Application for amendment of Schedule 7 entry for nicotine

 

29 June 2016

 

 

New Nicotine Alliance (AU)

(A National Not for Profit Organisation)

Ph. 0437 686 594

PO Box 3

Chelsea Vic 3196

www.nnalliance.org.au

 

 

CONTENTS

CONTENTS

 Confidentiality

MEDICINE DETAILS

APPLICANT'S DETAILS

DECLARATION

PART 1 - SUMMARY OF THE APPLICATION

Proposed Rescheduling

Overview

PART 2 – BODY OF THE APPLICATION

BACKGROUND

Current scheduling status

Historical context

Chemistry

DETAILED CLAIMS AGAINST THE REQUIREMENTS OF THE SCHEDULING POLICY FRAMEWORK

PART 2.1 Criteria Which Must Be Addressed – proposals to change Part 4 of the Poisons Standard – scheduling or rescheduling of substances

(A) Risks and Benefits Associated with the Use of a Substance

Risks

Benefits

(B) The purposes for which nicotine is to be used and the extent of use

Purpose

Extent of use

(C) Toxicity and Safety of nicotine

(D) Dosage, Formulation, labelling, packaging and presentation of a Substance

(E) Potential for Misuse/Abuse of nicotine

(F) Any Other Matter that May be Relevant to the Scheduling of nicotine

PART 2.2 – Consideration of the factors for Schedule 7 set out in Chapter 3 of the Scheduling Policy Framework

Overall conclusions

PART 3 - SUPPORTING DATA

Supporting Data

PART 4 – BIBLIOGRAPHY

References

 

 

Confidentiality

This application contains no material claimed to be commercial-in-confidence


MEDICINE DETAILS

1 Name of substance requiring scheduling

Nicotine

2 Active ingredient name(s)

N/A

3 Dosage form

N/A

4 Container type

N/A

5 Indications of medicine

N/A

6 Current poisons schedule (if applicable)

Schedule 7

7 Proposed poisons schedule

Unscheduled


Applicant’s Details

1 Applicant’s [Sponsor’s] name New Nicotine Alliance (AU)*
2 Applicant’s [Sponsor’s] Business Address

PO Box 3

Chelsea Vic 3196

3 Business name (if applicable) NA
4 Date of submission 29 June 2016
5 Contact person Donna Darvill
6 E-mail Address of contact person This email address is being protected from spambots. You need JavaScript enabled to view it.
7 Postal address of contact person

PO Box 3

Chelsea Vic 3196

8 Phone Number of contact person 0437686594
9 Fax Number of contact person NA

 

 

*The New Nicotine Alliance Australia is a not for profit organisation working towards improving public health through a greater understanding of risk-reduced nicotine products and their uses.  It receives no funding from tobacco, e-cigarette or pharmaceutical companies or their affiliates. http://nnalliance.org.au/


Declaration

We, the undersigned, on behalf of New Nicotine Alliance (AU):

  • declare that the information provided in this application is true and current;
  • undertake to treat as confidential information, and not publicly disclose, the notice of interim decision in respect of this application, until (if relevant i.e. following referral to an expert advisory committee) the interim decision is published pursuant to subsection 42ZCZP of the Therapeutic Goods Regulations 1990, or the final decision is published pursuant to subsection 42ZCZS of the Therapeutic Goods Regulations 1990.

Dr Attila Danko

President – New Nicotine Alliance (AU) This email address is being protected from spambots. You need JavaScript enabled to view it.
0428412353

28 June 2016

 

Donna Darvill

Board Secretary – New Nicotine Alliance (AU)
This email address is being protected from spambots. You need JavaScript enabled to view it.
0437686594

28 June 2016

 

Jennifer Stone

Board Member – New Nicotine Alliance (AU)
This email address is being protected from spambots. You need JavaScript enabled to view it.

28 June 2016

 


PART 1 - Summary of the Application

Proposed Rescheduling

The New Nicotine Alliance (AU) requests an amendment to Schedule 7 as detailed below (amending words in red and underlined)

NICOTINE except:

a. when included in Schedule 6;

b. in preparations for human therapeutic use; or

c. in tobacco prepared and packed for smoking; or

d. in preparations for use as a substitute for tobacco when packed and labelled:

(i) for use in an electronic nicotine delivery system (ENDS)

(ii) nicotine concentration up to 3.6%

(iii) maximum nicotine per container: 900mg

(iv) in a child resistant container

(v) labelled with the concentration of nicotine and other ingredients

(vi) labelled with the statement ‘Keep out of reach of children’

(vii) labelled with the statement ‘Not to be sold to a person under the age of 18 years’

 


Overview

The purpose of this application is to propose that nicotine in low-concentrations be exempted from Schedule 7 of the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) so that it may be available for self-administration with an electronic nicotine delivery system (ENDS, also known as ‘personal vaporiser’ or ‘electronic cigarette’) for the purpose of tobacco harm reduction (THR).

Harm reduction is a well-documented strategy to reduce the harm of a behaviour by substituting it with a less harmful behaviour. Tobacco harm reduction provides an alternative pathway for smokers who are unable or unwilling to quit nicotine. Tobacco harm reduction has huge potential to prevent death and disability from tobacco and reduce health inequalities.

The current position

All nicotine replacement therapy (‘NRT’) products currently available in Australia for ‘therapeutic’ use are classified in the lowest risk category (unscheduled). They are considered to be ‘therapeutic goods’ because they are for use in ‘quitting’ smoking or ‘reducing to quit’. These products deliver low doses of nicotine via the dermal and oro-mucosal route. The risk of toxicity is mitigated by their low nicotine content and by their packaging and labelling.

Nicotine in products for inhalation for therapeutic use is included in Schedule 4 of the SUSMP (‘prescription only’). All nicotine-containing products for therapeutic use are required to be included as ‘registered’ medicines in the Australian Register of Therapeutic Goods before they can be marketed in Australia.

Nicotine for use ‘as a tobacco substitute’ is covered by the Schedule 7 entry in the SUSMP which is given effect through State and Territory legislation. As a non-therapeutic purpose, this falls outside TGA’s jurisdiction. When the current Schedule 7 entry was formulated, ENDS had not been invented. These products first came into widespread use around 2006.

Marketing nicotine products for human use within the strictures of Schedule 7 is not feasible or practical. We are not aware of any approvals being issued to vendors to sell or individuals to possess and use non-therapeutic, non-pesticide nicotine under State or Territory legislation, nor are we aware of any State or Territory health department that has procedures in place to facilitate applications for approvals to sell, obtain, possess or use nicotine products for THR purposes. These nicotine products are in effect ‘prohibited’.

Prior consideration

The scheduling of nicotine was considered by the National Drugs and Poisons Committee (NDPSC) in October 2008. The proposed amendment was to exclude nicotine from Schedule 7 ‘in electronic cigarettes prepared and packed as an alternative to traditional smoking’. The committee agreed that the current scheduling remained appropriate and that the Schedule 7 parent entry for nicotine should remain unchanged (NDPSC Oct 2008).

Since that earlier consideration there has been considerable development in the public health understanding, smoker adoption and regulation of these products globally. This application will update the committee on these developments, with the conclusion that the scheduling of nicotine in Australia for non-therapeutic purposes should be amended.

Tobacco harm reduction (THR)

Most smokers want to quit and forty per cent of Australia smokers try to quit at least once each per year. 1 However, nicotine dependence is a powerful substance use disorder (DSM 5) and the great majority of attempts are unsuccessful. Even treatment with first-line pharmaceutical smoking cessation therapies only increases the percentage of smokers who are abstinent at 6 months by 10-15% over those on placebo, and half of these will subsequently relapse. 2

Tobacco harm reduction is a strategy to minimise the harm in smokers who are unwilling or unable to quit. 3 The rationale is to provide smokers with an alternative way of getting the nicotine to which they are addicted without the tobacco smoke that causes almost all of the adverse health effects of smoking.

Cigarette smoking is recognised as the most harmful way to use nicotine. 4 Nicotine can be delivered in less harmful forms. A recent review of drugs for harm reduction, found that only nicotine and opiates met all eight criteria for a maintenance drug. ‘While nicotine has not been promoted widely or used for maintenance, it has the potential to fulfil that role’. 5

Although nicotine is the main psychoactive agent in tobacco, it has relatively minor health effects. It is not a carcinogen, does not cause respiratory disease and has only minor cardiovascular effects. 6 Even in overdose, the risk of harm from nicotine is small. Most cases result in prompt vomiting and serious outcomes are rare. 7-9

THR is consistent with the National Tobacco Strategy 2012-2018 10 and is listed as one of the three pillars of the policy along with demand reduction and supply reduction. THR is a potentially powerful complement to other tobacco control policies, particularly for the relatively highly addicted and typically disadvantaged smokers who are likely to find it most difficult to quit. 3

The long-term use of snus in Sweden confirms the safety of nicotine when used as a long-term tobacco substitute in humans. Snus is a moist, smokeless, low-nitrosamine tobacco which is placed in the mouth and provides nicotine blood levels similar to smoking. The use of snus has resulted in Sweden having the lowest adult daily smoking rate in Europe (10.7% in 2015. OECD) with substantial public health benefits. 11-13 See section 2.1 (C) below.

An Australian study found 20% of current smokers were interested in trying a low-nitrosamine smokeless tobacco product (such as snus) as a smoking substitute if it was available. 14

Other examples of successful harm reduction strategies include clean needles and syringes to intravenous drug users to reduce the risk of infection and promoting condom use by sex workers.

Harm from tobacco in Australia

Currently 15.8% of Australians (aged 14+) smoke tobacco (3 million people) and smoking is increasingly concentrated in lower-socioeconomic and disadvantaged groups, and is the largest cause of health inequalities. 15

Smoking is the single greatest preventable cause of death and disease in Australia killing 15,500 smokers each year. 16 As many as two out of three lifelong smokers in Australia die as a direct consequence of their smoking 17 and smokers lose an average of about 3 months of life expectancy for every year smoked after the age of 35. 18, 19 Smokers who don’t quit lose around 10 years of life. 18, 19

Tobacco also causes harm from secondhand and thirdhand smoke, is the largest preventable cause of adverse pregnancy outcomes, causes fires, litter and associated environmental contamination of waterways through discarded cigarette butts and exacerbates poverty.

Electronic Nicotine Delivery Systems

The devastating burden of smoking-related disease suggests novel public health interventions are needed to reduce the harm from smoking. One such option is Electronic Nicotine Delivery Systems (ENDS).

For those who are unwilling or unable to quit smoking, nicotine can be inhaled using an ENDS for the purposes of harm reduction. ENDS are battery-powered devices that heat a liquid into an aerosol for inhalation. The liquid solution contains water, nicotine (0.3-3.6%), propylene glycol, vegetable glycerine and typically also flavourings.

As well as delivering nicotine, ENDS use addresses the behavioural, sensory and social components of the smoking ritual. Users (known as ‘vapers’) rate ENDS that contain nicotine as more satisfying than nicotine replacement therapy (NRT). 20 they also appeal to smokers who are interested in a non-medicalised approach to reducing their health risk or are looking for a long-term alternative to cigarettes rather than a therapeutic product for quitting.

Nicotine delivery is determined by the concentration of nicotine, the puffing technique and the device used. 21 Earlier models delivered low doses of nicotine. However, with improved technology, experienced users with more advanced devices can achieve blood levels similar to smoking, although the speed of nicotine delivery remains much slower than from cigarettes. 22

There is general consensus that nicotine delivered via ENDS is much less harmful than when delivered via smoking tobacco. An expert panel estimated the risk of harms of ENDS to be only 5% of the harms of smoking. 23 Two further reviews of the scientific literature on ENDS published by Public Health England and the Royal College of Physicians, concluded that the evidence supports this estimate. 3, 24 Paradoxically, the current Australian laws ban a less harmful form of nicotine intake (ENDS) while allowing the sale of the most lethal form of nicotine intake (tobacco cigarettes).

While ENDS aerosol may contain small amounts of other chemicals including volatile organic compounds, carbonyls, aldehydes, tobacco-specific nitrosamines (TSNAs) and metal particles, research indicates that they are present at much lower levels than in cigarette smoke.25 In normal conditions of use, toxin levels in inhaled ENDS aerosol are below prescribed threshold limit values for occupational exposure, in which case significant long-term harm is unlikely. 26

ENDS are very popular with a substantial minority of smokers and are more popular than nicotine replacement therapies. 20 Their use has been growing rapidly in Australia in spite of the current legal restrictions and difficulties of access. Many have switched completely from cigarettes to ENDS. Preliminary results from the Australian arm of the ITC 4 country survey found that 14.6% of smokers were current ENDS users in 2014, 27 rising from 0.8% in 2010 and 8.9% in 2013. 28 43% of Australian users reported using nicotine in an ENDS device. 28

The vast majority of ENDS use in Australia is by current smokers using them to reduce the number of cigarettes they smoke or to switch completely from cigarettes to ENDS as a complete substitute. 29, 30 There is little evidence of harm from ENDS use in Australia, in spite of many being sold without child resistant lids, warning labels etc.

Proposed change

This application proposes that nicotine in ENDS for non-therapeutic use (as a tobacco substitute) be exempted from Schedule 7. The current Schedule 7 classification is not appropriate for low concentrations of nicotine for use in ENDS. Schedule 7 substances include arsenic and strychnine and is described in the SUSMP as follows (page iv):

Dangerous Poison – Substances with a high potential for causing harm at low exposure and which require special precautions during manufacture, handling or use. These poisons should be available only to specialised or authorised users who have the skills necessary to handle them safely. Special regulations restricting their availability, possession, storage or use may apply.

Low concentrations of nicotine are at the low end of the toxicity range. An independent report on the acute oral toxicity of nicotine allocated different concentrations to EU CLP categories according to their toxicity. There are 4 toxicity category based on acute oral toxicity, ranging from 1 (fatal if swallowed) to 4 (harmful if swallowed). Concentrations of nicotine <2.5% were unclassified. Concentrations 2.5-16.6% were CLP category 4 (toxic if swallowed). 31

The proposed availability would be subject to limitations on nicotine concentration and the inclusion of safety warnings.

  • A maximum dose of nicotine per bottle of 900mg. The concentration of nicotine used for vaping is in the range of 0.3 to 3.6%. This would allow for the supply of a 30ml bottle of 3% nicotine or a 60ml bottle of 1.5% nicotine, as larger volumes are required for low concentrations. As the average volume used is about 3-4ml daily, a typical 30 ml bottle would last about 7-10 days.

  • Labelling and safety requirements would include
    • a child resistant container
      • labelled with the concentration of nicotine and other ingredients
      • labelled with the statement ‘Keep out of reach of children’
      • labelled with the statement ‘‘Not to be sold to a person under the age of 18 years’

It is appropriate to apply the same unscheduled classification as currently applies to the nicotine in tobacco-based cigarettes, loose tobacco for use in pipes and roll-your-own cigarettes, and currently marketed NRT products. A more detailed consideration of this issue in relation to the AHMAC ‘factors’ for Schedule 7 follows in Part 2.2, and is discussed below.

Removing low-concentration nicotine for use in ENDS from Schedule 7 would bring it within the jurisdiction of the Australian Consumer and Competition Commission (ACCC) under The Australian Consumer Law. This legislation includes a national product safety law and enforcement system with penalties, enforcement powers and consumer redress options. These provisions are adequate and appropriate for the control of the product. These provisions, combined with the proposed scheduling amendment are consistent with those adopted globally.

The existing medicinal controls applied by the Therapeutic Goods Administration to medicinal NRT products under a Schedule 4 listing are neither appropriate nor necessary for control of low-concentration nicotine for use in ENDS. The added consequence of the existing medicinal controls in Australia is that they cede the tobacco harm reduction opportunity wholly to Tobacco Companies due to the high cost and administrative barriers. The only medicinally approved ENDS device in the world is owned by British American Tobacco, and we understand that they are also using the disproportionate medicinal standards to gain approvals for a similar product in Australia.

Nicotine for therapeutic use (i.e. for use in ‘quitting’ smoking or ‘reducing to quit’), including therapeutic use in ENDS, would continue to be captured by the existing schedule 4 ‘parent’ entry for nicotine (unless exempt) and would continue to be regulated by the TGA, regardless of scheduling.

Legal issues and quality control

 Currently, hundreds of thousands of Australians are illegally using nicotine in ENDS as a less harmful alternative to smoking tobacco. Amending the SUSMP would allow these and other smokers to legally access nicotine for this purpose.

Current purchases are mainly made on the internet and through an unregulated black market 30 and there is no effective regulatory control. Regulation under consumer law will improve product safety and quality: it will facilitate high quality manufacturing practice, quality control, enforcement of safety standards, accurate labelling, restricted sales to minors, child resistant containers etc. The black market will also disappear as these products would no longer be contraband.

Public Health Impact

Removing low-concentrations of nicotine for harm reduction from the Poisons Standard has the potential to save hundreds of thousands of Australian lives. 32 Tobacco harm reduction provides an alternative pathway for smokers who are unable or unwilling to quit to get the nicotine to which they are addicted without the tobacco smoke that causes almost all of the adverse health effects of smoking. The popularity of ENDS will provide an opportunity to expand the number of smokers reached by THR.

In the UK alone, 1.3 million former smokers are currently using an ENDS as a safer alternative to combustible tobacco. 33 A recent representative survey of 27,460 EU citizens in the EU estimated that 6.1 million ex-smokers were currently using ENDS as a safer substitute to smoking and 9.2 million smokers were using them to reduce smoking. 83

A recent Reuters / IPSOS poll of US adults found that 7.35 million smokers (30% of 24.5 million ENDS users) have stopped smoking and are currently vaping instead.

The role of regulation

A balanced and proportionate regulatory approach will ensure the maximum public health benefit from ENDS. Regulation should allow smokers access to low-risk nicotine solutions while monitoring and minimising any potential harms, such as use by non-smoking children.

An appropriate regulatory approach would include:

  • Child resistant containers
  • Accurate labelling
  • No advertising or sale to people under 18 years
  • Restrained promotion carefully targeted at smokers, perhaps restricted to point of sale where tobacco products are sold
  • Restricted use in some smoke-free or confined spaces
  • Low or no tax to maintain a competitive advantage over tobacco
  • High manufacturing quality, with safe, pharmaceutical grade ingredients

According to the Royal College of Physicians, the net impact is likely to be strongly positive:

‘Promotion of the use of non-tobacco nicotine, including e-cigarettes, as widely as possible as a substitute for smoking, in the context of a regulatory framework designed to discourage use among youth and never-smokers, is therefore likely to generate significant health gains in the UK’. 3

A review by Franck concluded:

‘Overall, the available evidence supports the cautionary implementation of harm reduction interventions aimed at promoting e-cigarettes as attractive and competitive alternatives to cigarette smoking, while taking measures to protect vulnerable groups and individuals’. 34

 

Part 2 – Body of the Application

Background

Current scheduling status

ENDS containing nicotine for non-therapeutic use (e.g. as a tobacco substitute) are currently included in Schedule 7.

Historical context

Ref: Delegates’ reasons for final decisions, September 2011 (page 71 – 83):

The first-line pharmacological intervention for nicotine dependence from cigarette smoking is nicotine replacement therapy (NRT). NRT formats currently available over-the-counter (OTC) include chewing gum, lozenge and inhaler (absorbed via the buccal mucosa), patch (transdermal) and microtab (sublingual). Combination therapy with different types of NRT has also been tried as a means of increasing efficacy.

In June 1991, the Schedule 4 entry for nicotine was amended to include all preparations (except Schedule 3 chewing tablets) which could be used as an aid in smoking cessation, containing between 2 and 4 mg of nicotine or roll-on devices with 0.65 per cent or less of nicotine e.g. transdermal patches.

In August 1993, the NDPSC rejected a proposal to have 2 mg sublingual tablets rescheduled from Schedule 3 to Schedule 2 and 4 mg sublingual tablets rescheduled from Schedule 4 to Schedule 3. In November 1993, the NDPSC agreed that Schedule 4 remained appropriate for patch formulations. Subsequently, in November 1997, transdermal patches were included in Schedule 3.

Nicotine 2 mg chewing tablets were rescheduled to Schedule 2 in February 1997. However, at the same meeting the NDPSC decided that the higher dosage (4 mg) should only be rescheduled to Schedule 3 to facilitate the counselling of heavy smokers by a pharmacist.

Inclusion of nicotine gum and transdermal patches in Appendix H was agreed at the August 1998 meeting.

In November 1998, the NDPSC considered down-scheduling nicotine for inhalation, when packed in cartridges for use as an aid in withdrawal from tobacco smoking, from Schedule 4 to Schedule 3 and decided that Schedule 3 was appropriate. The NDPSC noted that this form of oral inhalation was similar in many respects to the chewing gum, being absorbed mainly in the mouth and throat. Data provided indicated that nicotine plasma levels obtained via the inhaler were similar to those obtained with the 2 mg chewing gum.

In February 1999, the NDPSC amended this Schedule 3 nicotine entry to ‘Nicotine as an aid in withdrawal from tobacco smoking in preparations for inhalation or sublingual use’.

In August 2001, the NDPSC agreed that nicotine lozenges would have a comparable safety profile to that of sublingual tablets, and so it was appropriate to also include lozenges in Schedule 3. Subsequently, lozenge preparations were down scheduled to Schedule 2 in June 2003. In February 2002, nicotine inhalers were rescheduled from Schedule 3 to Schedule 2.

In February 2010, the NDPSC considered an application to broaden the exemptions for specified NRT buccal dosage formats i.e. chewing gum and lozenges, to buccal preparations in general. The NDPSC decided to only down-schedule oromucosal sprays and did not support an exemption for oromucosal preparations in general, noting that this could potentially include preparations such as mouthwashes. The NDPSC was of the opinion that there was insufficient data for such a broad exemption.

In June 2010, the NDPSC noted a post-meeting submission requesting that the exemption either be reworded to all oral use or all oromucosal products which were bioequivalent to currently marketed oral dose formats. This request was not supported and the NDPSC confirmed its February 2010 decision.

Ref: NDPSC Record of Reasons October 2008 (page 126 – 143)

At the June 2008 Meeting, a member reported on a company marketing ‘electronic cigarettes’ via the internet. The company’s website made a number of claims relating to the ‘safety’ of the product when compared to smoking normal cigarettes. This issue was referred to the TGA by the jurisdiction.

At the October 2008 meeting the matter was further discussed with the outcome that the committee considered the current Schedule 7 classification remained appropriate.

Chemistry

Nicotine structure:

Chemical name: (S)-3-(1-Methylpyrrolidin-2-yl)pyridine,

molecular formula: C10H14N2 =162.2

Ref: Martindale online 22 May 2016.

 

Nicotine is a liquid alkaloid obtained from the dried leaves of the tobacco plant, Nicotiana tabacum and related species (Solanaceae). Tobacco leaves contain 0.5 to 8% of nicotine combined as malate or citrate. It is a colourless or brownish, volatile, hygroscopic, viscous liquid. Soluble in water; miscible with dehydrated alcohol.

When smoked, nicotine is distilled from burning tobacco and carried on tar droplets (particulate matter), which are inhaled. Nicotine has a plasma half-life of approximately 2 hours. It is metabolised in the liver primarily by the CYP2A6 enzyme into cotinine which is excreted by the kidneys. 35 Nicotine used in nicotine solutions for ECs is extracted from tobacco leaves.

Detailed Claims Against the Requirements of the Scheduling Policy framework

PART 2.1 Criteria Which Must Be Addressed – proposals to change Part 4 of the Poisons Standard – scheduling or rescheduling of substances

(A) Risks and Benefits Associated with the Use of a Substance

Risks

The safety and toxicity of nicotine is addressed in section 2C.

The proposed pack size restrictions for nicotine: max 3.6% and a maximum nicotine content per pack of 900mg are similar to some of the available NRT products as shown in the table below.

The average daily dose of liquid nicotine consumed in ENDS is similar to the daily maximum dose of liquid nicotine from Nicorette Mouth Spray, an unscheduled medicine. The maximum dose of Nicorette Mouth Spray is 64mg per day (64 sprays of 1mg/spray). The average daily nicotine intake from ENDS is 63mg (based on an average nicotine concentration of 1.8% and an average daily volume of 3.5ml). 33, 36 37, 38

Product Nicotine per dose unit Max pack size (dose units) Total amount of nicotine per max pack
Nicorette Inhaler AUST R 80874 15mg 20 300mg
Nicorette lozenge AUST R 205211 4mg

80

(4-pack)

320mg
Nicorette Patch   AUST R 203287 25mg 28 700mg
Nicorette Mouth Spray AUST R 197127 1mg

450

(3-pack)

450mg
Nicorette Gum 4mg AUSTR 12516 4mg 210 840mg
Tobacco intended for smoking Nil restriction Nil restriction
Nicotine quantity proposed 900mg

In addition, the proposed limits on nicotine concentration and quantity, prevention of access to the liquid except when within an ENDS in a sealed, child resistant container and labelling (‘keep out of reach of children’) will provide further assurance of the relative safety of ENDS.

Concerns that were recorded in the ‘record of reasons’ from the NDPSC meeting in October 2008 (mostly in comments on the proposed changes) with a response to these concerns are listed below.

That the nicotine may cause addiction in non-nicotine addicted users and of the potential for the product to give rise to new addictions to nicotine in children and adolescents.

After 10 years of real-world experience overseas, the available evidence does not support the gateway hypothesis, ie that ENDS may encourage nicotine addiction and progression to tobacco smoking in young people who would not otherwise have smoked.

It is rare for non-smoking youth to become regular ENDS users. In the UK, regular ENDS use is almost exclusively confined to young people who already smoke. 39, 40 Less than 0.2% of never-smoking youth vape regularly and there is no evidence of progression to smoking. 39

There is similar evidence from the US. The 2014 National Health Interview Survey found that current ENDS use is extremely low among never cigarette smokers (0.4%) ‘Conclusions: Extremely low e-cigarette use among never-smokers and longer-term former smokers suggest that e-cigarettes neither promote widespread initiation nor relapse among adults’. 41

Many cross-sectional studies have found that young people who use e-cigarettes are also more likely to smoke. 42, 43 This association has been incorrectly interpreted as a causal relationship. A more likely explanation is that young people who are more attracted to experimentation are more likely to try both products (‘common liability’). 44

Population evidence also supports the lack of a gateway effect. As ENDS use by adolescents is rising, adolescent smoking rates are falling and are now at record lows in many countries. For example, in the US, from 2011 to 2014, adolescent EC use rose from 1.5% to 13.4%. 45 However, adolescent smoking rates fell from 15.8% to an all-time low of 9.2%. If a gateway mechanism is operating, an increase in smoking rates would be expected.

One possible explanation for this reduction in smoking prevalence is that ENDS are preventing smoking uptake. Young people who experiment with e-cigarettes may otherwise have smoked in the absence of ENDS. Using an ENDS which may be more enjoyable and socially acceptable may prevent adoption of the more harmful behaviour. It is obviously better for young people not to use ENDS, but vaping is preferable to smoking and is at least 95% safer.

Two large studies have found that the introduction of bans on the sale of ENDS to adolescents was associated with a significant increase in adolescent smoking rates compared to states without bans. 46, 47 Such bans may be having the perverse consequence of eliminating a much less harmful substitute behaviour which is diverting users from smoking tobacco.

Furthermore, like adult smokers, some young people are using ENDS to help them quit smoking 48 ENDS bans remove this treatment option.

However, the great majority of adolescent EC users do not use nicotine-containing ENDS even when it is freely available. Only 20% of grade 12 ENDS users reported using nicotine solutions in the US (https://www.drugabuse.gov/related-topics/trends-statistics/monitoring-future/overview-findings-2015/monitoring-future-figures-2015) and 28% in Canada. 49

The warnings on cigarettes may help to turn young people to e cigarettes and nicotine addiction
Nicotine dependence develops rapidly in young smokers and 70% are already nicotine dependent before they are smoking daily. 50 Most adolescents want to quit, but quit rates are low. Young people who are already addicted to tobacco cigarettes who change to ENDS will reduce their risk of ill health by 95% compared to the risks from smoking tobacco.
The submission claimed that there was a real likelihood that these products could issue in a dual use of e cigarettes and tobacco according to the environment the smoker is in. The argument was that the smoker may increase the level of nicotine intake, by using electronic cigarettes at work for example and tobacco outside.

There is no evidence of increased nicotine intake from dual use. Smokers regulate their smoking behaviour to maintain their plasma nicotine levels within a comfortable range to avoid nicotine withdrawal symptoms. If levels get too high, symptoms of nicotine toxicity such as nausea, headache and dizziness can occur and smoking is reduced.

A recent study found that smokers using ENDS maintain their intake of nicotine, but reduce their smoke and toxin intake, resulting in an overall health benefit. 51

The same compensatory smoking occurs in dual users of cigarettes and quick acting NRT products (nicotine gum, lozenges etc). A review found that smokers concurrently using oral NRT products had unchanged nicotine concentrations. Furthermore, with dual use, ‘the number of cigarettes smoked per day was reduced by approximately 50% and carbon monoxide (CO) by 30%’. The authors concluded that ‘concurrent use of NRT products and cigarette smoking appears to be safe’. 52

The other argument was that the vapour emitted while using the product indoors, may not be harmless, and that this factor is unknown until further testing has been carried out.

Reviews of passive exposure to vapour have generally concluded that the risk to bystanders is very small. For example, Public Health England reviewed all the evidence and found that ‘ENDS release negligible levels of nicotine into ambient air with no identified health risks to bystanders’. 24

According to another review, ‘No long-term study has been conducted so far, but pollutant levels are much lower than from cigarettes and are likely to pose a much lower risk (if any) compared to cigarettes’. 53

A further comprehensive safety review concluded ‘it is safe to conclude that the effects of ENDS use on bystanders are minimal compared with conventional cigarettes’. 54

Furthermore, a study of nicotine residue (a marker of thirdhand smoke) in houses of ENDS users, smokers and non-users of nicotine-containing products found no difference in the amount of nicotine in the EC user and non-nicotine user homes (7.7 ± 17.2 vs. 7.2 ± 13.8; p > 0.05). Nicotine levels in non-smokers homes was significantly lower than that found in cigarette smokers’ homes (7.2 ± 13.8 vs. 1303 ± 2676 ug/m2; p<0.05). 55

All chemicals and ingredients contained in these products have not been established, and some additives contained in the scenting and flavouring ingredients are not known. Even though the claim was made that the product is free from carcinogens, the chemical agents remaining in the device have not been through any rigorous testing to prove their not detrimental status.

The constituents of cigarette smoke that harm health – including carcinogens –are either absent in ENDS vapour or, if present, they are at levels much below 5% of smoking doses (mostly below 1% and far below safety limits for occupational exposure. 24

Based on the chemical, toxicological and clinical studies to dates, Public Health England concluded that ENDS use is around 95% safer than smoking. This level of risk includes an allowance for the uncertainty of unknown risks over the long term. 24

‘The possibility of some harm from long-term ENDS use cannot be dismissed due to inhalation of the ingredients other than nicotine, but is likely to be very small, and substantially smaller than that arising from tobacco smoking. With appropriate product standards to minimise exposure to the other ingredients, it should be possible to reduce risks of physical health still further. Although it is not possible to estimate the long-term health risks associated with e-cigarettes precisely, the available data suggest that they are unlikely to exceed 5% of those associated with smoked tobacco products, and may well be substantially lower than this figure.’ 3

Given the significant delay between smoking initiation and smoking-related disease, many years are needed for research to characterize the full risk profile of ENDS. While waiting for full scientific certainty, considerable smoking-related illness and death will occur. The known benefits of ENDS strongly outweigh the likely small unknown risks.

The product undermines national anti-smoking and tobacco regulation policies and could ‘renormalise smoking’

In the UK, there is no evidence that ENDS are renormalising smoking. As e-cigarettes have become popular, quit attempts have increased and smoking prevalence has continued to fall 33 (also STS data: http://www.smokinginengland.info/latest-statistics)

According to Public Health England, ‘There is no evidence that ENDS are undermining the long-term decline in cigarette smoking among adults and youth, and may in fact be contributing to it’. 24

Similar trends are seen in the USA. ‘Data from 2014 National Health Interview Survey indicate that e-cigarettes have not been attracting adult non-smokers or promoting relapse in longer term former smokers. Moreover, the data are suggestive that some recent quitters may have done so with the assistance of e-cigarettes.’ 41

It is also possible that a growing acceptability of e-cigarettes could increase pressure on current smokers to quit tobacco cigarettes by virtue of these becoming perceived as socially undesirable predecessors of a ‘cleaner’, smoke-free device. 34

Other concerns raised about ENDS use

Concerns have been raised that ‘dual use’ of smoking and ENDS may prevent quitting and may be more harmful than smoking

Complete cessation of tobacco is always preferred. However, many smokers report dual use of tobacco cigarettes and ENDS. For example, the recent study in NSW reported that 9% of NSW smokers were also current users of ENDS. 30 For many users, there is typically a transition period of dual use after they start using e-cigarettes which ultimately leads to complete switching to ENDS, although some will relapse to smoking. 56, 57

Data from surveys of ENDS users and from clinical trials show consistently that smokers who use ENDS and smoke at the same time reduce their cigarette consumption, often substantially. Dual users maintain their intake of nicotine, but reduce their smoke intake. 38 This results in a significant reduction in exposure to carbon monoxide and other toxins compared to smoking alone. 51

According to Public Health England, ‘dual users of both tobacco and e-cigarettes are more likely to make an attempt to stop smoking than smokers who do not also use e-cigarettes, but it is not yet clear whether they are more likely to succeed.’ 24 This is similar to smokers who also use NRT and are approximately twice as likely in the following months to make a quit attempt, and to quit smoking, than those who do not. 58, 59

Nicotine is addictive and its use should not be encouraged
Initiation of regular use of nicotine in ENDS is confined almost exclusively to smokers. Smokers are already addicted to nicotine; therefore the use of a ‘cleaner’ form of nicotine delivery would not represent any additional risk of addiction.

Benefits         

The recent review by the Royal College of Physicians found that that ‘many smokers have succeeded in quitting simply by substituting electronic for tobacco cigarettes’ and that ‘harm reduction has huge potential to prevent death and disability from tobacco’. 3

The high popularity of ENDS as a substitute for cigarettes will allow them to reach a large numbers of smokers. As up to 2 in 3 Australian smokers die as a direct result of smoking 17 ENDS could save hundreds of thousands of Australian lives and dramatically reduce disease and health inequalities in Australia.

A recent report from England calculated that the availability of ENDS resulted in an estimated 16-20,000 additional long-term ex-smokers in 2014, who would not have stopped smoking with other methods if ENDS had not been available. 60 ENDS can also encourage quitting or reduce cigarette consumption even among those not intending to quit or rejecting other support. 24 (p6)

(B) The purposes for which nicotine is to be used and the extent of use

Purpose

The purpose of this application is to propose the sale of low concentrations of nicotine (3.6% or less) for use in ENDS to reduce the harm from tobacco by providing an alternative less harmful product for smokers. Under the harm reduction model, smokers who are unable or unwilling to quit would be encouraged to replace combustible tobacco with vapourised nicotine which is at least 95% safer than smoking. It is anticipated that many vapers will subsequently quit vaping altogether.

Australian vapers are already obtaining nicotine solutions on the internet from overseas or through an unregulated black market for this purpose. In a recent NSW survey of smokers and recent ex-smokers, the most common reasons for using an ENDS were ‘to help me quit smoking (32%), ‘to cut down on the number of cigarettes I smoke’ (32%) and ‘not as bad for your health as cigarettes’ (20%). 30 This highlights the advantage of a non-medicinal option.

Extent of use

The rate of uptake of ENDS by adult smokers in Australia has been rapid despite the very strict regulatory environment in Australia. In a national cohort of 1,500 current and former smokers, current use of ENDS increased from 0.6% in 2010 to 6.6% in 2013. 28 The rate of increase was the same over the same period as in the UK where ENDS are freely available.28 In 2014, the rate of current smokers using ENDS had increased to 14.6%. 27

A recent survey of 2,966 NSW adults (survey dates January 2014 – June 2015) found 9% of smokers and 7% of recent quitters were currently using ENDS. 30

The uptake of ENDS is expected to continue to increase in the future.

(C) Toxicity and Safety of nicotine

While nicotine in liquid form at high concentrations is toxic, the proposed exclusion from Schedule 7 is for the low concentrations of nicotine used in electronic cigarettes (≤3.6%). The overall health impact of ENDS use with nicotine represents a very low risk to consumers (around 5%) relative to the tobacco cigarettes it is intended to replace.

The classification of all NRT products currently available in Australia (e.g. gums, lozenges, buccal tablets, sprays, inhalations) as unscheduled attests to the safety of nicotine in this context. The inherent risk of nicotine in NRT is mitigated by its delivery system, slow absorption, low nicotine dose, total pack content and appropriate packaging and labelling.

Importance of the delivery system

Nicotine’s effects on the body and its toxicity are strongly linked to the speed of nicotine delivery and dose of nicotine delivered. This in turn is determined by the method of delivery.

Cigarettes. After a puff, nicotine is absorbed rapidly in the lungs and high levels of nicotine reach the brain in 10–20 seconds, faster than with intravenous administration, producing rapid behavioural reinforcement. Blood or plasma nicotine concentrations sampled in the afternoon in smokers generally range from 10 to 50 ng ml. 61

NRT. Nicotine is released much more slowly from NRT than from smoking. As well, the blood levels of nicotine from NRT are one third to two thirds that of smoking. As a result, the physiological effects of nicotine from NRT are substantially less than when delivered from smoking and there is a much lower addictive potential. 61

In the case of e-cigarettes, nicotine absorption is faster than from NRT but slower than smoking. Blood levels are generally considerably lower than from smoking, however experience vapers with more advanced technological devices can achieve blood nicotine levels similar to smoking.

TOXICITY

Nicotine is a toxic compound in a highly concentrated solution. Acute nicotine poisoning has an early clinical phase characterized by nausea, vomiting, abdominal pain, salivation, bronchorrhea, tachypnea, hypertension, tachycardia, miosis, tremor, muscle fasiculations, and seizures. The delayed phase consists of respiratory depression, dyspnea, bradycardia, hypotension, shock, mydriasis, weakness, muscle paralysis, and coma. 62

Lethal dose

Historically, the lethal dose of nicotine for a human adult was thought to be 60mg which was an estimate based on poor experiments in the nineteenth Century. This figure has recently been re-evaluated in the light of reports of non-fatal suicide attempts or accidents involving nicotine ingestion, leading to an estimate that the lower dose limit for fatal outcomes is likely to be 500–1,000 mg ingested nicotine. 7


Accidental poisoning

The risks from accidental poisoning are mitigated by several factors:

  • Immediate vomiting
    Most cases result in prompt vomiting and serious outcomes are rare.
    8, 9
  • Poor oral availability
    When nicotine is swallowed, it has a low bioavailability. Only 20 to 45% is absorbed into the blood stream and oral bioavailability is also reduced further by the hepatic first-pass metabolism.
    61
  • Low concentration used
    Standard concentrations of nicotine for vaping are 0.6 - 3.6%. The most popular strength is 1.8%.

The level of risk and frequency of risk also need to be considered.

  • Level of risk
    In a recent case series, there were 225 reports mostly by ingestion, to a poisons centre in Texas over a 5-year period. About half occurred in children aged <5 years, underscoring the importance of child resistant packaging and appropriate labelling. The clinical effects reported most often were those of nicotine poisoning: vomiting (20%), nausea (10%), headache (4%) and dizziness (5%). It was concluded that ‘most of our cases had no effects or mild manifestations ‘Reported exposures often do not have serious outcomes’ and there were no fatalities.
    63

    Worldwide there has been only ever two fatalities related to nicotine for use in ENDS
    64, 65 By comparison, in the US in 2014, there were 1,835 fatalities from all causes of poisoning (Table 21). 65
  • Frequency of risk
    With the increase in ENDS use, there has been a rise in calls to poison centres following accidental exposure. However, in 2013 in the US, nicotine accounted for 0.06% of the 2.6 million calls to Poisons Centres (data from American Association of Poison Control Centers Annual Report 2013 Table, A17 (
    http://www.aapcc.org/annual-reports/). With improved safety standards such as child resistant containers, the frequency of exposures has been falling since 2014 (page 1063).

Exposure to poisons is widespread in society and is associated with many products from which society benefits, such as bleach and laundry detergents. These are managed by common-sense, warning labels and child resistant containers.

Nicotine toxicity in users

Nicotine overdose or intoxication is unlikely to occur with vaping, since the amount consumed and absorbed is quite low. 54 Moreover, ENDS users titrate their nicotine intake as smokers do with tobacco cigarettes. If nicotine levels rise, the user reduces puffing frequency. Also nicotine is delivered much more slowly from ENDS than from tobacco cigarettes. 66

A recent study found that ENDS users puff more intensely (compensatory puffing) when using liquids with lower nicotine concentrations to deliver the desired nicotine level. 67 As a result, users of lower nicotine concentration solutions require larger volumes of fluid than those using higher concentrations. For this reason, higher concentrations are safer for the user as they reduce the amount of other chemicals delivered.

Intentional misuse

There are isolated reports of case studies of nicotine solution taken for suicide attempts. Most cases result in prompt vomiting and serious outcomes are rare.

  • Schipper reported a case of a 27-year old man who ingested 420mg of liquid nicotine and 5 units of wine. He vomited 3 times, had a sinus tachycardia and excessive salivation, but no other adverse effects. 9
  • Christensen recorded three suicide attempts which all resulted in vomiting but recovery within a few hours. One 36-year woman ingested 1500mg of nicotine. Two hours after ingestion the symptoms present were abdominal pain, nausea, and voluminous vomiting, oxygen saturation 100%, blood pressure (BP) 103/69, pulse (P) 70, Glasgow Coma Scale (GCS) 15. She was treated with activated charcoal and observed for 6 hours. 8

Transdermal absorption

Nicotine solution can be absorbed transdermally, for example during handing by users when refilling devices. However, transdermal absorption is slow and restricted to very small areas of the fingers or hands. Accidental spills over small areas are highly unlikely to be a serious health concern. One study found that from normal use with skin contact ‘This amount of nicotine is far below the dose absorbed at the level of the respiratory tract and not able to cause ill health’. 68

Absorption from nicotine patches is at a rate of 1mg per hour and takes several hours to for plasma levels to peak. In all cases, there is an initial lag time of about 1 h before nicotine appears in the bloodstream. 35

SAFETY

Risks from short term use

At commonly used doses, short-term nicotine use does not result in clinically significant harm. The safety of NRT products, which have typically been used for weeks or months in the context of an attempt to quit smoking, is well established. 69 The use of nicotine in electronic cigarettes is not associated with significant adverse effects. According to the Cochrane review, ‘None of the RCTs or cohort studies reported any serious adverse events (SAEs) that were considered to be plausibly related to ENDS use’. 70


Risks from long-term use

Long-term use of nicotine is regarded as low risk, based on studies of long-term snus and nicotine replacement therapy.

Snus

In Sweden, the long-term use of snus confirms the safety of long-term nicotine in humans when used for tobacco harm reduction. Snus is a moist, smokeless, low-nitrosamine tobacco which provides nicotine exposure similar to smoking. Snus has been used by Swedish men for over five decades as a non-therapeutic, less harmful alternative to smoking. 11

The use of snus as a tobacco substitute has led to substantial public health benefits in Sweden. Sweden has the lowest smoking prevalence in Europe and markedly lower rates of lung cancer, oral cancer and tobacco-related mortality compared to other countries. 12 A comprehensive review of snus found ‘scant support for any major adverse health effects of snus’. 13 The author concludes ‘switching to snus should improve the health prospects of those smokers who are unable or unwilling to relinquish nicotine’. The same benefits would be expected from switching to inhaled nicotine from ENDS.

Nicotine replacement therapy

The Lung Health study followed NRT users for up to 7.5 years demonstrating no association between sustained NRT use and cancer (lung, gastrointestinal or any cancer) or cardiovascular disease. 71, 72 In addition, a recent clinical trial comparing 8, 24 and 52 weeks of NRT treatment found that treatment duration was not associated with any adverse effects, further supporting the safety of extended NRT use. 73

Although there is little evidence on the safety of using nicotine for periods longer than 7.5 years, and no data on the safety of long-term use of nicotine by inhalation other than when delivered by tobacco smoke, it is widely accepted that any long-term hazards of nicotine are likely to be of minimal consequence in relation to those associated with continued tobacco use. 53, 54

In the UK, NRT is approved ‘for use as a substitute or partial substitute for smoking tobacco… without any restriction on its duration of use’. (https://www.gov.uk/drug-safety-update/nicotine-replacement-therapy-and-harm-reduction).

OTHER HEALTH EFFECTS OF NICOTINE

Cancer

Nicotine is not a carcinogen according to the International Agency for Research on Cancer. 74 A review of snus research found no evidence of increased smoking-related cancers in snus users from long-term use. 13 Animal studies suggest that nicotine may be a tumour promoter, but this has not been established in humans. There is no clinical evidence that NRT is associated with an increased risk of developing cancer. 6


Cardiovascular disease

Nicotine does have haemodynamic effects however it is not a major cause of the increased cardiac risk associated from smoking. NRT can be safely used as a cessation aid in patients with stable cardiac conditions, including angina and previous myocardial infarction. 6, 35

Pregnancy

Nicotine from smoking is harmful to the foetal brain and lungs and contributes to low birth weight. There is no evidence that the use of NRT is harmful to the foetus. 75

Respiratory disease

There is no evidence that nicotine causes respiratory disease in adult smokers. 6

Cytotoxicity

Nicotine is not cytotoxic. 76

Wound healing                         

Nicotine is a potent cutaneous vasoconstrictor and can impair wound healing. However, clinical trials using nicotine replacement medication to aid cessation in surgical patients indicate that the overall outcome is much better in individuals using nicotine therapy who quit smoking compared with continued smoking. 35

Positive health effects of nicotine

Nicotine

  • Enhances fine motor skills, attention and concentration, arousal and working memory. 77
  • Produces pleasure, and relief of negative affect. 78
  • Has positive effects on Alzheimer’s disease, Parkinson’s disease, ulcerative colitis
  • Assists with weight control

NICOTINE DEPENDENCE

Multiple factors contribute to the high level of addictiveness of smoking

  • Nicotine. Smokers largely smoke to avoid nicotine withdrawal
  • Other substances in tobacco smoke, such as monoamine oxidase inhibitors
  • Conditioned responses, by which certain moods, activities, people etc are associated with smoking and become smoking cues
  • The sensory and handling aspects of smoking also become associated with pleasurable effects of smoking
  • The positive effects of smoking such as arousal, stress relief (described above) 35

The use of nicotine by ENDS can generate the same effects, but without the other toxic products of combustion. However, nicotine is delivered much more slowly than from smoking and the physiological effects are therefore less intense.

ENDS users are less dependent than tobacco smokers and also less dependent than long-term nicotine gum users. 38 Etter found that ‘some vapers may be dependent on nicotine when used in e-cigarettes. They probably were already dependent on nicotine when they started vaping, and most of them declared that they vaped to avoid relapsing to smoking’. 38

JUSTIFICATION OF THE NICOTINE DOSE PROPOSED

This application proposes a

  • Maximum concentration of 3.6%
  • Maximum dose per pack of 900mg

These figures are based on the following

  • Commercially available nicotine solutions vary from 0.3% to 3.6%. Higher levels are generally needed to achieve initial smoking abstinence but users gradually reduce their nicotine concentration over time. 79 Higher doses are needed for first generation devices (cigalikes) which do not deliver nicotine as efficiently as second and third generation devices66
  • Some 20 to 30% of ENDS users use liquids above 2%. 80, 81 Heavier smokers who are more addicted to nicotine need a higher concentration of nicotine, at least initially.
  • Research supports the need for higher levels of nicotine-containing liquids (approximately 5%) to deliver nicotine more effectively and approach the nicotine-delivery profile of tobacco cigarettes. 66 The ENDS Tobacco Products Directive selected an upper limit of 2%, which is widely regarded as insufficient for many users
  • Nicotine concentrations up to 7.5% were exempt in the UK from Poisons Legislation for many years until the recent introduction of the TPD. (http://www.legislation.gov.uk/uksi/2015/966/pdfs/uksi_20150966_en.pdf) The availability of nicotine at this maximum concentration caused no known health and safety concerns for millions of vapers.
  • The safety of nicotine in overdose. People have ingested up to 1,500mg, which only led to nausea and vomiting and no other serious adverse effects. 8
  • The maximum dose of NRT in a single pack in Australia is 840mg (Nicorette 4mg gum, 210 pieces).

(D) Dosage, Formulation, labelling, packaging and presentation of a Substance

Under this proposal, nicotine would be exempted from Schedule 7 when used in low-concentrations (<3.6%) in ENDS as a tobacco substitute for non-therapeutic use and supplied in the following way:

  • nicotine concentrations up to 3.6%
  • maximum nicotine per container: 900mg
  • in a child resistant container
  • labelled with the concentration of nicotine
  • labelled with the statement ‘Keep out of reach of children’
  • labelled with the statement ‘Not to be sold to a person under the age of 18 years’

These restrictions will ensure that the use of ENDS involves minimal risk to consumers and substantially less risk than the tobacco cigarettes they are intended to replace.

(E) Potential for Misuse/Abuse of nicotine

Potential misuse/abuse of nicotine could fall under the following categories

Deliberate 82 or unintentional poisoning
see section 2C above

Use by minors or non-smokers
see section 2C above

(F) Any Other Matter that May be Relevant to the Scheduling of nicotine

Nicotine is freely available in tobacco intended for smoking which is the biggest preventable cause of death and illness in Australia. It is inappropriate to restrict nicotine in a purer, non-combustible form which is intended to reduce the harm from smoking. Nicotine is not risk free but when used in ENDS it is likely to be 95% or more safer than combusted tobacco. 24 Removing low-concentrations of nicotine for harm reduction from the Poisons Standard has the potential to save hundreds of thousands of Australian lives. 32, 60

PART 2.2 – Consideration of the factors for Schedule 7 set out in Chapter 3 of the Scheduling Policy Framework

Nicotine for agricultural use appears to be appropriately controlled within the criteria for Schedule 7. When presented in its pure form it may have a high toxicity and irritability (dermal, oral, inhalational, ocular) and a high health hazard.

However, Schedule 7 is not appropriate for nicotine in ENDS within the proposed limitations on concentration, pack content and labelling. It must be remembered that nicotine in ENDS is being used almost exclusively by smokers and recent ex-smokers for harm reduction. Any health risk from using nicotine for harm reduction must be compared to continuing to smoke and its well-known devastating health effects.

Please see the toxicology report by Bibra Consulting. 31

 The ‘factors’ for Schedule 7 from the AHMAC Scheduling Policy Framework for Medicine & Chemicals, February 2015 follow:

1. The substance has a high to extremely high toxicity

Acute LD50 (rat) is 50mg/kg or less. Acute dermal LD50 is 200mg/kg or less. Acute inhalation LC50 (rat) is 500mg/m3 (4 hours) or less. Dermal irritation is corrosive. Eye irritation is corrosive.

The Bibra report above states, ‘For nicotine, reported rat oral LD50 values range from 50-188 mg/kg bw, with most between 50-83 mg/kg bw’.

See also section 2C above. In the low concentrations used in nicotine solutions for ENDS, there is low risk of serious adverse health effects. There is no evidence of harm from inhalation, dermal exposure or eye irritation. Nicotine solutions for ENDS have been widely available since around 2006 and there is very little reported evidence of harm from its use. Doses inhaled are generally considerably lower than those from smoking.

The limitations on formulation, labelling and packaging in the proposed Schedule 7 entry will ensure that nicotine sold in use for ENDS involves minimal risk to consumers, considerably less than the tobacco cigarettes they are intended to replace.  

2. The substance has a high health hazard

The substance presents a severe hazard from repeated and unprotected use or a significant risk of producing irreversible toxicity, which may involve serious, acute or chronic health risks or even death if it is inhaled, taken internally or penetrates the skin.

See section 2C above. There is no evidence of serious health effects, except in pregnancy.

This risk does not apply to the low nicotine concentrations for vaping (0.3-3.6%). It may be applicable to the higher concentrations of nicotine covered in Schedule 7.

3. The dangers of handling the poison are such that special precautions are required in its manufacture, handling or use.

The dangers associated with handling the substance are too hazardous for domestic use or use by untrained persons and warrant restrictions on its availability, possession or use.

See section 2C above. Skin contact during handling is unlikely to have any significant clinical effect.

4. The substance has a high potential for causing harm at low exposure

The substance should be available only to specialised or authorised users who have the skills necessary to handle the substance safely. Restrictions on their availability, possession, storage or use may apply.

See section 2C above. Millions of users internationally are currently handling, storing and inhaling low concentration nicotine solutions. There is no evidence of serious harm so far and negligible risk from accidental or deliberate overdose.

Regulations would impose restrictions on nicotine concentration, bottle size and to give further protection.

 

Schedule 7 description / restrictions Applicable to ENDS?
Dangerous Poison – Substances with a high potential for causing harm at low exposure and which require special precautions during manufacture, handling or use Nicotine in ENDS within the proposed limitations does not have a “high potential for causing harm at low exposure” and does not “require special precautions during manufacture, handling or use”

Record keeping requirements, retailer must keep a record of the:

  1. a)Name and address of seller or supplier and purchaser; and
  2. b)Date of order and supply; and
  3. c)Approved name or trade name that identifies the poison to be supplied or sold; and
  4. d)Quantity supplied or sold; and
  5. e)Proof of purchaser authorisation must be recorded in jurisdictions where an authorisation is required for purchase.

(2) Records for sale or supply of Schedule 7 poisons must be kept for a minimum period of five years.

Ref: SUSMP, page 27

These requirements do not apply to the sale of tobacco products or NRT products. They are incongruous and inappropriate for nicotine use in ENDS.

Must be labelled:

  • with the signal heading: “DANGEROUS POISON (Ref: SUSMP Page 11);
  • with “Avoid contact with eyes”; and
  • with “Avoid contact with skin”

Ref: SUSMP Appendix F

For the reasons given above, the current Schedule 7 classification for nicotine in ENDS is not appropriate. Its use in ENDS does not fit the AHMAC criteria for Schedule 7.


Overall conclusions

The current Schedule 7 classification is not appropriate for low-concentration nicotine use in ENDS. Given the strength of the evidence presented, it is no longer appropriate or in the public interest to have low-concentrations of nicotine for use in ENDS more severely restricted than nicotine in tobacco or NRT.

In addition, the current restrictions are not effective with a large and growing number of Australian smokers and ex-smokers purchasing ENDS freely on the internet, from tobacconists, convenience stores and petrol stations and using them without apparent harm.

These products, while being freely available in the UK, Europe, the US and elsewhere, are effectively ‘prohibited’ in Australia. This puts the products beyond the reach of regulators and consumer protection and safety processes.

The body of evidence indicates that the hazard to health arising from long-term vapour inhalation from ENDS is unlikely to exceed 5% of the harm from smoking tobacco while offering real benefits from tobacco harm reduction, even in people not intending to quit or reduce smoking.

Paradoxically, the current laws ban a less harmful form of nicotine intake (ENDS) while allowing the sale of the most lethal form of nicotine intake (tobacco cigarettes).

This application offers an opportunity for Australian regulators to take a balanced ‘harm reduction’ approach by enabling and encouraging smokers to use ENDS in place of tobacco within a regulated legal framework.

This approach is consistent with and supportive of the objectives of the National Tobacco Strategy 2012-2018 10 : ‘reduce harm associated with continuing use of tobacco and nicotine products’ (‘A strategy to improve the health of all Australians by reducing the prevalence of smoking and its associated health, social and economic costs, and the inequalities it causes’) including priority area 7: ‘Consider further regulation of the contents, product disclosure and supply of tobacco products and alternative nicotine delivery systems’.

This proposed change has the potential to save hundreds of thousands of Australian lives. Any potential risks described above can be minimised with careful and proportionate regulation and monitoring. The initiative involves minimal public financial cost and will have a substantial positive public health impact.


Part 3 – Supporting Data

Supporting Data

Two recent comprehensive reviews of ENDS warrant special attention

1. McNeill A, Brose LS, Calder R, Hitchman SC. E-cigarettes: an evidence update, a report commissioned by Public Health England. London, Engl: Public Health England; August 2015 24. Available at https://www.gov.uk/government/publications/e-cigarettes-an-evidence-update. Reference 24

This was an independent evidence-based review that followed two previous Public Health England reviews on EC in 2014. All were based on literature reviews using systematic review methods. The 2015 review included a synthesis of scientific evidence published since the two 2014 reviews. 185 publications are referenced in the 2015 report.

Public Health England is an operationally autonomous executive agency of the Department of Health.

2. Royal College of Physicians, UK ‘Nicotine without smoke Tobacco harm reduction’. London, April 2016 3. Available at https://www.rcplondon.ac.uk/news/rcp-statement-e-cigarettes. Reference 3


PART 4 – Bibliography      

AHMAC Scheduling Policy Framework for Medicine & Chemicals, February 2015

The Australian Consumer Law, Competition and Consumer Act 2010

DIRECTIVE 2014/40/EU OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 3 April 2014 on the approximation of the laws, regulations and administrative provisions of the Member States concerning the manufacture, presentation and sale of tobacco and related products and repealing Directive 2001/37/EC

Final Decisions & Reasons for Decisions by Delegates of the Secretary to the Department of Health And Ageing, September 2011, P71-83, nicotine.

National Drugs and Poisons Schedule Committee Record of Reasons Meeting 54 October 2008, p126 – 143

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