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EC number: 200-661-7
CAS number: 67-63-0
GLP-guideline study according to OECD guideline 451 in rats is available
for IPA. The derived NOAEC is 5000 ppm.
The inhalation toxicity of IPA has been assessed in a 104-week
oncogenicity study in rats (Burleigh-Flayer and Benson, 1994). This
GLP study was conducted according to OECD test guideline 451.
IPA was administered by whole-body inhalation to groups of male
and female Fischer 344 rats (75 rats/sex) for6 hours/day 5
days/weekfor at least 104 weeks at nominal concentrations of 0
(control), 500, 2500, or 5000 ppm (measure concentrations of0,
504, 2509, or 5031 ppm, respectively). Ten
rats/sex/group were assigned to interim sacrifice at Week 73. Animals
were monitored for clinical observations, body and organ weights,
ophthalmology examinations, hematology, urinalysis and urine chemistry
examinations, gross pathology and microscopic examinations.
Exposure of rats to IPA vapour for 104 weeks produced clinical signs of
toxicity (including hypoactivity, lack of startle reflex, and/or
narcosis), changes in body weight, and urinalysis and urine chemistry
indicative of kidney changes (decrease in osmolality and increase in
total volume and/or protein) in the 2500 and 5000 ppm groups. At
terminal sacrifice, increased absolute and relative kidney weights were
noted in males at 2500 ppm and females at 5000 ppm. Macroscopic
changes such as granular kidney were noted in males and females of 2500
and 5000 ppm groups. A number of non-neoplastic histopathological
changes were observed, with the most significant being in the kidney. The
only neoplastic change observed was in male rats and was an increase in
interstitial cell adenomas of the testis considered to represent marked
hyperplasia and not autonomous growth. The increased
incidence was considered related to the unusually low frequency of
testicular tumors in the control group. No increases
in the incidence of neoplastic lesions were noted for female rats. In
summary, the report allows the conclusion that there no adverse exposure
related effects. Therefore, from the present report, a NOAEL of 5000 ppm
IPA can be derived.
GLP whole-body inhalation oncogenicity study in Fischer 344 rats with
IPA concentrations of 0, 500, 2500, 5000 ppm for 6 hours/day 5 days/week
for 104 weeks was conducted according to OECD Test Guideline 451 and in
compliance with GLP. Exposure
of rats to isopropanol vapor for 24 months produced clinical signs of
toxicity, changes in body weight, and urinalysis and urine chemistry
indicative of kidney changes in the 2500 and 5000 ppm groups. These
changes were considered by the study authors to be indicative of chronic
progressive nephropathy, a spontaneous lesion in aging rats which tends
to be more prominent in male than female rats. Based on human and animal
evidence relating to CPN, Hard et al. (2009)
concluded that this is a rodent-specific lesion which should not be
regarded as an indicator of human toxic hazard. The only neoplastic
lesion which was elevated was an increase in Leydig cell tumors in male
rats. This is also a common
spontaneous lesion in male rat which is very common in the rat strain
used for this evaluation, F-344. The authors observed that the
statistical significance attached to the frequency of this observation
was probably due to the unusually low incidence in the concurrent
control group. No increase in neoplastic lesions were noted in female
rats. It was concluded that
the NOAEL was 5000 ppm, equivalent to 12500 mg/m³.
shorter duration key study was a subchronic inhalation study in Fischer
344 rats and CD-1 mice with IPA administered at concentrations of 0,
500, 2500, 5000 ppm for 6 hours/day 5 days/week for 98 days
(Burleigh-Flayer et al.,1991). This study was conducted according
to OECD Test Guideline 413 and in compliance with GLP. During the 14th
week, male and female rats (excluding those animals designated for
neuroanatomic pathology evaluation) received 2 and 3 consecutive days of
exposure, respectively. The 10 female rats of the 500, 1500, and 5000
ppm group designated for neuroanatomic pathology evaluation were exposed
for 1 day during the 14th week; the male rats of the 500, 1500, and 5000
ppm group designated for neuroanatomic pathology evaluation were not
exposed during the 14th week. Male and female mice received 4 and 5
consecutive days of exposure during the 14th week, respectively. NOAECs
were not identified by the authors. Rats showed acute signs of toxicity
(including ataxia, narcosis, lack of a startle reflex, and/or
hypoactivity), decreases in absolute body weight and body weight gain,
and changes in hematology parameters in animals exposed to 1500 and 5000
ppm of isopropanol, increased relative liver weight in male and female
rats exposed to 5000 ppm, as well as increased motor activity for female
rats in the 5000 ppm group. Mice showed clinical signs of acute toxicity
(including ataxia, narcosis, lack of a startle reflex, and/or
hypoactivity) in animals exposed to 1500 and 5000 ppm of isopropanol,
increased body weight and body weight gain observed in female mice of
the 5000 ppm group, various changes in hematologic and serum clinical
chemistry parameters observed in female mice of the 5000 ppm group, and
increased relative liver weight in female mice of the 5000 ppm group.
information on the repeated dose inhalation toxicity of IPA also is
provided. A 78-week inhalation oncogenicity study based on OECD Test
Guideline 453 and conducted in compliance with GLP in CD-1 mice
identified a NOEL [equivalent
to a no-observed effect concentration (NOEC)] for
toxic effects of 500 ppm due to clinical signs of toxicity and increases
in body weights and body weight gains noted at the higher doses, and a
NOEL for oncogenicity effects of 5000 ppm (the highest dose tested) as
an increased frequency in neoplastic lesions was not noted
(Burleigh-Flayer and Wagner, 1993).
inhalation study in Fischer 344 rats and CD-1 mice conducted according
to OECD test guideline 412 was conducted according to GLP
(Burleigh-Flayer et al., 1990). Animals
were administered IPA for 6 hours/day, 5 days/week at 1000, 5000, 10000,
and 15000 ppm. Mortality
was observed in rats and mice at the highest two doses. Histologic
lesions observed in the kidneys of male rats at 1000 and 5000 ppm are
considered to be species and sex specific.
Gordon C. Hard, Kent J. Johnson, Samuel M.
Cohen; Critical Reviews in Toxicology; 2009, Vol. 39, No. 4, Pages
332-346; A comparison of rat chronic progressive nephropathy with human
The substance does not meet the criteria for classification and
labelling for repeated dose toxicity according to Annex VI of Regulation
(EC) No. 1272/2008.
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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