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Toxicity Effects

CAS Registry Number: 107-30-2

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 2.

Names 1

  • Bis(chloromethyl) Ether and Technical-Grade Chloromethyl Methyl Ether
  • Chloromethoxymethane

Human Toxicity Excerpts

  • ... /CNS effect/ causes loss of consciousness on appreciable exposure and, as good fat solvents, they cause dermatitis on repeated or prolonged skin contact. ... Enclosure and ventilation are to be employed /Chloromethyl ethers/[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 785] **PEER REVIEWED**
  • A PROSPECTIVE STUDY OF 125 WORKERS WAS CARRIED OUT FOR TEN YEARS TO INVESTIGATE THE INCIDENCE OF LUNG CANCER. SOME OF THE MEN WERE EXPOSED TO CHLOROMETHYL METHYL ETHER CONTAINING BIS(CHLOROMETHYL) ETHER AS AN IMPURITY. BRONCHOGENIC CARCINOMA WAS MARKEDLY INCREASED AMONG THEM, WITH A STRONG DOSE-RESPONSE RELATIONSHIP. AN UNEXPECTED INVERSE RELATIONSHIP WAS NOTED BETWEEN SMOKING AND THE INCIDENCE OF LUNG CANCER. THE NEOPLASMS (ALL SMALL-CELL CARCINOMAS) OCCURRED IN RELATIVELY YOUNG MEN. SYMPTOMS OF CHRONIC BRONCHITIS WERE REPORTED MORE OFTEN AMONG MEN EXPOSED TO CHLOROMETHYL ETHER, AND A DOSE-RESPONSE RELATIONSHIP WAS APPARENT, WITH SMOKING A COFACTOR. VENTILATORY FUNCTION WAS NOT SIGNIFICANTLY AFFECTED BY CHEMICAL EXPOSURE. PERIODIC SCREENING OVER THE FIRST FIVE YEARS OF THE STUDY SHOWED A DECREASE IN CHRONIC COUGHING AND AN INCREASE IN DYSPNEA WHILE CHEMICAL EXPOSURE WAS DIMINISHING.[WEISS W, BOUCOT KR; J AM MED ASSOC 234: 1139 (1975)] **PEER REVIEWED**
  • A historical prospective epidemiological study was conducted on workers exposed to chloromethyl methyl ether containing 0.5-4% bis(chloromethyl) ether as an impurity. The study period was 1948-1972. Follow-up procedures located 98.9% of the cohort, including those /workers/ separated from the plant. The cause of death was established for 95.3% of the 278 known deceased men. A CMME exposure rating system was established from employees' work histories and recollections of supervisors. This system approximated relative exposure concentrations and duration times. Analysis on an age-specific basis revealed a relative risk of lung cancer 3.8 times higher in 669 exposed vs 1616 unexposed workers, a significant increase. Although limited by a lack of quantitative environmental sampling data, dose-response relationships were established between lung cancer and intensity and/or duration of exposure.[Defonso LR, Kelton SC Jr; Arch Environ Health 31 (3): 125-30 (1976)] **PEER REVIEWED** PubMed Abstract
  • CHLOROMETHYL METHYL ETHER GAVE POSITIVE RESULTS AS A DNA-DAMAGING AGENT IN HUMAN LYMPHOCYTES WITH THE INHIBITION OF SCHEDULED (DUPLICATIVE) AND UNSCHEDULED (REPARATIVE) DNA SYNTHESES. IN THIS SHORT-TERM SYSTEM, POSITIVE RESULTS WERE NOTED ONLY AFTER METABOLIC ACTIVATION OF THE CHEMICALS.[PEROCCO P, PRODI G; CANCER LETT 13 (3): 213 (1981)] **PEER REVIEWED** PubMed Abstract
  • CHLOROMETHYL METHYL ETHER IS ALMOST INVARIABLY CONTAMINATED BY BIS(CHLOROMETHYL)ETHER, & THE LATTER MAY BE RESPONSIBLE FOR @ LEAST PART OF OBSERVED CARCINOGENIC ACTIVITY.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V4 244 (1974)] **PEER REVIEWED**
  • Excess oat cell carcinomas of the lung have been noted in several studies of exposed workers and in one of eight plants in another. Anecdotal reports have associated the occurrence of oat cell carcinomas of the lung with chloromethylation processes. Chloromethyl methyl ether is potent skin, mucous membrane, and respiratory tract irritant, which may produce pulmonary edema in high concentrations and chronic bronchitis with long-term inhalation.[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 995] **PEER REVIEWED**
  • IN A PRELIMINARY OBSERVATION DURING 5 YR PERIOD WHEN 111 CHLOROMETHYL METHYL ETHER WORKERS WERE STUDIED, 4 CASES OF /OAT CELL/ LUNG CANCER WERE DIAGNOSED. THIS REPRESENTS AN INCIDENCE 8 TIMES THAT OBSERVED IN A CONTROL GROUP OF 2,800 WITH A SIMILAR CIGARETTE SMOKING HISTORY (74-78%).[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V4 243 (1974)] **PEER REVIEWED**
  • IN STUDY INCL ABOUT 1800 EXPOSED WORKERS FROM 1948-1972, AGE-ADJUSTED DEATH RATE FROM RESP CANCER IN CHLOROMETHYL METHYL ETHER GROUP WAS 2.5 TIMES THAT OF CONTROL GROUP. DEATH RATES FROM OTHER CAUSES WERE COMPARABLE.[ALBERT ET AL, ENVIRON HEALTH PERSPECT 11: 209 (1975)] **PEER REVIEWED**
  • INDUSTRIAL EXPOSURE TO RATHER HIGH CONCN ... SUBJECT HAD SYMPTOMS OF SORE THROAT, FEVER, & CHILLS & WAS NOT ABLE TO WORK FOR 8 DAYS, AT WHICH TIME RECOVERY APPEARED COMPLETE. ANOTHER SUBJECT ... VERY SLIGHT EXPOSURE ... DIFFICULTY IN BREATHING FOR SEVERAL DAYS.[Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963., p. 1673] **PEER REVIEWED**
  • PRINCIPAL EFFECT ... IRRITATION ... LIQ CAUSING SEVERE IRRITATION OF SKIN & EYES; VAPOR EXPOSURE OF 100 PPM IS SEVERELY IRRITATING TO EYES & NOSE. SUCH A LEVEL IS DANGEROUS TO LIFE IN 4 HR. PULMONARY EDEMA OR PNEUMONIA MAY CAUSE DEATH ... DAYS OR WK AFTER EXPOSURE.[International Labour Office. Encyclopedia of Occupational Health and Safety. Volumes I and II. New York: McGraw-Hill Book Co., 1971., p. 480] **PEER REVIEWED**
  • Seventeen chemicals (solvents, insecticides and intermediates in the production of textiles and resins /including chloromethyl methyl ether/) were tested in a short-term in vitro system with human lymphocytes to determine their toxic action. The parameters studied were the tritiated thymidine uptake and cell viability in cultures grown with or without a rat liver metabolizing system ... . /Chloromethyl methyl ether/ lost its /cytotoxic effects/ in the presence of the metabolizing system ... and only chloromethyl methyl ether elicited unscheduled DNA synthesis acting as a DNA damaging agent.[Perocco P et al; Toxicol Lett 16 (1-2): 69-76 (1983)] **PEER REVIEWED** PubMed Abstract
  • The alpha-chloroether carcinogen chloromethylmethyl ether (CME) and its impurity bis(chloromethyl)ether (BCME) are direct-acting alkylating agents. Vinyl chloride (VC) is an indirect-acting carcinogen but its accepted carcinogenic intermediate, chloroethylene oxide, is also an alpha-chloroether. Both CME-BCME and VC have been in industrial use since about 1950. Hence, they were selected for comparison of potency as human carcinogens using numerous epidemiologic reports. There were 115 deaths due to angiosarcoma of the liver among several hundred thousand VC-exposed workers on the basis of reports from 10 countries during 1955 and 1984. Reports from five countries cited a total of 87 respiratory cancer deaths among only 3024 CME-BCME-exposed workers. If a recent court settlement in the United States is taken into account, the number of respiratory cancer deaths due to CME-BCME rises to 117. On the basis of these numbers of cancer deaths, and the levels and durations of exposure, it is concluded that VC is a weak human carcinogen compared to CME-BCME.[Van Duuren BL; Environ Res 49 (2); 143-51 (1989)] **PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • ... 30 FEMALE ICR/HA SWISS MICE ... INJECTED SC ONCE/WK WITH 300 UG CHLOROMETHYL METHYL ETHER ... IN 0.05 ML NUJOL ... FOR ... 685 DAYS. SARCOMAS @ INJECTION SITE WERE SEEN IN 10 MICE, THE FIRST ... APPEARING @ 308 DAYS ... MEDIAN SURVIVAL TIME ... 496 DAYS. ... NO DISTANT TUMORS. A CONTROL GROUP RECEIVING NUJOL ALONE ... NO LOCAL TUMORS ... .[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V4 242 (1974)] **PEER REVIEWED**
  • 14-DAY LC50 7 HR/DAY ARE 55 PPM RATS & 65 PPM HAMSTERS. ALL HAD RESP TRACT CONGESTION, EDEMA & HEMORRHAGE. SEVERE LIFE-SPAN SHORTENING IN 30-DAY-EXPOSED RATS. MUCOSAL CHANGES, INCL ATYPIA, INCR IN DOSE-RELATED MANNER.[DREW RT ET AL; ARCH ENVIRON HEALTH 30 (2): 61 (1975)] **PEER REVIEWED** PubMed Abstract
  • 74 RATS & 90 HAMSTERS @ 1 PPM CHLOROMETHYL METHYL ETHER 6 HR/DAY 5 DAYS/WK FOR LIFE: 2 RATS HAD MALIGNANT RESP TRACT TUMORS, 1 HAMSTER A LUNG ADENOCARCINOMA, ANOTHER HAMSTER A TRACHEAL SQUAMOUS PAPILLOMA. A PITUITARY TUMOR IN 1 RAT.[LASKIN ET AL; ARCH ENVIRON HEALTH 30 (2): 70 (1975)] **PEER REVIEWED** PubMed Abstract
  • A GROUP OF 50 MALE STRAIN A/He MICE WAS EXPOSED TO AN ATMOSPHERE CONTAINING A CONCENTRATION OF 0.006 MG/L (6 MG/CU M) CMME IN EXPOSURE CHAMBERS FOR 6 HOURS PER DAY ON 5 DAYS PER WEEK DURING 21 WEEKS. A TOTAL OF 25/50 ANIMALS AT RISK HAD LUNG TUMOURS, WITH AN AVERAGE OF 1.5 TUMOURS PER ANIMAL. IN A CONTROL GROUP EXPOSED TO FILTERED ROOM AIR FOR 130 DAYS AND HELD FOR 28 WEEKS, 20/49 MICE AT RISK HAD LUNG TUMOURS, WITH AN AVERAGE OF 0.9 TUMOURS PER MOUSE.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V4 242 (1974)] **PEER REVIEWED**
  • A cutaneous application of 0.1 ml of a 2% solution of CMME in benzene 3 times per week for 325 days to groups of 20 female ICR/Ha Swiss mice, observed further for a total of 540 days, gave no evidence of local tumorigenicity. However, the compound was active as an initiator. Administration of a single dose of 0.1 mg CMME in 0.1 ml benzene solution, followed 14 days later by thrice-weekly applications of 0.25 mg mixed phorbol esters in 0.1 ml acetone, resulted in 7 mice developing papillomas, the first one of which was seen at 259 days and 4 of which progressed to squamous cell carcinomas. The median survival time was 496 days. At a higher dose level, 1.0 mg CMME in 0.1 ml benzene given once followed by the promoting treatment, 5 mice developed papillomas, the first appearing at 140 days, and 1 of which progressed to a carcinoma. The average survival time was 488 days. Controls given a single cutaneous application of CMME at either dose level, followed by no treatment or by acetone, developed no tumors. Two of 20 mice treated with mixed phorbol esters alone had papillomas, the first appearing at 322 days and the median survival time being greater than 450 days. In a positive control group pretreated with 0.15 mg benzo[a]pyrene in 0.1 ml benzene followed by promotion with mixed phorbol esters 20/20 mice developed papillomas; the first of these appeared at 70 days, and 7 progressed to carcinomas. The median survival time was 439 days.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V4 241 (1974)] **PEER REVIEWED**
  • CHLOROMETHYL ETHER WAS FED ORALLY IN SINGLE DOSES TO RATS. DOSES OF 0.3 G/KG ALLOWED SURVIVAL, WHEREAS DOSES OF 1.0 G/KG CAUSED DEATH. ... IN RABBIT EYE AS A 1% SOLN IN PROPYLENE GLYCOL, SEVERE IRRITATION & NECROSIS DEVELOPED.[Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963., p. 1673] **PEER REVIEWED**
  • CHLOROMETHYL METHYL ETHER PRODUCED A STRIKING AND SIGNIFICANT INHIBITION OF GUANYLATE CYCLASE OVER A GENERAL CONCENTRATION RANGE OF 0.5-13 MMOL/L IN A VARIETY OF RAT TISSUES IN VITRO.[VESELY DL ET AL; ENZYME (BASEL) 23 (5): 356 (1978)] **PEER REVIEWED**
  • CHLOROMETHYL METHYL ETHER WAS INACTIVE AS CARCINOGEN BY SKIN APPLICATION TO MICE, BUT INDUCED SIZABLE PALPABLE LESIONS ADMIN SC TO RATS. IT ELICITED WEAK TUMOR RESPONSE WITH CROTON RESIN AS PROMOTING AGENT.[VAN-DUUREN BL ET AL; ARCH ENVIRON HEALTH 16 (4): 472 (1968)] **PEER REVIEWED** PubMed Abstract
  • CHLOROMETHYL METHYL ETHER, A WEAK OR INACTIVE INITIATOR OF MOUSE SKIN TUMORIGENESIS, PRODUCED NO CHANGE IN MACROMOLECULAR SYNTHESIS FOLLOWING A SINGLE APPLICATION (240 OR 480 UMOLES) TO MOUSE SKIN EPIDERMAL PREPARATIONS.[SLAGA TJ ET AL; CANCER RES 33 (4): 769 (1973)] **PEER REVIEWED** PubMed Abstract
  • IN ... 20 FEMALE SPRAGUE-DAWLEY RATS GIVEN WEEKLY SC INJECTIONS 3 MG CHLOROMETHYL METHYL ETHER IN 0.1 ML NUJOL FOR 300 DAYS, 1 RAT DEVELOPED A FIBROSARCOMA @ INJECTION SITE. MEDIAN SURVIVAL TIME WAS 478 DAYS ... ANIMALS ... EVALUATED @ 515 DAYS. CONTROL ANIMALS DEVELOPED NO TUMORS ... .[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V4 243 (1974)] **PEER REVIEWED**
  • MALE & FEMALE ICR SWISS MICE ... SINGLE SC INJECTION OF PREDETERMINED MAX TOLERATED DOSE OF 125 UL/KG BODY WT CHLOROMETHYL METHYL ETHER IN SOLN OF PEANUT OIL. All ANIMALS WERE KILLED @ 6 MO, & 17/99 MICE HAD PULMONARY TUMORS WITH A MULTIPLICITY OF 0.21. IN CONTROL GROUP OF 50 MICE /INJECTED WITH/ PEANUT OIL ALONE, 7/50 MICE HAD LUNG TUMORS WITH A MULTIPLICITY OF 0.14.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V4 242 (1974)] **PEER REVIEWED**
  • RABBIT SKIN TESTS USING THE UNDILUTED /CHLOROMETHYL ETHER/ RESULTED IN SEVERE HYPEREMIA, EDEMA, DENATURATION, & EVEN COMPLETE DESTRUCTION OF THE SKIN.[Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963., p. 1673] **PEER REVIEWED**
  • REPEATED INHALATION OF CHLOROMETHYL METHYL ETHER @ 2 PPM GAVE INCR IN INCIDENCE OF PULMONARY ADENOMAS IN STRAIN A MICE.[LEONG ET AL; ARCH ENVIRON HEALTH 22 (6): 663 (1971)] **PEER REVIEWED** PubMed Abstract
  • The carcinogenic potency of bis (chloromethyl) ether is greater than CMME. Attention was first called to the alpha-halo-ethers as alkylating carcinogens. Bis (chloromethyl) ether was found to be a potent alkylating carcinogen for mouse skin ... .[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 292] **PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LC50 HAMSTER 65 PPM 7 HR/DAY FOR 14-DAYS[DREW RT ET AL; ARCH ENVIRON HEALTH 30 (2): 61 (1975)] **PEER REVIEWED** PubMed Abstract
  • LC50 Hamster /ihl/ 5-7 ppm/6-7 hr[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 292] **PEER REVIEWED**
  • LC50 Mouse /ihl/ 5-7 ppm/6-7 hr[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 292] **PEER REVIEWED**
  • LC50 RAT 55 PPM 7 HR/DAY FOR 14-DAYS[DREW RT ET AL; ARCH ENVIRON HEALTH 30 (2): 61 (1975)] **PEER REVIEWED** PubMed Abstract
  • LC50 Rat /ihl/ 5-7 ppm/6-7 hr[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 292] **PEER REVIEWED**
  • LC50 Rat /inhalation/ 55 ppm/7 hr[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-183] **PEER REVIEWED**
  • LD50 Rat oral 0.5 g/kg[Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 372] **PEER REVIEWED**

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Absorption, Distribution And Excretion

  • None found

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Metabolism/Metabolites

  • None found

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Tsca Test Submissions

  • None found

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Footnotes

1 Source: the NTP's CEBS database.

2 Source: the National Library of Medicine's Hazardous Substance Database, 02/28/2017.

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