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.

Concise International Chemical Assessment Document 1

1,2-DICHLOROETHANE

First draft prepared by Ms K. Hughes and Ms M.E. Meek, Environmental Health Directorate, Health Canada

Please note that thelayout and pagination of this pdf file are not identical to the printed CICAD

Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization, and produced within the framework of the Inter-Organization Programme for the Sound Management of Chemicals.

World Health Organization Geneva, 1998 The International Programme on Chemical Safety (IPCS), established in 1980, is a joint venture of the United Nations Environment Programme (UNEP), the International Labour Organisation (ILO), and the World Health Organization (WHO). The overall objectives of the IPCS are to establish the scientific basis for assessment of the risk to human health and the environment from exposure to chemicals, through international peer review processes, as a prerequisite for the promotion of chemical safety, and to provide technical assistance in strengthening national capacities for the sound management of chemicals. The Inter-Organization Programme for the Sound Management of Chemicals (IOMC) was established in 1995 by UNEP, ILO, the Food and Agriculture Organization of the United Nations, WHO, the United Nations Industrial Development Organization, and the Organisation for Economic Co-operation and Development (Participating Organizations), following recommendations made by the 1992 UN Conference on Environment and Development to strengthen cooperation and increase coordination in the field of chemical safety. The purpose of the IOMC is to promote coordination of the policies and activities pursued by the Participating Organizations, jointly or separately, to achieve the sound management of chemicals in relation to human health and the environment.

WHO Library Cataloguing in Publication Data

1,2-Dichloroethane.

(Concise international chemical assessment document ; 1)

1.Ethylene dichlorides – toxicity 2.Ethylene dichlorides – administration and dosage 3.Dose-response relationship, Drug 4.Environmental exposure I.International Programme for Chemical Safety II.Series

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Printed by Wissenschaftliche Verlagsgesellschaft mbH, D-70009 Stuttgart 10 TABLE OF CONTENTS

FOREWORD ...... 1

1. EXECUTIVE SUMMARY ...... 4

2. IDENTITY AND PHYSICAL/CHEMICAL PROPERTIES ...... 5

3. ANALYTICAL METHODS ...... 5

4. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE ...... 5

5. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION ...... 5

6. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE ...... 5

6.1 Environmental levels ...... 5 6.2 Human exposure ...... 6

7. COMPARATIVE KINETICS AND METABOLISM IN LABORATORY ANIMALS AND HUMANS ...... 7

8. EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS ...... 7

8.1 Single exposure ...... 7 8.2 Irritation and sensitization ...... 7 8.3 Short-term exposure ...... 7 8.4 Long-term exposure ...... 7 8.4.1 Subchronic exposure ...... 7 8.4.2 Chronic exposure and carcinogenicity ...... 7 8.5 Genotoxicity and related end-points ...... 9 8.6 Reproductive and developmental toxicity ...... 9 8.7 Immunological and neurological effects ...... 9

9. EFFECTS ON HUMANS ...... 9

9.1 Case reports ...... 9 9.2 Epidemiological studies ...... 9

10. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD ...... 9

10.1 Aquatic environment ...... 9 10.2 Terrestrial environment ...... 11

11. EFFECTS EVALUATION ...... 12

11.1 Evaluation of health effects ...... 12 11.1.1 Hazard identification and dose–response assessment ...... 12 11.1.2 Criteria for setting guidance values for 1,2-dichloroethane ...... 12 11.1.3 Sample risk characterization ...... 13 11.2 Evaluation of environmental effects ...... 13

12. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES ...... 13

iii Concise International Chemical Assessment Document 1

13. HUMAN HEALTH PROTECTION AND EMERGENCY ACTION ...... 13

13.1 Human health hazards ...... 13 13.2 Advice to physicians ...... 13 13.3 Health surveillance advice ...... 14 13.4 Explosion and fire hazards ...... 14 13.4.1 Explosion hazards ...... 14 13.4.2 Fire hazards ...... 14 13.4.3 Prevention ...... 14 13.5 Spillage ...... 14

14. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS ...... 14

INTERNATIONAL CHEMICAL SAFETY CARD ...... 15

REFERENCES ...... 17

APPENDIX 1 — SOURCE DOCUMENTS ...... 22

APPENDIX 2 — CICAD FINAL REVIEW BOARD ...... 24

RÉSUMÉ D’ORIENTATION ...... 25

RESUMEN DE ORIENTACIÓN ...... 27

iv 1,2-Dichloroethane

FOREWORD While every effort is made to ensure that CICADs represent the current status of knowledge, new informa- Concise International Chemical Assessment tion is being developed constantly. Unless otherwise Documents (CICADs) are the latest in a family of stated, CICADs are based on a search of the scientific publications from the International Programme on literature to the date shown in the executive summary. In Chemical Safety (IPCS) — a cooperative programme of the event that a reader becomes aware of new infor- the World Health Organization (WHO), the International mation that would change the conclusions drawn in a Labour Organisation (ILO), and the United Nations CICAD, the reader is requested to contact the IPCS to Environment Programme (UNEP). CICADs join the inform it of the new information. Environmental Health Criteria documents (EHCs) as authoritative documents on the risk assessment of Procedures chemicals. The flow chart shows the procedures followed to CICADs are concise documents that provide produce a CICAD. These procedures are designed to summaries of the relevant scientific information take advantage of the expertise that exists around the concerning the potential effects of chemicals upon world — expertise that is required to produce the high- human health and/or the environment. They are based quality evaluations of toxicological, exposure, and other on selected national or regional evaluation documents or data that are necessary for assessing risks to human on existing EHCs. Before acceptance for publication as health and/or the environment. CICADs by IPCS, these documents have undergone extensive peer review by internationally selected experts The first draft is based on an existing national, to ensure their completeness, accuracy in the way in regional, or international review. Authors of the first which the original data are represented, and the validity draft are usually, but not necessarily, from the institution of the conclusions drawn. that developed the original review. A standard outline has been developed to encourage consistency in form. The primary objective of CICADs is character- The first draft undergoes primary review by IPCS and ization of hazard and dose–response from exposure to a one or more experienced authors of criteria documents to chemical. CICADs are not a summary of all available data ensure that it meets the specified criteria for CICADs. on a particular chemical; rather, they include only that information considered critical for characterization of the The second stage involves international peer risk posed by the chemical. The critical studies are, review by scientists known for their particular expertise however, presented in sufficient detail to support the and by scientists selected from an international roster conclusions drawn. For additional information, the compiled by IPCS through recommendations from IPCS reader should consult the identified source documents national Contact Points and from IPCS Participating upon which the CICAD has been based. Institutions. Adequate time is allowed for the selected experts to undertake a thorough review. Authors are Risks to human health and the environment will required to take reviewers’ comments into account and vary considerably depending upon the type and extent revise their draft, if necessary. The resulting second of exposure. Responsible authorities are strongly draft is submitted to a Final Review Board together with encouraged to characterize risk on the basis of locally the reviewers’ comments. measured or predicted exposure scenarios. To assist the reader, examples of exposure estimation and risk The CICAD Final Review Board has several characterization are provided in CICADs, whenever important functions: possible. These examples cannot be considered as representing all possible exposure situations, but are – to ensure that each CICAD has been subjected to provided as guidance only. The reader is referred to an appropriate and thorough peer review; EHC 1701 for advice on the derivation of health-based – to verify that the peer reviewers’ comments have guidance values. been addressed appropriately; – to provide guidance to those responsible for the preparation of CICADs on how to resolve any 1 International Programme on Chemical Safety (1994) remaining issues if, in the opinion of the Board, the Assessing human health risks of chemicals: derivation author has not adequately addressed all comments of guidance values for health-based exposure limits. of the reviewers; and Geneva, World Health Organization (Environmental – to approve CICADs as international assessments. Health Criteria 170).

1 Concise International Chemical Assessment Document 1

CICAD PREPARATION FLOW CHART

SELECTION OF PRIORITY CHEMICAL

SELECTION OF HIGH QUALITY NATIONAL/REGIONAL ASSESSMENT DOCUMENT(S)

FIRST DRAFT PREPARED

PRIMARY REVIEW AT PRODUCER LEVEL ( 1-2 OTHER DOCUMENT PRODUCERS) 1

RESPONSIBLE PRODUCER OFFICER (RO)

REVIEW BY IPCS CONTACT POINTS

REVIEW OF COMMENTS (PRODUCER/RO ), PREPARATION OF SECOND DRAFT 2

FINAL REVIEW BOARD 3

FINAL DRAFT 4

EDITING

APPROVAL BY DIRECTOR, IPCS

PUBLICATION

1 Revision as necessary. 2 Taking into account the comments from reviewers. 3 The second draft of documents is submitted to the Final Review Board together with the reviewers’ comments (6-10 CICADs are usually reviewed at the Final Review Board). In the case of pesticides the role of the Final Review Board is fulfilled by a joint meeting on pesticides. 4 Includes any revisions requested by the Final Review Board.

2 1,2-Dichloroethane

Board members serve in their personal capacity, not as representatives of any organization, government, or industry. They are selected because of their expertise in human and environmental toxicology or because of their experience in the regulation of chemicals. Boards are chosen according to the range of expertise required for a meeting and the need for balanced geographic representation.

Board members, authors, reviewers, consultants, and advisers who participate in the preparation of a CICAD are required to declare any real or potential conflict of interest in relation to the subjects under discussion at any stage of the process. Representatives of nongovernmental organizations may be invited to observe the proceedings of the Final Review Board. Observers may participate in Board discussions only at the invitation of the Chairperson, and they may not participate in the final decision-making process.

3 Concise International Chemical Assessment Document 1

1. EXECUTIVE SUMMARY teratogenic in experimental animals or that it induces reproductive or developmental effects at levels of exposure lower than those that cause other systemic This CICAD on 1,2-dichloroethane was prepared effects. by the Environmental Health Directorate of Health Canada based on an International Programme on Exposure to 1,2-dichloroethane by gavage for Chemical Safety (IPCS) Environmental Health Criteria 78 weeks induced a significant increase in the incidence (EHC) document (IPCS, 1995), which assesses the of tumours at several sites (including haemangiosar- potential effects on human health of indirect exposure to comas and tumours of the stomach, mammary gland, 1,2-dichloroethane in the general environment as well as liver, lung, and endometrium) in both rats and mice. the chemical’s environmental effects. Data identified as Although there were no significant increases in tumour of May 1993 (human health effects) and October 1994 incidence in rats or mice exposed via inhalation, repeated (environmental effects) were considered in these dermal or intraperitoneal application of 1,2- reviews. Information on the nature of the peer review dichloroethane resulted in an increase in lung tumours in process and the availability of the EHC document is mice. 1,2-Dichloroethane has been consistently geno- presented in Appendix 1. For this CICAD, the peer toxic in numerous in vitro assays in prokaryotes, fungi, review process prior to consideration by the Final and mammalian (including human) cells. Similarly, Review Board was covered by the peer review carried results were consistently positive for genotoxic activity out for the EHC. This CICAD on 1,2-dichloroethane was (as well as binding to DNA) in in vivo studies in rats, finalized and approved for publication, through mice, and insects. correspondence, by members of the Final Review Board, who also considered the peer review comments provided The lowest reported IC50s and EC50s for various during the development of the EHC. The composition of end-points in aquatic organisms were 25 and 105 the Final Review Board is outlined in Appendix 2. The mg/litre, respectively. The lowest reported LC50 value for International Chemical Safety Card (ICSC 0250) produced Daphnia was 220 mg/litre, whereas effects on by the IPCS (1993) has also been reproduced in this reproduction occurred at 20.7 mg/litre. The most document. sensitive freshwater vertebrate tested was the north- western salamander (Ambystoma gracile), in which 1,2-Dichloroethane (CAS no. 107-06-2) is a volatile, reduced larval survival was observed at 2.5 mg/litre. synthetic hydrocarbon that is used principally in the Only limited data are available on the effects of 1,2- synthesis of vinyl chloride monomer and other dichloroethane on terrestrial species. chlorinated solvents. It has also been used as a leaded gasoline additive and a fumigant, although its use as a Based on available data, 1,2-dichloroethane is gasoline additive is declining. The majority of environ- considered to be a probable human carcinogen, and mental releases are to ambient air, where it is moderately therefore exposure should be reduced to the extent persistent. However, it is not expected to contribute to possible. The carcinogenic potency (expressed as the ozone depletion. 1,2-Dichloroethane has a low potential dose associated with a 5% increase in tumour incidence), for bioaccumulation; inhalation in air is likely the primary derived on the basis of studies in which animals were source of human exposure. exposed by gavage, was calculated to be 6.2–34 mg/kg body weight per day. Guidance values for air (the Little information is available on the effects of principal source of human exposure) of 3.6–20 :g/m3 or 1,2-dichloroethane in humans. The few identified 0.36–2.0 :g/m3, calculated on the basis of a margin 5000- epidemiological investigations on its potential carcino- or 50 000-fold less than the estimated carcinogenic genicity are inconclusive. potency, have been derived; however, it should be noted that risks are overestimated on this basis, as 1,2-Dichloroethane is moderately acutely toxic in available data indicate that 1,2-dichloroethane is less experimental animals. Limited information on non- potent when inhaled. (Corresponding values for neoplastic effects presented in short-term, subchronic, ingestion are 1.2–6.8 :g/kg body weight per day or and chronic studies indicates that the liver and kidneys 0.12–0.68 :g/kg body weight per day.) These values are the principal target organs; lowest reported effect correspond to those considered by some agencies to levels for ingestion and inhalation were 49–82 mg/kg represent “essentially negligible” risk (i.e. 10–5 to 10–6 for body weight per day (increases in liver weight in rats a genotoxic carcinogen). Based on a sample estimate, exposed for 13 weeks) and 202 mg/m3 (effects on liver indirect exposure in the general environment is up to and kidney function in rats exposed for 12 months), approximately 300 times less than these values. respectively. Based on the results of a limited number of studies, there is no evidence that 1,2-dichloroethane is

4 1,2-Dichloroethane

2. IDENTITY AND PHYSICAL/CHEMICAL 5. ENVIRONMENTAL TRANSPORT, PROPERTIES DISTRIBUTION, AND TRANSFORMATION

1,2-Dichloroethane (CAS no. 107-06-2; ethylene The majority of 1,2-dichloroethane released to the dichloride, dichloro-1,2-ethane; see structural diagram environment is in emissions to air. 1,2-Dichloroethane is below) is a synthetic chemical that is a colourless liquid moderately persistent in air; its estimated atmospheric at room temperature. It is also highly volatile, with a lifetime is between 43 and 111 days. Small amounts of vapour pressure of 8.5 kPa (at 20ºC), and soluble in 1,2-dichloroethane are transported to the stratosphere, water, with a solubility of 8690 mg/litre (at 20ºC). The log where photolysis may produce chlorine radicals, which octanol/water partition coefficient of 1,2-dichloroethane may in turn react with ozone (Spence & Hanst, 1978; is 1.76. Additional physical/chemical properties are Callaghan et al., 1979). Some 1,2-dichloroethane may be presented in the International Chemical Safety Card, released in industrial effluents to the aquatic environ- reproduced in this document. ment, from where it is removed rapidly by volatilization (Dilling et al., 1975). 1,2-Dichloroethane may also leach H H to groundwater near industrial waste sites. It is not * * expected to bioconcentrate in aquatic or terrestrial Cl ) C ) C ) Cl species. * * H H

6. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE 3. ANALYTICAL METHODS

6.1 Environmental levels Analysis for 1,2-dichloroethane in environmental media is usually by gas chromatography, in combination Data considered to be most representative of with electron capture detection, flame ionization detec- current levels of 1,2-dichloroethane in environmental tion, or mass spectrometry. Detection limits range from media are summarized in Table 1. Mean concentrations 0.016 to >4 :g/m3 for air, from 0.001 to 4.7 :g/litre for of 1,2-dichloroethane in surveys of ambient air in non- water, and from 6 to 10 :g/kg for various foodstuffs source-dominated areas in cities are 0.07–0.28 :g/m3 in (ATSDR, 1992). Canada, <0.004–3.8 :g/m3 in Japan, and 1.2 :g/m3 in the United Kingdom and the Netherlands. Earlier surveys in the USA reported mean levels of 0.33–6.05 :g/m3; however, peak levels near chemical manufacturing plants 4. SOURCES OF HUMAN AND have ranged as high as 736 :g/m3 (US EPA, 1985). ENVIRONMENTAL EXPOSURE Mean levels in residential indoor air are reported to be <0.1 :g/m3 in Canada, 0.1–0.5 :g/m3 in the USA, and 3.4 :g/m3 in the Netherlands. There are no known natural sources of 1,2- dichloroethane. The principal use for 1,2-dichloroethane In drinking-water, mean 1,2-dichloroethane con- is in the synthesis of vinyl chloride monomer and, to a centrations are generally less than 0.5 :g/litre, based on lesser extent, in the manufacture of various chlorinated the results of surveys in Canada, the USA, Japan, and solvents. It is also incorporated into antiknock gasoline Spain. Although there are few recent data, 1,2-dichloro- additives (although this use is declining with the phase- ethane has only very rarely been detected in surface out of leaded gasoline in some countries) and has been water at concentrations greater than 10 :g/litre. used as a fumigant. Total annual production of 1,2- dichloroethane in Canada (1990) and the USA (1991) is 1,2-Dichloroethane has only rarely been detected about 922 and 6318 kt, respectively (CPI, 1991; Chemical in foodstuffs in extensive surveys in Canada and the Marketing Reporter, 1992). USA. Also, as 1,2-dichloroethane has low potential for bioaccumulation, food is unlikely to be a major source of exposure.

5 Concise International Chemical Assessment Document 1

Table 1: Levels of 1,2-dichloroethane in environmental media.

Medium Location Year Concentrations Reference Ambient air Canada 1988–1990 0.07–0.28 :g/m3 (means) T. Dann, unpublished data, 1992 Ambient air Japan 1992 <0.004–3.8 :g/m3 (means) Environment Agency Japan, 1993 Ambient air UK 1982, 1983 1.2 :g/m3 (mean) Clark et al., 1984a,b Ambient air Netherlands 1980 1.2 :g/m3 (mean) Guicherit & Schulting, 1985 Ambient air USA 1980–1982 0.33–6.05 :g/m3 (means) Singh et al., 1980, 1981, 1982 Indoor air (residential) Canada 1991 <0.1 :g/m3 (mean) Fellin et al., 1992 Indoor air (residential) USA 0.1–0.5 :g/m3 (means) US EPA, 1992 Indoor air (residential) Netherlands 1984–1985 3.4 :g/m3 (mean) Kliest et al., 1989 Drinking-water Canada 1988–1991 <0.05–0.139 :g/litre (mean) P. Lachmaniuk, personal communication, 1991 1990 <0.2 :g/litre (mean) Ecobichon & Allen, 1990 1982–1983 <0.1 :g/litre (mean) Otson, 1987 Drinking-water USA Early 1980s NDa – 19 :g/litre Letkiewicz et al., 1982 ND – 0.05 :g/litre Barkley et al., 1980 Drinking-water Japan 1976 <0.5–0.9 :g/litre Fujii, 1977 Drinking-water Spain 1987 2–22 :g/litre Freiria-Gandara et al., 1992 Surface water Canada 1981–1985 <0.08 :g/litre Kaiser et al., 1983; Comba & Kaiser, 1985; Kaiser & Comba, 1986; Lum & Kaiser, 1986 Surface water Japan 1992 0.01–3.4 :g/litre Environment Agency Japan, 1993 Food (34 groups) Canada 1991 <50 :g/kg (solids); <1 :g/litre Enviro-Test Laboratories, 1991 (liquids) 1992 <5 :g/kg (solids); <1 :g/litre Enviro-Test Laboratories, 1992 (liquids) Food (19 items) USA Not specified ND – 0.31 :g/kg Heikes, 1987, 1990 Not specified ND – 8.2 :g/kg Heikes, 1987 Food (231 items) USA Not specified <9–30 :g/kg Daft, 1988 a Detection limit not reported.

6.2 Human exposure that 20 of 24 hours are spent indoors (IPCS, 1994) and the range of concentrations in indoor or “personal” air in An example of estimated indirect exposure in the Canada and the USA of <0.1–0.5 :g/m3, is estimated to general environment is presented here. Exposure of the range from <0.03 to 0.1 :g/kg body weight per day. general population to 1,2-dichloroethane in environ- Based on a daily volume of water consumption for adults mental media may be estimated based on concentrations of 1.4 litres, a mean body weight of 64 kg (IPCS, 1994), determined in various media and reference values for and the mean levels of 1,2-dichloroethane in provincial body weight and consumption patterns. Owing to the surveys in Canada of <0.05–0.139 :g/litre, the mean availability of relevant data, exposure has been estimated intake from drinking-water is estimated to range from based primarily on data from North America. However, <0.001 to 0.003 :g/kg body weight per day. Intake of countries are encouraged to estimate total exposure on 1,2-dichloroethane in food is likely to be negligible, as it the basis of national data, possibly in a manner similar to has not been detected in extensive surveys and as it has that outlined here. low potential for bioaccumulation. Therefore, the principal source of exposure of the general population to Based on a daily inhalation volume for adults of 22 1,2-dichloroethane is indoor and outdoor air, with only m3, a mean body weight for males and females of 64 kg, minor amounts being contributed by drinking-water. the assumption that 4 of 24 hours are spent outdoors (IPCS, 1994), and the range of mean levels of 1,2- Few data on occupational exposure to 1,2- dichloroethane in ambient air of 0.07–0.28 :g/m3 in a dichloroethane were identified. In North America, survey of cities across Canada, the mean intake of 1,2- workers are exposed to 1,2-dichloroethane principally in dichloroethane from ambient air for the general the manufacture of other chemical substances; in such population is estimated to range from 0.004 to 0.02 :g/kg situations, the principal route of exposure is most likely body weight per day. The mean intake of 1,2- inhalation and, possibly, dermal contact. dichloroethane in indoor air, based on the assumption

6 1,2-Dichloroethane

7. COMPARATIVE KINETICS AND (Barsoum & Saad, 1934; McCollister et al., 1956; Smyth, METABOLISM IN LABORATORY ANIMALS 1969; Larionov and Kokarovtseva, 1976; Munson et al., AND HUMANS 1982; NIOSH, 1994a).

8.2 Irritation and sensitization 1,2-Dichloroethane is readily absorbed following Application of 1,2-dichloroethane to the skin of inhalation, ingestion, and dermal exposure and is rapidly and widely distributed throughout the body. Relative experimental animals has resulted in microscopic distribution of radioactivity (presumably as metabolites) changes and moderate oedema (Duprat et al., 1976; was similar in rats administered a single oral dose of Kronevi et al., 1981; Jakobson et al., 1982). Similarly, 150 mg/kg body weight and those exposed by inhalation histological changes and mild irritation in the eye have to 150 ppm (600 mg/m3) for 6 hours (Reitz et al., been observed in animals following direct application 1982). 1,2-Dichloroethane is rapidly and extensively (Kuwabara et al., 1968; Duprat et al., 1976). No metabolized in rats and mice, with principally sulfur- information on the sensitization potential of this containing metabolites being eliminated in the urine in a substance was identified. dose-dependent manner. Metabolism appears to be 8.3 Short-term exposure saturated or limited in rats at levels of exposure resulting in concentrations in blood of 5–10 :g/ml (Reitz et al., 1982). Levels of DNA alkylation were higher following Few data were identified on the toxicity of 1,2- exposure to a bolus dose of 150 mg/kg body weight by dichloroethane following short-term exposure. Degener- gavage compared with inhalation of 150 ppm (600 mg/m3) ation and necrosis of the liver and kidneys, accompanied over a 6-hour period (Reitz et al., 1982). by congestion and haemorrhage of the lungs and adrenal glands, were observed in small groups of rats, Available data suggest that 1,2-dichloroethane is rabbits, guinea-pigs, dogs, and pigs exposed to 1,2- 3 metabolized via two principal pathways. The first dichloroethane by inhalation at 6000 mg/m , 7 hours/day, involves a saturable microsomal oxidation mediated by for 6 days (Heppel et al., 1945). No effects on body or cytochrome P-450 to 2-chloroacetaldehyde and 2-chloro- organ weights, histology, or clinical chemistry were ethanol, followed by conjugation with glutathione. The noted in rats administered oral doses of up to 150 mg/kg second pathway entails direct conjugation with body weight per day for 2 weeks (van Esch et al., 1977; glutathione to form S-(2-chloroethyl)-glutathione, which Reitz et al., 1982). may be non-enzymatically converted to a glutathione 8.4 Long-term exposure episulfonium ion; this ion can form adducts with proteins, DNA, or RNA. Although DNA damage has 8.4.1 Subchronic exposure been induced by the P-450 pathway in vitro (Banerjee et al., 1980; Guengerich et al., 1980; Lin et al., 1985), several The results of subchronic studies in several lines of evidence indicate that the glutathione species of experimental animals indicate that the liver conjugation pathway is probably of greater significance than the P-450 pathway as the major route for DNA and kidneys are the target organs of 1,2-dichloroethane damage (Guengerich et al., 1980; Rannug, 1980; exposure; however, most of these studies were inade- quate to serve as a basis for establishing reliable no- Sundheimer et al., 1982; Inskeep et al., 1986; Koga et al., observed-effect levels or lowest-observed-effect levels, 1986; Simula et al., 1993). generally because of the inadequate documentation and the limited range of end-points examined in small groups of animals. In a series of early limited studies, 8. EFFECTS ON LABORATORY MAMMALS morphological changes in the liver were observed in several species following subchronic exposure (7 AND TEST SYSTEMS IN VITRO hours/day) to airborne concentrations as low as 800 mg/m3 (Heppel et al., 1946; Spencer et al., 1951; Hofmann et al., 1971). Increases in relative liver weight have been 8.1 Single exposure observed in rats following subchronic oral administration of doses of 49–82 mg/kg body weight per 1,2-Dichloroethane is moderately acutely toxic in day and above for 13 weeks (van Esch et al., 1977; NTP, experimental animals. For example, LC50s for rats 1991). exposed by inhalation for 6 or 7.25 hours ranged from 4000 mg/m3 (Spencer et al., 1951) to 6600 mg/m3 (Bonnet et al., 1980), whereas oral LD50s for rats, mice, dogs, and rabbits ranged from 413 to 2500 mg/kg body weight

7 Concise International Chemical Assessment Document 1

8.4.2 Chronic exposure and carcinogenicity there were significant increases in the incidences of adenocarcinomas and fibroadenomas (combined) of the Little information was presented on non-neoplastic mammary gland (6/59, 0/20, 15/50, and 24/50). Mortality effects in available chronic studies. Changes in serum was significantly higher in both males and females in the parameters indicative of liver and kidney toxicity were high-dose group, and there was a greater frequency of observed in groups of 8–10 male or female Sprague- clinical signs of toxicity in exposed rats compared with Dawley rats exposed to airborne concentrations as low controls. Chronic murine pneumonia was present in as 202 mg/m3 for 12 months, although histopathological 60–94% of rats in each group, although the incidence examinations were not conducted in this study was not related to dose (NCI, 1978). (Spreafico et al., 1980).

In a similar bioassay, B6C3F1 mice (n = 50 of each The carcinogenicity of 1,2-dichloroethane has sex in exposed groups; n = 20 matched controls; been investigated in a few limited bioassays in experi- n = 60 pooled controls) were administered time- mental animals (limitations include short duration of weighted-average doses of 97 or 195 mg/kg body weight exposure and high mortality). In an inhalation study, no per day (males) and 149 or 299 mg/kg body weight per significant increase in the incidence of any type of day (females) in corn oil by gavage, 5 days/week, for 78 tumour was reported in groups of 90 male or female weeks, followed by 13 weeks of observation. The Sprague-Dawley rats exposed to concentrations of incidence of hepatocellular carcinomas was significantly 1,2-dichloroethane up to 150 ppm (607 mg/m3), 7 hours/ increased in exposed males (4/59, 1/19, 6/47, and 12/48 in day, 5 days/week, for 78 weeks and observed until pooled vehicle controls, matched vehicle controls, low- spontaneous death (Maltoni et al., 1980). However, dose group, and high-dose group, respectively), mortality was high in this study, although it was not although the authors noted that the increase in the related to concentration, and incidence rates were not incidence of this tumour could not be convincingly adjusted for differential mortality among groups. There attributed to the test chemical, owing to the high was a non-significant increase in the incidence of variability of hepatocellular neoplasms among historical mammary gland adenomas and fibroadenomas in female controls. The incidence of alveolar/bronchiolar Sprague-Dawley rats (n = 50) exposed to 1,2-dichloro- adenomas was significantly increased in males in the ethane at 50 ppm (200 mg/m3), 7 hours/day, 5 days/ week, high-dose group (0/59, 0/19, 1/47, and 15/48) and in both for 2 years in an assay in which no other compound- groups of exposed females (2/60, 1/20, 7/50, and 15/48); related toxicity was observed (Cheever et al., 1990). No one female in the high-dose group had an increase in the incidence of any type of tumour was alveolar/bronchiolar carcinoma. The incidence of observed in groups of 90 male or female Swiss mice mammary gland adenocarcinomas was significantly exposed to concentrations of 1,2-dichloroethane up to increased in females at both doses (0/60, 0/20, 9/50, and 150 ppm (607 mg/m3), 7 hours/day, 5 days/ week, for 78 7/48). The incidence of endometrial stromal polyp or weeks and observed until spontaneous death (Maltoni endometrial stromal sarcoma (combined) in females was et al., 1980). significantly elevated at both doses (0/60, 0/20, 5/49, and 5/47). There was a dose-related increase in mortality in In contrast, there has been convincing evidence of females, but not in males; in addition, body weight was increases in tumour incidence in two species following decreased in females receiving the higher dose (NCI, ingestion. There were significant increases in the 1978). incidence of tumours at several sites in Osborne-Mendel rats (n = 50 of each sex in exposed groups; n = 20 The incidence of lung tumours (benign lung papil- matched controls; n = 60 pooled controls) administered lomas) was significantly increased in female non-inbred time-weighted-average doses of 47 or 95 mg/kg body Ha:ICR mice (n = 30) following repeated dermal applica- weight per day in corn oil by gavage, 5 days/week, for 78 tion of 1,2-dichloroethane, 3 times/week, for 440–594 weeks, followed by 32 weeks of observation. The days (van Duuren et al., 1979). Repeated intraperitoneal incidence of squamous cell carcinomas of the stomach injections of 1,2-dichloroethane resulted in a dose- was significantly increased in both groups of exposed related increase in the number of pulmonary adenomas males (0/60, 0/20, 3/50, and 9/50 in pooled [from per mouse in a screening bioassay in a susceptible strain concurrent studies] vehicle controls, matched vehicle (A/St), although none of these increases was significant controls, low-dose group, and high-dose group, (Theiss et al., 1977). Concomitant exposure to inhaled respectively). There were also significant increases in 1,2-dichloroethane and disulfiram in the diet resulted in the incidence of haemangiosarcomas in exposed males an increased incidence of intrahepatic bile duct (1/60, 0/20, 9/50, and 7/50) and females (0/59, 0/20, 4/50, cholangiomas and cysts, subcutaneous fibromas, and 4/50). The incidence of fibromas of the hepatic neoplastic nodules, interstitial cell tumours in the subcutaneous tissue was significantly increased in testes, and mammary adenocarcinomas in rats, compared exposed males (0/60, 0/20, 5/50, and 6/50). In females, with rats administered either compound alone or

8 1,2-Dichloroethane

untreated controls (Cheever et al., 1990). No potential to Effects on antibody levels and reversible effects on cell- initiate or promote tumour development was evident in mediated responses were also noted in mice exposed to three bioassays (van Duuren et al., 1979; Klaunig et al., 1,2-dichloroethane in drinking-water at concentrations 1986; Story et al., 1986; Milman et al., 1988), although the equivalent to doses of 3 mg/kg body weight per day and extent of histopathological examination was limited in above for 14 or 90 days (Munson et al., 1982). these studies. Data on the neurological effects of 1,2-dichloro- ethane have not been identified. 8.5 Genotoxicity and related end-points

1,2-Dichloroethane has been consistently 9. EFFECTS ON HUMANS demonstrated to be genotoxic in numerous in vitro (Table 2) and in vivo (Table 3) assays for a wide range of end-points. It has been mutagenic in Salmonella 9.1 Case reports typhimurium, especially in the presence of an exogenous activation system, and induces unscheduled DNA Acute incidental exposure to 1,2-dichloroethane by synthesis, induces gene mutation, and forms adducts inhalation or ingestion has resulted in a variety of effects with DNA in mammalian cells in vitro. It binds to DNA in humans, including effects on the central nervous in all reported in vivo studies in rats and mice. 1,2- system, liver, kidney, lung, and cardiovascular system Dichloroethane has also induced somatic cell and sex- (e.g. Hinkel, 1965; Suveev & Babichenko, 1969; Dorndorf linked recessive lethal mutations in Drosophila et al., 1975; Andriukin, 1979; Nouchi et al., 1984). Based melanogaster. on limited available data in humans, the lethal oral dose of 1,2-dichloroethane has been estimated to be between Available data on genotoxicity are consistent 20 and 50 ml. with the hypothesis that the glutathione pathway of conjugation (i.e. production of the glutathione epi- 9.2 Epidemiological studies sulfonium ion) is probably of greater significance than the P-450 pathway as the major route for DNA damage The potential carcinogenicity of 1,2-dichloroethane (Guengerich et al., 1980; Rannug, 1980; Sundheimer et al., in exposed human populations has not been extensively 1982; Inskeep et al., 1986; Koga et al., 1986; Simula et al., investigated. Mortality due to pancreatic cancer was 1993); mutation frequency in human cell lines has been significantly increased (standardized mortality ratio correlated with variations in levels of glutathione-S- [SMR] = 492, based on eight cases) in a group of 278 transferase activities (Crespi et al., 1985). workers at a chemical production plant who had been principally exposed to 1,2-dichloroethane in combination 8.6 Reproductive and developmental with other chemicals. Mortality due to this cause toxicity increased with duration of exposure. In addition, although the number of cases was small (i.e. four) and Based on the results of a limited number of the association with duration of exposure was less studies, there is no evidence that 1,2-dichloroethane is consistent, mortality due to leukaemia was also teratogenic in experimental animals and little convincing increased in these workers (Benson & Teta, 1993). evidence that it induces reproductive or developmental effects at doses below those that cause other systemic No association between occupational exposure to effects (Alumot et al., 1976; Vozovaya, 1977; Kavlock et 1,2-dichloroethane and brain cancer was noted in a small al., 1979; Rao et al., 1980; Lane et al., 1982). case–control study (Austin & Schnatter, 1983). Although the incidence of colon and rectal cancer 8.7 Immunological and neurological increased with concentration of 1,2-dichloroethane in effects drinking-water in an inherently limited ecological study, concomitant exposure to other substances may have Immunological effects, including reduced contributed to the observed effects (Isacson et al., 1985). resistance to streptococcal challenge, decreased pulmonary bactericidal activity in mice, and altered levels of antibody production in rabbits, have been observed following acute or subchronic exposure to 1,2-dichloroethane at 20 and 10 mg/m3 and above, respectively (Shmuter, 1977; Sherwood et al., 1987), whereas there were no effects in rats exposed to up to 800 mg/m3 for several days (Sherwood et al., 1987).

9 Concise International Chemical Assessment Document 1

Table 2: Genotoxicity of 1,2-dichloroethane in vitro (modified from ATSDR, 1992).

Result With Without Species (test system) End-point activation activation Reference PROKARYOTIC SYSTEMS

Salmonella typhimurium Gene mutation + + Milman et al., 1988 + + Barber et al., 1981 + + Kanada & Uyeta, 1978 + + Nestmann et al., 1980 + + Rannug et al., 1978 + + van Bladeren et al., 1981 + NT Rannug & Beije, 1979 + – Cheh et al., 1980 + – Moriya et al., 1983 – – King et al., 1979 + + Strobel & Grummt, 1987 NT +a Simula et al., 1993 S. typhimurium/spot test Gene mutation NT (+) Brem et al., 1974 (+) – Principe et al., 1981 NT – Buijs et al., 1984 S. typhimurium/Ara test (standard) Gene mutation + – Roldan-Arjona et al., 1991 S. typhimurium/Ara test (liquid) Gene mutation (+) (+) Roldan-Arjona et al., 1991 Streptomyces coelicolor Gene mutation NT – Principe et al., 1981 Escherichia coli K12/343/113 Gene mutation – – King et al., 1979 E. coli wp2 Gene mutation NT (+) Hemminki et al., 1980 – – Moriya et al., 1983

E. coli Pol A DNA damage NT (+) Brem et al., 1974 Bacillus subtilis/rec– assay DNA damage NT – Kanada & Uyeta, 1978 EUKARYOTIC ORGANISMS — FUNGI Aspergillus nidulans Gene mutation NT – Crebelli & Carere, 1988 NT – Principe et al., 1981 A. nidulans Mitotic segregation aberrations NT + Crebelli et al., 1984 A. nidulans Aneuploidy induction NT + Crebelli et al., 1988 Saccharomyces cerevisiae Mitotic recombination NT (+) Simmon, 1980 — ANIMAL SYSTEMS Hamster CHO/HGPRT Gene mutation + (+) Tan & Hsie, 1981 + (+) Zamora et al., 1983 Rat hepatocytes Unscheduled DNA synthesis NT + Williams et al., 1989 Mouse hepatocytes Unscheduled DNA synthesis NT + Milman et al., 1988 Mouse liver DNA DNA binding + NT Banerjee, 1988 Calf thymus DNA DNA binding + NT Prodi et al., 1986 Salmon sperm DNA DND binding + – Banerjee & van Duuren, 1979; Banerjee et al., 1980 Mouse BALB/c-3T3 Cell transformation NT – Milman et al., 1988 NT – Tu et al., 1985 Mouse C3H1OT½ Cell transformation NT +b Schultz et al., 1992 Syrian hamster embryo cells Cell transformation NT + Hatch et al., 1983 — HUMAN CELLS Human lymphoblasts AHH-1 Gene mutation NT + Crespi et al., 1985 Human lymphoblasts TK6 Gene mutation NT + Crespi et al., 1985 Human embryo epithelial-like EUE Gene mutation NT + Ferreri et al., 1983 cells Human peripheral lymphocytes Unscheduled DNA synthesis + – Perocco & Prodi, 1981

NT = not tested – = negative result + = positive result (+) = weakly positive or marginal result a Increase in cells expressing GSTA1-1. b Transformed cells induced tumours in nude mice.

10 1,2-Dichloroethane

Table 3: Genotoxicity of 1,2-dichloroethane in vivo (modified from ATSDR, 1992).

Species (test system) End-point Results Reference MAMMALIAN ASSAYS Mouse Dominant lethal mutations – Lane et al., 1982 Mouse/spot test Gene mutation (+) Gocke et al., 1983 Mouse bone marrow Sister chromatid exchange + Giri & Que Hee, 1988 Mouse bone marrow Micronuclei – King et al., 1979; Jenssen & Ramal, 1980 Mouse peripheral erythrocytes Micronuclei – Armstrong & Galloway, 1993 Mouse liver, kidney, lung, and stomach DNA binding + Prodi et al., 1986 Mouse liver, kidney, lung, and stomach DNA binding + Arfellini et al., 1984 Mouse forestomach and kidney DNA binding + Hellman & Brandt, 1986 Mouse liver DNA binding + Banerjee, 1988 Rat liver, kidney, spleen, lung, forestomach, DNA binding + Reitz et al., 1982 and stomach Rat liver, kidney, lung, and stomach DNA binding + Arfellini et al., 1984 Rat liver, kidney, lung, and stomach DNA binding + Prodi et al., 1986 Rat liver and kidney DNA binding + Inskeep et al., 1986 Rat liver and lung DNA binding + Baertsch et al., 1991 Rat liver DNA binding + Banerjee, 1988 Rat liver DNA binding + Cheever et al., 1990 Mouse liver DNA damage + Storer & Conolly 1983, 1985; Storer et al., 1984 Mouse liver DNA damage + Taningher et al., 1991 INSECT ASSAYS Drosophila melanogaster/somatic mutation Gene mutation + Nylander et al., 1978 D. melanogaster/somatic mutation Gene mutation + Romert et al., 1990 D. melanogaster/somatic mutation Gene mutation + Kramers et al., 1991 D. melanogaster/somatic mutation Gene mutation (+) Ballering et al., 1993 D. melanogaster/recessive lethal Gene mutation + Ballering et al., 1993 D. melanogaster/vermilion locus Gene mutation + Ballering et al., 1993 D. melanogaster/sex-linked recessive Gene mutation + King et al., 1979 D. melanogaster/sex-linked recessive Gene mutation + Kramers et al., 1991 D. melanogaster Chromosomal loss/gain +/+ Valencia et al., 1984 HOST-MEDIATED ASSAYS Escherichia coli K12/343/113 mouse host- Gene mutation – King et al., 1979 mediated assay

– = negative result + = positive result (+) = weakly positive or marginal result

10. EFFECTS ON OTHER ORGANISMS IN identified study in marine algae, an EC50 for carbon THE LABORATORY AND FIELD uptake of 340 mg/litre was reported in Phaeodactylum tricornutum (Pearson & McConnell, 1975). Toxicity thresholds (cell multiplication inhibition) were above 800 10.1 Aquatic environment mg/litre for three species of aquatic protozoa (Bringmann & Kühn, 1980). The effects of exposure to 1,2-dichloroethane on a number of aquatic organisms in the laboratory and field The lowest reported LC50 value for Daphnia was have also been investigated. In bacteria, the lowest 220 mg/litre (Leblanc, 1980), whereas the lowest EC50 (for 10% immobilization) was 150 mg/litre (Freitag et al., 1994). reported IC50s for inhibition of gas production and ammonia consumption were 25 and 29 mg/litre in Effects on reproductive success and growth were methanogens and Nitrosomonas, respectively (Blum & observed in Daphnia at 20.7 and 71.7 mg/litre, Speece, 1991). The most sensitive freshwater alga respectively. There were no effects on these end-points at 10.6 and 41.6 mg/litre, respectively (Richter et al., studied was Microcystis aeruginosa, in which an EC50 for inhibition of cell multiplication of 105 mg/litre was 1983). observed (Bringmann & Kühn, 1978); in the only

11 Concise International Chemical Assessment Document 1

Based on available data, the most sensitive limited bioassays, the production of a reactive inter- freshwater vertebrate species appears to be the north- mediate that alkylates DNA in vivo, and positive results western salamander, in which 9-day larval survival (4 in a range of in vitro assays for genotoxicity, 1,2- days post-hatch) was reduced at 2.5 mg/litre (Black et al., dichloroethane is considered to be a probable human 1982). carcinogen.

10.2 Terrestrial environment The carcinogenic potency of 1,2-dichloroethane has been calculated based on the increased incidence of Identified data on the toxicity of 1,2-dichloro- squamous cell carcinomas of the stomach, haemangio- ethane to terrestrial organisms are inadequate to permit sarcomas, fibromas of the subcutaneous tissue, and assessment. adenocarcinomas or fibroadenomas (combined) of the mammary gland in Osborne-Mendel rats exposed orally by gavage, as well as the increased incidence of 11. EFFECTS EVALUATION alveolar/bronchiolar adenomas, hepatocellular carcinomas, mammary gland adenocarcinomas, and endometrial stromal polyps or sarcomas (combined) in

11.1 Evaluation of health effects similarly exposed B6C3F1 mice; data from both the matched (same study) and pooled (concurrent studies) 11.1.1 Hazard identification and dose–response vehicle controls were incorporated. It should be noted, assessment however, that mortality was higher at the high dose in female mice and rats of both sexes than in other dose Based on limited available data in humans, the groups in this study. Therefore, these high-dose groups lethal oral dose of 1,2-dichloroethane has been estimated were not included in the derivation of quantitative to be between 20 and 50 ml. 1,2-Dichloroethane is estimates of carcinogenic potency. moderately acutely toxic by inhalation, based on the results of studies in experimental animals. Skin and eye Based on multistage modelling of these data, irritation may also be induced by 1,2-dichloroethane. amortized for continuous exposure for a standard duration of 104 weeks and corrected for the expected rate Owing to the limitations of the available studies in of increase in tumour formation in rodents in a standard humans, it is necessary to rely on available experimental bioassay of 104 weeks, the doses associated with a 5% data in animal species as a basis for derivation of no- increase in tumour incidence (TD0.05s) range from 6.2 to effect levels or quantitative estimates of carcinogenic 34 mg/kg body weight per day. Incorporation of a potency. However, in most of the identified short- scaling factor for the differences in body surface area term and subchronic studies, only a limited range of end- between rodents and humans was not considered points was examined and documentation was appropriate, as it is likely that the carcinogenicity of 1,2- incomplete. Similarly, little information on non- dichloroethane is due to a metabolite, rather than to the neoplastic effects was presented in the long-term parent compound. carcinogenicity bioassays. Lowest reported effect levels were 49–82 mg/kg body weight per day for 13 weeks 11.1.2 Criteria for setting guidance values for 1,2- (increases in liver weight in rats) for ingestion (NTP, dichloroethane 1991) and 202 mg/m3 (effects on liver and kidney function in rats exposed for 12 months) for inhalation As available data indicate that 1,2-dichloroethane (Spreafico et al., 1980). Based on limited data, there is no is a genotoxic carcinogen, exposure should be reduced evidence that 1,2-dichloroethane is teratogenic in to the extent possible. The following guidance is experimental animals or that it induces reproductive or provided as a possible basis for derivation of limits of developmental effects at doses below those that cause exposure and judgement of the quality of environmental other systemic effects. media by relevant authorities, based on the potential carcinogenicity of 1,2-dichloroethane in humans. Based Based on the limited evidence of carcinogenicity in on available data, air is believed to be the principal workers exposed principally to 1,2-dichloroethane in the source of exposure in the general environment (see most reliable epidemiological study conducted to date section 6.2) and, therefore, is the principal medium (Benson & Teta, 1993), the induction of both rare and addressed here. Available data are considered common tumours in rats and mice exposed by ingestion inadequate to serve as a basis for development of (NCI, 1978) and supporting evidence in other tolerable intakes for non-neoplastic effects.

12 1,2-Dichloroethane

Although it is desirable to reduce exposure to with ozone. However, the ozone depleting potential is genotoxic carcinogens to the extent possible, a value, for low (0.001 relative to CFC-11), and the compound is not example, 5000 or 50 000 times less than the TD0.05s might listed in the Montreal Protocol on Substances that be considered appropriate as a guidance value. This Deplete the Ozone Layer. margin (5000–50 000) affords protection similar to that associated with the range for low-dose risk estimates Terrestrial organisms will have the greatest generally considered by various agencies to be potential for exposure to 1,2-dichloroethane in ambient “essentially negligible” (i.e. 10–5 to 10–6). This air. However, available data on the effects of 1,2- corresponds to a range of airborne concentrations of dichloroethane are inadequate to allow the character- 3.6–20 :g/m3 or 0.36–2.0 :g/m3. (Corresponding values ization of risks in terrestrial species. for ingestion are 1.2–6.8 :g/kg body weight per day or 0.12–0.68 :g/kg body weight per day.) Although 1,2-dichloroethane may be released to surface waters or soil through industrial processes and It should be noted, however, that the risk of disposal, and although hydrolysis and microbial exposure in air is most likely overestimated, as the degradation are slow, the substance is not likely to

TD0.05s were based on a study in which the experimental persist in these media because of its volatility. A range animals were administered bolus doses of 1,2-dichloro- of toxicity tests in aquatic species have indicated that ethane by gavage, whereas exposure in the general effect levels are generally above 10 mg/litre. As population is likely to be mostly via inhalation. Based concentrations in surface waters are generally several on available data, the carcinogenic potency of 1,2- orders of magnitude less than those demonstrated to dichloroethane appears to be less following inhalation cause effects, it is likely that 1,2-dichloroethane poses than following ingestion of bolus doses, most likely negligible risk to aquatic organisms. because of inter-route variations in toxicokinetics. 12. PREVIOUS EVALUATIONS BY 11.1.3 Sample risk characterization INTERNATIONAL BODIES

Non-neoplastic effects in animals have been observed only at concentrations more than 700 000 times The International Agency for Research on Cancer greater than those in the principal medium of exposure (IARC, 1979) has classified 1,2-dichloroethane in group (air) in the general environment, based on the sample 2B (possibly carcinogenic to humans) based on suffi- estimation of exposure presented in section 6.2 for cient evidence of carcinogenicity in experimental indirect exposure in the general environment. Identified animals. data are inadequate to allow an estimation of exposure to 1,2-dichloroethane in the occupational environment. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) has evaluated 1,2-dichloroethane on Although, wherever possible, exposure to geno- three occasions (WHO, 1971, 1980, 1992). In its last toxic carcinogens should be reduced to the extent evaluation, the Committee concluded that this com- possible, indirect population exposure in the general pound is genotoxic in both in vitro and in vivo test environment, based on the sample estimate presented in systems and carcinogenic in mice and rats when section 6.2, is up to approximately 300 times less than a administered by the oral route. No acceptable daily guidance value that might be considered appropriate on intake (ADI) was therefore allocated. The Committee the basis of available dose–response data for carcino- expressed the opinion that 1,2-dichloroethane should 3 3 genicity (i.e. 3.6–20 :g/m or 0.36–2.0 :g/m , the not be used in food. TD0.05s divided by 5000 or 50 000). Identified data are inadequate to estimate exposure to 1,2-dichloroethane in In the current WHO Guidelines for drinking-water the occupational environment. quality (WHO, 1993), the concentrations of 1,2-dichloro- ethane in drinking-water estimated to be associated with Evaluation of environmental effects 11.2 excess risks of 10–4, 10–5, and 10–6 are 300, 30, and 3 :g/litre, respectively, based on linear multistage Because 1,2-dichloroethane is released principally modelling of the incidence of haemangiosarcomas in in emissions from industrial sources and because of its male rats in the NCI (1978) study. high volatility, the atmosphere is the predominant environmental sink for 1,2-dichloroethane. It is Information on international hazard classification moderately persistent in air. Stratospheric photolysis and labelling is included in the International Chemical may produce chlorine radicals, which may in turn react Safety Card reproduced in this document.

13 Concise International Chemical Assessment Document 1

vicinity. Because the substance is absorbed through the skin, do not touch or walk through the spilled material 13. HUMAN HEALTH PROTECTION AND without proper equipment. To avoid the flammability EMERGENCY ACTION hazard, remove wet or contaminated clothing immediate- ly, and use non-sparking tools for clean-up. Do not let the substance enter the drains or watercourses. Human health hazards, together with preventative and protective measures and first aid recommendations, The IDLH (Immediately Dangerous to Life or are presented on the International Chemical Safety Card Health) value for this substance is very low, at 50 ppm 3 (ICSC 0250) reproduced in this document. (200 mg/m ) (NIOSH, 1994b).

13.1 Human health hazards

1,2-Dichloroethane is highly flammable. On long- 14. CURRENT REGULATIONS, term or repeated exposure, it is considered to be a GUIDELINES, AND STANDARDS probable human carcinogen.

13.2 Advice to physicians Information on national regulations, guidelines, and standards is available from the International Register In case of emergency, it is important to wash skin of Potentially Toxic Chemicals (IRPTC) legal file. with soap and water after removing contaminated clothing. In the event of poisoning, the treatment is The reader should be aware that regulatory symptomatic and supportive. Survival for 48 hours decisions about chemicals taken in a certain country can usually implies complete recovery, although deaths have be fully understood only in the framework of the occurred up to 5 days after exposure. legislation of that country. The regulations and guidelines of all countries are subject to change and 13.3 Health surveillance advice should always be verified with appropriate regulatory authorities before application. Monitoring of both liver and kidney functions should be included in the health surveillance programme of humans exposed to 1,2-dichloroethane.

13.4 Explosion and fire hazards

13.4.1 Explosion hazards

1,2-Dichloroethane vapours of between 6 and 12% in air form an explosive mixture.

13.4.2 Fire hazards

1,2-Dichloroethane is highly flammable.

13.4.3 Prevention

Because of its low electroconductivity, 1,2- dichloroethane can generate electrostatic charges as a result of flow or agitation. Use only closed systems, ventilation, and explosion-proof electrical equipment. All equipment must be grounded.

13.5 Spillage

1,2-Dichloroethane is highly flammable. In the event of spillage, eliminate all sources of ignition in the

14 1,2-DICHLOROETHANE 0250 March 1995 CAS No: 107-06-2 Ethylene dichloride RTECS No: KI0525000 1,2-Ethylene dichloride UN No: 1184 Ethane dichloride

EC No: 602-012-00-7 ClCH2CH2Cl / C2H4Cl2 Molecular mass: 98.96

TYPES OF HAZARD/ ACUTE HAZARDS/SYMPTOMS PREVENTION FIRST AID/FIRE FIGHTING EXPOSURE

FIRE Highly flammable. Gives off NO open flames, NO sparks, and Powder, water spray, foam, carbon irritating or toxic fumes (or gases) NO smoking. dioxide. in a fire.

EXPLOSION Vapour/air mixtures are explosive. Closed system, ventilation, In case of fire: keep drums, etc., explosion-proof electrical equipment cool by spraying with water. and lighting. Prevent build-up of electrostatic charges (e.g., by grounding). Do NOT use compressed air for filling, discharging, or handling.

EXPOSURE AVOID ALL CONTACT! IN ALL CASES CONSULT A DOCTOR!

Inhalation Abdominal pain. Cough. Ventilation, local exhaust, or Fresh air, rest. Half-upright Dizziness. Drowsiness. Headache. breathing protection. position. Artificial respiration if Nausea. Sore throat. indicated. Refer for medical Unconsciousness. Vomiting. attention. Symptoms may be delayed (see Notes).

Skin Redness. Protective gloves. Remove contaminated clothes. Rinse and then wash skin with water and soap. Refer for medical attention.

Eyes Redness. Pain. Blurred vision. Safety goggles, face shield, or eye First rinse with plenty of water for protection in combination with several minutes (remove contact breathing protection. lenses if easily possible), then take to a doctor.

Ingestion Abdominal cramps. Diarrhoea Do not eat, drink, or smoke during Give nothing to drink. Refer for (further see Inhalation). work. Wash hands before eating. medical attention.

SPILLAGE DISPOSAL PACKAGING & LABELLING

Evacuate danger area! Collect leaking and spilled F Symbol Unbreakable packaging; put liquid in sealable containers as far as possible. T Symbol breakable packaging into closed Absorb remaining liquid in sand or inert absorbent R: 45-11-22-36/37/38 unbreakable container. Do not and remove to safe place. Do NOT wash away into S: 53-45 transport with food and feedstuffs. sewer (extra personal protection: self-contained Note: E Marine pollutant. breathing apparatus). UN Hazard Class: 3 UN Subsidiary Risks: 6.1 UN Pack Group: II

EMERGENCY RESPONSE STORAGE

Transport Emergency Card: TEC (R)-605 Fireproof. Separated from strong oxidants, food and feedstuffs and other NFPA Code: H 2; F 3; R 0; incompatible substances (see Chemical Dangers). Cool. Dry.

Prepared in the context of cooperation between the International IPCS Programme on Chemical Safety and the European Commission International © IPCS 1999 Programme on Chemical Safety SEE IMPORTANT INFORMATION ON THE BACK. 0250 1,2-DICHLOROETHANE

IMPORTANT DATA

Physical State; Appearance Routes of Exposure COLOURLESS, VISCOUS LIQUID, WITH CHARACTERISTIC The substance can be absorbed into the body by inhalation of ODOUR. TURNS DARK ON EXPOSURE TO AIR, MOISTURE its vapour, through the skin and by ingestion. AND LIGHT. Inhalation Risk Physical Dangers A harmful contamination of the air can be reached very quickly The vapour is heavier than air and may travel along the ground; on evaporation of this substance at 20
C. distant ignition possible. As a result of flow, agitation, etc., electrostatic charges can be generated. Effects of Short-term Exposure The vapour irritates the eyes, the skin and the respiratory tract. Chemical Dangers Inhalation of the vapour may cause lung oedema (see Notes). The substance decomposes on heating and on burning The substance may cause effects on the central nervous producing toxic and corrosive fumes including hydrogen system, kidneys, liver, resulting in impaired functions. chloride (ICSC # 0163) and phosgene (ICSC # 0007). Reacts violently with aluminium, alkali metals, alkali amides, Effects of Long-term or Repeated Exposure ammonia, bases, strong oxidants. Attacks many metals in Repeated or prolonged contact with skin may cause dermatitis. presence of water. Attacks plastic. This substance is probably carcinogenic to humans.

Occupational Exposure Limits TLV: 10 ppm; 40 mg/m3 (as TWA) (ACGIH 1994-1995).

PHYSICAL PROPERTIES

Boiling point: 83.5
C Relative density of the vapour/air-mixture at 20
C (air = 1): 1.2 Melting point: -35.7
C Flash point: 13
C c.c. Relative density (water = 1): 1.235 Auto-ignition temperature: 413
C Solubility in water, g/100 ml: 0.87 Explosive limits, vol% in air: 6.2-16 Vapour pressure, kPa at 20
C: 8.7 Octanol/water partition coefficient as log Pow: 1.48 Relative vapour density (air = 1): 3.42

ENVIRONMENTAL DATA

NOTES Depending on the degree of exposure, periodic medical examination is indicated. The symptoms of lung oedema often do not become manifest until a few hours have passed and they are aggravated by physical effort. Rest and medical observation are therefore essential. Immediate administration of an appropriate spray, by a doctor or a person authorized by him/her, should be considered.

ADDITIONAL INFORMATION

LEGAL NOTICE Neither the EC nor the IPCS nor any person acting on behalf of the EC or the IPCS is responsible for the use which might be made of this information

© IPCS 1999 1,2-Dichloroethane

REFERENCES Barsoum GS, Saad K (1934) Relative toxicity of certain chlorine derivatives of the aliphatic series. Quarterly journal of pharmacy and pharmacology, 7: 205–214.

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APPENDIX 1 — SOURCE DOCUMENTS Professor M. Lotti, Institute of Occupational Medicine, University of Padua, Padua, Italy (Chairperson)

International Programme on Chemical Safety Dr D.R. Mattison, University of Pittsburgh, Graduate School of — Environmental Health Criteria Monograph Public Health, Pittsburgh, PA, USA

No. 176 (1995) Dr J. Sekizawa, Division of Information on Chemical Safety, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan Copies of the Environmental Health Criteria document on 1,2- dichloroethane, prepared by the International Programme on Chemical Dr P. Sinhaseni, Department of Pharmacology, Chulalongkorn Safety, as well as the Health and Safety Guide (1991) and the University, Bangkok, Thailand International Chemical Safety Card (1993), may be obtained from: Dr S.A. Soliman, Pesticide Chemicals & Toxicology, King Saud International Programme on Chemical Safety University, Bureidah, Saudi Arabia World Health Organization Geneva, Switzerland Dr M. Tasheva, Department of Toxicology, National Center of Hygiene, Medical Ecology and Nutrition, Sofia, Bulgaria The first draft of the monograph, prepared by Ms K. Hughes of the Environmental Health Directorate, Health Canada, was circulated to Mr J.R. Taylor, Pesticides Safety Directorate, Ministry of IPCS Contact Points (approximately 150 government, industrial, Agriculture, Fisheries and Food, York, United Kingdom academic, and independent organizations and individuals) for comment in June 1994. The second draft, revised on the basis of the comments Dr H.M. Temmink, Department of Toxicology, Wageningen received, was also prepared by Ms K. Hughes. Dr E. Smith and Dr Agricultural Unviersity, Wageningen, The Netherlands P.G. Jenkins, both members of the IPCS Central Unit, were responsible for the scientific content and technical editing, respectively. Dr M.I. Willems, Department of Occupational Toxicology, TNO Nutrition and Food Research Institute, AJ Zeist, The Netherlands The monograph on 1,2-dichloroethane was finalized by the Core Assessment Group (CAG) of the Joint Meeting on Pesticides (JMP), which met in Geneva from 25 October to 3 November 1994. The Core Assessment Group reviewed and revised the draft monograph and Procedures for the preparation of an made an evaluation of the risks for human health and the environment Environmental Health Criteria document from exposure to 1,2-dichloroethane. Participants at the Core Assessment Group meeting were: The order of procedures that result in the publication of an EHC monograph is shown in the flow chart. A designated staff member of Dr T. Bailey, Ecological Effects Branch, Environmental Fate and IPCS, responsible for the scientific quality of the document, serves as Effects Division, US Environmental Protection Agency, Responsible Officer (RO). The IPCS Editor is responsible for layout Washington, DC, USA and language. The first draft, prepared by consultants or, more usually, staff from an IPCS Participating Institution, is based initially on Dr A.L. Black, Department of Human Services and Health, data provided from the International Register of Potentially Toxic Canberra, ACT, Australia Chemicals and reference databases such as Medline and Toxline.

Mr D.J. Clegg, Carp, Ontario, Canada The draft document, when received by the RO, may require an initial review by a small panel of experts to determine its scientific Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood, quality and objectivity. Once the RO finds the document acceptable as Abbots Ripton, Huntingdon, Cambridgeshire, United Kingdom a first draft, it is distributed, in its unedited form, to well over 150 EHC (Vice-Chairperson) Contact Points throughout the world who are asked to comment on its completeness and accuracy and, where necessary, provide additional Dr P.E.T. Douben, Her Majesty’s Inspectorate of Pollution, material. The Contact Points, usually designated by governments, London, United Kingdom (EHC Joint Rapporteur) may be Participating Institutions, IPCS Focal Points, or individual scientists known for their particular expertise. Generally, some four Dr P. Fenner-Crisp, Office of Pesticide Programs, US months are allowed before the comments are considered by the RO and Environmental Protection Agency, Washington, DC, USA author(s). A second draft incorporating comments received and approved by the Director, IPCS, is then distributed to Task Group Dr R. Hailey, National Institute of Environmental Health Sciences, members, who carry out the peer review, at least six weeks before their National Institutes of Health, Public Health Service, Department meeting. of Health and Human Services, Research Triangle Park, NC, USA

Ms K. Hughes, Priority Substances Section, Environmental Health The Task Group members serve as individual scientists, not as representatives of any organization, government, or industry. Their Directorate, Health Canada, Ottawa, Ontario, Canada (EHC Joint function is to evaluate the accuracy, significance, and relevance of the Rapporteur) information in the document and to assess the health and environmental risks from exposure to the chemical. A summary and Dr D. Kanungo, Division of Medical Toxicology, Central recommendations for further research and improved safety aspects are Insecticides Laboratory, Government of India, Ministry of also required. The composition of the Task Group is dictated by the Agriculture & Cooperation, Directorate of Plant Protection, range of expertise required for the subject of the meeting and by the Quarantine & Storage, Faridabad, Haryana, India need for a balanced geographical distribution.

Dr L. Landner, MFG, European Environmental Research Group Ltd, Stockholm, Sweden The three cooperating organizations of the IPCS recognize the important role played by nongovernmental organizations. Dr M.H. Litchfield, Melrose Consultancy, Fontwell, Arundel, West Representatives from relevant national and international Sussex, United Kingdom associations may be invited to join the Task Group as observers. While observers may provide a valuable contribution to the process, they can speak only at the invitation of the Chairperson.

22 Observers do not participate in the final evaluation of the When the Task Group has completed its review and the RO chemical; this is the sole responsibility of the Task Group is satisfied as to the scientific correctness and completeness of members. When the Task Group considers it to be appropriate, the document, it then goes for language editing, reference it may meet in camera. checking, and preparation of camera-ready copy. After approval by the Director, IPCS, the monograph is submitted to the WHO All individuals who as authors, consultants, or advisers Office of Publications for printing. At this time, a copy of the participate in the preparation of the EHC monograph must, in final draft is sent to the Chairperson and Rapporteur of the Task addition to serving in their personal capacity as scientists, inform Group to check for any errors. the RO if at any time a conflict of interest, whether actual or potential, could be perceived in their work. They are required to sign a conflict of interest statement. Such a procedure ensures the transparency and probity of the process.

EHC PREPARATION FLOW CHART

CommitmentCommitment toto draftdraft EHCEHC

Document preparation initiated

Possible meeting Revision as of a few experts Draft sent to IPCS Responsible Officer (RO) necessary to resolve controversial issues

Responsible Officer, Editor check for coherence of text and Responsible Officer, Editor check for coherence of text and readability (not language editing) readability (not language editing)

FirstFirst DraftDraft

International circulation to Contact Points (150+)

Comments to IPCS (RO)

Review of comments, reference cross-check; preparation of Task Group (TG) draft Working group, Editor if required Task Group meeting

Insertion of TG changes

Post-TG draft; detailed reference cross-check

EditingEditing French/Spanish translations of Summary Graphics Word-processing

Camera-ready copy Library for CIP Data

Final editing

Approval by Director, IPCS

WHO Publication Office routine procedure optional procedure Printer Proofs PublicationPublication

23 Concise International Chemical Assessment Document 1

APPENDIX 2 — CICAD FINAL REVIEW Professor S. Tarkowski, Department of Environmental Health Hazards, The Nofer Institute of Occupational Medicine, Lodz, BOARD Poland

Dr M. Wallen, National Chemicals Inspectorate (KEMI), Solna, Members Sweden

Dr A. Aitio, Institute of Occupational Health, Helsinki, Finland

Dr K. Bentley, Director, Environment Policy Section, Commonwealth Department of Human Services and Health, Canberra, Australia Secretariat Mr R. Cary, Toxicology and Existing Substances Regulation Unit, Health and Safety Executive, Merseyside, United Kingdom Dr M. Baril, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland Dr J. de Fouw, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands Dr L. Harrison, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland Dr C. DeRosa, Director, Division of Toxicology, Agency for Toxic Substances and Disease Registry, Atlanta, GA, USA Dr M. Mercier, Director, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood, Abbots Ripton, Huntingdon, Cambridgeshire, United Kingdom Dr P. Toft, Associate Director, International Programme on Chemical Safety, World Health Organization, Geneva, Dr W. Farland, Director, National Center for Environmental Switzerland Assessment, Office of Research and Development, US Environmental Protection Agency, Washington, DC, USA (Chairperson)

Dr T.I. Fortoul, Depto. Biologia Celular y Tisular, National University of Mexico and Environmental Health Directorate of the Health Ministry, Mexico D.F., Mexico

Dr H. Gibb, National Center for Environmental Assessment, US Environmental Protection Agency, Washington, DC, USA

Dr R.F. Hertel, Federal Institute for Health Protection of Consumers & Veterinary Medicine, Berlin, Germany

Mr J.R. Hickman, Environmental Health Directorate, Health Canada, Ottawa, Ontario, Canada

Dr T. Lakhanisky, Head, Division of Toxicology, Institute of Hygiene and Epidemiology, Brussels, Belgium (Vice- Chairperson)

Dr I. Mangelsdorf, Documentation and Assessment of Chemicals, Fraunhofer Institute for Toxicology and Aerosol Sciences, Hanover, Germany

Ms E. Meek, Head, Priority Substances Section, Environmental Health Directorate, Health Canada, Ottawa, Ontario, Canada

Dr K. Paksy, National Institute of Occupational Health, Budapest, Hungary

Mr D. Renshaw, Department of Health, London, United Kingdom

Dr J. Sekizawa, Division of Chemo-Bio Informatics, National Institute of Hygienic Sciences, Tokyo, Japan

Dr H. Sterzl-Eckert, GSF-Forschungszentrum für Umwelt und Gesundheit GmbH, Institut für Toxikologie, Oberschleissheim, Germany

24 1,2-Dichloroethane

RÉSUMÉ D’ORIENTATION chronique ou chronique indiquent que les principaux organes cibles sont le foie et le rein; les doses les plus faibles pour lesquelles on ait signalé un effet après La Direction de l’Hygiène du Milieu de Santé ingestion et inhalation sont respectivement de 49–82 Canada a rédigé ce CICAD (Document international mg/kg de poids corporel par jour (augmentation du poids succinct sur l’évaluation des risques chimiques) sur le du foie chez des rats exposés pendant 13 semaines) et 1,2-dichloréthane en s’inspirant d’un document de la 202 mg/m3 (effets sur les fonctions hépatique et rénale série Critères d’hygiène de l’environnement (CHE) du chez des rats exposés pendant 12 mois). D’après les Programme international sur la Sécurité chimique (PISC) résultats d’un petit nombre d’études, il n’y a pas de (IPCS, 1995), qui évalue les conséquences potentielles preuve que le 1,2-dichloréthane soit tératogène chez les pour la santé humaine d’une exposition indirecte au 1,2- animaux de laboratoire, ni qu’il induise des effets sur la dichloréthane dans l’environnement général ainsi que les reproduction ou le développement lorsque les niveaux effets de cette substance sur l’environnement. Les d’exposition sont inférieurs aux niveaux qui entraînent données prises en compte dans cette analyse sont celles d’autres effets systémiques. qui étaient disponibles en mai 1993 (effets sur la santé humaine) ou en octobre 1994 (effets sur l’environne- L’exposition au 1,2-dichloréthane par gavage ment). L’appendice 1 donne des informations sur la pendant 78 semaines a été suivie d’une augmentation nature du processus d’évaluation par les pairs et sur la significative de l’incidence des tumeurs de différents disponibilité du document CHE. Pour ce CICAD, c’est organes (notamment des hémangiosarcomes et des l’évaluation pratiquée lors de l’élaboration du document tumeurs de l’estomac, des glandes mammaires, du foie, CHE qui a fait office d’évaluation par les pairs préalable à des poumons et de l’endomètre), tant chez le rat que l’examen du Comité d’évaluation finale. Les membres du chez la souris. Il n’y a eu aucune augmentation Comité d’évaluation finale ont apporté les dernières significative de l’incidence des tumeurs chez des rats ou corrections à ce CICAD et en ont approuvé la des souris exposés par inhalation, mais l’administration publication par correspondance, après avoir examiné les répétée par voie dermique ou intrapéritonéale a observations présentées lors de l’élaboration du CHE provoqué une augmentation du nombre des tumeurs des dans le cadre de l’évaluation par les pairs. La poumons chez la souris. Le 1,2-dichloréthane s’est composition du Comité d’évaluation finale est indiquée à constamment révélé génotoxique dans de nombreuses l’appendice 2. La fiche internationale sur la sécurité épreuves in vitro sur des cellules de procaryotes, de chimique (ICSC 0250) produite par le PISC (IPCS, 1993) champignons et de mammifères (y compris des cellules est également reproduite dans ce document. humaines). De même, les résultats ont été constamment positifs en ce qui concerne l’activité génotoxique (ainsi Le 1,2-dichloréthane (CAS N/ 107-06-2) est un que la fixation sur l’ADN) dans des études in vivo chez hydrocarbure synthétique volatil utilisé principalement le rat, la souris et les insectes. dans la synthèse du chlorure de vinyle monomère et d’autres solvants chlorés. Il a également été utilisé Les valeurs les plus faibles de la CI50s et de la comme additif de l’essence au plomb et comme fumigant, CE50s qui aient été signalées pour différents effets sur mais son utilisation comme additif de l’essence est en des organismes aquatiques sont respectivement de 25 et déclin. La plus grande partie du 1,2-dichloréthane libéré 105 mg/litre. La CL50 la plus faible pour les daphnies était dans l’environnement se retrouve dans l’air ambiant où de 220 mg/litre, des effets ayant toutefois été observés sa persistance est modérée. Toutefois, il ne devrait pas sur la reproduction à 20,7 mg/litre. Le vertébré d’eau contribuer à la destruction de l’ozone. Le potentiel de douce le plus sensible a été une salamandre (Ambystoma bioaccumulation du 1,2-dichloréthane est faible; son gracile) chez laquelle on a constaté une réduction de la inhalation avec l’air est probablement la principale survie des larves à 2,5 mg/litre. On ne dispose que de source d’exposition humaine. données limitées sur la toxicité du 1,2-dichloréthane pour les espèces terrestres. On dispose de peu d’information sur les effets du 1,2-dichloréthane chez l’homme. Les quelques études D’après les données disponibles, le 1,2-dichlor- épidémiologiques qui ont été faites sur sa éthane peut être considéré comme un cancérogène cancérogénicité potentielle ne sont guère concluantes. probable pour l’homme, de sorte que l’exposition doit être réduite dans toute la mesure possible. Le potentiel Le 1,2-dichloréthane présente une toxicité aiguë cancérogène (exprimé par la dose associée à une aug- modérée chez les animaux d’expérience. Les quelques mentation de 5 % de l’incidence des tumeurs), calculé à données que l’on trouve sur ses effets non néoplasiques partir d’études de gavage, a été évalué à 6,2–34 mg/kg de dans des études de chronicité à court terme, sub- poids corporel par jour. En appliquant un facteur de

25 Concise International Chemical Assessment Document 1 sécurité de 5000 ou de 50 000 au potentiel cancérogène estimé, on arrive à une valeur guide pour l’air (principale source d’exposition humaine) de 3,6–20 :g/m3 ou 0,36–2,0 :g/m3; il faut cependant noter que cette méthode surestime les risques, car les données dispon- ibles montrent que le 1,2-dichloréthane est moins actif lorsqu’il est inhalé. (Les valeurs correspondantes pour l’ingestion sont respectivement de 1,2–6,8 ou 0,12–0,68 :g/kg de poids corporel par jour.) Ces valeurs correspondent à ce que certains organismes considèrent comme un risque “pratiquement négligeable” (c’est-à- dire 10!5–10!6 pour un cancérogène génotoxique). D’après une des estimations qui ont été faites, l’exposition indirecte dans un environnement normal est approximativement 300 fois inférieure à ces valeurs.

26 1,2-Dichloroethane

RESUMEN DE ORIENTACIÓN información sobre efectos no neoplásicos presentada en estudios de corta duración, subcrónicos y crónicos indica que los principales órganos afectados son el Esta reseña de la evaluación química internacional hígado y los riñones; los niveles mínimos de ingestión e del 1,2-dicloroetano ha sido preparada por la Dirección inhalación con efectos comunicados fueron de 49–82 de Higiene del Medio de Health Canada sobre la base mg/kg de peso corporal por día (aumento de peso del de un documento de la serie “Criterios de Salud hígado en las ratas expuestas durante 13 semanas) y 202 Ambiental” (EHC) del Programa Internacional de mg/m3 (efectos sobre la función hepática y renal en las Seguridad de las Sustancias Químicas (IPCS, 1995) en el ratas expuestas durante 12 meses), respectivamente. que se evalúan los efectos potenciales sobre la salud Los resultados de un número limitado de estudios, no humana de la exposición indirecta al 1,2-dicloroetano en aportaron indicios de que el 1,2-dicloroetano sea el medio ambiente general, así como los efectos ambien- teratogénico en animales de experimentación o que tenga tales de dicha sustancia química. En este análisis se efectos sobre la reproducción o el desarrollo a niveles de examinan datos obtenidos en mayo de 1993 (efectos exposición inferiores a los que causan otros efectos sobre la salud humana) y octubre de 1994 (efectos sistémicos. ambientales). En el apéndice 1 se proporciona infor- mación sobre el proceso de revisión científica y los La exposición al 1,2-dicloroetano administrado documentos disponibles de la serie EHC. Por lo que por sonda durante 78 semanas produjo un aumento respecta a esta reseña de la evaluación química inter- significativo de la incidencia de tumores en distintos nacional, el proceso de revisión científica previo al lugares (hemangiosarcomas y tumores en el estómago, examen realizado por el Comité de Revisión Final se ha las glándulas mamarias, el hígado, los pulmones y el cumplido mediante la revisión científica efectuada para la endometrio) tanto en ratas como en ratones. Aunque no elaboración del documento de la serie EHC. Comuni- hubo un aumento significativo de la incidencia de cándose por correspondencia, los miembros del Comité tumores en las ratas y los ratones expuestos por de Revisión Final ultimaron esta reseña de la evaluación inhalación, la aplicación cutánea o intraperitoneal química internacional del 1,2-dicloroetano, aprobaron su repetida de 1,2-dicloroetano se ha revelado sistemática- publicación y examinaron las observaciones dimanantes mente genotóxica en numerosas pruebas realizadas in de la revisión científica efectuada durante la preparación vitro en células de procariotas, hongos y mamíferos del documento de la serie EHC. La composición del (incluidas células humanas). Análogamente, se han Comité de Revisión Final figura en el apéndice 2. En el obtenido resultados invariablemente positivos indica- presente documento también se reproduce la Ficha Inter- dores de actividad genotóxica (así como enlaces con el nacional de Seguridad Química (ICSC 0250) emitida por el ADN) en estudios realizados in vivo con ratas, ratones e IPCS (1993). insectos.

El 1,2-dicloroetano (CAS n/ 107-06-2) es un Las CI50 y CE50 más bajas notificadas en relación hidrocarburo sintético volátil que se utiliza principal- con diversos puntos finales en organismos acuáticos mente en la síntesis del monómero cloruro de vinilo y de fueron de 25 y 105 mg/litro respectivamente. La CL50 más otros disolventes clorados. También se ha utilizado baja notificada para Daphnia fue de 220 mg/litro, como aditivo de la gasolina con plomo y como fumi- mientras que los efectos sobre la reproducción se gante, aunque su uso como aditivo de la gasolina se está produjeron con concentraciones de 20,7 mg/litro. El reduciendo. La mayor parte de la liberación en el vertebrado de agua dulce más sensible estudiado fue la entorno se produce en el aire ambiente, donde es moder- salamandra noroccidental (Ambystoma gracile), en la adamente persistente. Sin embargo, no parece que que se observó una reducción de la supervivencia de las contribuya al agotamiento de la capa de ozono. El 1,2- larvas con niveles de 2,5 mg/litro. Se dispone sólo de dicloroetano tiene un potencial de bioacumulación bajo; datos limitados sobre los efectos del 1,2-dicloroetano en la inhalación con el aire probablemente sea la principal especies terrestres. fuente de exposición humana. Teniendo en cuenta los datos disponibles, es Se dispone de poca información sobre los efectos probable que el 1,2-dicloroetano sea carcinógeno para el del 1,2-dicloroetano en el ser humano. Las pocas ser humano y, por lo tanto, la exposición a éste debería investigaciones epidemiológicas conocidas sobre su reducirse en la medida de lo posible. Sobre la base de carcinogenicidad potencial no son concluyentes. estudios realizados en animales expuestos a una administración por sonda, se ha calculado que la El 1,2-dicloroetano tiene una toxicidad aguda potencia carcinogénica (expresada como la dosis moderada en animales de experimentación. La escasa asociada a un aumento del 5% en la incidencia de

27 Concise International Chemical Assessment Document 1 tumores) oscila entre 6,2 y 34 mg/kg de peso corporal por día. Con respecto al aire (fuente principal de exposición humana), se han obtenido valores orientativos 3,6–20 g/m3 o 0,36–2,0 g/m3, calculados para un margen 5.000 a 50.000 veces inferior a la potencia carcinogénica estimada; sin embargo, hay que tener en cuenta que se han sobreestimado los riesgos, ya que los datos disponibles indican que el 1,2-dicloroetano inhalado resulta menos potente. (En cuanto a la ingestión, los valores correspondientes son de 1,2–6,8 g/m3 de peso corporal por día o 0,12–0,68 g/m3 de peso corporal por día.) Estos valores comportan lo que algunas entidades consideran como un riesgo “prácticamente insignificante” (es decir, 10–5 – 10–6 para un carcinógeno genotóxico). Según las estimaciones estadísticas, la exposición indirecta a través del medio ambiente general es aproximadamente 300 veces inferior a esos valores.

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