Octanal, 7-hydroxy-3,7-dimethyl-: Human health tier II assessment
25 November 2016
CAS Number: 107-75-5
- Chemical Identity
- Import, Manufacture and Use
- Existing Work Health and Safety Controls
- Health Hazard Information
- Risk Characterisation
- NICNAS Recommendation
This assessment was carried out by staff of the National Industrial Chemicals Notification and Assessment Scheme (NICNAS) using the Inventory Multi-tiered Assessment and Prioritisation (IMAP) framework.
The IMAP framework addresses the human health and environmental impacts of previously unassessed industrial chemicals listed on the Australian Inventory of Chemical Substances (the Inventory).
The framework was developed with significant input from stakeholders and provides a more rapid, flexible and transparent approach for the assessment of chemicals listed on the Inventory.
Stage One of the implementation of this framework, which lasted four years from 1 July 2012, examined 3000 chemicals meeting characteristics identified by stakeholders as needing priority assessment. This included chemicals for which NICNAS already held exposure information, chemicals identified as a concern or for which regulatory action had been taken overseas, and chemicals detected in international studies analysing chemicals present in babies’ umbilical cord blood.
Stage Two of IMAP began in July 2016. We are continuing to assess chemicals on the Inventory, including chemicals identified as a concern for which action has been taken overseas and chemicals that can be rapidly identified and assessed by using Stage One information. We are also continuing to publish information for chemicals on the Inventory that pose a low risk to human health or the environment or both. This work provides efficiencies and enables us to identify higher risk chemicals requiring assessment.
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.
These assessments are carried out by staff employed by the Australian Government Department of Health and the Australian Government Department of the Environment and Energy. The human health and environment risk assessments are conducted and published separately, using information available at the time, and may be undertaken at different tiers.This chemical or group of chemicals are being assessed at Tier II because the Tier I assessment indicated that it needed further investigation.
For more detail on this 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.
|Molecular Weight (g/mol)||172.26|
|Appearance and Odour (where available)||colourless to very pale yellow|
Import, Manufacture and Use
The chemical has reported commercial use in industrial cleaners.
The following international uses have been identified through: the European Union (EU) Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) dossiers; Galleria Chemica; the European Commission Cosmetic Ingredients and Substances (CosIng) database; the United States (US) Personal Care Products Council International Nomenclature of Cosmetic Ingredients (INCI) Dictionary; the US Environmental Protection Agency's Aggregated Computer Toxicology Resource (ACToR); Human & Environmental Risk Assessment (HERA) on ingredients of European household cleaning products; and the US National Library of Medicine's Hazardous Substances Data Bank (HSDB).
The chemical has reported cosmetic use as an ingredient in fragrances.
The chemical has reported domestic uses, including detergents, fabric conditioners, and household cleaning products, such as hand dishwashing cleaners and surface cleaners.
No known restrictions have been identified.
The chemical is listed on the following (Galleria Chemica):
- EU Cosmetics Regulation 1223/2009 Annex III—List of Substances which cosmetic products must not contain except subject to the restrictions laid down. The chemical has a maximum concentration of 1.0 % in ready for use preparation; and
- New Zealand Cosmetic Products Group Standard—Schedule 5 - Table 1: Components cosmetic products must not contain except subject to the restrictions and conditions laid down.
In both the EU and New Zealand restrictions, the presence of the chemical must be indicated in the list of ingredients when its concentration exceeds 0.001 % in leave-on products or 0.01% in rinse-off products.
The chemical is restricted under the International Fragrance Association (IFRA) Standards (47th amendment) with concentration limits in finished products from 0.1 % – 3.6 % (IFRA, 2013).
Existing Work Health and Safety Controls
The chemical is not listed on the Hazardous Substances Information System (HSIS) (Safe Work Australia).
No specific exposure standards are available.
No specific exposure standards are available.
Health Hazard Information
Based on oral administration studies in rabbits, the chemical is reduced to hydroxycitronellol following absorption, and subsequently oxidised to hydroxycitronellic acid which is excreted in the urine (WHO, 2000).
Based on the data available, the chemical is expected to have low toxicity following acute oral exposure.
In a study conducted in rats (strain unspecified; 10 animals/sex/dose), the chemical was administered once via oral gavage at doses of 200, 1600, 3200 or 6400 mg/kg bw. One male from the 3200 mg/kg bw group died within 48 hours post-administration. Clinical signs included delayed or intermittent respiration, dyspnoea, atony, and enlarged stomach. No further study details were provided. The median lethal dose (LD50) was determined to be > 6400 mg/kg bw (REACH). No deaths occurred in 10 rats (strain unspecified) after a single oral dose of the chemical at 5000 mg/kg bw (HERA, 2005).
Based on the data available, the chemical is expected to have low toxicity following acute dermal exposure.
In a study conducted in two rabbits (strain unspecified), application of the chemical at a single dose of 2000 mg/kg bw did not cause any mortalities. No further study details were provided (HERA, 2005; REACH).
In the absence of more comprehensive information, a recommendation to classify the chemical for this particular endpoint is not warranted.
In a study conducted in rats (strain unspecified), vapours of the chemical (atmospheric concentrations were not determined) did not cause any deaths or any treatment-related effects. No further study details were provided (REACH).
Corrosion / Irritation
The chemical has been reported to have caused some respiratory effects in mice.
A study in CF-1 female mice showed that exposure to aerosols of the chemical for one minute caused marked respiratory depression (mean arterial pressure (ED25) = 183 µg/L). Furthermore, a slight depressant effect on the lower respiratory tract upon inhalation of 621 µg/L via tracheal cannula was observed in another study conducted in mice (HERA, 2005).
The chemical is reported to be a slight to moderate skin irritant in animal studies. Prolonged occlusive application of the undiluted chemical caused moderate irritation in human subjects. Overall, the effects were not sufficient to warrant hazard classification.
In a study conducted in four New Zealand White (NZW) rabbits, 0.5 mL of undiluted chemical was applied semiocclusively to intact skin for four hours. The mean erythema and oedema scores were determined to be 0.8 and 0.1, respectively. Effects on the skin reversed within seven days (REACH). However, other studies conducted in rabbits gave moderate irritation effects. No further study details were provided (HERA, 2005). Studies conducted in guinea pigs reported either a lack of effects, or moderate skin irritation effects (HERA, 2005). An in vitro study conducted in keratinocytes from male albino rats showed mild irritant effects when exposed to the chemical (20 % solution) (HERA, 2005).
The chemical is considered to be an eye irritant. Based on the results from animal studies, the chemical is recommended to be classified as hazardous with the risk phrase 'Irritating to the eyes' (R36) in the Hazardous Substance Information System (HSIS).
In a study conducted in two Vienna White rabbits, 50 µL of the undiluted chemical was applied to one eye of each animal and was observed for eight days. The mean chemosis (at the 24 – 72 h observation period) score was 0.5 with effects being fully reversed within 72 hours. The mean corneal scores and conjunctival redness (at the 24 – 72 h observation period) were 2 and 1.25, respectively, with effects not being fully reversed within 8 days (REACH). In another study in accordance to the Draize procedures, the application of the undiluted chemical produced irritation to the iris and conjunctivae of rabbits (strain and numbers were not specified) which reversed after seven days (HERA, 2005).
Observation in humans
The application of the undiluted chemical on the skin under occlusion for 24 hours caused irritation in 2/22 volunteers (HERA, 2005). When administered under occlusion for 48 hours, the chemical (in acetone) produced a severe response at concentrations between 100–70 %, moderate skin irritation at concentrations between 70–40 % and mild skin irritation at concentrations below 40 % (HERA, 2005). However, application of the chemical (12 %) in petrolatum under occlusion for 24 hours did not cause any irritation effects in 223 subjects. In a human repeated insult patch test (HRIPT), application of the chemical (5 % in ethanol:diethyl phthalate (3:1)) under occlusion for 48 hours gave mild irritation reactions (HERA, 2005).
Based on information from animal studies and in humans (see Observation in humans), the chemical is considered to be a skin sensitiser. The chemical is recommended to be classified as hazardous with the risk phrase 'May cause sensitisation by skin contact' (R43) in the HSIS.
In a mouse local lymph node assay (LLNA) conducted in male CBA mice, the EC3 values of the chemical varied depending on the vehicle used. The EC3 value ranged from 19.3 % to 33 %: the lowest value was found using ethanol:diethyl phthalate (DEP) (1:3) as a vehicle (REACH). Another study reported a stimulation index of >3.0 and an extrapolated EC3 value of 13.6 % at induction doses of 100 %, 50 % and 25 % (HERA, 2005). In various guinea pig maximisation tests, the chemical was applied at doses of up to 10 % for intradermal application and up to 100 % for topical application (solvent vehicle was not reported). Topical challenge concentrations of up to 50 % produced positive reactions in 50 % of the treated animals. A Buehler test did not give positive results at concentrations of 2.5–5.0 % (solvent vehicle was not reported) (HERA, 2005).
Observation in humans
In a number of human maximisation tests, positive reactions were reported using induction concentrations of 10–12 % of the chemical in petrolatum. In one study, at a concentration of 12 % in petrolatum, 26 out of 298 subjects showed sensitisation reactions to the chemical (HERA, 2005). In another study, only 1 out of 110 subjects and only 1 out of 99 subjects reacted to 4 % and 20 % of the chemical, respectively, but positive results were seen at concentrations of 25 % and above in petrolatum (HERA, 2005). However, no reactions were observed when water or dimethyl phthalate was used as a vehicle for induction (HERA, 2005).
In a HRIPT, a total of 220 subjects did not show any reaction when tested with the chemical at concentrations of up to 5 % in DEP. During the second phase of the study, only two out of 193 subjects (who had no reactions during the first phase) had a reaction: one subject reacted to 0.3 % and 1.0 % and another subject to 3 % and 10 % of the chemical (HERA, 2005).
In a number of human patch tests using ethanol:DEP (3:1) as the vehicle, no reactions were observed during the first phase at concentrations of 2.5 % (HERA, 2005). For the studies which conducted a second phase of the treatment, positive reactions were observed. In one study, 4 out of 18, and 6 out of 15 subjects (who initially had no reactions to the chemical at concentrations of up to 7.5 %), reacted to the chemical at 2.5 %. In another study, 2 out of 17 subjects (who did not react to 5 % of the chemical during the first phase) reacted to a concentration of 2.5 % (HERA, 2005).
In studies that use ethanol as a vehicle, the following positive reactions were reported at (HERA, 2005):
- 20 %: 14 out of 73 subjects;
- 10 %: 6 out of 40 subjects;
- 7.5 %: 1 out of 38 subjects;
- 5 %: 0 out of 39 subjects; and
- 2.5 %: 3 out of 46 subjects.
Positive reactions were also reported from human patch test studies using fragrance blends containing the chemical in ethanol (HERA, 2005).
Repeated Dose Toxicity
Based on the data available, repeated oral exposure to the chemical is not considered to cause serious damage to health.
In a 2-year feeding study conducted in rats (strain unspecified), the chemical was administered daily in the diet at a concentration of either 0.1 % (20 animals/sex; approximately 80 mg/kg bw/d) or 0.5 % (60 animals/sex; approximately 400 mg/kg bw/d). Mortalities were reported in both groups. For the 0.1 % group, survival rates were 10/20 animals after 1 year, 7/20 animals after 1.5 year, and 5/20 animals after 2 years. In the 0.5 % group, survival rates were 50/60 animals after 1 year, 48/60 animals after 1.5 year, and 31/60 animals after 2 years. No toxic effects were reported in any of the treated groups (HERA, 2005; WHO, 2000; REACH). A conservative no observed effect level (NOEL) of 250 mg/kg bw/d was derived from this study by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) (WHO, 2000). However, it is uncertain how the NOEL value was derived given that is does not constitute either of the reported doses.
No data are available.
Based on the data available, repeated inhalation exposure to the chemical is not considered to cause serious damage to health.
In a 14-day study, Crl:CD rats (10 animals/sex/dose) were exposed to aerosols of the chemical at concentrations of 0.7, 7.0 or 70.0 mg/m3 (equivalent to 0.1, 1.0 or 10 ppm) for six hours per day, five days per week (mass median aerodynamic diameter (MMAD) range: 2.2–2.4; geometric standard deviation (GSD): 2.36–2.54). No mortalities were reported and no treatment-related effects were observed in any of the treated groups. The only effect observed, which was not considered treatment-related, was a yellow material found on various body surfaces of the high dose females. The no observed adverse effect concentration (NOAEC) value for this study was determined to be 70.0 mg/m3 (REACH).
Based on the weight of evidence from the data available, the chemical is not considered to be genotoxic.
A number of Ames tests conducted in Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538, with and without metabolic activation, gave negative results (HERA, 2005; REACH).
Negative results were obtained in two in vivo tests. In a micronucleus test, NMRI mice (four animals/group) were given a single intraperitoneal (i.p.) injection of the chemical at doses of 354 mg/kg bw, 603 mg/kg bw or 861 mg/kg bw. There were no increases in the number of micronucleated polychromatic erythrocytes (PCEs) reported. In a recessive lethal mutation assay in Drosophila melanogaster, a dose of 37 mmol/L of the chemical gave 0.33 %, 0.15 % and 0.0 % sex-linked recessive lethal mutations per chromosome in three broods. (HERA, 2005).
No data are available.
Reproductive and Developmental Toxicity
Based on the limited data available, the potential for reproductive or developmental toxicity from chemical exposure cannot be determined.
In a chick embryo study, the chemical in olive oil was administered by suprablastodermic injection during the third day of development. Doses of 860 and 2150 µg/embryo resulted in high mortality rates (>90 %). At 86 µg/embryo, the mortality rate was 50% and at 43 µg/embryo, the mortality rate was 18.7 % compared to 17.8 % in solvent controls. In all treated groups, abnormalities were observed; however, these were not described. The relevance of this study for human risk assessment is not known (HERA, 2005).
Other Health Effects
Critical Health Effects
The critical health effects for risk characterisation includes the local effect of skin sensitisation. The chemical can also cause eye irritation.
Public Risk Characterisation
Although use in cosmetic or domestic products in Australia is not known, the chemical is reported to be used in cosmetic or domestic products overseas. The main route of public exposure is expected to be through the skin, eye and inhalation from products containing the chemical when applied as aerosols or in perfumes.
The chemical is readily available and is expected to be widely distributed for use as raw fragrance materials. However, the distribution of these materials is expected to be controlled by members of IFRA. The restriction of the chemical under the IFRA Standard is expected to sufficiently manage the public risks associated with chemical exposure through fragrances (e.g. concentration limit in finished products of 0.1 % – 3.6 % of the chemical).
Occupational Risk Characterisation
Given the critical local health effects, the chemical could pose an unreasonable risk to workers unless adequate control measures to minimise dermal and ocular exposure are implemented. The chemical should be appropriately classified and labelled to ensure that a person conducting a business or undertaking (PCBU) at a workplace (such as an employer) has adequate information to determine the appropriate controls.
Assessment of the chemical is considered to be sufficient, provided that the recommended amendment to the classification is adopted, and labelling and all other requirements are met under workplace health and safety and poisons legislation as adopted by the relevant state or territory.
Products containing the chemical should be labelled in accordance with state and territory legislation (SUSMP, 2016).
Work Health and Safety
The chemical is recommended for classification and labelling under the current approved criteria and adopted GHS as below. This assessment does not consider classification of physical and environmental hazards.
|Hazard||Approved Criteria (HSIS)a||GHS Classification (HCIS)b|
|Irritation / Corrosivity||Irritating to eyes (Xi; R36)||Causes serious eye irritation - Cat. 2A (H319)|
|Sensitisation||May cause sensitisation by skin contact (Xi; R43)||May cause an allergic skin reaction - Cat. 1 (H317)|
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 consumers
Products containing the chemical should be used according to the instructions on the label.
Advice for industry
Control measures to minimise the risk from dermal and ocular exposure to the chemical should be implemented in accordance with the hierarchy of controls. Approaches to minimise risk include substitution, isolation and engineering controls. Measures required to eliminate, or minimise risk arising from storing, handling and using a hazardous chemical depend on the physical form and the manner in which the chemical is used. Examples of control measures that could minimise the risk include, but are not limited to:
- health monitoring for any worker who is at risk of exposure to the chemical[s], if valid techniques are available to monitor the effect on the worker’s health;
- minimising manual processes and work tasks through automating 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 solely be relied upon 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 the chemical 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 physical hazards of the chemical has not been undertaken as part of this assessment.
Approved Criteria for Classifying Hazardous Substances [NOHSC: 1008(2004)] Third edition. Accessed at http://www.safeworkaustralia.gov.au/sites/SWA/about/Publications/Documents/258/ApprovedCriteria_Classifying_Hazardous_Substances_NOHSC1008-2004_PDF.pdf
European Commission Cosmetic Ingredients and Substances (CosIng) database. Accessed Month 2016 at http://ec.europa.eu/consumers/cosmetics/cosing/
Galleria Chemica. Accessed April 2016 at http://jr.chemwatch.net/galleria/
Globally Harmonised System of Classification and Labelling of Chemicals (GHS) United Nations, 2009. Third edition. Accessed at http://www.unece.org/trans/danger/publi/ghs/ghs_rev03/03files_e.html
Human and Environmental Risk Assessment (HERA) on Ingredients of European Household Cleaning Products 2005. Hydroxycitronellal (CAS No. 107-75-5). Accessed April 2016 at http://www.heraproject.com/files/18-f-690e148d-cc02-21e8-70b0a865d56eeb60.pdf
International Fragrance Association (IFRA) Standards (47th amendment) – Restricted: Hydroxycitronellal (CAS No. 107-75-5). Accessed April 2016 at http://www.ifraorg.org/en-us/ingredients
Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Dossier. Hydroxycitronellal (CAS No 541-02-6). Accessed April 2016 at http://echa.europa.eu/registration-dossier/-/registered-dossier/12695/7/9/2
Safe Work Australia. Hazardous Substances Information System (HSIS). Accessed March 2016 at http://hsis.safeworkaustralia.gov.au/HazardousSubstance
The Poisons Standard (the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP)) 2016. Accessed April 2016 at https://www.comlaw.gov.au/Details/F2016L00036
The United States of America (USA) Environmental Protection Agency's Aggregated Computational Toxicology Resource (ACToR). Accessed March 2016 at http://actor.epa.gov/actor/faces/ACToRHome.jsp
TOXNET (Toxicology Data Network), US National Library of Medicine's Hazardous Substances Data Bank (HSDB). Accessed March 2016 at http://toxnet.nlm.nih.gov/
United States (US) Personal Care Product Council International Nomenclature of Cosmetic Ingredients (INCI) dictionary. Accessed May 2016 at http://gov.personalcarecouncil.org/jsp/gov/GovHomePage.jsp
World Health Organization (WHO) 2000. Toxicological evaluation of certain food additives and contaminants. WHO Food Additives Series No. 44. Geneva (CH): World Health Organization. Accessed April 2016 at http://www.inchem.org/documents/jecfa/jecmono/v44jec10.htm
Last update 25 November 2016