Bt Research 2015, Vol.6, No.4, 1-12
7
when compared to the control group. (Bishop et al.,
1999) reported that rats that received oral doses (1 x
10
12
spores/ml) for three weeks or a single subcutaneous
dose (1 x 10
6
) showed no effects on behavior, bacterial
infection, or pathologies in their internal organs. All
cultures of blood, heart, spleen and liver were negative
for the presence of
Bt
. De Lecadet and Barjac (1975)
demonstrated that rats excreted in the feces the
thuringiensin previously administered orally; the
presence of these toxins in the urine was negative and
that there was no thuringiensin accumulation in tissues.
(Meretoja et al., 1977) report that were not observed
megakaryocytes in the bone marrow or polymorphs in
blood cultures, which are typical defects of contamination
by chemicals, radiation, or infection. The same
authors did not observe the incidence of chromosomal
aberrations in the bone marrow cells, even in animals
that received a lethal dose of exotoxins. Despite all the
adverse effects of thuringiensins observed in mice,
there is only one report of human food poisoning
attributable to
Bt
(Jackson et al., 1995). However, it is
believed to be under-represented due to the lack of
differentiation between strains of
Bt
and
B. cereus
which is an opportunistic human pathogen capable of
causing gastroenteritis (Bishop et al., 1999).
Bt
strains
have been found in skin and corneal ulcers in humans,
but it is not proved they were the causative agent
(Samples and Buettner 1983; Green et al., 1990).
Fisher and Rosner (1959) exposed humans at doses of
a commercial preparation of
Bt
subsp.
thuringiensis
,
orally and via inhalation over five days, but there were
no adverse clinical indications. Numerous other tests
with
Bt
and vertebrates were performed without fatality
reports after oral or subcutaneous administration (Burges
1981; Siegel and Shadduck 1990; Drobniewski 1994).
The positive responses in some studies with rodents
have shown that they are good experimental models to
evaluate the toxicity of thuringiensins to humans
(Bishop et al., 1999). Assuming that the thuringiensins
intake, is the most likely way of humans come in
contact with this exotoxin, several studies have
investigated the dose required for a possible poisoning.
(Tan et al., 1997) suggested that the dose would be 10
5
cells/g. Belder and Elderson (2013) indicated an LD
50
acute oral of 170 mg/kg, or even more than 5000
mg/kg in rats. When injected intraperitoneally,
thuringiensins are toxic to vertebrates at a LD
50
for of
13-18 mg/kg body weight (Swadener, 1994). As many
Bt
products are wettable powders which can easily
enter the airways of vertebrates, studies have also
investigated the median lethal concentration (LC
50
) for
acute inhalation of thuringiensin in rats. Belder and
Elderson (2013) affirm that it ranges from 0.024 to
more than 0.3 mg/L, for approximately 4 h of exposure.
(Tsai et al., 2003) indicate that the LD
50
of the acute
intratracheal instillation of thuringiensin in rats is 4.4
mg/kg body weight. From these results, it is possible
to notice that the lethal doses of thuringiensins to
humans are much higher than those that are required
to cause lethality in target organisms.
7 Prohibition of Insecticides containing
Thuringiensins
Biopesticides containing thuringiensins in its formulation,
as Bitoxibacillin (Lipa, 1985), Muscabac (Carlberg,
1986), or Thuricide (Siegel, 2001), which are based on
Bt
subsp.
thuringiensis
, were widely used to control
the larvae of
M. domestica
(Mullens et al., 1988;
Mullens and Rodriguez 1988), besides flies that who
did infest sheds, pigsties and slaughter houses (Carlberg
et al., 1991; Meretoja et al., 1977; Mwamburi et al., 2009).
However, since Šebesta and Horska (1969) stated that
thuringiensins ware lethal to rats, the commercial use
of this toxin began to be criticized. Thus, its potential
toxic to mammals restricts its wide application in
biological control (Zhou et al., 2013) and, since 1999,
the World Health Organization (who) has recommended
not to use
Bt
thuringiensin-producing strains in the
formulation of biopesticides (Belder and Elderson
2013; Bishop et al., 1999; Mac Innes and Bouwer
2009; Palma et al., 2014; Siegel 2001; Veloorvalappil
et al., 2013; WHO 1999). For this reason, the
production of thuringiensins is a limiting factor in the
selection of new strains of
Bt
with potential use in
biological control of pests (Arango et al., 2002).
Whenever a new entomopathogenic microorganism is
presented as a candidate for use in biological control
practices, its effect on non-target organisms must be
investigated (Cantwell et al., 1966). Therefore, it is
recommended that tests be performed in order to
detect these undesirable exotoxins and, if the organism
is considered able to produce them, should ensure that
they are not present in doses of risk and that the
product does not come into contact with media that
allow its germination and/or growth at any time prior
to use (Belder and Elderson, 2013).
