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EC number: 947-397-5
CAS number: -
Oral: In a study according
OECD TG 422 in Wistar rats, the NOAEL for general, systemic toxicity of
the test item was 100 mg/kg bw/day based on the findings in the target
organ kidney. The NOAEL for reproductive performance and fertility of
the F0 parental rats and developmental toxicity in the offspring was
1000 mg/kg bw/day, the highest dose tested.
The stability of test substance in drinking
water was demonstrated for a period of 7 days at room temperature.
Concentration control analysis
The concentrations of the test item in
drinking water were found to be in the range of 91 to 101% of the
nominal concentration at two independent time points. Analyses
demonstrated a recovery of 101% in the low dose (100 mg/kg bw/day), 97%
in the mid dose (300 mg/kg bw/day) and 96% in the high dose (1000 mg/kg
bw/d) at the beginning of gestation. At the end of gestation a recovery
of 101% in the low dose (100 mg/kg bw/day), 95% in the mid dose (300
mg/kg bw/day) and 91% in the high dose (1000 mg/kg bw/d) was
After the analyses of samples collected at
the beginning of gestation, the analyses of the samples collected during
lactation period were performed and showed a recovery of 71% in the low
dose (100 mg/kg bw/d), 99% in the mid dose (300 mg/kg bw/day) and 75% in
the high dose (1000 mg/kg bw/day). Since these results did not confirmed
the aimed concentration of test substance preparations, the
corresponding reserve samples of this test substance preparation were
analyzed. In case of comparable analytical results to the one of the
main samples, a mistake in the test substance preparation could not be
excluded. In case of different analytical results, a mistake analytic
procedure would be likely. The reserve samples at the same time point
demonstrated a recovery of 100% in the low dose (100 mg/kg bw/day), 57%
in the mid dose (300 mg/kg bw/day) and 34% in the high dose (1000 mg/kg
bw/day). These results confirmed neither the aimed concentration in the
test substance preparation nor the concentration determined in the main
samples of the same time point before. The results of the reverse
samples were even contradictory. The author assessed the measurements of
this time point as biased by problems in analyses. Therefore, the
analyses of samples collected during lactation were judged as not
suitable to be used for the concentration control. The analyses of
further samples of the study were initiated, samples from a second
independent test substance preparation during gestation. As described,
these results were in good compliance with the expected values.
With regard to the analytical findings of
chemical and microbiological contaminants and the duration of
application, the diet was found to be suitable. The concentration of
microorganisms did not exceed 1x10E5/g feed.
Drinking water analyses
On the basis of the analytical findings, the
drinking water was found to be suitable. German Drinking Water
Regulation (Trinkwasserverordnung, Bundesgesetzblatt, 05 Dec 1990)
served as a guideline for maximum tolerable contaminant.
Bedding and Enrichment analyses
On the basis of the analytical findings,
bedding and cage enrichment were found to be suitable.
a study according to OECD TG 422 the test item was administered daily as
an aqueous preparation to groups of 10 male and 10 female Wistar rats
(F0 animals) by gavage at doses of 100, 300 and 1000 mg/kg bw/day.
Control animals were dosed daily with the vehicle drinking water. The
duration of treatment covered a 2 weeks premating period and mating
period in both sexes (mating pairs were from the same dose group),
approximately 7 days post-mating in males, the entire gestation period
as well as up to 13 days of the lactation period in females up to one
day prior to the day of schedule sacrifice of the animals.
parents' and the pups' state of health was checked each day, and
parental animals were examined for their mating and reproductive
performances. After 2 weeks of premating treatment the F0 animals were
mated to produce F1 generation pups. Mating was discontinued as soon as
sperm were detected in the vaginal smear. F0 animals were examined for
their reproductive performance including determination of the number of
implantation sites and the calculation of post-implantation loss for all
F0 females. A detailed clinical observation (DCO) was performed in all
animals before initial test substance administration and, as a rule,
thereafter at weekly intervals.
consumption of the F0 parents was determined once weekly during
premating. In dams, food consumption was determined for GD 0 - 7, 7 -
14, 14 - 20 and PND 1 - 4, 4 - 7, 7 - 10, 10 - 13. Body weights of F0
parents were determined once a week. During gestation and lactation
period, F0 females were weighed on GD 0, 7, 14 and 20 and on postnatal
days (PND) 1, 4, 7, 10 and 13. Estrous cycle data were evaluated for F0
generation females over a two-week period prior to mating until evidence
of mating occurred. Moreover, the estrous stage of each female was
determined on the day of scheduled sacrifice. The pups were sexed and
examined for macroscopically evident changes on PND 0. They were weighed
on PND 1, 4, 7 and 13. Their viability was recorded. At necropsy on PND
4, as a result of standardization, the surplus pups were sacrificed
under isoflurane anesthesia by decapitation. At necropsy on PND 13, one
selected male and one female pup per litter was sacrificed under
isoflurane anesthesia by decapitation, all other pups (on PND 13) were
sacrificed with CO2, under isoflurane anesthesia. All pups were examined
macroscopically for external and visceral findings.
distance measurements were conducted in a blind randomized fashion,
using a measuring ocular on all live male and female pups on PND 1. All
surviving male pups were examined for the presence or absence of
nipple/areola anlagen on PND 13. The number of nipple/areola anlagen
were counted. Blood samples were taken from all surplus pups at PND 4 as
well as one male and one female pup per litter at PND 13 by decapitation
under isoflurane anesthesia for determination of thyroid hormone
concentrations. Clinico-chemical and hematological examinations were
performed in 5 animals per sex and group towards the end of the
samples from all dams at PND 14 and all males at termination were taken
by puncturing the retrobulbar venous plexus under isoflurane anesthesia
for hormone measurement. At the end of the administration period a
functional observational battery was performed and motor activity was
measured in 5 parental males and females per group. All F0 parental
animals were sacrificed by decapitation, under isoflurane anesthesia,
and were assessed by gross pathology. Weights of selected organs were
recorded and a histopathological examination was performed.
stability of the test substance in drinking water was demonstrated over
a period of 7 days at room temperature.
all dose groups no test substance-related adverse findings of P0
parental animals regarding clinical examination, reproductive
performance and clinical pathology were reported. In pathology,
papillary necrosis in the kidneys of 7 out of 10 males and 5 out of 10
females was detected at the highest dose group of 1000 mg/kg bw/day. At
300 mg/kg bw/day papillary necrosis in the kidneys of one out of 10
males and one out of 10 females was observed. No substance-related
adverse findings were detected in the F1 pups at all dose levels.
the conditions of the combined repeated dose toxicity study with the
reproductive/developmental screening test in Wistar rats, the NOAEL for
general, systemic toxicity of the test item was 100 mg/kg bw/day based
on the findings in the target organ kidney. the NOAEL for reproductive
performance and fertility of the F0 parental rats and developmental
toxicity in the offspring was 1000 mg/kg bw/day (BASF SE, 2018).
Labelling, and Packaging Regulation (EC) No 1272/2008
available experimental test data are reliable and suitable for
classification purposes under Regulation (EC) No 1272/2008. As a result,
the substance is not considered to be classified for repeated oral dose
as amended for the tenth time in Regulation (EU) No 2017/776.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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