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EC number: 932-165-8
CAS number: -
Oral:NOAEL (subchronic, rat) = 3000 mg/kg bw/day (males)NOAEL (subchronic, rat) = 3300 mg/kg bw/day (females)NOAEL (subacute, rat) = 5110 mg/kg bw/day (males)NOAEL (subacute, rat) = 5221 mg/kg bw/day (females)
Within the Vinasses category, data on
repeated dose toxicity are only available for one subgroup of Vinasses,
e. g. Vinasses, residue of fermentation. However, all Vinasses subgroups
share a common origin and are therefore constituted of the same
components determining their toxicological properties. Thus, read-across
is performed based on a category approach (A detailed justification is
attached in IUCLID section 13).
of fermentation were tested for subchronic oral toxicity in Wistar rats
following OECD guideline 408 and in compliance with GLP (Appel, 2003).
The test material was fed ad libitum to groups of 5 male and female rats
at 2, 6 and 15% in the diet for 13 weeks. The corresponding mean dose
levels over the study period were 1000, 3000 and 8000 mg/kg bw/day in
males and 1200, 3300 and 9600 mg/kg bw/day in females. A negative
control group fed a plain diet, and a positive control group receiving
additional ammonium (derived from (NH4)2S04);
approx. 0.6% in diet, corresponding to 320 and 380 mg/kg bw/day in males
and females, respectively) were included.
There were no
unscheduled deaths during the test. No clinical signs of toxicity were
observed. A slight reduction in growth and slightly reduced food
consumption (during the first week of the study) were observed in the
high-dose group, which were probably related to the high level of
ammonium nitrogen in the test substance. Water consumption was generally
increased in a dose-related manner in treated animals.
No effects were
observed at neurobehavioural and ophthalmoscopic examinations as well as
in haematological values. Clinical chemistry parameters were generally
similar among the groups. However, albumin was decreased in females of
the ammonium-control group and of the high-dose group and the
albumin/globulin ratio was decreased in males of the ammonium-control
group and in females of the high-dose group. These changes were probably
related to the high level of ammonium nitrogen in the test substance.
The decrease in chloride in females of the high-dose group was
and density were similar among the treated groups. Urinary pH was lower
and urinary crystals were increased in males of the ammonium-control
group and of the high dose group. These changes were considered related
to the high level of ammonium nitrogen in the test substance.
Some changes were
found in the absolute and/or relative weight of kidneys, brain, liver,
testes and uterus. All changes were considered either chance findings or
related to the ammonium- level in the test substance, except for the
change in relative liver weights, which was considered treatment-related.
microscopic examination at autopsy did not reveal any treatment-related
changes. Measurement of fertility parameters did not show any
Based on the
overall results of the study, the NOAEL is considered to be 3000 mg/kg
bw/day in male and 3300 mg/kg bw/day in female rats.
In an earlier
subchronic study, rats (10 per sex) were dosed orally by gavage for 94
days with two types of Vinasses, residue of fermentation at 625, 1250
and 2500 mg/kg bw and 2500 mg/kg bw, respectively (van Eeken, 1985). A
control group (20 animals per sex) was treated with vehicle
(physiological saline). Observations and examinations included
mortality, clinical signs, body weight, clinical pathology, organ
weights and histopathology.
No clinical signs
or mortality occurred in relation to the test substance. Two animals
died due to a technical error during dosing. No effects were observed in
body weight (gain), haematological and clinical chemistry parameters as
well as at necropsy and histopathological examinations. Absolute and
relative kidney weights were slightly increased (only statistically
significant in the relative kidney weight). Since no morphological
changes were noted at microscopic examination and no changes in clinical
haematology was noted, this change of weight was considered not
Based on the
study results, the NOAEL was considered to be 2500 mg/kg bw/day for both
male and female rats which corresponds to the highest dose tested.
reliable subacute oral toxicity studies are available.
In a GLP-study
study following the US FDA Toxicological Principles for the Safety
Assessment of Direct Food Additives and Color Additives Used in Food
(1982), groups of Sprague-Dawley rats (10 per sex per dose) were fed
diets containing Vinasses, residue of fermentation at 500, 5000 and
50000 ppm ad libitum for 4 weeks (Richard, 1993). The corresponding mean
dose levels over the study period were 50, 498 and 5110 mg/kg bw/day in
males and 48, 486 and 5221 mg/kg bw/day in females. A negative control
group fed a plain diet as well as additional satellite groups for
immunological examinations consisting of 8 males per dose were included.
occurred and no treatment-related clinical signs were noted in any
group. The food consumption, body weight gain and food efficiency were
similar in control and treated groups. The water consumption was higher
in the 50000 ppm group when compared to the control group. This could be
attributed to the exogenous supply of sodium in the 50 000 ppm
preparations: i.e. a supply of 6.86 g of sodium per kg of mixture.
were noted at ophthalmological examination of the animals of the 50000
treatment-related haematological findings were noted. Regarding blood
chemistry, the only relevant finding was a higher level of aspartic
acid, hydroxyproline, glutamic acid, alanine and methionine in the males
of the 50000 ppm group compared to the controls; this was considered to
be related to the composition of the test material.
No effects in
urinalysis parameters were observed.
Changes in organ
weights included: a slight increase in relative kidney weight in males
given 50000 ppm; a slight decrease in absolute and relative adrenal
glands weight in males given 5000 ppm; a slight decrease in absolute
adrenal glands weight in males given 50000 ppm; a slight decrease in
absolute and relative thymus weight in females given 5000 ppm. Changes
were considered to be of no toxicological importance.
microscopic examinations were considered as being of no toxicological
importance. Changes observed were reported to be those which are
commonly recorded as spontaneous findings in the laboratory rat.
In the satellite
groups, no treatment-related changes were noted in the immune function
tests, except for a lower response to a T-dependent antigen and a slight
decrease in B-lymphocyte proliferation in response to lipopolysaccharide
at the 5000 ppm concentration. The relationship of these findings to the
treatment was considered to be very doubtful.
Based on the
study results, the NOAEL is considered to be 50000 ppm corresponding to
5110 and 5221 mg/kg bw/day in male and female rats, respectively, which
corresponds to the highest dose tested.
subacute GLP-study, following OECD guideline 407, groups of Wistar rats
(5 per sex per dose) were daily given Vinasses, residue of fermentation
at 0.75, 3 and 10 mL/kg bw/day by gavage for 28 days (Til, 1992).
Two female rats
of the high-dose group died in the course of the study. These deaths are
probably due to faulty dosing accompanied by regurgitation and
aspiration of the test substance, rather than to toxicity. Diarrhoea
occurred in all rats at the end of the 4-week study. Slightly decreased
body weights were observed in males receiving 10 mL/kg bw/day,
accompanied by decreased food intake and food efficiency. Water intake
was increased in this group in both sexes.
showed increased haemoglobin concentration, packed cell volume and red
blood cell count in males and females of the high-dose group. No further
noticeable changes were observed. Fasting blood glucose levels were
increased in the high-dose group in both sexes, while plasma blood
sodium concentration was decreased in females of this group. No further
toxicologically relevant changes were noted.
showed dose-related increases in the mid- and high-dose groups in both
sexes. Urinary density was slightly decreased in the high-dose group,
and increased in the low-dose group in both sexes.
In the high-dose
group, the relative kidney weight was increased in both sexes and that
of adrenals in males.
At autopsy, no
treatment-related gross alterations were observed. Microscopic
examination of the adrenals revealed hypertrophy of the zona glumerosa
in males of the high-dose group. Histopathological changes referable to
treatment were not seen in any other organs examined.
No obvious signs
of toxicity were noted in the mid-dose animals. Therefore the, NOAEL was
considered to be 3 mL/kg bw/day in both male and female rats.
In an earlier
study, three groups of five male and five female Wistar rats were given
one of three concentrates of Vinasses, residue of fermentation at 5000
mg/kg bw by gavage for 13 days (van Eeken, 1974). A control group was
treated with the vehicle (water) only. No mortalities occurred and no
effects were observed on clinical signs, body weight (gain), food
consumption, organ weights and at macroscopical examination.
various subgroups of Vinasses, namely (sugar) beet and (sugar) cane
Vinasses, are listed in the Catalogue of feed materials (Annex to
Commission Regulation (EU) No 242/2010). Several feeding studies in
different species have investigated the use of these Vinasses as protein
source likely to be used in replacement of soybean meal in livestock
effects on growth and slaughter performance and no indications for
toxicologically relevant changes were reported after feeding Vinasses,
residue of fermentation containing biomass of bakers yeast (Saccharomyces
cerevisiae) to young female goats at 2526 and 4995 mg/kg bw/day for
6 months (Ringdorfer, 2009); to dairy cows at 640 and 1296 mg/kg bw/day
for 12 weeks (Urdl and Schauer, 2009); to bulls at 2135 mg/kg bw/day for
356 days (Leitgeb, 2010); to pigs at 10428 mg/kg bw/day for 55 days and
at 5245 mg/kg bw/day for further 45 days (Windisch and Schedle, 2010).
In chicks fed
Vinasses, residue of fermentation containing biomass of bakers yeast (Saccharomyces
cerevisiae) at 8, 16 and 24 % in diet for 36 days, a significant
decrease in growth and slaughter performance was observed at the highest
concentration with slight evidence of dose-dependency (Windisch and
Leitgeb, 2009). The corresponding Vinasses mean dose levels over the
study period were 6438, 13197 and 20780 mg/kg bw/day. The decrease in
daily body weight gain was correlated with a decrease in daily feed
intake. The absolute weight of abdominal fat, heart, liver stomach and
individual body parts determined at the end of the study was also
significantly decreased at the highest dose level. However, except for
breast, the corresponding relative weights were not reduced and even a
slight dose-dependent increase was observed.
No effects were
reported for bulls fed Vinasses at 14% in the diet for 10 days (Stemme
et al., 2005). In the same study, pigs fed Vinasses at 16 and 43% in the
diet for 36 days showed no effects, except for osmotically driven
diarrhoea in animals from the 43% group, related to an unexpected high
sulfate content in the Vinasses used.
is not available.
The available data on the repeated dose
toxicity of the substance via the oral route are conclusive but not
sufficient for classification according to the DSD (67/548/EEC) and CLP
(1272/2008/EC) criteria. A specific target organ toxicity (STOT) cannot
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