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Scheduling delegate's final decisions, March 2016

Scheduling medicines and poisons

17 March 2016

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1.1 1,3-Dichloropropene

Part A - Final decisions on matters referred to an expert advisory committee

1. Scheduling proposals referred to the November 2015 meeting of the Advisory Committee on Chemicals Scheduling (ACCS#15)

1.1 1,3-Dichloropropene

Scheduling proposal

The chemicals scheduling delegate has referred the following scheduling proposal for consideration by the Advisory Committee on Chemicals Scheduling (ACCS):

  • In August 2015, the delegate received a request to consider amending an entry for 1,3-dichloropropene in Schedule 7 of the SUSMP to allow for 0.3 per cent or less in biocidal formulations.
Scheduling application

The reasons for the request were:

  • The applicant suggested it to be extremely difficult and not economically feasible to remove 1,3-dichloropropene to non-detectable levels after the production process from the antimicrobial products CTAS and cis-CTAC.
  • In the CTAC and cis-CTAC production process, 1,3-dichloropropene, one of the raw materials, is added in slight excess to ensure the complete reaction of other raw materials. Removal of the excess 1,3-dichloropropene is to a level of less than 0.3% in the final CTAC product. To reduce the level of 1,3-dichloropropene in the final product to a consistently non-detectable level would require additional processing steps and/or equipment addition to the current production process, and would not be economically feasible for continued long-term manufacture of the product.
  • The reasons outlined by the applicant for the request to down-schedule 1,3-dichloropropene are those of an economic nature and that the antimicrobial products CTAC and cis-CTAC, of which 1,3-dichloropropene is requested to be exempt from scheduling, are compliant to EU and US regulations. The consumables that CTAC and cis-CTAC are present in are quite broad, ranging from detergents, floor waxes and polishes, adhesives, construction materials, paints, inks, latex emulsions, metalworking fluids, and spinning fluids for textiles, as well as paper and paperboard packaging for dry foods. There is no outline of human health risks in their request, that is, the potential consequences that a down-scheduling of 1,3-dichloropropene may pose to human health.
Specific issues/questions raised by the delegate

The delegate asked the committee the following questions:

  • Does the ACCS support the applicant's proposal to create an exemption cut-off of 0.3% in the current Schedule 7 entry for 1,3-dichloropropene?
  • Should such an exemption be limited to its presence as an impurity in the specific substances mentioned in the applicant's submission; namely methanamine-3-chloroallylochloride (CTAC and cis-CTAC), or should it apply more broadly to biocidal products?
  • What weight should be given to the applicant's advice that CTAC and cis-CTAC containing up to 0.3% 1,3-dichlorpropene are compliant with EU and US regulations?
  • In Part 1, there is a general, exemption from the schedules when substances are present at a concentration below 10 mg/kg (0.001%). However, this exemption does not apply to substances listed in Schedule 7.
  • Appendix G provides for low level exemptions for substances, including some Schedule 7 substances such as arsenic, selenium (although there are additional exemptions in sub-clauses of their S7 entries). Would listing of 1,3-dichloropropene in Appendix G be an alternative to amending the Schedule 7 entry?
Substance summary
Chemical structure of 1,3-dichloropropene

Figure 1. Structure of 1,3-dichloropropene

No toxicity profile was on 1,3-dichloropropene nor the active ingredients CTAC and cis-CTAC by the applicant. The following information was extracted from NICNAS and Safe Work Australia websites.

An Environmental Health Criteria report on 1,3-dichloropropene can be found here at IPCS INCHEM.

Hazard classification

1,3-Dichloropropene is classified as hazardous, with the following risk phrases for human health in the HSIS:

  • T; R24/25 (acute toxicity);
  • Xn; R20–65 (acute toxicity, aspiration hazard); and
  • Xi; R36/37/38 (irritation).
Acute toxicity

No information provided by the applicant.

Repeated-dose toxicity

No information provided by the applicant.

Mutagenicity

No information provided by the applicant.

Genotoxicity

No information provided by the applicant.

Carcinogenicity

No information provided by the applicant.

1,3-Dichloropropene is listed in IARC Group 2B (possibly carcinogenic to humans) carcinogens.

Safe Work Australia place 1,3-dichloropropene as a Category 3 carcinogen. Substances suspected of having carcinogenic potential are those substances which have possible carcinogenic effects on humans but in respect of which the available information is not adequate for making a satisfactory assessment. There is some evidence from appropriate animal or epidemiological studies, but this is insufficient to place the substance in Category 2.

1.1 Animal studies

Technical-grade dichloropropene (containing 1% epichlorohydrin) was administered to mice and rats. Dose-related increases in the incidences of tumours of the urinary bladder, lung and fore stomach were observed in mice. In male rats, dose-related increases in the incidences of benign and malignant fore stomach tumours and benign liver tumours were reported; in female rats, benign fore stomach tumours were found.

In one study of subcutaneous administration in female mice, the cis isomers produced malignant tumours at the site of injection. However, skin application of the cis isomers to mice has not produced any conclusive results.

The International Agency for Research on Cancer (IARC) has reviewed many animal inhalation studies, but failed to demonstrate a relationship between inhalation exposure and tumour production.

1.2 Human studies

Two case reports of human malignancy were reviewed by the IARC. There are no epidemiological studies of human carcinogenicity known to the Exposure Standards Working Group.

2. Conclusion

Technical-grade dichloropropene (containing 1% epichlorohydrin) is carcinogenic to experimental animals through oral administration. Carcinogenicity of dichloropropene through inhalation has not been demonstrated in animals.

There is inadequate evidence for carcinogenicity of dichloropropene in humans.

3. Recommendation for carcinogen category

After reviewing the relevant data, the Exposure Standards Working Group is of the view that dichloropropene may have carcinogenic potential to humans, based on the limited evidence from animal studies, but the available information is not adequate for making a satisfactory assessment. The Working Group recommends that dichloropropene be classified as Category 3 carcinogen (Substance Suspected of having Carcinogenic Potential). The reader is encouraged to review the section on Carcinogens in the Guidance Note on the Interpretation of Exposure Standards for Atmospheric Contaminants in the Occupational Environment, for guidance on the classification system of carcinogens.

Reproduction and developmental toxicity

No information provided by the applicant.

Observation in humans

No information provided by the applicant.

Public exposure

No information provided by the applicant.

NICNAS IMAP states 1,3-dichloropropene has an exposure standard of 4.5 mg/m3 (1 ppm) time weighted average (TWA) (Galleria Chemica).

International regulations

The applicant outlined in their proposal that their antimicrobial CTAC and cis-CTAC substances, of which 1,3-dichloropropene is a product of their manufacture, are compliant to international regulations in the EU and USA. The international regulations for 1,3-dichloropropene, the substance in question, were not provided. These are outlined below.

1,3-dichloropropene is listed on the Health Canada List of prohibited and restricted cosmetic ingredients (The Cosmetic Ingredient 'Hotlist').

A TWA of 4–5 mg/m3 (1 ppm) in Canada, Denmark, Iceland, Norway, and the USA, and 0.5 mg/m3 (0.11 ppm) in Germany and Switzerland.

A STEL of 50 mg/m3 (10 ppm) in Ireland and South Africa, and 2 ppm in Canada (Saskatchewan).

Scheduling status

1,3-Dichloropropene is currently listed in Schedule 7 and Appendix J.

Appendix J, Part 2
Poisons Standard statements
1,3-dichloropropene Condition 1: Not to be available except to authorised or licensed persons.
Scheduling history

1,3-Dichloropropene was previously marketed in Australia but its withdrawal by the sponsor (Dow Chemical (Australia) Ltd) was notified to the PACC in 1987, due to recommendations by the Committee, that it would cease its sale and distribution in Australia of Telone II, which comprised 91% of 1,3-dichloropropene. Prior to 1994, commercial formulations included up to 1% of the known genotoxic carcinogen, epichlorohydrin, while post-1994 commercial formulations have included epoxidised soybean oil as a stabiliser.

In November 2000, at the #29 NDPSC meeting, Dow Agrosciences Australia Ltd had submitted data in support of the technical grade active constituent 1,3-dichloropropene and the registration of two end-use-products Telone® Soil Fumigant (1140g/L) and Telone® C-35 Soil Fumigant (825g/L + chloropicrin 460g/L). These products were proposed for use by professional and accredited fumigators in the treatment of a range of soil borne diseases, nematodes, wireworms and other plant parasites as a pre-planting soil fumigant. The proposal was to delete the Appendix J entry and reschedule 1,3-dichloropropene to Schedule 6. This proposal was not supported by the Committee who decided that the current Schedule 7 and Appendix J entries for 1,3-dichloropropene were to remain appropriate. This was made in part due to the Committee noting that the proposed use was limited to accredited fumigators and that this could be enforced as a Restricted Chemical Product (NRA registration) in some jurisdictions. However, other jurisdictions had no legislative mechanism apart from Schedule 7/Appendix J to enforce such controls over use. It was in addition, noted that the request for rescheduling had arisen as a consequence of the new toxicology evaluation and had not been requested by the company.

Pre-meeting public submissions

No public submission was received.

ACCS advice to the delegate

The Committee recommended that the Schedule 7 entry for 1,3-dichloropropene be amended as follows:

Schedule 7 - Amend Entry

1,3-DICHLOROPROPENE except when in biocidal formulations at 0.3 per cent or less.

The committee recommended an implementation date 1 June 2016.

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the Committee included: (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.

The reasons for the recommendations comprised the following:

  • manufacturing impurity in biocide and low risk to human health at concentrations of 0.3% or less in biocides
Delegate's considerations

The delegate considered the following in regards to this proposal:

  • Scheduling proposal;
  • ACCS advice;
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling factors1;
  • Other relevant information.
Delegate's interim decision

The delegate's interim decision is to accept the advice of the Committee and amend the Schedule 7 entry of 1,3-dichloropropene. The earliest practicable implementation date is warranted since the objective is to amend existing controls for biocidal products already on the market.

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

Schedule entry
Schedule 7 - Amend Entry

1,3-DICHLOROPROPENE except in biocidal preparations containing 0.3 per cent or less of 1,3-dichloropropene.

Public submissions on the interim decision

No public submissions were received.

Delegate's final decision

The delegate has confirmed the interim decision as no evidence has been received to alter the interim decision. The delegate has confirmed that the reasons for the final decision are in keeping with those for the interim decision.

Schedule entry
Schedule 7 - Amend entry

1,3-DICHLOROPROPENE except in biocidal preparations containing 0.3 per cent or less of 1,3-dichloropropene.

The proposed implementation date is 1 June 2016.


Footnotes

  1. Scheduling Policy Framework for Medicines and Chemicals (SPF, 2015)

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