Public Health Significance of Urban Pests
489
light on the mechanism by which the pesticide causes the carcinogenic effect often accom- pany these studies. Based on study outcomes, a weight-of-evidence approach is used to
decide if a pesticide is likely to pose a cancer risk to people PMRA, 2000.
The results obtained so far by the IARC include more than 60 pesticide AIs, most of which are no longer in common use. The AIs used also for urban pest control include: the
pyrethroids deltamethrin, fenvalerate and permethrin; the organophosphates dichlorvos, malathion, methyl parathion, parathion, tetrachlorvinphos and trichlorfon; and the syner-
gist piperonyl butoxide. T hese compounds were included in IARC Carcinogen Classifications
5
Group 3 agents not classifiable as to their carcinogenicity to people, except dichlorvos, which was classified as Group 2B an agent possibly carcinogenic to
people. Among other things, dichlorvos has been criticized on the basis of biochemical and toxicological considerations FAOWHO, 1994. More recently, the Scientific Panel
on Plant H ealth, Plant Protection Products and their Residues PPR Panel of the European Food Safety Authority considered the carcinogenic potential of dichlorvos in
animals to be not relevant to human beings, on the basis of mechanistic considerations PPR Panel, 2006. Also, among the compounds used in urban pest control, dichlorvos
and pyrethrum have been reported to cause allergic contact dermatitis Moretto, 2002.
Children especially in the first 6–12 months after birth are considered by some at higher risk of toxic effects from pesticide exposure, as their metabolic processes are immature
and they are less able to detoxify chemicals. In some instances, however, metabolic imma- turity may be beneficial, because the metabolic pathways that activate their toxic meta-
bolites are not yet developed. Infants and children are growing and developing, and their delicate developmental process can be disrupted. However, the data available suggests
that this possible increased susceptibility is evident at high doses, whereas young animals do not appear to be more susceptible to low doses that cause no toxic effects in adults see
the discussion in subsection 14.3.2.2 on pyrethroids.
Exposure to pesticides during pregnancy can have potentially adverse effects on fœtal growth and child neurodevelopment Landrigan et al., 1999. However, when specifi-
cally designed studies of developmental neurotoxicity were available for approved pesti- cides, these effects were not detected at levels lower than those observed in the usual stu-
dies of developmental toxicity, multigeneration reproductive toxicity, and acute and short-term neurotoxicity. In fact, when studies with 14 pesticides evaluated by the EPA
were reviewed by JMPR, among others, the comparison of the toxicity end-points and dose levels without toxic effects that is, NOAEL or the minimal dose causing toxic
effects that is, the lowest observed adverse effect level or LOAEL of each study and of four related studies that had been performed with each chemical showed that, in gene-
ral, the NOAELs and LOAELs did not differ significantly FAOWHO, 2005.
Exposure to disrupting substances during fœtal life can also contribute to the develop- ment of a number of diseases in adult life, including cancer Birnbaum Fenton, 2003.
Pesticides: risks and hazards
488
Therefore, there might be toxicity end- points that are specific to a specific route
and duration of exposure. For instance, a dietary risk evaluation that is usually defi-
ned as the acceptable daily intake ADI will usually use an end-point from a
long-term oral feeding study, while a short-term dermal exposure risk evalua-
tion might use an acute dermal toxicity study.
Toxicity end-points discussed in this chap- ter were chosen from chemical-specific
FAOWH O Joint Meeting on Pesticide Residues JMPR assessments WH O
IPCS, 2002 and EPA regulatory end- points EPA, 2000a, b. Fig. 14.3 shows the
ADI values for some commonly used pes- ticides.
14.3.1.3. Long-term effects
Long-term exposures occur to farmers and professional pesticide users. To a much les- ser extent, they also occur to the general population via residues in food and water and
by environmental exposure to pesticides from indoor and outdoor use for pest control. Identifying subjects who have been occupationally or non-occupationally chronically
exposed to pesticides is relatively easy, but toxicological evidence of exposure is seldom available. Moreover, extrapolation from current data to assess past exposures as well as the
risk associated with a given pesticide is difficult, since AIs and application practices dif- fer and change with time. This is particularly true in the general population where data
on exposure and biological monitoring are scanty or non-existent. Attention has been focused on the carcinogenicity, allergenicity and teratogenicity of pesticides, and most
recently on their effect on endocrine disruption and neurological development. However, the long amount of time it takes for these effects to develop and show clinically detecta-
ble signs hampers their identification in population studies. Evaluations of the carcino- genic potential of relatively few pesticides have been performed by the International
Agency for Research on Cancer IARC, even though carcinogenicity studies in animals are available for all pesticides. However, most of these studies have not been published in
the open literature. Several criteria are used by the IARC for choosing the compounds to be evaluated and include: evidence of human exposure and some experimental evidence
of carcinogenicity or some evidence or suspicion of a risk to people, or both.
The assessment of a pesticide’s potential to cause cancer requires a different kind of assess- ment and expression of risk. Assessing the risk of cancer from exposure to pesticides is
based on evidence from cancer studies in at least two species, usually the rat and the mouse, together with evidence from in vitro and in vivo genotoxicity studies. Dose levels
in these studies are much higher than expected for human exposures. Studies that shed
Fig. 14.3. ADI values for commonly used pesticides
Source: WHO IPCS 2002, EPA 2000a, b.
5
IARC Carcinogen Classifications: Group 1: known human carcinogen; Group 2A: probable human carcinogen; Group 2B: possi- ble human carcinogen; Group 3: not classifiable for human carcinogenicity; and Group 4: probably not carcinogenic to humans.
Public Health Significance of Urban Pests
491
of OPIDP follow a massive ingestion of an OP by suicidal people, and only a few cases involve careless occupational exposures to methamidophos. No human case was repor-
ted after residential exposure Moretto Lotti, 1998; Lotti Moretto, 2005. OPIDP is characterized by flaccid paralysis of the lower limbs, but the upper limbs might also be
affected in severe cases. The sensory peripheral nervous system is affected to a lesser deg- ree Moretto Lotti, 1998. The histopathology of OPIDP shows degeneration of long
and large-diameter axons in peripheral nerves and the spinal cord. OPIDP development is unrelated to inhibition of AChE, and the putative molecular target is a nervous sys-
tem protein called neuropathy target esterase Lotti, 1991. Since all commercial OP insec- ticides display high potency for AChE, OPIDP always develops after doses that cause
severe cholinergic syndrome.
Repeated exposures to OPs at doses that do not cause AChE inhibition do not cause either neuropsychiatric disorders or behavioural disturbances Lotti, 1991. Also, persistent elec-
troencephalogram EEG changes have been reported in industrial workers who had repeated accidental exposures to sarin a nerve agent similar in structure and biological
activity to some commonly used OP insecticides. The exposures caused symptoms and significant inhibition of red blood cell AChE. The toxicological significance of these EEG
changes has, however, been questioned Lotti, 1991.
Observational studies aimed at detecting mild peripheral neuropathy or changes in per- ipheral nerve functions have been performed on individuals with varying long-term, low-
level exposures to OPs. These studies include different occupational exposures, such as those that occur in sheep dip farmers, and exposures of military personnel during the
first Gulf War in 19901991, and they have been reviewed recently Lotti, 2002. It was concluded that these studies suffered from a number of limitations. For instance, they
did not accurately assess exposure and reported changes in peripheral nerves were usually mild and inconsistent, sometimes reversible and sometimes apparently irreversible,
because they were observed a long time after cessation of exposure. Understanding these changes is difficult, because of the lack of histopathological studies of tissues, follow-up
data and an experimental model for such peripheral nerve changes that seem different from classic OPIDP. In addition, electrophysiological results were usually examined toge-
ther as a group, and a correlation with clinical data was almost always missing. Finally, since these pesticides are far better inhibitors of AChE than neuropathy target esterase,
they are expected to cause peripheral neuropathy at doses that inevitably cause choliner- gic toxicity, irrespective of type of exposure.
ADIs of OPs vary between 0–0.0003 and 0–0.3 milligrams per kilogram body weight mgkg BW per day, depending on the AI considered, and acute reference doses ARfDs
measured in mgkg BW are roughly an order of magnitude higher WH O IPCS, 2006b.
14.3.2.2. Pyrethroids
