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 µmol/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 µl) 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 µl) at 2, 3 and 6 days of incubation. The approximate LD50 value varied between 50 and 100 µmol/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 Adams, E. M. et al. (1950) Vapor Toxicity of 1,1,1-Trichloroethane (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 Environ. Health, 10, 69-81 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 à 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 Van Dyke, R. A. & Wineman, C. G. (1971) Enzymatic Dechlorination Dechlorination of Chloroethanes and Propanes in vitro, Biochem. Pharmacol., 20, 463-470 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). 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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)