HUMAN HEALTH TIER II ASSESSMENT FOR Ethane, 1,1,2-trichloro-
CAS Number: 79-00-5
- Chemical Identity
- Import, Manufacture and Use
- Existing Work Health and Safety Controls
- Health Hazard Information
- Risk Characterisation
- NICNAS Recommendation
This assessment was carried out under the National Industrial Chemicals Notification and Assessment Scheme (NICNAS). This scheme has been established by the Industrial Chemicals (Notification and Assessment) Act 1989 (the Act), to aid in the protection of the Australian people and the environment by assessing the risks of industrial chemicals, providing information and making recommendations to promote their safe use.
As part of the reforms regarding Existing Chemicals, NICNAS has implemented a new framework to address the human health and environmental impacts of previously unassessed industrial chemicals listed on the Australian Inventory of Chemical Substances (AICS).
The Inventory Multi-tiered Assessment and Prioritisation (IMAP) framework was developed, with significant input from stakeholders. The framework provides a more rapid, flexible and transparent approach for the assessment of existing chemicals.
Stage One of this program, which will take four years, started 1 July 2012 and is examining 3000 chemicals meeting characteristics identified by stakeholders as needing priority assessment. This includes chemicals for which NICNAS already holds exposure information, chemicals identified as a concern or for which regulatory action has been taken overseas, and chemicals detected in international studies analysing chemicals present in babies’ umbilical cord blood.
The IMAP framework is a science and risk-based model designed to align the assessment effort with the human health and environmental impacts of chemicals. It has three tiers of assessment, with the assessment effort increasing with each tier. The Tier I assessment is a high throughput approach using tabulated electronic data. The Tier II assessment is an evaluation of risk on a substance-by-substance or chemical category-by-category basis. Tier III assessments are conducted to address specific concerns that could not be resolved during the Tier II assessment.
NICNAS assessments are carried out by staff employed by the Australian Government Department of Health and the Australian Government Department of the Environment. The human health and environment risk assessments are being conducted and published separately, using information available at the time, and may be undertaken at different tiers.
This chemical/group of chemicals is/are being assessed at Tier II because the Tier I assessment indicated that it needed further investigation.
For more detail on the new program please visit:www.nicnas.gov.au
NICNAS has made every effort to assure the quality of information available in this report. However, before relying on it for a specific purpose, users should obtain advice relevant to their particular circumstances. This report has been prepared by NICNAS using a range of sources, including information from databases maintained by third parties, which include data supplied by industry. NICNAS has not verified and cannot guarantee the correctness of all information obtained from those databases. Reproduction or further distribution of this information may be subject to copyright protection. Use of this information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner. NICNAS does not take any responsibility whatsoever for any copyright or other infringements that may be caused by using this information.
|Synonyms|| Ethane trichloride|
|Molecular Weight (g/mol)||133.405|
|Appearance and Odour (where available)||Transparent colourless liquid, with a sweet chloroform-like odour.|
Import, Manufacture and Use
No specific Australian use, import or manufacture information has been identified.
The following international uses have been identified through the European Union Registration, Evaluation and Authorisation of Chemicals (EU REACH) dossiers, Galleria Chemica, Substances and Preparations in the Nordic countries (SPIN) database, and other data sources via eChemPortal including the US Environmental Protection Agency's (EPA) Aggregated Computer Toxicology Resource (ACToR), and the US National Library of Medicine's Hazardous Substances Data Bank (HSDB).
The chemical has reported domestic use including in:
- lacquer and coating formulations; and
- aerosol paints.
The chemical has reported commercial use including:
- as a solvent in the manufacture of organic materials (fats, oils, waxes, resins).
The chemical has reported site limited use including:
- as an intermediate in the production of vinylidene chloride (1,1-dichloroethylene) and tetrachloroethanes.
No known restrictions have been identified.
US—California Proposition 65—No Significant Risk Levels (NSRLs) adopted in regulation for carcinogens. The NSRL for the chemical is 10 µg/d.
List of Substance Subject to Authorization, under REACH.
US TSCA Section 12(b)—List of Chemical Substances Subject to Export Notification Requirements.
Existing Work Health and Safety Controls
The chemical is classified as hazardous with the following risk phrases for human health in the Hazardous Substances Information System (HSIS) (Safe Work Australia):
TWA: 55 mg/m³ (10 ppm)
The following exposure standards are identified (Galleria Chemica):
An exposure limit (TWA) of 35–56 mg/m³ (8–10 ppm) and STEL (or KZG-W) of 30–275 mg/m³ (20–50 ppm) in different countries such as Argentina, Austria, Belgium, Brazil, Finland, Germany, Mexico, Philippines (skin), South Africa, Switzerland and United States of America (NIOSH, OSHA, TSCA and the following states Alaska, California, Hawaii, Idaho, Michigan, Minnesota, Oregon, Tennessee, Vermont, Wyoming).
Health Hazard Information
The primary metabolites identified in rats and mice given 1,1,2-trichloroethane by gavage were chloroacetic acid, S-carboxymethylcysteine, and thiodiacetic acid (HSDB 2012).
Ethane, 1,1,2-trichloro- is rapidly absorbed across biological membranes in both humans and a variety of mammalian species following exposure. The half-life following inhalation in mice was determined to be 49.3 minutes (HSDB 2012).
The chemical is currently classified with the risk phrase 'Harmful if swallowed (R22)' in Australia (Safe Work Australia, 2012). The data available support this classification.
The chemical has acute toxicity via the oral route (LD50 in mice = 378 mg/kg bw and in rats = 837 mg/kg bw) (OECD, 2000). In the mouse study a loss of righting reflex and sedation with irritation of the upper gastrointestinal tract and reddened or haemorrhagic lungs were seen, with deaths appearing to result from depression of the central nervous system (HSDB, 2012).
The chemical is currently classified with the risk phrase 'Harmful in contact with skin (R21)' in Australia (Safe Work Australia, 2012). The data available on guinea pigs are consistent with this classification.
In an acute dermal toxicity study on guinea pigs, the chemical was found to have a Lowest Published Lethal Dose (LDLo) of 970 mg/kg. In a second study in guinea pigs, the chemical was also found to kill all the test animals at a dose rate of 232 mg/cm² (0.5 ml applied to a 3.1cm² area of the back) (REACH, 2013).
In an acute dermal toxicity study on rabbits the chemical applied via the dermal route was reported to have an LD50 of 5377 mg/kg (HSDB, 2012).
The chemical is currently classified with the risk phrase 'Harmful by inhalation (R20)' in Australia (Safe Work Australia, 2012). The data available support this classification.
The chemical was reported to have moderate acute toxicity via inhalation (6 hours) (LC50 = 9000 mg/m³) in rats (SIAR 2000, HSDB 2012).
Observation in humans
Data on humans indicate that the chemical was a narcotic at low concentrations (OECD, 2000).
Corrosion / Irritation
The chemical is currently not classified as a skin irritant in Australia (Safe Work Australia, 2012). The data available support this classification.
When applied to the skin of rabbits the chemical showed mild irritation at a dose of 500 mg with 24 h exposure and severe irritation at a dose of 810 mg with 24 h exposure (OECD, 2000). Safework Australia criteria are based on a 500 mg amount of the test substance applied for 4 h.
The chemical is currently not classified as an eye irritant in Australia (Safe Work Australia, 2012). The data available support this classification.
The chemical was found to be a mild eye irritant at dose levels up to 500 mg with 24 h exposure.
Observation in humans
In humans, the chemical was reported to irritate the conjunctiva and the mucosa of the respiratory tract and the external skin (OECD, 2000).
No data are available. The chemical was highlighted as a potential protein binder via nucleophilic substitution at a halogenated sp3 carbon atom (OECD toolbox). However, when reading across from all of the protein binding chemicals that could also potentially undergo nucleophilic substitution at a halogenated sp3 carbon atom and eliminating all the chemicals with superfragments and where an alert was found for protein binding for skin sensitisation by OASIS v1.1, the chemical was predicted not to be skin sensitising (OECD toolbox).
Repeated Dose Toxicity
Based on the available information no hazard classification for repeat dose oral toxicity is recommended.
In a 90 day oral (drinking water) repeated dose toxicity study in mice, the chemical was present in the drinking water at concentrations of 20, 200 or 2000 mg/L. Daily intakes were estimated to be 0, 4.4, 46, and 305 mg/kg/day for males and 0, 3.9, 44, and 384 mg/kg/day for females. Effects reported included reductions in body weight gain (males), glutathione content (males), cytochrome P-450 content (females), aniline hydroxylase activities (females), haematocrit (females), haemoglobin (females), humoral immune status (both sexes) and increased alkaline phosphatase activity (both sexes). The NOELs for male and female mice in this study were 4.4 mg/kg bw/day and 3.9 mg/kg bw/day respectively (OECD, 2000).
In additional studies by gavage on rats and mice, the predominant effects seen were decreases in bodyweight and changes in liver biochemical parameters (European Commission, 2000).
No data are available.
There are three inhalation studies available for the chemical where the animals were exposed for 6 months to a 15 ppm (15 mg/L) concentration. The studies were carried out on rats, rabbits and guinea pigs with no adverse effects seen in any of the species (OECD, 2000).
Observation in humans
In humans, this chemical was reported to cause gastrointestinal tract complaints, fatty degeneration of the kidneys and lung damage through prolonged exposure (OECD, 2000).
Although the chemical was found to have mixed results in a range of in vitro and in vivo tests and computer modelling (suggesting that interaction between the chemical and DNA could occur) the latest micronucleus test in mice in vivo showed negative results. Therefore the weight of evidence suggests that this chemical is not genotoxic.
The chemical produced negative results in a number of bacterial reverse mutation assays and DNA damage and repair assays all with and without metabolic activation. Unscheduled DNA synthesis due to the chemical was tested in a range of mammalian cells in vitro with both positive and negative results, although in in vivo the chemical did not cause unscheduled DNA synthesis. Positive results were seen in a gene mutation assay and a yeast cytogenetic assay without metabolic activation and showed indications of an aneuploidy-inducing effect. Positive results were also seen in a micronucleus test in vitro and a comet assay both in human lymphocytes with and without metabolic activation and in a mouse cell transformation assay performed without metabolic activation. Additional computer modelling and mechanistic studies indicated a potential for DNA binding (European Commission, 2000; OECD, 2000).
The chemical has also been tested in an in vivo mammalian erythrocyte micronucleus test according to OECD Test Guideline 474. This test was conducted in mice by gavage at doses up to 400 mg/kg bw, based on severe toxicity at 800 mg/kg in a previous range-finding study. No increases in the number of micronucleated polychromatic erythrocytes in bone marrow cells were observed indicating that the chemical is not genotoxic in vivo (OECD, 2003).
The chemical is currently classified with the risk phrase 'Limited evidence of a carcinogenic effect (R40)' in Australia (Safe Work Australia, 2012). The data available support this classification.
The chemical is classified by the International Agency on Cancer (IARC) as not classifiable as to its carcinogenicity to humans (Group 3).
The chemical was tested for carcinogenicity in a two year study in male and female mice and rats by oral administration and also in rats by subcutaneous injection. In the study by oral administration, the chemical produced hepatocellular neoplasms and adrenal phaeochromocytomas in mice of each sex but did not significantly increase the proportion of rats with neoplasms at any site relative to untreated controls. In the study in rats by subcutaneous injection, the chemical did not increase the incidence of neoplasms (IARC, 1999).
Reproductive and Developmental Toxicity
In a developmental toxicity study, the chemical was administered by gavage to mice on days 8 to 12 of gestation at dose of 350 mg/kg bw/day with no adverse effects on embryo/foetal viability, and/or postnatal growth and viability (OECD, 2000).
Other Health Effects
Critical Health Effects
The critical effect for risk characterisation is carcinogenicity. The chemical also has acute oral, dermal and inhalation toxicity, as well as causing adverse effects following repeated oral exposure.
Public Risk Characterisation
No public exposure to the chemical is expected, based on the available use data.
Occupational Risk Characterisation
During product formulation, dermal and inhalation exposure of workers to the chemical may occur, particularly where manual or open processes are used. These may include transfer and blending activities, quality control analysis, and cleaning and maintenance of equipment. Worker exposure to the chemical at lower concentrations may also occur during use of formulated products containing the chemical. The level and route of exposure will vary depending on the method of application and work practices employed.
Given the critical long and short term systemic health effects of the chemical, the chemical may pose an unreasonable risk to workers if adequate control measures to minimise dermal and inhalation exposure to the chemical are not implemented. The chemical should be appropriately classified and labelled to ensure that a person conducting a business, or undertaking (PCBU), e.g. employer, at a workplace has adequate information to determine appropriate controls.
Based on the available data, the hazard classification in HSIS is considered appropriate.
Current risk management measures are considered adequate for the protection of public and workers’ health and safety, provided that all requirements are met under workplace health and safety and poisons legislation as adopted by the relevant state or territory. No further assessment is required.
Given the uses identified for the chemical, it is unlikely that the public will be exposed to this chemical. Hence, the public risk from this chemical is not considered to be unreasonable.
Work Health and Safety
The chemical is recommended for classification and labelling under the current approved criteria and adopted GHS as below:
|Hazard||Approved Criteria (HSIS)a||GHS Classification (HCIS)b|
|Acute Toxicity||Very toxic by inhalation (T+; R26)*||Fatal if inhaled - Cat. 1 (H330)|
|Irritation / Corrosivity||Irritating to eyes (Xi; R36)* Irritating to skin (Xi; R38)* Irritating to respiratory system (Xi; R37)*||Causes serious eye irritation - Cat. 2A (H319) Causes skin irritation - Cat. 2 (H315) May cause respiratory irritation - Specific target organ tox, single exp Cat. 3 (H335)|
|Sensitisation||May cause sensitisation by inhalation (Xn, R42)* May cause sensitisation by skin contact (Xi; R43)*||May cause allergy or asthma symptoms or breathing difficulties if inhaled - Cat. 1 (H334) May cause an allergic skin reaction - Cat. 1 (H317)|
|Carcinogenicity||Carc. Cat 3 - Limited evidence of a carcinogenic effect (Xn; R40)*||Suspected of causing cancer - Cat. 2 (H351)|
a Approved Criteria for Classifying Hazardous Substances [NOHSC:1008(2004)].
b Globally Harmonized System of Classification and Labelling of Chemicals (GHS) United Nations, 2009. Third Edition.
* Existing Hazard Classification. No change recommended to this classification
Advice for industry
Control measures to minimise the risk from dermal or inhalation exposure to the chemical should be implemented in accordance with the hierarchy of controls, which include: substitution, isolation and engineering controls. Measures required to eliminate or minimise risk arising from storing, handling and using a hazardous chemical are dependent on the physical form and the manner in which the chemical is employed. Examples of control measures which may minimise the risk include, but are not limited to:
- using closed systems or isolating operations;
- using local exhaust ventilation to prevent the chemical from entering the breathing zone of any worker;
- air monitoring to ensure control measures in place are working effectively and continue to do so;
- minimising manual processes and work tasks through automation of processes;
- work procedures that minimise splashes and spills;
- regularly cleaning equipment and work areas; and
- using protective equipment that is designed, constructed, and operated to ensure that the worker does not come into contact with the chemical;
Guidance on managing risks from hazardous chemicals are provided in the Managing Risks of Hazardous Chemicals in the Workplace—Code of Practice available on the Safe Work Australia website.
Personal protective equipment should not be relied upon on its own to control risk and should only be used when all other reasonably practicable control measures do not eliminate or sufficiently minimise risk. Guidance in selecting personal protective equipment can be obtained from Australian, Australian/New Zealand or other approved standards.
Obligations under workplace health and safety legislation
Information in this report should be taken into account to help meet obligations under workplace health and safety legislation as adopted by the relevant state or territory. This includes, but is not limited to:
- ensuring that hazardous chemicals are correctly classified and labelled;
- ensuring that (material) safety data sheets ((m)SDS) containing accurate information about the hazards (relating to both health hazards and physicochemical (physical) hazards) of hazardous chemicals are prepared; and
- managing risks arising from storing, handling and using a hazardous chemical.
Your work health and safety regulator should be contacted for information on the work health and safety laws in your jurisdiction.
Information on how to prepare an (m)SDS and how to label containers of hazardous chemicals are provided in relevant codes of practice such as the Preparation of Safety Data Sheets for Hazardous Chemicals—Code of Practice and Labelling of Workplace Hazardous Chemicals—Code of Practice, respectively. These codes of practice are available from the Safe Work Australia website.
A review of the chemical's physical hazards has not been undertaken as part of this assessment.
eChemPortal. Accessed September 2012 at http://www.echemportal.org/echemportal/substancesearch/substancesearchlink.action
Galleria Chemica. Accessed June 2012 at http://jr.chemwatch.net/galleria/
Hazardous Substances Data Bank (HSDB). National Library of Medicine. Accessed October 2012 at http://toxnet.nlm.nih.gov.
International Agency for Reseach on Cancer (IARC) 1999. Re-evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide. IARC Monographs Volume 71. f. Accessed September 2012 at http://monographs.iarc.fr/ENG/Monographs/vol71/volume71.pd.
OECD 2000. SIAR on 1,1,2-Trichloroethane (79-00-5). Accessed October 2012 at http://www.chem.unep.ch/irptc/sids/OECDSIDS/79005.pdf
OECD 2003. Assessment Report for Post-SIDS Testing Results SIAM 16, 1,1,2-Trichloroethane (79-00-5). Accessed March 2013 at http://www.chem.unep.ch/irptc/sids/OECDSIDS/TRICHLOROET.pdf
OECD QSAR Toolbox version 3.1. http://www.oecd.org/chemicalsafety/assessmentofchemicals/theoecdqsartoolbox.htm
REACH Dossier 2012. 1,1,2-Trichloroethane (79-00-5). Accessed September 2012 at http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances
Safe Work Australia (SWA). Hazardous Substances Information System (HSIS). Accessed October 2012 at http://hsis.safeworkaustralia.gov.au/HazardousSubstance
Substances in Preparations in Nordic Countries (SPIN). Ethane, 1,1,2-trichloro- (79-00-5). Accessed September 2012 at http://18.104.22.168/fmi/xsl/spin/SPIN/spinindustrial.xsl?-db=SPINstof&-skip=0&-max=1&casnr.op=eq&casnr=79-00-5&SPINnavn%3a%3anavn.op=eq&SPINnavn%3a%3anavn=&ec_nr.op=eq&ec_nr=&-lay=SpinIndustUse&-find.
The European Commision (EC) 2000. European Chemicals Bureau. International Uniform Chemical Information Database (IUCLID) on 1,1,2-trichloroethane (79-00-5).