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EC number: 925-259-5
CAS number: 140921-24-0
The purpose of a reproduction/developmental
toxicity screening test was to obtain initial information concerning the
effect of the test item Incozol EH on male and female reproductive
performance such as gonadal function, mating behavior, conception,
pregnancy, parturition as well as on development of the F1 offspring
from conception to day 4 post partum associated with oral administration
to rats at repeated doses.
Four groups of Hsd.Brl.Han: Wistar rats
(n=12/sex/group) were administered with the test item orally (by gavage)
once a day at 0 (vehicle), 1000, 300 and 100 mg/kg bw/day corresponding
to concentrations of 0, 200, 60 and 20 mg/mL. The application volume was
5 mL/kg bw. Control animals received the vehicle, Polyethylene glycol
400 (PEG 400). The suitability of the vehicle for the test item was
analytically verified up front. The concentration of the test item in
the dosing formulations was checked two times during the study. Incozol
EH concentrations in the dosing formulations varied in the acceptable
range between 91% and 106% of the nominal values and confirming the
proper preparation of the dosing formulations.
All animals of the parent (P) generation
were dosed prior to mating (14 days) and throughout mating. In addition,
males received the test item or vehicle after mating up to the day
before the necropsy (altogether for 41 days). Females were additionally
exposed through the gestation period and up to lactation days 3 or 4,
i.e. up to the day before necropsy (altogether for 41 – 44 days).
Observations included mortality, clinical signs, body weight, food
consumption, mating, pregnancy and delivery process, as well as
development of offspring. The dams were allowed to litter, and rear
their offspring up to day 4 postpartum. Litters were weighed and
offspring were observed for possible abnormalities and were euthanized
on postnatal day 4. All parental animals were subjected to gross
pathology one day after the last treatment. Histopathology examination
was performed on reproductive organs (testes, epididymides and ovaries)
in the control and high dose groups. The reproductive organs of
cohabited males and non-pregnant females in the low dose group were also
processed and evaluated histopathologically.
There was no mortality at any dose level
(1000, 300 and 100 mg/kg bw/day).
Adverse signs of systemic toxicity related
to the test item were not detected at any dose level, neither at the
daily nor the detailed weekly clinical observations. At the same
intervals, the behavior and physical condition of the animals was not
impaired at each dose level (1000, 300 or 100 mg/kg bw/day) during the
entire treatment period.
Body weight and body weight gain
The mean body weight gain of male animals at
1000 mg/kg bw/day was in a varying degree slightly reduced during the
treatment period. However, this slight change was not associated with
relevant or significant changes in the mean body weight. Therefore, this
observation was judged to be no toxicologically relevant adverse effect.
The mean daily food consumption was not
affected by the test item in male or female animals at 1000, 300 and 100
mg/kg bw/day during the entire study (pre-mating, post-mating, gestation
and lactation periods).
There were no test item related differences
between the control and test item treated groups in delivery data of
dams and in the reproductive performance of male and female animals.
Specific macroscopic alterations related to
the test item were not found at necropsy.
There were no test item related changes in
brain, testes and epididymides weights of male animals at any dose level.
Histopathological examinations of male and
female genital organs (ovaries, testes and epididymides) did not reveal
any test item related changes at any dose level.
No adverse findings on offspring development
(mortality, clinical signs, body weight) or at necropsy were detected in
the offspring terminated as scheduled.
Under the conditions of the present study,
Incozol EH administered at 1000, 300 or 100 mg/kg bw/day did not led to
signs of systemic toxicity and did not adversely influence the
reproductive performance (gonad function, mating behavior, conception,
pregnancy, parturition) in parental male and female Hsd.Brl.Han: Wistar
rats. The development of the F1 offspring from conception to day 4
postpartum after repeated oral administration was not impaired at any
dose level. Based on these observations the No Observed Adverse Effect
Levels (NOAEL) were determined as follows:
NOAEL for systemic toxicity of male/female
rats: 1000 mg/kg bw/day
NOAEL for reproductive performance of
male/female rats: 1000 mg/kg bw/day
NOAEL for F1 Offspring: 1000 mg/kg bw/day
Based on the results of the
reproduction/developmental toxicity screening test (OECD 421), the test
item was not classified and labelled according to Dierctive 67/548/EEC
(DSD) and to Regulation EC (No) 1272/2008 (CLP).
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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