WHO/SDE/WSH/03.04/90 English only

Dimethoate in Drinking-water

Background document for development of WHO Guidelines for Drinking-water Quality

© World Health Organization 2004

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Preface

One of the primary goals of WHO and its member states is that “all people, whatever their stage of development and their social and economic conditions, have the right to have access to an adequate supply of safe drinking water.” A major WHO function to achieve such goals is the responsibility “to propose ... regulations, and to make recommendations with respect to international health matters ....”

The first WHO document dealing specifically with public drinking-water quality was published in 1958 as International Standards for Drinking-water. It was subsequently revised in 1963 and in 1971 under the same title. In 1984–1985, the first edition of the WHO Guidelines for Drinking-water Quality (GDWQ) was published in three volumes: Volume 1, Recommendations; Volume 2, Health criteria and other supporting information; and Volume 3, Surveillance and control of community supplies. Second editions of these volumes were published in 1993, 1996 and 1997, respectively. Addenda to Volumes 1 and 2 of the second edition were published in 1998, addressing selected chemicals. An addendum on microbiological aspects reviewing selected microorganisms was published in 2002.

The GDWQ are subject to a rolling revision process. Through this process, microbial, chemical and radiological aspects of drinking-water are subject to periodic review, and documentation related to aspects of protection and control of public drinking- water quality is accordingly prepared/updated.

Since the first edition of the GDWQ, WHO has published information on health criteria and other supporting information to the GDWQ, describing the approaches used in deriving guideline values and presenting critical reviews and evaluations of the effects on human health of the substances or contaminants examined in drinking- water.

For each chemical contaminant or substance considered, a lead institution prepared a health criteria document evaluating the risks for human health from exposure to the particular chemical in drinking-water. Institutions from Canada, Denmark, Finland, France, Germany, Italy, Japan, Netherlands, Norway, Poland, Sweden, United Kingdom and United States of America prepared the requested health criteria documents.

Under the responsibility of the coordinators for a group of chemicals considered in the guidelines, the draft health criteria documents were submitted to a number of scientific institutions and selected experts for peer review. Comments were taken into consideration by the coordinators and authors before the documents were submitted for final evaluation by the experts meetings. A “final task force” meeting reviewed the health risk assessments and public and peer review comments and, where appropriate, decided upon guideline values. During preparation of the third edition of the GDWQ, it was decided to include a public review via the world wide web in the process of development of the health criteria documents.

During the preparation of health criteria documents and at experts meetings, careful consideration was given to information available in previous risk assessments carried out by the International Programme on Chemical Safety, in its Environmental Health Criteria monographs and Concise International Chemical Assessment Documents, the International Agency for Research on Cancer, the joint FAO/WHO Meetings on Pesticide Residues and the joint FAO/WHO Expert Committee on Food Additives (which evaluates contaminants such as lead, cadmium, nitrate and nitrite, in addition to food additives).

Further up-to-date information on the GDWQ and the process of their development is available on the WHO internet site and in the current edition of the GDWQ.

Acknowledgements

The first draft of Dimethoate in Drinking-water, Background document for development of WHO Guidelines for Drinking-water Quality, was prepared by Dr P. Toft, Canada, to whom special thanks are due.

The work of the following working group coordinators was crucial in the development of this document and others in the third edition:

Mr J.K. Fawell, United Kingdom (Organic and inorganic constituents) Dr E. Ohanian, Environmental Protection Agency, USA (Disinfectants and disinfection by-products) Ms M. Giddings, Health Canada (Disinfectants and disinfection by-products) Dr P. Toft, Canada (Pesticides) Prof. Y. Magara, Hokkaido University, Japan (Analytical achievability) Mr P. Jackson, WRc-NSF, United Kingdom (Treatment achievability)

The contribution of peer reviewers is greatly appreciated. The draft text was posted on the world wide web for comments from the public. The revised text and the comments were discussed at the Final Task Force Meeting for the third edition of the GDWQ, held on 31 March to 4 April 2003, at which time the present version was finalized. The input of those who provided comments and of participants in the meeting is gratefully reflected in the final text.

The WHO coordinators were as follows:

Dr J. Bartram, Coordinator, Water Sanitation and Health Programme, WHO Headquarters, and formerly WHO European Centre for Environmental Health Mr P. Callan, Water Sanitation and Health Programme, WHO Headquarters Mr H. Hashizume, Water Sanitation and Health Programme, WHO Headquarters

Ms C. Vickers provided a liaison with the International Chemical Safety Programme, WHO Headquarters.

Ms Marla Sheffer of Ottawa, Canada, was responsible for the scientific editing of the document.

Many individuals from various countries contributed to the development of the GDWQ. The efforts of all who contributed to the preparation of this document and in particular those who provided peer or public domain review comment are greatly appreciated.

Acronyms and abbreviations used in the text

ADI acceptable daily intake CAS Chemical Abstracts Service FAO Food and Agriculture Organization of the United Nations IPCS International Programme on Chemical Safety IUPAC International Union of Pure and Applied Chemistry JMPR Joint FAO/WHO Meeting on Pesticide Residues

LD50 median lethal dose NOAEL no-observed-adverse-effect level USA United States of America WHO World Health Organization

Table of contents

1. GENERAL DESCRIPTION...... 1 1.1 Identity ...... 1 1.2 Physicochemical properties ...... 1 1.3 Organoleptic properties...... 1 1.4 Major uses...... 1 1.5 Environmental fate...... 2

2. ANALYTICAL METHODS ...... 2

3. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE...... 2 3.1 Water...... 2 3.2 Food ...... 2

4. KINETICS AND METABOLISM IN LABORATORY ANIMALS AND HUMANS ...... 2

5. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS..3

6. EFFECTS ON HUMANS...... 4

7. GUIDELINE VALUE ...... 4

8. REFERENCES ...... 5

1. GENERAL DESCRIPTION

1.1 Identity

CAS No.: 60-51-5

Molecular formula: C5H12NO3PS2

The IUPAC name of dimethoate is O,O-dimethyl S-methyl-carbamoyl-methyl phosphorodithioate. Its chemical structure is shown below:

1.2 Physicochemical properties (IPCS, 1989)

Dimethoate is highly soluble in chloroform, methylene chloride, benzene, toluene, alcohols, esters and ketones; slightly soluble in xylene, carbon tetrachloride and aliphatic hydrocarbons; and fairly soluble in water.

Dimethoate is fairly stable in water, in acid solution and at room temperature; it is unstable in alkaline solution.

Property Value Melting point 45–52.5 °C Vapour pressure 1.1 × 10-3 Pa at 25 °C Volatility 1.107 mg/m3 Specific gravity (compared with water) 1.281 Octanol–water partition coefficient 5.959 Solubility in water up to 39 g/litre at 21 °C Half-life in aqueous media at pH 2–7, relatively stable at pH 9, 50% loss in 12 days

1.3 Organoleptic properties

The odour threshold of dimethoate is 0.010 mg/m3 (IPCS, 1989).

1.4 Major uses

Dimethoate is an organophosphorus insecticide with contact and systemic action. It was introduced in 1956 and is produced in many countries. It is a general-use chemical for use against a broad range of insects in agriculture and also for the control of the housefly (IPCS, 1989).

1 DIMETHOATE IN DRINKING-WATER

1.5 Environmental fate

Hydrolytic degradation is the main inactivating pathway of dimethoate in the environment. In moist air, it is degraded photochemically to hydrolytic and oxidation products. The half-life of dimethoate in different plants is between 2 and 5 days. Degradation in soil is dependent on the type of soil, temperature, moisture and pH level (IPCS, 1989). Dimethoate is not expected to persist in water.

2. ANALYTICAL METHODS

The concentration of dimethoate in water may be determined by extraction into dichloromethane and analysis by gas–liquid chromatography with flame photometric detection. The detection limit is 0.5 µg/litre (Frank & Logan, 1988).

3. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

3.1 Water

Only limited monitoring data on dimethoate in drinking-water are available. Dimethoate was not detected in 98 samples of drinking-water supplies in Canada. It was detected at trace levels (detection limit 0.01 µg/litre) in a private well in Nova Scotia. It was not detected in surveys of surface waters or rivers in Canada conducted between 1973 and 1985 (Health Canada, 1991).

3.2 Food

Dimethoate was found in 358 of 6391 food samples analysed in the USA; 96% of the samples had levels at or below 2 mg/kg (Hundley et al., 1988). IPCS (1989) has estimated a total daily intake from food of 0.001 µg/kg of body weight.

4. KINETICS AND METABOLISM IN LABORATORY ANIMALS AND HUMANS1

Dimethoate is rapidly and extensively absorbed from the gut and rapidly excreted. There was no accumulation in fat tissue. In rats and humans, up to 90% of radiolabel was found in the urine within 24 h. The report of a study with methylcarbamoyl- labelled dimethoate indicated that up to 18% of the administered label was excreted in expired air. Four metabolites with anticholinesterase activity have been identified in rats and humans. One seems to result from thiono oxidation, leading to the formation of the oxygen analogue of dimethoate (i.e., omethoate); this step was followed by hydrolysis to a thiocarboxyl product, said to be the main metabolite in rats and humans.

1 This section has been taken from FAO/WHO (1997). 2 DIMETHOATE IN DRINKING-WATER

5. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS2

Data on the acute oral toxicity of dimethoate gave LD50 values of about 310 mg/kg of body weight in rats, 150 mg/kg of body weight in mice and 55 mg/kg of body weight in hens. The signs of toxicity were those typical of cholinesterase inhibition. WHO (2001) has classified dimethoate as “moderately hazardous.”

In short-term and long-term studies at dietary concentrations of ≥75 mg/kg, there were minor reductions in body weight gain and food consumption. Apart from inhibition of cholinesterase activity, dimethoate had no effect on the composition of the blood or urine. The liver weights of animals treated at the higher doses tended to be lower than those of the control groups; there were, however, no microscopic changes, and the effect is unlikely to be of toxicological significance. Investigations of toxicity at higher doses were limited by effects due to cholinesterase inhibition. The NOAELs were thus generally based on reductions in acetylcholinesterase activity in the brain or erythrocytes. On the basis of minimal reductions in acetylcholinesterase activity of 10–20%, the NOAEL in a 12-month study in dogs at doses of 0, 5, 20 or 125 mg/kg was 5 mg/kg, equal to 0.2 mg/kg of body weight per day; in rats, the NOAEL in a life span study at doses of 0, 1, 5, 25 or 100 mg/kg was 1 mg/kg, equal to 0.04 mg/kg of body weight per day. In mice, a NOAEL was not identified, as cholinesterase activity was depressed at all doses after 52 weeks of treatment in a life span study at doses of 0, 25, 100 and 200 mg/kg.

The results of long-term studies of toxicity and carcinogenicity in mice (at 0, 25, 100 or 200 mg/kg) and rats (at 0, 5, 25 or 100 mg/kg) reported in 1986 and studies reported in 1977 indicate that dimethoate is not carcinogenic to rodents.

In a multigeneration study of reproductive toxicity conducted in 1989–1990 with doses of 0, 1, 15 or 65 mg/kg, reproductive performance of rats was impaired at the high dose. The NOAEL for reproductive toxicity appeared to be 15 mg/kg (equal to 1.2 mg/kg of body weight per day) and that for parental toxicity was 1 mg/kg (equal to 0.08 mg/kg of body weight per day) on the basis of cholinesterase inhibition, but the Meeting noted that there was some indication that reproductive performance may have been affected at lower doses. In a multigeneration study conducted in mice in 1965 at doses of 0, 5, 15 or 50 mg/kg, there was no overt effect on reproductive capacity, even in the presence of cholinergic toxicity. In a poorly reported study in rabbits, sperm numbers and quality were adversely affected at doses equivalent to one-tenth and one-hundredth of the LD50.

Studies of developmental toxicity in rats (at 0, 3, 6 or 18 mg/kg of body weight per day on days 6–15 of gestation) and rabbits (at 0, 10, 20 or 40 mg/kg of body weight per day on days 7–19 of gestation) provided no evidence of a teratogenic effect, although maternal toxicity was observed at the high dose in rats and at the high and middle doses in rabbits.

2 This section has been taken from FAO/WHO (1997). 3

DIMETHOATE IN DRINKING-WATER

After reviewing the data available on mutagenicity, JMPR concluded that although in vitro studies indicate that dimethoate has mutagenic potential, this potential does not appear to be expressed in vivo.

Undiluted dimethoate formulations were irritating to the eye in rabbits. Skin irritation was minimal and confined to slight, transient erythema. Dimethoate was not a skin sensitizer in guinea-pigs, but a 32.7% emulsifiable concentrate formulation induced sensitization in 1 of 10 guinea-pigs.

In hens given a single dose of 55 mg/kg of body weight by subcutaneous injection or orally, dimethoate did not induce delayed neurotoxicity.

6. EFFECTS ON HUMANS3

In a 39-day study in nine male and female volunteers, the NOAEL for cholinesterase inhibition was 0.2 mg/kg of body weight per day. This NOAEL was supported in seven other studies, each involving 6–20 volunteers who received doses ranging from 0.04 to 1.0 mg/kg of body weight per day for up to 57 days.

In a published paper, dimethoate was cited in four human cases of contact dermatitis, and sensitization was confirmed in these individuals by patch testing.

7. GUIDELINE VALUE

An ADI of 0.002 mg/kg of body weight was established for dimethoate on the basis of the apparent NOAEL of 1.2 mg/kg of body weight per day for reproductive performance in the study of reproductive toxicity in rats and applying a safety factor of 500. Although a safety factor of 100 would normally be used in deriving an ADI from a study of this type, the Meeting was concerned about the possibility that reproductive performance may have been affected at 1.2 mg/kg of body weight per day in this study and therefore used a higher-than-normal safety factor. No data are available to assess whether the effects on reproductive performance were secondary to inhibition of cholinesterase. The Meeting concluded that it was not appropriate to base the ADI on the results of the studies in volunteers, since the crucial end-point (reproductive performance) has not been assessed in humans.

Since the estimated total daily intake from food is far below the ADI, 10% of the ADI can be allocated to drinking-water. With this allocation to drinking-water, the guideline value for dimethoate is 6 µg/litre.

There may be a need to re-evaluate the toxicity of dimethoate after the periodic review of the residue and analytical aspects of dimethoate has been completed if it is determined that omethoate is a major residue.

3 This section has been taken from FAO/WHO (1997). 4 DIMETHOATE IN DRINKING-WATER

8. REFERENCES

FAO/WHO (1997) Pesticide residues in food — 1996 evaluations. Part II — Toxicological. Geneva, World Health Organization, Joint FAO/WHO Meeting on Pesticide Residues (WHO/PCS/97.1).

Frank R, Logan I (1988) Pesticide and industrial chemical residues at the mouth of the Grand, Saugeen and Thames rivers, Ontario, Canada, 1981–1985. Archives of Environmental Contamination and Toxicology, 17:741.

Health Canada (1991) Dimethoate. In: Guidelines for Canadian drinking water quality — supporting documents. Available at http://www.hc-sc.gc.ca/hecs-sesc/water/dwgsup.htm.

Hundley HK et al. (1988) Pesticide residue findings by the Luke method in domestic and imported foods and animal feeds for fiscal years 1982–1986. Journal of the Association of Official Analytical Chemists, 71(5):875.

IPCS (1989) Dimethoate. Geneva, World Health Organization, International Programme on Chemical Safety (Environmental Health Criteria 90).

WHO (2001) The WHO recommended classification of pesticides by hazard and guidelines to classification 2000–2002. Geneva, World Health Organization, International Programme on Chemical Safety (WHO/PCS/01.5).

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