PB 238 908
REVIEW OF THE ENVIRONMENTAL FATE OF SELECTED CHEMICALS
Shirley B. Radding, et al
Stanford Research Institute
Prepared for:
Environmental Protection Agency
10 January 1975
DISTRIBUTED BY:
Krai
National Technical Information Service
U. S. DEPARTMENT OF COMMERCE
5285 Port Royal Road, Springfield Va. 22151
This document has been approved for public release and sale.
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TECHNICAL REPORT DATA
(flax nod IfOaictiaa an Ou ramt btfare axaflcent)
'•BE1mN
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This report has been reviewed by the Office of Toxic Substances,
EPA, and approved for publication. Approval does not signify that
'•t'-">. contents nc 'ssarily reflect the views and policies of the
. Envx^uioiental Piotection Agency, nor does mention of trade names
, or commercial products constitute endorsement or recommendation for
use.
CONTENTS
I INTRODUCTION
II CONCLUSIONS
Ill LITERATURE SEARCH
Source and Subject Area
Results
IV EVALUATION OF DATA AND ESTIMATES OF RATES OF OXIDATION
OF ORGANIC COMPOUNDS IN THE ENVIRONMENT .-
Benzidlne
3,3'-Dicholqrbenzidine
1-Naphthylamlne
8-Proplolactone
4,4'-Methylenebis(2-chloroanlline)
Ethylenimine
Bis(chloromethyl)ether
REFERENCES
10
13
15
17
19
21
25
29
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SECTION I
INTRODUCTION
The Office of Toxic Substances (OTS), U.S. Environmental Protection
Agency (EPA) under Contract No. 68-01-2681 requested .that a literature
search and evaluation of the results be carried out for the following
chemicals: benzidlne and its salts, 3,3'-dichlorobenzidine, a-naphythy-
lamine, (3-propiolactone, 4,4'-methylenebis(2-chloroaniline), ethylenimine,
and bis(chldromethyl)ether. Also at their request, "some intelligent
guessing based on structural analogies for the chemicals" is reported in
cases where very little information was readily available. Although
all of these compounds are Known carcinogens, little is. known on their. •
fate in the environment. A literature search was instituted to determine
what information is available that will help determine potential environ-
mental contamination and fate of these compounds.
The fate of chemicals in the environment depends on a complex
variety of chemical, physical, and biological interactions, few of which
have been studied in sufficient detail to predict the likely rate of
change in concentration of any but the simplest organic compounds. Esti-
mation of the losses of carcinogenic material from manufacturing sites
and its eventual fate in the environment cannot be made on the basis of
published information. SRI was involved in such an effort recently and
was able only to bracket losses as either sl%, S2%, or S3%, on the basis
of the major production method. The ability to bracket losses even very
approximately is possible only for chemicals in large quantity production
6 ' • ' '
(>100 x 10 Ib/year), where considerable Information on the processes,
products, and by-products is readily available. . ' -
In the chemistry of the compounds considered in this study, empha'sis
was placed on searching for or estimating kinetic values for potentially
important pathways of degradation, including free radical oxidation,
photolysis arid hydrolytic reactions. With possibly a few exceptions, no
attempt was made to catalog or note the wide variety of chemical reactions
that these chemicals enter into under "laboratory conditions," inasmuch
as this term is vague and not likely to be of general value in assessing
the environmental fate of these materials.
Iri addition to the literature searches accomplished during the study,
independent calculations for free radical reactivity were made by
Dr. D. G. Hendry, at the request of Dr. T. Mill. In general, the kinetics
literature rarely provided rate data -for conditions close to those found
in the environment.
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SECTION II
CONCLUSIONS
Any attempt to quantify losses of a specific product during manu-
facture or use as an intermediate will require a major effort because of
such factors as the wide variations in: (1) production processes,
(2) product purification, and (3) product intermediate and end uses. The
minimum information re- red for such an undertaking would be detailed
process flow sheets ar , material balances, together with reaction kinetics
data and mixture component vapor pressures and solubilities as a function
of temperature and solution composition. The effectiveness of air,
ww^er. and solid waste pollution control measures at plant sites should
also be examined with some field verification of theoretical losses.
Very few references were found that were of much value in providing
rate data for evaluation, and the need for such reliable data has been
noted for each compound. The general fate of these compounds in the
environment and their toxic effects other than the carcinogenic proper-
ties have received little attention in the literature. Basic physical
data are frequently unavailable and environmental measurements wholly
so. Inferences concerning environmental movement are consequently
fragmentary. At best, we can eliminate several of the compounds as
probable hazards in freshwaters, but can say little with confidence •
regarding their decomposition products or their behavior in saltwaters.
Nor can we fully appraise their potential biotic Impacts, although
several compounds are clearly mutagenlc as well as carcinogenic. Table 1
summarizes our findings.
To efficiently utilize available resources, we recommend the follow-
ing sequence of steps be taken:
.3
Quantify the losses to the environment of the more biologically
significant compounds
Determine the basic physical and chemical, properties as related
to environmental processes (i.e. oxidation, hydrolysis)
Reappraise the potential environmental mobility of each compound
Determine the toxicity, mutagenicity, and teratogenicity of
those which appear most hazardous on the basis of mobility and
magnitude of release.
\
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Tmfclo 1
MT* 1
Raie
H11 gatloa/Hov eaten t
3,3'-Olcblon
aldina b«n*ldla«
1-Kapntbyl- B-f>rvplo- 4,4'HUthylenabia- Kthvl«6- Bls(cblo
aa>toe lactone fa-chtoroaallln»)_ IMJQ* aathyl^t
Re lei
air
Quantity
Fora (gas, aerosol, particle) .
Etwleaa* to wmter • .
Quantity
Porn (solution, particle)
Release to land
Quantity * ' •
Porn (Solution, patrtlcle)
Seasonal variations ton, quantity or locale of release
Tenporal variation of release (continuous, pulsed) '
Source density—poLat (*), diffuse (-)
Recipient bioaes (deciduous foreat, etc.)
Adsorption
HUMUS and other orcavte*—Tea (+). No (-)
Claya
pB d«pwnd*ac« of adsorption—Ya» (+), No (-)
locreaslttc aallaity effects on adsorption—greator adaorptlon (+)
Vaporisation rat**—ait* <*) . Low (->
Solubility in water . .
Chemical reactivity IB tte i m 11 niiBiinl
Sanaltlvlty to solar rain ation—«o sensitivity (-), adsorption ID solar reflon (+)
Identity of d«co»po*itio= product* •
Cneaucal reactivity of dacoapowition prodacta
Behavior ID scrotatc/a*a«robic envlronaenta
Propaaalty for BlcroUaJ oe«rada,tlon—lladtad {+), non« (-)
Transfer •echiBiaaa
Identification
Quantification
Efficiency of uptake . .
Soil/plant*
Soil/animal*
Water/plants
Vater/anlrals
Air/plants
Alr/anlsAla
Propensity to food ckaln transfer*
Biological Effects
Toxlclty ' ' •
Planta
Microbe* • .
Animal*
Toxlcity of )
Planta
Microbes
Animals
Allerceaicity
Care1noienic1ty
Planta
Mutacanlclty
Plaata
Microbe*
Anlamla
Taratocenlclty
Plant
Aniaala
iKpalrBeot of
. Pnyaloloflcal
Bahavloral
Predator
Pependancy of bieZoflcal lapact upon awdlua of occurrefice
• • Some darts, an a««ilaal«
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SECTION III
LITERATURE SEARCH
The abstracts were read and evaluated by a panel of experts, and
full-text copies of articles that seemed to be of Interest were ordered.
A total of approximately 150' articles was ordered.
Sources and Subject Area
Chemical Abstracts from 1941 through 1974 was searched for the
chemical activity of the compounds under study. Biological and environ-
mental information was searched for by using TOXLINE and DIALOG computer-
ized sources; Chemical "'stracts, 1936-1974; Biological Abstracts,
1963-1974; Selected WE ^r Resources Abstracts, 1973-1974; and Current
Contents (Biological u.id Medical Group)', 1973-1974.
To some exte-vt these sources are redundant, but the difficulty of
li-.Liing pertinent references made it necessary to verify the absence or
presence of material by hand searching secondary sources such as Chemical.
.Abstracts. Searching was done (1) by the Chemical Abstract Service
Number for each compound, (2) on synomyms for each compound, and (3) by
such terms as environmental fate, biodegradation, toxicity,. and waste-
water treatment.
In addition to the abstracts searched, references in pertinent
articles were scanned for further information, and selected reviews of
the' chemistry of classes of compounds were examined for pertinent data
or references.
Results
Some references were pulled from all the sources scanned. Those
found can be broken down according to compounds: Benzidine and its
salts, 73; 3,3'-dichlorobenzidine, 11; o-naphthylamine, 55;
8-propiolactone, 64; 4,4'-methylenebis(2-chloroaniline), 9; ethylenlmine,
91; and bis(chlorcmethyl)ether, 18.
6 .
\
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SECTION IV
EVALUATION OP DATA AND ESTIMATES OF RATES OF OXIDATION
OF ORGANIC COMPOUNDS IN THE ENVIRONMENT
Three important modes of oxidation of organic substances in the
environment can be identified. Two apply to the atmosphere, and one
applies to the aqueous phase. On the basis of our knowledge of the
chemistry of polluted and unpolluted air masses, the reactions of both
ozone (0 ) and the hydroxy radical (HOO are important in the atmosphere.
- 3
Our knowledge of the chemistry in the aqueous phase is much more uncer-
tain, but concentration estimates of the ubiquitous peroxy radical RO^:
(where R is H or an organic group) indicate its potential involvement.
Estimates of the half-life (t.) of a substrate (S), assuming dis-
* •
appearance solely by one reaction (for example, reaction with X), can
readily be made from the kinetic relation
- . dS = k [S][X]
/50% —
dS/[S] = /k [X]dt
. nrwl "^ x
100%
under conditions where X is replaced as consumed, resulting.in a constant
or steady-state concentration,
S"HH , ina „ _
100
S50
In 2A [X] = t.
Thus the half-life in the environment for various reactions can be
estimated if the concentration of the oxidizing species (X) and the rate
constant for a reaction are known. Calculated values of half-lives for
the various oxidizing species 'are given in this report for each compound
considered. The values for HO- and 0 in the gas phase are probably
3
accurate to a factor of 3, while the aqueous phase, values for RO • are
only order-of-magnitude estimates.
The half life (t, = In 2/k .[HO-]) assumes [HO-] = 3 x 10~15M
4 HO 67
(an average value estimated by H. Levy ). Values of k were estimated
101
from data reported by W. E. Wilson.
Reactions of ozone are important only in air, where typical concen-
-9
trations are ~2 x 10 M; in aged polluted air the concentration can
reach 10 times -this value. Where NO concentrations are high, such as
near a combustion source, the concentration of O can be essentially zero.
3
For calculation of half-life (t, - In 2/k [o ]) the clean air value was
used. .
The reactions of peroxy radicals (RO •, where R represents any
2
organic radical) are not important in air but-might be important in the
aqueous phase under some conditions. Concentrations of RO • equal to
~10 M are anticipated for water exposed to sunlight containing oxygen
and light-sensitive compounds that photodissociate. Half-lives
(t. ~ln 2/k [RO •]) use this concentration. The uncertainty limits
5 2*
range from 1/10 to 10 times reported values. Estimates for k were
44
based on data given by K. U. Ingold.
In each phase, the important mode of disappearance will be that by
the fastest reaction. The reactions of OH undoubtedly contribute to the
disappearance of all the compounds under study, to the extent that they
occur in the gas phase. Ozone appears to be less important, except in
the case of benzidine. In the aqueous phase, the reactions with RO • are
\
\.
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relatively slow, and other types of reactions, including biological, may
be important.
Although the rates of attack of the various oxidizing species can
be estimated, the .products of the reactions cannot be predicted with any
degree of certainty; only suggestions can be made. Aromatic amines may
initially form nltroso amines, amine oxides, hydroxylamines, ring hydroxyl-
ated products, and ring cleaved products. The other substances are
expected to react by oxidative cleavage reactions. In most cases, all
the products will react at rates comparable to those of the parent
substrates.
Benzidine
H2N,
Benzidine has a molecular weight of 184.23, melts at 128°C, is slightly
soluble in water, but is readily soluble (1 gm/5 ml) in boiling alcohol
or in ether (1 gm/50 ml). Benzidine appears to be resistant to both
physical and biological decomposition, and it is sufficiently volatile
and soluble to be widely dispersed. Consequently, it appears to model
fairly closely the properties of DDT, and should be regarded as a signi-
ficant hazard until physical properties pertinent to appraisals of environ-
mental transfers have been measured. The major uses of benzidine are
based on the conversion of the amino functions to dyestuffs via diazoti-
zation with the nitrite ion and coupling with aromatic acceptors, such
as napthols, and on the high-temperature reaction of the amino groups
with polyurethanes to effect cross-linking, with improvement in physical
properties. Both processes offer the possibility of benzidine being intro-
duced into the environment at high local levels, if precautions are not
taken. No literature was found that was helpful in evaluating this
96
possible hazard. It is interesting to note, however, that Takemura et al.
10
hypothesize that benzidine or 3-naphthylamine are possibly produced in
river water by the reduction of azo-dye wastes by Us or SO in the river
water. According to them it is easily demonstrated chromatographically
that if H S is bubbled for a few minutes through a pure azo dye solution,
aromatic amines are liberated from the azo dye.
Air'transfers cpnstitute a clear danger, as noted by several
puthprs, ' ' ' but benzidine in water is a probable hazard in the '
' 96
vicinity of dye and pigment factories only.
We would expect the principal chemical reactions of benzidine in air
or water to be oxidative degradation via free radical, photochemical, or
enzymlc processes. On the basis of the foregoing estimates of radical
and ozone concentrations in the environment, we estimate that benzidine
has half-lives of 1 day for reaction with either HO- or O3 in the air and
100 days for the reaction with RO radical in water.
We have found no publications concerning the photochemistry of
21
benzidine. By analogy with aniline, benzidine may undergo some cleavage
of NH bond, but this is most likely to occur below the solar cutoff at
15
approximately 300 nm. Benzidine absorbs strongly above 350 nm. Two
papers discussed the diazotization of waste waters containing .benzidine, -
27,38
as a means of removing the amine.
Experimental data on the rates of reaction of benzidine with radicals
and ozone and on photochemical reactions under environmentally realistic
conditions are not available. They would be of value for more reliable
estimates of half-lives. Products of such reactions and their toxicity
should also be determined.
Decomposition of benzidine in water is probably predominately
biologically mediated. However, it is resistant to biological decomposi-
70
tion and can be expected to persist in the environment.
11
\
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BenzidiTie is sparingly soluble in water, but considerably more so
45
than DDT and Is readily soluble in organic solvents. This suggests
that it may readily move through food chains.
No data are available on its movement through soils, although Lahav
.and Anderson noted changes in benzidine-soil mixtures during freeze-thaw
65
cycles, which might shed light on benzidine's behavior in soils, although
the implications are not clear. Benzldine does react readily with plant
products, however, which suggests that it would quickly adsorb to either .
32
suspended materials in waters or humlc materials in spils. Conse-
quently, we can expect fairly rapid immobilization of much of the environ-
mental benzldlne in soils or sediments. We have no assurance, however,
that biologically significant amounts will not be desorbed in salt waters
or the guts of bottom-feeding fishes.
Most studies on the toxic effect of benzldine have been related to
its carcinogenic activity. It is well known that the incidence of
bladder tumors among workers exposed to benzidine is high and that such
workers show increased levels of 8-glucuronidase in their blood. In
addition to producing bladder tumors, benzldine is reported to induce
81 79
hepatic tumors in mice, intestinal tumors in rats, and breast cancer.
40
in female rats. -
Little is known about the 'oxic effects of benzldlne other than its.
carcinogenic activity. Studies by Christopher and Jalram showed that
23
benzidine can be acutely toxic to rats when administered per os. One
gram of benzldlne mixed'with an unspecified amount of food and fed to six
rats killed all the rats within 38 days; the first rat died on day 34.
Post-mortem examination of the tissues showed epicardial petichlal,
hemorrhagic spots and venous congestion.
Rats given a sublethal dose of 100 mg/kg showed leucocytosis,
erythrocytopenia, thrombocytopenla and reduced catalase and peroxidase
12
91
activity after 8 hours. Chronic exposure to benzldine produced exces-
sive proliferation of bile capillaries, an increase in cystlne and serlne
in the liver, mild nephrosis, and a decrease in alkaline phosphatase in
77
the liver.
Cutaneous tests, performed in sensitized patients, showed that
85
benzidine can produce allergic reactions. In this study, a number of
amino and nltro compounds related to benzidine were evaluated. It was
found that the substituent group exerts a decisive influence on the
ailergenlc properties of aromatic diamines. Allergenlcity was intensified
by the presence of NH groups; however, NO groups diminished the effect,
. and CH groups slightly weakened it.
3
The noncarcinogenic effects of benzidine in nonmammalian species
are even less well known. When injected into chick embryos, benzidine
prevented neural tube closure and retarded embryonic development and
74
tissue transformation. Trout, bluegill sunfish, and larval- lamprey
died or showed signs of severe distress when exposed to 5 rag/jt benzidine
5
for 14 hours.
According to Ames, benzidine is not only carcinogenic but also
mutagenlc, causing frame shifts in Salmonella typhimurium histidine mutant.
3.3'-Dicholorbenzldine
Cl
Cl
3, 3'-Dichlorobenzidine (DCB) has. a molecular weight of 253.1, melts at
Q
132-3 C, is insoluble 'in water, and is readily soluble in ethanol,
benzene, and glacial acetic acid. It Is slightly soluble in hydrochloric
acid. Its.major uses appear to be as a dye and pigment intermediate and
as a curing agent for polyurethanes.
13
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DCB superficially appears to be a relatively immobile compound, but
it is disturbingly similar to DDT. This suggests that it may be concen-
trated in food chains. It should be regarded as a potentially hazardous-
46
pollutant. Like DDT, DCB is readily soluble in organic solvents, is
" ' 8T
sparingly soluble in water, and should accumulate in organisms. DCB
is packaged and distributed as a powder, suggesting that it is minimally
volatile. However, this is also true of DDT, which appears to have moved
102
extensively through the atmosphere. Its affinity for suspended par-
ticulates in water and for colloids in soils is not clear, but its basic
nature suggests that it -ay be fairly tightly bound to humlc materials
in soils. Soils may c> .sequently be moderate-to-long-term reservoirs.
Because of the haloge:. substitution, it Is likely the DCB has a lesser
rate of biodegradation than benzidine. It may be present in the waste
"*:re"is from ( tnts where it is produced or used for pigment or dye
manufacture, but the amount getting into the environment from these
sources is believed to be quite small. Since less than stoichoimetric
amounts are usually used, unreacted dlamine is not normally present in
the cured polyurethane elastomers made from dichlorobenzidlne. However,
the curing agents are often melted before mixing into the elastomer
formulations, so dichlorobenzidlne could possibly find its way into the
waste streams from plants where it is being used as a curing agent.
On balance, the paucity of data and the similarities to DDT indicate
that high priority should be given to a more thorough appraisal of environ-
mental release. If release levels are found to be high, studies should
be undertaken focusing on atmospheric and aqueous transport, persistence
in the soil, and propensity to move through food chains. Changes in •
toxlcity and mobility upon entry into salt waters .appear probable and
likewise warrant attention (cf. Ref. 3). No literature are uncovered
concerning the relevant chemical reactions. We estimate the half-lives
14
for reactions with HO radicals, O , and RO radical, in their respective
3 2
phases, to be 1, 1-10, and 100 days, respectively. The uv spectrum is
similar to that of benzidine, but Its photochemistry is unknown.
That DCB can cause cancer of the bladder is well known. Less well
defined are its effects other than as a carcinogen. No information on
91
its toxicity was found in the Merck Index, Volume II of Industrial
76 93
Hygiene and Toxicology, or the Handbook of Toxicology, Volume 1.
The compound is not listed in Volumes 1, 3, or 5 of the Water Quality
32.33.34 71
Criteria Data Book ' _' or in Water Quality Criteria.
In embryonic kidney tissue, DCB produced a variety of morphological
86
changes after injection of 8 to 10 mg into the embryos. Sololmskaya
reported that DCB activates monoamine oxidase and histaminase In rats;
92
however, after repeated doses, the compound inhibits these enzymes.
In monkeys DCB is excreted in the urine almost unchanged, in contrast
56
to benzidine, most of which occurs as various metabolites. In rats,
however, DCB undergoes considerable biotransformation. Four metabolites,
including benzidine, were identified in rat urine after ingestion of either
2
a single large dose or several small doses over a prolonged period.
Its classification as a carcinogen, in addition to the paucity of
information on other effects on biological systems, suggests that DCB
requires considerably more study before environmental limits can be set.
1-Naphthylamine
1-Naphthylamine has a molecular weight of 143.2 and a melting point
o o
of 50 C; it is insoluble in water (at 25 C), readily soluble in ether and
other solvents, and volatile.
15 .
\
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This amine is used as an intermediate for dyes and herbicides and
directly as an antioxidant in oils. Extensive listings in Chemical
Abstracts on naphthylamine failed to reveal much Information relevant to
its environmental chemistry.
We estimate the. half-life of 1-naphthylamlne towards HO radical,
O , and RO radical, in their respective phases, to be <1; 1-10, and
~100 days,, respectively.
Like benzidine, 1-naphthylamine absorbs light in the solar region
out to nearly 350 nm; however, no evidence indicates that this absorption
.leads to significant photochemistry. Ashkinazi reported .that sensitized
photoxidatlon with chlorophyll leads to colored intermediates with free
6
electron spin.
1-Naphthylamine is potentially a significant, generalized hazard in
the environment. This is suggested by its occurrence as a derivative of
azo-dye wastes in anaerobic waters and its heat tolerance. ' As a
60,61,62,63
substance that dissolves readily in organic solvents, it has
a high probability of movement through aquatic food chains, although this
uptake may be particularly sensitive to pH and salinity. The data bearing
on this are only suggestive, however, and were available only as abstracts
(cf. Refs. 60,61,62,63,81).
It is probable that moveme it through soils will be minimal if the
substance is introduced at the surface rather than at deeper layers. As
a weak base, 1-naphthylamlne can be expected to combine with humic acids
possibly being immobilized. • .* . •
. Little information was found on the biological effect of
1-naphthylamine except for its role as a carcinogen. Early work performed
93
by Pitini reported in the Handbook of Toxicology results in lethal dose
estimates of 3OO to 400 mg/kg for rabbits and dogs via subcutaneous
administration. Applegate reported that trout, bluegill sunflsh, and
16
larval lamprey did hot survive exposure to 5 mg/£ of 1-naphthylamine in
water for more than 12 hours.
The compound is reported to affect various biochemical and physio-
logical processes in laboratory animals. Increases In aryl hydrocarbon
.hydroxylase were observed in rat liver, lung, and kidney homogenates and
3
microsome preparations. A well-known effect of 1-naphthylamine and
almost all aromatic nltro and amine compounds is .its ability to produce
methemoglobenimia.
1-Naphthylamine does not appear to affect biological systems as
much as other compounds of the same class. .When equal doses of 1- and ;
2-naphthylamine were administered repeatedly to mice, 1-naphthylamine
produced focal adiposity in the liver, whereas 2-naphthylamine caused
59 .
diffused hyperplasia and edematous growth. 1-Naphthylamihe did not
inhibit incorporation of amino acids into proteins of rat liver slices;
however, marked inhibition was produced by 2-aminofluorene,
2-acetylaminofluorene, and 2-naphthylamine.
1-Naphthylaraine as well as 2-haphthylamine is oxidized by a mixed-
function amine oxidase. This enzyme was isolated from pig liver micro-
105
somes by Ziegler and coworkers. * - The compound is metabolized to various
18
products such as unconjugated N-(l-naphthyl)hydroxylamine and 1-amino-
24
2-naphthylglucoslduronide. N-(l-Naphthyl)hydroxylamine is a more
12
potent carcinogenic agent than 1-naphthylamlne.
Its high toxiclty to fish, as Indicated by the preliminary study of
Applegate and co-workers, suggests that more comprehensive studies should
be performed to determine maximum acceptable concentrations for natural
water bodies with respect to protection of aquatic species if it is
released in significant amounts into the environment.
g-Propiolactone
8-Propiolactone (BPL) has a molecular weight of 72.06, melts at
o o - -
-33.4 C, boils at 162 C with decomposition, and is soluble in water, oils,
'••• ' .• - • . -17
-------
or physiological media. It has a high chemical reactivity and readily
hydrolyzes in water.
This reactive lactone was formerly used as a sterilant, but currently
Its use is limited to production of acrylic acid and its esters and
polymers. Despite the high reactivity toward water, alcohols, amines,
and other nucleophllic agents, we have been unable to find recent data
on the kinetics of the hydrolysis of BPL from which to evaluate the half-
life of the lactone under environmental conditions. A further check of
older literature and the holdings of the Chemical Kinetics Center at the
National Bureau of Stant1 is (under Dr. David Garvin) might be worthwhile.
We estimate that tre half-lives of BPL toward HO radical, 0 , and
3
RO radical, In-their appropriate phases, are 1-10 days, >1 year, and
>1 year, respectively. These results, even in the absence of hydrolytic
data, fairly certainly indicate that radical oxidation or ozonization
are not important pathways for degradation in the environment.
In transit through the air, however, BPL may be a significant hazard,
although even here it appears that 11s reactivity would result in localiza-
tion of the hazard. It can be. expected to predominantly decompose to
ethylene and carbon dioxide, both essentially harmless compounds. Ethylene
is a plant hormone that affects flower and fruit development; the quanti-
ties produced by this pathway should be a trivial component of the anthro-
pogenic release of ethylene to the environment. The volatility of BPL
Is sufficient, however, to suggest that atmospheric dispersal would be
,50,54
rapid.
BPL has no significant absorption above 270 nm; therefore we would
not expect this lactone to exhibit any significant photochemistry in the
solar region. No citations were found concerning the occurrence or disposal
of BPL in waste water. It reacts readily with biological material,
so unhydrolyzed material should be rapidly adsorbed to suspended particu-
lates, particularly in eutrophic waters. Upon entry into salt waters,
18
it apparently reacts with chloride ions to form 3-chloroproplonic acid,
50
which seemingly is far less hazardous than BPL. Alterations of its
activity in fresh waters of varying acidity may occur, but the limited
data available suggest that such Interactions would be minimal in the
28
vicinity of neutrality (pH 7-8).
In view of its reactivity and rapidity of hydrolysis, it is unlikely
that BPL will be a significant hazard if released to soils or transported
to them through the air. Nor is it likely to be accumulated in biological
materials and transferred through food chains.
BPL was commonly used in cold sterilization of blood, plasma, and
various tissues for grafts. -Its viricldal, bacteriocidal, carcinogenic,
and mutagenic properties are relatively well known. A large percentage
of the published articles pertaining to the biological action of BPL
have been devoted to its use as a sterilant and its effects on tissues
in vitro. Most of the other articles have concerned carcinogenesis and
mutagenesis. No information was found concerning the toxicity of BPL to
plants or to terrestrial and aquatic wildlife.
BPL is highly toxic to laboratory animals. In rats the estimated
oral LD is 50-100 mg/kg; when the substance is administered intraperi-
tonially, the LD is about the same. In guinea pigs the LD is less
50 5O
than 5 ml/kg for application to the skin.
Its high toxicity to viruses, bacteria, and laboratory mammals, as
well as its relatively high solubility in water, suggests that BPL could
be highly toxic to aquatic life.
4,4'-Methylenebi3(2-chloroaniline)
Cl Cl
»2*(o} -CV
This compound has a molecular weight of 267 and a melting point of H0"c.
19
\
-------
The only commercial' use of this amine is as curing agent for
polyurethanes. Since less than stolchlometric amounts are usually used,
unreacted dlamine ±s not normally present in the cured polyethane
elastomers made from 4,4'-methyl_enebis(2-chloroaniline). However, the
diamine is often melted before mixing into the elastomer formulations,
so it could possibly find its way into the waste streams from plants
where it is being used as a curing agent.
No Information was uncovered concerning spectral or photochemical
properties. By analogy the compound.should behave much like
dlchlorobenzidine. We have estimated the half-lives of this amine
toward HO radical, O , and HO radical in the appropriate phase to be
similar to those of 3,3'-dichlorobenzldine: <1, 1-10, and ~10p days,
respectively. • •
4,4'-Methylenebis(2-chloroaniline)(MOCA) resembles DDT both
structually and physically. .It is almost insoluble in water, but soluble
47
in organic solvents, and apparently it has a low vapor pressure. The
69
most pertinent evaluation of its hazards, that of Linen et al. noted
that absorption through the skin is more Important than inhalation in
industrial settings, but this does not preclude the possibility that
inhalation is the dominant mode of uptake in nonlndustrial settings.
Sound appraisals of the propensity of MOCA to move through food
chains, to reside in soils, or to move through water are not possible
with the present data. In view of the experience with DOT and the
similarity of the two compounds, however, caution is warranted. High
priority should be given to appraisals of air and water transport, the
potential for food-chain accumulation, and residence times in soils if
the release rate to the environment proves to be significant.
The status of.MOCA as a carcinogen is in question. Grundmann and
Stelnhoff reported that rats maintained on a low protein diet containing
0.1% MOCA developed lung, liver, brain, and mammary tumors. ' The
survival of treated animals was less than that of controls.
On the other hand, Linch and coworkers did not* find any clinical
evidence of malignancy in dogs during the 'third year of a 6-year MOCA
69
feeding study; the dosage was not specified. These authors also stated
that surveillance of workers exposed to MOCA for 16 years showed no
symptoms of toxic effect.
The acute toxicity of MOCA, administered orally, to mice or rats,
is relatively low. The LD is 880 rag/kg and 21OO mg/kg in mice and
57 5°
rats, respectively. .The toxicity of MOCA to nonmammallan organisms and
plants is unknown.
The U.S. FDA has disallowed MOCA as a component of food-contacting
adhesive and polyurethane. resins, basing this decision on the work of. /
Grundmann and'Stelnhoff. The status of MOCA as a carcinogen should be
reevaluated, and its toxicity to wildlife, relative to amounts that occur
in the environment, -should be determined.
Ethylenimine
NH
we/ \c
Ethylenimine has a molecular weight of 43.07 and a boiling point of
o
56-7 C; it is miscible with water, flammable, and readily polymerizable.
It is used principally for treatment of paper: to a lesser extent, it is
used in high-energy fuels and as a chemotherapeutic agent.
It is volatile, highly toxic, flammable, and mutagenic in plants.
Two observations suggest that it is stable in the air. First, it is one
of the products of the photodecompo'sitlon of methylamine, suggesting that
72
It is Itself stable. Second, it retains its biological activity at
21
K
-------
g • •
room temperature for extended periods. Consequently, it is probably
capable of broad aerial dispersal, although one report suggests it
39
undergoes eventual photo-decomposition.
Hydrolysis of ethyleniraine has been studied in acidic and basic
o 19
aqueous systems near 25 C. From .the data of Bunnett and McDonald we
estimated the half-life in 1 M perchloric acid to be about 160 hours at
29.5 C. Pomonis and coworkers measured the rate in nearly neutral
o 79
phosphate buffers at 27 C. The rate of hydrolysis of ethylenimine at
2_
pH 7, with 0.2 M HPO , gives an estimated half-life of about 700
minutes; with 0.1 M HPO, ~, the half-life increases to 1300 minutes;
2-
extrapolating to zero H j at pH 7, the estimated half-life is over
2500 minutes or 41 hourj. At pH 8, the'half-life would be about ten times
longer if the same mechanism for hydrolysis was important.
lu the gas phase the half^lives of ethylenimine for reactions with
HO radical and O are estimated to be <1 day and >1 year, respectively;
3
in water, reaction with RO radical has an estimated half-life of >1 year.
Thus we conclude that the major pathway for chemical degradation will be
via hydrolytic decompositions in water or possibly by moisture in the
air. Ethylenimine does not absorb in the solar uv region; therefore we
would not expect any significant photochemical reaction.
There is no solid basis for' inference concerning the propensity of
ethylenimine to move through and be concentrated in food chains. However,
the possibility that it does so is strong, if all the foregoing supposi-
tions regarding aqueous hazards are correct.
Direct hazard to man potentially extends to impairment of reproduc-
tive ability, although the concentrations.used in the pertinent experi-
ments with rats were far in excess of any to be expected outside an
103
industrial setting.
22
Direct effects on plants are frequently reported to be beneficial,
although we question the generality of beneficial mutations. The species
and families in which mutagenic action has been reported are:
87
Graineae:
Barley
80
Wheat
Legumlnosaea: Kidney bean
100
Bean, common
„ 68
Pea
10
Solanaceae:
Malvaceae:
Cotton
30
Compositae: Cosmos, Zinnia, Crysanthemum
35
Oleaceae:
Red ash
84
Mutagenic effects have been observed in a number of plants, includ-
ing tomato, cotton, wheat, lupine, barley, kidney bean, and ash. In
tomato, treatment of seeds increased germination, flowering, plant
height, and pollen fertility. .The mutation frequency was higher in the
M generation than in the M generation. In cotton, the compound produced
mutants with larger cotton balls, thicker fibers, greater branching, and
longer growing period. Barley mutants were of higher protein content and
larger kernels. Exposure of pea seeds to ethylenimine inhibited plant
growth and development.
Ethylenimine, administered orally or by percutaneous absorption,
is highly toxic to laboratory mammals. It is extremely toxic when
inhaled. The compound has not been investigated extensively for carcino-
genecity. As a mutagen, it is relatively potent, and it has been used
to treat seeds of commercially Important plants to produce high-yield
mutants.
23
\
-------
According to Sutton, the LD is 15 mg/kg in rats via oral
95
admlnstration. As little as 0.014 ml/kg applied to the skin of the
guinea pig produced severe skin necrosis, and as little as O.OO5 ml
applied to the eye of the rabbit resulted, in severe corneal damage and
death. The LD in mice exposed to ethylenlmine in air was reported as
3.93 mg/i. Death after inhalation is usually delayed. Irritation to
the eyes and nasal passages is a frequent observation.
Although human subjects were not able to detect the presence of
3 •
0.05 mg/M of ethylenimine in air, EEG measurements showed desynchroniza-
14
tion of the or-rhythm in the cerebral cortex. Berzina also found that
exposure of rats to 0.001, 0.01, and 6.1 mg/M of ethylenimine for 95
days resulted in decreases in blood nucleic acid levels at 0.01 and
3 3 13'
0.1 mg/M , but not at 0.001 mg/M . He hypothesized that the reduction
of nucleic acids in blood was due to denaturation by ethylenimine.
Ethylenimine is reported to affect mammalian endocrine systems.
One- to 8-day exposure to 0.6 to 0,8 (ig/1 decreased thyroid activity and
increased slightly the weight coefficients of the hypophysis and adrenal
glands. : Ultramicroscopic examination of the adrenal medulla, following
a single injection of ethylenimine, showed endothelial rupture of the
medullary blood vessels 2 hours after the Injection, followed by complete
26
arrest of medullary circulation 8 to 9 hours after the injection.
Inhalation of the compound results in delayed lung injury with
congestion, 'edema, and hemorrhage. Kidney damage is almost always
observed after absorption of ethylenimine. Proteinuria, hematuria, and
elevated blood urea are frequently observed.
Effects of ethylenimine on renal function have been studied exten-
sively by James and Jackson. ' ' The compound and certain of its
derivatives cause intense and prolonged diuresis in rats.
24
In rats, Zaeva and coworkers found that exposure for 1.5 months to
19 mg/M produced testicular atrophy, deformation of spermatozoa, and
103
decreased sperm mobility. Pregnant rats exposed to 0.007-0.01 mg/jj
of ethylenimine in air for 20 days produced high embryo mortality.
Ethylenimine has been reported to produce chromosomal abberations
in human cell cultures, ' and hamster cell cultures. Chromosomal
abberations have also been observed in bone marrow cells of rats exposed
to 0.0006 to 0.024 mg/l in air for 2 to 30 days.
The effect of ethylenimine, on terrestrial and aquatic wildlife is
not known. It is unlikely that terrestrial mammals, and perhaps avion
species, will respond differently to ethylenimine than laboratory
species. The response of aquatic wildlife may be different because of
differences in environment. It is likely, however, that the compound may
be more toxic to aquatic organisms than to terrestrial forms if it is
stable in water; aquatic life forms are generally less tolerant .of
chemical pollutants than mammalian organisms.
Bi s (chl oromethyl ) ether
C1CH OCH Cl •
22
Bis(chloromethyl)ether (BCME) has a molecular weight of 115 and a
boiling point of 1O4 C; it is misclble with ethanol, ether, and other
organic solvents.
This ether is used only as an intermediate in preparation of textile
aids and anion exchange resins.
The high reactivity of BCME in alkylation reactions .is also reflected
73
in a high solvolytic reactivity in aqueous systems. A report on the
relative reactivity of BCME to chloromethyl methyl ether (CME), which is
1:5000 in MeOH/H O, also Included some data of Van Durren on the
solvolysis of BCME in OS? /HO at O°C with a rate constant 1, ~0. 35. rain"1,
25
-------
which is equivalent to a 2-minute half-life.' However, CME solvolyzes
o -3 -1
in.i-PrCH at 0 C with a rate constant of 7.4 • 10 sec or 1.6-minute
half-life. Assuming that BCME solvolyzes at 2 • 10 of this rate at
0°C or 1.5 • 10~ sec" , the half-life would be 1300 hours at 0°C or
o
about 200 hours at 25 C. This estimate is at least consistent with obser-
vations of Collier (private communication quoted in the Nichols and
Merritt paper) that CME has a half-life of 6 minutes in moist air,
whereas BCME is stable for this time period.
We estimate that BCME has half-lives toward HO radical, O , and RO
3 2
radical in corresponding hases of <1 day, >1 year, and >1 year,
respectively. In'aqueoi , systems it is clear that solvolysis (hydrolysis)
will far outweight radical oxidation as a significant route for removal
of BCME in the environment. No photochemistry was noted in Chemical •
/.. '- jt citatit.is on BCME; there is little or no absorption in the solar
region.
55 37
Two important papers by Kallos and Frankel described the forma-
tion of BCME from the reaction of HCHO and HC1 in the air in low ppb
levels when both HCHO and HC1 are present in 500-10,000 ppm. A paper
by Collier described detection of BCME in the environment at ppb levels
25
using mass spectrometry.
49 97
BCME is highly volatile and is moderately stable in humid air,
and significant atmospheric movement should be expected. It is unlikely,
however, that its dispersal will ever be more than a local problem. Even
though fractions of any release might reasonably be expected .to travel
as much as 200 miles, dilution to unmeasurable levels should occur within
a few miles or tens of miles at most. In very humid climates, such as
the Pacific Northwest, the high humidity and frequent rains can be expected
to enhance this localization, although the intensity of the enhancement
may be highly variable (cf. Ref. 37). Optimal dispersal should occur in
cool, humid regions, such as southern Canada and New England. The hazard
26
might consequently be in the order: New England Southeastern United
States >Pacific Northwest >Southwest. Formation of BCME in the atmos-
phere by reaction of formaldehyde and hydrogen chloride is improbable
55
at atmospheric concentrations.
In contrast, BCME is extremely unstable in water. It decomposes
with a half-life of 10-40 seconds. Fortunately, it fails to move from
water to air in measurable amounts prior to decomposition, even within
small reaction vessels where the ratio of surface area to volume is
55
considerably larger than in natural waters. It is probable that half-
lives in soils or organisms are comparably short and that food-chain
transfers are consequently nonexistent.
BCME is very irritating to the eyes and skin. When it is inhaled,
death can occur due to lung edema or secondary pneumonia. Hake and Roe,
reporting unpublished data from the Biochemical Research Laboratory
(Dow Chemical Company), stated that l.Og/kg, fed to rats caused death,
43
whereas 0.3g/kg allowed survival. The estimated LD by oral adminis-
5O
tratlon is 0.5g/kg. Severe eye irritation and necrosis developed when
a 1% solution in ethylene glycol was placed in the eyes of rabbits.
Rabbit skin tests with the full strength material produced severe
hyperemia, edema, and even complete skin destruction.
Exposure to 2000 ppm of the vapor for over 30 minutes can be lethal;
so can exposure to 100 ppm for 4 hours. These conclusions are based on
studies (Dow Chemical Company) with rats. Death due to inhalation of the
vapors is often delayed, occurring several days to several weeks after
exposure.
Chloromethyl ether concentrations high enough to be acutely toxic to
wildlife are unlikely to be found in the environment, unless an accidental
spill occurs. The highly irritating vapors would probably be avoided by
mobile terrestrial organisms. The toxiclty to fish and other aquatic
27
\
\
-------
organisms is not known. By direct contact or by contact with decomposi-
tion products such as chlorine, the toxlcity could be considerable.
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