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

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Immunological
effects in B6C3F 1
mice
Study of
developmental
immunotoxicity in
Sprague-Dawley rats
Effect on human
NK cell cytotoxic
function (tumour-cell
lysis) in vitro
Cytokine production
in vitro in
mononuclear cells
from humans
Immunological
effects in juvenile
male C57BL/6 mice
(age 1 month)
Immunological
effects in female
B6C3F 1
mice (age
4–6 weeks)
Immunological
effects in female
B6C3F 1
mice
Immunological
effects in offspring
of Balb/c mice
exposed on day 10 of
gestation to postnatal
day 11
Single
intraperitoneal.
dose at 100, 200 or
300 mg/kg bw
Oral gavage at
35 mg/kg bw per
day from day 10 of
gestation to postnatal
day 23
Decrease in percentage of
CD4 + CD8 + cells in thymus
and B220 + cells in spleen;
decreased splenic NK cell
activity; decreased IgG1
and IgG2a response to KLH
Decrease in pup survival
(postnatal days 2–14)
and body weight (males,
postnatal day 7). Primary
antibody (IgM) response
to SE and delayed-type
hypersensitivity response
to BSA decreased in males
only.
10 μmol/l (2.2 ppm) Decreased cytotoxic
function of NK cells (by
63–83%) and of T/NK
cells (by 61–65%) after
24 h and 6-day incubation
3 μmol/l (0.65 ppm) Cytokine (IFN-γ, IL-5)
production reduced by 12.3
and 14.8%, respectively;
no effect on TNF-α, IL-4,
IL-6 and IL-13.
0, 5, 25, 125 or
250 mg/kg bw per
day for 14 days
0, 25, 250 or
500 mg/kg bw per
day for 14 days
0, 75, 150, 225
or 300 mg/kg by
intraperitoneal
injection.
0.7 mg/dam per day,
equal to 23–35 mg/kg
bw per day (released
from a subcutaneous
implanted capsule)
Decrease of thymus and
spleen weights and organ
cellularity at ≥ 25 mg/kg;
transient changes in thymic
and splenic subpopulations
at ≥ 5 or ≥ 25 mg/kg,
respectively.
Decrease of thymus and
spleen weights, total spleen
cell numbers and fixed
macrophage function;
increased number of
splenic CD8+ T cells,
increased cytotoxic T
cell and mixed leukocyte
responses, reduced host
resistance to tumour
challenge
Effects on spleen and
thymus of all stressors.
Corticosterone comparable
to atrazine
Increase of HKSP-specific
IgM-secreting B cells;
increase in both T cell
proliferation and cytolytic
activity
Non-specific stress, as
indicated by plasma
corticosterone AUC, was
predictive of the immune
response
Effects in males only, may
be related to increased pup
mortality or reduced pup
body weight; NOAEL not
identified.
An effect attributable to
high concentration in vitro
Minimum effect that is
unlikely to impact the
allergic response; NOAEL
not identified.
Most effects no longer
present at 7 weeks
after treatment; the
decreases of thymic T-cell
populations at ≥ 5 mg/
kg bw per day (at day 1
only) are not predictive
of impaired function (i.e.
not considered to be an
adverse effect).
Spleen weight reduced
at ≥ 25 mg/kg bw per day
Cytotoxic T-cell response
increased at ≥ 25 mg/kg
bw per day
See Pruett et al. (2003)
Effects observed only in
males; no changes in the
number of CD8+ T-cell,
CD4+ T-cell or B220+
B-cell subpopulations
Pruett et al.
(2003)
Rooney et al.
(2003)
Whalen et al.
(2003)
Devos et al.
(2004)
Filipov et al.
(2005)
Karrow et al.
(2005)
Schwab et al.
(2005)
Rowe et al.
(2006)
BSA, bovine serum albumin; CFU-GM, colony-forming unit-granulocyte-macrophage; CFU-S, colony-forming unitspleen;
DMSO, dimethyl sulfoxide; IFN, interferon; IL, interleukin; KLH, keyhole limpet haemocyanin; NK, natural
killer; PHA, phytohaemagglutinin; SE, sheep erythrocytes; TNF, tumour necrosis factor;
ATRAZINE 37–138 JMPR 2007