Pesticide residues in food — 2007: Toxicological ... - ipcs inchem

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increase in steroidogenesis is the result of increased ACTH secretion, either through a direct effect
on the pituitary or through the release of corticotropin-releasing factor (CRF) in the central nervous
system (Laws et al., 2006).
(k)
Studies of immunotoxicity
The potential immunotoxicity of atrazine has been evaluated in a variety of mammalian and
non-mammalian animal models (Table 23). Considered overall, the reports indicate that modulation
of the immune system occurs after exposure to atrazine, albeit at doses greater than those known to
disrupt neuroendocrine function and suppress LH and prolactin release.
Table 23. Selected published studies of immunotoxicity with atrazine
Test system Dose/concentration Finding Comment Reference
Lymphatic response
in chicks (age
3 days)
150 ppm in feed for
21 days
Increased thymus
and bursa weight that
correlated with glycogen
content.
Stimulated immunological
reactions (antibody
titre, gamma-globulin
concentration, leukocyte
count)
Transient and reversible
suppression of humoralmediated
and cellmediated
responses;
activated macrophage
phagocytic activity.
CFU-S and CFU-GM
in bone marrow and
reticulocyte count in blood
reduced for 6–8 days after
treatment; leukocyte count
unaffected by treatment.
No effect on body
weight, spleen weight
or lymphocyte plaqueforming
ability when
challenged with foreign
protein
Cytokine (IFN-γ, IL-5,
TNF-α) production
significantly reduced by up
to 50–70% at ≥ 0.3 μmol/l
Cytokine (IFN-γ, IL-5,
TNF-α) production
reduced by up to 40–60%;
no effect on IL-8.
Decreased lymphocyte
activation with PHA
at concentrations of
10 -1 – 10 -2 mol/l (i.e.
concentration in leukocyte
suspensions: 22–216 ppm)
All parameters returned to
control levels by day 21.
Giurgea &
Koszta (1979)
E. coli challenge test
in Wistar rats
2 or 150 mg/kg bw
per day for 60 days
Inconsistent dose–response
relationship; NOAEL
could not be identified..
Giurgea et al.
(1981)
Mouse leukocyte
immunosuppression
and phagocytic
impairment
Single oral doses at
27.3, 109.4, 437.5
and 875.0 mg/kg bw
Absence of a dose–
response relationship;
authors did not attribute
the changes to a direct
effect of atrazine on
immune system
Transient response to a
single high dose. NOAEL
not identified.
Fournier et al.
(1992)
Haematopoietic
system (progenitor
cells in bone
marrow) in
atrazine-treated mice
Single
intraperitoneal dose
at 58.65 mg/kg bw
Mencoboni
et al. (1992)
Long-term exposure
of laboratory and
wild mice
10 ppb in water for
22–103 days
Atrazine in combination
with other chemicals not
considered here
Porter et al.
(1999)
Effect on cytokine
production in vitro
in mononuclear cells
from humans
Cytokine production
in vitro in
mononuclear cells
from humans
Exposure of sheep
leukocytes in vitro
0.03, 0.3 and
3 μmol/l (6.5, 65
and 647 ppb) in 1%
DMSO
3 μmol/l (0.65 ppm)
in 1% DMSO
Effect of 1% DMSO on
cellular uptake of atrazine
unknown
Hooghe et al.
(2000)
Authors concluded that the
effect was not mediated via
the glucocorticoid receptor.
Devos et al.
(2003
10 -6 – 10 -1 mol/l
(0.2–21 570 ppm)
in 1% DMSO;
added to leukocyte
suspensions in 1%
volumes
Limited biological
relevance because
concentration was at
or above the limit of
solubility for atrazine in
water (33 ppm)
Pistl et al.
(2003)
ATRAZINE 37–138 JMPR 2007