WHO/HSE/WSH/09.

01/1
English only

Temephos in Drinking-water:
Use for Vector Control in Drinking-water Sources and Containers

Background document for development of

WHO Guidelines for Drinking-water Quality
  World Health Organization 2009

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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 on
selected chemicals in 1998 and on microbial aspects in 2002. The third edition of the
GDWQ was published in 2004, the first addendum to the third edition was published
in 2005, and the second addendum to the third edition was published in 2008.

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 and 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 of potential health
concern in drinking-water. In the first and second editions, these constituted Volume 2
of the GDWQ. Since publication of the third edition, they comprise a series of free-
standing monographs, including this one.

For each chemical contaminant or substance considered, a lead institution prepared a

background 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 documents for the third edition
and addenda.

Under the oversight of a group of coordinators, each of whom was responsible for a
group of chemicals considered in the GDWQ, 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. The draft
documents were also released to the public domain for comment and submitted for
final evaluation by expert meetings.
During the preparation of background documents and at expert 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 Temephos in Drinking-water: Use for Vector Control in Drinking-
water Sources and Containers, Background document for development of WHO
Guidelines for Drinking-water Quality, was prepared by Dr A.V.F. Ngowi, Tanzania,
to whom special thanks are due.

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

Dr J. Cotruvo, J. Cotruvo Associates, USA (Materials and chemicals)

Mr J.K. Fawell, United Kingdom (Naturally occurring and industrial
contaminants)
Ms M. Giddings, Health Canada (Disinfectants and disinfection by-products)
Mr P. Jackson, WRc-NSF, United Kingdom (Chemicals – practical aspects)
Prof. Y. Magara, Hokkaido University, Japan (Analytical achievability)
Dr Aiwerasia Vera Festo Ngowi, Muhimbili University of Health and Allied
Sciences, United Republic of Tanzania (Pesticides)
Dr E. Ohanian, Environmental Protection Agency, USA (Disinfectants and
disinfection by-products)

The draft text was discussed at the Expert Consultation for the Fourth Edition of the
GDWQ, held in Singapore on 19–23 June 2008. The final version of the document
takes into consideration comments from both peer reviewers and the public. The input
of those who provided comments and of participants in the meeting is gratefully
acknowledged.

The WHO coordinator was Dr J. Bartram, WHO Headquarters. Ms C. Vickers

provided a liaison with the International Programme on Chemical Safety, WHO
Headquarters. Mr Robert Bos, Public Health and the Environment Programme, WHO
Headquarters, provided input on pesticides added to drinking-water for public health
purposes.

Ms Penny Ward provided invaluable administrative support at the Working Group

Meeting and throughout the review and publication process. 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

ARfD acute reference dose
CAS Chemical Abstracts Service
FAO Food and Agriculture Organization of the United Nations
GDWQ Guidelines for Drinking-water Quality
IUPAC International Union of Pure and Applied Chemistry
JMPR Joint FAO/WHO Meeting on Pesticide Residues
Kow octanol–water partition coefficient
LD50 median lethal dose
MOE margin of exposure
NOAEL no-observed-adverse-effect level
TDI tolerable daily intake
WHO World Health Organization
 Table of contents

1. GENERAL DESCRIPTION......................................................................................1
1.1 Identity .................................................................................................................1
1.2 Physicochemical properties .................................................................................1
1.3 Major uses and sources in drinking-water ...........................................................1
1.4 Environmental fate...............................................................................................1

2. HUMAN EXPOSURE...............................................................................................1

3. TOXICOLOGICAL SUMMARY .............................................................................2

4. PRACTICAL ASPECTS ...........................................................................................4

4.1 Analytical methods and analytical achievability .................................................4
4.2 Removal in water treatment .................................................................................4
4.3 Use for vector control in drinking-water sources ................................................4

5. CONCLUSIONS........................................................................................................5

6. RECOMMENDATIONS...........................................................................................5

7. REFERENCES ..........................................................................................................5
1. GENERAL DESCRIPTION

1.1 Identity

CAS No.: 3383-96-8

Molecular formula: C16H20O6P2S3

The IUPAC name for temephos is O,O,O',O'-tetramethyl O,O'-thiodi-p-phenylene

bis(phosphorothioate).

1.2 Physicochemical properties (WHO, 2005)

Property Value
Melting point 30–30.5 °C
Water solubility 30 µg/l at 25 °C
Log octanol–water partition coefficient (log Kow) 4.91 at 25 °C
Vapour pressure 8 × 10−6 Pa at 25 °C (extrapolated)

1.3 Major uses and sources in drinking-water

Temephos is a non-systemic organophosphorus insecticide, mainly used as a larvicide

to control mosquito on ponds, marshes, swamps and neighbouring ground at 0.1–0.5
kg/h; midge, black fly and other insects in public health; and fleas on dogs and cats. It
is also used for mosquito control in potable water. It is specified for use as a vector
control agent in drinking-water sources by WHO under the WHO Pesticides
Evaluation Scheme. Formulations for control of vectors are specified by WHO (2005,
2006). The recommendation for the use of temephos in potable water is that the
dosage should not exceed 1 mg/l.

Temephos is also used experimentally on cotton, alfalfa, citrus and other crops for
control of cutworms, thrips on citrus and Lygus bugs. It is sometimes mixed with
other insecticides for broader spectrum control. It is also used as a formulated powder
for the control of body lice (Pediculus humanus humanus) (FAO/WHO, 1978).

1.4 Environmental fate

Temephos has a relatively high log Kow and would be expected to adsorb to particles,
sediment and the sides of containers. It appears to be rapidly degraded under field
conditions (Lacorte et al., 1996). The primary means of degradation are sunlight and
microbiological action (USEPA, 2001). In order to extend its half-life in water in
containers, it would, therefore, be appropriate to exclude sunlight. The major
transformation products of temephos are temephos sulfoxide and temephos sulfone,
which are more water soluble.

2. HUMAN EXPOSURE

It is expected that exposure of the public through either food or drinking-water would
be low. However, there is a potential for direct exposure through drinking-water when
temephos is directly applied to drinking-water storage containers.

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TEMEPHOS IN DRINKING-WATER

3. TOXICOLOGICAL SUMMARY1

When given to rats as an oral dose, temephos was rapidly absorbed. At least 40% of
the administered dose was absorbed into the blood plasma. Clearance was rapid
(mostly within 48 h), with about 40% of an orally administered dose being excreted in
the urine and about 60% recovered in the faeces. Very little of the orally administered
dose remained in tissues, but most (about 3% of the administered material) was in
adipose tissue. Metabolism in rats is by S-oxidation to form the primary toxicant,
temephos sulfoxide, and by carboxylesterase-mediated hydrolysis to form 4,4′-
thiodiphenol. Temephos and these primary metabolites can undergo secondary
metabolism by glucuronidation or sulfation to form conjugates.

Temephos was of low acute oral toxicity in rats (LD50, 4000–13 000 mg/kg body
weight) and mice (LD50, 2062 mg/kg body weight). Temephos did not cause irritancy
to rabbits’ eyes or to the skin of rabbits or guinea-pigs. It was not a skin sensitizer
when tested on guinea-pigs in the Buehler test. In short-term studies with temephos
administered in the diet or by gavage in rats (28–92 days), rabbits (30–35 days) and
dogs (90–129 days), acetylcholinesterase activity in erythrocytes and, in some
instances, in the brain was measured, and animals were observed for clinical signs.
The overall NOAEL for clinical signs was 10 mg/kg body weight per day, as derived
from a study in rats treated by gavage for 28 and 44 days and from a study in rabbits
treated by gavage for 35 days. This NOAEL is supported by the absence of clinical
signs at 5.4 and 30 mg/kg body weight per day, the highest doses tested, in the
multigeneration study in rats and in a study of developmental toxicity in rabbits
treated by gavage, respectively. Additional support is provided by the presence of
mild signs in dogs given diets containing temephos at a concentration of 500 mg/kg
diet for about 11 weeks, approximately equivalent to 25 mg/kg body weight per day.
The NOAEL for biologically significant (i.e. 20% greater than control values)
inhibition of brain acetylcholinesterase activity was 54 mg/kg diet (2.3 mg/kg body
weight per day) in a 90-day dietary study in rats. In a 90-day dietary study in dogs,
“marked” inhibition (no control values provided) in brain and >95% inhibition of
erythrocyte acetylcholinesterase activity were reported after treatment at 500 mg/kg
diet (25 mg/kg body weight per day), and there was no inhibition of erythrocyte
acetylcholinesterase activity at 18 mg/kg diet (about 1 mg/kg body weight per day).
The overall NOAEL for biologically significant (i.e. 20% greater than control values)
inhibition of erythrocyte acetylcholinesterase activity was 1.8 mg/kg body weight per
day in a 99-day dietary study in rats. Occasional and inconsistent reductions of
erythrocyte acetylcholinesterase activity observed at lower doses in some studies in
rats were not considered to be significant. The Meeting noted that between 80% and
more than 90% inhibition of erythrocyte acetylcholinesterase activity was not
associated with clinical signs of cholinergic toxicity in a 99-day dietary study in rats
or in a limited 129-day dietary study in dogs, and this suggested that inhibition of
erythrocyte acetylcholinesterase activity was not an appropriate indicator of inhibition
of the activity of acetylcholinesterase in the peripheral nervous system. Consequently,
the Meeting considered that the critical end-point for human risk assessment was
inhibition of brain acetylcholinesterase activity, and the NOAEL was 2.3 mg/kg body
weight per day.

1
After FAO/WHO (2006).

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 TEMEPHOS IN DRINKING-WATER

In a study in human male volunteers who were prisoners, 10 men were given
temephos at a dose of 1.1 mg/kg body weight per day for 4 weeks, and 9 men took
temephos at a dose of 4.27 mg/kg body weight per day for 5 days. There was no
inhibition of cholinesterase activity in the plasma or in erythrocytes.

This study in human volunteers who were prisoners was considered to be ethically
acceptable according to the standards of the time it was performed (1967), although it
would not be acceptable by current standards applied to new studies. The Meeting
considered that the doses and the outcomes in this study in humans were not
sufficiently well described for the results of this study to be used in isolation to set an
ADI or an ARfD.

Hepatotoxicity was inconsistently seen in a series of briefly reported experiments in

rabbits. However, there was no evidence of any hepatotoxicity at doses of up to 30
mg/kg body weight per day in a well conducted and well reported study of
developmental toxicity in rabbits. In a long-term combined study of toxicity and
oncogenicity in rats, no adverse effects on neoplastic or non-neoplastic pathology
were found at any dietary dose tested, up to the highest dose of 15 mg/kg body weight
per day. Cholinesterase activities were not measured in this study.

Temephos gave uniformly negative results in an adequate range of tests for

genotoxicity in vitro and in vivo. The Meeting concluded that temephos is unlikely to
be genotoxic. Studies of reproductive toxicity in rats showed that temephos did not
adversely affect reproduction when given as oral doses of up to 125 mg/kg diet (5.4
mg/kg body weight per day) for up to three generations. In a one-generation study,
temephos at a dose of 500 mg/kg diet (22.5 mg/kg body weight per day) inhibited
erythrocyte cholinesterase in mothers (90%) and in 21-day-old pups (30%), but other
doses were not tested. There was no developmental toxicity or hepatotoxicity in
rabbits given temephos at oral doses of up to 30 mg/kg body weight per day.

Studies in hens showed that temephos did not have the potential to cause
organophosphate-induced delayed neuropathy and did not cause demyelination of
nerves. Although, for the purposes of vector control, temephos is used at a
concentration of up to 1 mg/l in drinking-water, only one report of an investigation of
possible effects in exposed people was available. Approximately 2000 people were
exposed to drinking-water containing temephos for 19 months without any adverse
effects on plasma or erythrocyte cholinesterase activity. No illness attributable to the
treatment was seen, and all eight babies born during the study period were normal.
The drinking-water was treated monthly with temephos. The intended concentration
of 1 mg/l was not achieved, and only one sample contained temephos at a
concentration of more than 0.5 mg/l.

Temephos is recommended by WHO for addition to potable water as larvicide

treatment at an application rate not exceeding 1 mg/l. Assuming that an adult
weighing 60 kg would consume 2 litres/day of drinking-water containing temephos at
1 mg/l, this would be equal to an oral exposure of 0.033 mg/kg body weight.
However, given the limited solubility of temephos in water, incomplete dissolution in
drinking-water would be expected, and this could result in actual exposures being
appreciably less than this estimate. Consequently, 0.033 mg/kg body weight per day

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TEMEPHOS IN DRINKING-WATER

was regarded as a worst-case upper limit of exposure. Some of the studies that were
critical to the assessment were of poor quality. The Meeting considered that the
database was insufficiently robust to serve as the basis for establishing an ADI or an
ARfD for temephos.

The Meeting concluded that the relevant NOAEL for human risk assessment is 2.3
mg/kg body weight per day on the basis of inhibition of brain acetylcholinesterase
activity in rats. This NOAEL provides a margin of exposure (MOE) from the
estimated oral exposure derived from drinking-water treated with temephos of about
70. The MOE for clinical signs and the (possibly secondary) effects on development
and reproduction are in the range of >160 (highest dose tested in rat multigeneration
study) to 900 (study of developmental toxicity in rabbits). In addition, reassurance is
provided by the MOEs of 130 and 33 based on the absence of clinical signs and
erythrocyte cholinesterase inhibition in the poorly described study in volunteers
treated for 5 or 14 days, respectively. In addition to this safety assessment, the
concerned WHO programmes will consider efficacy of the treatment and additional
relevant exposure scenarios before further recommending such a treatment and
deriving drinking-water guideline values.

4. PRACTICAL ASPECTS

4.1 Analytical methods and analytical achievability

Temephos can be extracted by using liquid–liquid or a solid-phase extraction method.

Temephos is analysed by liquid chromatography and thermospray mass spectrometry
coupled with online solid-phase extraction with a C18 cartridge. The limit of
detection and the linear range of calibration curve are 0.038 µg/l and 0.050–2 µg/l,
respectively (Lacorte & Barcelo, 1995). Temephos can also be analysed by high-
performance liquid chromatography with either an ultraviolet detector or a triple stage
quadrupole mass spectrometry detector after condensation. Mass spectrometric
detection is done by using an electrospray ionization source in positive ionization
mode. In this method, the limit of detection is 0.028 µg/l (Protocol of accepted
drinking-water testing methods). Gas chromatography with a nitrogen–phosphorus
detector is used for analysis of temephos (USEPA, 1995).

4.2 Removal in water treatment

The proposed use is unlikely to result in contamination of public water supplies,

although there may be a requirement to reduce levels in some storage containers. No
specific information is available on removal of temephos during water treatment.
However, the low aqueous solubility and high octanol–water partition coefficient (30
µg/l and 4.9, respectively; WHO, 2005) suggest that temephos should be removed by
adsorption onto activated carbon and possibly removed during coagulation.

4.3 Use for vector control in drinking-water sources

Temephos is one of the compounds recommended by WHO for mosquito larvicide
treatment in potable water at an application rate not exceeding 1 mg/l.

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 TEMEPHOS IN DRINKING-WATER

Formulations of temephos used for vector control in drinking-water in containers

should always be those approved for such a use, and users should carefully follow the
recommendations for use (WHO, 2005, 2006).

5. CONCLUSIONS

It is not appropriate to set a formal guideline value for temephos used as a vector
control agent in drinking-water. The NOAEL for human risk assessment for temephos
is 2.3 mg/kg body weight per day, as determined by JMPR in 2006 (FAO/WHO,
2006), giving a TDI of 0.023 mg/kg body weight with an uncertainty factor of 100.
Young animals do not appear to be significantly more sensitive than adults, and
exposure from food is considered to be low. Where temephos is used for vector
control in potable water, this will involve less than lifetime exposure. The maximum
dosage in drinking-water of 1 mg/l would be equivalent to approximately 70% of the
TDI (0.033 mg/kg body weight) for a 60-kg adult drinking 2 litres of water per day.
The exposure for a 10-kg child drinking 1 litre of water would be approximately 0.1
mg/kg body weight; for a 5-kg bottle-fed infant, the exposure would be approximately
0.15 mg/kg body weight, compared with the TDI of 0.023 mg/kg body weight.
However, the low solubility and the high log Kow of temephos indicate that it is
unlikely to remain in solution at the maximum recommended applied dose, and the
actual levels of exposure are likely to be much lower than those calculated.

6. RECOMMENDATIONS

In setting local guidelines or standards, health authorities should take into

consideration the potential for higher rates of water consumption in the area or region
under consideration. Consideration should be given to using alternative sources of
water for small children and bottle-fed infants for a period after an application of
temephos, where this is practical. However, exceeding the TDI does not necessarily
mean that this will result in adverse effects. The diseases spread by vectors are
significant causes of morbidity and mortality. It is therefore important to achieve an
appropriate balance between the intake of the pesticide from drinking-water and the
control of disease-carrying insects.

7. REFERENCES

FAO/WHO (1978) Temephos. Rome, Food and Agriculture Organization of the United Nations;
Geneva, World Health Organization (Data Sheets on Pesticides, No. 8 Rev. 1; VBC/DS/75.8 (Rev.1);
http://www.inchem.org/documents/pds/pds/pest8_e.htm).

FAO/WHO (2006) Temephos. In: Pesticide residues in food—Joint FAO/WHO Meeting on Pesticide
Residues. Rome, Food and Agriculture Organization of the United Nations; Geneva, World Health
Organization (FAO Plant Production and Protection Paper 187).

Lacorte S, Barcelo D (1995) Determination of organophosphorus pesticides and their transformation

products in river waters by automated on-line solid-phase extraction followed by thermospray liquid
chromatography–mass spectrometry. Journal of Chromatography A, 712:103–112.

Lacorte S, Ehresmann N, Barcelo D (1996) Persistence of temephos and its transformation products in
rice crop field waters. Environmental Science and Technology, 30(3):917–923.

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Ontario Ministry of the Environment (2008) Protocol of accepted drinking-water testing methods,
Version 1.0. Toronto, Ontario, Ontario Ministry of the Environment, Laboratory Services Branch
(PIBS 4465e01; http://www.ontario.ca/drinkingwater/stel01_046886.pdf).

USEPA (1995) Method 507: Determination of nitrogen- and phosphorus-containing pesticides in water
by gas chromatography with a nitrogen–phosphorus detector. In: Methods for the determination of
organic chemicals in drinking water, Supplement III. Washington, DC, United States Environmental
Protection Agency (EPA/600/R-95/131).

USEPA (2001) Temephos RED (Reregistration Eligibility Decision). Washington, DC, United States
Environmental Protection Agency (http://www.epa.gov/oppsrrd1/REDs/temephos_red.htm).

WHO (2005) WHO specifications and evaluations for public health pesticides—Temephos. Geneva,
World Health Organization (FAO/WHO Evaluation Report 340/2005;
http://www.who.int/whopes/quality/Temephos_eval_June_2007_corr_aug160807.pdf).

WHO (2006) Pesticides and their application for the control of vectors and pests of public health
importance, 6th ed. Geneva, World Health Organization, Department of Control of Neglected Tropical
Diseases, Pesticides Evaluation Scheme (WHO/CDS/NTD/WHOPES/GCDPP/2006.1;
http://whqlibdoc.who.int/hq/2006/WHO_CDS_NTD_WHOPES_GCDPP_2006.1_eng.pdf).