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

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Table 20. Relevant findings in a study of prenatal developmental toxicity in rats given
hydroxyatrazine by gavage
Finding
Dose (mg/kg bw per day)
0 5 25 100
Food consumption (g/day), days 8–12 23.4 23.7 22.6 20.6*
Total food consumption (g), days 6–16 229.4 236.7 223.3 210.1*
Body-weight gain (g), days 8–12 23.5 20.9 21.1 18.0
Net body-weight change (g), days 0–20 77.2 81.9 71.1 68.6
No. of rats pregnant 25 23 23 22
Postimplantatation loss (mean) 0.5 1.1 1.0 0.7
Postimplantation loss (%) 5.6 7.4 11.6 4.9
Mean No. of live fetuses 13.40 13.30 12.30 14.14
Mean fetal weights (g), males/females 3.61/3.43 3.71/3.51 3.55/3.35 3.47*/3.26*
Skeletal examination (No. of fetuses/litters) 177/25 159/23 147/22 160/22
Hyoid not completely ossified (No. of fetuses/litters) 11/5 26/9 14/8 27*/12*
Interparietal not completely ossified (No. of fetuses/litters) 35/14 57/19 42/14 70*/20*
Metacarpal not ossified (No. of fetuses/litters) 67/21 58/18 61/19 96*/21*
Proximal phalange not ossified (No. of fetuses/litters) 169/24 153/23 139/22 159*/22*
From Lindsay et al. (1989)
* p < 0.05; ** p < 0.01.\
compared with controls. All substances were without effect on [ 3 H]muscimol or [ 35 S]TBPS binding.
The results suggested that atrazine modulates benzodiazepine, but not the muscimol (GABA receptor
site) or TBPS (chloride channel), binding sites on GABA A
receptors (Shafer et al., 1999).
In a study on the effect of chlorotriazines on catecholamine metabolism in vitro using pheochromocytoma
(PC12) cells, intracellular norepinephrine (NE) and dopamine (DA) concentrations
and spontaneous NE release were measured after treatment with atrazine (0, 12.5, 25, 50, 100 and
200 µmol/l) for 6, 12, 18, 24 and 48 h.
Intracellular DA concentration was significantly decreased at 12.5 µmol/l and greater, while
intracellular NE concentration was significantly decreased at 100 µmol/l and greater. Similarly, there
was a dose-dependent inhibition of NE release at 50 µmol/l and greater. The GABA A
-receptor agonist,
muscimol (at 0, 0.01, 0.1, and 1.0 µmol/l) had no effect on either the release or on intracellular
catecholamine concentrations from 6 h until 24 h of treatment. Cell viability was somewhat lower
at 100–200 µmol/l, but the reduction in viability was significant only at 200 µmol/l at 24 h. The data
indicated that atrazine inhibits the cellular synthesis of DA mediated by the tyrosine hydroxylase,
and NE mediated by dopamine beta-hydroxylase, resulting in an inhibition of NE release. Thus, atrazine
presumably acts at the enzymatic steps or sites of DA biosynthesis to modulate monoaminergic
activity in PC12 cells (Das et al., 2000).
In a subsequent study on the effect of chlorotriazine metabolites on catecholamine metabolism
in vitro using PC12 cells, intracellular NE and DA concentrations and spontaneous NE release
were measured after treatment with hydroxyatrazine (0–400 µmol/l), DEA (0–200 µmol/l), DIA
(0–200 µmol/l) and DACT (0–160 μmol/l) for 3–24 h.
Hydroxyatrazine significantly decreased intracellular DA and NE concentrations in a dose- and
time-dependent manner, and caused also a significant inhibition of NE release from cells. In contrast,
ATRAZINE 37–138 JMPR 2007