Metribuzin
(endorsed 2011)
Guideline
Based on human health concerns, metribuzin in drinking water should not exceed 0.07 mg/L.
Related chemicals
Metribuzin (CAS 21087-64-9) belongs to the triazinone class of chemicals. Other pesticides in this class include hexazinone, metamitron and toltrazuril (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, metribuzin would not be a health concern unless the concentration exceeded 0.07 mg/L. Minor excursions above this level would need to occur over a significant period to be a health concern, as the health-based guideline is based on long-term effects.
General description
Uses: Metribuzin is a pre- and post-emergent herbicide for the control of broad-leaf weeds and grasses in agricultural crops.
There are registered products that contain metribuzin in Australia. The products are intended for professional use and are available as concentrated solutions, granular formulations or wettable powders to be applied in diluted form using ground boom and aerial sprays. Data on currently registered products are available from the Australian Pesticides and Veterinary Medicines Authority.
Exposure sources: The main source of public exposure to metribuzin and its metabolites is residues in food. Residue levels in food produced according to good agricultural practice are generally low.
Agricultural use of metribuzin may potentially lead to contamination of source waters through processes such as run-off, spray drift or entry into groundwater.
Typical values in Australian drinking water
No reports of metribuzin in Australian drinking waters have been identified.
Treatment of drinking water
No specific data on the treatment of metribuzin in drinking water have been identified.
Measurement
Metribuzin may be measured in drinking waters by gas chromatography with mass spectrometry, with a limit of reporting of 0.1 µg/L (QFSS 2009).
History of the health values
The current acceptable daily intake (ADI) for metribuzin is 0.02 mg per kg of bodyweight (mg/kg bw), based on a no-observed-effect level (NOEL) of 2 mg/kg bw/day from a long-term rat study. The NOEL is based on decreased absolute and relative heart weights. The ADI incorporates a safety factor of 100, and was established in 1982.
The acute reference dose (ARfD) of 0.25 mg/kg bw for metribuzin was established in 2007, based on a NOEL of 25 mg/kg bw/day from a developmental study in rats. The ARfD incorporates a safety factor of 100.
The previous health value was 0.05 mg/L (NHMRC and NRMMC 2004).
Health considerations
Metabolism: Metribuzin is rapidly absorbed via the gastrointestinal tract in rats. It is readily metabolised and rapidly excreted in the urine and faeces with little tissue retention after 96 hours. The major metabolite recovered from rats is N-acetylcysteine.
Acute effects: Metribuzin has low to moderate acute oral toxicity and low dermal toxicity. It is not a skin sensitiser.
Short-term effects: A short-term dermal study conducted in rabbits reported elevated serum levels of thyroid hormone (thyroxine) in female rabbits at doses of 200 mg/kg bw/day and above. Short-term dietary studies performed in rats reported increased absolute liver weights at the high dose of 4.5 mg/kg bw/day. Associated histopathological effects were not observed.
Long-term effects: Long-term dietary studies conducted in mice, rats and dogs showed the main effect to be changes in absolute and relative organ weights. In a 2-year study in mice, increased liver, spleen, and kidney weights and evidence of anaemia were observed at 500 mg/kg bw/day. In a 2-year study in rats, decreased relative and absolute heart weights were observed at 5.7 mg/kg bw/day, and effects on the thyroid hyperplasia and fluctuating levels of triiodothyronine and thyroxine at 13 mg/kg bw/day and above. In a 2-year study in dogs, anaemia, increased mortality, increased relative and absolute organ weights and lesions in heart, liver, kidney and adrenal glands were observed at 52.5 mg/kg bw/day. The overall NOEL was 2 mg/kg bw/day in rats, and this is the basis for the current ADI.
Carcinogenicity: Based on a 2-year study in rats, metribuzin is not considered to be carcinogenic.
Genotoxicity: Metribuzin is not considered to be genotoxic, based on in vitro and in vivo short-term studies.
Reproductive and developmental effects: A 2-generation reproduction study in rats and a developmental study in rats did not produce any evidence of effects on reproduction or foetal development. In the developmental study, effects on the dams included increased thyroid weights and fluctuations in thyroid hormones at doses of 75 mg/kg bw/day and above. The NOEL of 25 mg/kg bw/day from this study was used to set the ARfD.
Poisons Schedule: Metribuzin is 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 0.07 mg/L for metribuzin was determined as follows:
where:
2 mg/kg bw/day is the NOEL based on a long-term (2-year) study in rats.
70 kg is taken as the average weight of an adult.
0.1 is a 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.
NHMRC (National Health and Medical Research Council), NRMMC (Natural Resources Management Ministerial Council) (2004). Australian Drinking Water Guidelines. National Water Quality Management Strategy, Paper 6. NHMRC and NRMMC.
QFSS (Queensland Forensic and Scientific Services) (2009) QFSS, Personal communication.
Tomlin CD (ed) (2006). The Pesticide Manual: a world compendium, 14th edition, British Crop Production Council, UK.
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