Priority Existing Chemical Assessment Reports -

1,4-Dioxane

 

CHEMICAL IDENTITY

Chemical name (IUPAC)

• 1,4-Dioxane

Registry numbers

1,4-Dioxane is listed on the Australian Inventory of Chemical Substances (AICS).

• CAS number 123-91-1

• EINECS number 204-661-8

• EC number 603-024-00-5

• RTECS number JG8225000

Other names/trade names

• Diethylene dioxide

• Diethylene-1,4-dioxide

• 1,4-Diethylene dioxide

• Diethylene ether

• Diethylene oxide

• 1,4-Dioxacyclohexane

• 1,4-Dioxam

• 1,4-Dioxan

• Dioxan

• Dioxane

• p-Dioxane

• para-Dioxane

• Dioxyethylene ether

• Glycol ethylene ether

• NE 220

• Tetrahydro-1,4-dioxin

• Tetrahydro-para-dioxin

APPLICANTS

Albright & Wilson (Australia) P.O. Box 67878 Wetherill Park NSW 2164	Johnson & Johnson Pacific Pty Ltd Locked Bag 5 Botany, NSW 2019
APS Chemicals Abbott Road Seven Hills NSW 2147	Kodak 173 Elizabeth Street Cobung VIC 3058
Bronson & Jacobs Pty Ltd P.O. Box 22 Homebush NSW 2140	Merck Pty Ltd 207 Colchester Road Kilsyth VIC 3137
Clariant (Australia) Pty Ltd P.O. Box 23 Chadstone VIC 3148	Orica Pty Ltd 1 Nicholson Street Melbourne VIC 3000
Colgate-Palmolive Level 15 345 George Street Sydney NSW 2000	Sigma Aldrich Pty Ltd 2/14 Anella Avenue Castle Hill NSW 2154
Du Pont (Australia) Pty Ltd 49-59 Newton Road Wetherill Park NSW 2164	3M (Australia) Pty Ltd P.O. Box 144 St. Marys NSW 2760
Henkel (Australia) Pty Ltd 83 Maffra Street Broadmeadows VIC 3047

Overview

Assessment Findings

1,4-Dioxane was declared as a priority existing chemical (PEC) 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, however, due to its recent substitution (with other chemical(s)) by the sole company notifying (to NICNAS) this use, uncertainty exists over its continued use for this purpose. 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.

Based on the assessment of health effects, 1,4-dioxane should be classified in accordance with the ASCC Approved Criteria for Classifying Hazardous Substances, as 'Irritating to eyes and respiratory system' (risk phrase 36/37) and 'Carcinogen category 3' (risk phrase R40), which is in accord with the ASCC List of Designated Hazardous Substances.

In accordance with the Australian Code for the Transport of Dangerous Goods, 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 associated with 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 modeling indicate a potential risk for exposed workers, although it is uncertain whether 1,4-dioxane is still being used for this purpose in Australia.

The public health risk assessment concluded that the main potential source of exposure to the general public is from 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.

The environmental risk assessment indicates that the majority of 1,4-dioxane used and produced (as by-product) in Australia will be released to sewer. 1,4-Dioxane released to soil is likely to leach to groundwater. Fugacity modeling predicts a partitioning of 91% to water and 9% to air. Rapid degradation (half-life < 7 hours) of 1,4-dioxane is expected in the atmosphere, whereas biodegradation and photooxidation half-lives in surface and ground waters were estimated at between 1 month and several years. 1,4-Dioxane was classified as practically non-toxic to aquatic organisms and on account of its high hydrophilicity and partition coefficient (log Pow), the potential for bioaccumulation was considered negligible. Worst case scenarios for PEC/PNEC ratios for local and continental compartments suggest that 1,4-dioxane does not present a significant risk of adverse effects to the Australian aquatic environment. Similarly, 1,4-dioxane is considered unlikely to contribute to global warming or ozone depletion.

Recommendations (summary)

Recommendations for reducing potential occupational health and safety risks for 1,4-dioxane include: a revision of Material Safety Data Sheets (MSDS) and labels in accordance with ASCC requirements; specific workplace control measures for uses identified in Australia and a review of the ASCC exposure standard. In addition, an air monitoring survey is recommended to characterise 1,4-dioxane exposure to any workers potentially exposed during optical lens coating.

In the protection of public health, it is recommended that levels of 1,4-dioxane in consumer products be limited to 100 ppm. It was considered that the current Poison Schedule (SUSDP) classification, first aid instructions and safety directions for 1,4-dioxane are appropriate. With respect to the presence of 1,4-dioxane in pharmaceutical and food products, it is recommended that this report be forwarded to the Drug Safety Evaluation Branch of the Therapeutic Goods Administration (TGA) and the Australia and New Zealand Food Authority (ANZFA) for their consideration.

The usage and emissions of 1,4-dioxane are so low in Australia that risks for the environment were assessed as negligible and as such no specific recommendations are made.

Data gaps identified in this assessment report include: an animal skin irritation study carried out according to recognised testing guidelines and adequate data on fertility hazards. Further characterisation of the metabolic saturation level in humans and its relationship to cytotoxicity and other cellular perturbations would permit further refinement of health risk estimates and the occupational atmospheric exposure standard. Despite efforts by industry to reduce the quantity of 1,4-dioxane impurities in ethoxylated chemicals, there is a paucity of data on levels in end-use products in the public domain in Australia.