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Scheduling delegate's interim decisions and invitation for further comment: ACCS/ACMS, March and July 2017

Scheduling medicines and poisons

15 September 2017

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3.4 Lambda-cyhalothrin

Referred scheduling proposal

An application was submitted by the Australian Pesticides and Veterinary Medicines Authority (APVMA) to amend the existing entry for lambda-cyhalothrin in Schedule 6 of the Poisons Standard to include a subclause for emulsifiable granule formulations containing 25 per cent or less lambda-cyhalothrin.

Scheduling application

This was a general application. The applicant's proposed amendments to the Poisons Standard are:

Schedule 6 – Amend Entry

LAMBDA-CYHALOTHRIN:

  1. in aqueous preparations containing 25 per cent or less of microencapsulated lambda-cyhalothrin; or
  2. in other preparations containing 1.6 per cent or less of lambda-cyhalothrin; or
  3. in emulsifiable granule formulations containing 25 per cent or less lambda-cyhalothrin

except when included in Schedule 5.

The applicant's reasons for the request are:

  • Lambda-cyhalothrin is present in a number of registered agricultural products and its toxicity profile has been well established. It is a synthetic pyrethroid insecticide which contains only two (1R cis Z-S and 1S cis Z-R) of cyhalothrin's four possible stereoisomers. Lambda-cyhalothrin insecticidal activity is believed to be through interference with sodium channels in the nervous system of insects, leading to paralysis and, eventually, death;
  • The formulated proposed product is considered to have moderate oral, low dermal and low inhalation toxicity. The product was shown to cause slight skin irritancy and moderate eye irritancy in rabbits. The studies regarding skin sensitisation were inconclusive. However, considering that lambda-cyhalothrin has previously been shown to have a positive response for sensitisation, the product will be considered to be a skin sensitiser; and
  • Based on the product acute toxicity, and providing that adequate warnings and safety directions recommended in the present report are displayed on the product label, the product formulation containing lambda-cyhalothrin meets the Scheduling Policy Framework (2015) criteria for scheduling it to Schedule 6 of the Poisons Standard.

Current scheduling status and relevant scheduling history

Lambda-cyhalothrin is currently listed in Schedules 7, 6 and 5 as follows:

Schedule 7

LAMBDA-CYHALOTHRIN exceptwhen included in Schedule 5 or 6.

Schedule 6

LAMBDA-CYHALOTHRIN:

  1. in aqueous preparations containing 25 per cent or less of microencapsulated lambda-cyhalothrin; or
  2. in other preparations containing 1.6 per cent or less of lambda-cyhalothrin

except when included in Schedule 5.

Schedule 5

LAMBDA-CYHALOTHRIN:

  1. in aqueous preparations containing 1 per cent or less of lambda- cyhalothrin; or
  2. in aqueous preparations containing 2.5 per cent or less of microencapsulated lambda-cyhalothrin.

In November 1987, the Drugs and Poisons Schedule Committee (DPSC) decided to include first aid and safety directions for lambda-cyhalothrin.

In August 1990, the DPSC decided to include preparations containing 1% or less of lambda-cyhalothrin in Schedule 6 and all other preparations containing lambda-cyhalothrin in Schedule 7, based on the toxicity profile of lambda-cyhalothrin.

In November 1991, the DPSC decided to include aqueous preparations containing 1% or less of lambda-cyhalothrin in Schedule 5. The reason for this decision was that the water-based product containing 1% or less of lambda-cyhalothrin would be used by pest control operators therefore registration mechanism would be applicable.

In November 1994, the NDPSC considered toxicological data on microencapsulated suspensions containing 2.5% or less of lambda-cyhalothrin and decided to include them in Schedule 5.

In August 1999, the NDPSC decided to include microencapsulated preparations containing 25% or less of lambda-cyhalothrin in Schedule 6.

In August 2014, the ACCS decided to increase the allowed concentration in Schedule 6 from 1.5 to 1.6 per cent is ensure that the product formulation, when expressed in grams per 100 millilitre (as per Part I of the Poisons Standard), is covered by the amended entry.

Australian regulatory information

Lambda-cyhalothrin is not listed in the Therapeutic Goods (Permissible Ingredients) Determination No. 3 of 201, and is not an excipient or active in any products on the ARTG.

There are no adverse reports relating to lambda-cyhalothrin in the APVMA's Adverse Experience Reporting Program annual reportsfrom 1995-2013.

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Lambda-cyhalothrin was included in a residue-related review of sheep ectoparasiticide (pdf,1.14Mb)* by the APVMA. However, as products containing this active were discontinued during the course of the review, no outcomes could be applied to products.

International regulations

USA

Lambda-cyhalothrin was registered with the EPA in 1989 and is registered as a biochemical/conventional chemical. It is a restricted use, broad spectrum insecticide used to control most major aphid, caterpillar and beetle pests on a wide variety of crops and for public health pests such as mosquitoes and cockroaches in non-agricultural settings.[52])

Canada

Lambda-cyhalothrin is a registered pesticide with Health Canada.

UK

Lambda-cyhalothrin was first approved for use in the UK in 1988 (Advisory Committee on Pesticides, 1988).

EU

Lambda-cyhalothrin is currently a registered product with the European Chemicals Agency.

New Zealand

Lambda-cyhalothrin is currently a registered product.

Substance summary

Lambda-cyhalothrin is a synthetic pyrethroid insecticide which contains only two (1R cis Z-S and 1S cis Z-R) of cyhalothrin's four possible stereoisomers. Lambda-cyhalothrin insecticidal activity is believed to be through interference with sodium channels in the nervous system of insects, leading to paralysis and, eventually, death.

Table 3.4.1: Chemical information for Lambda-cyhalothrin
Property Lambda-cyhalothrin
Chemical structure chemical structure of Lambda-cyhalothrin
Molecular formula C23H19ClF3NO3
Molecular weight 449.9 g/mol
CAS name (R)-cyano(3-phenoxyphenyl)methyl (1S,3S)-rel-3-[(1Z)-2-chloro-3,3,3-trifluoro-1-propen-1-yl]-2,2-dimethylcyclopropanecarboxylate
CAS number 91465-08-06
IUPAC and/or common and/or other names 3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethyl-cyano(3-phenoxyphenyl)methyl cyclopropanecarboxylate (IUPAC); Cyhalothrine (other)
Table 3.4.2: Acute toxicity end-points for Lambda-cyhalothrin
Toxicity Species Lambda-cyhalothrin SPF (2015) Classification
Acute oral toxicity LD50 (mg/kg bw) Rat 310 Schedule 6
Acute dermal toxicity LD50 (mg/kg bw) Rat >5000 Nil
Acute inhalational toxicity LC50 (mg/m3/4h) Rat 2840 Schedule 6
Skin irritation Rabbit Moderate irritant Schedule 5
Eye irritation Rabbit Slight irritant Schedule 5
Skin sensitisation Guinea pig Sensitiser Schedule 5

Acute toxicity

The applicant provided acute toxicity studies with the formulated product in rats. Based on the APVMA's assessment of these studies, the product is considered to have moderate oral (LD50= 310 mg/kg bw), low dermal (LD50 > 5000 mg/kg bw) and low inhalation toxicity (LC50 4 h >2840 mg/m3).

Repeat-dose toxicity

In a 90-day feeding study in rats given cyhalothrin, the NOAEL was 50 ppm, equal to 2.6 mg/kg bw per day, on the basis of reduced body-weight gain and food consumption. In a 90-day feeding study in rats given lambda-cyhalothrin, the NOAEL was 50 ppm, equivalent to 2.5 mg/kg bw per day, on the basis of reduced body-weight gain and food consumption. In a 26-week study in dogs fed capsules containing cyhalothrin and a 1-year study in dogs fed capsules containing lambda-cyhalothrin, increased incidences of liquid faeces was observed, with an overall NOAEL of 0.1 mg/kg bw per day. The increased incidences of liquid faeces were observed from the first week of treatment. Other pyrethroids produce this effect, which may be the consequence of the local gastrointestinal equivalent of paraesthesia in the skin. In the two studies in dogs, signs of systemic neurotoxicity (ataxia, tremors, and occasionally convulsions) were observed, with an overall NOAEL of 0.5 mg/kg bw per day. Signs of systemic neurotoxicity were observed from the first week and generally occurred within a few hours after treatment.

Skin irritation

There were no mortalities or clinical signs of systemic toxicity. All treated sites exhibited well-defined erythema and very slight oedema 24 h after removing the dressings, and desquamation between Day 7 and Day 10. All treated sites were free of dermal lesions on Day 10. Lambda-cyhalothrin is considered a slight skin irritant.

Eye irritation

There were no mortalities or clinical signs of systemic toxicity. All treated eyes exhibited corneal opacity, iritis, and conjunctivitis following instillation of the test item. All treated eyes were free of ocular irritation by Day 10. Lambda-cyhalothrin is considered a moderate eye irritant.

Sensitization

The studies regarding skin sensitisation were inconclusive. However, considering that lambda-cyhalothrin has previously been shown to have a positive response for sensitisation, lambda-cyhalothrin is considered a skin sensitiser.

Genotoxicity

Lambda-cyhalothrin was tested for genotoxicity in an adequate range of assays, both in vitro and in vivo. No evidence for genotoxicity was observed in any test.

Carcinogenicity

Lambda-cyhalothrin is not carcinogenic in rodents. In view of the lack of genotoxicity of lambda-cyhalothrin and the absence of carcinogenicity shown by cyhalothrin in mice and rats, the JMPR (2007) concluded that lambda-cyhalothrin is unlikely to pose a carcinogenic risk to humans.

Reproduction and developmental toxicity

In a multigenerational dietary study with cyhalothrin in rats, the NOAEL for parental toxicity was 30 ppm, equivalent to 2.0 mg/kg bw per day, on the basis of a reduction in body-weight gain. The NOAEL for offspring toxicity was 30 ppm, equivalent to 2 mg/kg bw per day, on the basis of reduced body-weight gain during lactation. The NOAEL for reproductive toxicity was 100 ppm, equivalent to 6.7 mg/kg bw per day, i.e., the highest dose tested.

The effect of oral exposure to cyhalothrin on prenatal development was investigated in rats and rabbits. In a study of developmental toxicity in rats treated by gavage, the NOAEL for maternal toxicity was 10 mg/kg bw per day on the basis of a reduction in body weight and loss of limb coordination. The NOAEL for foetal toxicity was 15 mg/kg bw per day, i.e., the highest dose tested.

In a study of developmental toxicity in rabbits treated by gavage, the NOAEL for maternal toxicity was 10 mg/kg bw per day on the basis of reduced body-weight gain and food.

Neurotoxicity

In a study of acute neurotoxicity in rats given lambda-cyhalothrin by gavage, the NOAEL was 2.5 mg/kg bw per day on the basis of signs of neurotoxicity (increased breathing rate, urinary incontinence, salivation, reduced response to sound).

There were no signs of maternal or offspring toxicity observed in the developmental neurotoxicity study for lambda-cyhalothrin.

Observation in humans

In case reports in humans, no systemic effects were reported. In most cases exposure was by the dermal and inhalation routes. Predominant signs were skin paraesthesia, numbness, irritation of the skin, red eyes, coughing and sneezing.

Public exposure

The product use patterns, application methods and use rates are the same as the registered reference product which contains 250 g/L lambda-cyhalothrin in an emulsifiable concentrate microencapsulated formulation. Therefore, similar exposure is expected using either the proposed product, or the reference, provided that the same safety directions are applied while mixing/loading and using both products, which includes wearing the same PPE when opening the container and preparing spray and using the prepared spray. Therefore, new exposure estimates are not required. Post-application exposure is considered similar with the proposed product and with the reference product, provided that the same re-entry statements are displayed on both products' labels. Therefore, new post-application exposure estimates are not required.

Pre-meeting submissions

One (1) public submission was received that supported the proposal on the basis of the acute oral toxicity of lambda-cyhalothrin.
The public submission will be made available on the TGA website.

Summary of ACCS advice to the delegate

The committee recommended that the Schedule 6 listing for lambda-cyhalothrin be amended as follows:

Schedule 6 – Amend Entry

LAMBDA-CYHALOTHRIN:

  1. in aqueous preparations containing 25 per cent or less of microencapsulated lambda-cyhalothrin; or
  2. in emulsifiable granule formulations containing 25 per cent or less lambda-cyhalothrin; or
  3. in other preparations containing 1.6 per cent or less of lambda-cyhalothrin

except when included in Schedule 5.

The committee also recommended an implementation date of 1 February 2018.

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 and extent of use; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; and (e) the potential for abuse of a substance.

The reasons for the advice were:

  • Lambda-cyhalothrin is already used in Australian in aqueous preparations in a microencapsulated form. The product formulation change to emulsifiable granule is not expected to greatly increase the current use of lambda-cyhalothrin.
  • Use of emulsifiable granules containing 25% or less of lambda-cyhalothrin, in addition to the aqueous products containing microencapsulated lambda-cyhalothrin, is expected to be mainly commercial, resulting in an increased choice of agricultural insecticides available for end users.
  • There were no reported cases of adverse events involving lambda-cyhalothrin between 1995 and 2013, which suggests a low risk with the existing controls in place.
  • Lambda-cyhalothrin has moderate acute oral toxicity, is a slight skin irritant, is a skin sensitiser and a moderate eye irritant. It meets the Schedule 6 criteria. There is no evidence to suggest the emulsifiable formulation has increased toxicity to the end-user.
  • Lambda-cyhalothrin would be managed by APVMA registration processes and is expected to be in line with aqueous products containing microencapsulated lambda-cyhalothrin.
  • The potential for abuse of lambda-cyhalothrin is low to none.

Delegate's considerations

The delegate considered the following regarding this proposal:

  • Scheduling proposal
  • ACCS advice
  • Public Submissions received
  • Section 52E of the Therapeutic Goods Act 1989
  • Scheduling Policy Framework (SPF 2015)
  • Other relevant information

Delegate's interim decision

The delegate's interim decision is to amend the Schedule 6 listing for lambda-cyhalothrin to include emulsifiable granule formulations containing 25 per cent or less of lambda-cyhalothrin. The proposed Schedule entry is as follows:

Schedule 6 – Amend Entry

LAMBDA-CYHALOTHRIN:

  1. in aqueous preparations containing 25 per cent or less of microencapsulated lambda-cyhalothrin; or
  2. in emulsifiable granule formulations containing 25 per cent or less lambda-cyhalothrin; or
  3. in other preparations containing 1.6 per cent or less of lambda-cyhalothrin

except when included in Schedule 5.

The proposed implementation date is 1 February 2018, as this is the earliest possible implementation date.

The matters under subsection 52E(1) of the Therapeutic Goods Act 1989 considered relevant by the delegate included: (a) the risks and benefits of the use of a substance; (b) the purposes for which a substance is to be used and the extent of use of a substance; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; and (e) the potential for abuse of a substance.

The reasons for the interim decision are:

  • Lambda-cyhalothrin is already used in Australian in aqueous preparations in a microencapsulated form. The product formulation change to emulsifiable granule is not expected to greatly increase the current use of lambda-cyhalothrin.
  • Use of emulsifiable granules containing 25% or less of lambda-cyhalothrin, in addition to the aqueous products containing microencapsulated lambda-cyhalothrin, is expected to be mainly commercial, resulting in an increased choice of agricultural insecticides available for end users.
  • There were no reported cases of adverse events involving lambda-cyhalothrin between 1995 and 2013, which suggests a low risk with the existing controls in place.
  • Lambda-cyhalothrin has moderate acute oral toxicity, is a slight skin irritant, is a skin sensitiser and a moderate eye irritant. It meets the Schedule 6 criteria. There is no evidence to suggest the emulsifiable formulation has increased toxicity to the end-user.
  • Lambda-cyhalothrin would be managed by APVMA registration processes and is expected to be in line with aqueous products containing microencapsulated lambda-cyhalothrin.
  • The potential for abuse of lambda-cyhalothrin is low to none.

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