Vol. 21, No. 6
Books and Publications
Books from the World Health Organization
Ether, Environmental Health Criteria No. 206
1998, vi + 101 pages (available in English; French and
Spanish in preparation), ISBN 92 4 120878 3, CHF 20.-/USD 18.50; In
developing countries: CHF 14, Order no. 1100878. WH
1998, xix + 199 pages (English with summaries in French
and Spanish), ISBN 92 4 157206 X, CHF 42./USD 37.80; In developing countries:
CHF 29.40, Order no. 1160206. WHO Distribution and Sales, CH-1211 Geneva
27, Switzerland; E-mail: Publications@who.ch; Tel.: +41 22 791 24 76;
Fax: +41 22 791 48 57.
This book evaluates the risks to human health and the
environment posed by exposure to methyl tertiary-butyl ether
(MTBE). Used almost exclusively as a fuel additive, MTBE is blended
with gasoline to provide both octane enhancement and an increase in
oxygen content. MTBE currently numbers among the 50 chemicals produced
in the highest volume worldwide. Production and use are expected to
increase, particularly in countries where oxygenated or reformulated
gasoline is required in national programs aimed at reducing ambient
air levels of carbon monoxide and ozone or benzene and other volatile
A summary of sources of human and environmental exposure
is followed by an assessment of what is known about the chemical's environmental
behavior and fate. Studies demonstrate that, after discharge into air,
MTBE largely remains in the air, with smaller amounts entering soil
and water. Although atmospheric MTBE can partition into rain, data indicate
that atmospheric formation by hydroxyl radicals is a more important
pathway of removal.
Concerning environmental levels and human exposure, evaporative
emissions from oxygenated gasoline are identified as the main source
of exposure for the general population. Widespread exposure via inhalation
is noted to occur during time spent at service stations, while driving
cars, in public parking garages, and in homes with attached garages.
The report also cites data on exposure levels obtained in numerous studies
of urban air, in facilities where MTBE is manufactured or blended, and
in such occupational settings as service stations, garages, and the
transportation of neat MTBE and fuel mixtures through pipelines, barges,
railroad cars, and trucks.
A review of the kinetics and metabolism of MTBE draws
on toxicokinetic data derived from controlled studies in healthy adult
volunteers and in occupationally exposed workers. Data indicate that
MTBE is rapidly absorbed into the circulation following inhalation.
In rodents, the compound is likewise rapidly absorbed and distributed
following exposure by both inhalation and oral routes.
From studies in laboratory animals, the report identifies
the principal signs of intoxication as depression of the central nervous
system, ataxia, and labored respiration. Most effects on the central
nervous system are transient. From the few studies available, the report
concludes that MTBE is moderately irritating to the skin and eyes and
induces slight to severe respiratory irritation. Repeated exposure results
primarily in increases in organ weights and histopathological effects
in the kidneys of rats and the liver of mice. The report found no evidence
of adverse effects on reproduction, genotoxicity, or mutagenicity. Although
limited carcinogenicity studies showed significant increases in tumor
incidence, the report judged these findings inconclusive and thus inadequate
to support an assessment of carcinogenic risk in humans.
An evaluation of health effects in humans gives major
attention to several recent "outbreaks" of health complaints
in the United States that occurred shortly after the introduction of
MTBEblended gasoline. Symptoms most widely reported by consumers include
headache, eye and nose irritation, cough, nausea, dizziness, and disorientation.
The report also draws on findings from epidemiological studies of occupationally
exposed workers and from experimental studies of volunteers exposed
in inhalation chambers. Based on this evaluation, the report concludes
that MTBE alone, under common conditions of inhalation exposure,
is not likely to induce acute adverse health effects in the general
population. In making this conclusion, the report also notes that the
potential effects of mixtures of gasoline and MTBE, as well as
the manner in which most people are exposed to MTBE via oxygenated
fuels, have not been examined experimentally or in prospective epidemiological
Health Criteria No. 207
1998, xviii + 159 pages (English with summaries in French
and Spanish), ISBN 92 4 157207 8, CHF 36./USD 32.40; In developing countries:
CHF 25.20, Order no. 1160207.
This book evaluates the risks to human health and the
environment posed by exposure to acetone. Acetone is widely used as
an intermediate in chemical production and as a solvent for resins,
paints, inks, varnishes and lacquers, and in adhesives, thinners, and
cleanup products. Pharmaceutical applications include use as an intermediate
and solvent for drugs, vitamins, and cosmetics. Acetone is also used
in food processing as an extraction solvent for oils and fats and as
a precipitation agent in the purification of starches and sugars.
A discussion of sources of human and environmental exposure
covers both natural and anthropogenic sources. In the mammalian body,
studies show that acetone is formed endogenously from fatty acid oxidation,
is found as a natural metabolic component in blood, urine, and human
breath, and is exhaled. Acetone has been detected in a variety of plants
and foods and is emitted, in vapor form, from several tree species.
Acetone also occurs naturally as a biodegradation product of sewage,
solid wastes, and alcohols, and as an oxidation product of humic substances.
Concerning manmade sources of emissions, the report identifies the most
important sources in wastewater discharges from many industries, leaching
from industrial and municipal landfills, and evaporation of acetone
solvent from coating products such as paints, cleaners, varnishes, and
inks. Acetone may also be emitted from the combustion of wood and in
exhaust from automobile, diesel, and turbine engines.
A review of data on environmental behavior and fate cites
evidence from several studies of acetone levels detected in air, water,
soil, and biological analyses. Studies indicate that atmospheric acetone
is degraded by a combination of photolyis and reaction with hydroxyl
radicals. Acetone is readily biodegradable in soil and water. A discussion
of kinetics and metabolism draws on extensive data from absorption and
tissue distribution studies, radiolabeled metabolic and kinetic studies,
and studies of elimination and excretion. Abundant evidence shows that
acetone is rapidly absorbed via the respiratory and gastrointestinal
tracts and mainly distributed to nonadipose tissues. Under normal circumstances,
metabolism is the predominant route of elimination. Studies in humans
confirm the importance of such variables as diet, exercise, and alcohol
consumption as factors affecting kinetics.
A review of toxicity studies in laboratory mammals and
in vitro test systems concludes that acetone is only mildly toxic
to the liver, unless physiological processes are compromised, as in
diabetes mellitus. Some adverse effects on development and reproductive
function have been reported. One of the major adverse effects identified
is acetone's ability to potentiate the toxicity of other chemicals.
Extensive studies on the mechanisms of toxic action help elucidate the
possible mechanisms by which acetone enhances the neurotoxicity of ethanol.
A section on health effects in humans evaluates findings
from numerous case reports of accidental or intentional poisoning, studies
conducted in healthy volunteers, and studies of occupationally exposed
workers. The most commonly reported effects include irritation to the
nose, eyes, throat, and trachea. Studies also show that acetone can
produce neurobehavioral and other changes, including headache, dizziness,
confusion and, at high vapor concentrations, central nervous system
depression and narcosis. The report found no evidence that acetone is
either a skin or a respiratory tract sensitizer. Human studies confirm
the ability of acetone to potentiate, and in some instances antagonize,
the toxic effects of other chemicals. Those at greatest risk include
diabetics, alcoholics, and those undergoing prolonged fasting. The report
found no evidence that acetone is genotoxic or carcinogenic.
Concerning effects on the environment, the report concludes
that acetone, even in the case of accidental spills, is unlikely to
have a major or lasting adverse effect on the ecosystem.
WHO Monographs on Selected
Medicinal Plants, Volume 1
1999, v + 289 pages (available in English; French in preparation),
ISBN 92 4 154517 8, CHF 92./USD 82.80; In developing countries: CHF
64.40, Order no. 1150460.
This book provides a collection of 28 monographs covering
the quality control and traditional and clinical uses of selected medicinal
plants. Plants were selected for inclusion on the basis of their widespread
use, particularly in countries that rely heavily on medicinal plants
to meet primary health care needs. Monographs are provided for a number
of medicines traditionally used to treat such common complaints as diarrhea,
constipation, headache, appetite loss, sleep disorders, fatigue, and
mild respiratory, gastrointestinal, and skin disorders. Additional medical
applications assessed range from the lipid-lowering potential of garlic
powder preparations, through the possible antiplasmodial activity of
Fructus Bruceae, to the role of curcumin in promoting peptic ulcer healing
and reducing the associated abdominal pain.
In preparing and publishing these monographs, WHO aims
to encourage standardized scientific approaches to ensuring the safety,
quality, and efficacy of medicinal plants and their products. The monographs
are also intended to promote international harmonization in the quality
control and use of herbal medicines and to serve as models for the development
of national formularies. Draft monographs were finalized following review
by over 100 experts in 40 countries. Some 1 400 references to the literature
Each monograph follows a standard format, with information
presented in two parts. The first gives pharmacopoeial summaries for
quality assurance, botanical features, distribution, identity tests,
purity requirements, chemical assays, and active or major chemical constituents.
A section on definition provides the Latin binomial pharmacopoeial name,
the most important criterion in quality assurance. Latin pharmacopoeial
synonyms and vernacular names, listed in the section on synonyms and
selected vernacular names, are those names used in commerce or by local
The second part of each monograph begins with a list of dosage forms
and of medicinal uses categorized as uses supported by clinical data,
uses described in pharmacopoeias and in traditional systems of medicine,
and uses described in folk medicine, but not yet supported by experimental
or clinical data. Each monograph also includes an extensive review of
available data on experimental and clinical pharmacology, followed by
information on contraindications, such as sensitivity or allergy, warnings
or precautions (particularly in such special groups as pregnant and
breastfeeding women), adverse reactions, and dosage. A list of references
concludes the monograph.
Additional medicinal plants will be covered in a second
volume, which is currently undergoing review.