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Notice of final decisions to amend (or not amend) the current Poisons Standard, May 2020
Scheduling of chemicals and poisons
4.3 Nonanoic acid
4 Final decision(s) (without interim decision) made pursuant to regulation 2ZCZU
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4.3. Final decision in relation to Nonanoic acid
Pursuant to regulation 42ZCZU of the Regulations, a Delegate of the Secretary has made a final decision to amend the current Poisons Standard in relation to nonanoic acid as follows:
Schedule 5 - Amend Entry
except in preparations containing 10 per cent or less of nonanoic acid.
Reasons for the final decision (including findings on material questions of fact)
In making this final decision, I have considered the following:
- The Applicant's application to amend the current Poisons Standard with respect to nonanoic acid;
- Subsection 52E(1) of the Therapeutic Goods Act 1989, in particular (a) the risks and benefits of the use of a substance; (b) the purposes for which a substance is to be used and the extent of use of a substance; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; and (e) the potential for abuse of a substance;
- The Australian Health Ministers' Advisory Council's Scheduling Policy Framework (SPF 2018); and
- Scheduling Handbook (V 1.0, January 2018).
Findings on material questions of fact
An application was submitted by the Australian Pesticides and Veterinary Medicines Authority (APVMA) to amend the Poisons Standard with respect to nonanoic acid. The application proposes to amend the current Schedule 5 entry for nonanoic acid to include all pesticide uses of nonanoic acid in Schedule 5, with the previous cut off being limited to other preparations containing 10% or less of nonanoic acid.
The applicant's proposed amendments to the Poisons Standard are:
Schedule 5 - Amend Entry
except in preparations containing 10 per cent or less of nonanoic acid.
The applicant's reasons for the proposal are:
- Nonanoic acid (NNA) is a medium chain fatty acid, and is a naturally occurring carboxylic acid with a carbon chain length of nine. It is used in agricultural and veterinary (AgVet) chemical products as an herbicide, and may have other uses in therapeutic goods or fragrances.
- NNA has previously been considered for inclusion in the Poisons Standard. During the initial consideration, a range of cut-offs were considered, with the original APVMA proposal being for a 3% cut-off, a public submission cut-off of 4% being proposed, and an exemption for the use of the substance as an excipient in therapeutic goods being proposed. The Committee recommended inclusion of NNA in Schedule 6 rather than Schedule 5, with a cut-off to unscheduled of 10%. The delegate's final decision was to include NNA in Schedule 5 with a cut-off to unscheduled for preparations containing 10% or less of NNA.
- NNA has been used in a range of agricultural chemicals as an herbicide, both in combination with other actives (particularly glyphosate), but also as a stand-alone active constituent. Commercial products are available with high concentrations of NNA. It is available as products for use in the home garden, both in ready to use formulations and also as concentrated formulations which require dilution prior to use.
- A recent evaluation has indicated moderate eye irritancy resulting from exposure to a 1.8% formulation. Effects included reversible corneal opacity. The potential for eye irritation with these products is recognised, and can be mitigated with a combination of label warnings and personal protective equipment. However, the additional control of inclusion in Schedule 5 with the requirement for the appropriate signal heading would increase the level of protection.
- Noting the previous consideration for scheduling of NNA, and reflecting that there are other uses of NNA (for example it is included in the Australian Register of Therapeutic Goods (ARTG) ingredient list and may have uses as an excipient in fragrances), the proposed entry includes separate consideration for the pesticide use of NNA and other uses.
Current scheduling status
Nonanoic acid is currently listed in Schedules 5 of the Poisons Standard as follows:
NONANOIC ACID except in preparations containing 10 per cent or less of nonanoic acid.
In March 2016, the Advisory Committee on Chemicals Scheduling (ACCS #16) considered a proposal to create a new Schedule 5 entry for the use of nonanoic acid in agricultural preparations with a proposed exemption concentration cut-off at 3%. The ACCS recommended a Schedule 6 listing for NNA, noting the broad use pattern of NNA and given its irritancy, the schedule entry should not be restricted to agricultural uses only to capture other areas of potential public exposure.
The Committee advised that a 10% cut off for the substance was appropriate, below which the substance would not be scheduled. This cut off concentration was considered appropriate to avoid capturing its use in food additives and cosmetics.
The Delegate noted the advice from the ACCS that a new Schedule 6 entry be created for nonanoic acid with a cut-off to exempt in preparations containing 10% or less. The advice for a primary listing in Schedule 6 was based primarily on the potential for severe eye damage associated with exposure to this fatty acid, while most of the other toxicological criteria are consistent with SPF criteria for listing in Schedule 5. The Delegate noted comments made by the ACCS that the evaluation of the eye irritancy studies presented lacked rigour and that there is some uncertainty about the severity and reversibility of the lesions associated with concentrated solutions of the acid.
The Delegate decided to create a primary listing for NNA in Schedule 5, with an exemption for products containing 10% or less and was satisfied that there was sufficient evidence at the time that concentrations below 10% should cover most uses and natural occurrences of nonanoic acid in products available to the public, the risks of eye damage are sufficiently ameliorated to warrant scheduling controls unnecessary.
- According to the TGA Ingredient Database, nonanoic acid is:
- Available for use as an active ingredient in biologicals and prescription medicines;
- Available for use as an excipient ingredient in biologicals, devices, listed medicines and prescription medicines; and
- Not available as an equivalent ingredient in any application.
- The related substance, cetearyl nonanoate (also known as nonanoic acid cetearyl ester nonanoic acid cetyl/stearyl ester) is not available as an active ingredient in any application. However, it is available for use as excipient ingredient in export only, listed medicines, over the counter and prescription medicines.
- There are 27 products currently active on the Australian Register of Therapeutic Goods (ARTG) that contain nonanoic acid as an active ingredient. These include; 14 prescription medicines, 4 non-prescription medicines, 6 listed medicines, 1 medical device and 2 other therapeutic good (OTG) devices.
- According to the Therapeutic Goods (Permissible Ingredients) Determination No.1 of 2020, nonanoic acid is permitted to be included in listed medicines as follows:
Item Ingredient name Purpose Specific requirements 3465 NONANOIC ACID E
Permitted for use only in combination with other permitted ingredients as a flavour or a fragrance.
If used in a flavour the total flavour concentration in a medicine must be no more than 5%.
If used in a fragrance the total fragrance concentration in a medicine must be no more 1%.
E = excipient for a medicine meaning an ingredient that is not an active ingredient or a homoeopathic preparation ingredient
- Nonanoic acid is not listed on the TGA prescribing medicines in pregnancy database.
- There are no warning statements pertaining to nonanoic acid in the Therapeutic Goods (Medicines Advisory Statements) Specification 2019.
- There have been no reported adverse event for nonanoic acid recorded on the Database of Adverse Event Notifications (DAEN).
- There are 20 registered herbicide products with nonanoic acid listed as an active ingredient on the Public Chemical Registration Information System Search (PubCRIS).
- Between 2009-2019 the following adverse experiences were recorded for nonanoic acid in the APVMA Adverse Experience Reporting Program database (AERP):
- 1 report of a serious incident classified as related to human health reported occurring in 2017-2018.
- Nonanoic acid is included in the National Industrial Chemicals Notification and Assessment Scheme (NICNAS) Australian Inventory of Chemical Substances (AICS). However, there have been no assessments conducted by NICNAS on nonanoic acid that are publically available.
- On 30 September 1974 nonanoic acid was registered with the United States Environmental Protection Agency's (US EPA) Office of Pesticides Programs. It is registered for use as a antimicrobial, biochemical use and conventional chemical. Through the Pesticide Registration Review program, the EPA reviews all registered pesticides at least every 15 years, as mandated by the Federal Insecticide, Fungicide, and Rodenticide Act. The registration status of nonanoic acid currently being reviewed under this mandated review process.
- Nonanoic acid is not an approved drug product in the United States according to the United States Food and Drug Administration Approved Drug Products Database (Drugs@FDA).
- The European Chemicals Agency (ECHA) hazard classification & labelling for nonanoic acid identifies it as 'Warning! According to the harmonised classification and labelling (ATP07) approved by the European Union, this substance causes serious eye irritation, is harmful to aquatic life with long lasting effects and causes skin irritation.' It is approved for use as a biocide in the European Economic Area (EEA) and/or Switzerland, for: disinfection, repelling or attracting pests. It was granted approval for use in plant protection products in 2009 according to the European Union Pesticides Database.
- According to the European Commission database for information on cosmetic substances and ingredients database nonanoic acid is used in cosmetics in Europe, specifically it is used in cleansing, emulsifying, masking and perfume products.
- In New Zealand, nonanoic acid is classified as an approved hazardous substance according to the New Zealand Inventory of Chemicals (NZIoC). There are no approved medicines containing nonanoic acid that are registered with the New Zealand Medicines and Medical Devices Safety Authority (MedSafe).
- In Canada, there are currently 3 herbicide products containing nonanoic acid under review according to Canada's Pest Management Regulation Agency. Nonanoic acid is not registered as an active ingredient for use in medicines according to the Canadian (Health Canada) Drug Product Database.
Nonanoic acid (frequently referred to as pelargonic acid) is a naturally occurring carboxylic acid with a carbon chain-length of nine, belonging to the chemical class of saturated fatty acids commonly referred to as medium chain fatty acids (C8 to C12). It is a clear, colourless liquid with a weak odour. Nonanoic acid is soluble in aqueous solutions however it can readily form esters and partially dissociate into the pelargonate anion (CH3(CH2)7COO-) and the hydronium cation (H3O+) in an aqueous solution. The molecular weight (158.24 g/mol) and octanol-water partition coefficient (3.4 logPow) of nonanoic acid suggest that dermal penetration is possible. The structure of nonanoic acid is shown in Table 1.
Previous consideration of nonanoic acid by the ACCS in March 2016 considered that nonanoic acid has low systemic toxicity and is not corrosive. The acute oral and dermal toxicity in the rat is greater than 2000 mg/kg bw. It was noted that human clinical data indicates reversible moderate irritation, and eye irritation was considered to be slight to moderate. The evaluation considered at the time whether the eye irritation observed and the uncertainty in the data available was sufficient to classify nonanoic acid as an irreversible eye irritant (Schedule 6). Recent studies for octanoic acid and decanoic acid (in vivo eye irritation Good Laboratory Practice (GLP) test according to OECD TG 403 and a Bovine Corneal Opacity and Permeability (BCOP) test respectively) showed evidence for reversible eye irritation. On this basis Schedule 5 was recommended.
Nonanoic acid is now used relatively extensively as an herbicide in the home garden. A recent evaluation of an acute eye irritation study indicated moderate eye irritation following exposure to a product formulation containing 1.8% nonanoic acid.
|IUPAC and/or common and/or other names||
Pelargonic acid (INCI)
|Toxicity||Species||Previous Endpoint conclusions for nonanoic acid||XXXXXXX XXXXXXX Herbicide||SPF (2018) Classification for XXXXXXX XXXXXXX Herbicide|
|Acute oral toxicity||Rat||LD50 >2000 mg/kg bw||LD50 >2000 mg/kg bw (estimated)||-|
|Acute dermal toxicity||Rat||LD50 >2000 mg/kg bw||LD50 >2000 mg/kg bw (estimated)||Schedule 5|
|Acute inhalational toxicity||Rat||LC50 >5300 mg/m3 (whole body; 4-h)||LC50 >5000 mg/m3(whole body; 4-h) (estimated)||-|
|Skin irritation||Rabbit||Irritating||Slight (estimated)||-|
|Eye irritation||Rabbit||Irritating||Moderately irritating||Schedule 6|
|Skin sensitisation (Buehler)||Guinea pig||Non-sensitiser5||Non-sensitiser (estimated)||-|
Reasons for final decision
In determining that this matter will be a delegate-only decision I have taken into account the information provided in the application from the Applicant (APVMA), and the matters outlined under Section 52E of the Therapeutic Goods Act 1989 and the Scheduling Policy Framework (SPF, 2018). In particular, I note that:
- The proposed change to the Poisons Standard for the Schedule 5 entry for nonanoic acid is in response to new toxicity data. These data indicate that there is a risk to human health and safety from the use of this substance in pesticides (herbicides) that is not adequately mitigated by the current exemption in Schedule 5. The new information demonstrates that even low concentrations (ca 1.8%) of nonanoic acid are irritating to the eye and therefore, together with the overall toxicity profile of nonanoic acid, meets the criteria laid out in the SPF (2018) for a Schedule 5 entry without a concentration cut-off. The Applicant (APVMA) has indicated that various agricultural (pesticide) products containing nonanoic acid are currently available for use both commercially and in the home garden, thus highlighting its continued benefit for the agricultural industry. The proposed change is not expected to affect the benefits obtained from the use of agricultural products containing nonanoic acid or in other preparations that contain nonanoic acid (52E(1)(a)).
- The purpose and extent for which the substance is to be used has been adequately outlined by the Applicant. It has a demonstrable use as a herbicide both alone and in combination with other active constituents (ingredients) in commercial settings and in the home garden. The proposed change to the Schedule 5 entry for nonanoic acid is not expected to significantly alter the registered uses of the substance (52E(1)(b)).
- The toxicity of nonanoic acid has been previously considered by a Delegate of the Secretary of the Department of Health (Final decision published in June 2016) in response to an application prepared by the APVMA. Overall, nonanoic acid was found to be of low acute oral, dermal and inhalational toxicity and not a skin sensitiser, but was considered irritating to the eyes and skin. In addition, nonanoic acid was not genotoxic, did not show evidence for carcinogenicity, and was not a reproductive or developmental toxicant. Nonanoic acid has also be found to be irritating to epithelial and mucosal membranes. The current application by the APVMA, provides new information about the potential eye irritation of the substance, via the extrapolation from an eye irritation toxicity study in which a product containing a low concentration of nonanoic acid (ca 1.8%), was shown to be 'moderately' irritating to the eyes. The new data supports the Applicant's contention that the existing Schedule 5 exemption of 10%, does not adequately protect users of products that produce aerosols. This is particularly important for agricultural products that are routinely applied by spraying. Moreover, the data do not provide an alternative concentration cut-off that could see a lower exemption from Scheduling for agricultural products (52E(1)(c)).
- The dosage (application rate), formulation, labelling, packaging and presentation of the substance in agricultural products will largely be unaffected by the proposed change. The only exception would be for products that currently contain 10% or less of nonanoic acid and that do not have any other scheduled substance (active or non-active ingredient/constituent), that would now require an applicable Schedule 5 signal heading on its label. The proposed change to the Schedule 5 entry in the Poisons Standard will not affect nonanoic acid-containing products listed under the ARTG (52E(1)(d)).
- There is no information to indicate that the substance could pose a risk to human from abuse of the substance (52E(1)(e)).
- There were no other matters that were considered necessary to protect human health (52E(1)(f)).
Therefore, based on the information provided in the application, I have decided to amend the Poisons Standard in the manner set out in the application. The proposed amendment was not referred to an expert advisory committee.
Date of effect of the decision
1 June 2020