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Scheduling delegate's final decisions: ACCS, August 2014

Scheduling medicines and poisons

7 August 2014

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

2. Agriculture and Veterinary Chemicals

2.1 Propoxur

Scheduling proposal

In June 2014, the Australian Pesticides and Veterinary Medicines Authority (APVMA) through the Agriculture and Veterinary Chemicals Assessment Team (AVCAT) of the Office of Chemicals Safety (OCS) indicated the Secretariat that:

  • The current propoxur Schedule 5(d) entry does not specify the concentration ratio that should be present in a spray pack containing propoxur. As the concentration ratio is not provided, it is not clear whether the propoxur concentration in the spray pack should be g/kg or % and therefore this entry needs clarification.
Substance summary

Propoxur is a non-systemic insecticide which was introduced in 1959. Propoxur is not used on food crops. It is used against mosquitoes in outdoor areas, for flies in agricultural settings, for fleas and ticks on pets, as an acaricide, on lawns and turf for ants, on flowering plants, and in private dwellings and public buildings. It is also used as a molluscicide. It is effective against cockroaches, aphids and leafhoppers22,23.

Propoxur is one of the chemicals that have, to a large extent, replaced DDT in the control of black flies and mosquitoes. It is a nonsystemic insecticide with contact and stomach action that has longstanding residual poisonous or toxic activity when it is in direct contact with the target pest. Many formulations are available including ready-to-use liquids and aerosols, emulsifiable concentrates, wettable powders, granular baits, dusts and impregnated pet collars and strips.

Propoxur is one of a family of carbamate insecticides. These chemicals block the production and action of cholinesterase, an essential nervous system enzyme. These materials quickly paralyze the nervous systems of insects, gaining them a reputation of having a rapid "knockdown" effect.

Figure 8. Structure of propoxur

Structure of propoxur

Acute toxicity

No toxicity studies have been provided. Secretariat has obtained the following information from the World Health Organisation’s report on propoxur24.

The acute toxicity end-points for this chemical are listed in the below table.

Toxicity Species Propoxur SPF* classification
Acute oral toxicity LD50 (mg/kg bw) Rat 89.7 Moderate to high toxicity
Acute dermal toxicity LD50 (mg/kg bw) Rat >5000 Low toxicity
Acute inhalational toxicity LC50 (mg/m3/4h) Rat 654 Moderate to high toxicity
Skin irritation Rabbit Non-irritant
Eye irritation Rabbit Non-irritant
Skin sensitisation (Magnusson and Kligman test) Guinea pig Non-sensitiser

*Scheduling Policy Framework for Medicines and Chemicals (2010)

Repeat dose toxicity

Not provided. Secretariat has obtained the following information, including mutagenicity, carcinogenicity and reproduction toxicity, from the United States Extension Toxicology Network's report on propoxur25.

Prolonged or repeated exposure to propoxur may cause symptoms similar to acute effects. Propoxur is very efficiently detoxified (transformed into less toxic or practically nontoxic forms), thus making it possible for rats to tolerate daily doses approximately equal to the LD50 of the insecticide for long periods, provided that the dose is spread out over the entire day, rather than ingested all at once.

Mutagenicity

No information provided.

Propoxur did not cause mutations in six different types of bacteria. The evidence indicates that propoxur is not mutagenic.

Genotoxicity

No information provided.

Carcinogenicity

No information provided.

Reproduction and developmental toxicity

No information provided.

In female rats given high dietary doses of approximately 18 mg/kg bw/day of propoxur as a part of a three-generation reproduction study, reduced parental food consumption, growth, lactation, and litter size were observed. At 25 mg/kg bw/day administered to pregnant rats there was a decrease in the number of offspring. Dietary doses of approximately 2.25 mg/kg bw/day did not affect fertility, litter size, or lactation, but parental food intake and growth were depressed in the exposed group. This evidence suggests that reproductive effects in humans are unlikely at expected exposure levels.

Observation in humans

No information provided. Secretariat obtained the following information from the International Program on Chemical Safety (IPCS)26.

In a study undertaken to develop an oral administration of 110 and 116 mg/person produced no signs of illness. The level of urinary phenols reached 140 ppm in the absence of clinical signs of poisoning.

In persons engaged in spraying or other occupation exposure, urinary levels of 80 ppm are uniformly associated with illness.

In another study, 135 mg/person was administered to a male volunteer (1.5 mg/kg bw) and within 20 minutes after ingestion described clinical signs of poisoning due to the carbamate. Significant erythrocyte cholinesterase depression was evident coinciding with clinical signs of poisoning, while plasma cholinesterase depression was not observed. Two hours after the ingestion of propoxur, there were no signs of poisoning and the rapid disappearance of symptoms was consistent with the rapid recovery of erythrocyte cholinesterase activity. Absorption and excretion of propoxur was very rapid as evidenced by measurement of urinary phenols which reached a maximum value within four hours of almost 200 ppm. Of the total phenol content excreted, 81% was found within five hours after administration. In another experiment, a single dose of 0.36 mg/kg again produced a rapid fall of erythrocyte cholinesterase to 57% of normal within 10 minutes. Cholinesterase recovered to its normal value within three hours. Within 10 minutes of the administration of propoxur, short-lasting stomach discomfort, blurred vision, and moderate facial redness and sweating were evident in the volunteer.

A number of experiments were carried out to study the effect of storage or build-up of propoxur in the body. Human volunteers took doses of either 0.15 or 0.2 mg/kg at half-hour intervals for a total of five doses. In each subject a symptomless depression of erythrocyte cholinesterase to about 60% of normal was observed. At the cessation of dosing, enzyme recovery was rapid, being complete within two hours. Similarly pronounced and as a rule symptomless daily depression and reactivation of cholinesterase was observed in persons who are occupationally exposed to propoxur. Studies in humans have shown that depression of erythrocyte cholinesterase (rather than plasma cholinesterase) is a significant indicator of exposure to propoxur.

Public exposure

Not provided. Secretariat has obtained the following information from the Centers for Disease Control and Prevention's website27.

General population exposure to propoxur through the diet is likely to be limited because of usage restrictions. Estimated human intakes have been below recommended intake limits. Pesticide applicators are likely to have the highest exposures. Propoxur can be absorbed through the skin, lungs, and gastrointestinal tract. Propoxur does not accumulate in blood or tissues and is eliminated rapidly from the body.

International regulations

Not provided. Secretariat has obtained the following information.

In the US, the use of currently registered products containing propoxur in accordance with approved labeling will not pose unreasonable risks of adverse effects to humans.

Scheduling status

Propoxur is currently listed in Schedules 5 and 6.

SCHEDULE 5

PROPOXUR:

  1. when impregnated in plastic resin strip material containing 10 per cent or less of propoxur;
  2. in dust preparations containing 3 per cent or less of propoxur;
  3. in granular sugar-based fly baits containing 1 per cent or less of propoxur, a dark colouring agent and a separate bittering agent;
  4. in pressurised spray packs containing 10 g or less of propoxur; or
  5. in printed paper sheets for pest control containing 0.5 per cent or less of propoxur and in any case not more than 100 mg of propoxur per sheet.

SCHEDULE 6

PROPOXUR except when included in Schedule 5.

Scheduling history

Propoxur was first considered by the Poisons Schedule Sub-committee (PSC) in August 1974 when it was included in Schedule 6. In August 1975, the PSC decided based on the toxicity profile of propoxur to list dust preparations containing 3% or less of propoxur in Schedule 5 and all other preparations containing propoxur in Schedule 6.

In February 1978, the PSC considered an application to reschedule preparations containing 20% or less of propoxur from Schedule 6 to Schedule 5. The PSC decided not to reschedule propoxur due to insufficient information on the safety of the concentration level had been provided.

In November 1979, the PSC decided to create a Schedule 2 entry for preparations containing propoxur intended for external human therapeutic use. At this meeting, the PSC also considered an application to amend the Schedule 5 entry to include aerosol preparations containing 2% or less of propoxur and rejected this request.

In November 1981, the PSC decided to amend the Schedule 5 entry to include granular sugar-based fly baits containing 1% or less of propoxur. This amendment was based on the conditions that the preparation must also contains a dark colouring agent and a separate bittering agent.

In August 1983, the PSC considered a re-scheduling request, this time included with 2-year rat, dog and mouse studies, for surface sprays containing 20 g/L of propoxur. It was proposed to be included in Schedule 5. The committee decided to support the proposal and the Schedule 5 entry was amended to include: c) in aerosol packs containing 10 g or less of propoxur.

In November 1983, the PSC decided to include propoxur in Schedule 4.

In February 1985, the PSC decided to amend the Schedule 5 entry to include printed paper sheets for pest control containing 0.5% or less of propoxur and in any case not more than 100 mg of propoxur.

In November 1986, the Drugs and Poisons Scheduling Sub-committee (DPSC) decided to include propoxur in Appendix E with a statement 'If sprayed on skin, wash thoroughly. If sprayed in mouth, give milk or water'.

In August 1995, the National Drugs and Poisons Schedule Committee (NDPSC) noted that the then new acute oral LD50 studies in rat for propoxur, not previously considered by NDPSC, indicated an oral LD50 of 39 mg/kg, somewhat less than the previous LD50 of 90 mg/kg. Based on this information, the NDPSC foreshadowed a decision to move Schedule 6 entry to Schedule 7 and decided to delete the Schedule 6 entry. The NDPSC also decided to review the Schedule 5 listing.

In May 1996, the NDPSC decided to amend the Schedule 5 entry to include 'when impregnated in plastic resin strip material containing 10 per cent or less of propoxur'.

In May 1999, the NDPSC decided to delete the Schedule 4 entry.

Delegate's considerations

The delegate considered the following in regards to this proposal:

  • Scheduling proposal;
  • Public submissions received;
  • ACCS advice;
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling factors28;
  • Other relevant information.
Delegate-only final decision

The current wording of clause (d) in the Schedule 5 entry for propoxur allows pressurised spray products to contain up to 10g of propoxur, without specifying the pack size or the final concentration. The scheduling history relating to this clause is unclear, however it would appear to allow any pressurised spray product containing 10g propoxur or less in Schedule 5, irrespective of the pack size of concentration of active ingredient. Given the toxicity profile of propoxur, this is clearly inappropriate and an unintended outcome of a previous scheduling decision. Accordingly, the delegate proposes to make an editorial amendment to clause (d) to restrict the concentration of propoxur to 2%. This will have no regulatory impact on an existing product in the APVMA Pubcris list and ensures that any future pressurised spray product conforms to the SPF toxicological criteria for Schedule 5.

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegate included: c) the toxicity of a substance and d) the dosage, formulation, labelling, packaging and presentation of a substance.

Schedule entry

Schedule 5 - Amendment

PROPOXUR - Amend entry to read:

  1. d) in pressurised spray packs containing 2 per cent 10 g or less of propoxur; or

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Footnotes

  1. Propoxur (Baygon), Technology Transfer Network. United States Environmental Protection Authority.
  2. Propoxur, Pesticide Information Network, Extension Toxicology Network.
  3. Propoxur (pdf,188kb). WHO specifications and evaluations for public health pesticides.
  4. Propoxur, Extension Toxicology Network, Pesticide Information Profiles.
  5. Propoxur, JMPR 1973.
  6. Bio monitoring Summary, Carbamade insecticides - Propoxur, Centers for Disease Control and Prevention.
  7. Scheduling Policy Framework for Medicines and Chemicals (SPF, 2010)

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