You are here

Scheduling delegate's final decisions, March 2016

Scheduling medicines and poisons

17 March 2016

Book pagination

3.3 Clothianidin

Part B - Final decisions on matters not referred to an expert advisory committee

3. Agricultural and Veterinary Chemicals

3.3 Clothianidin

Scheduling proposal

In November 2015 the Office of Chemical Safety (OCS), based on an application made to the Australian Pesticides and Veterinary Medicines Authority (APVMA) for registration of a new insecticide product, requested that the delegate consider amending the entry for clothianidin in Schedule 5. The recommended amendment is as follows:

CLOTHIANIDIN in preparations containing 20 per cent or less of clothianidin except in gel preparations dispensed in sealed cartridges containing 1 per cent or less of clothianidin.

Scheduling application

The applicant has applied for a reconsideration of the scheduling entry for clothianidin, proposing that Maxforce Activ Cockroach Gel be exempt from scheduling. In support of the proposal for exemption from scheduling, the applicant stated that the product represents a limited risk to human health due to the:

  • Low acute toxicity, low irritation potential and non-sensitising nature of the end-use product;
  • Proposed use pattern and scale of use as a cockroach gel;
  • Indoor use in out of the way locations;
  • Proposed use by professional pest control operators;
  • Non-volatile and ready-to-use (no mixing required) formulation; and
  • Minimal exposure potential during product use due to specific application method (using a gel bait gun).
Substance summary
Chemical structure of clothianidin

Figure 14. Chemical structure of clothianidin

Toxicity of clothianidin

Clothianidin belongs to the neonicotinoid group of compounds and is thought to bind to the postsynaptic nicotinic acetylcholine receptor in insects. Insect death results from nerve excitation and paralysis.

Toxicity Species Clothianidin
Acute oral toxicity LD50 (mg/kg bw) Rat LD50 >5000
Mice LD50=465/389 (male/female)
Acute dermal toxicity LD50 (mg/kg bw) Rat LD50 >2000
Acute inhalational toxicity LC50 (mg/m3) Rat LC50 >6140
Skin irritation Rabbits Non-irritant
Eye irritation Rabbit Non-irritant
Skin sensitisation LLNA Mice Non-sensitiser
Short-term toxicity

Target/critical effect: Reduced food consumption and body weight gain (rats, mice and dogs) and increased plasma K+ and Na+ (mice) and haemoglobin (rats).

Lowest relevant oral NOEL (mg/kg bw/d): 90 (4-wk, mouse): based on reduced bodyweight gain and food consumption in both sexes, elevated plasma K+ and Na+ in females at 190 mg/kg bw/d.

Lowest relevant dermal NOEL (mg/kg bw/d): 300 (28-d, rat)

Lowest relevant inhalation NOEC (mg/m3): No inhalational study submitted.

Genotoxicity
The results are controversial. However the weight of evidence indicates that clothianidin is unlikely to be genotoxic or clastrogenic.

Long-term toxicity and carcinogenicity

Target/critical effect: Reduced plasma ALT. Increased hepatocellular hypertrophy and increased incidence of ovarian interstitial cell hyperplasia.

Carcinogenicity

Increased hepatocellular hypertrophy (male mice) and increased incidence of ovarian interstitial cell hyperplasia (rats).

Reproductive toxicity

Reproduction target/critical effect: Reduced bodyweight gains, higher food consumption, preputial separation and vaginal opening delayed in F1 pups, reduced sperm motility, increased incidences of still births, reduced thymus and spleen weights.

Reduced bodyweight gain in F1 pups.

Lowest relevant reproductive NOEL (mg/kg bw/d): Parental NOEL: 32.7 (2-gen, rats, oral)

Neonatal NOEL: 10.2 (2-gen, rats, oral)

Developmental toxicity

Developmental target/critical effect: Maternal: Reduced bodyweight gain and food consumption (rats). Death proceeded by weight loss, reduced food consumption, reduced faecal output, orange urine, decreased activity, loss of righting reflex (rabbits).

Developmental: Higher incidence of absent intermediate lobe of the lung (rabbits).

Lowest relevant developmental NOEL (mg/kg bw/d): Maternal NOEL: 10 (rabbit, oral)

Developmental NOEL: 25 (rabbit, oral)

Toxicity of the product - Maxforce Activ Cockroach Gel

No acute inhalational study was submitted on the formulated product. Information available indicate that inhalational exposure to the product is not expected to occur based on the non-volatile nature of clothianidin (vapour pressure: 3.8 × 10-11 Pa at 20°C) and the formulation type (gel). The active constituent, clothianidin, has low inhalational toxicity (LC50 >6140 mg/m3) in rats.

Toxicity endpoint Maxforce Activ Cockroach Gel
Oral Low toxicity*
Dermal Low toxicity*
Inhalational Low toxicity#
Skin irritation Non-irritant*
Eye irritation Non-irritant*
Skin sensitisation Non-sensitiser*

*Based on toxicological studies on the product - see Attachment A, Appendix II

#Based on toxicological studies on clothianidin - see Attachment A, Section 3.1

Observation in humans

No information was provided.

Occupational exposure

The qualitative exposure estimate determined that the potential for exposure during product use was low, and most likely based on dermal exposure to the product. The product is packaged as a ready-to-use formulation and applied using a specific type of equipment (e.g. a bait or calking gun). It is therefore considered that while the use pattern of the proposed product will potentially involve regular and ongoing application by professional applicators, it is expected to result in only limited dermal exposure. Based on the current qualitative exposure assessment a precautionary statement has been recommended when using the product (i.e. wash hands after use). This statement has been included in the recommended safety directions for the proposed product.

The occupational re-entry risks associated with the use of the product are expected minimal due to the intended use pattern of the product and limited post-application activities associated with the product.

Public exposure

The product will be applied by professional pest control operators in publicly accessible areas (e.g. domestic premises, food processing establishments, food storage facilities (except where grain is stored), food preparation areas, public buildings, small-scale animal housing and transportation vehicles).

The draft product label contains the statement 'Gel should be applied out of reach of children'. Furthermore, according to the applicant, the proposed product will be placed in 'locations which are usually not accessible for children' (where insects hide, where high transit of insects is expected). Accidental exposure to members of the public is therefore not expected to occur under the proposed conditions of use as described by the draft product label and the directions for use.

Consistent with the risk assessment considerations and to provide adequate warning regarding the potential risks associated with product use, the OCS recommended the following Precautionary/Warning Statements:

"Do not place bait in areas accessible to children"

International regulations

No information was provided.

Scheduling status

CLOTHIANIDIN is currently listed in Schedules 5 and 6.

Scheduling history

CLOTHIANIDIN was first considered for scheduling at the October 2002 meeting of the NDPSC. On the basis of its high acute oral toxicity in mice, clothianidin was included in Schedule 6. A cut-off was not established as the product considered at the time also had an acute toxicological profile consistent with inclusion in Schedule 6. Clothianidin first appeared in the SUSDP in June 2005.

CLOTHIANIDIN was subsequently considered by the scheduling committee in October 2006 in relation to a new product formulation. In that meeting, members considered a proposal for a new entry for CLOTHIANIDIN in Schedule 5 with a 20% cut-off, and consequential amendment of the existing Schedule 6 entry. At the product concentration proposed it was considered the toxicity profile was consistent with inclusion in Schedule 5.

Delegate's final decision
Schedule 6 - Amend Entry

CLOTHIANIDIN except

  1. When included in Schedule 5; or
  2. When in gel preparations dispensed in sealed cartridges containing 1 per cent or less of clothianidin.
Schedule 5 - Amend Entry

CLOTHIANIDIN in preparations containing 20 per cent or less of clothianidin except in gel preparations dispensed in sealed cartridges containing 1 per cent or less of clothianidin.

Implementation date: 1 June 2016.

The reasons for the final decision comprised the following:

  • The OCS evaluation suggests a low toxicity profile for the specific product that does not meet any of the SPF criteria for listing in the Schedules. The applicant agrees with the OCS scheduling recommendation.
  • While the previous scheduling decisions based on the acute toxicity profile of clothianidin are consistent with listing in Schedule 6 for the active, with products containing 20% or less down-scheduled to Schedule 5, the delegate is satisfied that the toxicity profile and use pattern of the gel-matrix cockroach bait is sufficiently lower that it does not meet any of the SPF criteria for scheduling. Accordingly, the delegate agrees to amend the current entries to exempt the specified product. It is noted that label warning statements, including those that recommend the product not be used in areas accessible to children, provide suitable warnings against inappropriate use and that they do not need reinforcement via the signal headings afforded by scheduling.
  • The delegate considered the relevant matters under subsection 52E (1) of the Therapeutic Goods Act 1989: (c) the toxicity of a substance; and (d) the dosage, formulation, labelling, packaging and presentation of a substance.
Delegate's considerations

The delegate considered the following in regards to this proposal:

  • Scheduling proposal;
  • OCS evaluation report;
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling factors1;
  • Other relevant information.

Footnotes

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

Book pagination