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Scheduling delegate's interim decisions and invitation for further comment: ACCS/ACMS, July 2016

Scheduling medicines and poisons

15 September 2016

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2.3 Phenol

Note

  • Red strikethrough text indicates text that has been deleted.
  • Green italicised text indicates text that has been added.
Referred scheduling proposal

An application was submitted to amend the existing Schedule 6 entry for phenol to include cosmetic use with an appropriate concentration cut-off and to consider appropriate Appendix E and F statements.

Scheduling history

Phenols were first included in Schedule 2 in January 1955 as carbolic acid (phenol), cresylic acid and other homologues containing 3% or more by weight of such poison except (a) in the provisions of Schedules 5 or 6; (b) in smelling salts; (c) a compound of a phenol with a metal. The Schedule 5 entry for carbolic acid was for all liquid substances containing less than 3% by weight of phenol or its homologues for use as a disinfectant. An entry was also included in Schedule 5 as phenyle when containing less than 3% phenol or its homologues for use as a disinfectant. Phenol and homologues (all preparations containing more than 3% of such substance) were also included in Appendix 1, advising on a statement requirement for the poison. There was no specific entry for phenol or carbolic acid in Schedule 6.

In February 1991, the Drugs and Poisons Schedule Standing Committee (DPSSC) considered an apparent conflict between entries in Appendix E for phenols and xylenols. The committee advised that standard statement 'J' be modified by the addition of "do not induce vomiting" in order to make it clearer. The committee felt that this proposal should be brought back to committee when a review of the issue of first aid for phenolic substances had been completed.

In August 1994, editorial amendments were made to the Schedule 2 entry for phenol to specify preparations for external use containing 3 per cent or less of phenol for human therapeutic use.

In November 1998, the National Drugs and Poisons Committee (NDPSC) agreed with working party recommendations to the New Zealand Ministry of Health to amend the Schedule 1 entry for phenol. The recommendations included adoption into Part 1, Schedule 1 of the Medicines Act of Phenol in medicines for injection, amendment of the part III entry to include phenol, in medicines other than for injection, containing more than 3 per cent of phenol. The committee deferred advice to remove the words 'for therapeutic use' from the current Schedule 4 entry for phenol, remove the wording 'For Human therapeutic use' in Schedule 2 and temperature references were replaced with separate entries for phenol, cresol and xylenol and replace the Schedule 6 entry with phenol, (including cresols and xylenols) or any homologue of phenol boiling below 220 degrees Celsius, except (a) for therapeutic use (b) in preparations containing 3 per cent or less of such substances.

Between February 1999 and February 2000, the National Drugs and Poisons Schedule Committee (NDPSC) considered a proposal to delete the words 'therapeutic use' from Schedule 4 and 2 entries for numerous substances, including phenols. It was agreed to amend the entries to remove this wording in February 2000.

Between February 2001 and October 2002, the National Drugs and Poisons Schedule Committee (NDPSC) considered the first aid instruction Appendix E Part 2 statements for phenols, replacing a,c,j,s with A, G3, E2, with S3 for concentrations below 25% phenols. The committee also agreed that the statement S4 should be included in first aid instructions (instead of S3) for phenols at concentrations above 25 per cent.

Current scheduling status

Phenol is currently listed in Schedule 6 for industrial use with a number of exceptions. It is also listed in Schedules 2, 4 and 5 for non-industrial uses. The Schedule 5 entry relates to use in animal feed.

Phenol

Schedule 6

PHENOL, including cresols and xylenols and any other homologue of phenol boiling below 220°C, except:

  1. when separately specified in these Schedules;
  2. when included in Schedule 5; or
  3. in preparations containing 3 per cent or less of such substances.

Schedule 5

PHENOL, including cresols and xylenols and any other homologue of phenol boiling below 220°C, when in animal feed additives containing 15 per cent or less of such substances, except in preparations containing 3 per cent or less of such substances.

Schedule 4

PHENOL in preparations for injection.

Schedule 2

PHENOL, or any homologue boiling below 220°C, for human therapeutic use except:

  1. when included in Schedule 4; or
  2. in preparations for external use containing 3 per cent or less of such substances.

Appendix E

PHENOLS:

Standard statements:

  • at 25 per cent and less: A [For advice, contact a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor (at once)], G3 (If swallowed, do NOT induce vomiting), E2 (If in eyes, hold eyelids apart and flush the eye continuously with running water. Continue flushing until advised to stop by a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor, or for at least 15 minutes), S3 (If on skin, remove any contaminated clothing, wash skin thoroughly with soap and water, then methylated spirit if available. Contact a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor)
  • above 25 per cent: A [For advice, contact a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor (at once)], G3 (If swallowed, do NOT induce vomiting), E2 (If in eyes, hold eyelids apart and flush the eye continuously with running water. Continue flushing until advised to stop by a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor, or for at least 15 minutes), S4 (If on skin, immediately remove any contaminated clothing, wash skin with methylated spirit or PEG (polyethylene glycol) 300 or 400 if available, then flush under running water until advised to stop by a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor)

PHENOLS in pressurised spray packs:

Standard statements: A [For advice, contact a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor (at once)], E1 (If in eyes wash out immediately with water)

Appendix F

PHENOL and any other homologue of phenol:

Safety directions: 1 (Avoid contact with eyes), 4 (Avoid contact with skin)

Safety direction: 5 (Wear protective gloves when mixing or using)

Creosote

Schedule 6

CREOSOTE derived from wood other than beechwood except:

  1. when included in Schedule 2;
  2. in preparations for human therapeutic use containing 10 per cent or less of creosote derived from wood other than beechwood; or
  3. in other preparations containing 3 per cent or less of phenols and homologues of phenol boiling below 220°C.
Cresols

Appendix E

CRESOLS

Standard statements: A [For advice, contact a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor (at once)], G3 (If swallowed, do NOT induce vomiting), E2 (If in eyes, hold eyelids apart and flush the eye continuously with running water. Continue flushing until advised to stop by a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor, or for at least 15 minutes), S3 (If on skin, remove any contaminated clothing, wash skin thoroughly with soap and water, then methylated spirit if available. Contact a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor)

CRESOLS in pressurised spray packs:

Standard statements: A [For advice, contact a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor (at once)], G6 (If sprayed in mouth, rinse mouth with water), E1 (If in eyes wash out immediately with water), S1 (If skin or hair contact occurs, remove contaminated clothing and flush skin and hair with running water)

Other relevant information

Public exposure

Although use in cosmetic and domestic products in Australia is not known, phenol has reported cosmetic and domestic uses overseas, where the general public may be exposed to phenol through dermal and/or inhalation routes.

Internationally phenol has reported potential domestic use including as a general disinfectant and in adhesives, paints, lacquers and varnishes. Phenol has reported cosmetic use with the following functions:

  • antimicrobial;
  • deodorant;
  • denaturants;
  • masking;
  • oral care; and
  • preservative.

Whilst use in cosmetics is prohibited in some countries there is reported use of phenol in cosmetics in the United States of America.

Phenol has reported non-industrial uses including in medical preparations including lotions, ointment, mouthwashes etc., and in pesticides.

International regulations

Phenol is listed on the following:

  • European Union Cosmetic Directive 76/768/EEC Annex II - List of substances which must not form part of the composition of cosmetic products;
  • New Zealand Cosmetic Products Group Standard - Schedule 4: Components cosmetic products must not contain; and
  • Health Canada List of Prohibited and Restricted Cosmetic Ingredients ("Hotlist").
Scheduling application

General application.

The applicant's proposed amendments to the SUSMP are as follows:

Schedule 6 - Amend Entry

PHENOL, including cresols and xylenols and any other homologue of phenol boiling below 220°C, except:

  1. when separately specified in these Schedules;
  2. when included in Schedule 5; or
  3. in preparations for cosmetic use containing 1 or less of such substances; or
  4. in preparations other than for cosmetic use containing 3 per cent or less of such substances.

The applicant's reasons for the request are:

  • Given the risk characterisation, it is advised that phenol remain in Schedule 6, but the allowable concentration of phenol in cosmetics/personal care products and domestic products be further restricted. The safety directions and warning statements should also be reviewed; and
  • The current entry for phenol is complex and includes additional chemicals, including cresols and xylenols. Any change to the scheduling of phenol will have flow on effects to these other chemicals. Within the cresols and xylenols, cresols are expected to represent worst case toxicity. The IMAP assessment for cresols (which is supportive of the current controls for cresols) should be taken into account in determining whether changes in cut-off concentrations should apply to the current entry as written in the SUSMP, or whether separate entries for phenol and homologues of phenols should be created.
  • In Australia, for industrial uses, phenol is currently listed in Schedule 6 of the SUSMP for preparations containing greater than 3 %. At concentrations greater than 3 %, a number of first aid instructions and safety directions relating to skin and eye contact apply. The current Schedule entry covers phenol and a number of substituted phenols;
  • Given that necrosis has been seen in humans following exposure to solutions diluted as 1 %, phenol may pose an unreasonable risk to public health, particularly in cosmetic products when purposely applied to the skin. The risks could be mitigated by reducing the concentration limit permitted in products without the need for safety directions. Typically, the risk of systemic effects would also be reduced for products containing lower concentrations of phenol; and
  • As vapours can readily penetrate the skin surface, safety directions relating to the use of phenol in the presence of adequate ventilation may also minimise risk associated with the use of products with higher phenol concentrations that come under Schedule 6.
  • although use in cosmetic and domestic products in Australia is not known, phenol has reported cosmetic and domestic uses overseas;
  • phenol has been reported to cause poisoning in humans by ingestion, skin absorption, and by inhalation;
  • necrosis of human skin has been reported at concentrations as low as 1 %;
  • local exposure to phenol may diminish the sensation of pain, possibly leading to less awareness and thus higher degrees of local damage; and
  • With respect to cresol, the use of the cresols in cosmetic and consumer products is not anticipated in Australia. Hence, the public risk from these chemicals is not considered to be unreasonable. In addition, cresols are less corrosive than phenol with corrosive effects not seen at or below 3 %.
Substance summary

Phenol (Figure 2.3) is colourless to light pink crystalline solid with a distinct aromatic, and somewhat sickening sweet and acrid odour.

Figure 2.3: Structure of phenol

Figure 2.3: Structure of phenol

Acute toxicity

The acute toxicity end-points for phenol are listed in Table 2.3 and are publically available in the NICNAS Human Health Tier II assessment report for phenol. Briefly, based on available data, phenol has moderate to high acute oral and dermal toxicity in animals. Limited data are available on acute inhalation toxicity. However, phenol is classified as hazardous with the risk phrase 'Toxic by inhalation' (T; R23) in HSIS (Safe Work Australia). Median lethal concentration (LC50) values on acute inhalation toxicity tests with animals are not available (ECB, 2006). Rats are reported to have tolerated phenol concentrations as high as 236 ppm (900 mg/m3) for eight hours, resulting in ocular and nasal irritation, loss of coordination, tremors, and prostration. Phenol has been reported to cause poisoning in humans from ingestion, skin absorption, and by inhalation. Signs and symptoms of acute toxicity of phenol in laboratory animals and humans are similar regardless of the route of administration. Oral toxicity of phenol in humans leading to the death of the victim is reported for doses as low as 140-290 mg/kg bw. Death following dermal application of phenol has been reported. Following skin contact, absorption is very rapid and the symptoms develop rapidly (within 15-20 minutes). Death can occur within 30 minutes to several hours. Skin necrosis and irreversible effects on the eyes have been observed in irritation studies in rabbits. Signs of respiratory irritation have been observed in a number of animal studies following acute and repeat inhalation exposure to phenol. There have been frequent reports of human experience with occupational exposure to phenol (since 1871). Based on these experiences, phenol has been reported to cause burns in humans. While a 10 % solution of phenol has been reported to produce corrosion in humans, occasionally skin necrosis has also been seen with solutions as dilute at 1 % (ECB, 2006). It has been noted that, due to the local anesthetic properties of phenol, no pain is experienced at initial contact with skin and a white wrinkled discolouration is formed.

Toxicity Species Phenol SPF (2015) Classification
Acute oral toxicity
LD50 (mg/kg bw)
Rats 340-530 mg/kg bw Schedule 6
Humans 140-290 mg/kg bw
Acute dermal toxicity
LD50 (mg/kg bw)
Rats 660-707 mg/kg bw Schedule 6
Acute inhalation toxicity
LC50 (mg/m3/4h)
Rats, Humans Limited data available* -
Skin irritation Humans, Rabbits Corrosive Schedule 7
Eye irritation Rabbits Corrosive Schedule 7
Skin sensitisation (Buehler) Guinea Pig Not sensitising* Appendix B or Schedule 5
Genotoxicity Mice

Positive (intraperitoneal)

Negative/equivocal (orally)

N/A
Carcinogenicity Rats, Mice Negative* N/A
Reproduction and developmental toxicity Rats, Mice Negative* N/A

* For more information see the NICNAS Human Health Tier II assessment report for phenol.

Genotoxicity

Phenol tested positive in several in vitro genotoxicity assays. For in vivo studies, while generally positive results have been obtained with the intraperitoneal route, negative or equivocal results have been obtained with the oral route. This route-related difference is likely to be due to the potential for first-pass detoxification of phenol when it is administered by the oral route, but not when administered intraperitoneally. The genotoxic potential of phenol appears to depend on the competing processes of activation to a genotoxic form and metabolic inactivation (e.g., by conjugation).

Carcinogenicity

Phenol was not carcinogenic in rats and mice up to and including the highest doses tested (450 and 375 mg/kg bw/d, respectively). Based on the extensive use of phenol over the years, there are no epidemiological data that reveals an association of exposure to phenol with increased tumour rates in humans (ECB, 2006).

Reproduction and developmental toxicity

There is no evidence of reproductive toxicity. Developmental effects were only observed secondary to maternal toxicity. Therefore, phenol is not expected to have specific developmental toxicity in humans.

Repeat dose toxicity

Repeated dose studies in animals showed toxic effects on target tissues such as the kidneys, liver, lungs, the haematopoietic system and nervous system, although effects were not consistent between studies. Based on the available data it appears that the toxicity of phenol is related to peak blood levels rather than total dose delivered.

Pre-meeting public submissions

One public submission was received that supported the scheduling proposal. However, the submission suggested a new entry for phenol, with exclusion to salts and derivatives, to apply for cosmetics except in preparations containing 0.1% or less of phenol. This would align with the EU standards and allow for products that contain phenol as an impurity.

The main points were:

  • No objection to the ban of phenol in cosmetics;
  • Phenols are currently listed in Annex II of the EU Cosmetic Regulations (banned in cosmetics in the EU); however, xylenol and cresol and potentially other derivatives of phenol with boiling points below 220°C are used in cosmetics with no regulatory restrictions;
  • A new entry for phenol, excluding salts and derivatives, be created to apply specifically to cosmetics; and
  • In line with EU requirements, propose that products containing up to 0.1% phenol be exempt from scheduling.

The public submission is available on the TGA website.

Summary of joint ACMS/ACCS Advice to the delegates

The committee advised that the current Schedule 6, 5 and 2 entries for phenol be amended as follows:

Schedule 6 - Amend entry

PHENOL, including cresols and xylenols and any other homologue of phenol boiling below 220°C, except:

  1. when separately specified in these Schedules; or
  2. when included in Schedule 5; or c) in preparations containing 1 per cent or less of phenols, and in preparations containing 3 per cent or less of such substances cresols and xylenols and other homologues of phenol.

Schedule 5 - Amend Entry

PHENOL, including cresols and xylenols and any other homologue of phenol boiling below 220°C, when in animal feed additives containing 15 per cent or less of such substances, except in preparations containing 1 per cent or less of phenol and in preparations containing 3 per cent or less of such substances cresols and xylenols and other homologues of phenol.

Schedule 2 - Amend Entry

PHENOL, or any homologue boiling below 220°C for human therapeutic use, except:

  1. when included in Schedule 4; or
  2. in preparations for external use containing 1 per cent or less of phenol and in preparations for external use containing 3 per cent or less of such substances cresols and xylenols and other homologues of phenol.

The committee advised that Appendix E and F entries be created as follows:

Appendix E - PHENOL when included in Schedule 6.

Standard Statements: A [for advice, contact a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor (at once)], E1 (if in eyes wash out immediately with water).

Warning Statements: 3 (corrosive liquid), 51 (irritant to skin, eyes, mucous membranes and upper respiratory tract).

Appendix F - PHENOL when included in Schedule 6.

Safety Directions: 2 (attacks eyes - protect eyes when using), 4 (avoid contact with skin), 8 (avoid breathing dust (or) vapour (or) spray mist).

The committee advised an implementation date of 1 February 2017.

Members agreed that the relevant matters under Section 52E (1) of the Therapeutic Goods Act 1989 included: (a) risks and benefits of the use of a substance; (b) the purpose for which a substance is to be used and the extent of use; and (c) the toxicity of a substance.

The reasons for the advice included:

  • Phenol displays human systemic toxicity, orally, by inhalation and through dermal absorption;
  • Necrosis of human skin has been reported at concentrations as low as 1 %;
  • Local exposure to phenol may diminish the sensation of pain, possibly leading to less awareness and thus higher degrees of local damage;
  • European Union and New Zealand have banned its used in cosmetic products, and it is included on Health Canada List of Prohibited and Restricted Cosmetic Ingredients;
  • Phenol is corrosive and is reported to induce skin necrosis in humans at a concentration of 1 %. This is especially problematic in the case of accidental skin exposure because the local anaesthetic properties of phenol may result in a delayed pain response resulting in chemical burns; and
  • Phenol has widespread industrial and minor therapeutic use.
Delegates' considerations

The delegate considered the following in regards to this proposal:

  • Scheduling proposal;
  • ACCS/ACMS advice;
  • Public submissions received;
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling Policy Framework (SPF 2015);
  • Other relevant information.
Delegates' interim decision

The delegates note and accept the ACCS-ACMS advice to amend the Schedule 6, Schedule 5 and Schedule 2 entries for phenol. The delegates note that this advice is primarily based on the acute toxicity profile for phenol including reports of human systemic toxicity orally, by inhalation and through dermal absorption. Phenol is corrosive and is reported to induce skin necrosis in humans at concentrations as low as 1 per cent. This is especially problematic in the case of accidental skin exposure because the local anaesthetic properties of phenol may result in a delayed pain response resulting in a higher degree of local damage.

The proposed implementation date is 1 February 2017.

The delegate considered the relevant matters under section 52E (1) of the Therapeutic Goods Act 1989: (a) risks and benefits of the use of a substance; (b) the purpose for which a substance is to be used and the extent of use; and (c) the toxicity of a substance.

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