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EC number: 206-354-4
CAS number: 330-54-1
Studies on oral sub-chronic and chronic repeated dose toxicity were available for Diuron. Oral 90-day NOAEL for rat (males): 100 ppm (6.7 mg/kg bw/day). Oral 12-Months NOAEL for Dog: 1.8 mg/kg bw/day.Studies on dermal sub-acute repeated dose toxicity were available for Diuron. Dermal 21-days NOAEL for rabbit: 250 mg/kg bw/day.Studies on inhalation sub-acute repeated dose toxicity were available for Diuron. Inhalation 21-days NOAEC for rat: 37.4 mg/m³ for male and 4.1 mg/m³ for female.
reliable repeated oral dose toxicity study comparable to OECD guideline
452, groups of 6 beagle dogs/sex were given food containing Diuron at 0,
50, 300 or 1800 ppm for a period of 52 weeks, equivalent to 0, 1.8, 11
or 64 mg/kg bw/d (Hoffmann & Schilde, 1985).All animals survived,
and no remarkable clinical signs of toxicity were found at dose levels
up to 64 mg/kg bw/d. In the top dose group, body weights were decreased
in both sexes towards the end of the study. Haematological parameters
were affected beginning at 300 ppm and being more pronounced at 1800
ppm. This was seen by reduced haemoglobin and erythrocyte counts and
increases in mean cell volume, indicating a hypochromic anaemic process,
accompanied by high incidences of Heinz bodies at the top dose level.
Compensation of the anaemic process was evident by increased
reticulocyte numbers. Histopathological examinations exhibited reactive
fat-deficient bone marrow with increased siderin content. Increased
incidences of iron-containing pigments were found in livers, spleens
and kidneys in the mid and high dose groups. Spleen and liver weights
were increased accordingly.The NOAEL
under the conditions of this study is 1.8 mg/kg bw/d for both sexes (50
repeated oral dose toxicity study comparable to OECD guideline 408,
groups of 20 male and 20 female Wistar rats received diets containing 0,
100, 250 and 2500 ppm Diuron over a period of 90 days, which was
equivalent to a mean test article intake of 0, 6.7, 17.0 and 176 mg/kg
bw/day for males and 0, 8.7, 23.3 and 214 mg/kg bw/day for females. Half
of the animals were allowed a 90-day recovery period after the treatment
period (Malley, 2004).There were no
test item-related mortalities or clinical signs of toxicity. Decreases
in body weight and weight gain were noted in top dose males and females.Statistically
significant changes in haematological parameters were observed during
the entire study. Red blood cell parameters were adversely affected in
males and females in a dose-dependent manner. Erythrocytes, haemoglobin
and haematocrit were decreased corresponding with increased numbers of
reticulocytes pointing to compensation of loss of blood oxygen carrying
capacity. Clinical chemistry revealed significant changes with regard to
increased bilirubin in both sexes. At the end of the treatment period,
liver weights were increased in males and females at 2500 ppm. At all
dose levels of females and at high dose level of males significant
increases in spleen weights were recorded. At necropsy,
histopathological examinations exhibited alterations of spleen, liver,
kidney and bone marrow consisting of increased haematopoiesis,
haemoglobin derived pigmentation and congestion. Moreover, animals of
both sexes in the two higher dose groups revealed hyperplasia of the
transitional epithelium of renal pelvic mucosa and urinary bladder
mucosa. After a 90-day recovery period, all substance-related
alterations had resolved in all males and the majority of females.Therefore,
the NOAEL was set 100 ppm, equal to 6.7 mg/kg bw/day for males. No NOAEL
for females could be set; the LOAEL was set 100 ppm, corresponding to
8.7 mg/kg bw/day for females.
In a supporting
oral repeated dose study comparable to OECD 452, groups of 10 male and
10 female Wistar rats were offered diets containing 0, 4, 10 and 25 ppm
Diuron over a period of six months, equivalent to 0, 0.3, 0.66 and 1.6
mg/kg bw/d for males and 0, 0.3, 0.77 and 1.8 mg/kg bw/d for females
(Schmidt and Karbe, 1986).No test
item-related mortalities or clinical signs of overt toxicity were
observed until end of treatment. No relevant changes in body weight or
food consumption were noted compared to the control group. Similarly to
the results of other subchronic studies, the blood system was the target
organ of Diuron-related adverse effects. This was evidenced by slightly
lowered haemoglobin concentrations in top dose females after 12 and 26
weeks and increased reticulocyte counts in males and females after 12
weeks and in females at termination. Morphometric evaluation of spleens
revealed an increased accumulation of ferriferous pigments in both sexes
at the top dose. Organ weights were not significantly affected.The
NOAEL was set 10 ppm, equal to 0.66 mg /kg bw/d in males and 0.77 mg/kg
bw/d in females.
Based on the
results of the repeated oral dose toxicity studies where consistent and
significant adverse changes in haematologic parameters s are seen,
Diuron therefore needs to be classified according to the criteria of
Directives 67/548/EEC (DSD) and 1272/2008/EC (CLP).
In a reliable 3
-week dermal repeated dose toxicity study equivalent or similar to OECD
Guideline 410, rabbits were administered doses of 0, 50 and 250 mg/kg
bw/d (Mihail and Schilde, 1984).Following
repeated administration of Diuron at dose levels up to 250 mg/kg bw/d,
no mortalities or toxic effects occurred. No behavioural changes were
noted. Examination of the skin according to Draize or skin fold
thickness determination did not show any alterations. Haematology,
urinalysis and blood chemistry exhibited no differences between the
groups. Neither relative nor absolute organ weights were affected.
Histopathology revealed congestion of the spleen in only one male
rabbit. No other toxicologically relevant histopathological findings
were noted. In this study, no test item-related signs of evident
systemic or dermal toxicity were noted (NOEL/NOAEL: 250 mg/kg bw/d).
In a subchronic
dermal toxicity study, Diuron suspended in cotton seed oil was
administered to Sprague-Dawley rats (12/sex/group) at doses of 0, 250,
500 or 1000 mg/kg bw/d for 13 weeks, 5/7 days a week for 6 hours to the
shaved skin of about 10 % of the body surface (Wandrag, 1996).No
mortalities or clinical signs directly related to the test item were
noted. However, three animals died without any earlier clinical
symptoms. High incidences of uroliths were found. Serum urea and
bilirubin were adversely affected.At
all dose levels, signs of haemolytic anaemia were observed as evidenced
by decreases in erythrocyte counts, haematocrit and haemoglobin and
increased mean corpuscular volume. According to this, no NOAEL could be
set. However this study was disregarded as only a short abstract on
method and result was available (Wandrag, 1996).
In a reliable
sub-acute inhalation study comparable to guideline OECD 412, Wistar rats
were exposed to nominal doses of 0, 20, 150 and 1000 mg/m3 (anal. conc.
achieved: 0, 4.1, 37.4 and 268.1 mg/m³) of an aerosol of Diuron for 6 h
per day, 5 days per week for 14 or 28 days. Rats exposed to
concentrations up to 37.4 mg/m³ Diuron did not exhibit any test
item-related signs of adverse effects. Therefore the LOAEC was
determined to be 268.1 mg/m³ in males and 37.4 mg/m³ in females based on
significant alterations in haematologic parameters and dark, enlarged
spleens at higher dose levels. The NOAEC was assessed to be 37.4 mg/m³
for male and 4.1 mg/m³ for female animals (Pauluhn, 1986b).
In an inhalation
study which was in principle conducted based on OECD guideline 412,
Wistar rats were exposed to nominal doses of 0, 20, 150 and 1000 mg/m3
(anal. concentrations were 0, 6.6, 47.6 and 311 mg/m³) of an aerosol of
Diuron for 6 h per day, 5 days per week for 21 days. Rats exposed to
concentrations up to 47.6 mg/m³ Diuron did not exhibit any test
item-related signs of adverse effects. Therefore, the LOAEC was set to
47.6 mg/m³, based on significant alterations in haematologic parameters
and congested spleens at higher dose levels. The NOAEC was determined to
be 6.6 mg/m³. (Pauluhn, 1986a).
on the available data on oral and inhalation repeated dose toxicity
Diuron needs to be classified:
STOT RE Category 2
data on repeated dose toxicity for the dermal route is conclusive, but
not sufficient for classification.
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