Metham

(endorsed 2011)

Guideline

Metham rapidly degrades to methylisothiocyanate (MITC) in the environment, hence the health-based guideline for metham has been based on the toxicity of MITC. Based on human health concerns, MITC in drinking water should not exceed 0.001 mg/L.

Related chemicals

Metham (CAS 144-5-54-7) belongs to the n-methyl-dithiocarbamate class of chemicals. There are no other pesticides in this class. A closely related class of chemicals is ethylenebis-dithiocarbamates, which includes mancozeb, metiram, and zineb. The insecticidal and fungicidal activity of metham sodium is due to degradation to methylisothiocyanate (MITC) in the environment. MITC is also a degradant of the pesticide dazomet (Tomlin 2006).

Human risk statement

With good water quality management practices, the exposure of the general population is expected to be well below levels that may cause health concerns.

If present in drinking water as a result of a spillage or through misuse, the degradation products of metham would not be a health concern unless the concentration exceeded 0.001 mg/L. Excursions above this level even for a short period are of concern as the health-based guideline is based on short-term effects.

With good water quality management practices, pesticides should not be detected in source waters used for drinking water supplies. Persistent detection of pesticides may indicate inappropriate use or accidental spillage, and investigation is required in line with established procedures in the risk management plan for the particular water source.

General description

Uses: Metham is a herbicide and insecticide for the control of tree roots, and soil-borne pests in ornamental, food and tobacco crops.

There are currently registered fumigant products that contain metham as its sodium salt. The products are for professional use only and are available as various liquids, suspensions or aqueous concentrates. Most products are for use as pre-plant soil fumigants and are applied by soil injection, rotary tiller, spot treatment, and trickle irrigation systems. Some products are for direct addition into pipes in sewage and wastewater collection systems. Methylisothiocyanate was formerly used as a soil fumigant in Australia. Data on currently registered products are available from the Australian Pesticides and Veterinary Medicines Authority.

Exposure sources: Metham is highly unstable in the environment and spontaneously hydrolyses to MITC. It is considered highly unlikely that residues of metham itself will be present in food, although it is possible there may be residues of MITC in food.

Agricultural use of metham may potentially lead to contamination of source waters by MITC through absorption into the soil moisture and subsequent leaching into groundwater. Some metham products are also added directly to sewer or wastewater pipes.

Typical values in Australian drinking water

No published reports on metham occurrence in Australian drinking water supplies were found. Based on the registered use patterns for metham, exposure from drinking water is not expected and no dietary risk mitigation is warranted (USEPA 2009).

Treatment of drinking water

Powdered activated carbon filtration, granulated activated carbon filtration, and reverse osmosis have been demonstrated to be highly effective processes at removing certain pesticides including dithiocarbamates (USEPA 2001a ). Metham has a hydrolysis half-live of less than 1 day in alkaline (pH 9) water and can be removed during lime-soda softening (pH 10~11) by alkaline hydrolysis (USEPA 2001b).

Measurement

Metham sodium and methyl isothiocyanate (MITC) can be analysed in water by high-performance liquid chromatography (Mullins and Kirkbright 1987, Dhoot et al. 1993). These methods can achieve a limit of quantitation (LOQ) of 1 μg/L for MITC and 70 μg/L for metham. Direct immersion solid phase microextraction followed by gas chromatography electron capture detector or gas chromatography nitrogen phosphorus detector analysis can achieve a LOQ of 0.5 μg/L for methyl isothiocyanate in water (Fuster et al. 2005).

History of the health values

An acceptable daily intake (ADI) has not been set for metham since ADIs are required only for pesticides with residues in food.

The current ADI for the degradant MITC is 0.0004 mg per kg body weight (mg/kg bw) based on a no-observed-effect level (NOEL) of 0.04 mg/kg bw/day from a 3-month study in dogs. In this study there were decreased testis weights, increased pancreas weights, and abnormal liver histology at the highest dose tested, 2 mg/kg bw/day. The ADI incorporates a safety factor of 100 and was established in 2004.

An acute reference dose (ARfD) has not been set for metham since ARfDs are required only for pesticides with residues in food.

The current ARfD for the degradant MITC is 0.0005 mg/kg bw/day based on a NOEL of 0.1 mg/kg bw/day from an acute oral dosing study in dogs. At the next highest dose tested of 0.5 mg/kg bw/day and above, haemorrhagic lesions in liver and kidneys were seen at necropsy. The ARfD incorporates a safety factor of 200 and was established in 2004.

A health value has not been previously established by NHMRC.

Health considerations

Metabolism: Metham sodium is readily and extensively absorbed via the gastrointestinal tract in rats. It is spontaneously hydrolysed to MITC and other alkyl isothiocyanates and isothiocarbamates including 1,3,-dimethylthiourea, ethylenethiourea (ETU), and carbon disulfide by passive chemical processes, and is rapidly excreted in the urine as mercapturic acid derivatives, and in the breath as carbon disulfide, almost completely within 48 hours.

Acute effects: Metham sodium has high acute oral toxicity in mice and moderate acute oral and dermal toxicity in rats. Metham sodium and its breakdown product MITC are skin sensitisers in humans. The breakdown product, MITC, has a similar acute oral and dermal toxicity to metham.

Short-term effects: In a 3-month oral study in dogs with the degradant MITC, an increased incidence and severity of periportal hepatocyte vacuolation and lipid deposition was seen at doses of 0.4 mg/kg bw/day and above, and decreased testis weights and increased pancreas weight at doses of 2 mg/kg bw/day. The NOEL in this study was 0.04 mg/kg bw/day and this is the basis for the current ADI for MITC.

Long-term effects: No long-term studies are available for metham (including metham sodium). In studies where the degradant MITC was added to the drinking water of rats at doses up to 2.7 mg/kg bw/day and in mice up to 27 mg/kg bw/day, the major toxicological findings were decreased food consumption and decreased bodyweight gain at doses of 2.5 mg/kg bw/day in rats, and at 14 mg/kg bw/day in mice.

Carcinogenicity: There are no carcinogenicity studies available for metham. Based on a 2-year study in mice and rats, there is no evidence of carcinogenicity for the degradant MITC.

Genotoxicity: Metham sodium and the degradant MITC were positive in some in vitro short-term assays, but based on the weight of evidence, neither is considered to be genotoxic.

Reproductive and developmental effects: There are no studies available on reproductive toxicity of metham sodium. A reproduction study in rats with the degradant MITC did not provide any evidence of reproductive toxicity at doses up to 10 mg/kg bw/day. In developmental toxicity studies with metham sodium, there were effects on reproduction and development, but only at dose levels well in excess of the likely level of human exposure.

Poisons Schedule: Metham and MITC are both included in Schedule 6 of the Standard for the Uniform Scheduling of Medicines and Poisons No.1, 2010 (the Poisons Standard)(DoHA 2010). Current versions of the Poisons Standard should be consulted for further information.

Derivation of the health-based guideline

The health-based guideline of 0.001 mg/L for the degradant of metham, MITC, was determined as follows:

$$\text{ 0.001 mg/L } = \dfrac{\text{ 0.04 mg/kg bodyweight/day x 70 kg x 0.1 }}{\text{ 2 L/day x 100 }}$$

where:

• 0.04 mg/kg bw/day is the NOEL for MITC based on a short-term (3-month) oral study in dogs.

• 70 kg is taken as the average weight of an adult.

• 0.1 is the proportionality factor based on the assumption that 10% of the ADI will arise from the consumption of drinking water.

• 2 L/day is the estimated maximum amount of water consumed by an adult.

• 100 is the safety factor applied to the NOEL derived from animal studies. This safety factor incorporates a factor of 10 for interspecies extrapolation and 10 for intraspecies variation.

References

NOTE: The toxicological information used in developing this fact sheet is from reports and data held by the Department of Health, Office of Chemical Safety.

DoHA (2010) The Poisons Standard; Schedule 1-Standard for the Uniform Scheduling of Medicines and Poisons, Department of Health and Ageing, Commonwealth of Australia, Canberra.

Dhoot JS, Del Rosario AR, Tamplin BR (1993). Simultaneous determination and confirmation of sodium N-methyldithiocarbamate (Metham SodiumR) and methyl isothiocyanate in water by high performance liquid chromatography with diode array detection. International Journal of Environmental Analytical Chemistry, 53(3):165-171.

Fuster S, Beltran J, Lopez FJ, Hernandez F (2005). Application of solid phase microextraction for the determination of soil fumigants in water and soil samples. Journal of Separation Science, 28(1):98-103.

Mullins FG, Kirkbright GF (1987). Determination of sodium N-methyldithiocarbamate (metham sodium) and methyl isothiocyanate in aqueous samples by high-performance liquid chromatography using a micellar mobile phase. Analyst, 112(5):701-3.

Tomlin CD (ed) (2006). The Pesticide Manual: a world compendium, 14th Edition, British Crop Production Council, UK.

USEPA (United States Environmental Protection Agency) (2001a) The Incorporation of Water Treatment Effects on Pesticide Removal and Transformations in Food Quality Protection Act (FQPA) Drinking Water Assessments, Office of Pesticide Programs Science Policy, USEPA, Washington, D.C.

USEPA (United States Environmental Protection Agency) (2001b) Pesticide Science Policies: Water Treatment Effects on Pesticide Removal and Transformation; Notice of Availability OPP-00731; FRL-6792-9, OPP-00731; FRL-6792-9, USEPA.

USEPA (United States Environmental Protection Agency) (2009) Amended Reregistration Eligibility Decision (RED) for the Methyldithiocarbamate Salts (Metamsodium, Metam-potassium) and Methyl Isothiocyanate (MITC), EPA 738-R-09-310, Prevention, Pesticides and Toxic Substances.