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OCR for page 202
vll
Toxicity of
Selectecl Organic
Contaminants in
Drinking Water
The compounds evaluated in this chapter were selected for essentially the
same reasons as those enumerated at the beginning of Chapter VI.
Chloroform is included because new information has become available since
it was evaluated in the first volume of Drinking Water and Health (National
Academy of Sciences, 1977~. Dibromochloropropane appears for the first
time in this report because of its occurrence in drinking water resulting
from its use in agriculture.
Toxicological information is required for a large number of solvents that
are appearing with greater frequency in wastewater, thereby posing a real or
potential hazard for contamination of drinking water. Among them are
nitrophenols, nitrobenzene, petroleum products, and polynuclear aromatic
hydrocarbons, which are also evaluated in this chapter. Table VII-1 sum-
marizes the acture and chronic SNARL's for the compounds reviewed in
this chapter.
Acetonitrile (CH3CN)
Nitriles characteristically contain a cyano group, C-N. Acetonitrile a
mononitrile having the formula CH3CN-is also known as methylcyanide,
cyanomethane, or ethanenitrile (National Institute for Occupational Safety
and Health, 1978a). A colorless liquid, acetonitrile is infinitely soluble in
water and has a molecular weight of 41.1. Because of their versatile
chemical reactivity, nitrites have many industrial uses, such as in the
manufacture of plastics, synthetic fibers, and elastomers, and as a solvent
202
OCR for page 203
Toxicity of Selected Organic Contaminants in Drinking Water 203
TABLE VII-1 Summation of Acute and Chronic
Exposure Levels for Organic Chemicals Reviewed
in this Chapter
Suggested No-Adverse-Response
Level (SNARL), mg/liter,
by Exposure Perioda
Chemical 24-Hour 7-Day Chronic
Nitrobenzene 0.035 0.005
Mononitrophenol 0.29
Dinitrophenol 0.11 b
Tr~nitrophenol 4.9 0.2
Benzene 0.25
2,4,6-Tr~chlorophenol 17.5 2.5
aSee text for details on individual compounds.
bThis is the average from two calculated SNARL's; see text for details.
in the extractive distillation that separates olefins from diolefins, butadiene
from butylene, and isoprene from isopentene (Merck Index, 1976; National
Institute for Occupational Safety and Health, 1978a; Pozzani et al., 1959~.
In 1964 approximately 1,575 metric tons of acetonitrile were used in the
United States (National Institute for Occupational Safety and Health, 1978a).
The major occupational exposures to nitrites occur primarily by the der-
mal and inhalation routes. Depending upon the amount absorbed, nitrites
may cause hepatic, renal, cardiovascular, gastrointestinal, and central
nervous system disorders, regardless of the route of administration.
Although these effects are usually attributed to the metabolic release of
cyanide, they may also be partly due to the intact molecule (National In-
stitute for Occupational Safety and Health, 1978a).
The time-weighted average (TWA) standard for nitrites published by
the National Institute for Occupational Safety and Health (NIOSH) is
based on reports indicating that certain nitrites are sources of cyanide
ions. The TWA for acetonitrile is 20 ppm for up to a 10-hour workshi* in
a 40-hour work week (National Institute for Occupational Safety and
Health, 1978a).
METABOLISM
There has been little work concerned with the metabolism and disposition
of acetonitrile. In studies by Dequidt and Haguenoer (1972) and Hague-
noer and Dequidt (1975a), rats received intraperitoneal injections of
OCR for page 204
204 DRINKING WATER AND HEALTH
acetonitrile in doses ranging from 600 to 2,340 mg/kg. The tissues were
analyzed for acetonitrile and both free and combined hydrogen cyanide
content. In general, acetonitrile was found to be rather evenly distributed
among the various organs, and hydrogen cyanide was found in nearly all
organs in varying concentrations. In subsequent studies, Haguenoer and
Dequidt (1975b) obtained similar results following the administration of
acetonitrile to rats via the inhalation route.
A series of studies have shown that humans absorb nitrites through the
skin (Sunderman and Kincaid, 1953; Wolfsie, 1960) and through the res-
piratory tract (Amdur, 1959; Dalhamn et al., 1968; McKee et al., 1962;
Pozzani et al., 19591. After absorption, nitrites may be metabolized to an
alpha-cyanohydrin or to inorganic cyanide, which is oxidized to thio-
cyanate and excreted in the urine. Nitriles also undergo other types of
reactions depending on the moiety to which the cyano group is attached.
The cyano group may be converted to a carboxylic acid derivative and am-
monia or may be incorporated into cyanocobalamin (National Institute for
Occupational Safety and Health? 1978a).
HEALTH ASPECTS
In general, adverse effects resulting from exposure to the nitrites' in-
cluding acetonitrile, occur primarily by the dermal and inhalation routes.
Depending on the amount absorbed, nitrites may cause toxic effects in-
volving the hepatic, renal, cardiovascular, gastrointestinal, and central
nervous systems. These effects may be due in part to the intact molecules,
but are also attributed to the metabolic release of cyanide. There are
substantial differences among the various nitrites with regard to the
amounts necessary to cause poisoning, the durations of exposure' and the
time intervals between exposure and manifestation of the adverse effects.
These differences are associated with the rate and extent of the release of
cyanide ion (Amdur, 1959; National Institute for Occupational Safety and
Health, 1978a).
Observations in Humans
Acute exposure of humans to acetonitrile by inhalation results in head-
ache, dizziness, profuse sweating, vomiting, giddiness, hypernea, difficul-
ty in breathing, palpitations, irregular pulse, convulsions, loss of con-
sciousness, and death, usually resulting from respiratory arrest (Amdur,
1959; Grabois, 1955; National Institute for Occupational Safety and
Health, 1978a). Most deaths have followed industrial exposures, and ef
OCR for page 205
Toxicity of Selected Organic Contaminants in Drinking Water 205
fects have generally been observed anywhere from 3 to 12 hours after ex-
posure (National Institute for Occupational Safety and Health, 1978a).
This delayed onset of effects has been explained by Amdur (1959) as a
slow release of cyanide and its metabolism to thiocyanate. There are ap-
parently no reports of toxicity in humans following ingestion of
acetonitrile.
Observations in Other Species
Acute toxic effects observed in animals include labored breathing, anuria,
ataxia, cyanosis, coma, and death. Tissue distribution studies indicate
that mononitriles are distributed uniformly in the various organs and that
cyanide metabolites are found in the spleen, stomach, and skin, smaller
amounts being present in the liver, lungs, kidneys, heart, brain, muscle,
intestines, and testes (Dequidt and Haguenoer, 1972; Pozzani et al.,
1959).
Most studies conducted in animals have been concerned with toxicity
following inhalation. Studies of orally adminstered acetonitrile have
shown LDso's in various species as follows: Sherman rats, 3.8 g/kg (Smyth
and Carpenter, 19481; rats, 1.34-6.68 g/kg (Pozzani et al., 1959~; and
guinea pigs, 0.14 g/kg (Pozzani et al., 1959~. Kimura et al. (1971) found
that the oral toxicity of acetonitrile varied according to the age of the rat.
The acute oral LD50's for 14-day-old, young adult, and adult rats were
0.16 g/kg, 3.1 g/kg, and 3.5 g/kg, respectively. Acetonitrile was
significantly more toxic in the 14-day-old rat than in the adult.
There are no studies dealing with subacute or chronic toxicity of
acetonitrile administered orally to animals.
Carcinogenicity, Mutagenicity, and Teratogenicity There are no
reports indicating any possible carcinogenic, mutagenic, or teratogenic ef-
fects of acetonitrile (National Institute for Occupational Safety and
Health, 1978a). Acrylonitrile (vinyl cyanide) is suspected of inducing
cancer in both animals and humans (National Institute for Occupational
Safety and Health, 1978c).
CONCLUSIONS AND RECOMMENDATIONS
Suggested No-Adverse-Response Level {SNARLJ
24-Hour Exposure There are no adequate data from which to
calculate a 24-hour or 7-day SNARL.
OCR for page 206
206 DRINKING WATER AND HEALTH
Chronic Exposure There are no adequate data from which to
calculate a chronic exposure SNARL.
Chloroform (CHCI3)
Chloroform was evaluated in the first and third volumes of Drinking
Water and Health (National Academy of Sciences, 1977, pp. 713-717;
1980a, pp. 203-204~. The following material, which became available
after these volumes were published, updates and, in some instances,
reevaluates the information in the earlier reports. Also included are some
references that were not assessed id the original report.
HEALTH EFFECTS
Observations in Humans
No new data.
Observations in Other Species
Hewitt et al. (1979) observed an increased uptake of glutamate-pyruvate
transaminase (GPl) and decreased uptake of indicator organic anions
and cations in kidney slices from male Swiss-Webster mice exposed to
chloroform. Pretreatment of the animals with mirex did not markedly
alter either the hepatotoxic or nephrotoxic effects of chloroform.
However, pretreatment with kepone potentiated chloroform hepatotoxic-
ity and may have increased chloroform-induced kidney damage. The
authors concluded that ingestion of kepone may increase the sensitivity of
the liver and kidneys to chloroform toxicity.
The toxicity of chloroform was more pronounced in males than in fe-
males of the following barrier-reared strains of mice: Tif:MAGf,
Tif:MF2f, C3H/TifBomf, DBA/JBomf, C57BL/6J/Bomf, and A/JBomf
strains. The C3H/TifBomf strain proved to be the most sensitive of the
several strains tested (Pericin and Thomann, 1979~. 2,3,7,8-Tetrachloro-
dibenzo-p-dioxin did not alter the acute toxicity of chloroform (Hook et
al., 1978), but Cornish et al. (1977) showed that the toxicity of chloroform
can be markedly potentiated by prior treatment with ethanol or phenobar-
bital.
Mutagenicity In studies by Agustin and Lim-Sylianco (1978),
chloroform showed DNA-damaging and chromosome-breaking (clasto-
genic) activity; however, it had no direct effect on base-pair and frame
OCR for page 207
Toxicity of Selected Organic Contaminants in Drinking Water 207
shift mutations. Chloroform also caused frame shift mutations in male
mice after metabolic activation. Vitamin E treatment decreased the
mutagenicity and clastogenicity of chloroform.
Clemens et al. (1979) reported genotypic differences in responses to the
toxic effects of chloroform that were manifestations of differences in renal
rather than hepatic responses or the ability to repair renal damage. In
these studies, the authors showed that DBA/2J male mice were more sen-
sitive to the 10-day lethal effect of chloroform than were C57BL/6J males,
whereas the sensitivity of B6D2F~ (C57BL/6J X DBA/2J) mice was in-
termediate. This relative order of sensitivity was preserved following
sublethal doses of labelled chloroform with respect to accumulation in
subcellular fractions and renal (but not hepatic) dysfunction. Kidneys
from mice of the three genotypes were able to repair tubular damage from
chloroform. Prior to toxic exposure to chloroform, covalent binding of
labeled chloroform to renal microsomes was greater in DBA than in
C57BL mice. Pretreatment with phenobarbital enhanced covalent bind-
ing by renal microsomes from DBA, but not from C57BL mice. Testoster-
one propionate and medroxyprogesterone acetate sensitized the kidneys of
both sexes in DBA/2J and C57BL/6J mice. Progesterone and hydrocorti-
sone sodium phosphate sensitized the kidneys to chloroform in DBA/2J
males but not in DBA/2J females or in C57BL/6J mice of either sex.
In the presence of metabolically active mouse liver microsomes and
bacteria, chloroform was not activated to mutagenic species (Greim et al.,
1977~. It also gave negative results in the Ames test and failed to increase
the frequency of sister chromatic exchange (SCE) in fibroblasts of Chinese
hamsters (Li et al., 1979~. Results from a study by White et al. (1979) also
indicated that chloroform did not increase SCE values. Simmon (1977)
reported that bromoform, dibromochloromethane, and bromodichloro-
methane are mutagenic whereas chloroform is not mutagenic in Salmo-
nella typhimurium strains TA1535 and TA100.
Carcinogenicity Reuber (1979) recently reviewed the literature con-
cerning the carcinogenicity of 14 organochlorine pesticides in mice. Car-
cinomas of the liver were observed most frequently in mice ingesting
chloroform, among other organochlorine compounds. When ad-
ministered orally in doses of 0.15 mg/kg/day in drinking water,
chloroform did not enhance the growth or metastasis of Lewis lung car-
cinoma or increase the number of Ehrlich ascites tumor cells in mice in-
oculated with tumor cells (Caper and Williams, 1978~. However, when ad-
ministered at 15 mg/kg/day in similar experiments it caused increases in
pulmonary tumor foci after inoculation with Lewis lung carcinoma cells
and in the number of Ehrlich ascites tumor cells. At both doses, it led to
OCR for page 208
208 DRINKING WATER AND HEALTH
more organ invasions by B16 melanoma after inoculation with the tumor
cells. When administered by oral intubation, it produced kidney tumors
in male Osborne-Mendel rats (Weisburger, 1977~.
A series of studies was conducted at the Huntington Research Center in
England, using beagle dogs, specific pathogen-free Sprague-Dawley rats,
and three stocks (C57BL, CBA, and CSI) of mice, which were given
chloroform in a toothpaste base (Heywood et al., 1979; Palmer e! al.,
1979; Roe et al., 1979~. The beagle dogs were given the mixture orally in
gelatin capsules 6 days/week for 7.5 years, followed by a 20- to 24-week
recovery period (Heywood et al., 1979~. Groups of males and females
received 0.5 ml/kg/day of the vehicle (toothpaste without chloroform),
and eight dogs of each sex remained untreated. The treated groups were
composed of eight dogs of both sexes, each receiving chloroform in doses
equivalent to 15 and 30 mg/kg/day in the toothpaste vehicle. Another
group of the same size received an equivalent amount of toothpaste (0.5
ml/kg/day) without chloroform. At the end of the exposure, a small
number of macroscopic and microscopic neoplasms were observed. One
dog in each chloroform-treated group had a malignant tumor, but there
were no tumors in the livers or kidneys of any dog. Overall, exposure to
chloroform in a toothpaste base was not associated with any effects on the
incidence of any kind of neoplasia.
Groups of 50 cesarean-derived specific pathogen-free male and female
Sprague-Dawley rats received either chloroform in doses equivalent to 60
mg/kg/day in a toothpaste base or the vehicle only by gavage 6 days/week
for 80 weeks. They were then observed for as long as 15 weeks more
(Palmer et al., 19791. Chloroform-treated rats of both sexes survived bet-
ter than the controls, although both groups had a high incidence of non-
neoplastic respiratory and renal diseases. There were consistent observa-
tions of decreases in plasma cholinesterase in female rats, which were
shown to be related to activity against butyrylcholine but not to acetyl-,B-
methylcholine. Tumors of various sites were observed in 39~o of chloro-
form-treated rats of both sexes examined histologically, compared with
38~o of the vehicle controls. There were no treatment-related effects on
the incidence of liver or kidney tumors. However, histological observations
of malignant mammary tumors were reported in more treated than con-
trol rats, but these differences were not statistically different.
In another study, mice were given chloroform in a toothpaste base by
gavage or in arachis oil in doses up to 60 mg/kg/day, 6 days/week for 8
weeks (Roe et al., 1979~. Control groups were left untreated or given the
vehicle only. In general, there were more survivors in the chloroform-
treated groups than in the control group. Treatment was not associated
with any type of neoplasia. In male, but not female, ICI mice receiving
OCR for page 209
Toxicity of Selected Organic Contaminants in Drinking Water -209
doses of 60 mg/kg/day, but not in those given 17 mg/kg/day, chloroform
in a toothpaste base was associated with an increased incidence of epi-
thelial tumors of the kidney. A more pronounced effect of the same kind
was observed in mice given chloroform at 60 mg/kg/day in an arachis oil
vehicle. This treatment was also associated with a higher incidence and
severity of nonneoplastic renal disease. At the dose levels tested, namely
113 and 400 times greater than the average human exposure resulting
from the use of toothpaste containing 3.5% chloroform, no adverse effects
were seen in the liver and there was no increased incidence of liver tumors,
even in the CBA strain with the greatest susceptibility to liver tumor for-
mation. At the 17 mg/kg/day level, which is 113 times greater than the
average exposure of humans from toothpaste, no excess of renal tumors
was observed in males of the particularly susceptible ICI strain.
Teratogenicity No new data.
CONCLUSIONS AND RECOMMENDATIONS
Suggested No-Adverse-Response Level (SNARLJ
The following calculations are for noncarcinogenic effects only.
24-Hour Exposure A SNARL of 22 mg/liter was calculated in Drink-
ing Water and Health, Volume 2 (National Academy of Sciences, 1980a).
Details of the calculation are contained in that volume.
7-Day Exposure This was calculated to be one-seventh (3.2 mg/liter)
of the 24-hour SNARL.
Chronic Exposure
form is a carcinogen in animals.
This value cannot be calculated because chloro
1,2-Dibrom~3-chloropropane (C3H5Br2CI)
1,2-Dibromo-3-chloropropane (DBCP) is an amber-brown liquid with a
low vapor pressure and solubility (O.l~o w/w), but it is miscible with
aliphatic and aromatic hydrocarbons and other solvents and oils. Its
molecular weight is 236.36.
Since the 1950's, DBCP has been used as a soil fumigant and nemato-
cide in emulsifiable concentrates, liquid concentrates. powders, granules,
and other formulations. It has been marketed under such trade names as
Negmagon, Fumazone, Nemaset, Nematox, and Nemafume.
OCR for page 210
210 DRINKING WATER AND HEALTH
DBCP is produced primarily by the bromination of allyl chloride at
room temperature. Technical grade DBCP has been shown to contain up
to loo impurities, including epichlorohydrin and allyl chloride. The
levels of these compounds and 14 other identified impurities may vary
among batches. In contrast to the other impurities' epichlorohydrin is
added intentionally as a stabilizer.
HEALTH ASPECTS
Observations in Humans
In August 1977, at the request of the Oil, Chemical, and Atomic Workers
Union (OCAW), the National Institute for Occupational Safety and
Health (NIOSH) inspected manufacturing facilities in California. In
September of that year. an emergency temporal standard for exposure to
DBCP was issued by the Occupational Safety and Health Administration
(OSHA). A permanent standard for DBCP exposure, which was established
on March 17, 1978, limits employee exposure to 1 ppb as an 8-hour time-
weighted average concentration. This OSHA standard also prohibited eye
and skin contact and provided for monitoring of employee exposure,
engineering controls, safe work practices, and various other regulatory re-
quirements. A rebuttable presumption against registration (RPAR) and
continued registration of pesticide products containing DBCP was issued
by the U.S. Environmental Protection Agency (EPA) on September 22,
1977 (U.S. Environmental Protection Agency, 1977~.
Both the OSHA standard and the EPA RPAR were based primarily on
toxicological findings in animals, suggesting that DBCP causes sterility
and is carcinogenic. The NIOSH recommendation for an occupational
exposure standard for DBCP was based not only on its carcinogenic and
sterilizing potential, but also on its ability to cause diminished renal func-
tion, degeneration and cirrhosis of the liver, and mutagenesis in chroni-
cally exposed employees.
Observations in Other Species
Acute Effects Studies by Torkelson et al. ( 1961 ) and by Rakh-
matullaev (1971) indicate that the acute oral LDso for DBCP in rats and
other animals such as guinea pigs, mice, rabbits, and chickens ranges
from 170 to 350 mg/kg. Mice and rabbits appear to be somewhat less sen-
sitive than chickens. Effects preceding death following lethal exposures to
DBCP included depression, analgesia, skeletal muscle incoordination,
and paralysis. DBCP produced slight irritation when applied to the eye,
OCR for page 211
Toxicity of Selected Organic Contaminants in Drinking Water 211
but corneal irritation was not noted. Dermal application of DBCP produced
only transient erythema in rabbits, but both single and repeated dermal
exposure produced subcutaneous necrosis with polymorphonuclear
leucocyte infiltration. Using a modified Draize technique, Torkelson et al.
(1961) reported a dermal LDso of 1,400 mg/kg in rabbits exposed for 24
hours to undiluted DBCP at 60 ppm. Inhalation exposure to vaporized
DBCP produced respiratory irritation, apathy, and ataxia. Clouding of
the lens and cornea and mortality occurred at higher concentrations. A
1-hour LC50 of 368 ppm was observed in rats, but delayed deaths and
kidney pathology were noted following inhalation exposures to concentra-
tions as low as 50 ppm.
Subchronic Effects
Torkelson et al. (1961) fed diets containing DBCP
concentrations of 0, 5, 20, 150, 450, and 1,350 mg/kg to male and female
rats for 90 days. Female rats exhibited increased kidney weights at )()
_ , . , ~ . . . . . . . . .
111~/~g alla a~ ~llg~ler aoses, retarded welgnt gain at doses of 150 mg/kg
and higher, and increased liver weight at 450 mg/kg. There were no
Growth effects in male rats fed diets oontninina lo then An m~r/lrn
~, ~^-~ 4 · ~ ~A A-459 / ~,5~ ~
~ ~ ~ ~ _ ~ ~ ~ . · · . . .. . ~
ulstologlca1 effects were minimal at all dosage levels in both sexes.
In contrast to the diet exposure studies, repeated inhalation exposure
produced poor growth, increased susceptibility to secondary infection,
and both gross and histological changes in the testes of male rats at the
lowest exposure rate tested (50 exposures of 7 hours daily, 5 days a week to
DBCP at 5 ppm). Hicher concentrations of DBCP produced mortality
_ ~ _ ~ ,,,
. · · . ^. .
and similar findings were observed in monkeys, guinea pigs, and rabbits.
Intramuscular injection of testosterone, cortisone, and ACTH (adrenocor-
ticotropic hormone) failed to protect male rats against the testicular ef-
fects of exposure to DBCP (Torkelson et al., 19611.
Mutagenicity DBCP was shown to be directly mutagenic to Salmo-
nella typhimurium TA1530 and Escherichia cold Poll A by Rosenkrantz
(1975~. Prival et al. (1977) reported that the compound is a direct weak
mutagen in Salmonella TA1535. Blum and Ames (1977) reported
mutagenic effects with DBCP in Salmonella TA100 with metabolic activa-
tion. The observation of Vogel and Chandler (1974) that 1,2-dibromo-
propane was also mutagenic in Drosophila could have been due to the
ability of vicinal 1,2-dibromides to rearrange in solution to fo'-',, reactive
bromonium ion. The substitution of a chlorine atom on the third carbon
of propane would probably not alter this property significantly. Thus,
DBCP would be expected to be mutagenic on the basis of its 1,2-dibro-
mide configuration. However, Biles et al. (1978), in a more recent reeval-
uation of the mutagenicity of DBCP, suggest that most, if not all, of the
OCR for page 212
212 DRINKING WATER AND HEALTH
mutagenic effects attributed to the technical grade of DBCP used in
previous mutagenesis assays is due to epichlorohydrin or to other highly
mutagenic contaminants in the technical product. Using Salmonella
typhimurium TA1535 with and without S-9 activation, these investigators
demonstrated mutagenic effects (increased revertants at doses ranging
from 0 to 1,600 ~g/plate) with technical DBCP, pure epichlorohydrin,
and distillates from the technical product. Pure (redistilled) DBCP did not
produce mutagenic effects even at high dosage levels. On the basis of the
mutagenesis assay data, these authors calculated that the mutagenic ef-
fect of technical DBCP can be attributed almost entirely to the presence of
the stabilizer epichlorohydrin in the technical product. They also observed
that the use of S-9 activation in the mutagenesis assay eliminated the
mutagenic activity of epichlorohydrin and produced a mutagenic effect
from pure DBCP, suggesting the formation of a mutagenic metabolite.
Allyl chloride, which is also an impurity in technical DBCP, was found to
be mutagenic in these studies, but the mutagenic potency of this contami-
nant is less than that of either epichlorohydrin or technical DBCP.
Carcinogenicity The EPA RPAR Final Position Document for DBCP
(U.S. Environmental Protection Agency, 1978) describes four studies that
attribute carcinogenic effects to DBCP in laboratory animals. The first of
these is the National Cancer Institute (NCI) (1978) bioassay of DBCP for
possible carcinogenicity. Partial results of this study have also been
published by Weisburger (1977), and preliminary observations on the car-
cinogenicity of DBCP were reported by Olson et al. (1973~. Two additional
studies, which were sponsored by Dow Chemical, were conducted at the
Hazelton Laboratories. The fourth study was a skin bioassay study con-
ducted by Van Duuren at the New York Medical Center. An earlier report
by Van Duuren (1977) describes the carcinogenicity of epichlorohydrin,
allyl chloride, and other DBCP-related halohydrocarbons.
When the NCI carcinogenicity bioassay was initiated in 1972, DBCP
was only one of several halohydrocarbons under test. It was administered
by gavage 5 days a week to male and female Osborne-Mendel rats at
dosage levels of 12 and 24 mg/kg for 14 weeks' after which the dosages
were increased to 15 and 30 mg/kg for a period of 73 or 64 weeks, respec-
tively. Similar studies with male and female B6C3F~ mice were also con-
ducted at higher concentrations of DBCP. The major conclusions of this
study were that, "In rats and mice of both sexes, statistically significant
incidences of squamous-cell carcinomas of the forestomach occurred in
each dosed group with a positive association between dose level and
tumour incidence." The NCI also concluded that DBCP is carcinogenic to
the mammary gland of female rats. Toxic nephropathy was observed in
OCR for page 278
278 DRINKING WATER AND HEALTH
Lyle, W. H., T.W.M. Spence, W.M. McKinneley, and K. Duckers. 1979. Dimethylfor-
mamide and alcohol intolerance. Br. J. Ind. Med. 36:63-66.
MacMath, I.F., and J. Apley. 1954. Cyanosis from absorption of marking-ink in newborn
babies. Lancet 2:895-896.
Maguire, H.C., Jr. 1973. The bioassay of contact allergens in the guinea pig. J. Soc. Cosmet.
Chem. 24:151-162.
Maguire, H.C., Jr., and M.W. Chase. 1972. Studies on the sensitization of animals with sim-
ple chemical compounds. XIII. Sensitization of guinea pigs with picric acid. J. Exp. Med.
135:357-375.
Makhinya, A.P. 1964. Effect of certain nitrophenols on the organoleptic qualities of water
and the sanitary conditions of water basins. Vopr. Gigieny Nasalen. Mest, Kiev, Sb.
5:43-46. [Chem. Absts. 64: 15580c, 1966.]
Makhinya, A. P. 1969. Comparative hygienic and sanita~y-toxicological studies of
nitrophenol isomers in relation to their normalization in river waters. Prom. Zagryazeniya
Vodoemov (9):84-95. [Chem. Absts. 72:047231c. 1970.]
Makotchenko, V.M, and Zh.B. Akhmetov. 1972. [in English summary] Adrenal cortex
function in chronic nitrobenzene poisoning of guinea pigs and the effect of hydrocortisone
on the course of poisoning. Farmakol. Toksikol. 35:247-249.
Malmgren, R.A., B.E. Bennison, and T.W. McKinley, Jr. 1952. Reduced antibody titers
in mice treated with carcinogenic and cancer chemotherapeutic agents. Proc. Soc. Exp.
Biol. Med. 79:484-4~.
Marshall, S., M.D. Whorton, R.M. Krauss, and W. Palmer. 1977. The effects of pesticides
on testicular function. J. Urol. 11 :257-259.
Matsuguma, H.J. 1967. Nitrophenols. Pp. 888-894 in R. E. Kirk and D . F. Othmer. eds.
Kirk-Othmer Encyclopedia of Chemical Toxicology. Vol. 13. Second edition. Wiley-
Interscience, New York.
Maxfield, M.E., J.R. Barnes, A. Azar, and H.T. Trochimowicz. 1975. Urinary excretion of
metabolite following experimental human exposures to DMF or to DMAC. J. Occup.
Med. 17:506-511.
Mazumdar, S., C. Redmond, W. Sollecito, and N. Sussman. 1975. An epidemiological
study of exposure to coal tar pitch volatiles among coke oven workers. J. Air Pollut. Con-
trol. Assoc. 25:382-389.
McAuliffe, C. 1966. Solubility in water of paraffin, cycJoparaffin, olefin, acetylene,
cycloolefin, and aromatic hydrocarbons. J. Phys. Chem. 70:1267-1275.
MaAuliffe, C.D. 1977. Evaporation and solution of C2 to C'0 hydrocarbons from crude oils
on the sea surface. Pp. 363-372 in D.A. Wolfe, J.W. Anderson, D.K. Button, D.C.
Malins, T. Roubal, and U. Varanasi, eds. Fate and Effects of Petroleum Hydrocarbons in
Marine Organisms and Ecosystems. Pergamon Press, New York.
McCann, J., and B.N. Ames. 1976. Detection of carcinogens as mutagens in the
Salmonella/microsome test: Assay of 300 chemicals: Discussion. Proc. Natl. Acad. Sci.
USA 73:950-954.
McCann, J., E. Choi, E. Yamasaki, and B.N. Ames. 1975. Detection of carcino?gens as
mutagens in the Salmonella/microsome test: Assay of 300 chemicals. Proc. Natl. Acad.
Sci. USA 72:5135-5139.
McKee, H.C., J.W. Rhoades, J. Campbell. and A.L. Gross. 1962. Acetonitrile in body fluids
related to smoking. Public Health Rep. 77:553-554.
Medyankin, A.V. 1975. Complex action of dimethyl formamide under conditions of a Jong-
term experiment. Gig. Sanit. (USSR) No. 9:39-42. [Chem. Absts. 83:202471d, 1975.]
Miller, E.C. 1978. Some current perspectives on chemical carcinogenesis in humans and ex-
perimental animals: Presidential address. Cancer Res. 38:1479-1496.
OCR for page 279
Toxicity of Selected Organic Contaminants in Drinking Water 279
Mitra, A.B., and G.K. Manna. 1971. Effect of some phenolic compounds on chromosomes
of bone marrow cells of mice. Indian J. Med. Res. 59:1442-1447.
Mitsuda, H., K. Mrakami, and F. Kawai. 1963. Effect of chlorophenol analogues on the
oxidative phosphorylation in rat liver mitochondria. Agr. Biol. Chem. 27:366-372.
Miyamoto, K., Y. Ikeda, and K. Kurata. 1975. Deficient myelination by 2,4-dinitrophenol
administration in the early stage of development. Teratology 12:204.
Moldeus, P., H. Vadi, and M. Berggren. 1976. Oxidative and conjugative metabolism of
p-nitroanisole and p-nitrophenol in isolated rat liver cells. Acta Pharmacol. Toxicol.
39:1 7-32.
Muravieva, S.I., G.N. Zaeva, K.P. Stasenkova, and N.N. Ordynskaya. 1975. [In Russian;
English summary.] Passage of dimethylformamide with urine depending upon the levels
and duration of its action. Gig. Tr. Prof. Zabol. 12:36-39.
Myslak, Z., J.K. Piotrowski, and E. Musialowicz. 1971. Acute nitrobenzene poisoning: A
case report with data on urinary excretion of p-nitrophenol and p-aminophenol. Arch.
Toxicol. 28:208-213.
Nabarro, J.D.N. 1948. A case of acute mononitrobenzene poisoning. Br. J. Med. 1:929-931.
National Academy of Sciences. 1976a. Fuels and Fuel Additives for Highway Vehicles and
Their Combustion Products: A Guide to Evaluation of Their Potential Effects on Health.
Committee on Toxicology, Assembly of Life Sciences, National Research Council. Na-
tional Academy of Sciences, Washington, D.C. 43 pp. (Available from National Technical
Information Service, Springfield, Va., as PB-254 088.)
National Academy of Sciences. 1976b. Health Effects of Benzene: A Review. Committee on
Toxicology, Assembly of Life Sciences, National Research Council. National Academy of
Sciences, Washington, D.C. (Available from National Technical Information Service,
Springfield, Va., as PB-254-388.)
National Academy of Sciences. 1977. Drinking Water and Health. Safe Drinking Water
Committee, Advisory Center on Toxicology, Assembly of Life Sciences, National Research
Council. National Academy of Sciences, Washington, D.C. 939 pp.
National Academy of Sciences. 1980a. Drinking Water and Health, Vol. 3. Safe Drinking
Water Committee, Board on Toxicology and Environmental Health Hazards, Assembly of
Life Sciences, National Research Council. National Academy Press, Washington, D.C.
1980. 415 pp.
National Academy of Sciences. 1980b. The Alkyl Benzenes. Committee on Alkyl Benzene
Derivatives, Board on Toxicology and Environmental Health Hazards, Assembly of Life
Sciences, National Research Council. National Academy Press, Washington, D.C.
National Cancer Institute. 1978. Bioassay of Dibromochloropropane for Possible Car-
cinogenicity. CAS No. 1836-75-5. National Cancer Institute Carcinogenesis Technical
Report Series No. 28. U.S Department of Health, Education. and Welfare, Public Health
Service. National Institutes of Health, Bethesda, Md. [DHEW (NIH) Publ. No. 78-828.]
National Cancer Institute. 1979. Bioassay of 2,4,6-Trichlorophenol for Possible Car-
cinogenicity. CAS No. %-06-2. National Cancer Institute Carcinogenesis Technical
Report Series No. 155. U.S. Department of Health, Education, and Welfare, Public
Health Service, National Cancer institute. National Institutes of Health, Washington,
D.C. 115 pp. [DHEW (NIH) Publ. No. 79-1711.]
National Institute for Occupational Safety and Health. 1976. Criteria for a Recommended
Standard ... Occupational Exposure to Epichlorohydrin. U.S. Department of Health,
Education, and Welfare, Public Health Service, Center for Disease Control. National In-
stitute for Occupational Safety and Health, Washington, D.C. [DHEW (NlOSH) Publ.
No. 76-206.]
National Institute for Occupational Safety and Health. 1977a. Criteria for a Recommended
OCR for page 280
280 DRINKING WATER AND HEALTH
Standard . . . Occupational Exposure to Refined Petroleum Solvents. U.S. Department of
Health, Education, and Welfare, Public Health Service, Center for Disease Control. Na-
tional Institute for Occupational Safety and Health, Washington, D.C. 247 pp. [DHEW
(NIOSH) Publ. 77-192.]
National Institute for Occupational Safety and Health. 1977b. Criteria for a Recommended
Standard ... Occupational Exposure to Alkanes (C5-C8). U.S. Department of Health,
Education, and Welfare, Public Health Service, Center for Disease Control. National In-
stitute for Occupational Safety and Health, Cincinnati, Ohio. 129 pp. [DHEW (NIOSH)
Publ. No. 77-151.]
National Institute for Occupational Safety and Health. 1978a. Criteria for Recommended
Standard . . . Occupational Exposure to Nitriles. U.S. Department of Health, Education,
and Welfare, Public Health Service, Center for Disease Control. National Institute for Oc-
cupational Safety and Heath, Washington, D.C. 155 pp. [DHEW (NIOSH) Publication
No. 78-212~1
National Institute for Occupational Safety and Health. 1978b. Current Intelligence Bulletin
30: Epichlorohydrin. U.S. Department of Health, Education, and Welfare, Public Health
Service, Center for Disease Control. National Institute for Occupational Safety and
Health, Cincinnati, Ohio. 12 pp.
National Institute for Occupational Safety and Health. 1978c. A Recommended Standard
for Occupational Exposure to ... Acrylonitrile. U.S. Department of Health, Education.
and Welfare, Public Health Service, Center for Disease Control. National Institute for Oc-
cupational Safety and Health, Cincinnati, Ohio. 14 pp. [DHEW (NIOSH) Publication No.
78-116.]
National Institute for Occupational Safety and Health. 1978d. Registry of Toxic Effects of
Chemical Substances. U.S. Department of Health, Education, and Welfare, Public
Health Service. National Institute for Occupational Safety and Health, Cincinnati, Ohio.
Nojima, K., K. Fukaya, and S. Kanno. 1975. Studies on photochemistry of aromatic
hydrocarbons. II. The formation of nitrophenols and nitrobenzene by the photochemical
reaction of benzene in the presence of nitrogen monoxide. Chemosphere No. 2:77-82.
Ogino, S., and K. Yasukura. 1957. Biochemical studies on cataracts. VI. Production of
cataracts in guinea pigs with dinitrophenol. Am. J. Ophthalmol. 43:939-946.
Olson, W.A., R.T. Habe~n~ann, E.K. Weisburger, J.M. Ward, and J.H. Weisburger. 1973.
Induction of stomach cancer in rats and mice by halogenated aliphatic fumigants. J. Natl.
Cancer Inst. 51:1993-1995
Pacseri, I., and L. Magos. 1958. Determination of the measure of exposure to aromatic nitro
and amino compounds. J. Hyg. Epidemiology. Microbial. Immunol. 2:92-110.
Palmer, A.K., A.E. Street, F.J.C. Roe, A.N. Worden, and N.J. Van Abbe. 1979. Safety
evaluation of toothpaste containing chloroform. II. Long term studies in rats. J. Environ.
Pathol. Toxicol. 2:821-833.
Papageorgiou, G., and C. Argoudelis. 1973. Cation-dependent quenching of the
fluorescence of chlorophyll a2 in veto by nitroaromatic compounds. Arch. Biochem.
Biophys. 156:134-142.
Parascandola, J. 1974. Dinitrophenol and bioenergetics: An historical perspective. Mol.
Cell. Biochem. 5:69-77.
Parke, D.V. 1956. Studies in detoxication. 68. The metabolism of [~4C]nitrobenzene in the
rabbit and guinea pig. Biochem. J. 62:339-346.
Parker, V.H. 1952. Enzymic reduction of 2,4-dinitrophenol by rat-tissue homogenates. Bio-
chem. J. 51:363-370.
Patty, F.A., ed. 1963. Industrial Hygiene and Toxicology. Toxicology. Vol. 2. Second edi-
tion. John Wiley & Sons, New York. 2,377 pp.
OCR for page 281
Toxicity of Selected Organic Contaminants in Drinking Water 281
PEDCo. Environmental, Inc. 1977. Assessment of Gasoline Toxicity. Prepared for U.S. En-
vironmental Protection Agency, Strategies and Air Standards Division, Research Triangle
Park, N.C. under Contact No. 68-02-2515, Task No. 12. PEDCo. Environmental, Inc.,
Cincinnati, Ohio. 107 pp.
Perbellini, L., F. Brugnone, and I. Pavan. 1980. Identification of the metabolites of
n-hexane, cyclohexane, and their isomers in men's urine. Toxicol. Appl. Pharmacol.
53:220-229.
Pericin, C., and P. Thomann. 1979. Comparison of the acute toxicity of clioquinol,
histamine, and chloroform in different strains of mice. Arch. Toxicol. ISS Suppl.
2:371-373. [Chem. Absts. 92: 1 22863d, 1980. ]
Perkins, R.G. 1919. A study of the munitions intoxications in France. Public Health Rep.
34:2335-2374.
Philips, F.S., S.S. Sternberg, and H. Marquardt. 1973. In viva cytotoxicity of polycyclic
hydrocarbons. Pp. 75-88 in T.A. Loomis, ed. Pharmacology and the Future of Man. Vol.
2. Toxicological Problems. Proceedings of the Fifth International Congress on Phar-
macology, San Francisco, Calif., July 23-28. 1972. S. Karger, Basel.
Piet, G.J., and F. De Grunt. 1975. Organic chloro compounds in surface and drinking water
of the Netherlands. Pp. 81-92 in M. Barthelemy and P. Recht, eds. Problems Raised by
the Contamination of Man and his Environment by Persistent Pesticides and Organo-
halogenated Compounds, European Colloquium, Luxembourg, 1974. Commission of the
European Communities, Luxembourg.
Piotrowski, J. 1967. Further investigations on the evaluation of exposure to nitrobenzene.
Br. J. Ind. Med. 24:60-65.
Piotrowski, J. 1977. Exposure Tests for Organic Compounds in Industrial Toxicology. U.S.
Department of Health, Education, and Welfare, Public Health Se~vice, Center for Disease
Control' National Institute for Occupational Safety and Health, Washington, D.C. 138
PP. lDHEW (NIOSH) Publ. No. 77-144.]
Potashnik, G., N. Ben-Aderat, R. Israeli, I. Yanaiinbar, and I. Sober. 1978. Suppressive ef-
fect of 1,2-dibromo-3-chloropropane on human spermatogenesis. Fertil. Steril. 30:444.
Potter, H. P. 1973. Dimethylformamide-induced abdominal pain and liver injury. Case
report. Arch. Environ. Health 27:340-341.
Pozzani, U.C. , C. P. Carpenter, P.E. Palm, C.S. Weil, and J.H. Nair, III. 1959. An in-
vestigation of the mammalian toxicity of acetonitrile. J. Occup. Med. 1:634-642.
Prival, M.J., E.C. McCoy, B. Gutter, and H.S. Rosenkranz. 1977. Tris(2,3-dibromopropyl)
phosphate: Mutagenicity of a widely used flame retardant. Science 195:76-78.
Pulkkinen, M.O. 1966a. Sulphate conjugation during development, in human, rat and
guinea pig. Acta Physiol. Scand. 66:115-119.
Pulkkinen, M.O. 1966b. Sulphate conjugation during pregnancy and under the influence of
cortisone. Acta Physiol. Scand. 66:120-122.
Pullman, A., and B. Pullman. 1955. Electronic structure and carcinogenic activity of
aromatic molecules. New developments. Adv. Cancer Res. 3:117-169.
Quarles, J.M., M.W. Sega, C.K. Schenley, and R.W. Tennant. 1979. Rapid screening for
chemical carcinogens: Transforming activity of selected nitroso compounds detected in a
transplacental host-mediated culture system. Natl. Cancer Inst. Monogr. 51:257-263.
[Chem. Absts. 91 :169290j, 1979. ]
Quebbemann, A.J., and M.W. Anders. 1973. Renal tubular conjugation and excretion of
phenol and p-nitrophenol in the chicken: Differing mechanism of renal transfer. J. Phar-
macol. Exp. Ther. 184:695-708.
Rakhmatullaev, N.N. 1971. Hygienic features of nematocide-Nemagon in connection with
sanita~r protection of water reservoirs. Gig. Sanit. 36:19-23.
OCR for page 282
282 DRINKING WATER AND HEALTH
Ramsay, D.H.E., and C.C. Harvey. 1959. Marking-ink poisoning: An outbreak of
methaemoglobin cyanosis in newborn babies. Lancet 1:910-912.
Rao, K.S., F.J. Murray, A.A. Crawford, J.A. John, W.J. Potts, B.A. Schwetz. J.D. Burek,
and C.M. Parker. 1979. Effects of inhaled 1,2-dibromo-3-chloropropane (DBCP) on the
semen of rabbits and the fertility of male and female rats. Toxicol. Appl. Pharmacol.
48:A137, Abstr. No. 273.
Rappe, C., H.R. Buser. and H.-P. 1979. Dioxins, dibenzofurans and other polyhalogenated
aromatics: Production, use, formation, and destruction. Ann. N.Y. Acad. Sci. 320:1-18.
Rasanen, L., M.L. Hattula, and A.U. Arstila. 1977. The mutagenicity of MCPA and its soil
metabolites, chlorinated phenols, catechols and some widely used slimicides in Finland.
Bull. Environ. Contam. Toxicol. 18:565-571.
Reddy, B.G., L.R. Pohl, and G. Krishna. 1976. The requirement of the gut flora in
nitrobenzene-induced methemoglobinemia in rats. Biochem. Pharmacol. 25:1119-1122.
Redmond, C.K., A. Ciocco. J.W. Lloyd, and H.W. Rush. 1972. Long-term mortality study
of steelworkers. VI. Mortality from malignant neoplasms among coke oven workers. J.
Occup. Med. 14:621-629.
Redmond, C.K., B.R. Strobino, and R.H. Cypress. 1976. Cancer experience among coke
by-product workers. Ann. N.Y. Acad. Sci. 271:102-115.
Reid, D.D., and C. Buck. 1956. Cancer in coking plant workers. Br. J. Ind. Med.
13:265-269.
Reuber, M.D. 1979. Carcinomas and other lesions of the liver in mice ingesting
organochlorine pesticides. Toxicol. Annul 3:231-256.
Reznik, Ya. B., and G.K. Sprinchan. 1975. [In Russian; English summary.] Gonadotoxic
effect of Nemagon. Gig. Sanit. No. 6:101-102.
Rigdon, R.H., and J. Neal. 1965. Effects of feeding benzo[~]pyrene on fertility' embryos,
and young mice. J. Natl. Cancer Inst. 34:297-305.
Rigdon, R.H., and E.G. Rennels. 1964. Effect of feeding benzpyrene on reproduction in the
rat. Experientia 20:224-226.
Roberts, M.S., R.A. Anderson, and J. Swarbrick. 1977. Permeability of human epidermis to
phenolic compounds. J. Pharm. Pharmacol. 29:677-683.
Robinson, D., J.N. Smith, and R.T. Williams. 1951b. Studies in detoxication. 40. The me-
tabolism of nitrobenzene in the rabbit. o-, m- and p-nitrophenols, o-, m- and p-amino-
phenols and 4-nitrocatechol as metabolites of nitrobenzene. Biochem. J. 50:228-235.
50:221-227.
Robinson, D., J.N. Smith, and R.T. Williams. 1951b. Studies in detoxication. 40. The
metabolism of nitrobenzene in the rabbit. o-, m- and p-nitrophenols, o-, m- and
p-aminophenols and 4-nitrocatechol as metabolites of nitrobenzene. Biochem. J.
50:228-235.
Robinson, J.R., J.S. Felton, R.C. Levitt, S.S. Thorgeirsson, and D.W. Nebert. 1975. Rela-
tionship between "aromatic hydrocarbon responsiveness" and the survival times in mice
treated with various drugs and environmental compounds. Mol. Pharmacol. 11:850-865.
Roe, F.J.C., A.K. Palmer, A.N. Worden, and N.J. Van Abbe. 1979. Safety evaluation of
toothpaste containing chloroform. 1. Long-term studies in mice. J. Environ. Pathol. Tox-
icol. 2:799-819.
Rosenkranz, H.S. 1975. Genetic activity of 1,2-dibromo-3-chloropropane, a widely-used
fumigant. Bull. Environ. Contam. Toxicol. 14:8-11.
Rusch, G.M., B.K.J. Leong, and S. Laskin. 1977. Benzene metabolism. J. Toxicol. Environ.
Health Suppl. 2:23-36.
Salmowa, J., J. Piotrowski, and U. Neuborn. 1963. Evaluation of exposure to nitrobenzene.
Absorption of nitrobenzene vapour through lungs and excretion of p-nitrophenol in urine.
Br. J. Ind. Med. 20:41-46.
OCR for page 283
OCR for page 285
OCR for page 286
OCR for page 287
OCR for page 288
Representative terms from entire chapter:
selected organic
Toxicity of Selected Organic Contaminants in Drinking Water 283
Sanotskii, I.V., S.I. Murav'eva, G.N. Zaeva, L.P. Anvaer, and N.N. Semiletkina. 1978.
Metabolism of dimethylformamide in relationship to the intensity of its action. Gig. Tr.
Prof. Zabol. (USSR No. 11:24-27.) 1Chem. Absts. 90: 17253r, 1979.]
Sax, N.I. 1968. Dangerous Properties of Industrial Materials. Third edition. Reinhold Book
Corp., New York. 1,251 pp.
Schaumburg, H.H., and P.S. Spencer. 1976. Degeneration in central and peripheral nerv-
ous systems produced by pure n-hexane: An experimental study. Brain 99:183-192.
Scheufler, H. 1976. Testing of chemical agents for embryotoxicity, teratogenicity and
mutagenicity, ontogenical reactions of the laboratory mouse: A critical analysis of the
methods. Biol. Rundsch. 14:227-229. [EMIC 76:024418/Chem. Absts. 85:186581, 1976.]
Scheufler, H., and H.A. Freye. 1975. Embryotoxic and teratogenic effect of dimethylfor-
mamide. Dtsch. Gesundheitswes. 30:455-459. [ETIC 75:015105].
Schlede, E., R. Kuntzman, S. Haber, and A.H. Conney. 1970a. Effect of enzyme induction
on the metabolism and tissue distribution of benzo(~)pyrene. Cancer Res. 30:2893-2897.
Schlede, E. , R.Kuntzman, and A. H. Conney. 1970b. Stimulatory effect of benzo(
284 DRINKING WATER AND HEALTH
Smith, R. P., A. A. Alkaitis, and P. R. Shafer. 1967. Chemically induced
methemoglobinemias in the mouse. Biochem. Pharmacol. 16:317-328.
Smyth, H.F., Jr., and C.P. Carpenter. 1948. Further experience with the range finding test
in the industrial toxicology laboratory. J. Ind. Hyg. Toxicol. 30:63-68.
Snyder, R., and J.J. Kocsis. 197S. Current concepts of chronic benzene toxicity. CRC Rev.
Toxicol. 3:265-288.
Snyder, R., L.S. Andrews, E.W. Lee, C.M. Witmer, M. Reilly, and J.J. Kocsis. 1977.
Benzene metabolism and toxicity. Pp. 286-301 in D.J. Jallow, J.J. Kocsis, R. Snyder, and
H. Vaninio, eds. Biological Reactive Intermediates: Formation, Toxicity, and Inactiva-
tion. Plenum Press, New York.
Sorrell, R.K., H.J. Brass. and R. Reding. 1980. A review of occurrences and treatment of
polynuclear aromatic hydrocarbons. Environ. Int. 4:245-254.
Spector, W.S., ed. 1956. Handbook of Toxicology: Acute Toxicities of Solids, Liquids and
Gases to Laboratory Animals. Vol. 1. W.B. Saunders, Co., Philadelphia, Pa. 408 pp.
Spencer, H.C., V.K. Rowe, E.M. Adams, and D.D. Irish. 1948. Toxicological studies on
laboratory animals of certain alkyldinitrophenols used in agriculture. J. Ind. Hyg. Tox-
icol. 30:10-25.
Spencer, P.S., M.C. Bischoff, and H.H. Schaumburg. 1978. On the specific molecular con-
figuration of neurotoxic aliphatic hexacarbon compounds causing central-peripheral
distal axonopathy. Toxicol. Appl. Pharmacol. 44:17-28.
Springer, E.L., M. Benjamin, W.C. Feist, L.L. Zoch, Jr.. and G.J. Hajny. 1977a. Chemical
treatment of chips for outdoor storage. Evaluation of sodium N-methyldithiocarbamate +
sodium 2,4-dinitrophenol treatment. Tappi 60:88-91. [Chem.Absts. 86: 108228v, 1977.]
Springer, E.L., W.C. Feist, L.L. Zoch, Jr., and G.J. Hajny. 1977b. Evaluation of chemical
treatment to prevent deterioration of wood chips during storage. Tappi 60:93-97. [Chem.
Absts. 86: 141865y, 1977. ]
Stamova, N., N. Gincheva, M. Spasovskii, A. Bainova, S. Ivanova, S. Kurkchiev, V.
Khristeva, M. Mukhtarova, N. Karadzhova, et al. 1976. Labor hygiene during the pro-
duction of Bulana synthetic fibers. Khig. Zdraveopaz. (Bulgarian) 19:134-140. [Chem.
Absts. 86: 175464u, 1977.]
Stein, K., J. Portig, and W. Koransky. 1977. Oxidative transformation of hex-
achlorocyclohexane in rats and with rat liver microsomes. Arch. Pharmacol. 298:115-128.
Stenback, F., and H. Garcia. 1975. Studies on the modifying effect of dimethyl sulfoxide
and other chemicals on experimental skin tumor induction. Ann. N.Y. Acad. Sci.
243:209-227.
Stephen, H., and T. Stephen, eds. 1963. Solubilities of Inorganic and Organic Compounds.
Vol. 1, Binary Systems, Part I. Pergamon, New York. 960 pp.
Stevenson, A., and R.P. Forbes. 1942. Nitrobenzene poisoning. Report of a case due to ex-
terminator spray. J. Pediatr. 21 :224-228.
Stjernsward, J. 1966. Effects of noncarcinogenic and carcinogenic hydrocarbons on
antibody-fo~,.ling cells measured at the cellular level in vitro. J. Natl. Cancer Inst.
36:1189-1195.
Stjernsward, J. 1969. Immunosuppression by carcinogens. Antibiot. Chemother. 15:213-233.
Stockdale, M., and M.J. Selwyn. 1971. Influence of ring substituents on the action of
phenols on some dehydrogenases, phosphokinases and the soluble ATPase from
mitochondria. Eur. J. Biochem. 21:416-423.
Stula, E.F., and W.C. Krauss. 1977. Embryotoxicity in rats and rabbits from cutaneous ap-
plication of amide-type solvents and substituted ureas. Toxicol. Appl. Pharmacol.
41:35-55.
Sulzberger, M.B., and F. Wise. 1933. Drug eruptions. II. Dermatitis eczematosa due to
drugs. Arch. Dermatol. Syphilol. 28:461-474.
Toxicity of Selected Organic Contaminants in Drinking Water 285
Sunderman, F.W., and J.F. Kincaid. 1953. Toxicity studies of acetone cyanohydrin and
ethylene cyanohydrin. AMA Arch. and. Hyg. Occup. Med. 8:371-376.
Swamy, S.A. l9S3. Suicidal poisoning by dinitrophenol. J. Indian Med. Assoc. 22:504-505.
Swenberg, J.A., G.L. Petzold, and P.R. Harbach. 1976. In vitro damage/alkaline elusion
assay for predicting carcinogenic potential. Biochem. Biophys. Res. Commun.
72:732-738.
Szybalski, W. 1958. Special microbiological systems. II. Observations on chemical
mutagenesis in microorganisms. Ann. N.Y. Acad. Sci. 76:475-489.
Tainter, M.L., A.B. Stockton, and W.C. Cutting. 1933. Use of dinitrophenol in obesity and
related conditions. A progress report. J. Am. Med. Assoc. 101:1472-1475.
Tanaka, K., N. Kurihara, and M. Nakajima. 1977. Pathways of chlorophenol formation in
oxidative biodegradation of BHC. Agr. Biol. Chem. 41:723-725.
Teranishi, K., K. Hamada, and H. Watanabe. 1975. Quantitative relationship between car-
cinogenicity and mutagenicity of polyaromatic hydrocarbons in Salmonella typhimurium
mutants. Mutat. Res. 31:97-102.
Thakker, D.R., H. Yagi, A.Y.H. Lu, W. Levin, A.H. Conney, and D.M. Jerina. 1976.
Metabolism of benzo[a]pyrene: Conversion of (+)-trans-7,8-dihydroxy-7,8-dihydrobenzo-
la]pyrene to highly mutagenic 7,8-diol-9, 10-epcxides. Proc. Natl. Acad. Sci. USA
73:3381-3385.
Thakker, D.R., H. Yagi, H. Akagi, M. Koreeda, A.Y.H. Lu, W. Levin, A.W. Wood, A.H.
Conney, and D. M. Jerina. 1977. Metabolism of benzo[a]pyrene. VI. Stereoselective
metabolism of benzo[alpyrene and benzo[a]pyrene 7,8-dihydrodiol to diol epoxides.
Chem. Biol. Interact. 16:281-300.
Thakker, D.R., M. Nordqvist, H. Yagi, W. Levin, D. Ryan, P. Thomas, A.H. Conney, and
D.M. Jenna. 1979. Comparative metabolism of a series of polycyclic aromatic hydrocar-
bons by rat liver microsomes and purified cytochrome P-450. Pp. 455-472 in P.W. Jones
and P. Leber, eds. Polynuclear Aromatic Hydrocarbons: Third International Symposium
on Chemistry and Biology-Carcinogenesis and Mutagenesis. Ann Arbor Science, knn
Arbor, Mich.
Torkelson, T.R., S.E. Sadek, V.K. Rowe, J.K. Kodama, H.H. Anderson, G.S. Loquvam,
and C.H. Hine. 1961. Toxicologic investigations of 1,2-dibromo-3-chloropropane. Tox-
icol. Appl. Pharmacol. 3:54S-5S9.
U.S. Bureau of Mines. 1976. International Petroleum Annual. U.S. Department of the In-
terior, Bureau of Mines, Division of International Petroleum and Natural Gas,
Washington, D.C.
U.S. Environmental Protection Agency. 1977. Rebuttable Presumption Against Registration
and Continued Registration of Pesticide Products Containing Dibromochloropropane
(DBCP). Fed. Reg. 42(184):48026, Thursday, Sept. 22.
U.S. Environmental Protection Agency. 1978. Final Position Document for Dibromo-
chloropropane (DBCP). Special Pesticide Review Division, Office of Pesticide Programs.
U.S. Environmental Protection Agency, Washington, D.C.
U.S. Environmental Protection Agency. 1979a. Benzene: Ambient Water Quality Criteria.
Criteria and Standards Division, Office of Water Planning and Standards. U.S. En-
vironmental Protection Agency, Washington, D.C. 79 pp. (Available from National
Technical Information Service, Springfield, Va., as PB-292-421.)
U.S. Environmental Protection Agency. 1979b. Chlorinated Phenols. Criteria and Standards
Division, Office of Water Planning and Standards. U.S. Environmental Protection Agency,
Washington, D.C. 109 pp. (Available from National Technical Information Service,
Springfield, Va., as PB-296-790.)
U.S. Environmental Protection Agency. 1979c. Nitrobenzene. Criteria and Standards Divi-
sion, Office of Water Planning and Standards. U.S. Environmental Protection Agency,
286 DRINKING WATER AND HEALTH
Washington, D. C. 61 pp. (Available from National Technical Information Service,
Springfield, Va., as PB-296-801.)
U.S. Environmental Protection Agency. 1979d. Nitrophenols. Criteria and Standards Divi-
sion, Office of Water Planning and Standards. U.S. Environmental Protection Agency,
Washington, D.C. 134 pp. (Available from National Technical Information Service,
Springfield, Va., as PB-296-802.)
U.S. Environmental Protection Agency. 1979e. Polynuclear Aromatic Hydrocarbons: Am-
bient Water Quality Criteria. Criteria and Standards Division, Office of Water Planning
and Standards. U.S. Environmental Protection Agency, Washington, D.C. 83 pp.
(Available from National Technical Information Service, Springfield, Va., as
PB-297-926. )
U.S. Environmental Protection Agency. 1979f. Toluene: Ambient Water Quality Criteria.
Criteria and Standards Division, Office of Water Planning and Standards. U.S. En-
vironmental Protection Agency, Washington, D.C. 97 pp. (Available from National
Technical information Service, Springfield, Va., as PB-296-805.)
U.S. International Trade Commission. 1976. Imports of Benzenoid Chemicals and Prod-
ucts, 1974. USITC Publication No. 762. U.S. International Trade Commission,
Washington, D.C. 99 pp.
U.S. Occupational Safety and Health Administration. 1978. Occupational exposure to 1,2-
dibromo-3-chloropropane (DBCP), occupational safety and health standards. Fed. Reg.
43(53):11514-11533, Friday, March 17.
Van Duuren, B.L. 1977. Chemical structure, reactivity, and carcinogenicity of
halohydrocarbons. Environ. Health Perspect. 21:17-23.
Vernot, E.H., J.D. MacEwen, C.C. Haun, and E.R. Kinkead. 1977. Acute toxicity and skin
corrosion data for some organic and inorganic compounds and aqueous solutions. Tox-
icol. Appl. Pharmacol. 42:417-423.
Vogel, E., and 1.L.R. Chandler. 1974. Mutagenicity testing of cyclamate and some
pesticides in Drosophila melartogaster. Experientia 30:621-623.
von Oettingen, W.F. 1941. B. The aromatic nitro compounds. 1. Nitro-benzene and its
derivatives. Pp. 76-92 in The Aromatic Amino and Nitro Compounds, Their Toxicity and
Potential Dangers: A Review of the Literature. Federal Security Agency, U.S. Public
Health Service, Washington, D.C. Public Health Bull. No. 271.
von Oettingen, W.F., ed. 1949. The nitrophenols. Pp. 232-285 in Phenol and Its
Derivatives: The Relation Between Their Chemical Constitution and Their Effect on the
Organism. Natl. Inst. Health Bull. No. 190. Washington,D.C.
Weast, R.C., and M.J. Astle, eds. 1978. Handbook of Chemistry and Physics. A Ready-
Reference Book of Chemical and Physical Data. 59th edition. CRC Press, West Palm
Beach, Fla. 2,488 pp.
Wedding, R.T.. C. Hansch, and T.R. Fukuto. 1967. Inhibition of malate dehydrogenase by
phenols and the influence of ring substituents on their inhibitory effectiveness. Arch.
Biochem. Biophys. 121:9-21.
Weisburger, E.K. 1977. Carcinogenicity studies on halogenated hydrocarbons. Environ.
Health Perspect. 21:7-16.
White, A.E., S. Takehisa, E.I. Eger, S. Wolff, and W.C. Stevens. 1979. Sister chromatic
exchanges induced by inhaled anesthetics. Anesthesiology 50:426-430.
Whorton, D., R.M. Krauss, S. Marshall, and T.H. Milby. 1977. Infertility in male pesticide
workers. Lancet 2:1259-1261
Whorton, M.D., and T.H. Milby. 1980. Recovery of testicular function among DBCP
workers. J. Occup. Med. 22:177-179.
William, R.T., ed. 1959. Detoxication Mechanisms: The Metabolism and Detoxication of
Toxicity of Selected Organic Contaminants in Drinking Water 287
Drugs, Toxic Substances and Other Organic Compounds. Second edition. John Wiley &
Sons, New York.
Williams, G.M., and M.F. Laspia. 1979. The detection of various nitrosamines in the
hepatocyte primary culture/DNA repair test. Cancer Lett. (Ireland) 6:199-206. [Chem.
Absts. 91 :50429w, 1979. ]
Windholz, M., S. Budavari, L.Y. Stroumtsos, and M.N. Fertig, eds. 1976. The Merck In-
dex. An Encyclopedia of Chemicals and Drugs. Ninth edition. Merck and Co., Inc.,
Rahway, N.J. 1,313 pp.
Wirtschafter, Z.T., and R. Wolpaw. 1944. A case of nitrobenzene poisoning. Ann. Intern.
Med. 21: 135-141.
Wislocki, P.G., A.W. Wood, R.L. Chang. W. Levin, H. Yagi, O. Hernandez, D.M. lerina,
and A.H. Conney. 1976a. High mutagenicity and toxicity of a dial epoxide derived from
banzo[a]pyrene. Biochem. Biophys. Res. Commun. 68:1006-1012.
Wislocki, P.G., A.W. Wood, R.L. Chang. W. Levin, H.Yagi, O. Hernandez, P.M.
Dansette, D.M. Jerina, and A.H. Conney. 1976b. Mutagenicity and cytotoxicity of
benzo(a)pyrene arene oxides, phenols, quinones, and dihydrodiols in bacterial and mam-
malian cells. Cancer Res. 36:3350-3357.
Wisniewska-Knypl, J.M., J.K. Jabonska, and J.K. Piotrowski. 1975. Effect of repeated ex-
posure to aniline, nitrobenzene, and benzene on liver microsomal metabolism in the rat.
Br. J. Ind. Med. 32:42-48.
Wolfe, M.A., V.K. Rowe, D.D. McCollister, R.L. Hollingsworth, and F. Oyen. 1956. Tox-
icological studies of certain alkylated benzenes and benzene. Experiments on laboratory
animals. AMA Arch. Ind. Health 14:387-398.
Wolfsie, J. H. 1960. Glycolonitrile toxicity. J. Occup . Med. 2:588-590.
Wood, A.W., P.G. Wislocki, R.L. Chang, W. Levin, A.Y.H. Lu, H. Yagi, O. Hernandez,
D. M. lerina, and A. H. Conney. 1976a. Mutagenicity and cytotoxicity of benzo(a)pyrene
benzo-ring epoxides. Cancer Res. 36:3358-3366.
Wood, A.W., W. Levin, A.Y.H. Lu, H. Yagi, O. Hernandez, D.M. Jerina, and A.H.
Conney. 1976b. Metabolism and benzol~x]pyrene and benzo[~]pyrene derivatives to muta-
genic products by highly purified hepatic microsomal enzymes. J. Biol. Chem. 251:
4882-4890.
Wood, A.W., W. Levin, R.L. Chang. H. Yagi, D.R. Thakker, R.E. Lehr, D.M. Jerina, and
A.H. Conney. 1979. Bay-region activation of carcinogenic polycyclic hydrocarbons. Pp.
531-551 in P.W. Jones and P. Leber, eds. Polynuclear Aromatic Hydrocarbons: Third ln-
ternational Symposium on Chemistry and Biology-Carcinogenesis and Mutagenesis. Ann
Arbor Science, Ann Arbor, Mich.
World Health Organization. 1970. European Standards for Drinking-Water. Second edi-
tion. World Health Organization, Geneva, Switzerland. 58 pp.
Wulff, L.M.R., L.A. Emge, and F. Bravo. 1935. Some effects of alpha dinitrophenol on
pregnancy in the white rat. Proc. Soc. Exp. Biol. Med. 32:678-680.
Yamada, Y. 1958. Studies on experimental chronic poisoning with nitrobenzene. Kobe J.
Med. Sci. 4:27-39.
Yang, S.K., J. Deutsch, and H.V. Gelboin. 1978a. Benzo[cx]pyrene metabolism: Activation
and detoxification. Pp. 205-231 in H.V. Gelboin and P.O.P. Ts'o, eds. Polycyclic
Hydrocarbons and Cancer: Environment, Chemistry, and Metabolism. Vol. 1. Academic
Press, New York.
Yang, S. K., P. P. Roller,
and H. V. Gelboin. 1978b. Benzo[a]pyrene metabolism:
Mechanism in the formation of epoxides, phenols, dihydrodiols, and the
7,8-diol-9,10-epoxides. Pp. 285-301 in P.W. Jones and R.I. Freudenthal, volume eds.
Carcinogenesis- Comprehensive Survey. Volume 3. Polynuclear Aromatic Hydrocar
2" DRINKING WATER AND H"LTH
loons: Second International Symposium on Analysis, Chemistry, and Biology. Raven
Press, New York.
Yasuhira, K. 1964. Damage to the thymus and other Iymphoid tissues from
3-methylcholanthrene, and subsequent thymoma production, in mice. Cancer Res.
24:558-569.
Yoshikawa, K., H. Uchino, and H. Kurata. 1976. [In Chinese; English summary.] Studies
on the mutagenicity of hair dye. Bull. Natl. Inst. Hyg. Sci. No. 94:28-32.
Zaebst, D.. and C. Robinson. 1977. Walk-Through Survey Report, Dupont May Plant,
Camden, South Carolina. National Institute for Occupatonal Safety and Health, Cincin-
nati, Ohio. 6 pp.
Zeitoun, M.M. 1959. Nitrobenzene poisoning in infants due to inunction with false bitter al-
mond oil. J. Trop. Pediatr. 5:73-75.
Zeligs, M. 1929. Aniline and nitrobenzene poisoning in infants. Arch. Pediatr. 46:502-506.
