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EC number: 204-137-9
CAS number: 116-37-0
Accuracy of preparation: The concentrations
analysed in formulations of Group 2, Group 3 and Group 4 were in
agreement with target concentrations (i.e. mean accuracies between 90%
and 110%). No test substance was detected in Group 1 formulations.
Homogeneity: Formulations of Group 2 and
Group 4 were homogeneous (i.e. coefficient of variation = 10%).
Stability: The Group 2 formulation was
stable when stored at room temperature under normal laboratory light
conditions for at least 6 hours. Formulations of Group 2 and Group 4
were stable when stored in a refrigerator for at least 8 days.
OECD 408 study (Sub-chronic toxicity study (90-day), oral route (gavage)
in rats) was performed with the 4,4’-Isopropylidenediphenol,
at the dose-levels of 0, 20, 60 and 180 mg/kg bw/day with approval of
ECHA for the 2010 Reach registration dossier. The test substance,
formulated in polyethylene glycol 400, was administered daily for at
least 90 days by oral gavage to SPF-bred Wistar rats. One control group
and three treated groups were tested, each consisting of 10 males and 10
analyses of formulations preparations were conducted during the study to
and stability over 6 hours. The
following parameters were evaluated: clinical signs daily; functional
observation tests in Week 12; body weight and food consumption weekly;
ophthalmoscopy at pretest and in Week 13; estrous cycle determination;
clinical pathology and macroscopy at termination; organ weights and
histopathology on a selection of tissues including spermatogenic staging
analyses confirmed that formulations of test substance in polyethylene
glycol 400 were prepared accurately and homogenously, and were stable
over at least 6 hours.
mg/kg (one male and one female) were found dead between after dosing on
Day 84 and 52, respectively. Histopathology revealed no cause of death
but the presence of watery-clear fluid in the thoracic cavity in both of
these animals suggest that these deaths were due to a gavage incident.
number of changes in red blood cell parameters were noted in both sexes
at 60 and 180 mg/kg, including lower red blood cell counts, lower
haemoglobin and haematocrit level, and higher mean corpuscular volume
and mean corpuscular haemoglobin. Means remained essentially within the
range considered normal for rats of this age and strain, and no
morphological correlates indicative of increased breakdown or production
of red blood cells were noted. Therefore, these haematological changes
were considered not indicative of an adverse effect on red blood cell
turn over. The higher liver to body weight ratio in males at 180 mg/kg
corresponded with the centrilobular hepatocellular hypertrophy of the
liver observed in most at 180 mg/kg (up to slight degree). Given the low
severity of liver hypertrophy, absence of morphological liver findings,
and only slight potentially supportive clinical biochemistry changes
(higher cholesterol and higher alanine aminotransferase activity in
males), these findings were considered adaptive and not adverse in
nature. The higher cholesterol levels of females at 180 mg/kg occurred
without any apparent morphological correlates.
clinical biochemistry changes at 180 mg/kg included lower potassium
level (males), higher urea and calcium level (females), and higher
inorganic phosphate level (males). At 60 mg/kg, clinical biochemistry
changes were confined to lower potassium level (males) and higher urea
level (females). As
these changes were slight in nature and also occurred in the absence of
any supportive morphological changes, these were considered not to be
adverse in nature.
parameters assessed in this study revealed no adverse changes. The trend
towards higher ovary weight among female dose groups was considered to
be related to the interstitial cell hypertrophy in the interstitial
gland of the ovaries in most females at 60 and 180 mg/kg (up to slight
degree). Ovaries are steroid synthezing organs and play a major role in
the endocrine system and reproductive system. The main precursor for the
production of all steroid hormone synthesis is cholesterol (or
cholesterylesters), that can be stored intracellular as lipid droplets
in the ovary. The histologic
morphology of the recorded interstitial cell hypertrophy, with fine
vacuolar appearance is suggestive for an exaggerated lipid storage which
can lead to increased organ weight. Since estrous cycle length was
normal for all examined females at 20, 60 and 180 mg/kg and the
interstitial gland hypertrophy was of a low severity, this finding was
considered to be non-adverse.
staging profiles were normal for all animals assessed.
histopathological correlates were found for the higher adrenal and
kidney to body weight ratio in males and lower heart weight in females
at 180 mg/kg. Therefore, these changes were considered not to be of
relevant clinical signs were noted during treatment. Functional
observation tests revealed no abnormalities, and ophthalmoscopy showed
no treatment-related changes. The slightly lower body weight gain of
males at 180 mg/kg was only minor in nature and well within the range
considered normal for rats of this age and strain, and was therefore
considered to be of no toxicological relevance.
changes in food intake occurred.
the results presented above, a No Observed Adverse Effect Level (NOAEL)
propoxylated (BPA+2PO) of
at least 180 mg/kg was established.
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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