
tion, loss of appetite, weight loss, weakness,
and disturbances of urinary and gastrointes-
tional function (Goldwater, 1957).

There is little or no correlation between uri-
nary mercury levels and severity of symp-
toms. While urinary mercury levels may
give some indication of the degree of expo-
sure, they are of limited value in diagnosis of
poisoning, since high levels can be found in
human subjects who are symptom free, and
low levels in those exhibiting marked evid-
ence of mercurialism. Albuminuria severe
enough to result in nephrotic syndrome can
occur (Goldwater, 1957).

V.B.2. Organic Mercury Compounds — The
organic compounds of importance in pesti-
cides are the aryl and alkylmercury com-
pounds.

V.B.2.1. Arylmercury Compounds — Cases
of clinical poisoning with phenylmercury
salts are rare in the literature in comparison
with inorganic and alkylmercury com-
pounds. However, the toxicity of the phen-
ylmercuries can not be discounted. One may
conclude from the animal data that these
compounds are highly toxic. In addition,
since phenylmercury is metabolized to inor-
ganic mercury in the liver, one may expect
kidney involvement resulting from toxic
doses of the compound. Phenylmercuric
acetate is irritating to the skin and may also
produce a delayed sensitivity (Sunderman,
et al., 1956). Hypersensitivity has been re-
ported to occur with several phenylmercury
salts (Matthews, 1968). Acrodynia (Hirsch-
man, et al., 1963; Matthes, et al., 1958;
Schrager, 1964) and neuromyasthenia (Mill-
er, et al., 1967) have been reported from
inhalation of phenylmercury vapors from

76

paints. Dunn reported four cases of mercury
poisoning resulting from the use of fiber
glass air filters containing phenylmercury
acetate from forced draft heaters. Becker, et
al., (1962), reported on 5 cases of nephrotic
syndrome associated with contact with mer-
cury. Three of these cases involved the use
of ammoniated mercury ointment, one asso-
ciated with the use of phenylmercury paint
additive, and one with a mercurial diuretic.

V.B.2.2. Alkylmercury Compounds — If
alkylmercury compounds come in contact
with the skin, dermatitis may develop. The
first symptoms are warmth, swelling and a
burning sensation. Later, blisters may form
which may break, producing a sodden, gray-
ish-white appearance. These symptoms may
occur at any time, from a few days to sever-
al weeks, after the first contact. Irritation of
the mucous membranes of the nose, mouth
and throat are often described in connection
with alkylmercury compounds. These sensa-
tions may come after a short exposure and
usually disappear quickly when the expo-
sure is terminated (Lundgren and Swensson,
1949),

V.B.2.2.1. Acute Poisoning — In acute al-
kylmercury poisoning, symptoms of in-
volvement of the respiratory tract and the
alimentary tract are described. Headache,
fatigue, and other nervous symptoms have
been reported. Myalgia has been noted and
albuminuria is a transient symptom (Lund-
gren and Swensson, 1949).

V.B.2.2.2. Chronic Poisoning — In chronic
poisoning, symptons are fatigue, headache,
impairment of memory and of concentra-
tion, numbness and tingling of lips and
tongue and later of the limbs, slurred
speech, increasing ataxia and impaired gait.
There may be concentric narrowing of the
visual fields and impairment of hearing. The
symptoms may first appear as long as 2
months after the exposure has ceased. The
sympsoms may increase, remain static, or
decrease. In cases of severe poisoning, the


possibility of occurrence of the risk.”
(Ruckelshaus, 1971, 6,10).

A product which has previously been regis-
tered may either be cancelled or suspended
if the Administrator determines that the
product does not comply with the provisions
under which it was registered. The initial
step in the administrative process, cancella-
tion of registration, is triggered whenever
the Administrator determines from all the
data before him that there is a substantial
question as to the safety of a product. The
cancellation decision does not turn on a sci-
entific decision alone. The statute leaves
room to balance the benefits of a pesticide
against its risks. In other words, the type,
extent, probability, and duration of potential
of actual injury to man, plants, and animals
will be measured in the light of the positive
benefits accruing from the responsible use of
the pesticide. In its consideration of a spe-
cific pesticide usage, the Agency is mindful
of its statutory directive and duty to the pub-
lic to place thc dictates of health and safety
over economic considerations in its scale of
values.

In the consideration of the term ‘‘safety’’
one must realize that this is never absolute
(Mrak, 1969). Health risks assumed by an
individual in his home or in the street are
accepted as inevitable and may be limited to
some extent by the individual. Health haz-
ards stemming from environmental expo-
sure to chemical agents are beyond the ca-
pacity of the individual to control. (Mrak,
1969).

In the consideration of ‘‘health’’ one must

realize that this encompasses more than an
absence of disease. Included is the feeling of

vii

well-being and capacity of happiness that
derives from a suitable environment - suita-
ble in the sense that makes possible the en-
joyment of nature and her bountiful provi-
sions of flora and fauna (Mrak, 1969).

Based on the above considerations, and as
directed by the Agency, the Working Group
will weigh the following criteria in determin-
ing the need for the continued registrations
of specific uses of mercurial pesticides:

(1) the nature and magnitude of the
foreseeable hazards associated with
each specific use will be evaluated.
These hazards may apply directly to
human health, or to domestic plants
and animals, or to wildlife, or to the
environment generally;

(2) the nature of the benefit conferred
by each use will be weighed. Some
uses are obviously more important
to public health and well-being than
others. The nature of the benefit, if
any, will be detailed;

(3) an attempt will be made to assess
the magnitude of the social cost of
foregoing any use recommended for
cancellation; and

(4) alternatives for each use will be
considered.

As the result of this review and the applica-
tion of the above criteria, the Working
Group will recommend the cancellation of
the registration for those uses which, in its
opinion, there is a substantial question of
safety.


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environment.” Environmental Science. Tech. 4
(9): 765 (1970).

Kleinfeld, M., Messite, J. Kooyman, O., Goldwater,
L.J. ‘Fingernail cystine content in chronic mer-
cury exposure.’ AMA Archives of Environmen-
tal Health 3, 676 (1961).

Kleingeller, A., and Cort, J.H. ‘Mechanism of ac-
tions of mercurial preparations on transport proc-
esses and the role of thiol groups in the cell mem-
brane of renal tubular cells."” Biochem. J. 67, 15-
24 (1957).

Koelsch, F “‘Gesundheitsschadigungen durch organ-
ische Quecksilberverbindungen. Arch. Gewerbe-
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Koeman, J.H., and Van Gederen, H. “Some prelimi-
nary notes on residues of chlorinated hydrocar-
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Netherlands.” Proc. 17th Internat. Symposium
Phytopharmacy, Gent. p. 1879 (1965).

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Kolbye, A.C. “Testimony before the Subcommittee
on Energy, Natural Resources, and the Environ-
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105


alkoxyalkyl compounds are less active and
produce a comparable effect at levels as high
as 30 x 10°7M. All of the mercurials studied
produced c-mitosis, however, there was a
difference in their effects. The aryl com-
pounds gave rise to distinctly more bridges
and fragments than the other mercurials.
The phenyl compounds produced a higher
frequency of multipolar spindles and other
spindle irregularities than the alkyl of alkox-
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compounds are 200 to 1,000 times more
effective than colchicine in producing c-mi-
tosis. Rats which have been maintained on
methylmercury for up to 8 months and in
which mercury has reached a steady state
showed no chromosomal aberrations in the
blood cells (Ahlberg. et al., loc cit, Berglund
and Berlin, 1969).

Asa result of the c-mitotic action, polyploid
as well as aneuploid cells occur. The mer-
curial compounds cause c-mitotic tumors,
and hook-like growths of the roots are also
observed, which represent incomplete tu-
morous action. Fahmy reported studies on
the cytologic effects of organic mercury
compounds, the results of which are in
agreement with the results given by Ramel.
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times less effective than organic mercury in
the production of c-mitosis (Nelson, et al.,
1971).

In a study with Drosophila melanogaster,
selected so that dysfunction of the sex chro-
mosomes in either the female or the male
would result in non-yellow (XXY) daughters
or yellow (Xo) sons, treatment of the female
larvae with aryl or alkylmercury resulted in
a significant increase in the number of ex-
ceptional daughters (XXY) showing irregu-
larities of meiotic chromosomal disjunction
(Ramel, 1967). It has been shown that meth-
ylmercuric hydroxide binds to DNA and
causes irreversible denaturation of DNA in
vitro. Therefore, it may be suspected that
methylmercury could induce mutations. Fol-
lowing the results of the Drosophila study,

14

Ramel (1969) concluded methylmercury
induces mutations, but the mutagenic effect
should be considered minimal. He considers
the genetic risks may be recognized at two
levels. First, if a sufficiently high concentra-
tion should reach the gonads, a segregation
disturbance like the one with Drosophila
may occur. In these cases, one may expect
the human defects will increase which are
caused by the additional chromosome, e.g.,
Down’s Syndrome or Klinefelters Syn-
drome. Secondly are the teretogenic effects
of methylmercury; the accumulation in the
fetus may cause disturbances in chromo-
some segregation during development (Ra-
mel, 1969).

As reported earlier, rats which have been
maintained on methylmercury for 7 to 8
months, until a steady state for mercury is
reached, showed no chromosomal aberra-
tions in any blood cells.

Oharazawa (1968) carried out investigations
on the effects of ethylmercuric phosphate on
mouse embryos with particular emphasis on
embryopathy, teratology, and cytogenetics.
Prior to the experiments, the LD«o of ethyl-
mercuric phosphate was determined as 76
mg/kg for the normal, nonpregnant female
mouse of the ICR-JCL strain. To study pos-
sible fetal malformations induced by ethyl-
mercuric phosphate, 40 mg/kg of the com-
pound was injected subcutaneously on the
10th day of pregnancy. Controls received
only distilled water and no other treatment.
On the 19th day, the mice were sacrificed
and the fetuses removed for comparison
between the two groups. There were no dif-
ferences between food and water intake of
the two groups. The incidence of young
from one litter was not significant. The
weights of the young in the treated group
were decreased. There was a 31.6% inci-
dence of cleft palate among the treated mice,
but no malformations of the bones or skin
were found. The mice were similarly treated
with ethylmercuric phosphate for the chro-
mosome studies. Sacrifice was at 5,9, and 19


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(1969),

101


PR Notice. These cancellations were the
result of implementing the recommendations
of a National Academy of Sciences, Nation-
al Research Council Advisory Committee to
abolish ‘‘no residue’’ and ‘‘zero tolerance”’
registrations. Registrations are being contin-
ued on certain other pesticides based on
pending petitions for finite tolerances or
upon request of a Federal Agency.

VII.A.4. Algicide Use in Swimming Pool —
Aglimycin 200 and Algimycin 300 are prod-
ucts containing phenylmercuric acetate for
the control of algae in swimming pools.
These products were first registered in 1962,
under protest, as provided in the Federal
Insecticide, Fungicide, and Rodenticide Act
of 1947. It was the decision of the United
States Department of Agriculture that the
registrant had not clearly demonstrated the
safety of the products. Termination of the
registrations was affected in 1964, pursuant
to Public Law 88-305 eliminating registra-
tions under protest. The firm reapplied for
registration in 1964 with supplemental data.
Questions were raised by the United States
Department of Agriculture, Food and Drug
Administration, and the Public Health Serv-
ice regarding the data submitted by the firm
purporting to show an adequate margin of
safety to humans when used as directed.
The products were registered in 1965 with
the provision that specific additional data
would be submitted. Since that date, regis-
trant has failed to furnish all the data set
forth by the United States Department of
Agriculture. Notice of cancellation of the
registrations for Algimycin 200 and Algimy-
cin 300 was made on July 22, 1969. The re-
gistrant requested an advisory committee to
review the cancellation action.

VII.B. Currently Registered Uses

In May 1970, the Department of Health,
Education, and Welfare, acting under the
provisions of the Interagency Agreement on
Pesticide Registrations, requested the for-

86

mation of a registration review panel for the
purpose of considering the current registra-
tions of mercurial pesticides. As provided
by the Interagency Agreement, the panel
was composed of representatives of the
Department of Agriculture, the Department
of Interior, and the Department of Health,
Education, and Welfare.

The panel was dissolved on January 20,
1971, following the transfer of all pesticide
responsibilities to the Environmental Pro-
tection Agency. However, the panel submit-
ted their report, although incomplete, so that
it would be available to those responsible for
pesticide regulatory activities.

This report, ‘“‘A Report on the Mercury
Hazards in the Environment,” contain no
unified recommendations for actions to be
taken with the currently registered uses of
pesticides. However, it does contain recom-
mendations from the individual panel mem-
bers. Without exception, the members rec-
ommended cancellation of the registrations
of all alkylmercury containing pesticides.
The members were also in agreement that
only the registrations for essential uses of
pesticides containing inorganic mercury or
arylmercury compounds should be retained.
However, even these registrations should
not be retained if the use poses a water con-
tamination hazard. Consideration has been
given this report in the present study.

While it would be ideal to follow the outline
of uses employed in Chapter 1 of this report,
this was not done in consideration of the
human hazards associated with the use of
mercurial pesticides. Therefore, the uses
have been categorized under two headings:
VII.B.1. Pesticides Containing Alkylmercury
Compounds, and VII.B.2. Pesticides Con-
taining Metallic Mercury, Arylmercury or
Inorganic Mercury Compounds. The human
toxicity of the alkylmercuries is discussed
under VII.B.1. without regard to the envi-
ronmental contamination potentials. The


mercury after administration of phenylmer-
curic acetate as after mercuric acetate. On
the whole, there was a significant positive
regression for both compounds relating dos-
age level with storage. Forty-three percent
of the mercury ingested as mercuric acetate
appeared in the feces, whereas only 20 per-
cent of mercury ingested as phenylmercuric
acetate appeared in the feces. This figure is
not in agreement with Clarkson who found
only 2% absorption of mercuric chloride by
the oral route. One possible explanation for
the tow fecal excretion of mercury after
mercuric acetate ingestion is that of Hughes
cited above. The bivalency of the mercuric
ion causes it to link protein of the intestinal
mucosa, becoming fixed and thus limiting its
absorption and also excretion in the feces.
However no firm conclusions may be drawn
from fecal excretion, since Ulfvarson (1962)
has shown that a significant proportion of
absorbed mercury is excreted by the fecal
route.

In the study of Swensson, Lundgren, and
Lindstrom, cited above, phenylmercuric
acetate, an arylmercury compound, was
absorbed to a much greater extent than ei-
ther mercuric chloride or mercuric nitrate as
indicated by blood levels of mercury. Much
higher levels were also reached in the brain,
kidney, and liver. These findings are in
agreement with Fitzhugh, et al. (1950). Ulfv-
arson (1962) also found much higher levels
of mercury in blood plasma, brain, liver, and
kidneys in rats dosed with phenylmercuric
acetate than those dosed with mercuric ni-
trate.

The absorption after oral administration
appears to be much greater for the alkylmer-
cury compounds than for either inorganic
mercury or arylmercury compounds.
Swensson, et al. (1959) found much higher
levels of mercury in the tissues of animals
fed methylmercuric hydroxide or cyano
(methylmercuric) guanidine than in the tis-
sues of animals fed mercuric chloride. Ulfv-

52

arson (1962) found that methylmercuric
cyanide, methylmercuric hydroxide, and
methylmercuric propandiolmercaptide were
absorbed to about the same extent via the
oral route. In reviewing the available data on
both man and the rat, Berglund and Berlin
(1969) concluded that the intestinal absorp-
tion of methylmercury is more than 90%.

Clarkson (1971) studied the rate of absorp-
tion of inorganic and methylmercury com-
pounds, labelled with 203 Hg in food by
whole-body counting techniques. The exper-
imental results indicated that when mercuric
chloride was added to food, absorption
across the gastrointestinal tract was small,
averaging less than 2% of the daily intake.
When the total body burden of mercury was
plotted against the time on diet, in days, the
curve showed a sharp rise within the first
day of administration of radioactive food
and a sharp fall after the animals were re-
turned to normal food. The sharp rise and
fall were equal in magnitude and corre-
sponded to approximately 25% of the daily
intake. Such curves are typical of isotopes
that are poorly absorbed by the gastrointes-
tinal tract. The rapid rise and fall correspond
to the effect on whole-body count of the iso-
tope’s entry into and removal from the gas-
trointestinal tract, respectively. The curve
also exhibits a slowly rising phase during the
remainder of the times the animals are fed
radioactive food. The slope of the curve cor-
responds to the daily net absorption of the
isotope into the blood stream and body tis-
sues. When radioactive methylmercury
chloride was fed in the diets of the animals,
the curve describing the whole-body counts
was entirely different from those above. The
whole-body count rose continuously
throughout the period of exposure. The
curves suggest that the absorption of meth-
ylmercury from food is practically com-
plete.

Clarkson’s data are difficult to reconcile with
the data of Fitzhugh, et al. and with the high


Table 1, Maximum mercury concentration in air measured at scattered
mineralized and nonmineralized areas
of the western United States*

Sample location

Maximum Hg concentration (ug/m?)!
Ground surface 400 feet above ground?

Ord mine, Mazatzal Mins., Ariz.
Silver Cloud Mine, Battle Mtn., Nev.
Dome Rock Mtns., Ariz.

Mercury mines

20.000 (50)
2.000 (50)
0.128 (6)

0.108 (4)
0.024 (8)
0.057 (20)

Base and precious metal mines

Cerro Colorado Mtns., Ariz.
Cortez gold mine, Crescent Valley, Nev.

Coeur d’Alene mining district, Wallace, Idaho

San Xavier, Ariz.

1.500 (5)
0.180 (60)
0.068 (40)

0.024 (2)
0.055 (4)

0.025 (3)

Porphyry copper mines

Silver Bell mine, Ariz.
Esperanza mine, Ariz.
Vekol Mtns., Ariz.

Ajo mine, Ariz.

Mission mine, Ariz.
Twin Buttes mine, Ariz.
Pima mine, Ariz.
Safford, Ariz.

0.053 (3)
0.032.(3)
0.032 (4)
0.030 (3)
0.024 (3)
0.020 0.022 (3)
0.013 (3)
0.007 (2)

Unmineralized areas

Blythe, Calif.
Gila Bend, Calif.
Salton Sea, Calif.
Ativaca, Ariz.

0.009 (20)
0.004 (2)
0.004 (2)
0.003 (2)

‘Number of measurements shown in parentheses.

? Samples taken from single-engine aircraft.
*From Wallace, ef al., 1971.

trations of 100 pgim3 or larger have been
reported within industrial buildings (Wal-
lace, et al., 1971).

III.C. Water — Contact of water with soil
and rock during storm runoff, percolation
into the ground, and movements under-
ground where different geochemical stresses
prevail, results in a natural distribution of
mercury in water. Surface waters, except
where they are influenced by special geolog-
ic conditions, or more recently by man-made
pollution, generally contain Jess than 0.1 ppb
mercury. This reflects the relatively low
concentration of mercury in rain water and
the relatively tight binding of mercury in

48

organic and inorganic materials over which
the water passes in its travel through the
environment. A recent reconnaissance of
tiver waters in 31 states showed that 65% of
the samples tested were below 0.1 ppb, 15%
exceeded 1.0 ppb, and only 3% were more
than 5.0 ppb - the maximum considered safe
for drinking water (Fleischer, et al., 1970).

Because of mercury’s tendency to sorb
readily on a variety of earth materials, parti-
culate matter suspended in water and bot-
tom sediments of streams are more likely to
contain high concentrations of mercury than
the water itself. The best estimate is that
suspended matter may contain from 5 to 25


Il. Fabrics and Textiles

1. Fungistats
A. Mercury compounds

(1) Phenylmercuric acetate: fungistat
for mildew control: industrial use in finishing
processes. [Ref. I-P-08-00]

(a) 25 to 180 ppm in final rinse.
(b) 30 to 90 ppm by padding.
(c) 150 to 225 ppm by spraying.

(2) Phenylmercuric borate and chlor-
ide: fungistat, industrial use in finishing
process. (Ref. I-P-08-10.01] 2.0 Ib of a 1.1%
PMB plus 0.10% PMC soln./100 gal in finish-
ing bath = 26.5 ppm PMB plus 2.4 ppm
PMC.

(3) Phenylmercuric oleate: fungistat;
consumer use on awnings, boat covers, navy
tops, curtains, sail covers. [Ref. I-P-14-00]

(a) 2000 to 2800 ppm alone or with
TBTO and zinc naphthenate, by brush.

(b) coatings for outdoor fabrics: 0.05
to 0.5% of a 30% product. based on weight
of coating. (Ref. I-P-14-00.02]

(4) Phenylmercuric propionate: fungis-
tat: industrial use in finishing process. [Ref.
I-P- 15-00] 250 to 500 ppm by impregnation.

(5) Phenylmercuric triethanol ammon-
ium lactate: fungistat for mildew, rot and
decay: industrial use in finishing process.
[Ref. I-P-17-00] 560 to 1130 ppm by impreg-
nation or in size.

(6) Pyridy! mercuric chloride: (0.06%
plus 7.5%) alkyl dimethyl benzyl ammonium
chloride: industrial use in finishing process.
[Ref. I-A-08-10.02] 1.2 to 1.3% of mixture
retained on fabric by padding.

B. Substitute compounds

(1) Alkyl amine salts of tetrachloro-
phenol (alone or with TBTO): fungistat: in-
dustrial use in finishing process. [Ref. I-A-
6-00.01]

(a) cotton, sisal, jute. hemp and simi-
lar materials: 10.000 to 20.000 ppm alone or
1090 ppm plus 210 ppm TBTO.

10

(b) carpet underlay: 1500 ppm plus
250 ppm TBTO.

(2) Alkyl dimethyl benzyl ammonium
chlorides: fungistat: industrial processes.

(a) padding to retain 1.2 to 1.3% by
weight of a mixture of quaternary plus o-
phenylphenol and 2, 3-thiobis (4-chloro-
phenol). [Ref. I-A-08-10.02]

(b) 1500 to 6000 ppm quaternary by
finishing equipment. [Ref. I-A-08-15.02]

(c) 5000 ppm quaternary plus 250
ppm TBTO by spraying. [Ref. I-A-08-15.02]

(d) 500 to 2500 ppm quaternary plus
150 to 500 ppm TBTO by padding or other
suitable equipment. [Ref. I-A-08-15.02]

(3) Ammonium hydroxide Cg fatty
acid-silver complex: fungistat, consumer
use. [Ref. I-A-25-00.01] 800 ppm spray.

(4) Bis (tributyltin) oxide: fungistat:
industrial use in finishing process. [Ref. I-B-
9-00.03]

(a) 250 to 500 ppm on clothing, etc.

{b) 500 to 1000 ppm on awnings, etc.

(S) Captan: fungistat: industrial use in
finishing process. {Ref. I-C-10-00.16] Depos-
it 0.90 to 1.7% by weight of fabric.

(6) 4-or 6-chloro-2-phenylphenol: fun-
gistat; consumer use. 2000 ppm spray,
sponge or dip. [Ref. 1-C-18-00.01]

(7) 4-chloro-3, 5-xylenol: — fungistat;
consumer use. [Ref. I- -21-00] 1200 ppm
alone or 600 to 2000 ppm in combination
with other fungistats.

(8) Copper 8-quinolinolate: fungistat;
industrial use in finishing process. [Ref. I-C-
34-00.03] 0.02 to 1.0% metallic copper equiv-
alent deposited. Note: objectionable color
for many types of fabric.

(9) Dehydroabiethylamine salt of pen-
tachlorophenate: Industrial use in finishing
process. (Ref. I-D-02-00.01]

(a) indoor fabrics: 0.25 to 1.25% by
weight of fabric.

(b) outdoor fabrics: 0.8 to 1.5% by
weight of fabric.


Final rinse (leather to be used in clothing):
1.0 02/100 gal.

(6) Tributyltin salicylate plus 40.9%
Diisobutylphenoxyethoxyethyl dimethyl
benzyl ammonium chloride and 6.5% isopro-
phanol: [Ref. I-D-13-00.03] Fatliquor and
long bath: 0.5% of formulation by weight of
leather.

C. Comparative effectiveness and impact

(1) Substitute chemical products are
more expensive than the mercury materials.

XV.

1. Logs, lumber (sap stain and mold during
seasoning, storage and shipment):

A. Mercury compounds

(1) Ethylmercury phosphate: [Ref. I-E-
07-00.01] 150 to 300 ppm solution, or 72 to
1200 ppm plus sodium pentachlorophenate,
or 225 to 450 ppm for heavy timbers.

(2) Phenylmercuric acetate:  [Ref.
T-P-08-00.08] 2 pints of 5% PMA plus 25%
sodium trichlorophenate/75 gal (approxi-
mately 1600 ppm PMA).

(3) Phenylmercuric hydroxide: [Ref. I-
P-09-50.01] 1 to 2 gal of 0.2% PMH plus
14.54% sodium pentachlorophenate and
3.16% sodium metaborate/40 to 50 gal.

(4) Phenylmercuric lactate: [Ref. I-P-
10-00.01; I-S-15-00.02; I-S-21-00.01] Use 1 to
2 gal of 0.4% PML plus 1.0% sodium octa-
borate and 22.82% technical sodium pen-
tachlorophenate/100 gal, 1 to 2 gal 0.4%
PML plus 13.3% sodium metaborate and
22.82% technical sodium pentachlorop-
henate/100 gal, or 2 to 3 gal of 3.19% PML
plus 49.23% sodium trichlorphenate/100 gal
for western species including Douglas Fir,
Hemlock and pine.

i

B. Substitute compounds

(1) 2.0% Bis (tributyltin) oxide plus
4.5% 1-(Alkyl amino)-1, 3-amino propane

(2) Weare not familiar with the various
problems of color, hand and other quality
factors which may influence the usability of
substitute materials.

(3) Based on the fact that the industry
failed to respond to the Federal Register
request for views and comments, we believe
‘that the impact of withdrawal of mercury
registrations will have little impact on the
tanning industry.

Wood

monoacetate, 21.0% sodium tetrachloro-
phenate and 5.7% sodium salts of other
chlorphenols: [Ref. I-A-07-00.01] 0.5 to
0.75% solution

(2) 2.5% -Phenylphenol plus 2.5%
pentachlorophenol: [Ref. I-P-19-00.02] dip
in above formulation

(3) 14.4% Potassium _pentachloro-
phenate plus 1.5% alkyl amino-3-aminopro-
pane, 8.3% potassium trichlorophenate and
1.7% of other potassiums salts of chlorophe-
nols: [Ref. I-P-25-00.02] Use 0.5 to 0.75% of
above formulation in water. Dip or spray.

(4) 13 to 65% Sodium borate plus 27.7
to 36.0% sodium pentachlorophenate and
4.0 to 12.3% sodium carbonate: [Ref. I-S-04-
00.01] 10 0 20 Ib formulation/100 gal.

(5) Sodium pentachlorophenate: [Ref.
I-S-15-00.02] 3 to 12 Ib/100 gal.

(6) Sodium tetrachlorophenate: [Ref. I-
S-21-00.01] 4.8 Ib/100 gal.

C. Comparative effectiveness and impact

(1) Mercury compounds are the most
effective, require much smaller dosage rates
and control more fuhgus species than the
substitute materials. The mercury com-
pounds are also much less expensive.

(2) The impact of withdrawal of mercu-
ty for this use will be great on the manufac-
turers of such formulations and will be very

39


CHAPTER 2

ANALYTICAL METHODS FOR MERCURY

Probably the single most important cause of
the sudden increase in apprehension over
mercury in the environment has been the
rapid strides made in analytical methods
used to detect trace amounts of mercury and
its compounds. It can now be found in hith-
erto unsuspected substrates.

II.A. Colorimetric — For years the classical
method for determination of mercury was
the AOAC dithizone spectrophotometric
procedure (Horwitz, 1970). In this proce-
dure the sample, for instance, grain or tis-
sue, is digested with nitric and sulfuric acids
under reflux. Even after the solution be-
comes clear, indicating complete destruction
of most of the organic matter, some of the
organic mercury may still be so bound that it
will not complex with dithizone reagent. In
such a case, the results would be low. Fur-
ther, some mercury can be lost by volatiliza-
tion or absorption on the glass container.

Then, too, copper, gold, silver, palladium
and platinum in trace amounts interfere giv-
ing high results. In the same manner, lead,
zinc, nickel, and cobalt in larger amounts
cause high results. The mercury dithizone
complex is not stable to light and breaks
down readily giving low results.

However, within the limits of its sensitivity
and problems of interference, the dithizone
method is satisfactory. A description of the
method follows:

A sample equivalent to not more than 10 g
dry weight is digested with HNO, and
H)SOyq under reflux in a special apparatus
designed to prevent loss of Hg by volatiliza-
tion. The mercury is extracted from the di-
gest with a chloroform solution of dithizone
and is then separated from copper as a mer-

cury thiosulfate complex. The complex is
decomposed and the mercury again taken up
in a chloroform solution of dithizone. The
absorbance of the dithizone solution is mea-
sured at 490 nm and the mercury determined
by comparison with the absorbance of
standards.. As little as 34g of Hg may be
determined. For a dry produce such as grain
using a 10-g sample, 3 g would be equivalent
to a sensitivity of 0.3 ppm. With fish and
other high moisture products a larger sample
could be used. Assuming the use of a 20-g
sample, the sensitivity of the method would
be better than 0.2 ppm.

The method has little value in studying cases
of mercury poisoning because of the larger
amount of sample needed, the low limit of
sensitivity and the many interferences.

Reviews of the methods for colorimetric
analysis are given by Sandell (1959) and by
Snell & Snel! (1949).

II.B. Atomic Absorption — Even the advent
of atomic absorption spectrophotometry did
not immediately result in improvement in
mercury analysis as mercury is one of the
least sensitive of the metals to this method.
However, a number of modifications of
classical atomic absorption analysis permit
greater sensitivity, reproducibility and ease
of analysis. Some of these developments are
as follows:

Jacobs and Goldwater (1960) digested sam-
ples of apples with permanganate, extracted
the mercury with a chloroform solution of
dithizone, evaporated, off the CHC1,, vola-
tized the mercury by heating the dry dithi-
zone residue, swept the mercury vapor
through a quartz windowed cell in a modified

43


Meshkov, Glezer, and Panov (1963) studied
the effects of lethal and toxic doses of die-
thylmercury on the kidneys of rats. In these
experiments, albino rats were administered
doses of 25 to 100 mg/kg of body weight of
diethylmercury. The animals at the 100 mg/
kg dosage level died within 24 hours and
were found to have pronounced degenera-
tive changes in the kidneys, involving prima-
rily the proximal tubules. The loops of
Henle and the straight tubules in the medulla
were almost unchanged. The lower doses of
25 to 50 mg/kg produced similar renal
changes in 10 to 20 days. The exact nature of
the histochemical change produced depend-
ed upon the extent of the degenerative proc-
esses. In the early stages (sublethal doses),
there is a decrease in the nuclear DNA con-
centration of the epithelial cells of the proxi-
mal and thin segments, while the cytoplas-
mic RNA content increases. Further changes
in the tubules are accompanied by a marked
reduction in the DNA and RNA content.
Sublethal doses produced _ significant
changes in the ultrastructure of the proximal
tubular epithelium: appearance of large
numbers of vacuoles in the cytoplasm, de-
struction of the membranes of the endo-
plasmic reticulum, swelling and splitting the
cell membrane, and, most important, de-
struction of the mitochondrial apparatus,
swelling of the mitochondria and granular
disintegration of their cristae.

In the experiments cited earlier, Swensson
(1952) limited his histological examinations
to the central nervous system, particularly
the spinal cord, although, the cerebellum
was also examined. Cell injuries were dem-
onstrated in the, granular cell layer of the
.cerebellum, in the Purkinje’s cells in the
cerebellum and in the cells of the spinal
cord. The same changes were observed with
all compounds studied; methylmercuric
chloride, ethylmercuric chloride, methyl-
mercuric dicyandiamide, ethylmercuric di-
cyandiamide, and phenylmercuric acetate.
No essential differences were noted between

the compounds. Injury to the myelin
sheaths in the spinal cord were noted as well
as selective Marchi degeneration in the pos-
terior columns of the cord. Swensson found
that injury to nerve cells occurred even after
very small doses. When the injuries were
sufficiently extensive, nerve symptoms
arose. The degree of severity was clearly
connected with the degree of severity of the
poisoning and, to some extent with the peri-
od of time elapsing after the administration
of the compound.

V.A.2. Chronic Toxicity — Fitzhugh, et al.,
(1950) showed, that although inorganic mer-
cury compounds are more acutely toxic than
organic mercury compounds, phenylmercu-
tic acetate was more toxic, chronically, than
was mercuric acetate. Significant toxicity in
the form of kidney damage was observed
from 0.5 ppm dietary mercury in the form of
phenylmercuric acetate. Ten to twenty times
this amount of mercury in the form of mer-
curic acetate was required to cause similar
damage. Mercury was accumulated in the
liver and kidneys of animals fed phenylmer-
curic acetate, although no damage of a func-
tional nature was observed. There was con-
siderably more mercury stored in these or-
gans after feeding phenylmercuric acetate
than after feeding mercuric acetate. The
results indicated that as the mercury concen-
tration increased 100 times, the organ con-
centration was increased only about 10 times
for both compounds. This suggests that
there is a saturation phenomenon present,
with excretion increasing with the dose.

V.A.3. Genetic and Teratogenic Effects —
Experimentally, in certain systems of plants
and in drosophilia, organic mercurials may
produce genetic mutations and chromoso-
mal aberrations.

Organic mercurials cause c-mitosis in the
cells of Allium cepa roots. The aryl and alkyl
compounds are most active and produce this
effect at levels as low as 15 x 107M. The

73


(3) Comparative effectiveness and im-
pact

(a) Some substitute compounds im-
part odors to finished paint film that may be
undesirable in food processing areas.

(b) Listed substitute compounds
cannot be considered inclusive. Paint pre-
servative compounds used for water-based
paints or synthetic emulsion-type paints may
also be substituted.

(c) Substitute compounds appear to
be adequate.

(d) Impact on industry expected to
be small, impact on consumer expected to
be negligible.

5. Paints, varnishes, stains
A. Fungistatic (mildew control)

(1) Mercury compounds
(a) Chloromethoxy-acetoxymercu-
ripropane: [Ref. I-C-14-00.01] Mfg. use la-
bel, no directions for use.

(b) Di (phenylmercury) dodecylsuc-
cinate: [Ref. I-D-21-00.01]
(aa.) Household use: 3750 ppm
added to paint.
(bb.) Industrial use: add in amount
required.

(c) Phenylmercuric acetate: [Ref. I-
P-08-00.09]
(aa.) Preservation: 0.1 to 0.25 Ib/
100 gal.
(bb.) Mildew control: 1.0 to 3.0 Ib/
100 gal.
(cc.) Preservation of protein col-
loid components: 0.23 to 0.3 Ib/100 gal.
(dd.) Preservation of carbohydrate
components: 0.1 to 0.15 Ib/100 gal.
(d) Phenylmercuric borate: [Ref. I-P-
08-10.01] Mold control: 0.2 to 3.0 Ib/100 gal.
(e) Phenylmercuric hydroxide: [Ref.
T-P-09-50.01] Aqueous systems: 4500 to 9000
ppm residual in coating.
(f) Phenylmercuric oleate: [Ref. I-P-
14-00.01 and .02]
(aa.) Mildew on paint film, decay
on stained surfaces as household or com-

mercial use: 1200 ppm plus 14.250 ppm of
pentachlorophenol added to coating.

(bb.) Industrial use:
333 to 1666 ppm by weight of coating: 1.0 to
6.66 Ib actual/100 gal.

(g) Phenylmercury propionate: [Ref.
I-P-1500.01] Mildew control: 1.5 to 4.0 Ib
actual/100 gal.

(2) Substitute compounds

(a) Alkyl dimethyl benzyl ammonium
chloride: [Ref. I-A-08-25.06] Mildew con-
trol: aqueous systems—366 ppm plus 610
ppm TBTO.

(b) Alkyl dimethyl ethybenzy! am-
monium cyclohexyl sulfamate: [Ref. I-A-17-
00.01] Aqueous exterior systems (latex): 600
to 800 ppm by weight.

(c) Barium metaborate: [Ref. I-B-01-
00.91]

(aa.) 8.35% by weight of paint.

(bb.) 0.09 to 0.36% by weight for
preservation of finished colors containing
protein.

(cc.) 0.09 to 0.27% by weight for
preservation of finished colors containing
carbohydrates.

(d) trans-1, 2-Bis (propylsulfonyl)
ethene: (Ref. I-B-07-80.01] 3000 to 5000 ppm
by weight—for oil-based paints.

(e) Bis (tributyltin) oxide: (Ref. I-B-
09-00.01 and .02]

(aa.) Household use in aqueous
systems: 610 ppm by volume.

(bb.) Industrial use: 500 to 1000
ppm by weight of polyvinyl acetate formula-
tions;

1500 to 3000 ppm by weight of acrylic for-
mulations;

2500 to 3500 ppm by weight of styrenebuta-
diene formulations;

0.92 Ib/100 gal of interior paint;

6 to 9 Ib/100 gal of exterior paint;

8 to 12 Ib/100 gal of roof paint.

(f) Captan: [Ref. I-C-10-00.15 and
16]

(aa.) Household uses: 1.0 oz/gal of
oil-based paint.


CHAPTER 3

PREVALENCE OF MERCURY IN THE ENVIRONMENT

Mercury is one of the elements which make
up the earth. In its elemental state at the
earth’s surface, it is a silvery liquid metal,
approximately 13 1/2 times as heavy as wa-
ter. Mercury is the only metal which occurs
in the liquid state at ordinary earth tempera-
tures. Like other liquids, it vaporizes and
condenses in a pattern determined by its
own vapor pressure and the barometric pres-
sure of the environment in which it exists.
Mercury is absorbed and is bound tightly by
a variety of materials such as plant fibers
and soils. It reacts with a variety of inorgan-
ic and organic compounds to form simple
and complex molecules ranging from cinna-
bar, a mercury sulfide and the most common
ore mineral, to the metallo-organic complex-
es which are used in pesticides and which
are now found as a contaminant in fish
(Fleischer, et al., 1970). At this point in time,
it is difficult to separate the ‘‘natural’’ back-
ground levels of mercury from those which
are man-made. Certainly, a portion of the
mercury found in water, soil, plants, and
animals arises from ‘‘natural’’ sources. In
areas where mercury pollution is known to
occur from sources such as agricultural run-
off, industrial wastes, and mining opera-
tions, increases above the ‘“‘natural’” levels
can be expected. There remains, however,
the question of just how much of the remain-
ing background is due to the combustion of
paper products and fossil fuels, the smelting
of ores, weathering of paints, and other ac-
tivities of man.

III.A. Minerals and Rocks — Cinnabar is the
most commonly found mercury-bearing
mineral. It contains 86% mercury by weight.
Cinnabar is generally found in mineral veins
or fractures, as impregnations, or having
replaced quartz, in rocks near recent volcan-
ic or hot-spring areas. The mercury content

of broad categories of rocks in the earth’s
crust range from 10 to 20,000 ppb. Less than
20% of recorded rock samples have more
than 1,000 ppb. Igneous rocks are the basic
sources of mercury. These contain less than
200 ppb of mercury and average about 100
ppb. The mercury content of soils averages
about 100 ppb and varies within relatively
narrow limits. The background concentra-
tion of soils in California are 20 to 40 ppb.
The Franciscan Formation of California, in
which most of the State’s mercury mines are
located, has background levels of 100 to 200
ppb; anomalies in soils around these mercu-
ty deposits are in the range of 10,000 to
100,000 ppb (Fleischer, et al., 1970).

III.B. Atmosphere — Because of the tenden-
cy of mercury to vaporize, it is distributed in
the environment through aerial circulation.
The atmosphere measured at ground level
near mercury ore deposits may contain as
much as 20,000 ng/m3 of mercury. The con-
centrations over the ocean usually measure
less than 1 ng/m3. Land sources of airborne
mercury apparently are subject to meteoro-
logical controls, i.e, mercury released into
the air as a function of barometric pressure,
time of day, and season. Rain serves to wash
the mercury from the atmosphere. Immedi-
ately after a rainfall, mercury concentration
in the air are negligible even near ore depos-
its (Wallace, et a/., 1971). The same author
lists the air concentrations of mercury at
various mineralized and nonmineralized
areas of the United States in Table 1. Air
over urban industrial areas contains mercury
levels higher than background, and several
measurements have indicated average val-
ues of 0.01 (Chicago, Ill.), 0.10 (Cincinnati,
Ohio), and 0.17 (Charleston, W. Va.) ug/
m”’. Concentrations of | to 14 »g/m3 have
been cited for New York City. Air concen-

47


This syndrome, which has become to be
known as the ‘‘Minamata disease’’ is char-
acterized by widespread involvement of the
central nervous system with granular cell
degeneration of the cerebellum, and lesser
involvement of the basal ganglia, hypothala-
mus, midbrain, and cerebral cortex. The
relative ease with which methylmercury
passes the ‘‘blood-brain barrier’ in humans
accounts for the severe neurologic manifes-
tations.

The staff of the Kumamoto University, in a
series of carefully planned investigations,
first identified the causative factor of Mina-
mata disease as heavy consumption of fish
contaminated with an organic form of mer-
cury, later identified as methylmercury.
Similar findings were made by the staff of
the University of Niigata in the Niigata City
and Agano River outbreaks (Nelson, et al,
1971).

The first warning of the mercury problem in
Sweden came in the early 1950’s when the
populations of the yellow bunting dropped
catastrophically. Deaths, reproductive fail-
ures and population declines of both seed-
eating and raptorial birds were soon noted
(Otterlind, et al, 1964). Toxicity from mercu-
ry used in seed dressings to prevent cereal
diseases was suspected. Investigations
proved this assumption to be correct. It was
soon discovered that mercury pollution was
serious in Swedish lakes, and that leakage
from pulp mills and chlor-alkali factories
was responsible.

Late in 1965, West6d determined that the
mercury she found in eggs, fish, and some
other meats was methylmercury. West06
observed that both fish and mammals could
convert small amounts of inorganic mercury
to methylmercury in their livers. It was
shown that Swedish eggs had four times the
mercury content of eggs from the rest of
continental Europe. Johnels published an
opinion that inorganic mercury could be

iv

converted to methylmercury by microorgan-
isms in anaerobic ecosystems such as mud
on lake bottoms. In 1965, it was shown that
the mercury in samples of eggs, meat and
fish from Sweden was 80 to 100% methyl-
mercury. Subsequently, mercury has been
shown to be methylated by aquarium and
natural sediments (Jerisen and Jernelov,
1969).

Because of mercury contamination, the
marketing of fish from certain lakes and riv-
ers has been banned in Sweden. This deci-
sion is based on a temporary limit of 1 mg
Hg/kg of body weight with a recommenda-
tion not to eat fish from fresh waters more
than once a week. Recent investigations in
Denmark, Finland and Norway have dem-
onstrated similar elevated mercury concen-
trations in fish from coastal waters.

The National Poisons and Pesticides Board
of Sweden revoked the licenses for alkyl-
mercury compounds in Agriculture on Feb-
ruary 1, 1966. In the year following this ban,
the mercury content of Swedish eggs fell
almost to the level of the rest of continental
Europe or one-third of the level reported in
1966.

In 1969, following warnings of significant
mercury pollution in the central provinces,
studies were initiated by the Canadian Wild-
life Services to define the situation. Follow-
ing these studies, several commercial catch-
es of fish (walleye, northern pike, bass and
jackfish) taken from Lake Winnipeg, Cedar
Lake, Saskatchewan River, and Red River
in Manitoba Province were seized by the
Canadian Federal Department of Fisheries
and Forestries, because they contained mer-
cury residues ranging from 5 to 10 ppm (Sea-
gran, 1970). The Canadian Government then
publicly embargoed all commercial fish tak-
en from Lake Saint Clair effective March 23,
1970.

In the United States, results of analytical
studies on fish and wildlife showed mercury


induces a whole sequence of secondary
changes which may ultimately affect the
physiological state of the whole cell (Pas-
sow, et al., 1961).

IV.D.2. Organ Level — All of the generaliza-
tions concerning the cells are valid when
considering the actions of mercury on organ
systems and on the intact animal. The matter
is complicated by the fact that, in the or-
gans, several cell populations of different
susceptibilities may exist in a complex ana-
tomical arrangement. In animals, the effec-
tive concentration of mercury at the cellular
sites of damage and the time of exposure are
determined by the patterns of absorption,
distribution, deposition, and excretion (Pas-
sow, et al., 1961).

IV.D.3. Chemical Interactions — Most
heavy metals, including mercury, are capa-
ble of forming complexes with ligands con-
taining sulfur, nitrogen, or oxygen as elec-
tron donors. Nitrogen is the preferred donor
in the formation of coordination com-
pounds. Oxygen rarely forms coordination
complexes, but when present in such disso-
ciable groups as carboxyl and phosphoryl,
forms strong ionic bonds with heavy metals.
In any living cell, the following ligands are
present:

—OH, —COOH. —PO,H,. —SH. —NH),
—imidazole

These ligands, which form the integral parts
of almost any molecule of biological signifi-
cance, are frequently essential to the normal
functioning of the cells. Mercury does not
have the same affinity for the different li-
gands. While it apparently has little affinity
for —COO-groups, it has high affinity for —
NH, and —SH groups (Gurd and Wilcox,
1956: Klotz and Klotz. 1959).

Hydroxyl groups of water can participate in

complex formation and in the formation of
insoluble hydroxides. These complexes may

64

have a very complicated structure, and their
electrochemical behavior may be quite dif-
ferent from the behavior of simply hydrated
ions. Chloride ions also form strong com-
plexes with mercury (Sillen, 1949). Com-
plications in pharmacological studies arises
immediately after dissolving mercury in
water. In addition, all the listed biological
ligands contain dissociable protons. Mercu-
ry ions will replace these protons in complex
formation (Passow, et al., 1961).

Mercury binding by biological materials is
strong but not specific with regards to the
ligands. The only rules that can be estab-
lished are concerned with affinities. Chelate
formation may introduce specificity patterns
that invalidate the lists of relative affinities
(Martell and Calvin, 1952). Many metabol-
ites like amino acids or dicarboxylic acids
are capable of forming chelates. Chelate
formation generally leads to an increase of
association constants. Since chelating
agents may exhibit high specificity toward
mercury cations, the rules regarding orders
of affinities of mercury for ligands can be
applied to biological systems only with cau-
tion. For example, if mercury, which has a
high affinity toward sulfhydryl groups, pro-
duces a pharmacological effect, it is not
permissible to ascribe the effect to the inac-
tion of sulfhydryl groups. The observations
must be supplemented by studying the ef-
fects of additional sulfhydryl reagents (Cal-
vin, 1954). The arrangement of ligands with-
in a single macromolecule may also favor
chelate formation. Chelates of high specific-
ity play an important role in the inactivation
of enzymes by metals (Malmstrom and Ro-
senberg, 1959).

IV.D.4. Action on Enzyme Systems — Mer-
cury is potentially able to combine with all
of the components of an enzyme system.
The possibilities of metal interactions with
the enzyme or with the enzyme-coenzyme-
substrate complex are manifold, because of
the presence of many reactive ligands. The


late/3000 cu ft of greenhouse space, as re-
quired.

(8) Copper sulfate, basic: [Ref. I-C-36-
00.09] 2.0 Ib metallic copper equivalent/100
gal. As required.

(9) Copper dihydrazinium sulfate: [Ref.
1-C-28-00.01] 3000 to 4000 ppm solution, as
necessary. Roses only.

(10) Copper oleate: (Ref. 1-C-30-50.03]
Up to 4 tbs./gal as necessary. Homeowner
use.

(11) Copper oxychloride: [Ref. I-C-32-
00.06] 2.12 Ib as metallic copper equivalent/
100 gal (2545 ppm) as necessary.

(12) Copper oxychloride sulfate, basic:
(Ref. I-C-33-00.07 and .08] 1.2 to 2.2 Ib as
metallic copper equivalent/100 gal (2640 to
6940 ppm) as necessary.

(13) Copper sulfate, basic: [Ref. I-C-
36-00.09 and .10] 3.0 to 3.18 Ib metallic cop-
per equivalent/100 gal (approx. 3600 ppm) as
necessary.

(14) Copper-Zinc-Chromate Complex:
[Ref. I-C-40-00.03 and .04] 1.8 Ib actual/100
gal or 1.7 to 2.3 Ib/acre dust.

(15) 2, 6-Dichloro-4-nitroaniline: [Ref.
1-D-09-00.06] 0.28 to 0.56 1b/100 gal or.0.64
to 1.8 Ib as a dust/acre at 5- to 14-day inter-
vals.

(16) Cycloheximide: [Ref.  I-D-16-
00.01] 2.0 ppm solution at 3- to 7-day inter-
vals.

(17) Ferbam: [Ref. I-F-01-00.08 and
.09] 0.76 to 1.14 Ib/100 gal or dust to cover at
7- to 10-day intervals

(18) Folpet: (Ref. I-F-02-00.05 and .06]
0.5 to 1.0 Ib/100 gal (600 to 1200 ppm)

(19) Glyodin: [Ref. I-G-02-00.02] 200 to
480 ppm solution as required.

(20) Maneb: (Ref. I-M-02-00.09 and
.10] 0.8 to 1.2 1b/100 gal (1000 to 1500 ppm)
or 1.2 to 2.4 Ib dust/acre.

(21) Karathane (dinocap): [Ref. I-M-14-
00.04] 1.5 to 3.84 Ib/100 gal as necessary.

(22) 3 (2-methylpiperidino) propyl 3, 4-
dichlorobenzoate: [Ref. I-M-26-00.01] 0.25

to 0.5 Ib/100 gal (300 to 600 ppm) at 7-day
intervals.

(23) Nabam: (Ref. I-N-01-00.08] 0.43 to
0.86 1b/100 gal at 7-day intervals.

(24) Potassium polysulfide: [Ref. I-P-
27-00.01] 3 fl oz of 2.9% solution/100 gal at 7-
to 10-day intervals.

(25) 8-Quinolinol sulfate: [Ref. I-Q-03-
00.01] 180 to 390 ppm solution at 7-day inter-
vals.

(26) Sodium o-phenylphenate: [Ref. I-
S-16-00.07] 514 to 1030 ppm at 7- to 14-day
intervals.

(27) Streptomycin: [Ref. I-S-23-00.03]
50 to 200 ppm at 3- to 7-day intervals.

(28) Sulfur: (Ref. I-S-24-00.09 through
.11] 4.75 to 5.6 1b/100 gal or dust to cover at
5- to 10-day intervals.

(29) 1, 2. 4, 5-Tetrachloro-3-nitroben-
zene: [Ref. I-T-03-00.01] 1 0z/10,000 cu ft of
greenhouse space by vaporization.

(30) Tetrachloroisophthalonitrile: [Ref.
I-T-05-00.01] 0.75 to 1.126 Ib/100 gal or 8.0
gm/4000 cu ft of greenhouse space by vapor-
ization.

(31) Thiram: [Ref. I-T-10-00.03 through
-05] 0.65 Ib/100 gal or 5.0 to 12.0% dusts.

(32) Zine ion-maneb complex: [Ref. I-
Z-04-00.07 through .09] 1.2 Ib/100 gal at 7- to
10-day intervals.

(33) Zineb: [Ref. I-Z-10-00.09] 1.125 to
1.5 1b/100 gal as required

(34) Ziram: (Ref. I-Z-11-00.05 and .06]
1.14 to 6.3 Ib/100 gal at 7- to 10-day inter-
vals.

C. Comparative effectiveness and impact

(1) Most substitute compounds are
more effective than mercury compounds
against the foliar diseases of flowering and
foliage plants.

(2) Impact of withdrawal of mercury
compounds for such uses will be insignifi-
cant on manufacturer and consumer.

19


The mouse excretes methylmercury in the
bile and also via the intestinal mucosa (Berg-
lund and Berlin, 1969). Clarkson (1970)
demonstrated that the rat excretes methyl-
mercury in the form of methylmercury cys-
teine in the bile. This is completely re-
sorbed in the upper gastrointestinal tract,
since none is detectable in the large intes-
tine. The rate of turnover of epithelial cells
may be a determining factor in the rate of
excretion of methylmercury, since studies
have shown some accumulation of mercury
in the mucosal epithelium. The turnover of
epithelial cells in rats is five times faster than
the turnover in man. This correlates with the
difference observed in rate of elimination of
methylmercury in the two species (Berglund
and Berlin, 1969).

Biotransformation of methylmercury to in-
organic mercury occurs before excretion.
About 40% of the total mercury excretion
was found to be inorganic mercury. About
50% of the fecal excretion and from 5S to 20%
of the urinary excretion is inorganic mercu-
ry. Enterohepatic circulation of mercury
from methylmercuric chloride is important
in the distribution and excretion of mercury.
About 10% of an administered dose is ex-
creted in the first day. This falls to about 3%
by the 10th day. During this period only
about 3% is excreted in the feces. Almost all
of the mercury present in the bile was in the
form of methylmercury cysteine and inor-
ganic mercury bound to protein. The cys-
teine complex is rapidly and completely
reabsorbed in contrast to the inorganic mer-
cury. Other sources of mercury in the feces
are the sheddings of intestinal epithelium,
pancreatic secretion, and some secretion
from the pylorous. Biotransformation within
the intestinal lumen in the cecum is the ma-
jor source of inorganic mercury in the feces.

Enzyme systems may participate in the me-
tabolism of organomercurials. Studies by
Clarkson (1969) indicate that different com-
pounds release inorganic mercury at differ-

62

ent rates. Paramercurbenzoate was metabol-
ized the fastest and methylmercury the
slowest of seven compounds studied. These
studies indicate the nephrotoxic action of
mercurials may be related to the rate of their
biotransformation.

The metabolism of methylmercury has been
studied in man by Aberg, et al. (1969). After
the oral administration of ?03Hg-labeled
methylmercury, 203g was detected in the
whole blood within 15 minutes and reached a
maximum blood concentration within 6
hours. The blood/plasma quotient remained
constant for 24 days. The orally adminis-
tered methylmercury was almost completely
absorbed. The principal route of excretion
was by the feces with 13 to 14.2% of the
dose excreted during the first 10 days and
33.4 to 34.7% of the dose excreted in 49
days. The urinary excretion was low and
accounted for only 0.18 to 0.27% in 10 days
and 3.29 to 3.33% in 49 days. Urinary excre-
tion was still taking place at 71 days. The
biological half-life of methylmercury in man
was estimated at 70.4 to 74.2 days. During
the 240-day test period, there was never any
measurable amount of mercury in the
sperm. Only traces of mercury were found
in the hair. Step scanning revealed the main
uptake of 2°3Hg was in the abdominal cavity
with possible localization in the cerebellum.
Whole-body measurements over a 240-day
period did not reveal any marked difference
in the biological half-life in any region. Miet-
tinen, et al. (1969) fed burbot containing
bound 23Hg methylmercury to humans. His
results were similar to those reported by
Aberg.

Mercury may be excreted by rats through
volatilization. In an experiment designed to
determine if mercury is lost from animals
through volatilization, Clarkson (1965) in-
jected 2 Hg complexed with glutathione
into the hearts of rats. The animals were
placed in a chamber so constructed that
urine, feces, and air circulating through the


to application of this type of product to a 10-
by 15-cm area on each hand or arm (300 cm?
total skin area) from which a theoretical 720
# g mercury could penetrate skin in a 24-
hour day. According to these studies, the
urinary excretion rate may be as little as 4%
in 5 days, indicating a possible problem of
heavy metal poisoning from skin absorption.
Cases of nephrotic syndrome in humans
from topical use of ammoniated mercury
have been reported (Becker, 1962; Silver-
bert, et al., 1967).

Mercury is absorbed slowly through intact
skin and much more rapidly through broken
skin. The mucosa offers little resistance to
penetration of mercury. Instillation of 0.1 mI
of a 0.05% solution of phenylmercuric ace-
tate into the vaginal tracts of rats (9 # g/kg)
resulted in about 28% residue of mercury in
the kidney and liver combined immediately
following a 24-hour exposure.

IV.B. Distribution

The distribution of mercury in the organs
and tissues of animals after absorption var-
ies with the form in which the mercury is
administered and with the species of the
animal studied. Mercury derived from inor-
ganic and aryl compounds appears to accu-
mulate in the liver and kidneys, whereas
mercury derived from alkyl compounds is
more evenly distributed throughout the
body. There are considerable species differ-
ences in the distribution patterns of mercury
among different mammalian species — most
pronounced is the low brain content of mer-
cury in the rat as compared with other
species after the administration of alkylmer-
cury compounds.

IV.B.1. Blood — The distribution of mercu-
ry in the blood between the red blood cells
and the plasma is dependent upon the type
of mercury administered. There appear to be
significant differences between the red blood
cell/plasma distribution characteristics of

metallic mercury, inorganic mercury, aryl-
mercury, and alkylmercury. Some species
variations have been noted.

Metallic mercury, inhaled as mercury vapor,
results in a higher concentration of mercury
in the red blood cells than in the plasma.
After inhalation of mercury vapors, 67% of
the mercury in monkeys’ blood and 84% of
the mercury in rabbits’ blood was bound to
the red blood cells (Berlin, 1969).

Inorganic mercury accumulates in the plas-
ma of the blood. This has been demonstrat-
ed after oral administration to rats and intra-
venous administration to rats, rabbits, and
dogs by Swensson, et al. (1959a; 1959b). In
rabbits and monkeys injected with inorganic
mercury, the red blood cell level was ap-
proximately 25% of the blood mercury level
(Berlin, 1969). Inorganic mercury reacting
with the red blood cells binds to hemoglobin,
not only with the sulfhydryl groups but also
with the imidazole residues (Resnik, 1964).

Mercury derived from .arylmercury com-
pounds is bound to the red blood cells to a
greater extent than is mercury derived from
inorganic compounds. Berlin (1969) states it
is evenly distributed between the plasma and
the red cells, while Swensson (1959a, 1959b)
states that phenylmercury compounds are
bound mainly to the red blood cells. In either
case, it appears to be intermediate between
inorganic mercury and alkylmercury. °

Mercury derived from alkylmercury com-
pounds is bound mainly to the red blood
cells (Swensson, et al., 1959a, 1959b). Burg-
land and Berlin (1969) reported that. in all
species studied, 90% of the methylmercury
in the blood is bound to the red blood cells.
The fraction in the plasma varies with the
species; in man 10%, in the rat 4.5%, in the
rabbit 10%, and in the squirrel monkey 9%.
Takeda (1968a) found that, of the alkylmer-
cury compounds studied (methylmercuric

55


all, of the problem organisms. Substitute
materials are less broad and frequently re-
quire combinations of materials to aid effec-
tiveness.

(3) Mercury compounds are useful on a
broad range of fabric and textile substrates
(cotton, jute, wool, etc.). Substitute materi-
als are adapted to more specific uses.

(4) Mercury compounds are less expen-
sive than substitute materials, frequently by
a factor of 10.

(5) Mercury compounds do not impart
objectionable coloration nor do they affect
the “hand”? of textiles as do many substitute
compounds.

(6) Impact of withdrawal of mercury
for use on fabrics and textiles may affect
financial situation of certain economic poi-
son formulators and may require revision of
certain Federal specifications. Impact on
consumer of treated goods should be slight
to moderate.

2. Bacteriostats
A. Mercury compounds

(1) Phenylmercuric borate: (1.1%) and
alkyl (40% C, 50% C14. 10% Cy) dimethyl
benzyl ammonium chloride (0.12%) and
Phenylmercuric chloride (0.10%): [Ref.
3673-10] Add 2 Ib product to 100 gal of fin-
ishing bath; for cotton, wool, nylon and ray-
on fibers.

(2) Pyridyl mercuric acetate (2%) and
alkyl (67% Cy, 25% Cy4. 7% Cig, 1% Cg-
Cg) dimethylbenzyl ammonium chorides
(7.5%): [Ref. 5817-2]

2% solution of product at 100°F, 60-65% wet
pickup by fabric resulting in 1.2 to 1.3% of
product on fabric (types not specified)

(3) Phenylmercuric triethanolamm-
onium lactate (22.5%): [Ref. 6516-4] Typical
formula: 3.75 Ib product to makeup 100 gal
of water. Padding application from aqueous
solution sufficient to deposit 0.25% of prod-
uct manufactured dry weight of fabric (un-
specified).

12

B. Substitute compounds

(1) Bis (tributyltin) oxide (0.84%) and
dialkyl (alkyl from coconut oil fatty acids)
dimethyl ammonium chloride (1.25%): [Ref.
10466-2] 1.25% product on weight of goods.

(2) Alkyl (average = C)5) amine salts of
tetrachlorophenol (100%): [Ref. 3090-46]
0.25% to 2% product based on weight of dry
fabric.

(3) Bis (tri-n-butyltin) oxide (25%):
(Ref. 6390-2] 0.1 to 0.2% product based on
dry weight of fabric.

(4) n-alkyl (60% Cy4, 30% Cy¢, 5% Cy),
5% C1) dimethyl benzyl ammonium choride
(50%): [Ref. 6390-9] Apply to leave 0.25%
product on dry weight of fabric.

(5) n-alkyl (60% C4, 30% Cjg. 5% Cy.
5% Cyg) dimethyl benzyl ammonium 2 ethyl
hexoate (25%): [Ref. 6390-13] 0.1% pickup
or 0.025% active ingredient on dry weight of
fabric.

(6) Tributyltin neodecanoate (98%).
[Ref. 8314-5] 0.025% to 0.05% product based
on weight of fabric.

(7) Zine dimethyldithiocarbamate
(46%) and zinc mercaptobenzothiazole (4%):
{Ref. 1965-26] 2.5% product by weight of
cloth.

(8) Sodium pentachlorophenate (79%)
(Ref. 464-125] 0.1% to 0.75% by weight of
treated material.

(9) 2, 2 -methylenebis (4-chlorophenol):
(Ref. 824-6] 40% solution used to deposit
0.5% to 1.0% on fabric, concentration of
product in pad liquor varies with percent
pickup.

C. Comparative effectiveness and impact

(1) Substitute compounds exhibit great-
er substantivity to fabrics than mercurials.

(2) Substitute compounds appear to be
satisfactory.

GB) Impact on certaiin individual firms
selling mercurials may be substantial, im-

pact on industry and consumer expected to
be minimal.


A-08-15.01] 5000 ppm quaternary and 250
ppm TBTO, spray surfaces.

(2) Bis (tributyltin) sulfosalicylate:
(Ref. I-B-12-00.01] 0.5% by weight of rub-
ber.

(3) 4-Chloro-3, 5-xylenol: [Ref. I-C-21-
00.02] As required.

(4) Dehydroabietylamine pentachloro-
phenate: [Ref. I-D-02-00.01] 0.5 to 1.0% by
weight.

(5) Salicylanilide:
0.5% by weight.

(6) Ziram: [Ref. I-Z-11-00.07] 0.5% by
weight of formulation containing 46% ziram
plus 4% zinc-2-mercaptobenzothiazole.

(Ref. 1-S-01-00.01]

2. Bacteriostats
A. Mercury compounds

Phenylmercuric hydroxide (17%): [Ref. Reg.
No. 6516-3] Chlorinated rubber coatings for
fabrics: 0.5 Ib product/99.5 Ib media.

B. Substitute compounds

(1) Ziram (Zinc dimethyldit-
hiocarbamate) and Zinc 2-mercaptoben-
zothiazole (total Zn metallic 19.8%): [Ref.
Reg. No. 1965-19] 0.2 to 1.5% product by
weight of finished media.

(2) 1-(3-chloroallyl)-3, 5,  7-triaza-1-
azoniaadamantane chloride (90%): [Ref.
Reg. No. 464-327]0.5 to 0.15% product by
weight.

(3) Sodium pentachlorophenate (90%):
[Ref. Reg. No. 464-125] 0.3% product by
weight.

(4) Sodium o-phenylphenol: [Ref. Reg.
No. 464-78] 0.3% product by weight.

(5) Captan (N-trichloromethylthio-4-
cyclohexene-1, 2-dicarboximide (90%):
(Ref. Reg. No. 1965-11] 0.4% product by
weight of latex.

(6) Dehydroabietylamine pentachloro-
phenate (45%): [Ref. Reg. No. 2829-55] 0.5
to 1% active ingredient based on weight of
finished product.

(7) 4-chloro-3, 5-xylenol (100%): [Ref.
Reg. No. 4026-4] Product recommended for
neoprene and rubber preservation, no dos-
ages stipulated.

C. Comparative effectiveness and impact

(1) Substitutes appear to be adequate.

(2) Impact on industry expected to be
minimal.

(3) Cost to consumer expected to in-
crease.

XI. Sanitizers

1. Dust and cleaning cloth (bacteriostatic)
A. Mercury compounds
Phenylmercuric oleate (0.01%): [Ref. Reg.

No. 8618-1] Product inpregnated into fabric
using mineral oil.

B. Substitute compounds

(1) Dilauryl dimethyl ammonium brom-
ide (0.25%): [Ref. Reg. No. 303-56] 1 fluid
ounce/6 inches mop or cloth.

(2) n-Alkyl (50%C 15, 30%C 14, 17%Ci¢,
3%C jg) dimethyl ethylbenzyl ammonium
chloride, and n-alkyl (60%Cj4, 30%C,,

S%C 19, 5%C jg) dimethylbenzyl ammonium
chlorides. (0.2% total): [Ref. Reg. No. 1270-
92] 1 fluid ounce/6 inches of mop or cloth.

(3) Lauryl pyridinium salt of 5-chloro-
2-mercaptobenzothiazole: [Ref. Reg. No.
1750-42] Spray on cloth undiluted.

(4) Dialkyl (1%C,g, 8%Cg,  7%Cig
A8%C 19, 17% C14, 9%C jg, 10%C 8) dimethyl
ammonium chloride: [Ref. Reg. No. 1878-9]
Mix 1 1/2 gal product with 55 gal mineral oil
and add 2.5 to 3 gal/100 Ib dry weight cloth.

(5S) 2, 2’-methylenebis (3, 4, 6-trichlo-
rophenol) (0.5%): [Ref. Reg. No. 2915-29] 6
to 16 ounces per mop depending on size.

29


times as much mercury as the water around
it in areas of industrial pollution (Fleischer,
et al., 1970).

Sea water contains from 0.03 to 2.0 ppb
mercury, depending on area, depth, and ana-
lytical procedures. Mercury concentrations
increase from surface values of 0.10 ppb to
0.15 - 0.27 ppb at greater depths. The deple-
tion of mercury in surface waters is attribut-
ed to its uptake by plankton and subsequent
conveyance to depths by the biological ac-
tivities of the marine food web (Wallace, et
al.. 1971).

In the United States, the range of mercury
levels in rivers is from less than 0.1 ppb to
6.0 ppb. Wallace, et al., 1971 give a table of
mercury content of selected rivers in the
United States in 1970. In Minamata Bay,
Japan, the values of mercury in water aver-
aged from 1.6 to 3.6 ppb. Oceanic mercury is
generally present as an anionic complex
(HgC1,") which does not have a pronounced
tendency to bind to particulate substances
and subsequently settle out as do mercury
compounds in freshwater situations (Wal-
lace, et al., 1971).

111.D. Plants — Terrestrial plants, like
aquatic organisms, absorb minor elements,
including mercury, from the soils in which
they grow at rates depending on the quality
of the environment and the genetic charac-
teristics of the plants. Unlike aquatic organ-
isms, there seems to be little tendency for
terrestrial plants to concentrate mercury
above environmental levels. Typical soils
contain from 30 to 500 ppb mercury, and
most of the plants which grow in them are
likely to contain less than 500 ppb. When
soil concentrations of mercury are extreme-
ly high (40,000 ppb) in the vicinity of cinna-
bar deposits, plants growing in them actually
are likely to have mercury contents far be-
low the level of their environment, for ex-
ample, 1000 to 3000 ppb. Even in these in-
stances, it is primarily the plants which are

rooted through the surface soil into the mer-
cury ore which have high mercury contents
(Fleischer, et al., 1970).

Smart (1968) reported results of studies car-
tied out by various workers in the field
which indicated translocation of mercury to
fruit, tuber or seed following the foliar appli-
cation of mercury fungicides. For example,
tomatoes from untreated plants contain 0.01
ppm mercury, while tomatoes from plants
which have been treated with mercurial fun-
gicides contain 0.10 ppm.

Lindberg (1961) has also reported on the
translocation of mercury from the leaves to
the grain in plants which have had foliar
treatment with phenylmercuric acetate. The
translocation of mercury from treated seed
to harvested grain is small. Westermark et
al., (1966), found 0.01 ppb mercury in grain
grown from treated wheat seed containing
15 ppm mercury. Lagerwerff of the United
States Department of Agriculture, in coop-
eration with Emry of the Oak Ridge -Nation-
al Laboratory and with analytical chemists
of the National Bureau of Standards, dem-
onstrated that leaves of corn plants grown
from seed treated with ethylmercury-o-sul-
fonanilide, contained 0.14 ppm mercury
(Mercurial Pesticide Review Panel Report).

It is known that plants take up and concen-
trate mercury from the soil or water to a var-
iable extent. Marine algae, for example,
have been found to contain from 0.023 to
0.037 ppm mercury. This is several hundred
times the accepted concentration of mercury
in sea water. Trees and shrubs growing near
known cinnabar veins contain up to 3.5 ppm
mercury. Rice from paddies treated with
mercurial pesticides have higher mercury
content, e.g., Japanese rice versus rice from
other countries. However, Yamada (1970)
treated rice with 2 3Hg-treated phenylmer-
curic acetate and failed to grow rice witha
higher mercury content than the ‘“‘normal’”’
background. Again, on the other side of the

49


C. Comparative effectiveness and impact

(1) Mercury is a highly effective fungi-
cide at very low dosage rates, and the spec-
trum of organisms it controls is broadened
by formulating with PCNB.

(2) Substitute compounds must be used
at dosages from 30 to almost 400 times more
than mercury.

(3) The cost of using substitute materi-
als is 50 to 1000 times the cost of mercury.

(4) Substitute compounds are some-
times as effective as mercury when used as
directed for this purpose.

(S) The impact of withdrawal of mercu-
ty for this use will be very slight on industry
but will add to the farm cost of growing cot-
ton.

2. Tobacco
A. Mercury compounds

Hydroxymercurichlorophenol: (Ref. I-H-06-
00.01] For seed beds only, where plants are
withdrawn and transplanted: 0.0143 to
0.0214 Ib/10 sq ft (9.15 Ib/acre). For damp-
ing-off control.

B. Substitute compounds

(1) Chloranil (shade tobacco only):
(Ref. I-C-12-00.03] 0.5 Ib/25 gal as a drench.

(2) Formaldehyde: [Ref. I-F-03-00.02] |
gal of 8000 ppm solution.

(3) Methyl bromide: [Ref. I-M-06-
00.02] 1 to 2 Ib/100 sq ft with tarpaulin, or 20
to 50 gal of 69.0% formulation/acre by chisel
method.

(4) Tetrahydro-3, 5-dimethyl-2H, 1, 3,
5-thiadiazine- 2-thione (Mylone): [Ref. I-T-
07-00.01] 4.1 Ib/80 to 100 sq yd.

C. Comparative effectiveness and impact

(1) Substitute materials are about as
effective as mercury.

(2) Mercury is much less expensive to
purchase and apply, but substitute chemi-
cals also contro! other diseases at the same
time.

(3) Mercury has not been used exten-
sively for this purpose in recent years, and
the impact on manufacturer and consumer
of withdrawal of mercury for this use will be
negligible. Note: The manufacturer of this
mercury product has stated that it is being
withdrawn from production. Registration
has continued to cover stocks still in dealers
hands.

3. Farm and Greenhouse Equipment
A. Mercury compounds

Cyano (methylmercuric) guanidine: [Ref. I-
C-46-00.03] For farm machinery, green-
house benches, empty flats, pots, tools and
walks. Plant pathogen disinfection. 1.7 ppm
spray or dip. No food contamination.

B. Substitute compounds

Alkyl dimethyl benzyl ammonium chlorides.
[Ref. I-A-08-05.01 and I-A-08-50.01] 1800 to
5900 ppm.

C. Comparative effectiveness and impact

(1) Mercury compounds are far more
effective than substitute materials for this
use and at very low dosage rates.

(2) Impact of withdrawal of mercury
for this use will be severe on nurserymen
and potato growers; slight on manufactur-
ers.


Sticke! reports that the seed-eaters respond-
ed more promptly, and that levels of mercu-
ry in pheasants were back to normal the year
after the ban. The methoxymethylmercury
dressings which are now used (only when
and where needed) are less toxic and are
much more easily excreted than are the
methylmercury dressings.

The half-life of mercury in birds does not
appear to be excessive by comparison with
that in mammals. The half-life in chickens is
35 days. Male quail excrete mercury slowly,
while the female excretes it much more rap-
idly due to excretion in eggs. Pheasants have
a relatively rapid loss of mercury.

The reproduction of birds has been greatly
reduced by dietary exposure to mercury.
Hatchability is reduced, but there appears to
be no drop in egg production. The pheasant
eggs with demonstrated poor hatchability
contained 1.3 to 2 ppm mercury.

VI.F. Mercury in Farm Animals — There are
afew reported injuries of livestock from the
feeding of mercury-treated seed grain.
Loosemore, et al., (1967), reported experi-
mental results with pigs fed grain treated
with 6 ppm mercury. Pigs which survived 10

84

to 21 days on the mercury-treated grain suf-
fered tubular necrosis of the kidneys, and
their livers contained 60 ppm mercury. Their
kidneys contained 65 ppm mercury.

Trabash (1970) reported condemnation of 7
cattle carcasses in Oregon, because of mer-
cury content. The kidneys of one of the
animals contained 67 ppm mercury; muscle
ranged from 0.1 to 1.63 ppm among the 7
carcasses. Kahrs reported on a herd of
swine fed for several weeks a diet one-half
of which consisted of seed grain treated with
methylmercuric dicyandiamide. Almost all
of this herd of 44 adults and 5 litters of pigs
died within a 3 month feeding period (Mer-
curial Pesticide Review Panel Report).

West66 (1967) reported that hens fed grain
treated with methylmercury lay eggs with
higher mercury content than those fed grain
treated with alkoxyalkyl mercury com-
pounds. Tehning (1967) found that hens fed
grain containing 18.4 ppm methylmercury in
half their feed intake laid eggs with more
than 20 ppm methylmercury in the albumin.
Other workers have reported lower amounts
of methylmercury in eggs of chickens fed
treated grain.


Treatment Treatment
‘Avdp. 02. 28.6% | Soak time Avdp. 02. 28.6% Soak time
Name of Seed perk S pounds in normal Name of Seed per 15 pounds in normal
seed solution seed solution
Calendula Loz. 60 min, Humulus loz. 60 min,
Calla Lily --~ 60 min. Hyacinth (bulb) --- 2 hrs.
Campanula Loz. 30 min, Ipomeoa loz. 60 min,
Carnary Bird Flower loz, 60 min, Jonquil (bulb) - 2 hrs.
Canterbury --- 15 min, Kochia wou. 30 min.
Cardiospermum Hor. 60 min, Kudzu Vine Loz. 60 min,
Carnation loz. 30 min. * Larkspur loz. 60 min.
Celosia plumosa loz. 30 min. Lavatera Loz. 60 min,
Centaurea Loz. 30 min, Lupinus hou. 60 min.
Chrysanthemum Loz. 30 min. Marigold Kor. 60 min.
Clarkia Yor. 60 min. Mignonette Koz. 60 min.
Clematis Loz. 60 min. Myosotis wor. 60 min.
Convolvulus Loz. 60 min, Narcissus (bulb) — 2hrs.?
Coreopsis loz. 30 min. Nasturtium loz. 30 min.
Cosmos Koz. Pansy Loz. 30 min.
Crimson Flax loz. Peony (Roots) --- 30 min.?
Crocus Petunia Kor. 30 min.
Daffodil (bulb) Phlox loz. 30 min.
Dahlia (Tuber) Poppy woz. 30 min.
Dahlia (Seed) ---- Portulaca hoz. 30 min.
Delphinium 30 min. Pyrethrum Kou. 30 min.
Digitalis 30 min. Salpiglossis loz. 60 min.
Dimorphoteca ---- Salvia Aor. 30 min,
Eschscholtzia 90 min. Scabiosa Loz. 60 min.
Four O'Clock 60 min, Stevia loz. 60 min.
Freesia (Corms) 60 min, Stock won. 30 min.
Gaillardia 15 min, Sweet Alyssum on. 60 min.
Geum Sweet Pea loz. 30 min.
Gladiolus (Corms) 7 his. Sweet William loz. 30 min,
Globeamaranth 30 min. Tuberose --- 30 min,
Godetia 60 min. (bulb)
Gypsophila 60 min. Tulip (bulb) --- 2 hrs.
Helianthus 30 min. Valerian Loz. 30 min,
Helichrysum 30 min, Verbena loz. 30 min.
Heliotrope 60 min. Violet Loz. 30 min,
Hibiscus 90 min. Wallflower loz. 30 min,
Hollyhock 30 min. Zinnia Loz. 60 min,
*Preplanting treatment only.
? Use extra strength solution.
>Use double strength solution.
B. Substitute compounds: C. Comparative effectiveness and impact:
Thiram: (Ref. I-T-10-00.08] dust thoroughly (1) Mercury compounds are more
with 4 to 12% dusts effective than the available substitute com-

36


CHAPTER 6

ECOLOGIC EFFECTS OF MERCURY CONTAMINATION

Sources of mercury in the environment,
both natural and man-made have been con-
sidered. While all forms of mercury are tox-
ic to life, it has been pointed out that aryl-
mercury, or methylmercury specifically, has
the most profound effect on animal life. It
has been demonstrated that all forms of
mercury may be transformed into methyl-
mercury in an aquatic environment.

VI.A. Biotransformation of Mercury — The
methylation of mercury in sediments in river
and lake bottoms is the process which, to a
substantial degree, is responsible for current
and potentially future contamination of
aqueous systems and their associated biota.
Indirectly this methylation process may also
play, through the evaporation of dimethyl-
mercury, a large role in atmospheric trans-
port of mercury.

Natural methylation of mercury was sus-
pected in the Minamata episode (Fujiki 1963
cited in Wood, et al., 1968), but the suspi-
cion was put aside as being of no signifi-
cance when methylmercury was identified in
the discharge from the acetaldehyde plant
(Irukayama, et al., 1962). Mercury has been
shown to be methylated by aquarium and
natural sediments (Jensen and Jernelov,
1969) and enzymatically by extracts of meth-
anogenic bacteria (Wood et al., 1968). These
workers also found that small amounts of
methylmercury were produced nonenzyma-
tically. Both groups found both monomethyl
and dimethyl mercury as initial products,
with high mercurial concentration favoring
the monomethyl form (Wood et al., 1968),
and alkaline pH favoring the dimethyl form
(Larsson 1970). The latter compound de-
composes to monomethy! form at an acid

pH. Jensen and Jernelov (1968) suggest that
the methylation might proceed as follows:

Hg2+__\ CH3Hg*___\ (CH3))Hg
He?+_s (CH3)7He __\ CH3Hg
Wood et al., (1968) suggest the following
scheme of methylation by Methanobacter-

ium omelianskii or by solutions of methyl-
cobalamin:

neutral pH

He2 +

(CH) Hg

2CH3-By 2Bi2
acid pH

CH,Hgt + CHy

enzymatic
regeneration

The tendency of alkaline pH to favor a high-
er production of the more volatile dimethyl
form also would produce a larger discharge
of methylated mercury by evaporation into
the atmosphere; contrarily, a more acid pH
should then favor (1) a higher proportion of
the less volatile monomethyl form, (2) ready
decomposition of the smaller proportion of
the dimethyl compound, and (3) a greater
total retention, with less loss to the atmos-
phere (Larsson 1970). These mechanisms
have been cited as possible factors (Hohnels
1970) leading to the contamination of remote
acid lakes with high levels of mercury in
fish, in the absence of known sources of
contamination. All forms of mercury appear
to be directly or indirectly capable of con-
version to methylmercury (Jernelov 1969).

79


rats appeared lethargic and squeaked when
touched, and after 5 weeks these rats also
showed fine tremors when lifted by their
tails.

In a third series of experiments, rats were
exposed to the same mercury vapor concen-
tration for 7 hours per day for 5 days per
week for 18 successive weeks. The resulting
symptoms were similar to those in the first
and second experiments but appeared more
slowly, the only difference being that the
rats showed a slight increase in weight dur-
ing the experiment.

The author calculates that if the results ob-
tained in rats in these experiments with mer-
cury vapor at | mg Hg/M3 can be applied to
a man breathing 10 M*/day for 5 days with
the maximum allowable concentration of
mercury vapor of 0.1 mg/m3, then the daily
absorption might be expected to be about
500 w g, with a total excretion over 7 days of
approximately 2.5 mg. If the total exposure
were short, the bulk of the mercury would
be eliminated in a few days, but if the expo-
sure continued for several weeks, the result-
ing accumulation of mercury would be ex-
creted for a considerable time and could
amount to several hundred micrograms per
day (Gage, 1961).

Kosmider (1965) studied the pathogenetic
mechanisms of poisoning in rabbits resulting
from the inhalation of mercury vapors. In
these experiments, rabbits were exposed to
mercury vapor concentrations of 10.6 mg/m?
for I to 5 hours daily for 30 days. This expo-
sure resulted in the alteration of function of
anumber of enzymes and damage to several
organs.

IV.A.3. Absorption through the Skin — All
forms of mercury may be absorbed through
the intact skin. Laug, et al. (1947 a,b,c) stud-
ied the dermal absorption in rats and rabbits
of several of the official mercurial oint-
ments. The preparations studied were Mild
Mercurous Chloride Ointment, NF (Calomel

54

Ointment) which contains 30% HgCl:
Strong Mercurial Ointment, NF (Mercurial
Ointment) which contains 50% Hg: Mild
Mercurial Ointment, NF (Blue Ointment)
which contains 10% Hg; and Ointment of
Oleated Mercury, USP which contains 23%
Hg. Both Strong Mercurial Ointment, NF
and Mild Mercurial Ointment, NF contain
finely divided metallic Hg. A small amount
(5%) of mercuric oleate is added to the mer-
cury in the preparation of the ointment to
form a film over the globules of mercury to
facilitate the dispersion in the ointment.

It was determined that dermal absorption of
mercury was proportional to (1) the duration
of contact, and (2) the area of skin exposed.
The mercury content of the kidneys of rats
after 24 hours continuous skin contact to 8%
of the body surface with 0.4 g of Mild Mer-
curous Chloride Ointment, NF was about
90-fold that found in the controls (27.2 wg
Hg versus 0.3ug Hg/g wet kidney) and about
130-fold after 48 hours contact. In this exper-
iment, mercury levels in rat liver increased
by 10- to 20-fold (0.8 yw g at 48 hours versus
0.06 yt g/g wet liver of controls). The great-
est absorption occurred with Ointment of
Oleated Mercury, which gave 30.1 w g/g wet
tissue.

The vehicle in which mercury is suspended
and the particle size of mercury have an in-
fluence on the dermal absorption. However.
the concentration of mercury in the test oint-
ments appeared to have little influence on
total mercury absorbed. The kidney concen-
trations of mercury after application of Mild
Mercurial Ointment and Strong Mercurial
Ointment were almost identical.

Recent studies in humans conducted by the
Food and Drug Administration with a 1%
ammoniated mercury. bleach cream to which
3% ° Hg had been added, showed that an
average of 2.4 « g/cm? mercury penetrated
intact skin in a 24-hour period (unpublished
data). The author extrapolates these results


Jernelov suggests that phenylmercuric ace-
tate slimicides are more efficient sources of
mercury for subsequent methylation than is
inorganic mercury.

Although methylation of mercury will occur
anaerobically, it appears to be more efficient
in aerobic systems.

VII.B. Sweden — Wildlife served its tradi-
tional role as an early warning system for
man when problems with mercury arose in
Sweden. About 1955, several ornithologists
in various parts of Sweden observed a de-
cline in the populations of some seed-eating
birds. The increase in the number of birds of
prey found ill or dead also attracted atten-
tion. In 1958, Borg drew attention to the fact
that birds found dead and sent to the State
Veterinary Medical Institute had remarkably
high residues of mercury in their livers and
kidneys. Studies of shot and trapped birds
also revealed high levels. The conclusion
was that the large numbers of dead speci-
mens of seed-eating birds (pheasants, par-
tridges, pigeons, finches) and birds of prey
(eagles, buzzards, hawks, falcons, owls) in
particular, and of corvine birds indicated a
very general poisoning in birds. The source
of the mercury was attributed to the use of
mercury compounds in agriculture. The de-
cline in the population of several bird species
in Sweden was attributed to the use of pesti-
cides (Johnels and Westermark, 1969).
News of the Minamata problem in Japan led
to broader and deeper studies (Nelson, et
al., 1971).

Analyses soon revealed that mercury pollu-
tion was serious in Swedish lakes and rivers
and that seed dressings were not the sources
of this contamination. Waste and leakage
from pulp mills and chlor-alkali factories
were chiefly responsible. The result was lo-
cal and spotty contamination, often heavy.
Many lakes and streams remained free or
nearly free of mercury. Even today, most
waters of Sweden are not and need not be
monitored. This localization of contamina-

80

tion means that one must look at the right
spots to find it. Early efforts to repeat the
Swedish findings in the United States, failed
because the animal samples that were taken
did not come from near sources of mercury,
despite the fact that they were taken from
some of the most polluted estuaries of the
eastern United States (Nelson, et al/., 1971).

It was evident in Sweden that mercury from
seed dressings was responsible for the de-
cline of seed-eating birds. The birds of prey
obtained their high levels of mercury from
fish. As stated above, the levels of mercury
in the rivers and streams arose chiefly from
industrial waste and to a smaller extent from
agricultural runoff. Mercury levels up to 9.8
ppm were recorded in Swedish fish.

It became apparent that mercury contamina-
tion of the Swedish environment was even
more widespread than had been previously
believed. In order to assess the historical
development of this contamination, neutron
activation analyses of the mercury content
of bird feathers from museum specimens
collected over the previous century were
performed (Johnels and Westermark, 1969).
These studies revealed that in birds with a
terrestrial food chain, a nearly constant level
of mercury was maintained from the middle
of the previous century until 1940. Subse-
quently, an increase in the mercury concen-
tration of feathers occurred amounting to at
least 10 to 20 times the previous level. Short-
ly after 1940, liquid treatments for seed grain
using alkylmercury ingredients replaced
dusting with other types of organic mercury
compounds in many of the developing na-
tions, because of the reduced hazards and
inconvenience to operators dressing grain
with specially designed machines. The si-
multaneous appearance of increased mercu-
ry accumulations in birds with a terrestrial
food chain thus suggests that the alkylmer-
cury seed-dressings are the main source of
contamination of the terrestrial environ-
ment. In contrast, fish-eating birds showed a
gradual increase in mercury content since


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£7

Compounds

Vil. 8. Turf Disease Control—Continued

th,
“ontioy
te rin,

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ounces actual per 1000 square feet

(9)

Chioroneb
[Ref. I-C-12-00.02]

2.6

3.9 to 5.9

10)

Copper-zinc-chromate
complex
{Ref. 1-C-40-00.04]

gal. of
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Crystal violet-
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green

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2, 4-Dichloro-6-
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[Ref. 1-D-07-00.03]

2to4

2to4 2to4 2to4d

(13)

p-(Dimethylamino)
benezenediazo sodium
sulfonate

[Ref. I-D-14-00.02]

14to1l8

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Cycloheximide
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318

318

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Folpet
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(16)

Maneb
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2.4 to 6.4

48 to 6.4 24 to 6.4

7)

Pentachloronitro-
benzene
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2.15 to
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78.4 to
158.4

16.0 to
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Chiorophthalonil
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15 to
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15 to 1.5 to
3.0 6.0

45t0
6.0



SUMMARY

Although the toxic properties of mercury
and its compounds have long been recog-
nized, it is only recently that the impact on
man and the environment of the extensive
increase in industrial and agricultural uses
has come to light. The first warnings of the
hazard to the environment resulting from the
agricultural use of mercury came from Swe-
den in the 1950’s where the drastic decline in
the populations of both seed-eating and rap-
torial birds was linked to mercury-treated
seeds. At about the same time the effects of
industrial pollution on humans became ap-
parent in Japan where the first poisonings
from mercury-contaminated fish occurred in
Minamata in 1953. This was followed in 1965
by a similar occurrence in Niigata. Soon it
was realized that mercury pollution of lakes
and rivers from industrial pollution was also
a serious problem in Sweden. In 1970 sys-
tematic surveys of fish and wildlife in both
Canada and the United States led to the real-
ization that North America was also faced
with the mercury problem.

Human poisonings resulting from exposure
during the manufacture, formulation, and
use of mercurial pesticides or from the acci-
dental ingestion of mercury-treated grain
date as far back as the use of these pesti-
cides, especially the alkylmercury pesti-
cides. While the accidental ingestion of mer-
cury-treated grain has resulted in many poi-
sonings and deaths in foreign countries, it
was not until the recent highly publicized
incident in Alamogordo, New Mexico, in
1969 that the American public became aware
of this potential hazard.

Inorganic and organic mercury are used in
pesticides. The organic compounds that
have gained importance all have the general
structure R-Hg-X, where R is an organic
radical, alkyl, alkoxyalkyl, or aryl. The
group X is bound to mercury with a bond
more or less having the character of a salt

and originating from organic or inorganic
substances with dissociable hydrogen ions,
e.g. acids, amides. phenols, or thiols. At
present, some one hundred combinations of
different organic radicals and anions are
used in commercial preparations of mercury
fungicides.

All alkylmercury compounds used for seed
treatments and all mercury compounds used
as slimicides, algicides, and in laundries
have previously been cancelled. The regis-
trations of products containing hydroxymer-
curichloropheno! bearing directions for use
on vegetable and field crop fields, the regis-
trations of products containing hydroxymer-
curinitrophenol bearing directions for use on
potatoes and sweet potatoes, and the regis-
trations of products containing phenylmer-
curic acetate or phenylmercuric ammonium
acetate bearing directions for use on apples,
cherries, peaches, strawberries, and sugar-
cane have previously been cancelled as the
result of implementing the NAS, NRC Advi-
sory Committee recommendations to abol-
ish ‘‘no residue’’ and ‘‘zero tolerance’’ reg-
istrations.

Inorganic and arylmercury compounds are
more acutely toxic than the alkyl com-
pounds. The arylmercuries are relatively
rapidly degraded in the body to inorganic
mercury, and their tissue distribution resem-
bles inorganic mercury. Accumulation of
mercury from these compounds is mainly in
the liver and kidneys. The placenta is an
effective barrier to the entry of these com-
pounds. In addition, they are rapidly excret-
ed in the urine and feces. In contrast, the
alkylmercuries are better absorbed, show a
more even tissue distribution and are more
slowly metabolized. They readily cross the
“blood-brain barrier’’ in man. They are able
to cross the placental barrier, where accu-
mulation in the fetus may exceed that in

ix


(a) 2000 to 5000 combined quaternar-
ies plus 600,000 ppm ethanol as low pressure
bomb spray, or

(b) 2500 to 5000 ppm combined qua-
ternaries plus 750 to 2000 ppm brominated
salicylanilides and 630,000 ppm ethanol or
isopropanol as low-pressure bomb spray.

(13) 2, 2’-methylenebis-(3, 4, 5-trichlo-
rophenol): [Ref. I-M-13-00.03] 200 ppm plus
400 ppm 2, 2’ methylenebis (4-chlorophenol)
as low pressure bomb spray.

(14) o-Phenylphenol:[Ref. I-P-19-00.03]
1000 to 2000 ppm plus various amounts of
other fungistats, mostly as low-pressure
bomb sprays.

(15) Sodium dimethyldithiocarbamate

(a) plus sodium 2-mercaptoben-
zothiazole [Ref. I-S-09-00.06]

(b) 1400 to 5800 ppm

(c) plus 120 to 500 ppm

(d) as wash, mop, sponge or spray.

(16) Sodium g-phenylphenate: [Ref. I-
S-16-00.08] 1500 ppm plus 930 ppm methyl
salicylate and 9300 ppm isopropanol as a
spray.

(17) Zineb: [Ref. I-Z-10-00.15) 10,000
ppm as low-pressure bomb spray.

C. Comparative effectiveness and impact

(1) Substitutes are available which are
as effective as mercury compounds for fun-
gistasis on surfaces.

(2) Impact of withdrawal of these uses
will be slight to the consumer but may be
more severe on the manufacturer.

XIV. Tanneries (bacteriostats and fungistats)
A. Mercury compounds

Phenylmercuric acetate

For hides and skins (in cellars of meat pack-

ing plants and tanneries): [Ref. I-P-08-00.09]

305 ppm solution of a combination of PMA,
sodium pentachlorophenate and sodium

38

trichlorophenate. For processing: (Ref. I-P-
08-00.10 and I-P-08-00.11] soaking - 0:05 to
0.10 Ib PMA (I) plus 0.25 to 0.50 Ib potas-
sium trichlorophenate (11/1000 Ib. Add to
soak water. pickling - 0.03 Ib (I) plus 0.15 to
0.25 Ib 11/1000 Ib wet stock. Add to pickling
solution.

Chrome tanning: 0.03 to 0.06 Ib (I) plus 0.15
to 0.30 Ib (I1D/1000 Ib wet stock. Add to
chrome liquor.

Vegetable tanning: 0.03 to 0.06 Ib (I) plus
0.15 to 0.30 Ib (11/1000 Ib of tanned stock.
Add to wash water or to final bleaching liq-
uor.

Samming: Treat sawdust with 0.05 Ib (I) plus
0.25 Ib (IT)/S0 gal of water [120 ppm (I) plus
600 ppm (II).

Fatliquoring: 500 to 1500 ppm (1) plus 2500
to 7500 ppm (II) on weight of fatliquor.

B. Substitute compounds

(1) Pentachlorophenol: [Ref. I-P-05-
00.03] 0.1 to 3.5% in processing solution or
dressing formulations.

(2) 22.5% of potassium pentachloro-
phenate plus 22.5% of potassium 4 (or 6)-
chloro-2-phenylphenate: [Ref. I-P-25-00.01]
Pickling: 0.1% by weight of stock. Chrome
tanning: 0.1% by weight of stock. Vegetable
tanning: 0.3% by weight of stock. Brusting,
pearling or staining: 0.1% solution. Dying
and fatliquoring: 0.1 to 0.2% solution.

(3) Sodium g-phenylphenate: [Ref. I-S-
16-00.09] 0.1 to 3.5% by weight of process-
ing solutions.

(4) 17.5% of sodium tetrachlorophenate
plus 7.7% of sodium o-phenylphenate: [Ref.
I-S-21-00.01] :

Soaking: 1 to 2 1b/100 gal.
Pickling: 3 to 5 Ib/1000 Ib stock. Chrome and
vegetable tanning: 3 to 5 Ib/1000 Ib stock.

(5) Tetrahydro-3, 5-dimethyl-2H, 1, 3,
5-thiadiazine-2-thione: (Ref. I-T-07-00.03]
Soaking: 2 to 4 0z/100 gal.

Padding, tanning, fatliquoring and coloring:
0.5 to 1.5 02/100 gal.


RECOMMENDATIONS CONCERNING THE REGISTRATIONS
OF MERCURIAL PESTICIDES

The Special Pesticide Review Group has
reviewed and evaluated the registered uses
of mercurial pesticides on a use-by-use,
benefit-versus-risk basis. Based on this eval-
uation, the Special Pesticide Review Group
makes the following recommendations con-
cerning the continued registration of these
pesticides.

RECOMMENDATION 1:

Suspend immediately the registrants for all
pesticide products containing alkylmercury
compounds.

The recommendation of suspension of all
alkylmercury-containing pesticides is based
on the high toxicity of these compounds to
humans. The volatility and toxicity of the
alkylmercuries present not only a hazard in
the use of the pesticides containing these
compounds but also an unnecessary hazard
in their manufacture, formulation, and stor-
age. The alkylmercuries have a propensity
for accumulating in the brain and producing
an insidious onset of symptoms associated
with damage to the central nervous system.
The registrations forseed dressings contain-
ing these compounds have been previously
suspended. It is now considered that all oth-
er pesticides containing alkylmercury com-
pounds present an ‘imminent hazard to the
public’’ and their registrations should be
suspended.

RECOMMENDATION 2:

In addition to the suspension recommended
above, the Committee further recommends
that in the absence of an imminent hazard
finding, all other products containing mercu-

Vili

ry be cancelled except those intended for
use as seed dressings for the prevention of
stinking smut in wheat and leaf stripe smut
in growing barley. The Group also recom-
mends that the Administrator request the
Secretary of Agriculture to develop alterna-
tive methods for the prevention of these di-
seases in wheat and barley. When this has
been accomplished, the Environmental Pro-
tection Agency will cancel these two remain-
ing uses of mercurial pesticides.

RECOMMENDATION 3:

Initiate monitoring activities to determine (1)
the effect of the decreased use of mercury
stemming from the cancellation of mercury-
containing pesticides on the general level of
mercury in the environment, and (2) the
effect of the continued use of mercury-
treated wheat and barley on the mercury
levels in man and his environment in the re-
gions in which these seeds are used.

RECOMMENDATION 4:

Continue research on the effects of mercury
in the environment, especially in the areas of
(1) development of more sensitive methods
of determining the effects in humans of low
level exposure to mercury; and (2) the bio-
transformation of mercury compounds.

RECOMMENDATION 5:

The nonpesticidal uses of mercury should
be reviewed by the other components of the
Agency with the goal of eliminating other
sources of mercury contamination of the
environment.


XIL Seed Treatments

3. Flax
2 Pa
¥ §
£. 5 & » §& /,
$F & $ $ & é% /
&? é & ¥ és °
€ 9
ounces actual per bushel
Damping-off, 0.057 1.02 2.05 0.75 24 0.95
Root Rots, to to to to 1.45 to to
Seed decay 0.114 146 2.21 3.20 3.2 1,26
1uUsed only as supplemental treatment to suitable standard seed protectants.
2Used only in combination with Captan.
XIL. Seed Treatments
4. Oats
# ¥
s RS ¢
= 3 Ri
ez 5 3 G =
if ¢ & s ¥ é #
x¢ F ¢ ¢ £ RS &
& é a ¢ 9 é
< - &
x
ounces actual per bushel
0.019
Leaf stri to
0.038
Seed decay “eC 1.92
Seedling blights 0.90 210
Covered smut, 0.75 0.47 1200
Loose smut to 0.18 to to
2.10 0.53 1600
‘Used as supplemental treatment to suitable standard treatments.
?In combination with Captan.
XII. Seed Treatments
5. Rice
# & Fa
= ~ if $
és $ s gf s ex
x? £ £ / & / & & /§8s
es ¢ & &é $ & £
= & o
ounces actual per 100 pounds
Damping-off, 0.042
Seed rots to 1.7-3.75 1.9-2.4 72 1.0 1.55-3.3 1.6-3.2
0.084

Used only as a supplemental treatment to suitable standard seed protectants.

32



pounds after a single injection.’ Arch. Indust.
Health, 20: 432 (1959a).

Swensson, A., and Ulfvarson, U. “‘Toxicite des com-
poses organomercurials employes comme fungi-
cides.’ Revue de I’Hygiene Progressionnelle, 15
(3): 5 (1963).

Swensson, A., and Ulfvarson, U. ‘Toxicology of or-
ganic mercury compounds used as fungicides.””
Occup. Health. Rev. 15:5 (1963).

Swensson, A., and Ulfvarson, U. **Distribution and
excretion of mercury compounds in rats over a
long period after a single injection.’ Acta. Phar-
macol. et Toxicol. 26: 273 (1968).

Swenssen, A., and Ulfvarson. U. ‘‘Distribution and
excretion of various mercury compounds after
single injections in poultry." Acta. Pharmacol. et
Toxicol. 26: 259 (1968).

Swedish Royal Commission on Natural Resources.
“The mercury problem: Symposium concerning
mercury in the environment.’* Stockholm. Swe-
den, Jan. 24-26 (1966). Oikos Supp. 9:9 (1967).

Szkolnik, M., Hickey. K.D., Broderick, E.J., and
Lisk. D.J. ‘Mercury residues of apple fruit as
related to application schedules and to the colori-
metric and the neutron activation analyses.”
Plant Disease Reporter 49: 568 (1965).

Tada. O. ‘‘Measurement method of mercury for the
purpose of health administration.’ Digest of Sci-
ence of Labour, 25 (1): 34 (1970).

Takeda. Y., Kunagi, T.. Hosheno, O., and Ukita, Y.
“Distribution of inorganic aryl and alkylmercury
compounds in rats."’ Toxicol. Appl. Pharmacol.,
13: 156 (1968a).

Takeda. Y., Kunugi. T.. Teras. T.. and Ukita, T.
“*Mercury compounds in the blood of rats treated
with ethylmercuric chloride." Toxicol. Appl.
Pharm. 13: 165 (1968b).

Takeda, Y.. and Ukita. T. ‘Metabolism of ethylmer-
curic chloride 703Hg. in rats."* Toxicol. Appl.
Pharm. 17: 181 (1970).

Takeshita, A.. and Uchida, M. ‘‘The mercury com-
pound in the brain and urine of the rat on oral
administration of methylmethylmercuric sulfide.
Kumamoto Med. J.. 16 (3/4): 178 (1963).

Takeuchi, T. ‘Pathological studies of Minamata dis-
ease—occurrence of neurological disease in mice
by feeding with fish." Kumamoto Med. J. (Jap.
edition) (Supp. 1) 31: 290 (1957).

Takeuchi. T. “Discussion on the cause of Minamata
disease from the standpoint of pathologic stud-
ies..’ Summary of reports on the study of Mina-
mata disease.’ K. Sera, ed. August 20, 1959:
Kumamoto, Japan (1959).

Takeuchi. T. *‘Minamata disease after a lapse of ten
years and its pathological changes.’ Japan Med.
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114

Takeuchi, T. ‘‘Biological reactions and pathological
changes of human beings and animals under the
condition of organic mercury contamination.””
International Conference on Environmental Mer-
cury Contamination, Ann Arbor, Mich. (1970).

Takeuchi, T.. ef al. ‘‘Pathological studies of the en-
cephalopathia in the Minamata district."" Kuma-
moto Med. J. (Jap. edition) (Supp. 1) 31:37 (1957).

Takeuchi, T., et al. Pathological studies on Minamata
disease—with special reference to the histopath-
ological findings in the central nervous system.”*
Kumamoto Med. J. (Jap. edition) (Supp. 1) 31:
262 (1957).

Takeuchi, T., et al. ‘Pathological studies of cats af-
fected by Minamata disease." Kumamoto Med.
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Takeuchi, T., et al. “Pathological studies on Minama-
ta disease in crows and other birds.” Kumamoto
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Takeuchi, T., et al. “‘A pathological study of Minama-
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Takeuchi. T., and Matsumoto, H. ‘Minamata disease
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heavy metals, particularly organic mercury com-
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(1968).

Tankawa. I., Nunoda, E. Niigata. ‘The spectropho-
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Tatetsu, M., Harada, M. ‘‘Mental deficiency due to
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181 (1968).

Tatton, J. O'G., and Wagstaffe, P.J. ‘Identification
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Taugner, R., and Wacker, E.E.R. ‘‘Renal storage and
excretion of mersalyl 203Hg. in rats.”’ Virchows.
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Taylor, W., Guirgis, H.A., Stewart, W.K. ‘‘Investiga-
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seed dressings.’ Arch. Environ. Health 19: 505
(1969)

Teisinger, J.. et al. ‘Pulmonary retention and excre-
tion of mercury vapours in man.”’ Indust. Med.
Surg.. 34: 580 (1965).


(10) Dialkyl dimethyl ammonium chlor-
ide: fungistat; industrial use in finishing
process. [Ref. I-D-04-20.02] Deposit 28.1 to
3750 ppm quaternary plus 142.5 to 1250 ppm
TBTO by weight.

(11) Diisobutylphenoxyethoxyethyl
dimethyl benzyl ammonium chloride: fun-
gistat, industrial use in finishing process.
[Ref. I-D-13-00.04] 1635 to 2045 ppm quater-
nary plus 468 to 585 ppm tributyltin ben-
zoate by weight of fabric.

(12) Dodecyl-di — (beta-hydroxyethyl)
benzyl ammonium chloride: fungistat; in-
dustrial use in finishing process. [Ref. I-D-
26-10.01] For suitings, linings, blankets,
upholstery fabrics, carpets and other articles
seldom, if ever, laundered. 0.2 to 1.0 gram/
liter of water by exhaustion or padding.

(13) N-Dodecylquanidine _ terephthal-
ate: fungistat; industrial use in finishing
process. [Ref. I-D-27-90.01] For awnings,
tents, tarpaulins, sails and similar textiles:
2500 to, 5900 ppm by padding.

(14) Lauryl pyridinium salt of 5-chloro-
2-mercaptobenzothiazole: fungistat; —in-
dustrial use in finishing process. [Ref. I-L-
01-00.01]

(a) For burlap: 3375 to 10,000 ppm.

(b) Duck, mattress ticking, similar
fabrics: 1250 plus 2500 ppm.

(c) Industrial fabrics and yarns: 5000
plus 10,000 ppm.

(15) 2, 2 -Methylenebis - (3, 4, 6-tri-
chlorophenol): fungistat: industrial uses,
finishing process. [Ref. I-M-13-00.03]

(a) -200 to 2500 ppm.
(b) 2500 to 6000 ppm plus 2500 to
6000 ppm o-phenylphenol.

(16) 10, 10 Oxybisphenoxarsine: fun-
gistat; industrial uses in finishing process.
[Ref. I-O-03-00.01] For cotton fabrics to be
coated with thermoplastic systems: 400 to
1000 ppm by padding.

(17) Pentachlorophenol: consumer use.
30,000 to 50,000 ppm as a soak. (Ref. I-P-05-
00.01)

(18) Sodium dimethyldithiocarbamate:
fungistat; industrial uses in finishing proc-

ess. [Ref. I-S-09-00.05] 1.38% plus 0.12%
sodium 2-mercaptobenzothiazole by pad-
ding to 100% wet pick up. Set with zinc ace-
tate.

(19) Sodium pentachlorophenate: fun-
gistat: industrial use in finishing process.
[Ref. I-S-15-00.04] For suit linings. uphol-
stery fabrics: 1000 to 5000 ppm by dipping.
padding or spraying.

(20) Sodium orthophenylphenate: fun-
gistat for preservation of unfinished cloth
and yarns. [Ref. I-S-16-00.10] 0.2 to 1.0%.

. (21) Sodium salt of 2-mercaptoben-
zothiazole: fungistat; industrial use in finish-
ing process. [Ref. I-S-20-00.01] 0.2% by
weight deposited on fabric.

(22) Thiram: fungistat; industrial uses.
[Ref. I-T-10-00.08] For belting, ducks, other
heavy industrial fabrics: 1875 to 3750 ppm
by weight of fabric.

(23) 3, 4, 5-Tribromosalicylanilide:
fungistat; industrial use in finishing process.
[Ref. I-T-11-00.01 and 0.2]

(a) For fabrics to be coated with vi-
ny! thermoplastics: 20,000 ppm prior to coat-
ing.

(b) Other textiles: 500 to 7500 ppm by
weight.

(24) Tributyltin acetate: fungistat; in-
dustrial use in finishing process. [Ref. I-T-
12-00.01] Deposit 1.8% of product by weight
of fabric by padding.

(25) Zinc dehydroabietylammonium 2-
ethylhexoate: fungistat; industrial use in
finishing process. [Ref. I-2-03-00.01] 2.0 to
2.5% or more by weight of fabric of a formu-
lation containing 42.8% plus 29.2% zinc
ethylhexoate and 19.2% 2-ethylhexoate salt
of magnesium quinolinolate.

C. Comparative effectiveness and impact.

(1) Various mercury compounds are
used as fungistats in textile finishing at levels
of 25 to 1130 ppm by impregnation. Substi-
tute materials are used at levels from 200 to
20,000 ppm.

(2) Mercury compounds are ‘‘broad
spectrum’’ fungistats controlling most, if not

at


(bb.) Industrial use: 3600 to 9000
ppm by weight of paint.

(g) 4-Chloro-3, 5-xylenol: [ref. I-C-
21-00.01 and .02]

(aa.) Household use: 1.0 fluid 0z of
45% solution/gal of interior, oil or emulsion
formulations.

(bb.) Industrial use: in amounts
required.

(h) Copper 8-quinolinolate: [Ref. I-
C-34-00.01 and .02]

(aa.) Commercial use: 0.75 pint of
10.0% solution/gal.

(bb.) 10,000 ppm by weight of sol-
ids or by total weight of paints, varnishes or
sealers.

(i) Parachlorometacresol: [Ref. I-P-
01-00.01] 500 to 1500 ppm by weight of
aqueous system paints.

(j) Potassium o-phenylphenate: (Ref.
I-P-26-00.01]

(aa.) Preservation: 0.15 to 2.0 per-
cent by weight.

(bb.) Mildew control: 10,000 to
20,000 ppm by weight of polyvinyl acetate
formulation.

(k) Potassium 2, 4, 6-trichlorophen-
ate: (Ref. I-P-28-80.01] Mildew control: 3750
to 22,500 ppm by weight.

(1) Sodium o-phenylphenate: [Ref. I-
S-16—00.09]

Preservation: 2000 to 5000 ppm by weight of
oil- or water-based formulations.

(m) 2, 3, 5, 6-Tetrachloro-4-methyl-
sulfonyl pyridine: [Ref. I-T-02-00.01] 500 to
30,000 ppm by weight of alkyl, latex or oil
formulations.

(n) Tetrahydro-3,
3-. 5-thiadiazine-2-thione:
00.03]

5-dimethyl-2H-1,
[Ref. I-T-07-

(aa.) Interior paint mildew: 1000
to 20,000 ppm by weight of paint.

(bb.) Aqueous components
molds: 100 to 5000 ppm. by weight of sus-
pension.

(0) 2-(4-Thiazolyl)
(Ref. I-T-09-00.02 and .03]

benzimidazole:

6

(aa.) Exterior paints:
0.25 to 2.0 Ib/100 gal.

(bb.) Interior paints:
0.1 to 1.0 1b/100 gal.

(p) 3. 4’, 5-Tribromosalicylanilide:
[Ref. I-T-11-00.02] 1000 ppm by weight of
butadiene - styrene latex formulation.

(q) Tributyltin salicylate: [Ref. I-T-
12-80.01] Amount as required.

(r) Zineb: [Ref. I-Z-10-00.14]
Household use: 1.0 to 1.5 ounces/gal.

(3) Comparative effectiveness and im-
pact

(a) Very little is known about the
comparative effectiveness of mercury and
substitute compounds in paints. Mercury is
compatible with most types and formula-
tions of both oil- and water-based types.
Most substitute compounds are limited as to
type of paint and specific formulation in
which they can be used or that has been test-
ed.

(b) The industry recognizes the need
to develop substitute materials but has indi-
cated that time is needed to test compounds
now available.

(c) The impact of withdrawal of mer-
cury from the pesticide uses in paints, var-
nishes and lacquers would be very severe on
the manufacturers and could leave the pub-
lic in a “‘distress situation’’ in regard to mil-
dew control on paint films, particularly in
areas with severe mildewing conditions.

B.Paint and premanufactured paint com-
ponents preservation (bacteriostatic):

(1) Mercury compounds
Phenylmercuric acetate (100% powder):
[Ref. Reg. No. 8489-5]

(a) Preservative for polyvinyl ace-
tate, acrylic and butadiene-s styrene sys-
tems. Package stability for aqueous systems
such as paint and carbohydrate thickener
solutions: 2 to 4 ounces product/100 gal me-
dia by weight.

(b) Preservation of protein colloids
and systems containing same: 4 to 8 ounces
product/100 gal media by weight.


levels up to 117 ppm in éagles from Minne-
sota and up to 4.4 ppm in fish collected from
the North Fork of the Holston River. As a
result of this information, restrictions on
sport and commercial fishing have been
placed on waters within at least 18 states as
of September 1970 (Celeste and Shane,
1970).

In the fall of 1970, the Food and Drug Ad-
ministration found that canned tuna sold in
the United States contained up to 1.2 ppm
mercury (average 0.37 ppm) and that frozen
swordfish ranged from 0.18 to 2.4 ppm (aver-
age 0.93 ppm). The Food and Drug Adminis-
tration set an interim guideline of 0.5 ppm
mercury in fish.

A 21 member ad hoc committee of experts
reviewed the Food and Drug Administra-
tion’s data on mercury contamination of
swordfish and were unable to suggest any
basis on which swordfish consumption might
be continued without possible health hazard.
Accordingly, the FDA issued the statement

in May 1971 that the ‘‘public stop eating this
fish until and unless the situation can be
remedied.”

On May 20, 1971, at a Senate subcommittee
hearing on chemical pollution, the first case
of mercury poisoning in the United States
from eating fish was reported. Dr. Roger C.
Herdman, New York State Deputy Health
Commissioner, reported the case of a house-
wife, age 44. He stated that she became
“rigidly committed’’ to a weight loss pro-
gram. She started eating 10 oz of swordfish a
day, plus some shrimp, for 10 months ‘‘with-
out interruption.’ She lost 45 Ib but began
suffering lethargy, visual complaints and
tremor. Still, two or three times a year until
last November, she again ate swordfish for 3
to 6 weeks. In May 1966, she began having
serious trouble speaking, walking, and un-
derstanding along with loss of memory and
dizziness. Doctors told her it was probably
psychosomatic, and she saw a psychiatrist
once a week for 2 1/2 years. Only recently
did a hair sample reveal a high mercury con-
centration (Washington Post, May 21, 1971).


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Kim, S., and Hiramo, A. ‘Neurotoxic effect of alkyl-
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104

Kirby, A.H.M., and Bennett, M. “Phytotoxic effects
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Kispatic, J. ‘Seed moistening. a new method of cereal
seed treatment.’’ Agron. Glas. 30(4): 289 (1968)
[CA 72(9):42124k, Mar. 2, 1970.]

Kitagawa, T., Abe, T., ‘‘Formation of phenyl mercury
compounds due to decomposition of acetic acid
phenyl mercury.. III. Determination of methyl!
mercury compounds in commercial agriculture
chemicals."* Anzen Kogaku 8 (3): 163 (1969).

Kitamura, S. ‘Quantitative estimation of mercury.”
Summary of reports on the study of Minamata
disease. K. Sera, ed. August 20, 1959: 9 Kuma-
moto, Japan (1959).

Kitamura, S. ‘Problems of harm from mercurial agri-
cultural chemicals.’’ Special edition -‘‘Agricul-
tural chemical poisoning.”* Accident Medicine, I]
(5): 504 (1968).

Kitamura, S. “‘Organic mercury poisoning Minamata
disease in Niigata.” J. of Clinical Sci., 4 (8): 954
(1968).

Kitamura, S. ‘‘Organic mercury poisoning - Minamata
disease in Niigata.’ Kankocho Kogai Senmon
Shirvo, 4 (1): 61 (1969).

Kitamura, S., et al. “Chemical and toxicological stud-
ies on the Minamata disease.’ Kumamoto Med.
J. (Jap. edition) (supp. 1) 31:54 (1957a).

Kitamura, S. et al. “Epidemiological investigation of
the unknown central nervous disorder in the Min-
amata district." Kumamoto Med. J. (Jap. edition)
(Supp. 1) 31:299 (1957c).

Kitamura, S. et al. ‘Chemical studies on Minamata
disease."’ Kumamoto Med. J. Jap. edition) (supp.
1) 31:311 (1957).

Kitamura, S., et al. ‘Epidemiological studies on the
nervous disease of unknown etiology occurred in
Minamata district (Minamata disease)."" Kuma-
moto Med. J. (Jap. edition) (supp. 2) 31: 238
(1957b). \

Kiwimae, A., et al. ‘““Methylmercury compounds in
eggs from hens after oral administration of mer-
cury compounds.”’ J. of Agric. Food Chem. 17
(5): 1014 (1969).

Kiycura, R. “Water pollution and Minamata disease."
Proceedings of the International Conference,
London, 1962, Adv. Water Pollution Res. Vol. 3.
p. 291-302 (1962). :

Klotz, J.M., and Klotz, T.A. “The role of sulfur in
some metal-proteins."’ In Benesch, R.B., Be-
nesch, R.E., Boyer, P.H., Klotz, J.M., Middle-
brook, W.R., Sgent-Gyorgyi, A.G., and Schwarz,
eds. Sulfur in Proteins, Academic Press, New
York (1959).

Klein, A.K. ‘Report on mercury.” J. Assoc. Offic.
Agr. Chem. 35: $37 (1952).


tion of mercury in the urine of rats was not
as rapid as that observed with phenylmercu-
ty, nor was there any appreciable excretion
of the unchanged compound. However, to-
tal mercury levels in the kidneys showed a
marked increase. In addition, the fecal ex-
cretion of mercury over a 7-day period fol-
lowing administration of ethylmercury was
only one-twentieth of that observed in the
phenylmercury study, suggesting the liver
was not involved in the metabolism and ex-
cretion of ethylmercury. Chicks did not
show accumulation of mercury in the kid-
neys following the administration of ethyl-
mercury, and it appeared the liver was the
major organ involved in detoxication. A
comparison of the excretion of mercury in
rats fed 203Hg-labeled phenylmercuric ace-
tate or mercuric acetate showed that 68% of
the activity from a single dose of phenylmer-
curic acetate accumulated in the feces, and
12.6% of the inorganic mercury was excret-
ed in the feces and only | to 4% in the urine
(Ellis and Fang, 1967).

Swensson, et al. (1959) studied the distribu-
tion and excretion of 203Hg-labeled mercuric
nitrate, phenylmercuric acetate and methyl-
mercuric hydroxide in rats and dogs. There
was a continuous outflow of mercury from
the various organs until 32 to 64 days after
the initial injection when the organs were
practically free from mercury. The kidney
level of mercury fell very slowly after meth-
ylmercury. This was probably due to a con-
tinuous supply from other parts of the body
that were being depleted of mercury. There
were considerable differences between the
rate of excretion of the three compounds.
The mercury concentration was appreciably
lower in the case of methylmercury than af-
ter mercuric nitrate or phenylmercury. The
total excretion within 4 hours of injection
was essentially lower for the methylmercury
compound than for the other two. The meth-
yl and phenyl compounds were excreted
most rapidly at the beginning of the experi-
ment when the concentration of mercury in

the blood was highest, the rate decreasing
with the fall in concentration of mercury in
the blood was highest, the rate decreasing
with the fall in concentration in the blood.
After the injection of inorganic mercury, a
high initial excretion was followed by a peri-
od of anuria, after which only traces of urine
with a very high mercury content were ex-
creted. The rate of urinary excretion was
greater after phenylmercury than with meth-
ylmercury. Although, in both cases, there
was a steady excretion of mercury which
was related to the concentration in the
blood. The anuria following mercuric nitrate
administration suggests that this compound
is more toxic to the kidneys than the organic
compounds.

Gage (1964) studied the distribution and ex-
cretion of mercury after the subcutaneous
injection of phenylmercuric acetate and of
methylmercuric dicyanidamide in the rat.
He found that phenylmercury is readily ab-
sorbed from the injection site and is rapidly
removed from the blood by the tissues.
Some concentration and probably some
metabolism of phenylmercury occurs in the
skeletal muscles, but the bulk is removed
from plasma by the liver and the kidneys
where it is rapidly metabolized and excreted
with only a small proportion appearing un-
changed in the feces and urine. Absorption
of methylmercury was rapid from the injec-
tion site and was taken up by all tissues,
especially in the skeletal muscle and intes-
tine. The major route of excretion is through
the gut, but the ratio of organic mercury in
the liver and feces indicates methylmercury
is also excreted by this route more slowly
than phenylmercury acetate. With both
methylmercury and phenylmercury, there is
a high content of mercury in the hair; with
methylmercury the concentration is greater
than in any other tissue, and there may be an
appreciable excretion of mercury by this
route. There is no evidence whether the
mercury is excreted in sebum or incorporat-
ed into the hair proteins.

61


V. Food and Feed Containers
(Sacks, Seed Bins, and Containers for Treat-
ed Seed Subject to Diversion to Food and Feed

Uses)

1. Mercury compounds

Hydroxymercurichlorophenol: [Ref. I-H-06-
00.05] 690 ppm suspension. Spray or dip
before refilling. Fungistat.

2. Substitute compounds
None registered.
3. Comparative effectiveness and impact

a. Several substitute materials could be
accepted for this use, particularly the non-

VI.

1, Mercury compounds

A. Metallic mercury: (Ref. Reg. Nos.:
140-20; 223-12; 372-19; 1091-5; 1471-3; 5231-
3: 6253-3; 9850-1] 9.0 or 10% mercury for
louse control applied as an ointment.

B. Ammoniated mercury: 5.0% [Ref.
Reg. Nos. 994-5] (3.9% metallic mercury)
for louse control applied as an ointment.

C. Metallic mercury: (10%) plus Mercury
oleate (0.8%) [Ref. Reg. No. 4476-30; 6253-
3] For louse control applied as an ointment.

2. Substitute compounds

A. Premium grade Malathion: 1% dust for
head and body lice [Ref. Reg. No. 241-68]
(Basic manufacturer of malathion does not
market for this purpose).

B. Carbaryl (Sevin): 5% dust for crab,
head and body lice [Ref. Reg. No. 9734-3]

C. Lindane: 1% dust is registered for use
by the military or under prescription from a
physician.

16

residual disinfectants such as the hypochlor-
ites. Quaternary compounds, TBTO, etc.
would require tolerances for use on seed
which could be diverted to food or feed
uses. Copper naphthenate and zinc petrole-
um sulfonate can also be used.

B. Impact of withdrawal of this use for
mercury would be negligible. Note: The
manufacturer has indicated that the product
is being discontinued. Registration remains
in effect to cover stocks still on distributors
shelves. !

Humans

D. Thanite: 5% water emulsion [Ref.
Reg. No. 718-1]

E. Products containing pyrethrins, saba-
dilla, and larkspur have also been registered
for control of lice on humans; however, we
can not identify any products which are cur-
rently being marketed for this purpose.

F. DDT has been registered for control of
lice on humans; however, all uses of DDT
have been cancelled, and administrative
hearings are to take place in the near future.

3. Comparative effectiveness and impact

The primary problems with products used
against lice are in two areas:

(1) resistance in certain parts of the
world has developed to one or more of the
chemicals registered for control of lice;

(2) Malathion and certain of the other

compounds are not readily available to the
general public.


cific formulations or processes. Thus, sub-
stitute materials may not be available for all
paint formulations, certain tanning process-
es or other uses. Conversely, the fact that no

substitute is presently registered for a spe-
cific formulation or process does not mean
that one is not known which can be regis-
tered for such use.

I. Coatings

1. Adhesives
A. Mercury compounds

Phenylmercuric acetate: [Ref. I-P-08-00.09]
For preservation of product: 45 to 250 ppm
For mildew control after application: 3500 to
15,000 ppm based on total wet weight.

B. Substitute compounds

(1) Alkyl dimethyl benzyl ammonium
chloride: [Ref. I-A-08-45.05] fungistat: 800
ppm by weight. [Ref. I-A-08-50.01] preser-
vative: 50,000 ppm plus other fungistats.

(2) Bis (tributyltin) oxide: [Ref. I-D-09-
00.02] fungistat: use in amount required.

(3) 4-Chloro-3, 5-xylenol: [Ref. I-C-21-
00.02] fungistat: use as required.

(4) Dehydroabietylamine pentachloro-
phenate: [Ref. I-D-02-00.01] fungistat: 1700
to 8000 ppm by weight of adhesive.

(5) Hexahydro-1, 3, 5-triethyl-s-tria-
zine: [Ref. 1-H-04-00.01] fungistat: 100 ppm
by weight.

(6) Monoethanolammonium 2-mercap-
tobenzothiazole: [Ref. I-M-21-00.01]

(a) 2000 to 4000 ppm for low protein
adhesives by weight.

(b) 800 to 12,000 ppm for high protein
adhesives by weight.

(7) Parachlorometacresol: [Ref. I-P-01-
00.01] fungistat: 500 to 1500 ppm by weight
of product.

(8) Sodium o-phenylphenate: (Ref. I-S-
16-00.08] preservation: 500 to 1000 ppm by
weight.

(9) Vinylene bisthiocyanate: [Ref. I-V-
01-00.01]

(10) Tetrahydro-3, 5-Dimethyl-2H-1, 3,
5-thiadiazine-2-thione (Mylone): [Ref. I-T-
07-00.01) 0.01 to 0.5% by weight of suspen-
sion.

2

(11) Ziram: [Ref. I-Z-11-00.07] (1) plus
zinc-2-mercaptobenzothiazole (2) 180 ppm
(1) plus 20 ppm (2) to 2300 ppm (1) plus 50
ppm (2) by weight.

C. Comparative effectiveness and impact

(1) In general, mercury compounds are
effective at lower dosages and against a
broader spectrum of fungi than are the sub-
stitute materials.

(2) Impact of withdrawal of mercury
uses as pesticides in adhesives should be
minimal.

2. Coatings for outdoor fabrics
A. Fungistatic:

(1) Mercury compounds
Phenylmercuric oleate [Ref. I-P-14-00.0] 500
to 5000 ppm by weight of coating.

(2) Substitute compounds

(a) None specifically identified by
label claims but might include products used
in sealers and sizings, and certain plastics.

(b) Bis (tributyltin) oxide: [Ref. I-S-
09-00.02] For furniture and similar items (vi-
nyl) 4,000 to 10,000 ppm by weight of nonvo-
latile components of formulation.

(3) Comparative effectiveness and im-
pact

(a) Comparative effectiveness un-
known.

(b) Impact of withdrawal of mercury
for this use on industry and consumer is also
unknown.

B. Bacterial preservatives:

(1) Mercury compounds
Phenylmercuric hydroxide 17% (powdered):
[Ref. 6516-3]

Paint (unspecified) coatings for fabrics: 0.5
Ib product per 99.5 Ib media.


17

Compounds

VIL. 8. Turf Disease Control

Pin,
"opp

£
£
CG

2%, lay

No,

‘ounces actual per 1000 square feet

A. Mercury compounds:

(1) Cyano (methyl-
mercuric) guanidine
[Ref. 1-C-46-00.02]

033

.033 066 033

066

066

(2) Hydroxymercuric -
chlorophenol:
(Ref. I-M-06-00.01]

823

-300 823

-300

-300

-800

@) Mercurie chioride
[Ref. 1-M-04-00.01]

(4) Mercuric chloride
plus
4 Mercurous-chloride
[Ref. I-M-04-00.01]

3- 9

6 -24

3- 9

6-24

(S) Mercurie dimethyt -
dithiocarbamate
[Ref. 1-M-04-05.01]

444

A44 444

AdG

444

(6) Methyimercuri
‘tetrahydroendo -
methano hexachloro
phthalimide
[Ref. I-M-15-00.01]

(7) Mercurous chloride
{Ref. I-M-05-00.01]

9-15

(8) Phenylmercuric
acetate
{Ref. I-P-08-00.04]

() Phenylmercuric
dimethyldithio-
carbamate
[Ref. IP-09-00.01]



VII.B.2.6. Feed Containers — These are
sacks, seed bins, and containers for treated
seeds subject to diversion to food and feed
use. This use presents not only an environ-
mental contamination hazard but also a po-
tential human health hazard.

RECOMMENDATION:
Cancel this use of mercury.

VI.B.2.7. Humans — These registrations
are for Mild Mercurial Ointment (Blue Oint-
ment) as a treatment for pediculosis pubis.
This product contains elemental mercury
which is absorbed through the intact skin.
Fatal accidents have been reported in which
the entire body surface was covered with
Blue Ointment.

RECOMMENDATION:

Cancel the registrations for Mild Mercurial
Ointment as a treatment for pediculosis pu-
bis.

VII.B.2.8. Ornamental Plants

1, Bulbs and Corms — The mercurial fungi-
cides are used to control root, stem, and
bulb rots. The registrations include alkyl,
aryl, and inorganic mercury compounds. In
Washington and Oregon, bulb dipping vats
have capacities up to 10,000 gallons. The
drainage of the vats after treatment of the
bulbs and corms has been completed poses a
significant potential for contamination of the
soil and water.

2. Cuttings — Only alkylmercury com-
pounds are employed in this use.

3. Flowering and Foliage Plants — These
uses are directly on the foliage of the plants
or on the soil in which they are planted. This
usage pattern provides a direct contamina-
tion of the environment.

92

4. Trees and Shrubs — This use provides a
direct contamination of the environment
with mercury.

RECOMMENDATION:

Cancel the registrations for the use of mer-
curials on ornamental plants.

VII.B.2.9. Paper — Mercurials are used for
moldproofing paper, paperboard, and wall-
paper. This use provides a direct contamina-
tion of the environment with mercury.

RECOMMENDATION:

Cancel the registrations for the use of mer-
curials in paper.

VII.B.2.10. Plastics — Mercurials are used
as fungistats in the plastic films. The use of
plastics thus treated range from garbage
bags, shower curtains, to almost any non-
food use of plastics. Garbage bags treated
with mercury are often misused for the stor-
age of foods.

RECOMMENDATION:
Cancel the registrations for the use of mer-
curials in plastics.

VII.B.2.11. Rubber — The use of mercurials
in rubber is similar to the use in plastics.

RECOMMENDATION:

Cancel the registrations for the use of mer-
curials in rubber.

VII.B.2.12. Sanitizers— This category in-
cludes impregnated dust cloths and floor
wax. Mereury from this usage pattern will
eventually enter the sanitary sewers.

RECOMMENDATION:

Cancel the registrations for the use of mer-
curial pesticides in sanitizers.


CHAPTER 7

THE HAZARDS OF MERCURIAL PESTICIDE USE

Approximately one million pounds of metal-
lic mercury were used in the United States in
1969 in the production of pesticide chemi-
cals. About 85% of this one million pounds
_was used in preserving and mildew-proofing
paints while the remainder was used in agri-
culture, the paper and pulp industry, and in
miscellanéous pesticides. The pesticide uses
of mercury are the largest dissipative or
nonrecyclable uses in this country today.

Elemental, inorganic, and organic mercury
are used in pesticides. The organic com-
pounds that have gained importance all have
the general structure R-Hg-X, where R is an
organic radical, alkyl, alkoxyalkyl, or aryl.
The group X is bound to mercury with a bond
more or less having the character of a salt
and originating from organic or inorganic
substances with dissociable hydrogen ions,
e.g., acids, amides, phenols, or thiols. At
present, some hundred combinations of dif-
ferent organic radicals and anions are used
in commercial preparations of mercury fun-
gicides.

The different compounds of mercury differ
in their solubility, volatility, and their toxici-
ty to man and animals. Therefore, in consid-
eration of the hazard of a particular use,
both the nature of the compound and the
usage pattern must be considered.

VII.A. Cancelled or Suspended Uses

Steps have already been taken that have
reduced or eliminated certain uses of mercu-

ry.

VII.A.1. Paper and Pulp —The paper and
pulp use fell sharply in 1965 consequent to
Food and Drug Administration action re-
quiring that paper used to wrap food be free
of mercury. Although, the 1969 paper and

pulp use was above the 1968 level, it was
only 25% of the 1964 level. This use will be
reduced to zero as the result of the August 7,
1970, cancellation of the registered uses of
all mercury products bearing the claims or
directions for use as slimicides, algicides, or
for use in laundering. These cancellations
were based on the potential of these uses to
result in contamination of water.

VII.A.2, Alkylmercury Seed Treatments—As
aresult of the poisonings in Alamogordo, N.
Mex., which resulted from the ingestion of
pork from hogs fed seed treated with cyano
(methylmercuri) guanidine, all registrations of
products containing this compound were
suspended February 18, 1970. On March 4,
1970, and ad hoc committee appointed by
the National Academy of Sciences, National
Research Council recommended that all
compounds containing a short chain alkyl
group bonded chemically to a mercury atom
through a carbon-mercury bond should be
considered toxicologically alike regardless
of the associated anion until proven other-
wise by a detailed review of appropriate
data. Accordingly, a notice of suspension of
the registrations containing alkylmercury
compounds bearing directions for use as
seed treatments was issued March 9, 1970.

VII.A.3. ‘‘Zero Tolerance’’ and ‘‘No Resi-
due’’ Registrations —The registrations of
products containing hydroxymercuri-
chlorophenol bearing directions for use on
vegetable and field crop seeds, the registra-
tions of products containing hydroxymercu-
rinitrophenol bearing directions for use on
potatoes and sweet potatoes, and the regis-
trations of products containing phenylmer-
curic acetate or phenylmercuric ammonium
acetate bearing directions for use on applies,
cherries, peaches, strawberries, and sugar-
cane were cancelled by the March 12, 1971,

85


(2) Substitute compounds

(a) Alkyl (50%C}, 30%C 4, 17%C jg.
3%C\,) dimethyl ethylbenzyl ammonium
cyclohexylsulfamate (80%): [Ref. 1839-36]
0.1% to 0.2% product by weight.

(b) 1-@O0chloroally!)-3, 5, 7-triaza-1-
azoniadamantave chloride (90%): [Ref. 464-
327)

(a) latex paints: 2000 ppm product.
(b) polyvinyl acetate latex: 250
ppm product.

(c) Sodium 2-pyridinethiol 1-oxide
(40%): [Ref. 1258-843] 1.15 Ib product/10,-
000 Ib emulson, 115 ppm product.

(d) Captan (N-trichloromethylthio-4-
cyclohexene-1, 2-dicarboximide) (90%):
(Ref. 1965-11]

0.2% to 0.5% product by weight of total
formula.

(e) Alkyl (5% caprylyl, 7% capryl,
56% lauryl. 18% myristyl, 7% palmityl, 5%
stearyl, 2% linoleyl) hydrochlorides (25%):
[Ref. 8489-13]

0.15% to 0.3% product based on total weight
of composition.

(3) Comparative effectiveness and im-
pact

A. Mercury compounds are color-
less. Some substitute chemicals impart un-
desirable colors.

B. Substantivity of some substitute
chemicals to fabric greater than mercury
compounds.

C. Substitute chemicals appear to be
adequate.

D. Impact on industry expected to be
minimal. Increase in costs to consumer ex-
pected.

3. Cements and plasters (see also 7)

A. Fungistatic

(1) Mercury compounds
Phenylmercuric acetate: (Ref. I-P-08-00.09}
For preservation: 45 to 250 ppm by dry
weight. For fungistat after application: 3500
to 15,000 ppm.

(2) Substitute compounds
Bis (tributyltin) oxide: [Ref. I-B-09-00.02]

Tape-joint compounds: 150 ppm by weight.
(3) Comparative effectiveness and im-

pact

(a) Bis (tributyltin) oxide is generally
comparable in effectiveness to PMA. Other
substitute materials are probably available
but cannot be identified specifically from
label claims.

(b) Impact of withdrawal of mercury
for this use should be insignificant.

B. Cement (bacterial preservative)

(1) Mercury compounds
Phenylmercuric acetate (95%) powder: [Ref.
6515-7] 2 ounces product per bag of cement
(size not specified).

(2) Substitute compounds

(a) 2, 3, 5, 5-Tetrachloro-4-(methyl-
sulfonyl) pyridine (82%): (Ref. 464-353]
1.0% to 2.0% product by weight of formula-
tion.

(b) Sodium pentachlorophenate
(79%): [Ref. 464-125] 1.0% product by
weight in water: 0.5% to 3.0% of solution by
weight of product in which incorporated.

(c) Dehydroabietylamine pentachlo-
rophenate (40%): [Ref. 2829-56] 0.5% to 2%
product by weight of media.

(3) Comparative effectiveness and im-
pact

(a) Other chemical compounds, al-
though not specifically recommended for
this application, may also be used.

(b) Substitute compounds appear to
be adequate.

(c) Impact on industry may be signif-
icant in that sufficient substitute compounds
for a variety of building applications may
not be available. Impact on consumer may
also be significant where preservation
against bacteria in humid climates is a ne-
cessity. Mercurials have had a long history
of use in building applications and are
known to be highly effective.

4. Paints
A. Antifouling marine coatings
(1) Mercury compounds
(a) Mercuric oxide: [Ref. Reg. No.

3


posed to mercury during the sanding of a
boat bottom. There are safer and equally
effective substitutes available for this use.

VII.B.2.2.2. Other Coatings — Adhesives,
Starches, Glues, Emulsions, etc. — These
uses include glues for labels of cans, wallpa-
per paste, glues for various fabrics, spac-
kling compounds, joint cements. These are
in liquid or dry form which are ultimately to
be applied by dispersion in water. Phenyl-
mercuric acetate and phenylmercuric am-
monium acetate are used for preservation of
the products at levels of 45 to 250 ppm. For
mildew control in finished products, phenyl-
mercuric acetate or phenylmercuric ammo-
nium acetate levels range from 3,500 to 15,-
000 ppm.

RECOMMENDATION:

(a) Interior paints — The Committee recom-
mends the cancellation of this use, because
of the environmental contamination poten-
tial. The Committee believes there is insuffi-
cient evidence to consider this use as a hu-
man health hazard.

(b) Exterior paints — The Committee rec-
ommends cancellation of this use, because
of environmental contamination.

(c) Shipbottom antifouling paints — The
Committee recommends cancellation of this
use, because of direct contamination of wa-
ter with mercury, and because of acute tox-
icity to humans.

(d) The Committee considers the use of
mercury in adhesives, starches, glues, emul-
sions, etc., to be equivalent to paint use and
recommends that the registrations be can-
celled.

VII.B.2.3. Fabrics and Textiles — Mercurial
pesticides are used as mildew preventatives
in fabrics and textiles.

Indoor Use — These fabrics are used as
bedding, dust cloths, mops, rugs, shoe lin-
ings, etc. As such articles will come into inti-
mate contact with humans.

Outdoor Use — These fabrics and textiles
are used as awnings, sails, tarpaulins, etc.

RECOMMENDATION:

The Committee recommends that all regis-
trations be cancelled.

VI.B.2.4. Fibers and cordage — These uses
include the interior components of furniture,
mattresses, pillows, etc., air-conditioner
filters, and rope and twine.

The use in interior components of furniture,
mattresses, pillows, etc., and the use in air-
conditioner filters may act to increase the
body burden of mercury. These uses present
a potential human health hazard.

The uses in rope and twine constitute an
environmental hazard.

RECOMMENDATION:

The Committee recommends cancellation of
the uses on interior components of furni-
ture, mattresses, pillows, and the use in air-
conditioner filters.

The Committee recommends cancellation of
the registrations in rope and twine.

VII.B.2.5. Food, Feed, and Tobacco Crops
— These uses of mercury result in a direct
contamination of the environment. Alterna-
tives are available. (See Chapter 1).

RECOMMENDATION:

Cancel the food, feed, and tobacco crop
uses of mercury.

91


Berlin, M. H., and Ullberg, S. ‘Accumulation and
retention of mercury in mouse.’’ I. An autoradi-
ographic study after a single intravenous injection
of mercuric chloride. Arch. Environ. Health, 6:
589 (1963a.)

Berlin, M., and Ullberg, S. ‘‘Accumulation and reten-
tion of mercury in mouse. II. An autoradiographic
comparison of phenylmercuric acetate within
inorganic mercury.”’ Arch. Environ. Health, 6:
602 (1963b).

Berlin, M., and Uliberg, S. ‘*Accumulation and reten-
tion of mercury in mouse. III. An autoradiogra-
phic comparison of methylmercuric dicyandiam-
ide with inorganic mercury.”’ Arch. Environ.
Health, 6: 610 (1963c).

Berman, E. ‘*Determination of cadmium, thallium and
mercury in biological materials by atomic absorp-
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that methylmercury had a greater ease of
penetration into the central nervous system.

Ulfvarson (1962) administered 203Hg-labeled
mercuric nitrate, methylmercuric hydrox-
ide, methylmercuric dicyandiamide, phenyl-
mercuric hydroxide, and methoxyethyl-
mercuric hydroxide subcutaneously to rats
at a dosage level of 0.1 « gm Hg per gram of
body weight every other day. He analyzed
the radioactivity in the tissues at 6, 16, and
18 days. He concluded that radioactivity
found in the brain could be attributed to the
blood content of this organ and that there is
no reason to believe that alkyl compounds
have a greater affinity for the brain.

In a series of experiments on the rabbit by
Swensson et al. (1959b), intravenous injec-
tions of methylmercuric hydroxide were
given at approximately 10 mg mercury per
kilogram of body weight, corresponding to
approximately the LDsy. He compared the
brain concentrations of mercury resulting
from this dose to the concentration in an ear-
lier study in which only | mg mercury per
kilogram of body weight was administered.
The mercury contents of the organs agree
closely with the amount injected, except the
brain where the-increase in the mercury con-
tent was much less than would be expected
from the increase in dose.

Berlin, et al. (1965) demonstrated that, al-
though the blood-brain barrier is a relative
hindrance to methylmercury penetration,
the diffusion of mercury into the brain can
be accelerated by the simultaneous adminis-
tration of dimercaprol (BAL).

Short-chain alkylmercury compounds may
accumulate more in the brain than do the
long-chain compounds. Takeda, et al. (1968)
found that the brain/blood ratios for ethyl-
mercury were higher than those for n-butyl-
mercury. When ethylmercuric chloride was
administered, the concentration of mercury
in the brain was 2 to 3 times higher than in

plasma, while the concentration in the brain
was approximately equal to that in plasma
when n-butylmercuric chloride was adminis-
tered. Sebe, et al. (1962) studied the toxicity
of a number of alkylmercury compounds.
The alkyl compounds containing a R-Hg, or
R-Hg-S radical, with a methyl, ethyl, or n-
propyl chain administered orally to rats were
toxic to the central nervous system and in-
duced paralysis of the legs. Isopropylmer-
cury compounds and other alkylmercury
compounds with 4 to 5 carbon atoms were
shown not to cause injuries to the nervous
system. Suzuki, et al. (1963) studied the dis-
tribution of mercury in mice administered
methyl, ethyl, or propylmercuric acetate.
The highest concentration of mercury in the
brain was obtained with ethylmercuric ace-
tate. In addition, the mercury in the brain
resulting from the administration of the
ethylalkyl compound was more rapidly dissi-
pated than that from the methyl or propyl
derivatives. In a later study, Suzuki, et al.
(1964) compared the distribution of mercury
resulting from the administration of n-butyl,
isobutyl, propyl, and amylmercuric ace-
tates. The mercury concentration in the
brain was lowest for the amyl compound.
There was no marked difference in the up-
take of mercury in the brain from the other
acetates. However, when graded doses of
the compounds were given, there was a very
marked increase in mercury concentration in
the brain in relation to dose for the n-pro-
pylmercuric acetate.

In three separate studies, Berlin, et al.
(1963a, 1963b, 1963c) used an autoradiogra-
phic technique to differentiate the distribu-
tion of mercuric chloride, phenylmercuric
acetate, and methylmercuric dicyandiamide.

With mercuric chloride, Berlin, et al. found
that the brain takes up mercury slowly and
retains it for a long time in comparison with
other organs, but appreciable levels are ac-
cumulated only in parts which constitute a
small fraction of the total brain tissue. They

37


cage could be collected and analyzed for
203g content. As soon as the animals were
placed in the chamber, volatile mercury
began to build up in the air sampler. It was
determined that the radioactivity in the air
sampler was not due to volatile release from
the urine and feces. In a series of experi-
ments in which animals were given varying
amounts of 23Hg, volatile excretion varied
from 0 to 7% of the administered dose and
averaged approximately 4%.

There seems to be a steady state between
intake, distribution and excretion of mercu-
ry. Gage (1964) demonstrated that rats re-
ceiving repeated subcutaneous doses of
phenylmercuric acetate reached a steady
state by the end of the second week when
excretion balanced intake. No significant
amount of mercury was found in the brain.
In contrast, rats receiving similar doses of
methylmercury dicyanidiamide showed no
indication of reaching a steady state after 6
weeks. Further, there was an accumulation
of organic mercury in all tissues, particularly
in the erythrocytes and the brain. Although
these short-term studies with methylmercu-
ty failed to demonstrate a steady state, Ber-
glund and Berlin (1969b) showed that the
continuous administration of dietary methyl-
mercury (I-5 ppm) to rats resulted in a
steady state between body burden and ex-
cretion in about 6 months. At equilibrium,
the daily excretion corresponded to about
2% of the body burden. There was a linear
correlation between dose and body burden.

The highest concentration of methylmercury
in the brain was 8 m g/g of brain tissue.
There were no effects on body weight or
conditioned behavior and no pathologic or
anatomic changes were observed.

IV.D. Chemical Interactions and Biological
Activity

Mercury is capable of combining with a wide
variety of organic molecules. Because of its

interactions with ligands present in proteins,
it is a particularly potent enzyme inhibitor.
The enzyme systems or other biologically
important molecules known to be inactivat-
ed by mercury would include all of the es-
sential chemical components of the cell.

The action of mercury depends upon biolog-
ical factors, the chemical composition, and
the structural as well as the functional or-
ganization of cells. In living systems, large
numbers of reactive substances compete for
traces of mercury. Each chemical constitu-
ent has a certain significance in relation to
cellular function, but the relative importance
of the individual substances in maintaining a
specific function varies greatly. Consequent-
ly, mercury binding will occur simultaneous-
ly at ‘‘sensitive’’ and ‘‘insensitive’’ sites,
and the toxic action may be produced by
only a small proportion of the total mercury
fixed. This tends to obscure the relation
between mercury binding and pharmacologi-
cal response (Passow, H., Rothstein, A.,
and Clarkson, T. W., 1961).

IV.D.1. Cellular Level — Cell structure gov-
erns the accessibility of sensitive ligands and
decisively influences the time course of
mercury action. The cell membrane as a
diffusion barrier protects the ‘cell interior
from poisonous action of the metal. On the
other hand, sensitive ligands located within
the membrane structure or on the outer cell
surface are separated from the large reser-
voir of protective complex-forming sub-
stances inside the cell. Therefore, functions
associated with the cell membrane are par-
ticularly susceptible to the action of mercu-
ry.

The first reactions of mercury are with the
ligands of the cell surface, with associated
disturbances of membrane function. Next, a
redistribution of the metal may take place.
As mercury penetrates into the cell, addi-
tional effects develop; and the initially inhib-
ited functions may begin to recover. The
inactivation of one sensitive site usually

63


(c) Chloromethoxypropylmercuric
acetate (0.002%. based on total weight of tile)
and copper pentachlorophenate (0.02%):
[Ref. Reg. No. 10591-1]

Product component of white latex paint and
clay primer applied to ceiling tile and wall-
board applied at rate of 0.013 pounds prod-
uct (in latex paint) per 1000 square feet of
surface.

(2) Substitute compounds

(a) 1-G-chloroally!)-3, 5. 7-triza-1-
azoniaadamantane chloride (90%): [Ref.
Reg. Nos. 464-327]

0.1% to 0.2% product by weight of formula-
tion.

(b) 2, 3, 5, 6-Tetrachloro-4-(methyl-
sulfonyl) pyridine (82%): [Ref. Reg. No.
464-353]

0.5 to 1.0% by weight of formulation.

(c) Captan (N-trichloromethylthio-4
cyclohexene-I, 2-dicarboximide) (90%):
[Ref. Reg. No. 1965-11]

0.25% to 1.0% product by weight of formu-
lation.

(d) Alkyl (5% caprylyl, 7% capryl,
56% lauryl, 18%. myristyl, 7% palmityl, 5%
stearyl, 2%. linoleyl) hydrochlorides (25%):
[Ref. Reg. No. 8489-13]

0.15 to 0.3% product on total weight of me-
dia.

(e) Phenol (1.41%), Sodium borate
(0.47%) and Sodium phenate (0.24%): [Ref.
Reg. No. 8383-1] 2% to 5% by weight of ac-
tive ingredients.

(f) 2-(Thiocyanomethylthio) benzo-
thiazole (32%) and 2-Hydroxypropyl metha-
nethiosulfonate (28%): [Ref. Reg. No. 1448-
27
0.03 to 0.05% product based on formula
weight.

(g) Alkyl (50%C,5, 30%C 4, 17%Ci¢,
3%C jg) dimethyl ethylbenzyl ammonium
cyclohexylsulfamate (80%): [Ref. Reg. No.
1839-36]

0.1 to 0.2% product by weight of formula-
tion.

(3) Comparative effectiveness and im-
pact

(a) Comparative costs of substitutes
and mercury compounds not known.

(b) Substitute compounds appear to
be adequate.

(c) Impact on industry expected to be
minimal, consumer impact somewhat varia-
ble.

(d) Impact on uses of product in criti-
cal hospital areas requiring low bacterial
counts cannot be assessed.

D. Vinyl latex interior paint (bacteriostatic
finish)

(1) Mercury compounds
Phenylmercuric acetate: [Ref. Reg. No.
10751-1]

Component of paint, 0.27% by weight.

(2) Substitute compounds

(a) Phenol (1.4%) and Sodium borate
(0.47%), and Sodium phenate (0.24%): [Ref.
Reg. No. 8383-1]

2 to 5% by weight of active ingredients.

(b) 1-(3-chloroallyl)-3, 5, 7-triaza-l-
azoniaadamantane chloride (90%): [Ref.
Reg. No. 464-327]

0.1 to 0.2% product by weight of formula-
tion.

(c) Sodium —__2-pyridinethiol-1-oxide
(90%): [Ref. Reg. No. 1258-842]

(aa.) 0.5 Ib/10,000 Ib formulation.

(d) Captan (N-trichloromethylthio-4
cyclohexene-1, 2-dicarboximide) (90%):
[Ref. Reg. No. 1965-11]

0.25 to 1.0% product by weight of paint.

(e) Alkyl (5% caprylyl, 7% capryl,
56% lauryl, 18% myristyl, 7% palmityl, 5%
stearyl, 2% linoleyl) hydrochlorides (25%):
[Ref. Reg. No. 8489-13] 0.15 to 0.3% prod-
uct based on total weight of media.

, (f) 2-(Thiocyanomethylthio) benzo-
thiazole (32%) and 2-Hydroxypropyl metha-
nethiolsulfonate (29%): [Ref. Reg. No. 1448-
27) 0.03 to 0.05% product based on formula
weight.

(8) Alkyl (50%C jy, 30%C 4, 17%C 46,
3%C\g) dimethyl ethyibenzy! ammonium

cyclohexylsulfamate (80%): [Ref. Reg. No.
1839-36]


VII.B.2.13. Seed Treatments — Petitions
for tolerance are pending for some uses of
mercurial pesticides as seed treatments.
Substitutes are available for all uses except
for stinking smut on wheat and striped smut
on barley.

RECOMMENDATION:

Cancel all registrations for use as seed treat-
ment except for stinking smut on wheat and
stripped smut on barley.

VII.B.2.14. Tanneries — Mercurials are
employed in the tanning process as fungi-
stats. The liquor from this process is a po-
tential contaminant of the environment.

VII.B.2.15. Wood — Mercurial pesticides
are used to prevent sap stain in freshly
sawed logs and lumber and as a preservative
of wood against fungi. These uses are a di-
rect contamination of the environment with
mercury.

RECOMMENDATION:

Cancel the use of mercurial pesticides as
preservatives for wood against sap stain and
fungi.

VII.B.2.16. Sterilization of Dental and Sur-
gical Instruments — The solution in which
instruments are sterilized is discarded into
the sanitary sewage system and contami-
nates water with mercury.

RECOMMENDATION:

Cancel the uses of mercurial pesticides for
the sterilization of dental and surgical instru-

ments,

VII.B.2.17. Surfaces — As fungistats on
commercial, institutional and household sur-
faces such as cabinets, floors, walls, ceil-
ings, garbage cans, lockers, masonry, tile,
refrigerator and other hard surfaces; blan-
kets, canvas goods, carpets, clothing, cubi-
cle curtains, hampers, laundry bags, leather
goods, linens, mattresses, uniforms, uphol-
stery and similar porous surfacés. These
uses bring mercury into intimate contact
with humans and also provide a contamina-
tion of the environment.

RECOMMENDATION:

Cancel the uses of mercurial pesticides on
environmental surfaces.

VII.B.2.18. Miscellaneous

1. Seam and Bedding Compounds — These
compounds are used in boat-building and
provide a direct contamination of water.

2. Broomcorn — Mercurial pesticides are
used in the process of dying broomcorn as a
fungistatic agent to prevent discoloration.

3. Cellulose Sponges — Cellulose sponges
are dipped in solutions of phenylmercuric
acetate for preservation. Disposal of these
solutions after use will provide a direct con-
tamination of the environment.

4. Milk and Urine Samples — Mercuric
chloride is added to milk and urine samples
as a preservative. Disposal of these samples
will provide a direct contamination of water.
RECOMMENDATION:

Cancel the registrations of mercurial Pesti-
cides for the above uses.

93


III. Fibers and Cordage

|. Fungistats
A. Mercury compounds

(1) Phenylmercuric acetate: [Ref. I-P-
08-00.10] For interior components of furni-
ture and mattresses (alpha cellulose, cotton,
latex impregnated curled hair, sisal, etc.)
fungistat: 150 to 300 ppm by spraying.

(2) Phenylmercuric borate and phenyl-
mercuric chloride plus alkyl dimethyl benzyl
ammonium chloride: [Ref. I-A-08-45.05] For
cotton, wool. and synthetic fibers fungis-
tat: 0.22 Ib of PMB plus 0.020 Ib of PMC
plus quaternary/100 gal by dip, spray, or
brush (264 ppm PMB plus 24 ppm PMC).

(3) Phenylmercuric oleate plus zinc
naphthenate: [Reg. No. 2553-6 and I-P-14-
00.01] For rope, twine.

(a) Household use: dip cordage to
saturate fibers in 2.5% PMO plus 12.5% zine
naphthenate.

(b) Household use: dip cordage to
saturate all fibers in 0.6% PMO plus 7.125%
pentachlorophenol.

(c) Industrial use: animal, vegetable
and synthetic filling material for furniture,
mattresses, pillows: spray with 10 parts of
30% PMO in 90 parts of spray oil and water
(30,000 ppm PMO).

B. Substitute compounds

(1) Alkyl! dimethyl benzyl ammonium
chlorides: [Ref. I-A-08-45.02, Reg. No.
3533-29] Air conditioning filters: 1000 ppm
or 2.8% mixture of quaternary, sodium di-
methyl-dithiocarbonate and sodium 2-mer-
captobenzothiazole.

(2) Copper naphthenate cordage:
{Ref. I-C-30-00.01] 1.0 to 2.0% metallic cop-
per equivalent.

(3) Copper 8-quinolinolate cordage:
[Ref. I-C-34-00.01] To, retain 1.0% or more
actual.

(4) Creosote - cordage: [Ref. I-C-41-
00.01] 40 to 100% dip.

(5) Dialkyl dimethyl ammonium chlor-
ide: [Ref. I-D-04-20.01]

(a) Air conditioning filters: Deposit
1432 ppm quaternary plus 285 ppm benzoic
acid and 263 ppm salicylic acid by dip.
spray, or sponge.

(b) For interior components of furni-
ture and mattresses: 1.3 Ib quaternary plus
0.26% TBTO by spraying; or 0.0375 Ib qua-
ternary plus 0.05% TBTO in dye beck or
padder: or 0.025% quaternary plus 0.008%
TBTO for cotton batting only.

(6) Lauryl pyridinium salt of 5-chloro-
2-mercaptobenzothiazole: [Ref. I-L-01-
00.01] Industrial use in finishing process:

(a) Burlap: 3,375 to 10,000 ppm.

(b) Duck, mattress ticking, similar
fabrics: 1200 to 2500 ppm.

(c) Industrial fabrics to yarns: 5,000
to 10,000 ppm.

(7) Pentachlorophenol cordage: [Ref.
1-P-05-00.01] 3.0 to 5.0% by dipping.

(8) Sodium o-phenylphenate: [Ref. I-
S-16-00.08] Air filters: spray using 0. 5
SOPP plus 0.2% sodium propionate and
0.2% 2, 2-methylenebis ( 3, 4, 6-trichloro-
phenol)

(9) Zinc dehydroabietylammonium 2-
ethylhexoate cordage: [Ref. I-Z-03-00.01]
Use 2.5 to 5.0% or more by weight.

(10) Zinc naphthenate cordage: [Ref.
I-Z-05-00.01] Use 1.8 to 5.0% product as a
dip.

C. Comparative effectiveness and impact

(1) Several substitute materials are
available for use on air conditioning filter
fibers and interior components of furniture
and mattresses.

(2) The impact of withdrawal of mer-
cury on fibers and cordage would appear to
be slight on industry and insignificant on the
consumer.

2. Bacteriostats

A. Mercury compounds

(1) Phenylmercuric acetate (30%):
{Ref. 3090-127] 1 lb product per 3333 Ib ma-

13


B. Substitute compounds
None.

C. Impact
Unknown. Mercury is thought to be of
doubtful necessity or value in this use. Sub-
stitute materials should not be difficult to

find.

4. Milk sample preservation (for dairy herd
improvement)

A. Mercury compounds

Mercuric chloride (32.2%): (Ref. Reg. No.
2955-9] One tablet weighing 0.28 grams to

42

140 ml of milk sample; preservation for
Babcock laboratory test.

B. Substitute compounds

Potassium dichromate (65.9%): (Ref. Reg.
No. 2955-21] 1 tablet weighing 0.23 grams
added to 180 ml milk provides preservation
for 3 weeks.

C. Comparative effectiveness and impact

(1) Substitute compounds cannot pre-
serve milk samples as long as mercurial.

(2) Substitute chemical is satisfactory.

(3) Impact on industry expected to be
minimal; consumer impact may call for in-
creased cost.


upper limit for the natural release of mercu-
ry due to chemical weathering can be esti-
mated by comparison with the correspond-
ing figures for sodium. The sodium leached
by weathering is almost completely carried
to the sea by rivers, 8 x 107 tons per year
(runoff of rivers, 3.2 x 10!3 tons per year:
noncyclic sodium in river waters, 2.5 ppm).
In the weathered rock masses, the ratio of
mercury to sodium can be estimated to be
the same as the ratio of their lithospheric
abundances (2.8 x 10°), which yields an
upper limit of 230 tons per year for leached
mercury. The amount of mercury released is
probably less than this estimate, because
proportionally more mercury than sodium is
absorbed on clays, hydroxides, organics,
and so forth (Joensuu, 1971).

Another source of mercury is the burning of
fossil fuels and ores. In order to estimate the
amount of mercury released into the atmos-
phere by the burning of coal, Joensuu ana-
lyzed samples of 36 American coals by
means of a mercury vapor detector that had
been modified to eliminate organic vapors
which interfere in the detection process. The
mercury content of the Illinois coal samples
that were analyzed contained an average of
180 x 10° g/g mercury. The author applied a
more conservative estimate of 1 ppm to the
yearly production of coal and concluded that
about 3,000 tons of mercury per year are re-
leased to the environment by the burning of
coal.

The burning of fossil fuels by man contrib-
utes more than 13 times as much mercury to
the environment as does the natural weath-
ering process. The use of pesticides contrib-
utes over two times as much mercury to the
environment as does the natural weathering
process. It is obvious that man is contribut-
ing a substantial amount to the ‘‘natural’’
background of mercury, and we must elimi-
nate all but the essential dissipative uses of
mercury.

VII.B.2.2, Coatings

VII.B.2.2.1. Paints, Varnishes, and Stains
— This is a highly significant use of mercu-
ry. In 1969, 720,000 pounds of metallic mer-
cury were used in paint as follows:

Interior latex 0.0.0... e eee 45,000 Ib
Exterior latex - 351,000 Ib
Exterior oil .. + 324,000 Ib

Mercurials are added to interior water-
thinned (latex) paints to prevent spoilage
during manufacture and in the container dur-
ing storage. The concentration employed for
this use ranges from 0.015 to 0.02% mercury
as the metal. Solvent-thinned interior paints
do not require the use of mercury for preser-
vation.

Mercurials are used in exterior water-
thinned paints both for preservation in the
container and as a fungicide to minimize dis-
coloration from mold or mildew growth on
the dry paint film. For this use, mercury, as
the metal, is used in the range of 0.05 to
0.09%. Solvent-thinned exterior paints may
also contain mercury to prevent mold
growth on the dry film.

The mercury compounds generally used in
paints are:

Phenylmercuric acetate
Phenylmercuric oleate

Diphenyl mercuric dodecenyl succinate
Phenylmercuric propionate
Chlormethoxypropylmercuric acetate

(1) Interior Paints — In order to satisfy the
labeling requirements under the Federal
Hazardous Substances Labeling Act, acute
oral and dermal toxicity studies were carried
out by Hazleton Laboratories for the Na-
tional Paint, Varnish, and Lacquer Associa-
tion. These studies indicated paint could
contain up to 0.2% elemental mercury with-
out hazard of acute oral or dermal toxicity or
dermal irritation.

89


C. Comparative effectiveness and impact

(1) Mercury compounds have a broad
spectrum of turf pathogen control at high
efficiency for low dosage rates. Substitute
compounds are usually used in combination
to achieve broad spectrum control at higher
dosage rates, higher cost and more difficult
application procedures.

(2) The impact of withdrawal of mercu-
ry for turf disease control will be very se-
vere on some manufacturers, on golf greens
management budgets and on turf quality.

9. Turf Weed Control (Crabgrass)
A. Mercury compounds

Phenylmercuric acetate: [Ref. Reg. Nos.
702-14, 1001-14, 1001-24, 1439-173, etc.]

(a) 0.25 to 0.4 oz actual/1000 sq ft.

(b) 0.0003 0z actual plus 0.1391 oz
dimethylamine salt of 2, 4-D and 0.005 oz
isopropyl N-(3-chlorophenyl) carbamate/
1000 sq ft.

(c) 0.009 oz actual plus 2.25 oz Thir-
am/1000 sq ft.

B. Substitute compounds

(1) Octyl ammonium methanersenate
plus dodecylammonium methanearsenate
{Ref. Reg. No. 2853-6] 0.64 oz actual
each of /1000 sq ft.

(2) Calcium methanearsenate [Ref.
Reg. Nos. 264-147 and 2853-4] 0.83 0z ac-
tual/1000 sq ft.

(3) Disodium methanearsenate: [Ref.
Reg. No. 572-199] 0.76 oz actual/1000 sq ft.

(4) Monosodium acid methanearsenate:

[Ref. Reg. No. 728-79] 0.52 oz actual/1000
sq ft.

C. Comparative Effectiveness and Impact

(1) Substitute materials are about equal
to mercury for crabgrass control in post-
emergence application and are safer from
point of view of injury to desirable grasses.

(2) Other substitute materials are avail-
able for use before crabgrass emerges.

(3) Impact of withdrawal of mercury
for this use will be minimal.

10. Turf Weed Control (moss)
A. Mercury compounds

(1) Phenylmercuric acetate: [Ref. Reg.
Nos. 538-5, 24, 36] 0.02 to 0.51 0z actual/
1000 sq ft.

(2) Phenylmercuric triethanol ammon-
ium lactate: [Ref. Reg. No. 802-233] 0.17 to
0.5 02 actual/1000 sq ft.

B. Substitute compounds

(1) Ferrous ammonium sulfate: [Ref.
Reg. No. 7923-3] 9.8 Ib actual/100 sq ft.

(2) Ferrous sulfate: [Ref. Reg. No.
7404-3] 2.0 Ib actual/1000 sq ft.

(3) Ferrous sulfate heptahydrate: [Ref.
Reg. No. 5584-17] 1.5 Ib actual/1000 sq ft.

C. Comparative effectiveness and impact

(1) Substitute materials are equally
effective for moss control but require much
higher dosage.

(2) Impact of withdrawal of mercury
for moss control will be minimal.

VII. Paper (mold resistant)

1. Mercury compounds

Phenylmercuric acetate: [Ref. I-P-08-00.10]
A. Beater application: 0.8 Ib/ton of fiber,
dry weight.

B. Coating application: 0.1 to 0.3 Ib/side/

ton or 150 to 225 ppm as a spray.

C. Calender application: 0.1 to 0.3 Ib/

side/ton or 0.5% solution.

25


0.1 to 0.2% product by weight of formula-
tion.

(h) 2, 3. 5, 6-Tetrachloro-4-(methyl-
sulfonyl) pyridine (82%): latex media: [Ref.
Reg..No. 464-353] .
0.5.to 1.0% product by weight latex media.

(3) Comparative effectiveness and im-
pact

(a) Substitute compounds appear to
be adequate.

(b) Impact on industry and consumer
appear to be minimal.

6. Sealers and Sizings
A. Mercury compounds

(1) Phenylmercuric acetate: [Ref. I-P-
8-00.09]
(a) Preservation: 0.1 to 0.25 1b/100
gal.
(b) Mildew control: | to 3 Ib/100 gal.
(c) Preservation of carbohydrate so-
lutions: 0.1 Ib/100 gal.
(d) Preservation of protein solutions:
0.23 to 0.3 Ib/100 gal.
(2) Phenylmercuric oleate: [Ref. I-P-14-
00.01] mildew control: 1200 ppm by weight
of formulation.

B. Substitute compounds

(1) Alkyl dimethyl benzyl ammonium
chlorides: (Ref. I-A-08-45.05]

Preservation: 50.000 ppm plus other fungis-
tats.

(2) 4-Chloro-3, 5-xylenol: [Ref, I-C-21-
00.02] As required.

(3) Copper 8-quinolinolate: [Ref. I-C-
3400.02] 1.0% by weight.

(4) Monoethanolamine 2-mercapto-
benzothiazole: [Ref. I-M-21-00.01] 0.15 to
0.4% by weight.

(5) Sodim o-phenylphenate: [Ref. I-S-
16-00. 10] 2.0% by weight.

(6) Tetrahydro-3, 5-dimethyl-2H, -1, 3,
5-thiadiazine-2-thione (Mylone): [Ref. I-T-
07-00.03]

100 to 5000 ppm by weight.

C. Comparative effectiveness and impact

(1) Substitute compounds are generally
less effective than mercury at comparable
dosage rates.

(2) Mercury compounds are less expen-
sive and adapted to use in a wider range of
products than are substitutes.

(3) Impact of withdrawal of mercury
for these uses should have slight to moder-
ate effect on manufacturers and consumers.

7. Textures and other dry products ultimate-
ly applied by dispersion in water (see also I, 3
cements and plasters).

A. Mercury compounds

Phenylmercuric acetate: [Ref. I-P-08-00.09]
(a) Preservation: 45 to 250 ppm by
weight.
(b) Mildew control: 3500 to 15,000
ppm by weight.

B. Substitute compounds
None identified.
8. Wallpaper coatings

A. Mercury compounds

Di(phenylmercury) dodecenylsuccinate:
(Ref. I-D-21-00.01]
Add to deposit 0.01 ounce of a 10.5 or 12.0%

product/square yard of finished paper.
B. Substitute compounds

(1) 3, 4, 5-Tribromosalicylanilide( [Ref.
I-T-11-00.02] .
Incorporate 0.1% into plastic laminate be-
fore calendering.

(2) See additional probable substitutes
under IX - Plastics.

C. Comparative effectiveness and impact

(1) Substitute compounds must be em-
ployed at higher concentrations than mercu-
ry to achieve comparable fungistasis.

(2) Mercury has a broader spectrum of
fungal control than most substitute com-
pounds.

(3) Impact of withdrawal of mercury
for this use would appear to be slight.


acute oral toxicity of the inorganic mercuri-
als as compared with the organic mercurials.

IV.A.2. Absorption through the Lungs —
Metallic mercury and all of its compounds
are absorbed in the lungs. The organomer-

curials vary in their volatility and, therefore,
differ in their hazards via the inhalation
route. The following table of the saturated
vapor concentrations of organic mercurial
compounds and of metallic mercury comes
from Swensson and Ulfvarson (1963).

Saturated Vapor Concentration of Some Mercurial

Fungicides at 20°C
Saturated
Organomercury Anion Vapor Cons,

ug/M?

methylmercury chloride 94,000
” bromide 94,000

” iodide 90,000

” acetate 75,000

” hydroxide 10,000

” toluenesulfonate 15,000

” benzoate 2,000

” dicyandiamide 300

ethyl mercury chloride 8,000
” bromide 7,000

” iodide 9,000

” dicyandiamide 400

” monohydrophosphate 50
methoxyethylmercury chloride 2,600
” acetate 2
phenylmercury acetate 17
” chloride 5

” nitrate 1

” methanedinaphthyldisulfonate 2
metallic mercury 14,000

In a study in which mice were exposed to a
vapor stream of air containing various or-
ganomercurials, Swensson (1952) found the
chlorides were more toxic than the dicy-
anamides of alkylmercury compounds. This
is in agreement with the lower vapor pres-
sure of the latter. Gage (1961) has shown in
his experiments in which rats were exposed
to an atmosphere containing | mg of mercu-
ry per cubic meter of air for varying periods,
that absorption is rapid and complete and
the turnover in all tissues, except the brain,
is rapid; most of the mercury is removed
within a week after exposure has ceased.

In a study designed to measure the absorp-
tion, distribution, and excretion of inhaled
mercury vapor, female rats were exposed 24
hours per day for 28 days to a concentration
of 1 mg Hg/M? of air. The rats survived but
lost weight, became lethargic, and showed
slight tremors, especially when lifted by
their tails.

A second series of rats were given repeated
continuous exposures to the same concen-
tration of mercury vapor for 100 hours from
Monday through Friday in each week for six
weeks. Asa result, growth was retarded, the

53


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FOREWORD

Charge — In a statement issued on March
18, 1971, the Administrator of the Environ-
mental Protection Agency said that ‘*Active
internal review is being initiated as to the
registrations of products containing benzene
hexachloride. lindane. chlordane, endrin,
heptachlor and toxaphene, all products con-
taining mercury, arsenic, or lead, and all
others deemed necessary for review. The
function of review is not to make another
study of pesticides, but to identify which, if
any. of the presently registered products
present substantial questions of safety
which should trigger the administrative
process of cancellation.’’ (Ruckelshaus,
1971)

In order to activate this review process, a
Special Review Group was established by
the Commissioner of the Office of Pesticides
to set priorities and appoint working groups
to study the individual pesticides in ques-
tion. Accordingly, the first Working Group
was established and assigned the task of:

(1) reviewing the currently registered
uses of mercurial pesticides,

Q2

evaluating these uses in terms of
human safety and contamination of
the environment, and

(3) based on this evaluation, making
recommendations for cancellation
of registrations which present a
substantial question of safety or of
environmental contamination.

Basis for Approach — In ‘‘Reasons Under-
lying the Registration Decisions Concerning
Products Containing DDT, 2,4,5,-T, Aldrin
and Dieldrin,”” (Ruckelshaus, 1971) the En-
vironmental Protection Agency interpreted
its responsibilities under the Federal Insecti-
cide, Fungicide and Rodenticide Act and

vi

under the Food, Drug and Cosmetic Act as
being required to:

(1) register new economic poisons if
they meet certain standards of effi-
cacy and safety, and

(2) undertake a continuous review of
previously registered pesticides in
order to insure continued compli-
ance with these requirements in the
light of the developing scientific
data and concern for public health.
If this continuing review raises any
substantial questions of safety, no-
tices of cancellation must be issued
which initiate the administrative
process of review.

In continuing to define the Agency’s respon-
sibilities, the document interprets the thrust
of the Federal Insecticide, Fungicide and
Rodenticide Act as prohibiting:

(1) those economic poisons which do
not contain directions for use which
are necessary and adequate for the
protection of the public, and

(2) those economic poisons which do
not contain a warning or caution
statement which is adequate to pre-
vent injury to man, vertebrate ani-
mals, or vegetation (except weeds).

The final decision with respect to whether a
particular product should be registered ini-
tially or should continue to be registered
depends upon the intricate balance struck
between the benefits and dangers to public
health and welfare resulting from its use.
“The fact that the danger results solely from
misuse does not determine that such danger
is to be ignored but that this consideration
has a possible bearing on the magnitude and


environmental contamination potentials of
mercurial pesticides are considered in detail
under VII.B.2. before the listing of the spe-
cific pesticide uses. Individual uses will be
discussed at length where necessary: other-
wise reference will be made to the particular
hazard, if any, which the use involves.

VII.B.1. Pesticides Containing Alkylmercu-
ry Compounds — The different members of
the homologous series of alkylmercury
compounds behave in the same manner and
can cause the same type of poisoning. The
anion of the compounds has no influence on
the biological reaction of mammals but may
influence some of the physical characteris-
tics of the salt, such as volatility.

The acute toxicity of the alkylmercury com-
pounds is lower than the acute toxicity of
the soluble inorganic mercury compounds
and of the arylmercury compounds. How-
ever, the alkylmercury compounds are ab-
sorbed from the gastrointestinal tract to a
much greater extent than are the inorganic
or arylmercury compounds.

The greatest physiological distinction be-
tween the alkyl and aryl or inorganic mercu-
ry compounds isthe distribution of mercury
within the body after single or repeated ad-
ministrations. Inorganic mercury com-
pounds disappear rapidly from the blood,
and the blood concentrations of mercury
remain low even after repeated administra-
tions. The arylmercury compounds disap-
pear rapidly after a single administration,
but after repeated administrations, there is a
considerable increase in the blood content of
mercury. The greatest increase by far is
caused by the alkylmercury compounds.

Inorganic compounds of mercury give con-
centrations of mercury in the kidneys of
from 100 to 1,000 times that found in the
blood. The arylmercury compounds give
kidney concentrations of from 2 to 100 times

that found in the blood. However, this con-
centration increases with time as the result
of the conversion of phenylmercury to inor-
ganic mercury in the liver. The concentra-
tion of alkylmercury compounds in the kid-
ney is about 1.0 to 1.4 times that in the
blood.

The concentration of mercury in the liver
after inorganic mercury administration is
from 5 to 20 times that found in the blood.
The arylmercury compounds give about 2
times that in the blood. The alkyl com-
pounds give a liver concentration of only
about 0.2 to 0.4 times that in the blood.

The mercury concentration in the brain after
the administration of inorganic mercury
salts is about equal to the blood concentra-
tion. After the administration of aryl com-
pounds, it is only 1 to 3% of that in the
blood. Alkylmercury compounds give a
brain concentration of only about 4 to 6% of
that found in the blood. However, as the
mercury in the blood is much higher after
the administration of the alkylmercury com-
pounds, the mercury retained in the brain
after the administration of this compound is
by far higher than after equivalent amounts
of the other compounds of mercury.

The placenta is an effective barrier to mercu-
ty derived from inorganic or arylmercury
compounds. However, this is not true’ with
alkylmercury compounds. After the admin-
istration of these compounds, the mercury
concentrations in the fetus may reach higher
levels than those found in the maternal tis-
sues. The chromosome-damaging and tera-
togenic effects of the alkylmercury com-
pounds are greater than those of inorganic or
arylmercury compounds.

The alkylmercury compounds are excreted
much more slowly than are the aryl or inor-
ganic mercury compounds. This indicates a

87


(6) o-benzyl-p-chlorophenol (1.0%):
(Ref. Reg. No. 4878-17] Used undiluted as a
dip. :

(7) 4-and 6-chloro-2-phenylphenol
(1.0%): [Ref. Reg. No. 6831-5] 25 fluid
ounces/100 Ib dry cloth.

C. Comparative effectiveness and impact

(1) Substitute compounds are ade-
quate.

(2) Impact on industry and consumer
expected to be negligible.

2. Floor Covering Finishes (bacteriostatic)
A. Mercury compounds

Phenyl mercuric acetate (0.025%): [Ref.
Reg. No. 52-145] Used undiluted for institu-
tional floor care.

B. Substitute compounds

(1) 2, 2’ methylenebis (3, 4, 6-trichloro-
phenol): [Ref. Reg. No. 824-1] 1% to 4%
product by weight of media.

(2) Alkyl (derived from fatty acids of
coconut oil) amine hydrochlorides: [Ref.
Reg. No. 4313-37] 0.063% product by weight
of media.

(3) Sodium pentachlorophenate (79%):
[Ref. Reg. No. 464-299] 0.025 to 0.15% prod-
uct by weight of formulation.

(4) 1-@-chloroallyl)-3, 5, 7-triaza-1-
azoniaadamantane chloride (90%): [Ref.
Reg. No. 464-327] 0.025% product by weight
of formulation.

(5) 4-chloro-3, 5, -xylenol (100%): [Ref.
Reg. No. 4026-4] Dosage not stated.

C. Comparative effectiveness and impact

(1) Substitute compounds are ade-
quate.

30

(2) Impact on industry and consumer
expected to be negligible.

3. Floor Wax (bacteriostatic)
A. Mercury compounds

Phenyl mercuric acetate: [Ref. Reg. No. 52-
145] Applied to floor undiluted.

B. Substitute compounds

(1) 2-Bromo-2-nitropropane-1, 3-diol:
[Ref. Reg. No. 1839-60] .05 to 0.1% product
by weight of formula.

(2) Dialkyl (1%Cy, 8%C, 7%Cy9.
48%C 19, 17% C14, 9%C 6, 10%C)g) dimethyl
ammonium chloride: [Ref. Reg. No. 1839-8]
1.5 to 2% product by weight of formula.

(3) 1-(3-chloroallyl)-3, 5, 7-triaza-1-
azoniaadamantane chloride: [Ref. Reg. No.
464-327] 0.025% product by weight of for-
mula.

(4) 4-chloro-3, S-xylenol: [Ref. Reg.
No. 4026-4] Dosage not specified.

(5) 2,2’ methylenebis (3, 4, 6-trichlo-
rophenol): [Ref. Reg. No. 824-1] 1 to 4%
product by weight of formulation.

(6) 2, 2’-methylenebis (4-chlorophen-
ol): [Ref. Reg. No. 824-6] | to 7% product by
weight of formulation.

C. Comparative effectiveness and impact

(1) Substitute compounds are ade-
quate.

(2) Impact on industry and consumer
expected to be nil.


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£€

XIi, Seed Treatments

6. Sorghum
& - 2
© é Z . = °
= s & © § Md
e 3 8 eS ¢ oy
se/ F S/F /F/88/ Ff FS/ES/E/EF/SFR/S ESE
a? & eT /9e/ g/é & /é
z
‘ounces actual per 100 pounds Icu/Saior'®
Covered kernel smut, | 0.019 1200
Loose smut to | 1.9-3.0 07-14 0.57-1.34 | 2.4% 2.57 1,34-1.79 1.07-1.43 | to
0.038 1600
Damping-off, 0.019
Seed decay to | 1.93.0 | 1.9-2.9 | 0.7-1.4 1.0 | 1.8-2.3 | 0.57-1.34 | 0.5? 0.125 | 1.34-1.79]1.32-1.41
0.038

"In combination with Dexon.
?In combination with Terrazole.

? Used only as

supplement to suitable standard seed treatments.

“p-(Dimethyamino) benzenediazo sodium sulfonate.
27.6% Sodium dimethyl dithiocarbamate + 2.4% Sodium 2-mercaptobenzothiazole.
¢In combination with PCNB.

7 In combination with Captan.