1,4-Dioxane Priority Existing Chemical No
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National Industrial Chemicals Notification and Assessment Scheme 1,4-Dioxane Priority Existing Chemical No. 7 __________________________________ Full Public Report June 1998 © Commonwealth of Australia 1998 ISBN 0 642 47104 5 This work is copyright. Apart from any use permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from AusInfo. Requests and inquiries concerning reproduction and rights should be addressed to the Manager, Legislative Services, AusInfo, GPO Box 84, Canberra, ACT 2601. ii Priority Existing Chemical Number 7 Preface This assessment was carried out under the National Industrial Chemicals Notification and Assessment Scheme (NICNAS). This Scheme was established by the Industrial Chemicals (Notification and Assessment) Act 1989 (the Act), which came into operation on 17 July 1990. The principal aim of NICNAS is to aid in the protection of people at work, the public and the environment from the harmful effects of industrial chemicals, by assessing the risks associated with these chemicals. NICNAS is administered by the National Occupational Health and Safety Commission (NOHSC) and assessments are carried out in conjunction with Environment Australia (EA) and the Therapeutic Goods Administration (TGA), who carry out the environmental and public health assessments, respectively. NICNAS has two major programs: one focusing on the risks associated with new chemicals prior to importation or manufacture; and the other focussing on existing chemicals already in use in Australia. As there are many thousands of existing industrial chemicals in use in Australia, NICNAS has an established mechanism for prioritising and declaring chemicals as Priority Existing Chemicals (PECs). This Full Public PEC report has been prepared by the Director (Chemicals Notification and Assessment) in accordance with the Act. Under Sections 60D and 60E of the Act, applicants were provided with a draft copy of the report for correction of errors and variation of content (for a period of 56 days). Concurrently, the report was also available to the public for variation of content (as notified in the March 1998 edition of the Commonwealth Chemical Gazette) for a period of 28 days. No requests for variation were received and a final report was prepared according to Section 60F of the Act. During all stages of preparation, the report has been subject to internal peer review by NICNAS, EA and TGA. This report was also peer reviewed by the Netherlands National Institute of Public Health and Environmental Protection (RIVM), as part of its collaborative work with Australia on 1,4-dioxane in the OECD ‘Existing Chemicals Program’. In accordance with Section 62 of the Act, publication of this report revokes the declaration of 1,4-dioxane as a PEC. However, under Section 64(2) of the Act, an introducer of 1,4-dioxane must inform the Director of any circumstances that may require a further assessment of risks to human health and the environment. For further details refer to Section 14 (Secondary Notification) in this report. For the purposes of Section 78(1) of the Act, copies of Full Public Reports for New and Existing Chemical assessments may be inspected by the public at the Library, Worksafe Australia, 92-94 Parramatta Road, Camperdown, Sydney, NSW 2050 (between 10 am and 12 noon and 2 pm and 4 pm each weekday). Summary Reports are published in the Commonwealth Chemical Gazette, which is also available to the public at the above address. 1,4-Dioxane iii Copies of this and other PEC reports can be purchased from NICNAS either by using the prescribed application form at Appendix 4 of this report, or directly from the following address. 92 Parramatta Road CAMPERDOWN NSW 2050 AUSTRALIA Tel: +61 2 9577 9437 Fax: +61 2 9577 9465 or +61 2 9577 9244 Further information, available on request (Tel: +61 2 9577 9578) include: · NICNAS Service Charter; · information sheets on NICNAS Company Registration; · information sheets on PEC and New Chemical assessment programs; · application forms for New Chemical and PEC assessments; · subscription details for the Commonwealth Chemical Gazette; and · subscription details for the NICNAS Handbook for Notifiers. PEC and New Chemical Summary Reports together with other information on NICNAS activities can be found on the NOHSC Web site [http://www.worksafe.gov.au]. iv Priority Existing Chemical Number 7 Overview Assessment findings 1,4-Dioxane (CAS No. 123-91-1) was declared a Priority Existing Chemical on 3rd May 1994 due to concerns over possible human carcinogenicity, its potential for widespread occupational and public exposure and high degree of partitioning to, and persistence in, the aquatic environment. In Australia, 1,4-dioxane is used as a solvent in chemical synthesis, research and analysis (mainly laboratory applications) and in adhesive products used in celluloid film processing. During the period this assessment was underway, 1,4-dioxane was also used in optical lens manufacture as a surface coating agent. Until 1st January 1996, 1,4-dioxane was used in large quantities as a stabiliser in 1,1,1-trichloroethane. 1,4-Dioxane is also produced in trace amounts as an unwanted by-product in the manufacture of ethoxylated chemicals, in particular, surfactants. Occupational and environmental exposure may occur from any of the above sources, as well as during formulation and use of ethoxylated chemicals. Exposure to the general public may occur from use of consumer products containing ethoxylated chemicals (e.g., detergents, cosmetics/toiletries, pharmaceuticals and food products) containing 1,4-dioxane as an impurity, in addition to its reported natural occurrence in certain foods. 1,4-Dioxane is absorbed by inhalation, dermal and oral routes. Metabolism in rats and humans appears to be similar, with the vast majority of the dose being rapidly excreted in urine as b- hydroxyethoxyacetic acid (HEAA) and small amounts of unchanged 1,4-dioxane being eliminated in urine and expired air. Evidence from animal studies indicates that metabolism may involve cytochrome P-450 and that saturation occurs at high doses, as indicated by an increase in unmetabolised 1,4-dioxane and a change in elimination kinetics. There is also some evidence to suggest that metabolic saturation is associated with toxicity, particularly hepatotoxicity. In animals, 1,4-dioxane is distributed to liver, kidney, spleen, lung, colon and skeletal muscle, with evidence of selective uptake by liver and kidney. 1,4-Dioxane exhibits low acute toxicity, but has been shown to cause irritation of eyes and respiratory tract in humans and animals. Short-term exposure to high levels of 1,4-dioxane is associated with severe kidney and liver damage in animals and humans. A number of human fatalities have been reported in the literature from occupational exposure (combined inhalation and skin contact) to high levels of 1,4-dioxane. The cause of death in all cases was reported as kidney failure (haemorrhagic nephritis). Liver necrosis and CNS nerve fibre damage were also reported at autopsy. Chronic effects seen in animals include lesions (neoplastic and non-neoplastic) in kidney, liver, nose, testes, lung and spleen. The critical organ for adverse effects in chronic animal studies is the liver, where effects include hepatocyte degeneration, hyperplasia, adenoma, carcinoma and cholangioma (bile duct tumour). The chronic no observed adverse effect levels (NOAELs) in rats are 111 ppm (105 mg/kg/d) for inhalation and 10-40 mg/kg/d for oral exposure to 1,4- dioxane. A reliable NOAEL for chronic dermal effects has not been determined. Effects from long term exposure to 1,4-dioxane in humans are not well characterised. Several epidemiological studies have been carried out in workers potentially exposed to 1,4-dioxane, with one study (comparative mortality study) indicating a significant increase in liver cancer, although potential exposure to other hepatotoxic chemicals, including alcohol, were confounding factors. 1,4-Dioxane v Based on the assessment of health effects, 1,4-dioxane should be classified in accordance with the NOHSC Approved Criteria for Classifying Workplace Hazardous Substances (NOHSC, 1994a), as ‘Irritating to eyes and respiratory system’ (risk phrase 36/37) and ‘Carcinogen Category 3’ (risk phrase R40), which is in accord with the NOHSC List of Designated Hazardous Substances (NOHSC, 1994b). In accordance with the Australian Code for the Transport of Dangerous Good by Road and Rail (FORS, 1998), 1,4-dioxane meets the criteria for assignment to ‘Class 3 (Flammable Liquid) - packaging group II’. The occupational risk assessment concluded that, for known Australian work situations, potential atmospheric concentrations of 1,4-dioxane are unlikely to reach levels likely to cause acute effects, including eye or respiratory irritation. In addition, it is unlikely that workers in these occupations will be at risk from chronic adverse health effects related to 1,4-dioxane exposure, as margins of safety/exposure are generally high for inhalation and/or dermal exposure. In the absence of any monitoring data for workers involved in optical lens manufacture and the potential for inhalation exposure during the coating process, estimates for 1,4-dioxane exposure were obtained using the UK EASE model. Results from this modelling indicate a potential risk for exposed workers. The public health risk assessment concluded that the main potential source of exposure to the general public is from exposure to consumer products containing 1,4-dioxane as an impurity. No analytical data were available on levels of 1,4-dioxane in consumer products in Australia, however levels were estimated from data on surfactant composition submitted by applicants and notifiers. A so-called ‘worst case scenario’ for daily intake (inhalation and dermal exposure) for 1,4-dioxane from consumer products (not including pharmaceuticals or food products) was calculated at around 7mg/kg based on an assumed level of 30 ppm 1,4-dioxane in end-use products. This represents a margin of safety of >1000 (with respect to the chronic animal (oral) NOAEL) and therefore 1,4-dioxane was not considered to pose a significant health risk to the general public.