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    1,1,1-TRICHLOROETHANE

    Explanation

         This substance was evaluated for an acceptable daily intake for
    man by the Joint FAO/WHO Expert Committee on Food Additives in 1980
    (see Annex, Ref. 54). No toxicological monograph was issued.

         Since the previous evaluation, additional data have become
    available. This information is summarized and discussed in the
    following monograph.

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

    Absorption, distribution and excretion

         1,1,1-trichloroethane was rapidly absorbed through the lungs and
    the gastrointestinal tract. It was also absorbed through intact skin
    (Stewart, 1968; Fukabori et al., 1977; Tsuruta, 1975). After
    inhalation in mice it was found in blood, brain, kidney, and liver. A
    first order pharmacokinetic model for both uptake and elimination was
    found to fit the empirical data (Holmberg et al., 1977). After i.p.
    injection (700 mg/kg) into the rat, 98.7% was expired unchanged, 0.5%
    was expired as carbon dioxide, the remainder was excreted in the urine
    as the glucuronide of 2,2,2-trichloroethanol and trace amounts of
    uncharacterized metabolites were found in the carcass (Hake et al.,
    1960). Trichloroacetic acid was identified as a metabolite in
    the urine of rats (Eben & Kimmerle, 1974). Less than 0.5% of
    1,1,1-trichloroethane was found to be dechlorinated in vitro by rat
    liver microsomes (Van Dyke & Wineman, 1971). In an inhalation study
    with human subjects the absorption rate of 1,1,1-trichloroethane was
    not constant, but changed continuously throughout the study. For an
    eight hour exposure period, retention ranged from 26 to 32%. Pulmonary
    excretion of the solvent over a period of six days accounted for 90%
    of the absorbed material. Urinary excretion of the metabolites was
    slow, over a period of 12 days with most being eliminated during the
    first eight days. The proportion of metabolized solvent was low, since
    only an average of 1.8% of the retained solvent was excreted as
    dechloracetic acid and 4.2% as trichloroethanol (Humbert & Fernandez,
    1977).

    Effects on enzyme and other biochemical parameters

         Rats exposed to 20 Ámol/l (489 ppm) (0.0489%) of
    1,1,1-trichloroethane for six hours/day for four days were found to
    have a marked sequestration of the solvent in the perirenal fat. The
    solvent was detectable in the fat as well as brain and liver 17 hours
    after the end of the four day exposure. Further exposure for two hours
    on the fifth day was found to increase the brain and liver solvent

    content 100-fold but in fat only 10-fold. No effect was found on brain
    glutathione but decreased brain RNA content and increased acid
    proteinase activity was observed. Liver microsomal cytochrome P-450
    content decreased as exposure time was increased (Vainio et al., 1978;
    Savolainen, 1977). 1,1,1-trichloroethane was reported to degrade the
    haeme moiety of cytochrome P-450. Degradation appeared to require
    metabolic activation since NADPH was a requirement for binding
    (Ivanetich et al., 1978).

    TOXICOLOGICAL STUDIES

    Special studies on carcinogenicity

         The in vitro transforming potential of 1,1,1-trichloroethane
    was shown in a Fischer rat embryo cell system (F1706). Rat embryo cell
    subcultures containing genetic information of the murine type "C" RNA
    oncovirus were treated with a minimally toxic concentration of the
    compound (99 Ál) in growth medium for 48 hours. After several
    subcultures, the transformed cells were inoculated into newborn
    Fischer rats. After 68 days there was a 100% (N=8) tumour incidence at
    the site of injection. By 82 days postinoculation, acetone, the
    negative control, did not induce tumours (N=13) (Price et al., 1978).

         Groups of 50 male and 50 female B6C3F1 mice, five weeks of age
    were administered technical grade 1,1,1-trichloroethane (containing 3%
    para-dioxane and 2% impurities) in corn oil by gavage at two dosage
    levels, five days per week for 78 weeks. The dosage, levels were
    increased twice during the experiment. The time-weighted average doses
    for the high- and low-dose mice were 5615 and 2807 mg/kg bw per day.
    An untreated group of 20 mice of each sex were used as negative
    controls; carbon tetrachloride was used in positive-control animals;
    no vehicle-control animals were used.

         About half of the treated and control males died within one year
    of exposure. Five per cent. of the control, 18% of the low-dose, and
    40% of the high-dose females died within one year. At 90 weeks, 15
    low-dose males, 11 high-dose males, 2 negative-control males, 23
    low-dose females, 13 high-dose females, and 11 negative-control
    females remained alive and all survivors were killed in the 90th week.
    There was a moderate depression of body weight throughout the study in
    both sexes. Almost all organs, tissues, and gross lesions were
    histologically examined. Hepatocellular adenoma, carcinoma, or
    neoplastic nodules were found in four of 49 high-dose males. No other
    liver tumours were found in treated or negative-control mice.
    Virtually 100% of positive-control animals developed hepatocellular
    carcinoma (National Cancer Institute, 1977). Because of the short
    survival times, this study was not considered an adequate test of
    carcinogenicity and is currently being re-run.

         Groups of 50 male and 50 female Osborne-Mendel rats, seven weeks
    of age, were administered technical-grade 1,1,1-trichloroethane
    (containing 3% para-dioxane and 2% impurities) in corn oil by gavage
    at two dosage levels (750 and 1500 mg/kg bw per day) five days per
    week for 78 weeks. An untreated group of 20 rats of each sex were used
    as negative controls; carbon tetrachloride treated animals served as
    positive controls. All surviving animals were killed at 117 weeks of
    age. Treated animals exhibited early mortality when compared to
    controls. Only 3% of treated rats survived to termination of the
    experiment. Only one proliferative hepatocellular lesion (adenoma)
    occurred in rats treated with 1,1,1-trichloroethane. None occurred in
    the negative-control group and several neoplastic nodules and
    hepatocellular carcinomas occurred in the positive-control animals
    (National Cancer Institute, 1977). Because of poor survival rates this
    test of carcinogenicity is being re-run.

         Groups of 96 male and 96 female Sprague-Dawley rats were
    administered 1,1,1-trichloroethane via inhalation at a concentration
    of 875 or 1750 ppm (0.0875 or 0.1750%) for six hours per day, five
    days per week for 12 months. Groups of 192 untreated rats of each sex
    served as controls. Rats were then held for observation until 30
    months from the start of the experiment. No adverse effects were seen
    in treated animals with respect to growth, demeanour, haematology,
    urinalysis or mortality. Tissues from all animals were saved and
    examined histologically. No discernible increase in tumours occurred
    in treated animals over controls (Rampy et al., 1978).

    Special studies on mutagenicity

         1,1,1-trichloroethane was weakly mutagenic in Salmonella
    typhimurium strain TA-100 with or without a microsomal activation
    system (Simmon et al., 1977). Additional Salmonella studies have
    shown negative results (Schumann et al., 1980). Results of a 29-test
    battery of mutagenicity assays of the National Toxicology Programme on
    1,1,1-trichloroethane were described as "overwhelmingly negative"
    (Schumann et al., 1980).

    Special studies on reproduction

    Chicken embryo

         Groups of fertilized chicken eggs were injected with 1,1,1-
    trichloroethane and olive oil (total volume 25 Ál) at 2, 3 and 6 days
    of incubation. The approximate LD50 value varied between 50 and
    100 Ámol/egg. The eggs were examined after 14 days of incubation.
    Gross external malformations were observed in 21% of the survivors and
    3.6% of the vehicle controls. The malformations reported included
    exteriorization of viscera, profound oedema, and eye and skeletal
    abnormalities Elovaara et al., 1979).

    Rat

         Groups of Sprague-Dawley rats and Swiss-Webster mice were exposed
    to 1,1,1-trichloroethane by inhalation for seven hours daily on days
    6-15 of gestation at a concentration of 875 ppm (0.0875%) in air. A
    commercial grade containing 5.5% inhibitors and impurities was used
    giving a concentration of 50 ppm (0.005%) in the exposure chamber. A
    significant increase was reported in absolute weight of the liver of
    rats but not mice. The relative liver weights were unaffected in both
    species. No other maternal toxicity was uncovered.

         Certain soft tissue and skeletal abnormalities occurred in the
    litters of exposed mice and rats that did not occur in litters of
    control mothers. In mice, one of 13 litters had short tails, cleft
    palates, and extra sternebra. Split and malaligned sternebra were
    evident in two of 13 litters. In rats, 4% of the litters had
    supernumerary vertebra. These effects were not statistically
    significant, however. It was concluded that 1,1,1-trichloroethane
    (875 ppm) (0.0875%) caused little or no maternal, embryonal or foetal
    toxicity and that it was not teratogenic in either species under the
    experimental conditions (Schwetz et al., 1975).

    Acute toxicity
                                                                                    
    Animal       Route          LD50                       Reference
                                                                                

    Mouse        Oral     11.2 g/kg                   Torkelson et al., 1958

                 i.p.     4.7 g/kg                    Gehring, 1968

                 i.p.     5 g/kg                      Klaassen & Plaa, 1966

                 inhl     13 500 ppm (1.35%)/10h      Gehring, 1968

                 inhl     3 911 ppm (0.3911%)/2h      Horiguchi & Horiuchi, 1971

    Rat          Oral     10.3-12.3 g/kg              Torkelson et al., 1958

                 i.p.     3.8 ml/kg                   Klaassen & Plaa, 1969

                 inhl     18 000 ppm (1.8%)/3h        Adams et al., 1950

    Guinea-pig   Oral     9.5 g/kg                    Torkelson et al., 1958

    Rabbit       Oral     5.7 g/kg                    Torkelson et al., 1958

    Dog          i.p.     3.1 g/kg                    Klaassen & Plaa, 1967
                                                                                
    
    Short-term studies

         Groups of male CF-1 strain mice were exposed to
    1,1,1-trichloroethane at either 250 or 1000 ppm (0.025 or 0.1%) by
    inhalation in air continuously for 14 weeks. Serial sacrifice of
    control and high-exposure groups of mice from weeks 1 through 14
    demonstrated significant alterations in the centrilobular hepatocytes
    was shown by electron microscopy. These changes consisted of
    vesiculation of the rough endoplasmic reticulum, loss of attached
    polyribosomes, increased smooth endoplasmic reticulum, microbodies,
    ballooned cisternae of the rough endoplasmic reticulum, and
    triglyceride droplets. These effects were milder to minimal in the
    low-exposure group. Necrosis of individual hepatocytes, inflammatory
    infiltration, and hypertrophied Kupffer cells occurred in 40% of the
    high-exposure group after 12 weeks (McNutt et al., 1975).

         Groups of rats and cats were exposed to 1,1,1-trichloroethane
    vapour at 73 ppm (0.0073%) four hours per day from 50 to 120 days.
    Minor changes in the conditioned reflex activity of the cats were
    found. Venous hyperaemia was observed in the liver, kidneys, heart,
    and lungs of rats after 50 days and was more pronounced after 120
    days. Protein dystrophy of the liver parenchymal cells was observed in
    rats examined after 120 days of exposure. Emphysematous enlargement of
    alveoli and bronchial epithelium swelling were noted in rats after 50
    days and was more pronounced after 120 days. There were small amounts
    of mucus and detached epithelial cells in the bronchial lumen. The
    peribronchial nodules were hyperplastic (Tsapko & Rappoport, 1972).

    OBSERVATIONS IN MAN

         At least 30 fatalities associated with exposure to
    1,1,1-trichloroethane have been reported in the literature. In all of
    these cases death was due to severe depression of the CNS; autopsy
    also revealed damage to the lungs, liver, and kidneys. One case of
    possible hypersensitivity has been reported where neurological effects
    were minimal while liver and renal damage was prominent though
    reversible (Halevy et al., 1980; Bass, 1970; Caplan, 1976; Nathan &
    Toseland, 1979). The pharmacodynamics of human intoxication has also
    received attention (Stewart, 1961; Astrand, 1973; Seki, 1975).

         Exposure of male employees in four printing plants at average
    concentrations of 4, 25, 28, and 53 ppm (0.0004, 0.0025, 0.0028, and
    0.0053%) has been investigated. Tests of vibrational sense, routine
    laboratory examinations in haematology and urinalysis, and medical
    interviews did not reveal any adverse effects. From the measured
    decline in urinary concentrations of total trichloro- compounds, the
    biological half-life of 1,1,1-trichloroethane was determined to be
    8.7 ▒ 1.8 hours (N=7) (Seki et al., 1975).

         An epidemiological study of 151 matched pairs of employees was
    conducted in two adjacent textile plants, one of which used inhibited
    1,1,1-trichloroethane as a cleaning solvent. The eight-hour TWA (time-
    weighted-average) concentration ranged from 4 to 217 ppm (0.0004 to
    0.0217%); exposure duration ranged from less than one to five years.
    Cardiovascular and hepatic observations were of primary interest but
    other health parameters were also studied. Statistical analysis of the
    data did not reveal any exposure-related clinical findings (Kramer et
    al., 1978).

         Twenty-two female employees in a factory utilizing
    1,1,1-trichloroethane as the only solvent were exposed to air
    concentrations ranging from 110 to 990 ppm (0.011 to 0.099%) over a
    six-year period. The women were divided into three risk groups and
    compared with a reference group. No significant difference was
    observed between exposed and unexposed females with respect to
    clinical features, motor conduction, and psychometric data. "Neurotic"
    type complaints (such as headache, anxiety, nervousness, insomnia,
    etc.) were higher in the exposed group but this increase was not
    significant (Maroni, 1977).

    Comments

         1,1,1-trichloroethane is rapidly absorbed through the lungs and
    the gastrointestinal tract. The absorbed 1,1,1-trichloroethane is
    primarily excreted through the lungs, with lesser amounts excreted in
    the urine. Metabolites identified in the urine of man include
    trichloracetic acid, and 1,1,1-trichloroethanol. Inhalation of
    1,1,1-trichloroethane by rats and cats resulted in changes in the
    liver, as well as venous hyperaemia in the liver, kidney, heart and
    lungs. 1,1,1-trichloroethane caused little or no maternal or
    foetal toxicity in mice and rats, nor was it teratogenic.
    1,1,1-trichloroethane has not been demonstrated to be mutagenic in
    bacterial systems.

         Oral administration of 1,1,1-technical-trichloroethane to mice
    resulted in liver tumours. However, this carcinogenicity study, as
    well as a similar study in rats, is not considered adequate to
    determine if 1,1,1-trichloroethane is carcinogenic because of the poor
    survival of the test animals. The studies are being repeated.

    EVALUATION

    No ADI allocated.

    FURTHER WORK OR INFORMATION

         Results of ongoing life-time studies in rodents.

    REFERENCES

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         (Methyl Chloroform) Determined by Experiments on Laboratory
         Animals, Arch. Ind. Hyg. Occup. Med., 1, 225-236

    Astrand, I. et al. (1973) Methylchloroform Exposure. I. Concentration
         in Alveolar Air and Blood at Rest and During Exercise, Work
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    Bass, M. (1970) Sudden Sniffing Death, J.A.M.A., 212, 2075-2079

    Caplan, Y. H. (1976) 1,1,1-Trichloroethane: Report of a Fatal
         Inhalation, Clin. Toxicol., 9, 69-74

    Dowty, B. J., Carlisle, D. R. & Laseter, J. L. (1975) New Orleans
         Drinking Water Sources Tested by Gas Chromatography-Mass
         Spectrometry, Environ. Sci. Technol., 9, 762-765

    Eben, A. & Kimmerle, G. (1974) Metabolism, Excretion and Toxicity of
         Methylchloroform in Acute and Subacute Exposed Rats, Arch.
         Toxikol. 31, 233-242

    Elovaara, E. Hemminki, K. & Vainio, H. (1979) Effects of Methylene
         Chloride, Trichloroethane, and Trichloroethylene,
         Tetrachloroethylene, and Toluene on the Development of Chick
         Embryos, Toxicology, 12, 111-119

    EPA (1980) Ambient Water Quality Criteria for Chlorinated Ethanes,
         U.S. Environmental Protection Agency, Publication No.
         440/5-80-029, pp. 118

    Fukabori, S. et al. (1977) On the Cutaneous Absorption of
         1,1,1 Trichloroethane, J. Sci. Labour, 53, 89-95

    Gehring, P. J. (1968) Hepatotoxic Potency of Various Chlorinated
         Hydrocarbon Vapours Relative to Their Narcotic and Lethal
         Potencies in Mice, Toxicol. Appl. Pharmacol., 13, 287-298

    Hake, C. L. et al. (1960) The Metabolism of 1,1,1-Trichloroethane by
         the Rat, Arch. Environ. Health, 1, 101-105

    Halevy, J., Pitlik, S. & Rosenfeld, J. (1980) 1,1,1-Trichloroethane
         Intoxication: A Case Report with Transient Liver and Renal
         Damage. Review of the Literature, Clin. Toxicol., 16, 467-472

    Holmberg, B., Jakobson, I. & Sibvardsson, K. (1977) A Study on the
         Distribution of Methylchloroform and n-Octane in the Mouse During
         and After Inhalation, Scand. J. Work Environ. Health, 3,
         43-52

    Horiguchi, S. & Horiuchi, K. (1971) An Experiment of 1,1,1-
         Trichloroethane Vapor Exposure to mice (Supplementary Report on
         the Toxicity of 1,1,1-Trichloroethane I.), Jap. J. Ind. Health,
         13, 226-227

    Humbert, B. E. & Fernandez, J. G. (1977) Exposition au 1,1,1-
         Trichloroethane; Contribution Ó l'etude de l'absorption, de
         l'excretion et du Metabolism sur des Sujets Humains, Arch. Mal.
         Prof. Med. Trav., 38, 415-425

    IRAC (1979) Monographs on the Evaluation of the Carcinogenic Risk of
         Chemicals to Humans, Vol. 20, pp. 515-531

    Ivanetich, K. M. et al. (1978) Organic Compounds - Their Interaction
         with and Degradation of Hepatic Microsomal Drug Metabolizing
         Enzymes In Vitro, Drug Metab. Dispos., 6, 218-225

    Klaassen, C. D. & Plaa, G. L. (1966) Relative Effects of Various
         Chlorinated Hydrocarbons on Liver and Kidney Function in Mice,
         Toxicol. App. Pharmacol., 9, 139-151

    Klaassen, C. D. & Plaa, G. L. (1969) Comparison of the Biochemical
         Alterations Elicited in Livers from Rats Treated with Carbon
         Tetrachloride, Chloroform, 1,1,2-Trichloroethane, and 1,1,1-
         Trichloroethane, Biochem. Pharmacol., 18, 2019-2029

    Kramer, C. G. et al. (1978) Health of Workers Exposed to 1,1,1-
         Trichloroethane: A Matched-Pair Study, Arch. Environ. Health,
         33, 331-342

    Maroni, M. et al. (1977) A Clinical, Neurophysiological, and
         Behavioral Study of Female Workers Exposed to 1,1,1-
         Trichloroethane, Scand. J. Work Environ. Hlth, 3, 16-22

    McConnell, G., Ferguson, D. M. & Pearson, C. R. (1975) Chlorinated
         Hydrocarbons and the Environment, Endeavor, 34, 13-18

    McNutt, N. S. et al. (1975) Hepatic Lesions in Mice after Continuous
         Inhalation Exposure to 1,1,1-Trichloroethane, Lab. Invest.,
         32, 642-654

    Nathan, A. W. & Toseland, P. A. (1979) Goodpasture's Syndrome and
         Trichloroethane Intoxication, Brit. J. Clin. Pharmac., 8,
         284-286

    National Cancer Institute (1977) Bioassay of 1,1,1-Trichloroethane for
         Possible Carcinogenicity, Technical Report Series No. 3, DHEW
         Publication No. (NIH) 77803, Washington, D.C., U.S. Department of
         Health and Human Services, pp. 1-70

    NIOSH (1976) Criteria For A Recommended Standard Occupational exposure
         to 1,1,1-Trichloroethane (Methyl Chloroform), U.S. Dept of
         Health, Education, and Welfare, Publication No. 76-184, pp. 118

    NIOSH (1978) Current Intelligence Bulletin 27 Chloroethanes: Review of
         Toxicity, U.S. Dept of Health, Education, and Welfare,
         Publication No. 78-181, pp. 21

    Pearson, C. R. & McConnell, G. (1975) Chlorinated C1 and C2
         Hydrocarbons in the Marine Environment, Proc. R. Soc. Lond. B.,
         189, 305-332

    Price, P. J., Hassett, C. M. & Mansfield, J. I. (1978) Transforming
         Activities of Trichloroethylene and Proposed Industrial
         Alternatives, In Vitro, 14, 290-293

    Rampy, L. W. et al. (1978) Results of Long-term Inhalation Toxicity
         Studies on Rats of 1,1,1-Trichloroethane and Perchloroethylene
         Formulations (Abstract). In: Proceedings of the First
         International Congress on Toxicology, Plaa, G. L. & Duncan, W.
         A. M. eds, Academic Press, New York, p. 562

    Savolainen, H. et al. (1977) Trichloroethylene and 1,1,1
         Trichloroethane: Effects on Brain and Liver after Five Days
         Intermittent Inhalation, Arch. Toxicol., 38, 229-237

    Schumann, A. M., Norris, J. M. & Watanabe, P. G. (1980) Comments on
         the Carcinogen Assessment Group's Carcinogenic Assessment of
         Methyl Chloroform, Dow Chemical U.S.A., Midland, MI, 48640,
         pp. 1-7

    Schwetz, B. A., Leong, B. K. J. & Gehring, P. J. (1975) The Effect of
         Maternally Inhaled Trichloroethylene, Perchloroethylene, Methyl
         Chloroform, and Methylene Chloride on Embryonal and Fetal
         Development in Mice and Rats, Toxicol. Appl. Pharmacol., 32,
         84-96

    Seki, Y. et al. (1975) Trichloro-Compounds in the Urine of Humans
         Exposed to Methyl Chloroform at Sub-Threshold Levels, Int.
         Arch. Arbeitsmed. 34, 39-49

    Simmon, V. F., Kauhanen, K. & Tardiff, R. G. (1977) Mutagenic Activity
         of Chemicals Identified in Drinking Water. In: Scott, D.,
         Bridges, B. A. & Sobels, F. M. eds, "Progress in Genetic
         Toxicology", Amsterdam, Elsevier/North Holland, pp. 249-258

    Stewart, R. D. (1968) The Toxicology of 1,1,1-Trichloroethane, Ann.
         Occup. Hyg., 11, 71-79

    Stewart, R. D. et al. (1961) Human Exposure to 1,1,1-Trichloroethane
         Vapor: Relationship of Expired Air and Blood Concentrations to
         Exposure and Toxicity, Ind. Hyg. J., 22, 252-262

    Torkelson, T. R. et al. (1958) Toxicity of 1,1,1-Trichloroethane as
         Determined on Laboratory Animals and Human Subjects, Ind. Hyg.
         J. 19, 353-362

    Tsuruta, H. (1975) Percutaneous Absorption of Organic Solvents,
         Ind. Health, 13, 227-236

    Tsapko, V. G. & Rappoport, H. B. (1972) Effect of Methylchloroform
         Vapors on Animals, Farmakol. Toksikol. (Kiev), 7, 149-151

    Vainio, H., Pfaffli, P. & Savolainen, H. (1978) Comparison Between
         the Acute Toxicity of 1,1,1-Trichloroethane and 1,1,2-
         Trichloroethylene (Abstract). In: Plaa, G. L. & Duncan, W. A. M.,
         eds, Proceedings of the First International Congress on
         Toxicology, Academic Press, New York, p. 554

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    WHO/FAO (1980) Evaluation of Certain Food Additives, 23rd report of
         the Joint FAO/WHO Expert Committee on Food Additives, Technical
         Report Series, 648, World Health Organization, Geneva, 1980

    ANNEX

    REPORT AND OTHER DOCUMENTS RESULTING FROM PREVIOUS MEETINGS ON THE
    JOINT FAO/WHO EXPERT COMMITTEE ON FOOD ADDITIVES

         Documents marked with an asterisk may be obtained on request
    from: Division of Environmental Health, World Health Organization,
    1211 Geneva 27, Switzerland, or from Food Standards and Food Science
    Service, Food and Agriculture Organization of the United Nations,
    00100 Rome, Italy.

    1.   General principles governing the use of food additives (First
         report of the Expert Committee). FAO Nutrition Meetings Report
         Series, No. 15, 1957; WHO Technical Report Series, No. 129, 1957
         (out of print).

    2.   Procedures for the testing of intentional food additives to
         establish their safety for use (Second report of the Expert
         Committee). FAO Nutrition Meetings Report Series, No. 17, 1958;
         WHO Technical Report Series, No. 144, 1958 (out of print).

    3.   Specifications for identity and purity of food additives
         (anti-microbial preservatives and antioxidants) (Third report
         of the Expert Committee). These specifications were subsequently
         revised and published as Specifications for identity and purity
         of food additives, vol. I. Antimicrobial preservatives and
         antioxidants, Rome, Food and Agriculture Organization of the
         United Nations, 1962 (out of print).

    4.   Specifications for identity and purity of food additives (food
         colours) (Fourth report of the Expert Committee). These
         specifications were subsequently revised and published as
         Specifications for identity and purity of food additives, vol.
         II. Food colours, Rome, Food and Agriculture Organization of
         the United Nations, 1963 (out of print).

    5.   Evaluation of the carcinogenic hazards of food additives (Fifth
         report of the Expert Committee). FAO Nutrition Meetings Report
         Series, No. 29, 1961; WHO Technical Report Series, No. 220, 1961
         (out of print).

    6.   Evaluation of the toxicity of a number of antimicrobials and
         antioxidants (Sixth report of the Expert Committee). FAO
         Nutrition Meetings Report Series, No. 31, 1962; WHO Technical
         Report Series, No. 228, 1962.

    7.   Specifications for the identity and purity of food additives
         and their toxicological evaluation: emulsifiers, stabilizers,
         bleaching and maturing agents (Seventh report of the Expert
         Committee). FAO Nutrition Meetings Report Series, No. 25, 1964;
         WHO Technical Report Series, No. 281, 1964 (out of print).

    8.   Specifications for the identity and purity of food additives
         and their toxicological evaluation: food colours and some
         anti-microbials and antioxidants (Eighth report of the Expert
         Committee). FAO Nutrition Meetings Report Series, No. 38, 1965;
         WHO Technical Report Series, No. 309, 1965 (out of print).

    *9.  Specifications for identity and purity and toxicological
         evaluation of some antimicrobials and antioxidants. FAO
         Nutrition Meetings Report Series, No 38A, 1965; WHO/Food
         Add/24.65.

    *10. Specifications for identity and purity and toxicological
         evaluation of food colours. FAO Nutrition Meetings Report
         Series, No. 38B, 1966; WHO/Food Add/66.25.

    11.  Specifications for the identity and purity of food additives
         and their toxicological evaluation: some antimicrobials,
         antioxidants, emulsifiers, stabilizers, flour-treatment agents,
         acids, and bases (Ninth report of the Expert Committee). FAO
         Nutrition Meetings Report Series, No. 40, 1966; WHO Technical
         Report Series, No. 339, 1966.

    12.  Specifications for the identity and purity of food additives
         and their toxicological evaluation: some emulsifiers and
         stabilizers and certain other substances (Tenth report of the
         Expert Committee). FAO Nutrition Meetings Report Series, No. 43,
         1967; WHO Technical Report Series, No. 373, 1967.

    *13. Toxicological evaluation of some antimicrobials, antioxidants,
         emulsifiers, stabilizers, flour-treatment agents, acids, and
         bases. FAO Nutrition Meetings Report Series, No. 40A,B,C;
         WHO/Food Add/67.29.

    14.  Specifications for the identity and purity of food additives
         and their toxicological evaluation: some flavouring substances
         and non-nutritive sweetening agents (Eleventh report of the
         Expert Committee). FAO Nutrition Meetings Report Series, No. 44,
         1968; WHO Technical Report Series, No. 383, 1968.

    15.  Toxicological evaluation of some flavouring substances and
         non-nutritive sweetening agents. FAO Nutrition Meetings Report
         Series, No. 44A, 1968; WHO/Food Add/68.33.

    *16. Specifications and criteria for identity and purity of some
         flavouring substances and non-nutritive sweetening agents. FAO
         Nutrition Meetings Report Series, No. 44B, 1969; WHO/Food
         Add/69.31.

    17.  Specifications for the identity and purity of food additives
         and their toxicological evaluation: some antibiotics (Twelfth
         report of the Expert Committee). FAO Nutrition Meetings Report
         Series, No. 45, 1969; WHO Technical Report Series, No. 430, 1969.

    *18. Specifications for the identity and purity of some antibiotics.
         FAO Nutrition Meetings Report Series, No. 43A, 1969; WHO/Food
         Add/69.34.

    19.  Specifications for the identity and purity of food additives
         and their toxicological evaluation: some food colours,
         emulsifiers, stabilizers, anticaking agents and certain other
         substances (Thirteenth report of the Expert Committee). FAO
         Nutrition Meetings Report Series, No. 46, 1970; WHO Technical
         Report Series, No. 445, 1970.

    20.  Toxicological evaluation of some food colours, emulsifiers,
         stabilizers, anticaking agents, and certain other substances.
         FAO Nutrition Meetings Report Series, No. 46A; WHO/Food Add/
         70.36.

    *21. Specifications for the identity and purity of some food
         colours, emulsifiers, stabilizers, anticaking agents, and
         certain other food additives. FAO Nutrition Meetings Report
         Series, No. 46B; WHO/Food Add/70.37

    22.  Evaluation of food additives: specifications for the identity
         and purity of food additives and their toxicological
         evaluation: some extraction solvents and certain other
         substances; and a review of the technological efficacy of some
         antimicrobial agents (Fourteenth report of the Expert
         Committee). FAO Nutrition Meetings Report Series, No. 48, 1971;
         WHO Technical Report Series, No. 462, 1971.

    *23. Toxicological evaluation of some extraction solvents and
         certain other substances. FAO Nutrition Meetings Report Series,
         No. 48A, 1971; WHO/Food Add/70.39.

    *24. Specifications for the identity and purity of some extraction
         solvents and certain other substances. FAO Nutrition Meetings
         Report Series, No. 48B, 1971; WHO/Food Add/70.40.

    *25. A review of the technological efficacy of some antimicrobial
         agents. FAO Nutrition Meetings Report Series, No. 48C, 1971;
         WHO/Food Add/70.41.

    26.  Evaluation of food additives: some enzymes, modified starches,
         and certain other substances: toxicological evaluations and
         specifications and a review of the technological efficacy of
         some antioxidants (Fifteenth report of the Expert Committee).
         FAO Nutrition Meetings Report Series, No. 50, 1972; WHO Technical
         Report Series, No. 488, 1972.

    27.  Toxicological evaluation of some enzymes, modified starches,
         and certain other substances. FAO Nutrition Meetings Report
         Series, No. 50A, 1972; WHO Food Additives Series, No. 1, 1972.

    28.  Specifications for the identity and purity of some enzymes and
         certain other substances. FAO Nutrition Meetings Report Series,
         No. 50B, 1972; WHO Food Additives Series, No. 2, 1972.

    29.  A review of the technological efficacy of some antioxidants and
         synergists. FAO Nutrition Meetings Report Series, No. 50C,
         1972; WHO Food Additives Series, No. 3, 1972.

    30.  Evaluation of certain food additives and the contaminants
         mercury, lead, and cadmium (Sixteenth report of the Expert
         Committee). FAO Nutrition Meetings Report Series, No. 51, 1972;
         WHO Technical Report Series, No. 505, 1972, and corrigendum.

    31.  Evaluation of mercury, lead, cadmium and the food additives
         amaranth, diethylpyrocarbonate, and octyl gallate. FAO
         Nutrition Meetings Report Series, No. 51A, 1972; WHO Food
         Additives Series, No. 4, 1972.

    32.  Toxicological evaluation of certain food additives with a
         review of general principles and of specifications (Seventeenth
         report of the Expert Committee). FAO Nutrition Meetings Report
         Series, No. 53, 1974; WHO Technical Report Series, No. 539, 1974,
         and corrigendum.

    33.  Toxicological evaluation of certain food additives including
         anticaking agents, antimicrobials, antioxidants, emulsifiers,
         and thickening agents. FAO Nutrition Meetings Report Series,
         No. 53A; WHO Food Additives Series, No. 5, 1974.

    34.  Evaluation of certain food additives (Eighteenth report of the
         Expert Committee). FAO Nutrition Meetings Report Series, No. 54,
         1974; WHO Technical Report Series, No. 557, 1974, and
         corrigendum.

    35.  Toxicological evaluation of some food colours, enzymes, flavour
         enhancers, thickening agents, and certain other food additives.
         FAO Nutrition Meetings Report Series, No. 54A, 1975; WHO Food
         Additives Series, No. 6, 1975.

    36.  Specifications for the identity and purity of some food colours,
         flavour enhancers, thickening agents, and certain food additives.
         FAO Nutrition Meetings Report Series, No. 54B, 1975; WHO Food
         Additives Series, No. 7, 1975.

    37.  Evaluation of certain food additives: some food colours,
         thickening agents, smoke condensates, and certain other
         substances (Nineteenth report of the Expert Committee). FAO
         Nutrition Meetings Report Series, No. 55, 1975; WHO Technical
         Report Series, No. 576, 1975.

    38.  Toxicological evaluation of some food colours, thickening
         agents, and certain other substances. FAO Nutrition Meetings
         Report Series, No. 55A. WHO Food Additives Series, No. 8, 1975.

    39.  Specifications for the identity and purity of certain food
         additives. FAO Nutrition Meetings Report Series, No. 55B, 1976;
         WHO Food Additives Series, No. 9, 1976.

    40.  Evaluation of certain food additives (Twentieth report of the
         Expert Committee). FAO Food and Nutrition Series, No. 1, 1976;
         WHO Technical Report Series, No. 599, 1976.

    41.  Toxicological evaluation of certain food additives. FAO Food
         and Nutrition Series, No. 1A, 1978; WHO Food Additives Series,
         No. 10, 1978.

    42.  Specifications for the identity and purity of certain food
         additives. FAO Food and Nutrition Series, No. 1B, 1977.

    43.  Evaluation of certain food additives (Twenty-first report of
         the Joint FAO/WHO Expert Committee on Food Additives). WHO
         Technical Report Series, No. 617, 1978.

    44.  Summary of Toxicological data of certain food additives. WHO
         Food Additives Series No. 12, 1977.

    45.  Specifications for identity and purity of some food additives,
         including antioxidants, food colours, thickeners, and others.
         FAO Nutrition Meeting Report Series, No. 57, 1977.

    46.  Specifications for identity and purity of thickening agents,
         anticaking agents, antimicrobials, antioxidants and
         emulsifiers. FAO Food and Nutrition Paper, No. 4, 1978.

    47.  Guide to specifications - General notices, general methods,
         identification tests, text solutions, and other reference
         materials. FAO Food and Nutrition Paper, No. 5, 1978.

    48.  Evaluation of certain food additives (Twenty-second report of
         the Joint FAO/WHO Expert Committee on Food Additives). WHO
         Technical Report Series, No. 631, 1978.

    49.  Summary of toxicological data of certain food additives and
         contaminants. WHO Food Additives Series, No. 13, 1978.

    50.  Specifications for the identity and purity of certain food
         additives. FAO Food and Nutrition Paper, No. 7, 1978.

    51.  Evaluation of certain food additives (Twenty-third report of
         the Joint FAO/WHO Expert Committee on Food Additives). WHO
         Technical Report Series, No. 648, 1980.

    52.  Toxicological evaluation of certain food additives. WHO Food
         Additives Series, No. 14, 1979.

    53.  Specifications for identity and purity of food colours,
         flavouring agents, and other food additives. FAO Food and
         Nutrition Paper, No. 12, 1979.

    54.  Evaluation of certain food additives (Twenty-fourth report of
         the Joint FAO/WHO Expert Committee on Food Additives). WHO
         Technical Report Series, No. 653, 1980.

    55.  Toxicological evaluation of certain food additives. WHO Food
         Additives Series, No. 15, 1981.

    56.  Specifications for identity and purity of food additives
         (sweetening agents, emulsifying agents, and other food
         additives). FAO Food and Nutrition Paper, No. 17, 1980.
    


    See Also:
       Toxicological Abbreviations
       Trichloroethane, 1,1,1- (EHC 136, 1992)
       Trichloroethane, 1,1,1- (PIM 540)
       Trichloroethane, 1,1,1- (IARC Summary & Evaluation, Volume 71, 1999)