Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 930-690-7
CAS number: -
1: Food Consumption of Females (Mean Values in g/animal/day)
Dose Group (mg/kg bw/day)
Mean of Means
Dunnett's test based on pooled variance significant at the 5 % (*) or 1
% (**) level
2: Percentage Body Weight Gain (Mean Values)
3: Selected Reproduction Data Parameters
Number of Dams
% of corpora lutea
No. dams affected
% of implantation sites
Implantation site scars
Fisher’s Exact Test significant at the 5 % (*) or 1 % (**) level
test significant at the 5 % level
4: Body Weights of Live Foetuses (Mean Values in g)
Dose group (mg/kg bw/day)
Males and Females
The developmental toxicity of the test material was investigated in a
study which was conducted under GLP conditions and in accordance with
the standardised guidelines OECD 414 and EU Method B.31.
During the study, the test material was administered by oral gavage to
groups of mated female Wistar rats at dose levels of 0 (corn oil vehicle
control), 50, 100 and 250 mg/kg bw/day. The females received treatment
from day 6 to day 19 post coitum. During the treatment period the
females were observed for mortality and morbidity as well as for any
adverse clinical signs. Body weights and food consumption were recorded.
On day 20 post coitum the females were sacrificed, subjected to necropsy
and the foetuses removed by caesarean section. Post mortem examination
included a gross macroscopic examination of all internal organs with
emphasis on the uterus, uterine contents, position of foetuses in the
uterus and the number of corpora lutea were counted and recorded.
Foetuses were removed from the uterus, sexed, weighed individually,
examined for gross external abnormalities and then sacrificed. Half of
the litter was subjected to skeletal examination while the other half
was subjected to visceral examination.
Treatment caused salivation at 50 and 250 mg/kg bw/day, mainly at 250
mg/kg bw/day in a dose-dependent manner. Slightly lower food consumption
and lower body-weight gain were observed in all test material-treated
groups. These values did not deviate by more than 11, 8 and 13 % from
the control group for food consumption and by more than 5, 5 and 6 % for
body weight, at 50, 100 and 250 mg/kg bw/day.
In the observations deriving from the hysterectomies, test
material-related embryofoetal toxicity was observed at 250 mg/kg bw/day
with an increase in post-implantation losses.
Treatment led to a decrease in mean foetal body weight in all test
material-treated groups. These values did not deviate by more than 6 %
at 50 mg/kg bw/day and 14 % at 100 and 250 mg/kg bw/day. At the external
examination, no findings were recorded.
The skeletal examination of the foetuses did not reveal any
toxicologically relevant alterations. The slight delay in ossification
in some litters at 100 and 250 mg/kg bw/day compared to the control
group can be considered a variation without pathological meaning and
secondary to lower foetal body weight.
The visceral examination revealed the following: at 250 mg/kg bw/day
there were five litters with one foetus each with abnormalities: three
foetuses with diaphragmatic hernia, one foetus with asymmetric nasal
septum and one foetus with oval-shaped eyes; at 100 mg/kg bw/day one
foetus had abnormality with dilation of cerebral aqueduct; at 50 mg/kg
bw/day one foetus had abnormalities, such as severe dilation of cerebral
ventricles, no recognisable ocular structures and asymmetry of nasal
structures. Finally, two litters from the control group showed
abnormalities, i.e. one foetus with oval shaped lens and one foetus with
interrupted ureter and renal pelvis severely dilated.
The diaphragmatic hernia could be considered related to the test
material as it was only observed at 250 mg/kg bw/day. There was no
evidence of a compound-related effect in the number of occurrences in
the remaining abnormalities found in the test material-treated groups.
Furthermore, there was an increase in the incidence of common
variations, such as left-sided umbilical artery and bilateral azygos
vein, in the test material-treated groups. Other common variations,
mainly involving urogenital morphology (dilated renal pelvis, and
dilated and/or convoluted ureter, malpositioned kidney, malpositioned
cranial testis) in addition to other findings (additional small lobe and
dark-area in the liver) were recorded in all groups including the
control group. These alterations should be regarded as spontaneous
variations with limited pathological relevance.
Therefore, based on the results of this study, the top dose tested of
250 mg/kg bw/day is considered the No Observed Adverse Effect Level
(NOAEL) for maternal toxicity. Although there were decreases in food
consumption and body weight at 250 mg/kg bw/day, the decreases in body
weight gain were not greater than 5 - 6 %.
With respect to the effects on embryofoetal development, 50 mg/kg bw/day
is considered to be the NOAEL based on the lower foetal body weight (14
%) at 100 and 250 mg/kg bw/day and the increase in the post-implantation
losses at 250 mg/kg bw/day.
Regarding the potential for teratogenic effects, 100 mg/kg bw/day is
considered to be the NOAEL based on the diaphragmatic hernia recorded at
250 mg/kg bw/day.
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.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again