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EC number: 617-116-8
CAS number: 80573-04-2
Repeat dose short-term, sub-chronic and chronic toxicity studies are
available. The results show that balsalazide disodium, and hence
balsalazide acid, are of low toxicological concern.
The short term toxicity studies performed in rats and dogs did not
produce any treatment related effects up to the highest dose tested
(2000 mg/kg bw/day). In the longer term studies, 26 and 96 weeks in
rats, adverse effects were seen in the stomach, kidney and bladder.
However, these effects indicated low systemic toxicity of the test
substance and hence balsalazide acid. In the 96 week study, these
effects manifested themselves at dose levels of 100 and 500 mg/kg bw/day.
Maximum plasma levels of BSZ were reached within 2 hours. The median
Cmax on Day 1 was 0.595, 1.55 and 3.65 nmol/mL, respectively, in the
low, mid and high dose groups. The plasma levels declined progressivly
with time and were still measurable at 8 hours (low and mid doses) and
24 hours (high dose). There was no apparent accumulation of BSZ over
time. The urinary recovery of BSZ was <1% of the dose.
The urinary recovery for 4 -ABA was 0.5 - 5.2% of the dose. The urinary
recovery for 4 -ASA was 1.3 - 10.5%.
The median plasma AUC of NASA was 7.3, 26.6 and 28.6 nmol.h/mL on day 27
and urinary recoverywas 0.054 - 0.57% of the dose. Plasma and urinary
levels of NABA were below the limit of detection.
Plasma levels of the drug and its metabolites wwere not determined. The
urinary excretion of BSZ was very low (0.062 - 0.152%) as compared to
total 5 -ASA ranging from -4.18% to 11.97% of the dose. The urinary
excretion of 4 -ABA was -1.6 - 6.7% of the dose.
The mode of action of toxicity and its relevance to humans has not been
assessed. However, the sodium salt of balsalazide acid has been
authorised for use as a pharmaceutical for the treatment of inflammatory
The only adverse effects of repeated exposure to balsalazide acid (in
the form of balsalazide disodium salt) were seen in the 96 week oral
repeated dose toxicity study in rats, where dose levels of 100 and 500
mg/kg/day produced a decrease in body weight gain, an increase in kidney
weights and some gross changes in the kidneys. These effects were
considered to be treatment-related and hence the LOAEL was assigned as
100 mg/kg bw/day.
However, these effects are not considered to trigger classification of
balsalazide acid as STOT-RE 2. According to the Guidance on the
Application of the CLP Criteria (Version 5.0, July 2017), the guidance
value for STOT-RE category 2 classifications is 10 – 100 mg/kg bw/day
based on 90 day oral repeated dose toxicity studies in rats. When
Haber’s rule is used to adjust these standard guidance values for a 96
week study, the equivalent classification range is then 1.5 – 13 mg/kg
bw/day. Since the lowest dose tested in the 96 week study was at least
an order of magnitude above this range, there is no available test data
to justify classification. Therefore, balsalazide does not need to to be
classified for repeated dose toxicity (STOT-RE).
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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