This report contains the collective views of an international group of
    experts and does not necessarily represent the decisions or the stated
    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization.

    Published under the joint sponsorship of
    the United Nations Environment Programme,
    the International Labour Organisation,
    and the World Health Organization

    World Health Orgnization
    Geneva, 1984

         The International Programme on Chemical Safety (IPCS) is a
    joint venture of the United Nations Environment Programme, the
    International Labour Organisation, and the World Health
    Organization. The main objective of the IPCS is to carry out and
    disseminate evaluations of the effects of chemicals on human health
    and the quality of the environment. Supporting activities include
    the development of epidemiological, experimental laboratory, and
    risk-assessment methods that could produce internationally
    comparable results, and the development of manpower in the field of
    toxicology. Other activities carried out by the IPCS include the
    development of know-how for coping with chemical accidents,
    coordination of laboratory testing and epidemiological studies, and
    promotion of research on the mechanisms of the biological action of

        ISBN 92 4 154092 3  

         The World Health Organization welcomes requests for permission
    to reproduce or translate its publications, in part or in full.
    Applications and enquiries should be addressed to the Office of
    Publications, World Health Organization, Geneva, Switzerland, which
    will be glad to provide the latest information on any changes made
    to the text, plans for new editions, and reprints and translations
    already available.

    (c) World Health Organization 1984

         Publications of the World Health Organization enjoy copyright
    protection in accordance with the provisions of Protocol 2 of the
    Universal Copyright Convention. All rights reserved.

         The designations employed and the presentation of the material
    in this publication do not imply the expression of any opinion
    whatsoever on the part of the Secretariat of the World Health
    Organization concerning the legal status of any country, territory,
    city or area or of its authorities, or concerning the delimitation
    of its frontiers or boundaries.

         The mention of specific companies or of certain manufacturers'
    products does not imply that they are endorsed or recommended by the
    World Health Organization in preference to others of a similar
    nature that are not mentioned. Errors and omissions excepted, the
    names of proprietary products are distinguished by initial capital






     2.1. Chemical and physical properites of methylene chloride
     2.2. Analytical methods


     3.1. Production, uses, disposal of wastes
          3.1.1. Production levels and processes
          3.1.2. Uses
          3.1.3. Disposal of wastes
     3.2. Environmental transport and distribution


     4.1. Air
     4.2. Water
     4.3. Food
     4.4. Occupational exposure
     4.5. Controlled exposure


     5.1. Absorption
          5.1.1. Animal studies
          5.1.2. Human studies
     5.2. Distribution
          5.2.1. Animal studies
          5.2.2. Human studies
     5.3. Metabolic transformation
          5.3.1. Animal studies
          Enzyme pathway
          5.3.2. Human studies
     5.4. Excretion
          5.4.1. Animal studies
          5.4.2. Human studies



     7.1. Short-term exposures
          7.1.1. Inhalation exposure
          7.1.2. Oral exposure
          7.1.3. Intraperitoneal exposure
          7.1.4. Effects on the eye and skin
     7.2. Long-term exposure and carcinogenicity
          7.2.1. Inhalation exposure
          7.2.2. Oral exposure
     7.3. Mutagenicity
     7.4. Effects on reproduction and teratogenicity


     8.1. Short-term exposures
          8.1.1. Controlled studies
          8.1.2. Accidental exposures
          8.1.3. Effects on the skin and eyes
     8.2. Long-term exposure
          8.2.1. Occupational exposure
          8.2.2. Mortality studies



     10.1. Occupational exposure
     10.2. Food
     10.3. Storage and transport




Dr C.M. Bishop, Health and Safety Executive, London, England

Dr V. Hristeva-Mirtcheva, Institute of Hygiene and
   Occupational Health, Sofia, Bulgaria

Dr R. Lonngren, National Products Control Board, Solna, Sweden

Dr M. Martens, Institute of Hygiene and Epidemiology,
   Brussels, Belgium

Dr W.O. Phoon, Department of Social Medicine & Public Health,
   Faculty of Medicine, University of Singapore, National
   Republic of Singapore

Dr L. Rosenstein, Assessment Division, Office of Toxic
   Substances, US Environmental Protection Agency, Washington
   DC, USA

Mr C. Satkunananthan, Consultant, Colombo, Sri Lanka

Dr G.O. Sofoluwe, Oyo State Institute of Occupational Health,
   Ibadan, Nigeria

Dr A. Takanaka, Division of Pharmacology, Biological Safety
   Research Center, National Institute of Hygienic Sciences,
   Tokyo, Japan

Dr R.G. Tardiff, Life Systems, Inc., Arlington, VA, USA

 Representatives of Other Organizations

Dr J.P. Tassignon, European Chemical Industry Ecology and
   Toxicology Centre, Brussels, Belgium


Dr M. Nakadate, Division of Information on Chemical Safety,
   National Institute of Hygienic Sciences, Tokyo, Japan

Dr R. McGaughy, Carcinogen Assessment Division, US
   Environmental Protection Agency, Washington, DC, USA


Dr M. Gilbert, International Register of Potentially Toxic
   Chemicals, United Nations Environment Programme, Geneva,

Dr K.W. Jager, Scientist, International Programme on Chemical
   Safety, World Health Organization, Geneva, Switzerland

Dr M. Mercier, Manager, International Programme on Chemical
   Safety, World Health Organization, Geneva, Switzerland

Dr F. Valic, Scientist, International Programme on Chemical
   Safety, World Health Organization, Geneva, Switzerland

Dr G.J. Van Esch, National Institute for Public Health,
   Bilthoven, Netherlands  (Temporary Adviser)

Dr T. Vermeire, National Institute for Public Health,
   Bilthoven, Netherlands,  (Temporary Adviser)

    The WHO Task Group for the Environmental Health Criteria for 
Methylene Chloride met in Brussels from 19 to 22 September, 1983.  
Professor A. Lafontaine opened the meeting and welcomed the 
participants on behalf of the host government, and Dr M. Mercier, 
Manager, IPCS, on behalf of the heads of the three IPCS co-
sponsoring organizations (ILO/WHO/UNEP).  The Group reviewed and 
revised the second draft criteria document and made an evaluation 
of the health risks of exposure to methylene chloride. 

    The efforts of Dr G.J. Van Esch and Dr T. Vermeire, who were 
responsible for the preparation of the draft, and of all who helped 
in the preparation and the finalization of the document are 
gratefully acknowledged. 

                             * * *

    Partial financial support for the publication of this criteria 
document was kindly provided by the United States Department of 
Health and Human Services, through a contract from the National 
Institute of Environmental Health Sciences, Research Triangle Park, 
North Carolina, USA - a WHO Collaborating Centre for Environmental 
Health Effects. 


    A partly-new approach to develop more concise Environmental 
Health Criteria documents has been adopted with this issue.  While 
the document is based on a comprehensive search of the available, 
original, scientific literature, only key references have been 
cited.  A detailed data profile and a legal file on methylene 
chloride can be obtained from the International Register of 
Potentially Toxic Chemicals, Palais des Nations, 1211 Geneva 10, 
Switzerland (Telephone No. 988400 - 985850). 

    The document focuses on describing and evaluating the risks of 
methylene chloride for human health and the environment. 

    While every effort has been made to present information in the 
criteria documents as accurately as possible without unduly 
delaying their publication, mistakes might have occurred and are 
likely to occur in the future.  In the interest of all users of the 
environmental health criteria documents, readers are kindly 
requested to communicate any errors found to the Manager, 
International Programme on Chemical Safety, World Health 
Organization, Geneva, Switzerland, in order that they may be 
included in corrigenda, which will appear in subsequent volumes. 


    Methylene chloride (dichloromethane) is widely used as a multi-
purpose solvent and paint remover.  The assessment of its toxicity 
can be complicated by the  presence of stabilizers and other 
solvents, frequently found in commercial products.  Methylene 
chloride can be measured by gas chromatographic techniques at 
minimum concentrations of approximately 0.02 µg/m3 in air and 
0.1 µg/litre in water. Exposure to methylene chloride can be 
roughly estimated by the determination of its levels in blood or 
expired air.  Exposure to methylene chloride will result in 
elevated carboxyhaemoglobin levels in blood, which can be measured.  
However, blood carboxyhaemoglobin levels can give a false picture 
of exposure when either exercise or smoking is involved. 

    High concentrations have been measured in industrial indoor 
environments and during the use of methylene chloride as a paint 
remover.  The general population is exposed to much lower levels of 
the solvent in ambient air, drinking-water, and food. 

    About 80% of the world production of methylene chloride is 
estimated to be released into the atmosphere, but photodegradation 
takes place at a rate that makes accumulation in the atmosphere 
unlikely.  Initial products are phosgene and carbon monoxide, which 
are transformed into carbon dioxide and hydrochloric acid.  In 
surface water, volatilization is the major process of removal, 
hydrolysis and photodegradation being insignificant.  The solvent 
is readily biodegradable, aerobically.  Bioaccumulation seems 
unlikely in the environment.  The behaviour of the compound in soil 
has yet to be determined. 

    The major route of human exposure is through inhalation. 
Methylene chloride vapour is rapidly absorbed via the lungs and the 
gastrointestinal tract, uptake being directly proportional to 
exposure.  It also increases with exercise and with the amount of 
body fat.  The absorbed compound, which is distributed to all body 
tisses the placenta and blood-brain barrier.  Absorption of liquid 
methylene chloride via the skin is slow.  At current exposure 
levels, most of the methylene chloride taken up is metabolized to 
carbon monoxide and probably carbon dioxide, mainly in the liver, 
kidneys, and lungs.  With high exposures, the microsomal cytochrome 
P-450 enzyme system becomes saturated and some partitioning of 
unmetabolized methylene chloride may occur in fat.  Even at low 
exposure levels, carboxyhaemoglobin levels in the blood can be 
sustained for many hours after exposure, because of delayed 
conversion of methylene chloride from fat. 

    The toxicity of methylene chloride may be influenced by factors 
such as exposure to exogenous carbon monoxide, obesity, and an 
increased workload.  The predominant effects of methylene chloride 
on human beings are elevated carboxyhaemoglobin saturation of the 
blood and central nervous system depression.  The normal levels of 
blood carboxyhaemoglobin in man are exceeded in non-smoking, 
sedentary individuals after inhalation exposure to a methylene 
chloride concentration of 400 mg/m3 for 7.5 h.  The lowest-observed 

adverse acute effect level, for inhalation exposure of non-smoking, 
healthy individuals, was approximately 694 mg/m3 with 1.5 - 3 h 
of exposure.  Some neurobehavioural changes were observed at this 
exposure level.  Two cases of permanent damage to the central 
nervous system in high, long-term occupational exposures (5 years 
at 2290 - 12 500 mg/m3 and 3 years at 1735 - 3470 mg/m3, 
respectively) have been reported.  In spite of many reports of 
fatty degeneration in the liver and tubular degeneration in the 
kidneys of animals, there is no clear evidence of liver or kidney 
damage in human beings. 

    The vapour is moderately irritating to the eyes and respiratory 
tract while the liquid is irritating to the skin.  Patients with 
heart disease may be at increased risk if exposed to high levels of 
methylene chloride; this may particularly occur during the use of 
paint removers. 

    Results of  in vitro studies showed that methylene chloride 
was weakly mutagenic in bacteria and fungi.  Some mutagenic effects 
were also observed in  Drosophila melanogaster, but the results of 
most tests on mammalian somatic cells, including human cells, were 

    In 2 inhalation studies on rats, the incidence of benign 
mammary tumours was not increased in exposed male or female rats 
compared with controls, but the total number of mammary tumours in 
treated animals increased in a dose-related manner.  In the study, 
an increase in salivary gland region sarcomas was found in male 
rats.  In Golden Syrian hamsters, no significant increases in 
tumour incidences were found.  In a drinking-water study with rats 
and mice, no significant increases in tumour incidences were found, 
while an increased incidence of foci or areas of altered liver 
cells was observed. 

    In 2 human epidemiological mortality studies, there was no 
excess mortality due to cancer compared with control populations.  
Animal experimental data and human epidemiological data are 
inadequate for assessing whether or not methylene chloride should 
be considered carcinogenic for animals and man. 

    There is only limited evidence that methylene chloride is 
teratogenic in animals. 


2.1.  Chemical and Physical Properties of Methylene Chloride

    Methylene chloride (CH2Cl2) is nonflammable and nonexplosive 
when mixed with air.  It hydrolyses very slowly in the presence of 
moisture.  It also reacts with hydroxyl radicals.  No appreciable 
decomposition occurs at room temperature when the dry compound 
comes into contact with common metals.  Phosgene and hydrochloric 
acid are formed by contact with hot surfaces or flames. 


CAS registry number:    75-09-2

RTECS registry number:  PA 8050000

Common synonyms:        DCM, dichloromethane, methane dichloride, 
                        methylene bichloride, methylene dichloride, 
                        methylenum chloratum

Trade names:            Aerothene MM, Freon 30, Narkotil,
                        Solaesthin, Solmethine

Some physical data on methylene chloride

physical state                    liquid
colour                            colourless
odour                             ethereal
relative molecular mass           84.93
melting point                     -95 °C
boiling point                     40 °C
water solubility                  20 g/litre, 20 °C
log n-octanol-water partition     1.25
density                           1.33 g/ml, 20 °C
relative vapour density           2.93
vapour pressure                   46.52 kPa (349 mm Hg) at 20 °C
surface tension                   28.12 dyne/cm at 20 °C
flame limits                      0.5-2.3 g/litre in oxygen
                                  0.5-0.8 g/litre in air

Conversion factors for methylene chloride and carbon monoxide:

methylene chloride                1 ppm = 3.47 mg/m3 air
carbon monoxide                   1 ppm = 1.14 mg/m3 air

2.2.  Analytical Methods

    A summary of methods for the sampling and determination of 
methylene chloride in air, water, sediments, food, breath, blood, 
and urine is presented in Table 1. 

Table 1.  Sampling, preparation, analysis
Medium  Specifi-   Sampling          Analytical          Detection   Comments            References
        cation     method            method              limit
air     occupa-    on charcoal de-   gas chromatography  10 µg per   recommended range   White et al.
        tional     sorption with     with flame ioniza-  sample (1   350 - 10 400 mg/m3  (1970)
                   carbon disul-     tion detection      litre       (1 litre sample)    NIOSH (1984)
                   fide                                  sample)                         
air     occupa-                      direct reading                  a non-specific      Saltzman 
        tional                       detector tube                   cheap method to     (1972)
                                                                     estimate exposure

air     occupa-                      infra-red spectros-             continuous monito-  Baretta et al.
        tional                       copy                            ring and breath     (1969)

air     occupa-                      photodetection      3-6 mg/m3   suitable for con-   Nelson &
        tional                                           (for CCl4)  tinuous monito-     Shapiro (1971)
                                                                     ring when methy-
                                                                     lene chloride is
                                                                     the only contam-    

air     ambient                      gas chromatography  0.017       direct analysis     Grimsrud &
                                     and mass spectro-   µg/m3                           Rasmussen       
                                     metry                                               (1975)

Table 1.  (contd.)                         
Medium  Specifi-   Sampling          Analytical          Detection   Comments            References
        cation     method            method              limit
water   drinking-                    gas chromatography  0.1 µg/     sparging, trap-     Nicholson et 
        water                        with electrolyte    litre       ping in line on     al. (1977)
                                     conductivity detec-             gas chromatography
                                     tion                            column

water   drinking-                    gas chromatography  0.2 µg/     direct aqueous in-  Fujii (1977)
        water                        and mass spectro-   litre       jection, diglycerol
                                     metry                           as liquid phase on

sediment           cooling, extrac-  gas chromatography  0.1-1 mg/   also used for       Dietz &
                   tion with pen-    with flame ioniza-  litre       drinking-water      Traud (1973)
                   tane              tion detection                  analysis

food               extraction by     gas chromatography  1 mg/kg     analysis of spice   Page &
                   vacuum distil-    with electron cap-              oleoresins          Kennedy (1975)
                   lation washing    ture detection

blood                                gas chromatography              head-space analysis Di Vincenzo et
urine                                with flame-ioniza-              (blood, urine),     al. (1971)
breath                               tion detection      0.7 mg/m3   direct analysis


3.1.  Production, Uses, Disposal of Wastes

3.1.1.  Production levels and processes

    World production in 1980 amounted to 570 kilotonnes of which 
270 kilotonnes were produced in Western Europe (CEFIC, 1983).  In 
the USA, production increased from 180 kilotonnes in 1971 (Gordon, 
1976) to 254 kilotonnes in 1980 (IRPTC; 1984) and 269 kilotonnes in 
1981 (USITC, 1982).  In Japan, 35 kilotonnes were produced in 1980 
(IRPTC, 1984). 

    Two processes are important:  the chlorination of methyl 
chloride, obtained from the reaction of methanol and hydrogen 
chloride, and the direct chlorination of methane (IARC, 1979). 

    Additives may include 0.0001 - 1% of stabilizers such as: 
amines, 4-cresol, hydroquinone, methanol, 2-methylbut-2-ene, 
1-naphthol, nitromethane + 1,4 dioxane, phenol, resorcinol, and 

3.1.2.  Uses

    Methylene chloride is used as:  a solvent, a blowing agent for 
polyurethane, a component of paint remover, a degreasing solvent, 
and as a propellant in aerosols such as insecticides, hair sprays, 
shampoos, and paints.  Methylene chloride is being increasingly 
used as a replacement for fluorocarbons in aerosols.  As a solvent, 
it is used in pharmaceutical applications, in the manufacture of 
photographic and synthetic fibres, and, as an extraction solvent, 
for naturally-occurring, heat-sensitive substances such as edible 
fats, cocoa, butter, caffeine, and beer flavouring in hops.  It is 
also used as a component in fire-extinquishing products, as an 
insecticidal fumigant for grains, and as a coolant and refrigerant 
(Gordon, 1976; IARC, 1979). 

3.1.3.  Disposal of wastes

    Methylene chloride can be destroyed by incineration, sometimes 
after adsorption by activated carbon.  End products are carbon 
dioxide, water, and hydrochloric acid, which can be recovered 
(Gordon, 1976). 

3.2.  Environmental Transport and Distribution

    Approximately 80% of the world production of methylene 
chloride is emitted into the atmosphere during its use as a 
solvent, and in paint removers, aerosols, solvent degreasers, 
and fumigants.  Minor losses occur during production and shipping.  
In the USA alone, emissions in 1975 amounted to 177 kilotonnes 
(Gordon, 1976).  Volatilization also appears to be the major 
process by which methylene chloride is lost from water (Dilling 
et al., 1975).  Under field conditions, half-lives of 33 and 38 
days were estimated for river water (Zoeteman et al., 1980). 

    Once in the troposphere, hydroxyl radicals can attack the 
compound yielding mainly carbon dioxide and hydrogen chloride and 
minor quantities of carbon monoxide and phosgene (Pearson & 
McConnell, 1975; Cox et al., 1976; Spence et al., 1976).  Phosgene 
readily hydrolises to hydrochloric acid and carbon dioxide.  Cox et 
al. (1976) estimated a lifetime for methylene chloride in the 
troposphere of 0.3 years, with respect to oxidation by hydroxyl 
radicals.  Photodegradation and hydrolysis in water do not seem to 
take place to any significant extent (Dilling et al., 1975).  
Methylene chloride is absorbed on dry bentonite clay and peat moss 
but not significantly on limestone and silica sand (Dilling et al., 

    The available reports show that methylene chloride is readily 
biodegradable.  The compound was rapidly degraded aerobically by 
microorganisms from settled domestic waste water containing 
methylene chloride concentrations of 5 and 10 mg/litre (Tabak et 
al., 1981).  After adaptation, sewage microorganisms and a 
 Pseudomonas species were found to degrade methylene chloride 
aerobically and to use it for growth at concentrations below 425 
mg/litre (Brunner et al., 1980; Rittman & McCarty, 1980).  Similar 
results were obtained by Stucki et al. (1981) using hyphomicrobium 
species.  Methylene chloride was dehalogenated by aerobic 
microorganisms from municipal activated sludge yielding carbon 
dioxide and chloride, after adaptation only.  The compound was 
toxic above a concentration of 1000 mg/litre (Klechka, 1982). 


    It can be seen from the uses and the physical and chemical 
properties of methylene chloride that the main route of human 
exposure is through vapour inhalation, sometimes accompanied by 
direct skin and eye contact, both at the place of work and at home.  
Much lower levels of human exposure can occur through inhalation of 
methylene chloride in ambient air and through its ingestion via 
drinking-water, food, and beverages. 

4.1.  Air

    The background concentration of methylene chloride at surface 
level at 40 °N latitude was found to be about 0.12 µg/m3 by Cox et 
al., (1976) and 0.17 µg/m3 by Singh et al., (1982).  In the air of 
7 cities in the USA during 24-h sampling periods, concentrations 
ranged between 0.17 and 196.75 µg/m3, while average concentrations 
varied from 1.35 to 6.76 µg/m3 (Singh et al., 1982).  The highest 
detected concentrations in drinking-water have been less than 5 
µg/litre (Saunders et al., 1975; Fujii, 1977; US National Academy 
of Science, 1977). 

4.2.  Water

    Few reports contain data concerning the occurrence of 
methylene chloride in natural waters.  In a survey in the 
USA, 8% of  finished-water supplies tested contained methylene 
chloride, but only 1% of the raw-water supplies (US National 
Academy of Sciences, 1977).  Water from a sewage treatment plant 
contained a methylene chloride concentration of 8.2 mg/litre before 
treatment, 2.9 µg/litre after treatment but before chlorination, 
and 3.4 µg/litre after chlorination (Bellar et al., 1974).  These 
results show that methylene chloride is formed during the 
chlorination of water.  Concentrations of 1 - 2 µg/litre (Bauer, 
1978) and 5 µg/litre (Zoeteman et al., 1980) were reported at the 
same point in the river Rhine. 

4.3.  Food

    One report is available describing the occurrence of the 
extractant methylene chloride in 15 out of 17 spice-oleoresins at 
levels between 1 and 83 mg/kg wet weight (Page & Kennedy, 1975). 

4.4.  Occupational Exposure

    Methylene chloride exposure was investigated in a variety of 
jobs in the USA including:  servicing of diesel engines, spray-
painting of booths, plastic tank construction, ski manufacture, 
cleaning foam heads, and cleaning nozzles in plastic manufacture.  
The concentrations ranged from below the detection limit to 257 
mg/m3 air.  In a chemical plant, an 8 h, time-weighted average 
exposure was measured of 3040 mg/m3 with an exposure range from 
below the detection limit to 19 150 mg/m3 (NIOSH, 1976).  In 
cellulose-acetate-fibre-producing plants in Czechoslovakia and the 
USA, methylene chloride concentrations in air in a total of 335 

samples ranged from 100 to 17 000 mg/m3 (Kuzelova & Vlasak, 1966; 
NIOSH, 1976).  The median 8-h, time-weighted average concentrations 
in another plant producing cellulose acetate fibre in the USA, 
ranged from 280 to 1650 mg/m3 (Ott et al., 1983).  In a beauty 
salon, where methylene chloride exposure stemmed from its use as an 
aerosol propellant in sprays, daily mean background concentrations 
were below 6.9 mg/m3, while peak concentrations of 451 mg/m3 were 
reached, directly after spraying coiffures (Hoffman, 1973). 

4.5.  Controlled Exposure

    Methylene chloride is widely used at home in paint removers and 
aerosol sprays.  Most paint-stripping formulations contain about 
80% by weight of methylene chloride, often in combination with 
methanol.  Breathing zone concentrations were measured during the 
use of a paint remover under controlled conditions with normal 
ventilation, (70 m3/h).  The maximum concentration was 4430 mg/m3 
during the 3 h studies, the averages, in various experiments, ranging 
between 2270 and 2730 mg/m3 (Stewart & Hake, 1976).

    In a detailed study on exposure levels during the use of paint 
removers, the time-weighted averages in a room without ventilation 
varied between 460 and 2980 mg/m3 during the first 6 h following 
application.  Grab samples showed levels of up to 3410 mg/m3, 30 
min after application.  In studies  with the door open, the levels 
were between 60 and 490 mg/m3 (Otson et al., 1981). 


5.1.  Absorption

5.1.1.  Animal studies

    From the moment of application, dermal absorption of liquid 
methylene chloride in mice increased linearly with time at a rate 
of 0.1 mg per cm2 per min (Tsuruta, l975).  Rapid absorption 
occurred in rats after both oral ingestion and inhalation of 
methylene chloride.  A steady state plasma concentration, attained 
after 2 h of vapour exposure, was not proportional to the exposure 
level at low concentrations (McKenna et al., 1982).  Almost 
directly after oral application, peak concentrations of methylene 
chloride could be detected in expired air (McKenna & Zempel, 1981).  
In rats, methylene chloride readily passed the placenta (Anders & 
Sunram, 1982) and the blood-brain barrier (e.g., Fodor & Winneke, 

5.1.2.  Human studies

    Dermal exposure of volunteers to liquid methylene chloride 
resulted in maximum levels of the compound in expired air, 30 min 
after exposure (Stewart & Dodd, 1964).  After 0.5 - 8 h of 
inhalation exposure to concentrations ranging from 173 to 1740 
mg/m3, blood and expired air concentrations and thus, total 
uptake of methylene chloride, were found to be directly 
proportional to the magnitude of exposure, in sedentary 
individuals.  The concentration in blood increased gradually and 
appeared to be slowly reaching a plateau over 8 h.  In the lungs, 
the uptake was rapid and remained almost constant after 1 h of 
exposure.  The concentration in expired air at the end of the 
respiration cycle was 2.3 - 2.8 times lower than that in inspired 
air.  Repeated exposures did not result in higher blood or expired-
air levels.  The uptake varied between 55 and 75% of the total 
exposure in sedentary individuals.  The absolute uptake increased 
during exercise, but uptake relative to total exposure decreased 
(DiVincenzo et al., l972; Astrand et al., 1975; DiVincenzo & 
Kaplan, 1981a,b).  In another study on human volunteers, the uptake 
of methylene chloride, at steady-state with respect to expired air 
within 2.5 - 3 h in 6-h exposures, seemed to deviate from a linear 
increase when the exposure level was above 690 - 870 mg/m3 
(McKenna et al., 1980).  The absolute uptake in a 1-h exposure to 
2600 mg/m3 was proportional to the body weight and to the amount of 
body fat.  The uptake in relation to total exposure was almost the 
same for both slim and obese persons, reflecting an increase in 
respiratory volume with body weight (Engström & Bjurström, 1977).  
Methylene chloride was found to cross the placenta (Vosovaja et 
al., 1974) and the blood-brain barrier (e.g., Putz et al,. 1976). 

5.2.  Distribution

5.2.1.  Animal studies

    Forty-eight hours after a single oral ingestion of labelled 
methylene chloride at 1 mg/kg body weight or inhalation during 6 h 
at 170 mg/m3 by rats, the percentages of radioactivity in the skin 
and carcass were 7.5% and 30% of the body burden, respectively. 

    At higher exposures, retention was less.  Unmetabolized 
methylene chloride was not detected.  In rats and mice, most 
radioactivity was retained in the liver, kidneys, and lung 
(Bergman, 1979; McKenna & Zempel, 1981; McKenna et al., 1982).  
Body autoradiography in mice also indicated metabolites in tissues 
with a high rate of protein synthesis such as the pancreas, thymus, 
and salivary glands (Bergman, 1979).  Directly after short vapour 
exposures, the highest amounts of volatile radioactivity, which 
probably represented unmetabolized methylene chloride and were 
found in the adipose tissue, brain, and blood, diminished rapidly 
within 2 h (Carlsson & Hultengren, 1975; Bergman, 1979).  After 
repeated exposure of rats to methylene chloride concentrations in 
air of 1735 mg/m3 and 3470 mg/m3 during a 2-week period, the 
concentration of the compound in perirenal fat increased, while 
that in the brain decreased.  Exposure to a time-weighted average  
concentration of 3470 mg/m3, involving short intervals at high 
concentrations, resulted in greater accumulation than exposure to a 
constant concentration of 3470 mg/m3 (Savolainen et al., 1981). 

    In liver microsomes of rat, methylene chloride was found to be 
bound to lipids and proteins, but only after metabolic activation 
in the presence of NADPH and oxygen.  Pretreatment of rats with 
phenobarbital increased the binding (Anders et al., 1977).  In 
whole liver cells, this binding was enhanced by oxygen and 
decreased by phenobarbital pretreatment or glutathione depletion.  
Nucleic acids were not alkylated (Cunningham et al., 1981).   In
 vivo binding of labelled metabolites was observed in rat liver.  
Radioactivity was mainly found in the acid-soluble and protein 
fractions and, to a lesser extent in the lipid and nucleic acids 
fractions.  The labelling pattern was similar to that of 
formaldehyde (Reynolds & Yee, 1967). 

5.2.2.  Human studies

    The average concentration of methylene chloride in the adipose 
tissue of obese men was found to decline from 10.2 to 1.6 mg/kg, 
between 1 and 22 h after a single, 1-h exposure to 2600 mg/m3.  The 
concentration was not measured just after exposure.  Even though 
obese subjects had lower concentrations of methylene chloride in 
adipose tissue than slim subjects, the former had a greater 
fraction of the uptake in their adipose tissue (Engström & 
Bjurström, 1977). 

5.3.  Metabolic Transformation

5.3.1.  Animal studies

    The metabolism of methylene chloride was found to be a 
saturable process.  Forty-eight hours after inhalation, 55% of the 
uptake was expired unchanged at 4920 mg/m3, 30% at 1700 mg/m3, 
and 5% at 170 mg/m3, respectively (McKenna et al., 1982). 

    In these studies, the major metabolites were carbon monoxide 
and carbon dioxide found in expired air.  This was also observed in 
other studies with rats, mice, and rabbits (e.g., Kubic et al., 
1974; Roth et al., 1975; McKenna & Zempel, 1981).  McKenna  et al 
(1982) reported that, after inhalation exposure, about 60% of all 
metabolites represented these 2 compounds at all exposures, without 
a clear predominance of either one of them.  After oral 
application, this value was about 80% (McKenna & Zempel, 1981).  
The balance was mostly retained as unidentified metabolites in the 
carcass and skin, while small quantities of unidentified 
metabolites were recovered in the urine and faeces. 

    Rats inhaling a low dose of labelled methylene chloride in a 
closed rebreathing system excreted 47% of the administered label as 
carbon monoxide and 29% as carbon dioxide.  No radioactivity was 
detected in the carcass.  The initial rate of carbon monoxide 
production was constant at all exposures; this also points to a 
saturable enzymatic conversion (Rodkey & Collison, 1977a,b). 

    Endogenous carbon monoxide production following exposure to 
methylene chloride leads to accumulation of carboxyhaemoglobin in 
blood.  In a study on rats, McKenna et al. (1982) measured steady-
state carboxyhaemoglobin levels of 3 and 10 -13% of saturation, 
respectively, after 1 h of exposure to 173 mg/m3 and after 2.5 - 
3 h of exposure to 1730 and 5200 mg/m3.  The carboxyhaemoglobin 
levels in the blood of rats rose with increasing exposure until a 
plateau was reached at about 12% of saturation (Fodor et al., 
1973).  This was also found during long-term exposures (Burek et 
al., 1984).  Enzyme pathway

    Two pathways that have been proposed on the basis of  in vitro  
experiments are:  

(a) The conversion of methylene chloride to carbon monoxide by
    the hepatic microsomal cytochrome P-450 1-dependent mixed
    function oxidase system (Kubic & Anders, 1975, 1978; Jongen et
    al., 1982).  It is proposed that the metabolism starts by a
    rate-limiting oxygen insertion, followed by rearrangement to
    formyl chloride, which decomposes to carbon monoxide.  The
    formyl chloride may be involved in macromolecular binding.
    Phenobarbital pretreatment increases binding to cytochrome
    P-450 and the rate of conversion  in vitro, but not  in vivo 
   (Haun et al., 1972; Kubic et al., 1974; Roth et al., 1975).

(b) The conversion of methylene chloride to formaldehyde,
    formic acid, and chloride by the hepatic cytosol fraction
    (Ahmed & Anders, 1976, 1978; Jongen et al., 1982).  In this
    conversion, it is proposed that binding of glutathione to
    methylene chloride is followed by hydrolysis via glutathione
    transferase (EC  Carbon dioxide will be the main
    product.  The resulting S-hydroxymethyl glutathione may yield
    formaldehyde or formic acid.  Formic acid may inhibit
    cytochrome  c oxidase (EC (Nicholls, 1975).

5.3.2.  Human studies

    DiVincenzo & Kaplan (1981a,b) exposed volunteers for 7.5 h to 
concentrations of methylene chloride up to 694 mg/m3.  Less than 5% 
of the uptake was excreted unchanged via the lungs, while 30% of 
the metabolized methylene chloride was converted to carbon 
monoxide.  It was suggested that the rest was converted to carbon 
dioxide.  Exercise increased both the biotransformation to carbon 
monoxide and the blood carboxyhaemoglobin levels.  An increased 
workload did not further elevate the carboxyhaemoglobin levels, 
because of increased excretion of carbon monoxide.  Smoking had a 
additive effect on the carboxyhaemoglobin values, as was found with 
carbon monoxide exposure by Fodor et al. (1973). 

    Blood carboxyhaemoglobin levels increased in direct proportion 
to the level and the duration of exposure up to 694 mg/m3.  There-
after, a plateau seemed to be reached.  Peak carboxyhaemoglobin 
saturation was reached, either at the end of the exposure or, at 
high uptakes, shortly afterwards.  Nonsmoking subjects have control 
values between 0.4 and 2.0% of saturation, while smokers generally 
have control values between 2 and 8%.  An 8-h exposure of non-
smokers to a methylene chloride concentration of 350 mg/m3 
appeared equivalent to an 8-h exposure to a carbon monoxide 
concentration of 43 mg/m3, leading to a carboxyhaemoglobin level 
of 5% of saturation (Stewart et al., 1972; Fodor & Roscavanu, 1976; 
Stewart 1981a).  During repeated exposures to methylene chloride 
over 5 working days, carboxyhaemoglobin levels did not show any, 
or only a slight increase, compared with levels following single 
exposures, and returned to pre-exposure levels over the weekend.  
Occupational exposure of non-smokers to a time-weighted average of 
114 mg/m3 resulted in carboxyhaemoglobin levels of between 0.8 and 
2.5% of saturation (DiVincenzo & Kaplan, 1981a; Fodor & Roscavanu, 
1976).  Residual elevated carboxyhaemoglobin levels associated 
with, and proportional to, the level of previous-day exposure to 
methylene chloride was found both in smoking and non-smoking 
industrial workers, in equal measure.  In this epidemiological 
study, the dose-related increases in the carboxyhaemoglobin levels 
and alveolar carbon monoxide concentration were correlated with a 
decrease in the oxyge pressure.  Sex, race, and age of the subjects 
were found to be unimportant in predicting carboxyhaemoglobin 
levels in contrast to smoking and time of venipuncture (Ott et al., 
1983).  In the blood of workers exposed to methylene chloride 
concentrations ranging from 552 to 760 mg/m3, but not to carbon 
monoxide, the carboxyhaemoglobin levels rose to 8.3% after 8 h and 
dropped to base-line values of about 4.5% at the start of the new

work day (Ratney et al., 1974).  Kuzelova & Vlasak (1966) detected 
formic acid in the urine of workers exposed to methylene chloride 
for long periods. 

5.4.  Excretion

5.4.1.  Animal studies

    The concentrations of methylene chloride in the blood and 
expired air of rats and dogs, after exposure to methylene chloride, 
declined exponentially and were directly proportional to the level 
of exposure (DiVincenzo et al., 1972; McKenna & Zempel, 1981; 
McKenna et al., 1982).  In rats, the excretion from blood after 
inhalation was resolved in a fast and a slow first order process 
with half-lives of respectively 2 and l5 min.  The fast and slow 
processes in the excretion in expired air of rats, after oral 
ingestion, had half-lives of 13 and 46 min.  After a high oral dose 
of 50 mg/kg body weight, the concentration of methylene chloride in 
the expired air was constant for 1 h and then declined.  The 
excretion of carbon dioxide and carbon monoxide after oral intake 
and inhalation also followed 2 first order processes with half-
lives of 1.4 - 2.7 h for the first 24 h after exposure and of 6.7 - 
17.3 h, thereafter. 

    The disappearance of carboxyhaemoglobin from the blood was 
exponential with a half-life of 23 - 35 min.  At high exposures, 
blood carboxyhaemoglobin levels remained elevated for 60 - 90 min 
following exposure (McKenna & Zempel, 1981; McKenna et al., 1982). 

5.4.2.  Human studies

    After exposure, expired air and blood concentrations of 
methylene chloride measured were directly proportional to the 
concentration of the vapour.  Elimination of methylene chloride 
occurred rapidly, mainly through expiration.  An initially rapid 
phase of elimination had a half-life of less than 1 min.  The 
elimination of carbon monoxide in the expired air and of 
carboxyhaemoglobin from blood was more gradual and returned to 
pre-exposure values about 24 h after exposure to up to 694 mg/m3 
for 7.5 h.  The half-lives for the observed 2 phases of elimination 
were reported to be 1.5 h and 10 - 15 h, respectively (McKenna et 
al., 1980; DiVincenzo & Kaplan, 1981b).  Pulmonary excretion of 
carbon monoxide increased when exposure was continued with 
exercise.  Excretion of methylene chloride via the urine was 
negligible (DiVincenzo & Kaplan, 1981b).  In contrast, Stewart et 
al. (1976) reported a biological half-life following exogenous 
carbon monoxide exposure of only 5 h.  Moreover, after short 
exposures to 1740 mg/m3, blood carboxyhaemoglobin levels continued 
to rise for several hours (Astrand et al., 1975).  These data 
suggest a delayed conversion of methylene chloride from fat 
(Engström & Bjurström, 1977).  Methylene chloride has been found in 
breast milk (Vosovaja et al., 1974). 


    A summary of studies on the acute toxicity of methylene 
chloride in aquatic organisms is presented in Table 2. 

    No experimental bioconcentration factor was available, but the 
low log  n-octanol-water partition coefficient of 1.25 (Hansch et 
al., 1975) and the rather high water solubility suggest that 
bioaccumulation is very limited.  A bioconcentration factor in fish 
of 5 can be calculated according to the method of Veith et al. 

Table 2.  Acute aquatic toxicity
Organism   Description       t     pH    Dissolved Hardness  Flow/1  Parameter    Concen-   Reference     
                             (°C)        oxygen    (mgCaCO3/ stat                 tration                 
                                         (mg/      litre)                         mg/litre                
algae       Chlorella vul-    19    6.5                               3-h EC50     27 000    Hutchinson et 
            garis, Chlamy-                                                         & 17 400  al.  (1978)2  
            domonas angulosa                                                       respec-                 
crustacea  water flea        22    7.4-  6.5-9.1   173       stat    48-h LC50    220       Le Blanc      
            (Daphnia magna)         9.4                               no-observed  68        (1980)3       
                                                                     effect level                         
fish       fathead minnow    12    7.8-  >5.0                stat     96-h LC50    310       Alexander et  
            (Pimephales)            8.0                                                      al. (1978)4   
fish       fathead minnow    12    7.8-  >5.0                flow     96-h LC50    193       Alexander et      
            (Pimephales             8.0                               96-h EC50    99        al. (1978)4   
fish       bluegill sunfish  21-   7.9-  9.7-3.0   32-48     stat    96-h LC50    220       Buccafusco et     
            (Lepomis macro-   23    6.5                                                      al. (1981)5     
fish       sheepshead        25-                             stat    96-h LC50    330       Heitmuller et     
           minnow            31                                      no-observed  130       al. (1981)6       
            (Cyprinodon                                               adverse-                                 
            variegatus)                                               effect level                                    

1)  Flow through or static method.
2)  EC50 for growth inhibition by determination of 14CO2 uptake, no analysis for methylene chloride 
3)  15 daphnias/concentration, < 24 h of age, no analysis for methylene chloride reported.
4)  Dechlorinated, sterilized lake water, analysis for methylene chloride by gas chromatography.
5)  10 juvenile fish/concentration, deionized reconstituted water; no aeration, no analysis for 
    methylene chloride reported. 
6)  10 juvenile fish/concentration, sea water with salinity of 1.0 - 3.1%, no aeration, no analysis for  
    methylene chloride reported.


7.1.  Short-Term Exposures

    In short-term exposure studies, effects on organs after 
inhalation of methylene chloride are mainly limited to the liver, 
kidneys, and heart but central nervous system depression also 
occurs.  There are not sufficient data to indicate definitely the 
effects after oral and dermal exposure.  Acute mortality data are 
shown in Table 3. 
Table 3.  Acute mortality after oral intake or inhalation of methylene 
Species  Route        Vehicle    Parameter   Value          Reference
rat      oral         none       LD50        3000 mg/kg     Kimura et al.
                                             body weight    (1971)

rat      inhalation   -          2-h LC50    79 000 mg/m3   Kashin et al.

rat      inhalation   -          6-h LC50    52 000 mg/m3   Bonnet et al.

mouse    inhalation   -          7-h LC50    56 230 mg/m3   Svirbely et 
                                                            al. (1947)

mouse    inhalation   -          6-h LC50    49 100 mg/m3   Gradiski et 
                                                            al. (1978)

mouse    inhalation   -          2-h LC50    51 500 mg/m3   Kashin et al.

dog      oral         mucil-     LD50        3000 mg/kg     Barsoum & 
                      age of                 body weight    Saad (1934)

guinea-  inhalation   -          6-h LC50    40 200 mg/m3   Balmer et 
pig                                                         al. (1976)

    The slope of the regression line giving the probability units 
of the percentage mortality as a function of the logarithm of the 
concentration is rather steep for both rats and mice, the 
difference between the LC10 and the LC90 being less than 14 000 
mg/m3 (Gradiski et al., 1978; Bonnet et al., 1980). 

7.1.1.  Inhalation exposure

    No macroscopic lesions were found in rats at the 6-h LC50 of 
52 000 mg/m3 (Bonnet et al., 1980).  After 6 h of exposure to 
17 350 mg/m3, the concentration of triglycerides was increased in 
the liver of guinea-pigs, and reduced in the serum (Balmer et al., 

1976; Morris et al., 1979).  Histopathological liver changes, 
consisting of the appearance of lipid droplets, were first seen 
in guinea-pigs at 18 000 mg/m3 (Morris et al., 1979).  Slight 
to moderate vacuolization in the liver was seen after 6 h at 
38 520 mg/m3.  In addition, lungs showed congestion and 
haemorrhage; behavioural changes were also noted (Balmer et al., 
1976).  Heppel et al. (1944) did not find organ lesions related 
to exposure at 17 350 mg/m3 in studies on dogs, monkeys, rats, 
rabbits, and guinea-pigs, with the exception of moderate 
centrilobular fatty degeneration of the liver and pneumonia in 
3 out of 14 guinea-pigs.  At 34 700 mg/m3, dogs also showed 
fatty degeneration. 

    After continuous exposure to methylene chloride concentrations 
of 87 and 347 mg/m3 for 100 days, slight cytoplasmatic vacuolization 
with positive fat stains were noted in livers of rats as well as 
tubular degeneration in kidneys.  Similar changes and a decrease in 
the microsomal cytochrome P-450 content were found in the livers of 
mice exposed to a concentration of 347 mg/m3 (Haun et al., 1972). 

    Similar changes in the liver were found in dogs and monkeys 
exposed continuously to a methylene chloride concentration of 
3470 mg/m3.  The dogs also showed vacuolar changes in the renal 
tubules.  After 4 weeks, they exhibited abnormal haematology, 
increased activities of serum glutamic pyruvic transaminase 
(SGPT) (EC, isocitric dehydrogenase (EC, 
bromosulphthalein (BSP) retention.  Additional effects at 17 350 
mg/m3 were oedema of the brain in dogs and encephalomalacia in 
monkeys (Haun et al., 1972). 

    The effects on the mouse liver were studied microscopically 
by Weinstein & Diamond (l972) and Weinstein et al. (1972) during 
continuous exposures.  At 347 mg/m3, fatty infiltration, 
vacuolization, and enlarged nuclei persisted up to the end of the 
10-week exposure, while an increase in triglycerides concentration 
was reversible.  At 17 350 mg/m3, body weights fell, and relative 
liver weights increased up to the end of the 168-h exposure.  Fatty 
infiltration, an increase in the triglycerides concentration, and 
hydropic degeneration of the endoplasmic reticulum gradually 
disappeared.  Protein synthesis was depressed.  Necrosis was 
observed in a few hepatocytes. 

    No consistent increase of the total liver microsomal concentration 
of cytochrome P-450 was found after repeated exposure of rats, but 
the metabolic activity of liver microsomal enzymes increased  in 
 vitro and  in vivo (Norpoth et al., 1974; Toftgard et al., 1982; 
Kurppa & Vainio, 1981). 

    Cardiac effects such as arrhythmia, tachycardia, and hypotension 
was found in monkeys and rabbits exposed for 1 - 5 min to levels of 
methylene chloride exceeding 60 000 mg/m3 (Belej et al., 1974; 
Taylor et al., 1976). 

    Central nervous system depression was noted in dogs, monkeys, 
rats, rabbits, and guinea-pigs during each daily session of 
repeated exposure to a methylene chloride concentration of 34 700 
mg/m3 for 7 h/day, 5 days per week, for 6 months.  All animals 

became inactive, some time after initial excitement (Heppel et al., 
1944).  Mice continuously exposed to a level of 17 350 mg/m3 showed 
decreased activity, and water and food intake, and changes in 
appearance, which disappeared after 168 h (Weinstein & Diamond, 

    Central nervous system depression resulting in reversible 
narcosis occurred in dogs, mice, and guinea-pigs after 2 - 6 h of 
exposure to levels of methylene chloride between 13 900 and 20 800 
mg/m3 (Flury & Zernick, 1931).  During exposure for 1.5 h to 
17 350 mg/m3, rats showed decreased running activity (Heppel & 
Neal, 1944).  The sleep-wakefulness patterns were disturbed in rats 
from a level of 3470 mg/m3 upwards, as shown mainly by a reduction 
in Rapid-Eye Movement sleep (Fodor & Winneke, 1971). 

7.1.2.  Oral exposure

    A single oral dose of 1000 mg/kg body weight resulted in a 
decreased cytochrome P-450 content in liver microsomes of rats 
(Moody et al., 1981). 

    Rats, receiving methylene chloride in the drinking-water at a 
concentration of 125 mg/litre for 13 weeks, did not show any 
effects on behaviour, body weight, haematology, urinalysis, blood 
glucose, plasma-free fatty acids, and the estrus cycle (Bornmann & 
Loeser, 1967). 

7.1.3.  Intraperitoneal exposure

    One intraperitonal injection of methylene chloride at 510 mg/kg 
body weight in rats, slowed down the sciatic motor conduction 
velocity by 11%, and gave rise to a carboxy-haemoglobin level of 
6.8% of saturation (Pankow et al., 1979). 

7.1.4.  Effects on the eye and skin

    Duprat et al. (1976) and Ballantyne et al. (1976) exposed 
rabbits once to 0.5 ml of methylene chloride by ocular instillation.  
Moderate to severe changes were seen in the conjunctiva, together 
with increased corneal thickness and intraocular tension.  All 
effects were reversible.  Vapour exposure of the eyes caused slight 
increases in corneal thickness and intraocular tension. 

    Application of methylene chloride to the skin of rabbits caused 
severe erythema and oedema with necrosis and acanthosis (Duprat et 
al., 1976). 

7.2.  Long-Term Exposure and Carcinogenicity

7.2.1.  Inhalation exposure

    Groups of 129 male and 129 female Sprague Dawley rats and 107 - 
109 male and 107 - 109 female Golden Syrian hamsters were exposed 
to methylene chloride (99% pure) at 0, 1730, 5200,and 12 100 mg/m3 

for 2 years, 6 h/day and 5 days per week (Burek et al., 1984).  The 
survival rate of high-exposure female rats was reduced.  Slight 
exposure-related effects consistent with fatty infiltration were 
seen in the livers of both sexes at all exposures.  Mean corpuscular 
volume, mean corpuscular haemoglobin, and carboxyhaemoglobin were 
increased in both sexes at all exposures.  An increased, dose-
related incidence of salivary gland region sarcomas was observed in 
males at the 2 highest exposures (the authors assume that the 
effect might have been due to the combination of viral infection 
and methylene chloride exposure).  The total number of benign 
mammary tumours in the rats increased in a dose-related manner in 
both sexes, most pronouncedly in females.  It was noted that the 
Sprague-Dawley rats used in this study have a very high incidence 
of spontaneous mammary tumours.  This incidence was not increased 
in exposed rats compared to controls. 

    In hamsters, elevated haematocrit, haemoglobin levels (both 
dose-related), mean corpuscular volume, mean corpuscular 
haemoglobin, and carboxyhaemoglobin were found in both sexes. 
There was no significant increase in the incidence of tumours. 

    Groups of 90 male and 90 female Sprague Dawley rats were 
exposed to 99.5% pure methylene chloride at 0, 173, 694, and 1730 
mg/m3 for 20 (male) or 24 (female) months, 6 h per day and 5 days 
per week.  Two additional groups of 30 female rats were each 
exposed for 6 months to 1730 mg/m3 followed by 6 months without 
exposure and vice versa. 

    There was an increase in the incidence of foci of altered 
hepatocytes at 1730 mg/m3, in surviving females, and at 694 and 
1730 mg/m3, in surviving males.  When these liver alterations in 
interim kills and end kills were combined, no increase was found.  
Hepatocellular vacuolization was noted in males and females 
receiving high doses and multinucleated hepatocytes in females 
receiving high doses.  The number of female rats with benign 
mammary tumours was not increased, but the total number of mammary 
tumours in the female rats was increased at 1730 mg/m3 (Nitschke 
et al., 1983). 

7.2.2.  Oral exposure

    Groups of 85 male Fischer 344 rats received 99% pure methylene 
chloride in the drinking-water for 24 months at levels of 6, 52, 
125, and 235 mg/kg body weight per day. Groups of 85 female rats 
received 6, 58, 136, and 263 mg/kg body weight per day.  Duplicate 
control groups comprised a total of 135 rats of each sex.  A high 
dose recovery group was only treated for 18 months. 

    Slight reductions in weight gain, water intake, and food 
consumption were found at the 2 highest doses.  Survival was not 
affected.  Dose-related increases were noted in mean haematocrit, 
haemoglobin levels, and red blood cell counts at the 3 highest 
doses.  Decreases in serum alkaline phosphatase (EC 
activity in males and in creatinine, blood urea nitrogen, serum-
protein, and cholesterol in both sexes were also dose-related. 

    At the 2 highest doses, a dose-related increased incidence of 
fatty livers was reversible.  At all levels, except the lowest, the 
incidence of foci or areas of altered hepatocytes was increased in 
a dose-related manner. 

    In the liver of females, a total of 0, 1, 2, 1 and 4 neoplastic 
nodules were observed at 0, 6, 58, 136, and 263 mg/kg, respectively, 
while 2 hepatocellular carcinomas were observed at both 58 and 263 
mg/kg, against none in the control groups.  This incidence of 
carcinoma was within the range of historical control values.  In 
treated males, these incidences were comparable to those of the 
controls.  No earlier onset of nodules or carcinoma was observed 
(NCA, 1982), 

    In the same project, groups of 100 - 200 male and 50 - 100 
female B6C3F1 mice received food grade methylene chloride in the 
drinking-water for 24 months at levels of approximately 60, 125, 
175, and 235 mg/kg body weight per day.  Duplicate control groups 
comprised a total of 125 male and 100 female mice. 

    The survival of the treated female mice was better than that of 
the controls.  At the highest dose level in both sexes, the 
leukocyte count was increased at week 52, but not at the end of the 

    A very slightly increased incidence of hepatocellular adenomas 
and carcinomas, alone or combined, was found in the treated males.  
There was no dose relation.  The only significant increase was 
found for carcinomas in males at 235 mg/kg, which was nevertheless 
very close to the average historical incidence for B6C3F1 mice in 
the performing laboratory.  A slightly increased incidence of 
Harderian gland neoplasms were observed in males at 125 and 235 
mg/kg.  The significance of this finding is unclear (NCA, 1983). 

    At the time of the evaluation of this document, the results of 
an inhalation study in progress in the US National Institute of 
Environmental Health Sciences were not available (NTP, 1984). 

7.3.  Mutagenicity

    The numbers of revertants of  Salmonella typhimurium TA98, 
TA100, and TA1535 were increased 3- to 7-fold in a dose-related 
manner, when plates were exposed to the vapour of methylene 
chloride of undisclosed purity at levels up to 200 g/m3 air.  
Metabolic activation by either induced rat liver S9 fraction, 
cytosol fraction, or microsomal fraction increased the mutagenicity 
(Simmon et al., 1977; Jongen et al., 1978, 1982; Nestmann et al., 
1980, 1981; Gocke et al., 1981).  It was shown that the direct 
mutagenicity of methylene chloride could be attributed to bacterial 
metabolic pathways similar to those in the rat (Green, 1983). 

    A dose-related increase in the frequency of gene conversions, 
mitotic recombinations, and reversions was found for cultures of 
 Saccharomyces cerevisiae strain D7, but not for strains D4 and D3, 
exposed to methylene chloride of undisclosed purity.  Strain D7 

contains more cytochrome P-450 than strain D4 and could, perhaps, 
activate methylene chloride (Simmon et al., 1977; Callen et al., 

    No mutagenicity was detected in the recessive lethal test on 
 Drosophila melanogaster fed, or injected with, 1 - 2% methylene 
chloride (Abrahamson & Valencia, 1980).  A 2-fold increase in the 
number of recessive lethals was found after the feeding of 1 - 5% 
methylene chloride in 2% dimethylsulfoxide (Gocke et al., 1981). 

    Methylene chloride was not mutagenic in several tests in which 
mammalian somatic cells, including human cells were used (Gocke et 
al., 1981; Jongen et al., 1981; Perocco & Prodi, 1981; Andrae & 
Wolff, 1983; Burek et al., 1984).  A weakly positive effect on SCEs 
was observed in vapour-exposed Chinese hamster V79 cells (Jongen et 
al., 1981).  The same test was negative with and without metabolic 
activation in a suspension of Chinese hamster ovary cells, while 
mitotic delays and chromosome aberrations were found (Thilagar & 
Kumaroo, 1983).  Transformation of vapour-exposed Syrian hamster 
embryo cells by SA7 adenovirus was enhanced in a dose-related 
manner (Hatch et al., 1983). 

7.4.  Effects on Reproduction and Teratogenicity

    Rats received methylene chloride in the drinking-water at a 
level of 125 mg/litre during a period of 13 weeks before mating.  
No effects were found on the female fertility index, litter size, 
survival of pups at 4 weeks, and the number of resorptions 
(Bornmann & Loeser, 1967).  Fetuses of 19 rats exposed to a 
methylene chloride concentration of 4340 mg/m3 air on days 6 - 15 
of pregnancy, for 7 h/day, showed an increased incidence of dilated 
renal pelvis.  Fetuses of 12 mice, exposed similarly, showed an 
increased incidence of extra sternebrae.  The maternal weight of 
mice increased.  Rat and mice dams had carboxyhaemoglobin levels as 
high as 12.5% during exposure (Schwetz et al., 1975).  Groups of 18 
rats were exposed before and during, or only during 17 days of 
pregnancy to a methylene chloride concentration of 15 600 mg/m3 
air for 6 h/day.  Blood carboxyhaemoglobin levels of dams ranged 
from 7.2 to 10.1% of saturation.  Relative and absolute liver 
weights were increased.  Fetal body weights decreased (Hardin & 
Manson, 1980).  In the same study, 4 groups of 10 rats each were 
exposed under the same conditions and were allowed to deliver their 
litters for neurobehavioural testing.  Changes in the general 
activity of pups were found from the age of 10 days in both sexes, 
to 150 days in males only (Bornschein et al., 1980). 

    Exposure of pregnant rats to methylene chloride may lead to 
exposure of the fetus to both methylene chloride and carbon 
monoxide (Anders & Sunram, 1982). 


8.1.  Short-Term Exposures

8.1.1.  Controlled studies

    Neurobehavioural changes were observed at low exposures. 
After 1.5 - 3 h of exposure to 694 mg/m3, vigilance disturbance 
and an impaired combined tracking monitoring performance were found 
(Putz et al., 1976).  The critical flicker frequency, a measure for 
sensory function, was reduced after 95 min of exposure to 1040 mg/m3 
(Fodor & Winneke, 1971).  After 4 h of exposure to 2610 mg/m3, 
psychomotor performance was decreased (Winneke, 1974).  Visually 
evoked response alterations, also a measure of sensory function, 
were seen after 1 h of exposure to 2400 mg/m3, while exposed 
subjects experienced lightheadedness.  Blood and urine variables, 
except carboxyhaemoglobin levels, were normal in this study after 
1 - 2 h of exposure to levels of methylene chloride between 739 and 
3420 mg/m3.  No eye, nose, or throat irritation was observed 
(Stewart et al., 1972).  Most neurobehavioural effects observed 
were less pronounced or absent with carbon monoxide exposures 
resulting in comparable carboxyhaemoglobin levels (Winneke, 1974; 
Putz et al., 1976).  The odour threshold for methylene chloride is 
743 mg/m3 (Leonardos et al., 1969). 

8.1.2.  Accidental exposures

    The increase in blood carboxyhaemoglobin saturation following 
methylene chloride exposure has already been discussed.  The most 
prominent effect of methylene chloride exposure is a reversible 
central nervous system (CNS) depression, ultimately resulting in 
narcosis, for example, after 30 min of exposure to 69 000 mg/m3 
(Moskowitz & Shapiro, 1952).  High carboxyhaemoglobin levels (up to 
50%) have been measured in the blood of unconscious subjects (Fagin 
et al., 1980). 

    Signs of CNS-depression, narcosis, irritation of the eyes and 
respiratory tract, lung oedema, and sometimes death were found 
after accidental exposures to methylene chloride or paint remover 
containing this compound (Moskowitz & Shapiro, 1952; Hughes, 1954; 
Bonventre et al., 1977; Fagin et al., 1980).  Three myocardial 
infarctions in one subject were reported to have followed 3 
exposures to a paint remover containing methylene chloride over a 
period of approximately 8 months.  The subject was exposed in a 
poorly ventilated room, and concentrations may have been very high 
(Stewart & Hake, 1976).  Electrocardiographic changes resembling 
those after carbon monoxide poisoning were found in an exposed man 
with a history suggesting ischaemic heart disease (Benzon et al., 
1978).  Three probable cases of phosgene poisoning occurred after 
the use of methylene chloride-based paint remover near a source of 
heat (Gerritsen & Buschmann, 1960; English, 1964). 

8.1.3.  Effects on the skin and eyes

    Several reports already discussed indicate the irritative 
action of methylene chloride on the eyes and skin. 

    Slight erythema was found, when methylene chloride-containing, 
aerosol-spray deodorants were used twice a day for 12 weeks by 75 
men and women (Meltzer et al., 1977).  On direct contact, methylene 
chloride caused a burning sensation and pain (Stewart & Dodd, 

8.2.  Long-Term Exposure

8.2.1.  Occupational exposure

    The few reports available deal with small groups of 
occupationally-exposed subjects.  Workers exposed occupationally to 
a time-weighted average of 114 mg/m3 had carboxyhaemoglobin levels 
of between 0.8 and 2.5%.  No effects were found on clinical 
chemistry, haematology, or electrocardiograms (DiVincenzo & Kaplan, 
1981a).  Cherry et al. (1981) did not find any exposure-related, 
long-term damage in 29 subjects as evidenced by subjective 
symptoms, neurobehavioural tests, motor nerve conduction velocity, 
electrocardiograms, and clinical examinations.  The men had been 
exposed for several years to levels of methylene chloride ranging 
from 260 to 347 mg/m3.  Age-matched controls were used.  In a 
study without a control group, neurasthenic disorders and 
irritation of the eyes and respiratory passages were experienced by 
half of the 33 workers exposed to methylene chloride for an average 
of 2 years.  Digestive disorders were reported by one-third of 
these workers.  Formic acid was found in the urine.  No other 
deviations were found during the internal, nervous, eye, and 
laboratory examinations.  The methylene chloride concentrations 
measured varied between 100 and 17 000 mg/m3 (Kuzelova & Vlasak, 
1966).  Irreversible damage to the central nervous system with 
acoustic and optical illusions and hallucinations was diagnosed in 
1 man, who had been exposed for 5 years to methylene chloride at 
levels ranged from 2290 to 12 500 mg/m3 (Weiss, 1969).  Another 
man, exposed for 3 years to levels of methylene chloride ranging 
from 1735 to 3470 mg/m3 showed a bilateral temporal lobe 
degeneration (Barrowcliff & Knell, 1979).  A case of delirium and 
seizures was reported of a man who was exposed to methylene 
chloride during 4 years. The man reported a 12-month history of 
intermittent headache, nausea, blurred vision, shortness of breath, 
and transient memory disturbances.  Neuro-psychological and EEG 
examinations revealed a dysfunction of the right hemisphere.  All 
symptoms and signs cleared with removal from the workplace (Tariot, 
1983).  In 46 subjects exposed to methylene chloride concentrations 
of 6 - 34 mg/m3 for several years, an excess (not significant) of 
digestive disorders and hypotonia was found over controls, while 
symptoms of gall bladder pathology and swollen liver were frequent.  
No details were given concerning drinking or smoking habits (Kashin 
et al., 1980). 

    A clinical laboratory evaluation of 266 exposed volunteer 
workers and 251 reference volunteer workers from two cellulose 
di- and tri-acetate plants in the USA, taking into account smoking 
habits, race, sex, age, intensity of exposure, and time of 
venepuncture, revealed increases in red cell counts, haemoglobin 
levels and haematocrit among white women exposed to a methylene 

chloride level of approximately 1650 mg/m3.  Carboxyhaemoglobin 
levels were elevated in all exposed groups at all exposure levels 
(section 5.3).  A dose-related increase was observed in serum 
bilirubin for exposed subjects of both sexes.  A total of 24 
exposed male volunteers and 26 reference male volunteers from the 
above 2 industries were also selected for 24-h electrocardiographic 
monitoring.  Three exposed and 8 reference workers had reported a 
history of heart disease.  Neither increased ventricular or 
supraventricular ectopic activity nor increased episodic ST-segment 
depression was found to be associated with methylene chloride 
exposure (Ott et al., 1983). 

    In women occupationally exposed to an average methylene 
chloride concentration of 86 mg/m3, the compound was found in the 
placenta, fetus, and breast milk (0.07 mg/litre milk average) 
(Vosovaja et al., 1974). 

8.2.2.  Mortality studies

    When the mortality experience of 334 deceased male industrial 
workers, who had been exposed to levels of methylene chloride up to 
1210 mg/m3, was compared with that of the non-exposed industrial 
workers and the New York State male populations, no excess age-and 
cause-specific mortality was found.  A total of 751 male workers 
with exposures for up to 30 years were subsequently followed up for 
mortality for 13 years.  No excess mortality was found compared 
with 2 internal and 2 external control groups (Friedlander et al., 
1978).  The data on this cohort have been updated with 4 more 
years.  The mortality was consistent with that of industrial 
controls and less than that expected of the New York State controls 
(Hearne & Friedlander, 1981). 

    The mortality experience of 1271 male and female workers of a 
cellulose di- and tri-acetate plant with time-weighted-average 
exposures to methylene chloride of between 486 and 1648 mg/m3, 
for a period up to 23 years, was compared with that of corresponding 
USA populations and a reference cohort of 948 workers in a 
cellulose diacetate plant, where no methylene chloride was used.  
The mortality, specified by cause (with a focus on ischaemic heart 
disease), sex, race, and for each cause, duration of exposure, 
length of follow-up, and employment status was comparable to that 
of the USA populations.  The mortality rate among white men was 
higher than that of the reference cohort for the following 
categories:  all causes, diseases of the circulatory system, 
ischemic heart disease, and all external causes.  Observed deaths 
in the reference group were considerably fewer than the USA 
experience for each of these categories.  According to the authors, 
the mortality trends for cardiovascular disease can be explained by 
expected geographical differences (Ott et al., 1983). 


    Human exposure is mainly through inhalation.  Absorption via 
the skin is slow.  Methylene chloride is rapidly absorbed via the 
gastrointestinal tract and crosses the placenta and blood-brain 

    Acute effects

    The odour threshold for methylene chloride is 743 mg/m3
(Leonardos et al., 1969).  The predominant effects of methylene 
chloride in human beings are central nervous system depression and 
the production of elevated carboxyhaemoglobin levels in the blood.  
These effects are reversible.  Mild behavioural disturbances (e.g., 
disturbances of vigilance) have been reported following exposure to 
694 mg/m3 of methylene chloride in air for 1.5 - 3 h (Putz et al., 
1976) and impairment of psychomotor performance after a 4-h 
exposure to 2610 mg/m3 (Winneke, 1974).  Narcosis occurred 
following exposure to 69 000 mg/m3 for 30 min (Moskowitz & Shapiro, 
1952).  Individuals with heart disease may be especially at risk, 
when exposed to methylene chloride, because of the hypoxia induced. 

    The minimum observed effect level for short-term inhalation 
exposure was approximately 690 mg/m3 (Putz et al., 1976). 

    Chronic effects

    The predominant chronic effects in human beings are nervous 
system depression and an elevated carboxyhaemoglobin saturation of 
the blood.  However, no exposure-related subjective symptoms, 
neurobehavioural effects, motor nerve conduction velocity changes, 
electrocardiogram changes, or clinical effects were noted in 
workers exposed to methylene chloride levels of between  260 -347 
mg/m3, compared with age-matched controls (Cherry et al., 1981). 

    Methylene chloride has been shown to cross the placenta and has 
been found to accumulate in fetal tissue and breast milk (Vosovaja 
et al., 1974).  In one study designed to assess teratogenic 
potential (Schwetz et al., 1975), rats and mice were exposed by 
inhalation to 4340 mg/m3 during days 6 - 15 of gestation.  The 
results of this study indicated an increased incidence of extra 
sternebrae in mice as well as a greater incidence of dilated renal 
pelvis in rats.  In another study (Hardin & Manson, 1980), rats 
were exposed by inhalation to a methylene chloride concentration of 
15 600 mg/m3 for 6 h/day, before and/or during 17 days of pregnancy.  
The purpose of this study was to ascertain whether exposure before 
and during gestation has a greater effect on the conceptus than 
exposure only before gestation.  No significant effects were 
reported, except that the pups of rats exposed during gestation had 
lower fetal body weights.  In the same study, additional groups of 
rats were similarly exposed and allowed to litter, in order to 
evaluate the potential for behavioural teratogenic effects 
(Bornschein et al., 1980).  As early as 10 days of age, both male 
and female pups exhibited treatment-related effects in general 
activity tests.  Changes in the general activity of male pups were 

still demonstrable 150 days post partum.  While results of the 
previous studies (Schwetz et al., 1975; Hardin & Manson, 1980) tend 
to indicate that the teratogenic hazard is minimal, the results of 
the neurobehavioural study of Bornschein et al. (1980) suggest the 
possiblity of delayed behavioural effects. 

    Only one reproduction study was available, which precludes 
assessment of a potential reproduction hazard.  In this study 
(Bornmann & Loeser, 1967), no reproductive impairment was found 
when rats were allowed to mate after receiving 125 mg of methylene 
chloride per litre of drinking-water for 13 weeks. 

    Results of  in vitro studies showed that methylene chloride
was mutagenic in bacteria and fungi.  However, most tests on 
mammalian somatic cells, including human cells, were negative. 

    In 2 inhalation studies in rats the incidence of benign mammary 
tumours was elevated neither in male nor in female rats, but the 
total number of mammary tumours was increased in a dose-related 
manner (Nitschke et al., 1983; Burek et al., 1984).  In the study 
of Burek et al. (1984), an increase of salivary gland region 
sarcomas was found in male rats.  In Golden Syrian hamsters, no 
significant increases in tumour incidences were found.  In a 
drinking-water study with rats and mice, no significant increases 
in tumour incidences were found, while an increased incidence of 
foci or areas of altered liver cells was observed (NCA, 1982, 
1983).  In two epidemiological mortality studies, there was no 
excess mortality due to cancer compared with control populations 
(Friedlander et al., 1978; Ott et al., 1983).  The data are 
inadequate for assessing whether or not methylene chloride is to be 
considered carcinogenic for animals and man.  According to a 
previous reevaluation of all available published epidemiological, 
experimental, and short-term test data, an IARC Working Group 
concluded that methylene chloride could not be classified as to its 
carcinogenicity for human beings (IARC, 1982). 

    A no-observed-adverse-effect level for long-term inhalation 
exposure was of the order of 260 - 350 mg/m3 (Cherry et al., 1981).  
A lowest-observed-effect level could not be derived from the 
available human data. 


10.1.  Occupational Exposure

    Maximum allowable concentrationsa are 49 mg/m3 (14 ppm, ceiling 
value) in the USSR, 250 mg/m3 (70 ppm, TWA) in Sweden, 360 mg/m3 
(100 ppm, TWA) in the Federal Republic of Germany, 700 mg/m3 (200 ppm, 
TWA) in the Netherlands, 360 mg/m3 (100 ppm, TWA) in the USA. 

10.2.  Food

    The Council of Europe (1978) recommends a maximum of 5 mg/kg 
wet weight in food.  The Food and Drug Administration (1977) in the 
USA allows maxima of 30 mg/kg wet weight in spice oleoresins, 2.2% 
in hops, and 10 mg/kg wet weight in coffee. 

10.3.  Storage and Transport

    The United Nations Committee of Experts on the Transport of 
Dangerous Goods (1984) qualifies methylene chloride as a toxic 
substance (Class 6.1) with minor danger for packing purposes 
(Packing Group III).  Packing methods and a label are recommended.  
The Inter-Governmental Maritime Consultative Organizationb (1981) 
also qualifies methylene chloride as a toxic substance (Class 6.1) 
and recommends packing, stowage, and labelling methods for maritime 
transport in glass bottles, cans, and drums.  It is stressed, that 
phosgene fumes are formed when methylene chloride is involved in a 
fire and that stowage should be under shaded conditions away from 
radiant heat. 

    The label recommended by both organizations is:


a Values quoted in national lists.
b Now the International Maritime Organization.


ABRAHAMSON, S. & VALENCIA, R.  (1980)  Evaluation of 
substances of interest for genetic damage using  Drosophila 
 melanogaster.  In:  Mutagenicity of methylene chloride, 
Oakridge, Tennessee, National Toxicology Program, Cellular and 
Genetic Toxicology Science Applications Inc.

AHMED, A.E. & ANDERS, M.W.  (1976)  Metabolism of 
dihalomethanes to formaldehyde and inorganic halide I.  In 
 vitro studies.  Drug Metab. Dispos., 4: 357-361.

AHMED, A.E. & ANDERS, M.W.  (1978)  Metabolism of 
dihalomethanes to formaldehyde and inorganic halide II. 
Studies on the mechanism of the reaction.  Biochem. Pharmacol., 
27: 2021-2025.

Toxicity of perchloroethylene, trichloroethylene, 
1,1,1-trichloroethane, and methylene chloride to fathead 
minnows.  Bull. environ. Contam. Toxicol., 20: 344-352.

ANDERS, M.W. & SUNRAM, J.M.  (1982)  Transplacental passage of 
dichloromethane and carbon monoxide.  Toxicol. Lett., 12: 

ANDERS, M.W., KUBIC, V.L., & AHMED, A.E.  (1977)  Metabolism 
of halogenated methanes and macromolecular binding. 
 J. environ. Toxicol., 1: 117-124.

ANDRAE, U. & WOLFF, T.  (1983)  Dichloromethane is not 
genotoxic in isolated rat hepatocytes.  Arch. Toxicol., 52: 

ASTRAND, I., OVRUM, P., & CARLSSON, A.  (1975)  Exposure to 
methylene chloride. I. Its concentration in alveolar air and 
blood during rest and exercise and its metabolism.  Scand. J. 
 Work Environ. Health, 1: 78-94.

ophtalmic toxicology of dichloromethane.  Toxicology, 6: 

BALMER, M.F., SMITH, F.A., LEACH, L.J., & YUILE, C.L.  (1976)  
Effects in the liver of methylene chloride inhaled alone and 
with ethyl alcohol.  Am. Ind. Hyg. Assoc. J., 37: 345-352.

BARETTA, E.D., STEWART, R.D., & MUTCHLER, J.E.  (1969)  
Monitoring exposures to vinyl chloride vapor: breath analysis 
and continuous air sampling.  Am. Ind. Hyg. Assoc. J., 30: 537-544.

BARROWCLIFF, D.F. & KNELL, A.J.  (1979)  Cerebral damage due 
to endogenous chronic carbon monoxide poisoning caused by 
exposure to methylene chloride.  J. Soc. Occup. Med., 29: 12-14.

BARSOUM, G.S. & SAAD, K.  (1934)  Relative toxicity of certain 
chlorine derivatives of the aliphatic series.  Q. J. Pharm. 
 Pharmacol., 7: 205-214.

BAUER, U.  (1978)  [Halogenated carbohydrates in drinking- and 
surface water, results of measurements in 1976/77 in the 
Federal Republic of Germany (Drinking-water from 100 towns, 
surface water from Ruhr, Lippe, Main, Rhein).] 
 WaBoLu-Berichte, 3: 64-74 (in German).

BELEJ, M.A., SMITH, G.A., & AVIADO, D.M.  (1974)  Toxicity of 
aerosol propellants in the respiratory and circulatory system. 
IV. Cardiotoxicity in the monkey.  Toxicology, 2: 381-395.

BELLAR, T.A., LICHTENBERG, J.J., & KRONER, R.C.  (1974)  The 
occurrence of organohalides in chlorinated drinking water. 
 J. Am. Water Works Assoc., 66: 703-706.

BENZON, H.T., CLAYBON, L., & BRUNNER, E.A.  (1978)  Elevated 
carbon monoxide levels from exposure to methylene chloride. 
 J. Am. Med. Assoc., 239: 2341.

BERGMAN, K.  (1979)  Whole-body autoradiography and allied 
tracer techniques in distribution and elimination studies of 
some organic solvents: benzene, toluene, xylene, styrene, 
methylene chloride, chloroform, carbon tetrachloride and 
trichloroethylene.  Scand. J. Work Environ. Health, 
5(Suppl. 1): 1-263.

D.  (1980)  Détermination de la concentration léthale 50 des 
principaux hydrocarbures aliphatiques chlorés chez le rat. 
 Arch. Mal. prof. Méd. Trav. Sécur. soc., 41: 317-321.

BASTOS, M.L.  (1977)  Two deaths following accidental 
inhalation of dichloromethane and 1,1,1-trichloroethane. 
 J. anal. Toxicol., 1: 158-160.

BORNMANN, G. & LOESER, A.  (1967)  [The question of the 
chronic toxic action of dichloromethane.]  Z. Lebensm. Unters. 
 Forsch., 136: 14-18 (in German).

Behavioral toxicity in the offspring of rats following 
maternal exposure to dichloromethane.  Toxicol. appl. 
 Pharmacol., 52: 29-37.

BRUNNER, W., STAUB, D., & LEISINGER, T.  (1980)  Bacterial 
degradation of dichloromethane.  Appl. environ. Microbiol., 

BUCCAFUSCO, R.J., ELLS, S.J., & LE BLANC, G.A.  (1981)  Acute 
toxicity of priority pollutants to bluegill  (Lepomis 
 macrochirus). Bull. environ. Contam. Toxicol., 26: 446-452.

McKENNA, M.J.  (1984)  Methylene chloride: A two-year 
inhalation toxicity and oncogenicity study in rats and 
hamsters.  Fundam. appl. Toxicol., 4: 30-47.

CALLEN, D.F., WOLF, C.R., & PHILPOT, R.M.  (1980)  Cytochrome 
P-450 mediated genetic activity and cytotoxicity of seven 
halogenated aliphatic hydrocarbons in  Saccharomyces 
 cerevisiae. Mutat. Res., 77: 55-63.

CARLSSON, A. & HULTENGREN, M.  (1975)  Exposure to methylene 
chloride. III. Metabolism of 14C-labelled methylene chloride 
in rat.  Scand. J. Work Environ. Health, 1: 104-108.

CEFIC  (1983)   Statement on methylene chloride. Joint 
 assessment of commodity chemicals, Brussels, Conseil Européan 
du Fédération de l'Industrie Chimique (JACC, Report No. 4).

(1981)  Some observations on workers exposed to methylene 
chloride.  Br. J. ind. Med., 38: 351-355.

COUNCIL OF EUROPE  (1978)   Substances used in plastic 
 materials coming into contact with food, Strasbourg, Council 
of Europe (P-SG(78)26).

(1976)  Photochemical oxidation of halocarbons in the 
troposphere.  Atmos. Environ., 10: 305-308.

(1981)  Covalent binding of halogenated volatile solvents to 
subcellular macromolecules in hepatocytes.  Life Sci., 29:1207-1212.

DIETZ, F. & TRAUD, J.  (1973)  [Determination of low molecular 
weight halogenated hydrocarbons in water and sludge using gas 
chromatography.]  Vom Wasser, 41: 137-155 (in German).

Evaporation rates and reactivities of methylene chloride, 
chloroform, 1,1,1-trichloroethane, trichloroethylene, 
tetrachloroethylene, and other chlorinated compounds in dilute 
aqueous solutions.  Environ. Sci. Technol., 9: 833-838.

DI VINCENZO, G.D. & KAPLAN, C.J.  (1981a)  Uptake, metabolism, 
and elimination of methylene chloride vapor by humans. 
 Toxicol. appl. Pharmacol., 59: 130-140.

DI VINCENZO, G.D. & KAPLAN, C.J.  (1981b)  Effect of exercise 
or smoking on the uptake, metabolism, and excretion of 
methylene chloride vapor.  Toxicol. appl. Pharmacol., 59: 141-148.

DI VINCENZO, G.D., YANNO, F.J., & ASTILL, B.D.  (1971)  The 
gas chromatography analysis of methylene chloride in breath, 
blood, and urine.  Am. Ind. Hyg. Assoc. J., 32: 387-391.

DI VINCENZO, G.D., YANNO, F.J., & ASTILL, B.D.  (1972)  Human 
and canine exposures to methylene chloride vapor.  Am. Ind. 
 Hyg. Assoc. J., 33: 125-135.

DUPRAT, P., DELSAUT, L., & GRADISKI, D.  (1976)  Pouvoir 
irritant des principaux solvents chlorés aliphatiques sur la 
peau et les muqueuses oculaires du lapin.  J. Eur. Toxicol.,
9: 171-177.

ENGLISH, J.M.  (1964)  A case of probable phosgene poisoning. 
 Br. med. J., 1: 38.

ENGSTROM, J. & BJURSTROM, R.  (1977)  Exposure to methylene 
chloride; content in subcutaneous adipose tissue.  Scand. J. 
 Work Environ. Health, 3: 215-224.

FAGIN, J., BRADLEY, J., & WILLIAMS, D.  (1980)  Carbon 
monoxide poisoning secondary to inhaling methylene chloride. 
 Br. med. J., 281: 1461.

FLURY, F. & ZERNIK, F.  (1931)   [Harmful gases, vapours, 
 mists, smokes, and dusts,] Berlin, Julius Springer, pp. 
311-312 (in German).

FODOR, G.G. & ROSCOVANU, A.  (1976)  Increased blood-CO- 
content in humans and animals by incorporated halogenated 
hydrocarbons.  Zentralbl. Bakt. Hyg. I. Abt. Orig. B., 
162: 34-40.

FODOR, G.G. & WINNEKE, H.  (1971)  Nervous system disturbances 
in men and animals experimentally exposed to industrial 
solvent vapors. In: Englund, H.M., ed.  Proceedings of the 2nd 
 International Clean Air Congress, New York, Academic Press, 
pp. 238-243.

[Endogenous CO formation resulting from incorporated 
halogenated hydrocarbons of the methane series.]  Luft,
33: 258-259 (in German).

FOOD AND DRUG ADMINISTRATION  (1977)  US Code. In:  Federal 
 Register, Title 21, parts 173.255, 175.105, 177.1580, pp. 430, 
438, 443, 527.

FRIEDLANDER, B.R., HEARNE, T., & HALL, S.  (1978)  
Epidemiologic investigation of employees chronically exposed 
to methylene chloride.  J. occup. Med., 20: 657-666.

FUJII, T.  (1977)  Direct aqueous injection gas chromatography-mass 
spectrometry for analysis of organohalides in water at 
concentrations below the parts per billion level.  J. Chromatogr., 
139: 297-302. 

GERRITSEN, W.B. & BUSCHMANN, C.H.  (1960)  Phosgene poisoning 
caused by the use of chemical paint removers containing 
methylene chloride in ill-ventilated rooms heated by kerosene 
stoves.  Br. J. ind. Med., 17: 187-189.

GOCKE, E., KING, M.-T., ECKHARDT, K., & WILD, D.  (1981)  
Mutagenicity of cosmetics ingredients licensed by the European 
Communities.  Mutat. Res., 90: 91-109.

GORDON, J.  (1976)   Air pollution assessment of methylene 
 chloride, Maclean, Virginia, Mitre Corporation (Mitre 
Technical Report MTR-7334).

FRANCIN, J.M.  (1978)  Toxicité aiguë comparée par inhalation 
des principaux solvants aliphatiques chlorés.  Arch. Mal. prof. 
 Méd. Trav. Sécur. soc., 39: 249-257.

GREEN, T.  (1983)  The metabolic activation of dichloromethane 
in a bacterial assay using Salmonella typhimurium.  Mutat. 
 Res., 118: 277-288.

GRIMSRUD, E.P. & RASMUSSEN, R.A.  (1975)  Survey and analysis 
of halocarbons in the atmosphere by gas chromatography-mass 
spectrometry.  Atmos. Environ., 9: 1014-1017.

HANSCH, C., VITTORIA, A., SILIPPO, C., & JOW, P.Y.C.  (1975)  
Partition coefficients and the structure-activity relationship 
of the anaesthetic gases.  J. Med. Chem., 18: 546-548.

HARDIN, B.D. & MANSON, J.M.  (1980)  Absence of 
dichloromethane teratogenicity with inhalation exposure in 
rats.  Toxicol. appl. Pharmacol., 52: 22-28.

S.  (1983)  Chemical enhancement of viral transformation in 
Syrian hamster embryo cells by gaseous volatile chlorinated 
methanes and ethanes.  Cancer Res., 43: 1945-1950.

(1972)  Continuous animal exposure to low levels of 
dichloromethane. In:  Proceedings of the 3rd Annual Conference 
 on Environmental Toxicology, Ohio, Wright-Patterson Air Force 
Base, Aerospace Medical Research Laboratory, pp. 199-208 
(AMRL-TR-130, Paper No. 12).

HEARNE, T. & FRIEDLANDER, B.R.  (1981)  Follow-up of methylene 
chloride study.  J. occup. Med., 23: 660.

Acute toxicity of 54 industrial chemicals to sheepshead 
minnows (Cyprinodon variegatus).  Bull. environ. Contam. 
 Toxicol., 27: 596-604.

HEPPEL, L.A. & NEAL, P.A.  (1944)  Toxicology of 
dichloromethane (methylene chloride). II. Its effect upon 
running activity in the male rat.  J. ind. Hyg. Toxicol., 26: 

PORTERFIELD, V.T.  (1944)  Toxicology of dichloromethane 
(methylene chloride). I. Studies on effects of daily 
inhalation.  J. ind. Hyg. Toxicol., 26: 8-16.

HOFFMAN, C.S.  (1973)  Beauty salon air quality measurements. 
 CTFA Cosmet. J., 5: 16-21.

HUGHES, J.P.  (1954)  Hazardous exposure to some so-called 
safe solvents.  J. Am. Med. Assoc., 156: 234-237.

MASCARENHAS, R.A., & SHIU, W.Y.  (1978)  The correlation of 
the toxicity to algae of hydrocarbons and halogenated 
hydrocarbons with their physical-chemical properties.  Environ. 
 Sci. Res., 16: 577-586.

IARC  (1979)   Some halogenated hydrocarbons, Lyons, 
International Agency for Research on Cancer, pp. 454-465 
(Monographs on the Evaluation of the Carcinogenic Risk of 
Chemicals to Humans, Vol. 20).

IARC  (1982)   Chemicals, industrial processes and industries 
 associated with cancer in humans, Lyons, International Agency 
for Research on Cancer, p. 111 (Monographs on the Evaluation 
of the Carcinogenic Risk of Chemicals to Humans, Supplement 4).

 International maritime dangerous goods code, London, IMCO.

IRPTC  (1984)   Data profile on methylene chloride, Geneva, 
International Register of Potentially Toxic Chemicals, United 
Nations Environment Programme.

JONGEN, W.M.F., ALINK, G.M., & KOEMAN, J.H.  (1978)  Mutagenic 
effect of dichloromethane on Salmonella typhimurium.  Mutat. 
 Res., 56: 245-248.

G.M., BERENDS, F., & KOEMAN, J.H.  (1981)  Mutagenicity 
testing of dichloromethane in short-term mammalian test 
systems.  Mutat. Res., 81: 203-213.

(1982)  The effect of glutathione conjugation and microsomal 
oxidation on the mutagenicity of dichloromethane in  Salmonella 
 typhimurium. Mutat. Res., 95: 183-189.

MIKHAILOVSKAJA, L.F., & SHMUTER, L.M.  (1980)  [Experimental 
and clinico-hygienic investigations of methylene chloride 
toxicity.]  Vrach. Delo., 1: 100-103 (in Russian).

KIMURA, E.T., EBERT, D.M., & DODGE, P.W.  (1971)  Acute 
toxicity and limits of solvent residue for sixteen organic 
solvents.  Toxicol. appl. Pharmacol., 19: 699-704.

KLECHKA, G.M.  (1982)  Fate and effects of methylene chloride 
in activated sludge.  Appl. environ. Microbiol., 44: 701-707.

KUBIC, V.L. & ANDERS, M.W.  (1975)  Metabolism of 
dihalomethanes to carbon monoxide. II.  In vitro studies.  Drug 
 Metab. Dispos., 3: 104-112.

KUBIC, V.L. & ANDERS, M.W.  (1978)  Metabolism of 
dihalomethanes to carbon monoxide. III. Studies on the 
mechanism of the reaction.  Biochem. Pharmacol., 27: 2349-2355.

CAUGHEY, W.S.  (1974)  Metabolism of dihalomethanes to carbon 
monoxide. I.  In vivo studies.  Drug Metab. Dispos., 2: 53-57.

KURPPA, K. & VAINIO, H.  (1981)  Effects of intermittent 
dichloromethane inhalation on blood carboxy-haemoglobin 
concentration and drug metabolizing enzymes in rat.  Res. 
 Commun. chem. Pathol. Pharmacol., 32: 535-544.

KUZELOVA, M. & VLASAK, R.  (1966)  [The effect of methylene 
chloride on the health of workers in production of film-foils 
and investigation of formic acid as a methylene-dichloride 
metabolite.]  Prac. Lek., 18: 167-170 (in Czech).

LE BLANC, G.A.  (1980)  Acute toxicity of priority pollutants 
to water flea  (Daphnia magna).   Bull. environ. Contam. 
 Toxicol., 24: 684-691.

LEONARDOS, G., KENDALL, D., & BARNARD, N.  (1969)  Odor 
threshold determination of 53 ororant chemicals.  J. Air 
 Pollut. Control Assoc., 19: 91-95.

MCEWEN, J.D., VERNOT, E.H., & HAUN, C.C.  (1972)   Continuous 
 animal exposure to dichloromethane, Ohio, Wright-Patterson Air 
Force Base, Aerospace Medical Research Laboratory 
(AMRL-TR-72-28, Systemed Corporation Report No. W 71005).

MCKENNA, M.J. & ZEMPEL, J.A.  (1981)  The dose-dependent 
metabolism of 14C-methylene chloride following oral 
administration to rats.  Food Cosmet. Toxicol., 19: 73-78.

R.J., NITSCHKE, K.D., & CHENOWETH, M.B.  (1980)  The 
pharmacokinetics of inhaled methylene chloride in human 
volunteers. In:  The 19th Annual Meeting of the Society of 
 Toxicology, Washington DC, 9-13 March (Paper No. 176).

MCKENNA, M.J., ZEMPEL, J.A., & BRAUN, W.H.  (1982)  The 
pharmacokinetics of inhaled methylene chloride in rats. 
 Toxicol. appl. Pharmacol., 65: 1-10.

R.  (1977)  Skin irritation, inhalation toxicity studies of 
aerosols using methylene chloride.  Drug Cosmet. Ind., 
120: 38-40.

(1981)  Correlations among the changes in hepatic microsomal 
components after intoxication with alkyl halides and other 
hepatotoxins.  Mol. Pharmacol., 20: 685-693.

MORRIS, J.B., SMITH, F.A., & GARMAN, R.H.  (1979)  Studies on 
methylene chloride-induced fatty liver.  Exp. mol. Pathol.,
30: 386-393.

MOSKOWITZ, S. & SHAPIRO, H.  (1952)  Fatal exposure to 
methylene chloride vapor.  Am. J. ind. Hyg. occup. Med., 
5: 116-123.

NCA  (1982)   Methylene chloride, Final Report, 24-month 
 chronic toxicity and oncogenicity study in rats, Hazleton 
Laboratories America Inc., National Coffee Association 
(Project No. 2112-101).

NCA  (1983)   24-Month oncogenicity study of methylene chloride 
 in mice. Final Report, Hazelton Laboratories America Inc., 
National Coffee Association (Project No. 2112-101).

NELSON, G.O. & SHAPIRO, E.G.  (1971)  A field instrument for 
detecting airborne halogen compounds.  Am. Ind. Hyg. Assoc. J., 
32: 757-765.

MUELLER, J.C.  (1980)  Mutagenicity of constituents identified 
in pulp and paper mill effluents using the Salmonella/ 
mammalian-microsome assay.  Mutat. Res., 79: 203-212.

(1981)  Mutagenicity of paint removers containing dichloro- 
methane.  Cancer Lett., 11: 295-302.

NICHOLLS, P.  (1975)  Formate as an inhibitor of cytochrome- C 
oxidase.  Biochem. Biophys. Res. Commun., 67: 610-616.

NICHOLSON, A.A., MERESZ, O., & LEMYK, B.  (1977)  
Determination of free and total potential heloforms in 
drinking water.  Anal. Chem., 49: 814-819.

NIOSH  (1976)   Criteria for a recommended standard: 
 occupational exposure to methylene chloride, Washington DC, US 
Department of Health, Education and Welfare (DHEW Publication 
No. (NIOSH) 76-138).

NIOSH  (1984)  In: Eller, P.M., ed.  Manual of analytical 
 methods, 3rd ed., Cincinnati, Ohio, US Department of Health 
and Human Services, Vol. 1.

MCKENNA, M.J.  (1983)   Methylene chloride: a two-year 
 inhalation toxicity and oncogenicity study in rats, Midland, 
Michigan, Dow Chemical Company (Report submitted to the US 
Food and Drug Administration by Toxicology Research 
Laboratory, Health and Environmental Sciences).

NORPOTH, K., WITTING, U., & SPRINGORUM, M.  (1974)  Induction 
of microsomal enzymes in the rat liver by inhalation of 
hydrocarbon solvents.  Int. Arch. Arbeitsmed., 33: 315-321.

NTP  (1984)   Review of current DHHS, DOE, and EPA research 
 related to toxicology, Research Triangle Park, North Carolina, 
National Toxicology Program, US Department of Health and Human 
Services, Public Health Service.

OTSON, R., WILLIAMS, D.T., & BOTHWELL, P.D.  (1981)  
Dichloromethane levels in air after application of paint 
removers.  Am. Ind. Hyg. Assoc. J., 42: 56-60.

WILLIAMS, P.R.  (1983)  Health evaluation of employees 
occupationally exposed to methylene chloride.  Scand. J. Work 
 Environ. Health, 9(Suppl. 1): 1-38.

PAGE, B.D. & KENNEDY, B.P.C.  (1975)  Determination of 
methylene chloride, ethylene dichloride, and trichloroethylene 
as solvent residues in spice oleoresins, using vacuum 
distillation and electron capture gas chromatography.  J. AOAC, 
58: 1062-1068.

PANKOW, D., GUTEWORT, R., GLATZEL, W., & TIEZE, K.  (1979)  
Effect of dichloromethane on the sciatic motor conduction 
velocity of rats.  Experientia (Basel), 35: 373-374.

PEARSON, C.R. & MCCONNELL, G.  (1975)  Chlorinated C1 and C2 
hydrocarbons in the marine environment.  Proc. R. Soc. Lond. 
 B., 189: 305-332.

PEROCCO, P. & PRODI, G.  (1981)  DNA damage by haloalkanes in 
human lymphocytes cultured  in vitro. Cancer Lett., 13: 213-218.

PUTZ, V.R., JOHNSON, B.L., & SETZER, J.V.  (1976)  A 
comparative study of the effects of carbon monoxide and 
methylene chloride on human performance.  J. environ. Pathol. 
 Toxicol., 2: 97-112.

RATNEY, R.S., WEGMAN, D.H., & ELKINS, H.B.  (1974)  In vivo 
conversion of methylene chloride to carbon monoxide.  Arch. 
 environ. Health, 28: 223-226.

REYNOLDS, E.S. & YEE, A.G.  (1967)  Liver parenchymal cell 
injury V. Relationships between patterns of chloromethane-C14 
incorporation into constituents of liver  in vivo and cellular 
injury.  Lab. Invest., 16: 591-603.

RITTMAN, B.E. & MCCARTY, P.L.  (1980)  Utilization of 
dichloromethane by suspended and fixed-film bacteria.  Appl. 
 Microbiol., 39: 1225-1226.

RODKEY, F.L. & COLLISON, H.A.  (1977a)  Biological oxidation 
of 14C-methylene chloride to carbon monoxide and carbon 
dioxide by the rat.  Toxicol. appl. Pharmacol., 40: 33-38.

RODKEY, F.L. & COLLISON, H.A.  (1977b)  Effect of 
dihalogenated methanes on the  in vivo production of carbon 
monoxide and methane by rats.  Toxicol. appl. Pharmacol., 40: 39-47.

ROTH, R.P., DREW, R.T., LO, R.J., & FOUTS, J.R.  (1975)  
Dichloromethane inhalation, carboxyhaemoglobin concentrations, 
and drug metabolizing enzymes in rabbits.  Toxicol. appl. 
 Pharmacol., 33: 427-437.

SALTZMAN, B.E.  (1972)  Direct reading colorimetric 
indicators. In:  Air sampling instruments for evaluation of 
 atmospheric contamination, 4th ed., ACGIH, Cincinnati, Ohio, 

R.A., SWINNERTON, J.W., & SAALFELD, F.E.  (1975)  
Identification of volatile organic contaminants in Washington 
DC municipal water.  Water Res., 9: 1143-1145.

(1981)  Dose-related effects of dichloromethane on rat brain 
in short-term inhalation exposure.  Chem.-Biol. Interactions, 
34: 315-322.

SCHWETZ, B.A., LEONG, B.K.J., & GEHRING, P.J.  (1975)  The 
effect of maternally inhaled trichloroethylene, perchloro- 
ethylene, methyl chloroform, and methylene chloride on 
embryonal and fetal development in mice and rats.  Toxicol. 
 appl. Pharmacol., 32: 84-96.

SIMMON, V.F., KAUHANEN, K., & TARDIFF, R.G.  (1977)  Mutagenic 
activity of chemicals identified in drinking water.  Dev. 
 Toxicol. environ. Sci., 2: 249-258.

SINGH, H.B., SALAS, L.J., & STILES, R.E.  (1982)  Distribution 
of selected gaseous organic mutagens and suspect carcinogens 
in ambient air.  Environ. Technol., 16: 872-880.

SPENCE, J.W., HANST, P.L., & GAY, B.W.  (1976)  Atmospheric 
oxidation of methyl chloride, methylene chloride and 
chloroform.  J. Air Pollut. Control Assoc., 26: 994-996.

STEWART, R.D. & DODD, H.C.  (1964)  Absorption of carbon 
tetrachloride, trichloroethylene, tetrachloroethylene, 
methylene chloride, and 1,1,1-trichloroethane through the 
human skin.  Am. Ind. Hyg. Assoc. J., 25: 439-446.

STEWART, R.D. & HAKE, C.L.  (1976)  Paint-remover hazard.  J. 
 Am. Med. Assoc., 235: 398-401.

BARETTA, E.D., & DODD, H.C.  (1972)  Experimental human 
exposure to methylene chloride.  Arch. environ. Health, 
25: 342-348.

STEWART, R.D., HAKE, C.L., & WU, A.  (1976)  Use of breath 
analysis to monitor methylene chloride exposure.  Scand. J. 
 Work Environ. Health, 2: 57-70.

(1981)  Dehalogenation of dichloromethane by cell extracts of 
Hyphomicrobium DM2.  Arch. Microbiol., 130: 366-371.

VON  (1947)  The toxicity and narcotic action of mono-chloro- 
mono-bromomethane with special reference to inorganic and 
volatile bromide in blood, urine and brain.  J. ind. Hyg. 
 Toxicol., 29: 382-389.

TABAK, H.H., QUAVE, S.A., MASHNI, C.I., & BARTH, E.F.  (1981)  
Biodegradability studies with organic priority pollutant 
compounds.  J. Water Pollut. Control Fed., 53: 1503-1518.

TARIOT, P.N.  (1983)  Delirium resulting from methylene 
chloride exposure: case report.  J. clin. Psych., 44: 340-342.

(1976)  Cardiac depression by haloalkane propellants, 
solvents, and inhalation anesthetics in rabbits.  Toxicol. 
 appl. Pharmacol., 38: 379-387.

THILAGAR, A.K. & KUMAROO, V.  (1983)  Induction of chromosome 
damage by methylene chloride in CHO cells.  Mutat. Res., 
116: 361-367.

TOFTGARD, R., NILSEN, O.G., & GUSTAFSSON, J.-A.  (1982)  Dose 
dependent induction of rat liver microsomal P-450 and 
microsomal enzymatic activities after inhalation of toluene 
and dichloromethane.  Acta pharmacol. toxicol., 51: 108-114.

TSURUTA, H.  (1975)  Percutaneous absorption of organic 
solvents 1. Comparative study of the in  vivo percutaneous 
absorption of chlorinated solvents in mice.  Ind. Health, 
13: 227-236.

DANGEROUS GOODS  (1984)   Transport of dangerous goods, 3rd 
revised ed., New York, United Nations.

US ITC  (1982)   Synthetic organic compounds, Washington DC, US 
International Trade Commission, US Production and Sales.

US NATIONAL ACADEMY OF SCIENCES  (1977)   Drinking-water and 
 health, Washington DC, NAS (A report of the Committee on Safe 

(1980)  An evaluation of using partition coefficients and 
water solubility to estimate bioconcentration factors for 
organic chemicals in fish. In: Eaton, J.G., Parrish, P.R., & 
Hendricks, A.C., ed.  Aquatic toxicology, Philadelphia, 
Pennsylvania, American Society for Testing and Materials, 
pp. 116-129.

[Levels of methylene chloride in biological fluids of pregnant 
or lactating workers of an industrial rubber products 
company.]  Gig. Tr. Prof. Zabol., 4: 42-43 (in Russian).

WEINSTEIN, R.S. & DIAMOND, S.S.  (1972)  Hepatotoxicity of 
dichloromethane with continuous inhalation exposure at a low 
dose level. In:  Proceedings of the 3rd Annual Conference on 
 Environmental Toxicology, Ohio, Wright-Patterson Air Force 
Base, Aerospace Medical Research Laboratory, pp. 209-222 
(AMRL-72-130, Paper No. 13).

WEINSTEIN, R.S., BOYD, D., & BACK, K.C.  (1972)  Effects of 
continuous inhalation of dichloromethane in the mouse: 
morphologic and functional observations.  Toxicol. appl. 
 Pharmacol., 23: 660-679.

WEISS, G. VON  (1969)  [Toxic encephalosis resulting from 
occupational contact with methylene chloride.]  Zentralbl. 
 Arbeitsmed. Arbeitsschutz, 17: 282-285 (in German).

WHITE, L.D., TAYLOR, D.G., MAUER, P.A., & KUPEL, R.E.  (1970)  
A convenient optimized method for the analysis of selected 
vapors in the industrial atmosphere.  Am. Ind. Hyg. Assoc. J., 
31: 225-232.

WINNEKE, G.  (1974)  Behavioral effects of methylene chloride 
and carbon monoxide as assessed by sensory and psychomotor 
performance. In: Xintaras, C., Johnson, B., & de Groot, I., 
ed.  Behavioral toxicology, Washington DC, US Government 
Printing Office, pp. 130-144.

ZOETEMAN, B.C.J., HARMSEN, K., & LINDERS, J.B.H.J.  (1980)  
Persistent organic pollutants in river water and groundwater 
of the Netherlands.  Chemosphere, 9: 231-249.

    See Also:
       Toxicological Abbreviations
       Methylene chloride (EHC 164, 1996, 2nd edition)
       Methylene chloride (HSG 6, 1987)
       Methylene chloride (PIM 343)