Tridemorph

Tridemorph is a systemic fungicide that first gained commercial clearance in 1969(1). An evaluation document to be published later in the year by the UK's Pesticide Safety Directorate (PSD) will report concern over its potential reproductive effects on spray operators. Until recently there has been very little human health and environmental information in the public domain on this active ingredient, yet it is used widely over numerous crops in many countries around the world.

What is tridemorph
It is used to control the fungus Erysiphe graminis in cereals, Mycosphaerella species in bananas, and Caticum solmonicolor in tea. Tridemorph is formulated with the fungicide carbendazim, to extend its spectrum of use in cereal disease control(2). It is also used with a number of other fungicides including: cyproconazole, fenbuconazole, fenpropi-morph, flusilazole, propiconazole, tebucon-azole, triadimenol(3).
Tridemorph is applied onto many crops across the world, but very little data on usage and production is in the public domain. It was developed in the 1960s by the German multinational BASF who sell tridemorph under the trade name Calixin. In Europe, it is used in Austria, Belgium, Finland, Germany, Greece, Italy, Ireland, Luxembourg, Netherlands, Spain and UK(4). It is applied widely on banana plantations Latin America, especially Costa Rica and Ecuador(5).
In the UK there are 29 approved products, predominately for use against powdery mildew on cereals but also on root crops. There are no home garden products(6). In 1997, tridemorph was most commonly used on winter barley (61,207 kg) followed by wheat (50,588 kg) and spring barley (18,411 kg)(7).

Acute toxicity
The acute oral LD50 (the dose required to kill half a population of laboratory test animals) for tridemorph is 650 mg/kg for rats. It is classified by the World Health Organisation as Class II a 'moderately hazardous' pesticide(8). It is harmful if swallowed and irritating to eyes and skin(9). Tests show it is moderately to severely irritating to rabbit skin and rabbit eyes. Prolonged or repeated exposure may cause dermatitis and/or conjunctivitis. Inhalation of tridemorph vapour may cause adverse health effects (specific effects not stated). Laboratory rats survived an 8 hour exposure to air saturated with tridemorph vapour(10).

Chronic effects
Until recently, very little data was in the public domain. On 19 March 1999, Jeff Rooker the UK Agriculture Minister announced that the use of tridemorph would be restricted due to concerns over its reproductive effects. PSD, an executive agency of the Ministry of Agriculture, Fisheries and Food (MAFF) has considered the data under the UK Review Programme, and will produce a full evaluation later in the year. The Advisory Committee on Pesticides, which advises UK Ministers on pesticide safety, considered PSD's review of tridemorph in February 1999 and made a number of recommendations (see below)(11).

Reproductive effects
Ministers and officials at MAFF became concerned after BASF, the main manufacturer of tridemorph, provided new information that identified a possible risk of harm to the unborn child if the mother is exposed to tridemorph while working with the chemical. The company submitted its data as part of its obligation under the Food and Environment Protection Act 1985 to provide any new information on the potentially dangerous effects of a pesticide product. The data comprised developmental toxicology studies in the rat and rabbit, and a literature review of developmental studies in vivo and in vitro.
PSD assessed these studies and concluded that tridemorph was capable of inducing abnormalities, primarily cleft palate, during the development of the rat foetus. In rabbits, it did not appear to be teratogenic. Scientists at PSD consider this difference was not addressed, and from the available information, it was not possible to determine whether the effects seen in rats would be produced in humans. They were nevertheless worried about the severity of effects, the steepness of a dose response curve they had produced and absence of a clear no observed adverse effect level (NOAEL) in the rat developmental study. The officials found it necessary to apply an increase safety factor in establishing the acceptable daily intake for consumers (ADI), acute reference dose for consumers (ARfD), and admissible operator exposure level (AOEL). Based on this data PSD set the following end-point values based on the rat development study with a safety factor of 1,000 fold:

A temporary ADI of 0.01 mg/kg, based on the minimal effect of 10 mg/kg body weight per day
An AOEL of 0.01 mg/kg bw/d
An ARfD of 0.01 mg/kg bw/d

For many teratogenic compounds, adverse effects on foetal development can be produced by a single exposure at a crucial period during pregnancy. According to PSD, this was an important factor when considering those working with products containing tridemorph.
Furthermore, the studies showed that the AOEL was exceeded when exposures to operators, resulting from the use of products containing tridemorph, were estimated. Although PSD said it was possible to reduce these exeedances by imposing requirements for the use of additional personal protective equipment (PPE), making changes to the maximum application rates of products, and imposing a requirement to apply products only via tractors in closed cabs; the possibility of single exposures resulting from splashes and spillages during mixing and loading would still present a significant risk to women of child bearing age. On this basis, the Agriculture Minister specified the following requirements, following advice from PSD and the ACP:

All approval holders should carry out an active information campaign to alert users of the products to the fact that the use of tridemorph by women of child bearing age may carry a risk of adverse reproductive effects. This includes warnings on the labels of products.
Closed transfer systems must be used when transferring formulations containing tridemorph from the container to the spray tank.
Application formulations containing tridemorph must be restricted to vehicles where the operator is protected by a closed cab.
For all formulations containing tridemorph, the maximum individual dose must not exceed 375g active ingredient per hectare. Approval for uses were revoked where the maximum individual dose exceeded this limit.
The following additional PPE requirements were specified for all formulations containing tridemorph:
Operators must wear suitable protective gloves when handling contaminated surfaces.
The packaging for all formulations containing tridemorph was restricted to 'wide-neck' containers only.

Other reports of reproductive effects
In 1995 tridemorph was listed as teratogenic (a substance that may cause birth defects) in Sax and Lewis Dangerous Properties of Industrial Materials(12). It has also been identified as a potential endocrine disruptor by Germany's Federal Environment Agency(13) because of concerns over its effect on mammalian ovaries. In 1990 the US publication Pest Line reported: "Embryoethality, cleft palate and other anomalies, and maternal toxicity were reported in a study of pregnant rats and mice."(14)

Environmental fate
In rats, following oral consumption, tridemorph is rapidly absorbed, and is almost completely eliminated within two days. Residues in cereal grains at harvest are <0.05 mg/kg. Its half-life in soils has been measured at 20-50 days in laboratory tests, and 14-34 days in field tests(15).
    It is not often detected in water because of the lack of adequate analytical techniques. In the UK, the Working Party on the Incidence of Pesticides in Water noted in 1996 that it was one of the most significant widely used fungicides for which methodology was lacking(16).
    Tridemorph is harmful to fish and/or other aquatic life. Users are reminded not to contaminate surface waters or ditches with the chemical or used container17. The LC50 [the concentration required to kill half a population of laboratory test animals] (96 hr) for trout is 3.4 mg/litre(18).
    For bees, the LD50 (24 hr) is >200mg-bee(19).

Data gaps
In the UK, MAFF requires that further data (unspecified) from the approval holders to supplement the existing data package (see also above Reproductive effects)(20).

Conclusions
There is little data about tridemorph in the public domain. After years of use, PSD is only just about to publish an evaluation. The substance will not be reviewed by the European Union under the Registration Directive. The US EPA has no factsheet, nor has the US academic source Cornell University, which publishes a number of factsheets on pesticides on the net. No evaluation on toxicology or food residues has been published by Codex, the joint UN FAO/WHO food standards agency and there are no MRLs for food. Notwithstanding the lack of data, in the UK, tridemorph was the 18th most widely used active ingredient (by area) on arable crops in 1996, and the 23rd by weight(21).

References
1. Tomlin, CDS, The Pesticide Manual, British Crop Protection Council, 1997, pp1,242-1,243.
2. Ibid.
3. R. Whitehead, The UK Pesticide Guide 1999,
4. Active substances in authorised Plant Protection Products, European Commission, September 1995.
5. TE Lacher, SR Mortensen, KA Johnson and RJ Kendall, Environmental aspects of pesticide use on banana plantations, Pesticide Outlook, 1997, Vol 6, No. 6:24-27.
6. Pers. comm. Pesticides Safety Directorate, an Executive Agency of MAFF, 5 May 1999.
7. Pers. comm., Miles Thomas, Pesticide Usage Survey Group, MAFF, Central Science Laboratory, May 1999.
8. WHO Classification of Pesticides by Hazard 1998-1999, International Programme on Chemical Safety, WHO/PCS/98.21.
9. Op. cit. 3.
10. Pestline, Material Safety Data Sheets for Pesticides and Related Chemicals, Vol II, Occupational Health Services Inc. 1991.
11. Op. cit 6.
12. Dangerous Properties of Industrial Materials", 7th Ed., by N. Irving Sax and Richard J. Lewis. 1995.
13. ENDS Report 290, March 1999.
14. Op. cit. 10.
15. Op. cit. 1.
16. Pesticides in Water, Report of the Working Party on the Incidence of Pesticides in Water, Department of the Environment, HMSO, London, 1996.
17. Op. cit. 3.
18. Op. cit. 1.
19. Op. cit. 1
20. Op. cit. 6.
21. Pesticide Usage Survey Report, No. 141: Arable Farm Crops in Britain 1996, MAFF, 1997.

[This article first appeared in Pesticides News No.44, June 1999, p20-21]