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EC number: -
CAS number: -
An OECD 414 oral rat toxicity study was performed according to GLP.
In the 28 -day oral repeated dose toxicity, changes were noted in body
weight gain, haematology and clinical biochemistry and microscopic
findings in the liver 4,4’-Isopropylidenediphenol, oligomeric reaction
products with 1 - chloro-2,3-epoxypropane, reaction products with
butan-1-ol and 3-aminomethyl-3,5,5 - trimethylcyclohexylamine is
considered to induce toxicological changes at 500 and 1000 mg/kg.
Based on the effects observed as effects on liver were also observed in
the control group, the No Observed Adverse Effect Level (NOAEL) was
considered to be 500 mg/kg/day.
Increased salivation and noisy respiration were evident in animals of
both sexes treated with 200 mg/ kg bw/day and to a lesser extent in
animals of both sexes treated with 100 mg/kg bw/day during the treatment
period. Incidences of a stained snout, labored respiration, decreased
respiratory rate, hunched posture and fur loss were also evident in some
females treated with 200 mg/kg bw/day, a stained snout and sneezing was
also evident in some surviving males treated with 200 mg/kg bw/day and a
decreased respiratory rate and hunched posture was also evident in one
male treated with 100 mg/kg bw/day. Noisy respiration remained evident
in one male and one female that were previously given 200 mg/kg bw/ day
during the treatment-free period. The male treated with 200 mg/kg bw/day
that was found dead on Day 48 had previously only shown increased
salivation and noisy respiration and at necropsy, a dark
liver and dark lungs were evident. Microscopically, moderate prostatic
inflammation, unilateral lymphoid aggregates and urothelial hyperplasia
in the kidneys and adrenal cortical hypertrophy were evident and
although the adrenal change was most likely to indicate stress and be
secondary to the prostatic inflammation, the actual cause of death in
this animal was undetermined.
Males treated with 200 and 100 mg/kg bw/day showed a reduction in body
weight gain and food consumption throughout the treatment period and
reductions in food conversion efficiency were also evident, which
generally followed the fluctuations in body weight gain. Following the
twenty-eight day treatment-free period, males that were previously given
200 mg/kg bw/day showed significant recovery in both body weight gain
and food consumption. Females treated with 200 mg/kg bw/day showed a
slight reduction in body weight gain during the first week of treatment,
however, recovery was evident thereafter.
Hematological investigations at the end of the treatment period revealed
increased neutrophil count in both sexes treated with 200 and 100 mg/kg
bw/day and increased total leukocyte count in males treated with 200
mg/kg bw/day. The increase in neutrophil count persisted in females
previously given 200 mg/kg bw/day after the treatment-free period. These
findings were most likely associated with the microscopic mesenteric
lymph node changes identified at 200 and 100 mg/kg bw/day. Histiocytosis
with granulomas was evident in animals of both sexes from all treatment
groups, varying from minimal to moderate in severity and following a
dose-dependent response. At 200 and 100 mg/kg bw/day the more severe
grades of histiocytosis were often accompanied by minimal abscesses.
Histiocytosis in the mesenteric lymph nodes is likely to represent
accumulation of material, indicating delayed clearance of an exogenous
or endogenous material. At the higher grades, abscesses comprised of
degenerating histiocytes with small numbers of inflammatory cells.
Following the twenty-eight day recovery period, histiocytosis with
granulomas and abscesses were evident in both sexes previously treated
with 200 mg/kg bw/day, however, when compared with non‑recovery animals,
the incidence of abscesses was lower, whereas histiocytosis persisted at
much the same incidence and severity.
At the end of the dosing phase, blood chemistry investigations in
treated animals identified statistically significant changes in some
parameters that may indicate minor perturbations in hepatic metabolism.
in treated animals. However in the absence of any associated microscopic
hepatic changes these intergroup differences were considered not to
represent an adverse effect of treatment. Any other minor intergroup
differences resulting from blood chemistry, hematological or organ
weight investigations were also considered to be of no toxicological
Repeated dose toxicity: via oral route - systemic effects
(target organ) digestive: cecum; digestive: liver; digestive: stomach
Based on the above assessment on oral
repeated dose toxicity, 4,4’-Isopropylidenediphenol, oligomeric reaction
products with 1-chloro-2,3-epoxypropane, reaction products with
butan-1-ol and 3-aminomethyl-3,5,5-trimethylcyclohexylamine does not
need to be classified according to Council Directive 2001/59/EC (28th
ATP of Directive 67/548/EEC) and accordingCLP (Regulation (EC) No
1272/2008 Of The European Parliament And Of The Council) as
implementation of UN-GHS in the EU.
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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