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EC number: 295-765-2
CAS number: 92128-68-2
Repeat dose studies on two C5 non-cyclics streams and two major components of these streams have been considered. There is evidence of specific target organ toxicity in several studies. A finding common to several of the studies is kidney changes characteristic of hyaline droplet nephropathy in male rats. This male rat-specific effect is considered not to be relevant to humans. Although C5 non-cyclics streams may contain low levels of benzene and/or toluene, the maximum levels present are below those which would warrant classification for specific target organ systemic toxicity after repeated exposure.
dose studies have been conducted by the inhalation route on two of the
UVCB C5 non-cyclic category streams (CAS 68476-55-1 Pyrolysis C5 and CAS
68602-79-9 Hydrotreated C5). In addition data are available for the
marker substance isoprene and potential major components 1,3 pentadiene and
2-methyl-2 butene .
Pyrolysis C5 stream (CAS No.68476-55-1) has been tested in a 28-day
repeated dose study in rats at concentrations of 0, 98, 302 or 1012 ppm
(HLS, 2004a). No general systemic effects were observed during the
routine clinical examination in motor activity. Histopathological
changes (minimal centrilobular hepatocyte hypertrophy) were seen at 1012
ppm in both sexes. In male rats only higher kidney weights and renal
cortical tubules with hyaline droplets were apparent in all treatment
groups. The kidney effects observed in male rats is a well studied
phenomenon known as hyaline droplet nephropathy. This phenomenon has
been extensively evaluated and is a male rat-specific phenomenon and is
considered not adverse or relevant for human risk assessment. It can be
concluded that the NOAEC is 302 ppm.
Hydrotreated C5 stream (CAS No.68602-79-9) has been tested in a 28-day
repeated dose study in rats at concentrations of 0, 939, 3145 or 8059
ppm (HLS, 2004b). Other than lethargy and increased salivation observed
at 8502 ppm, no other treatment-related clinical signs were noted. There
were no treatment related changes were observed in body weight, motor
activity or in the functional observational battery.In both sexes at
8502 ppm and females at 3033 ppm, atrophy and some ‘disorganisation’ of
the olfactory epithelium of nasal turbinates were noted. Basophilic
cortical tubules were increased in incidence and severity in the kidneys
of all male exposure groups and females at 3033 and 8502 ppm. Male rats
in all treatment groups had renal cortical tubules with hyaline droplets
and, as for Pyrolysis C5, this nephropathy is not considered relevant
for human risk assessment.In the liver of males at 8502 ppm there was
minimal centrilobular hepatocyte hypertrophy and slightly higher liver
weights than controls.It was concluded that the NOAEC was 992 ppm.
and component substance data
for the marker substances benzene (Classification: DSD -Toxic T,
R48/23/24/25; CLP - STOT-RE Category 1, H372) and toluene
(Classification: DSD - Harmful Xn, R48/20; CLP - STOT-RE Category 2,
H373) which are known to cause target organ toxicity are not considered
in this instance since levels will not exceed the thresholds for
classification according to DPD and CLP.
marker substance isoprene is not classified for repeat dose toxicity
under DSD. In brief, there is a clear species difference in response to
exposure to isoprene, with mice being more sensitive than rats.In rats
findings were essentially limited to splenic fibrosis and interstitial
cell hyperplasia of the testis.In contrast, in mice non-neoplastic
toxicities include spinal cord degeneration, partial rear limb
paralysis, testicular atrophy, olfactory epithelial degeneration,
forestomach epithelial hyperplasia and macrocytic anaemia (NTP, 1994;
Placke et al., 1996). The overall repeat dose NOAEC for rats is 220 ppm
(613 mg/m3) based on splenic fibrosis in males in a two-year
study (NTP, 1999). The
overall repeat dose LOAEC in mice is 70 ppm (195 mg/m3) based
on increased incidence of spinal cord degeneration after 26 weeks
exposure and 26 weeks recovery period, with no NOAEC identified in the
Melnick et al (1994) study. However, it is of note that this effect was
not reproduced in the chronic oncogenicity study, which also showed a
clear NOAEC at 10 ppm (Placke et al, 1996).
potentially major component, 2 -methyl-2 -butene, is not currently
classified under DSD but, considering self-classification, does not
warrant classification for repeat dose toxicity under DSD or a STOT-RE
classification under CLP. Similarly, 1,3-pentadiene does not warrant
classification. In a combined repeat oral dose and
reproductive/developmental toxicity screening study with 1,3-pentadiene
in rats (EBSI, 1992a) effects were limited to a transient decrease in
food consumption in the high dose (1000 mg/kg day) females.No other
treatment-related effects were observed in parents or their
offspring.The NOAEL for repeat dose toxicity was 100 mg/kg/day.
Melnick RL et al
(1994). Isoprene, an endogenous hydrocarbon and industrial chemical,
induces multiple organ neoplasia in rodents after 26 weeks of inhalation
exposure. Cancer Res., Vol. 54, pp. 5333-5339.
C5 non-cyclics streams and the major components demonstrate functional
disturbance or morphological change which has toxicological significance
only at doses in excess of the levels which warrant classification under
DPD or CLP.
streams within this category contain less than 1% benzene and less than
10% toluene and therefore do not require a classification for this
endpoint under DPD or 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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