Exposure period
Species (Strain)
No/sex/group
|
Dose levels |
Results |
NOAEL |
Reference |
| Atrazine |
Two-generation study
Rats (Charles River (CRCD,
VAF/PLUS))
30/sex/group
|
0, 10, 50, 500 mg/kg of feed (equal to 0, 0.8, 3.8, 39 mg/kg bw/day in m and
to 0, 0.9, 3.7, 43 mg/kg bw/day in f)
technical atrazine (97% pure)
|
3.8(m)/3.7(f) mg/kg bw/day and above: Decreased pup weight in the second generation
(according to WHO 1996a, but according to EC 1996a and US-EPA 2001 decreased male
pup weight in both generations were only found at the highest dose).
39(m)/43(f) mg/kg bw/day: Decreased body weight gain and food
consumption in parental rats; increased relative testis weight.
|
3.7 mg/kg bw/day for parental toxicity (stated as 2.5 mg/kg bw/day in EC 1996a)
0.8 (WHO) - 3.7
(US-EPA) mg/kg
bw/day for reproductive
toxicity
|
Ciba-Geigy 1987 - quoted from EC 1996a, US-EPA 2002a, WHO 1996a |
Every 48 hours for 12 days followed by mating four weeks later to unexposed
males
Rats (Fischer 344)
f
|
0, 120 mg/kg bw/day by gavage |
Litter size and pup survival were not statistically different between control
and treated groups. Mild neurobehavioral effects (increased activity level in
female pups; increased avoidance response in male pups but decreased in female
pups) were observed in the pups when tested at about 70 days of age. |
< 120 mg/kg bw/day for developmental toxicity |
Peruzoviæ et al. 1995 – quoted from ATSDR 2001 |
Gestation days 6-15
Rats (Sprague-Dawley)
26/dams/group
|
0, 5, 25, 100 mg/kg bw/day by gavage
technical atrazine (98% pure)
|
100 mg/kg bw/day: One dead dam; decreased body weight gain and food consumption
in dams; salivation and increased alopecia in dams; increased incidence of incomplete
ossification of various bones in foetuses. |
25 mg/kg bw/day for maternal and developmental toxicity |
Ciba-Geigy 1989 – quoted from US-EPA 2002a |
Gestation days 6-15
Rats (Charles River CD)
27/dams/group
|
0, 10, 70, 700 mg/kg bw/day by gavage
technical atrazine (98% pure)
|
70 mg/kg bw/day and above: Decreased body weight gain in dams; delayed or
absent ossification at several sites in foetuses.
700 mg/kg bw/day: 21 dead dams; decreased food consumption in
dams; salivation, oral and nasal discharge, ptosis, swollen abdomen,
blood on the vulva, enlarged stomachs and adrenals, and discoloured
lungs in dams; increased post-implantation loss; reduced foetal weights.
|
10 mg/kg bw/day for maternal and developmental toxicity |
Ciba-Geigy 1984 – quoted from ATSDR 2001, IARC 1999a, US-EPA 2002a |
Gestation days 1-8 (dams were necropsied on day 8 or 9)
Rats (Holtzman,
Sprague-Dawley, Long
Evans, Fischer 344)
dams
|
0, 50, 100, 200 mg/kg bw/day by gavage
Dams were dosed prior to the
diurnal or nocturnal surges of
prolactin.
|
An increase in post-implantation loss as well as a decreased serum luteinizing
hormone and progesterone level was observed in Holtzman rats at the two highest
doses. Decreased serum luteinizing hormone was also observed in the other rat
strains at 100-200 mg/kg bw/day. An increase in serum oestradiol was observed
in Sprague-Dawley rats at the highest dose. An increase in pre-implantation loss
was observed in Fischer 344 rats at the two highest doses. |
50 mg/kg bw/day |
Cummings et al. 2000 – quoted from ATSDR 2001, US-EPA 2002a |
Gestation days 6-10 or 11-15
Rats (Fischer 344,
Sprague-Dawley, Long
Evans)
7-16 dams
|
0, 25, 50, 100, 200 mg/kg bw/day by gavage |
The Fischer 344 strain rat was most sensitive to the effects of atrazine on
pregnancy showing full-litter resorption at doses at or above 50 mg/kg bw/day
when dosed on gestation days 6-10. In Sprague-Dawley and Long Evans rats full-litter
resorption occurred only at 200 mg/kg bw/day. No full litter resorption occurred
when rats were dosed on gestation days 11-15 suggesting that the full-litter resorption
is maternally mediated and consistent with loss of luteinizing hormone support
of the corpora lutea. |
25 mg/kg bw/day |
Narotsky et al. 2001, 2002 – quoted from Toxline abstract, US-EPA 2002a,b |
Post-natal days 1-4, 6-9 or 11-14
Rats (Wistar)
dams
|
0, 6.3, 13, 25, 50 mg/kg bw/day by gavage twice daily |
Atrazine suppressed suckling-induced prolactin release in dams from a dose
of 13 mg/kg bw/day. This suppression resulted in an increased incidence and severity
of prostate inflammation in the male offspring. The critical period for this effect
was post-natal days 1-4 and 6-9. |
6.3 mg/kg bw/day for developmental toxicity |
Stoker et al. 1999 – quoted from ATSDR 2001, US-EPA 2002a |
Post-natal days 21-46
Rats (Wistar and
Sprague-Dawley)
f
|
0, 10, 30, 100 mg/kg bw/day by gavage |
30 mg/kg bw/day and above: Delayed vaginal opening (which is a marker of female
puberty in the rat) in Sprague-Dawley rats.
100 mg/kg bw/day and above: Delayed uterine growth and vaginal
opening in Wistar rats.
|
10 mg/kg bw/day in Sprague-Dawley rats and 30 mg/kg bw/day in Wistar rats
for developmental toxicity |
Ashby et al. 2002 |
Post-natal days 22-41
Rats (Wistar)
f
|
0, 12.5, 25, 50, 100, 200 mg/kg bw/day by gavage |
50 mg/kg bw/day and above: Delayed vaginal opening.
100 mg/kg bw/day and above: Altered oestrous cyclicity.
200 mg/kg bw/day: Reduced body weight; reduced weight of adrenal,
kidney, pituitary, ovary and uterine.
No alterations in thyroid hormones consistent with no histopathological
changes of the thyroid. |
25 mg/kg bw/day for developmental toxicity |
Laws et al. 2000 – quoted from ATSDR 2001, US-EPA 2002a |
Post-natal days 22-47
Rats (Sprague-Dawley)
m
|
0, 50, 100,200 mg/kg bw/day (and possibly other doses) |
100 mg/kg bw/day and above: Decreased serum and intratesticular
testosterone levels and seminal vesicle and ventral prostate weights.
200 mg/kg bw/day: Decreased serum LH.
|
50 mg(kg bw/day for developmental toxicity |
Trentacoste et al. 2001 – quoted from US-EPA 2002b |
Post-natal days 23-53
Rats (Wistar)
m
|
0, 13, 25, 50, 100, 150, 200 mg/kg bw/day by gavage |
13 mg/kg bw/day and above: Delayed preputial separation (which is a marker
of male puberty in the rat).
50 mg/kg bw/day and above: Reduction in ventral prostate weights.
200 mg/kg bw/day: Reduction in seminal vesicle weights; decreased level of intratesticular
testosterone on post-natal day 45 but not 53; increased level of serum oestrone,
oestradiol, and the thyroid hormone T3. |
< 13 mg/kg bw/day for developmental toxicity |
Stoker et al. 2000 – quoted from ATSDR 2001, Stoker et al. 2002, US-EPA
2002a |
Post-natal days 46-48 or 22-48
Rats (Sprague-Dawley)
m
+in vitro experiments
|
0, 50 mg/kg bw/day by gavage |
In both acutely and chronically treated animals, serum and intratesticular
levels of testosterone were significantly reduced by approximately 50 %.
An in vitro experiment demonstrated that atrazine directly inhibited
Leydig cell testosterone production.
|
< 50 mg/kg bw/day |
Friedmann 2002 |
Gestation days 7-19 Rabbits (New Zealand white)
19/dams/group
|
0, 1, 5, 75 mg/kg bw/day by gavage
technical atrazine (96% pure)
|
5 mg/kg bw/day and above: Decreased body weight gain and food consumption
in dams (according to EC 1996a and WHO 1996a, but according to ATSDR 2001, IARC
1999a and US-EPA 2002a these effects were only found at the highest dose).
75 mg/kg bw/day: Clinical signs (stool changes, blood in the cage or on
the vulva) in dams; increased resorption rate and post-implantation loss;
reduced foetal weights; delayed ossification in foetuses.
|
1(EC, WHO) - 5 (ATSDR, US-EPA, IARC) mg/kg bw/day for maternal toxicity
5 mg/kg bw/day for
developmental toxicity
|
Ciba-Geigy 1984 - quoted from ATSDR 2001, IARC 1999a, EC 1996a, US-EPA 2002a,
WHO 1996a |
| Simazine |
Three-generation study
Rats
|
Up to 100 mg/kg of feed (equivalent to 5 mg/kg bw/day)
Technical simazine (purity not
specified)
|
No reproductive effects reported. No further details given. |
5 mg/kg bw/day for reproductive toxicity |
Ciba-Geigy 1965 - quoted from WHO 1996b |
Two-generation study
Rats (Sprague-Dawley)
30/sex/group
|
0, 10, 100, 500 mg/kg of feed (equivalent to 0.5, 5, 25 mg/kg bw/day)
simazine (97% pure)
|
5 mg/kg bw/day and above: Reduced food consumption and body weights in parental
rats. |
0.5 mg/kg bw/day for parental toxicity
25 mg/kg bw/day for
reproductive toxicity
|
Ciba-Geiga 1991 – quoted from EC 1996b |
Gestation days 6-15
Rats (Sprague-Dawley)
|
0, 10, 50, 100, 300, 600 mg/kg bw/day
simazine (purity not specified)
|
50 mg/kg bw/day and above: Decreased maternal body weight gain and food consumption;
increased incidence of incomplete skeletal ossification in foetuses.
300 mg/kg bw/day and above: Marked increase in abortions; hypoplasia
of the lungs in association with dystopia cordis (malposition of the heart)
in foetuses.
|
10 mg/kg bw/day for maternal and developmental toxicity |
Ciba-Geigy 1976,1977 - quoted from EC 1996b, WHO 1996b |
Gestation days 6-15
Rats (Sprague-Dawley)
|
0, 30, 300, 600 mg/kg bw/day
simazine (98% pure)
|
300 mg/kg bw/day and above: Decreased maternal body weight gain and food consumption;
increased incidence of skeletal variations (increased incidence of poor ossification
in several sites, rudimentary 14th ribs, missing teeth) in foetuses. |
30 mg/kg bw/day for maternal and developmental toxicity |
Ciba-Geigy 1986 - quoted from EC 1996b, WHO 1996b |
Gestation days 7-19 Rabbits (New Zealand white)
19/dams/group
|
0, 5, 75, 200 mg/kg bw/day
simazine (97% pure)
|
75 mg/kg bw/day and above: One dead dam in each group; decreased food consumption
and body weight loss in dams; clinical signs (stool changes, tremors, decreased
motor activity) in dams; lower number of viable foetuses and reduced foetal weights;
increased occurrence of floating and fully-formed ribs and decreased ossification
of the patellae in foetuses. |
5 mg/kg bw/day for maternal and developmental toxicity |
Ciba-Geigy 1984 - quoted from EC 1996b, WHO 1996b |
| Terbutylazine |
Two-generation study
Rats (Sprague-Dawley)
28-32/sex/group
|
0, 6, 60, 300 mg/kg of feed (equivalent to 0.3, 3, 15 mg/kg bw/day)
terbutylazine (purity not
specified)
|
3 mg/kg bw/day and above: Decreased body weight gain and food consumption
in parental rats.
15 mg/kg bw/day: Slightly higher number of infertile pairings; slightly
higher pup mortality and retarded pup growth.
|
0.3 mg/kg bw/day for parental toxicity
3 mg/kg bw/day for
reproductive toxicity
|
Ciba-Geiga ? – quoted from WHO 1998b |
Gestation days 6-15
Rats (Tif/RAIf)
24/dams/group
|
0, 1, 5, 30 mg/kg bw/day by gavage
technical terbutylazine (96%
pure) in an aqueous 3% corn
starch vehicle
|
30 mg/kg bw/day: Decreased body weight gain and food consumption in dams;
delayed or absent ossification of phalanges in foetuses. |
5 mg/kg bw/day for maternal and developmental toxicity |
Ciba-Geigy 1990 – quoted from US-EPA 1995, WHO 1998b |
Gestation days 7-19 Rabbits (New Zealand white)
16-22/dams/group
|
0, 0.5, 1.5, 4.5 mg/kg bw/day by gavage
technical terbutylazine (99%
pure) in 1% methyl cellulose
|
No signs of maternal and developmental toxicity.
In a preliminary study, body weight loss was observed at 12.5 mg/kg
bw/day but not at 5 mg/kg bw/day in the rabbit.
|
4.5 mg/kg bw/day for maternal and developmental toxicity |
Ciba-Geigy 1983 – quoted from US-EPA 1995, WHO 1998b |
Gestation days 7-19 Rabbits (Russian Chbb:HM)
21/dams/group
|
0, 0.5, 1.5, 5 mg/kg bw/day by gavage
terbutylazine (purity not
specified)
|
1.5 mg/kg bw/day and above: Dose-related decreased food consumption in dams.
5 mg/kg bw/day: Increased body-weight loss during treatment
(compensated by a body-weight gain during the post-treatment period).
No developmental toxicity was observed.
|
0.5 mg/kg bw/day for maternal toxicity
5 mg/kg bw/day for
developmental toxicity
|
Ciba-Geiga ? – quoted from WHO 1998b |
| Cyanazine |
Three-generation study
Rats (Long-Evans)
|
0, 3, 9, 27, 81 mg/kg of feed (equivalent to 0, 0.15, 0.45, 1.4, 4.1 mg/kg
bw/day)
technical cyanazine (purity not
specified)
|
4.1 mg/kg bw/day: Reduced body weight gain in parental rats; increased brain
weight and decreased relative kidney weight in F3b female weanlings.
No significant effects on reproductive parameters.
|
1.4 mg/kg bw/day for parental toxicity
4.1 mg/kg bw/day for
reproductive toxicity
|
Shell Chemical Co. 1969 - quoted from WHO 1998a |
Two-generation study
Rats (Sprague-Dawley)
|
0, 25, 75, 150, 250 mg/kg of feed (equal to 0, 1.8, 5.3, 11, 19 mg/kg bw/day
in dams and to 0, 3.8, 11, 23, 37 mg/kg bw/day in dams during lactation)
cyanazine (100% pure)
|
1.8 mg/kg bw/day and above: Dose-related decreasing body weight of parental
rats.
11 mg/kg bw/day and above: Decreased pup viability and decreased
mean pup body weight during lactation.
|
<1.8 mg/kg bw/day for parental toxicity
3.8 mg/kg bw/day for
reproductive toxicity
|
E.I. duPont de Nemours and Co. 1987 - quoted from WHO 1998a |
Gestation days 6-15
Rats (Fischer 344)
30/dams/group
|
0, 1.0, 2.5, 10, 25 mg/kg bw/day by gavage (suspended in a 0.2% Methocel emulsion)
cyanazine (99% pure)
|
10 mg/kg bw/day and above: Maternal body weight reductions.
25 mg/kg bw/day: Microphthalmia/
anophthalmia, diaphragmatic hernia associated with liver protrusion in foetuses.
|
2.5 mg/kg bw/day for maternal toxicity
10 mg/kg bw/day for
developmental toxicity
|
Shell Chemical Co. 1981, Lu et al. 1982 - quoted from WHO 1998a |
Gestation days 6-15
Rats (Fischer 344)
70/dams/group
|
0, 5, 25, 75 mg/kg bw/day by gavage in an aqueous suspension of 0.25% methyl
cellulose
cyanazine (98% pure)
|
5 mg/kg bw/day and above: Maternal body weight reductions partly associated
with lower food intake during the dosing period; alterations in skeletal ossification
sites in foetuses.
25 mg/kg bw/day and above: Clinical signs in dams;
microphthalmia/anophthalmia, diaphragmatic abnormalities associated
with liver protrusion, dilated brain ventricles, cleft palate in foetuses.
75 mg/kg bw/day: Deaths, gastrointestinal and liver lesions, increased
duration of gestation, increased number of resorptions in dams;
decreased survival and body weight in foetuses.
|
<5 mg/kg bw/day for maternal and developmental toxicity |
Shell Oil Co. 1985 - quoted from Iyer et al. 1999, WHO 1998a |
Gestation days 6-15?
Rats (Sprague-Dawley)
|
0, 3, 30 mg/kg bw/day
cyanazine (purity not specified)
|
30 mg/kg bw/day: Maternal body weight reductions and increased incidence of
piloerection.
No developmental toxicity was observed.
|
3 mg/kg bw/day for maternal toxicity
30 mg/kg bw/day for
developmental toxicity
|
Shell Chemical Co. 1983 - quoted from WHO 1998a |
Gestation days 6-18 Rabbits (New Zealand white)
22/dams/group
|
0, 1, 2, 4 mg/kg bw/day by gelatine capsules
cyanazine (98% pure)
|
2 mg/kg bw/day and above: Anorexia, weight loss, death, and abortion in dams;
alterations in skeletal ossification sites, decreased litter size, increased post-implantation
loss.
4 mg/kg bw/day: Microphthalmia/
anophthalmia, dilated brain ventricles, domed cranium, thoracoschisis in foetuses.
|
1 mg/kg bw/day for maternal and developmental toxicity |
Shell Oil Co. 1982- quoted from Iyer et al. 1999, WHO 1998a |
| Desethyl atrazine (DEA) |
Gestation days 6-15 Rats (Tif/RAIf Sprague-Dawley)
24/dams/group
|
0, 5, 25, 100 mg/kg bw/day by gavage |
25 mg/kg bw/day and above: Decreased maternal body weight gain and food consumption.
100 mg/kg bw/day: Increased incidence of fused sternebrae, and poor
ossification in one site in foetuses.
|
5 mg/kg bw/day for maternal toxicity
25 mg/kg bw/day for
developmental toxicity
|
Ciba-Geiga 1992 – quoted from EC 1996a, US-EPA 2002a |
Gestation days 6-10 Rats (Fischer 344)
7-16 dams
|
0, 44, 87, 131 mg/kg bw/day by gavage |
44 mg/kg bw/day and above: Delayed parturition and maternal weight loss.
131 mg/kg bw/day and above: Altered pregnancy maintenance.
|
<44 mg/kg bw/day |
Narotsky et al. 2002 – quoted from Toxline abstract, US-EPA 2002b |
Post-natal days 23-53
Rats (Wistar)
m
|
0, 11, 22, 43, 87, 174 mg/kg bw/day by gavage |
22 mg/kg bw/day and above: Delayed preputial separation (which is a marker
of male puberty in the rat); reduction in seminal vesicle weights.
87 mg/kg bw/day and above: Reduction in ventral and lateral prostate
and anterior pituitary weights; decreased body weight.
174 mg/kg bw/day: Reduction in epididymal weights.
No differences were observed in the levels of serum oestrone, oestradiol,
testosterone and the thyroid hormones.
|
11 mg/kg bw/day for developmental toxicity |
Stoker al. 2002 |
| Desisopropyl atrazine (DIA) |
Gestation days 6-15 Rats (Tif/RAIf Sprague-Dawley)
24/dams/group
|
0, 5, 25, 100 mg/kg bw/day by gavage |
25 mg/kg bw/day and above: Decreased maternal body weight gain and food consumption;
increased incidence of fused sternebrae in foetuses.
100 mg/kg bw/day: Increased incidence of absent or poor ossification in
several sites in foetuses.
|
5 mg/kg bw/day for maternal and developmental toxicity |
Ciba-Geiga 1992 – quoted from EC 1996a, US-EPA 2002a |
Gestation days 6-10 Rats (Fischer 344)
7-16 dams
|
0, 40, 80, 120 mg/kg bw/day by gavage |
40 mg/kg bw/day: Maternal weight loss.
80 mg/kg bw/day and above: Altered pregnancy maintenance and
delayed parturition.
|
< 40 mg/kg bw/day |
Narotsky et al. 2002 – quoted from Toxline abstract, US-EPA 2002b |
Post-natal days 23-53
Rats (Wistar)
m
|
0, 10, 21, 40, 80, 161 mg/kg bw/day by gavage |
21 mg/kg bw/day and above: Delayed preputial separation (which is a marker
of male puberty in the rat).
40 mg/kg bw/day and above: Reduction in ventral prostate weights.
80 mg/kg bw/day and above: Reduction in lateral prostate and seminal
vesicle weights; decreased level of serum testosterone; decreased body
weight.
161 mg/kg bw/day: Reduction in epididymal and anterior pituitary
weights.
No differences were observed in the levels of serum oestrone, oestradiol
and the thyroid hormones.
|
10 mg/kg bw/day for developmental toxicity |
Stoker al. 2002 |
| Desethyldesisopropyl atrazine (DACT) |
Gestation days 6-16 Rats (Sprague-Dawley)
26/dams/group
|
0, 2.5, 25, 75, 150 mg/kg bw/day by gavage
desethyldesisopropyl atrazine
(98% pure)
|
25 mg/kg bw/day and above: Decreased maternal body weight gain; dose-related
increase in incomplete ossification sites in foetuses.
75 mg/kg bw/day and above: Decreased fetal body weights.
150 mg/kg bw/day: Increased resorptions and post-implantation losses;
decreased number of live foetuses; increased incidence of absent renal
papilla and pitted kidneys in foetuses.
|
2.5 mg/kg bw/day for maternal and developmental toxicity |
Ciba-Geiga 1989 – quoted from US-EPA 2002a |
Gestation days 6-10 Rats (Fischer 344)
7-16 dams
|
0, 17, 34, 68 mg/kg bw/day by gavage |
34 mg/kg bw/day and above: Delayed parturition and maternal weight loss.
68 mg/kg bw/day and above: Altered pregnancy maintenance.
|
17 mg/kg bw/day |
Narotsky et al. 2002 – quoted from Toxline abstract, US-EPA 2002b |
Post-natal days 22-41
Rats (Wistar)
f
|
0, ?,17, 34,? mg/kg bw/day |
34 mg/kg bw/day and above: Delayed vaginal opening. |
17 mg/kg bw/day for developmental toxicity |
Laws et al. 2002 – quoted from US-EPA 2002b |
Post-natal days 23-53
Rats (Wistar)
m
|
0, 4.4, 8.4, 17, 34, 84, 135 mg/kg bw/day by gavage |
8.4 mg/kg bw/day and above: Delayed preputial separation (which is a marker
of male puberty in the rat).
84 mg/kg bw/day and above: Reduction in seminal vesicle, epididymal
and anterior pituitary weights; increased level of serum oestrone;
decreased body weight.
135 mg/kg bw/day and above: Reduction in ventral prostate weights.
No differences were observed in the levels of serum oestradiol,
testosterone and the thyroid hormones.
|
4.4 mg/kg bw/day for developmental toxicity |
Stoker al. 2002 |
| Hydroxyatrazine |
Gestation days 6-16 Rats (Sprague-Dawley)
26/dams/group
|
0, 5, 25, 125 mg/kg bw/day by gavage
hydroxyatrazine (98% pure)
|
125 mg/kg bw/day: Decreased food consumption, and enlarged, mottled kidneys
in dams; decreased fetal body weights; increased incidence of incomplete ossification
sites in foetuses. |
25 mg/kg bw/day for maternal and developmental toxicity |
Ciba-Geiga 1989 – quoted from US-EPA 2002a |
Gestation days 6-10 Rats (Fischer 344)
7-16 dams
|
0, 91, 273, 457 mg/kg bw/day by gavage |
91 mg/kg bw/day and above: Altered pregnancy maintenance.
457 mg/kg bw/day: Maternal weight loss.
|
<91 mg/kg bw/day |
Narotsky et al. 2002 – quoted from Toxline abstract, US-EPA 2002b |
Post-natal days 22-41
Rats (Wistar)
f
|
Doses not stated |
Hydroxyatrazine did not delay vaginal opening at the doses tested. |
|
Laws et al. 2002 – quoted from US-EPA 2002b |
Post-natal days 23-53
Rats (Wistar)
m
|
0, 11, ? mg/kg bw/day by gavage |
11 mg/kg bw/day and above: Delayed preputial separation (which is a marker
of male puberty in the rat). |
<11 mg/kg bw/day for developmental toxicity |
Stoker – quoted from US-EPA 2002b |