Agriculture Reference
In-Depth Information
A clear majority of the toxicity and carcinogenicity assessments involves
the administration of SEM into various species. Some of the detected side
effects include lathyrism (a collagen cross linking disease) in rats, death and
fetus retardation in hamsters, tissue abnormalities such as hemorrhaging in the
brain, liver and intestine, abnormalities in bone formation and underdeveloped
testes in rats injected with low doses of SEM hydrochloride saline solution
during various days of gestation [64-65].
However, there are some conflicting results on the carcinogenicity of the
compound. While it has been shown that there is a significant incidence of
lung tumors in mice administered with low doses (≤ 0.1%) of SEM
hydrochloride, it has been reported that SEM hydrochloride produces negative
results in what concerns to potential carcinogenicity [15]. More recent work
evaluated the effect of semicarbazide exposure on the endocrine pancreas,
showing the existence of small differences between control and experimental
groups fed with low doses of hydrochloride semicarbazide [66].
Nitrofurantoin [N-(5-nitro-2-furfurylidene)-1-aminohydantoin] and
nifuroxazide [(5-nitro-2-furfurylidene) hydrazide] are prescribed as a first-line
prophylaxis therapy for acute or recurrent urinary tract infections and
nocosomial urinary tract infections, and as therapy for acute diarrhea of
bacterial origin in humans, respectively. Recently, pulmonary injuries
associated to the use of nitrofurantoin for more than 6 months have been
reported [58]. Both compounds have been demonstrated to be mutagenic in
bacteria [34], but only a few studies have investigated their mutagenic action
in higher organisms.
In vitro
, NFT increased the frequency of sister-chromatid
exchange (SCE) in Chinese hamster ovary cells.
In vivo
, NFT did not induce
micronuclei in reticulocytes from the bone marrow of rats and did not show a
significant effect in the mouse spot test. However, this compound has been
classified as a borderline inducer of sex-linked recessive lethal mutations in
Drosophila melanogaster
[58]. A cytogenetic analysis of peripheral blood
lymphocytes of children treated with NFT reported a statistically significant
correlation between cumulative dose of this compound and SCE frequency
after 1 month of the therapy [67]. According to these data, recent experiments
in mice showing an increase in the frequency of micronuclei by nitrofurantoin,
suggest the need for reevaluating the genotoxic potential of this compound
[68].
The views of the European Food Safety Authority (EFSA) on the presence
of the nitrofurazone metabolite semicarbazide in food have been made public
some years ago (European Food Safety Authority, 2005). On the basis of the
difference in magnitude between experimental animals and humans (including
