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EC number: 251-718-8
CAS number: 33885-52-8
Repeated dose toxicity (OECD TG 422): NOAEL = 83 mg/kg bw, Target organs
were liver and especially kidneys on which the NOAEL is based.
Pinyl Isobutyraldehyde is an aldehyde, which likely oxidises in the
gastrointestinal tract into its respective acid. Reduction into the
alcohol can also occur as was shown in the bioaccumulation study.
Repeated dose/Reproscreen study (OECD TG 422)
Introduction and Method. Potential toxic
effects of the test substance after repeated exposure was investigated
in an at least 28 -day repeated dose toxicity study with the combined
reproduction/developmental toxicity screening test in rats, performed
according to OECD guideline and in accordance with GLP principles. Pinyl
iso butyraldehyde alpha was administered by daily oral (dietary
admixture) to male and female Wistar Han rats at dose levels of 450,
1800 and 7200 ppm (10 rats/sex/dose level, intended doses were 37.5, 120
and 450 mg/kg bw). A control group of 10 rats/sex was given the vehicle
(Basic powdered diet). Males were treated for 31 days, i.e. 2 weeks
prior to mating, during mating, and up to termination. Females were
treated during 2 weeks prior to mating, during mating, during
post-coitum, and up to the day before necropsy (i.e. on day 13 of
lactation for females delivered, on day 25 of gestation for unmated
females and on study Day 55 for failed to mate female).
Dietary exposure analysis: Throughout the
pre-mating period, the achieved intake of test item was generally lower,
at all dose levels, than the theoretical concentrations for males and
females (-18 to -31 %). During the gestation period, the achieved test
item concentration was close to the nominal concentration at the low and
mid dose level, whereas at the high dose level, the decreased achieved
concentration ranged from -18 to -32 %. During the lactation period, due
to higher food consumption in treated females, the achieved intake of
test item was markedly higher than the theoretical concentrations (+31
to + 121 %). In addition, after 24-hour storage in the food hopper at
room temperature, a decrease in test item formulation concentration of
approximately -20 % was noted when compared with the nominal
concentrations. The intake on a mg/kg bw bases was 21, 83 and 246 mg/kg
bw using the lower intake for either males or females.
Clinical signs: There was no death or clinical
sign during the study. There were decreased mean body weight gains and
food consumption at 1800 and 7200 ppm in both sexes up to the end of the
gestation period, leading to a relevant lower body weight at 7200 ppm
(246 mg/kg bw).
Functional battery observations: There was no
obvious effect of treatment on the auditory, pupillary and righting
reflexes or open field tests for the males or females at any dose level.
Lower gripping strength in treated rats was considered to be the
consequence of slightly lower body weights and not a direct effect of
the test item.
Heamatology, Clinical chemistry and T4 levels: There were
no test item-related changes.
Organ weights and histopathological effects: For males and
females at 7200 ppm (246 mg/kg bw), test item induced changes in organ
weights a.o. increase in relative liver weight up to 25% without showing
histopathological changes. At this 7200 ppm, relative kidney weights in
males only were increased up to 18%. This increase was associated with
tubular degeneration and tubular basophilia for males without hyaline
droplets and therefore the effects were not considered to be due to
alpha-hydrocarbon nephropathy. This means that this effect has to be
taken into account for the derivation of the NOAEL.
In view of the instability of the substance, the intake of the
substance was lower than anticipated for all doses. The substance may
have volatilised and/or degraded due to oxidation of the aldehyde. At
7200 ppm (246 mg/kg bw) slight (maximum -9%) body weight decrease was
considered treatment related. Several organ weights were increased e.g.
liver, thyroid and kidney. No histopathological effects were seen in
most organs but in kidneys tubular effects were seen in males, which
could not be attributed to alpha-hydrocarbon nephropathy in absence of
hyaline (eosinophilic) droplets. Based on these results and specifically
the histopathological effects in the kidneys, the dose of 1800 ppm,
corresponding to at least 83 mg/kg bw/day, respectively, was considered
as the parental No Observed Adverse Effect Level (NOAEL).
Based on the available data, Pinyl Isobutyraldehyde does not need to be
classified for repeated dose toxicity in accordance with the criteria
outlined in EU CLP (EC no. 1272/2008 and its amendments).
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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