Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 259-515-6
CAS number: 55184-72-0
source information was taken into account for DNEL calculation:
A key Combined
repeated dose toxicity with reproduction/developmental toxicity
screening test in Wistar rats was conducted under GLP conditions with
the registered substance by oral gavage administration at dose levels at
0, 100, 300 and 1000 mg/kg bw/day (Hargitai, 2021). The study did not
result in test item related mortality or clinical signs.Test item
related adverse effects were observed on body weight parameters and food
consumption in High dose (1000 mg/kg bw/day) males and females (for
females during gestation and lactation periods, no effect was seen in
the pre-mating period).At the functional observation battery (FOB) and
locomotor activity measurement, there were no changes in animal
behaviour, general physical condition or in the reactions to different
type of stimuli in test item treated groups when compared to control.No
test item-related adverse effects were seen in the clinical pathology
parameters. Test item related non-adverse changes (increased Alanine
aminotransferase activity in the Mid dose males and High dose males and
females, as well as increased Alkaline phosphate activity in High dose
females) were considered to be linked to the adaptive response seen in
the liver during microscopic examination (hepatocellular hypertrophy and
vacuolation which was observed only in High dose animals, but not in Mid
or Low dose animals). No test item-related effects were observed in the
organ weights of the test item treated animals compared to controls.
Hyperkeratosis of the non-glandular gastric mucosa of the stomach was
identified at the High dose level (1000 mg/kg bw/day), as test
item-related adverse change. Mid and Low dose stomach samples of both
sexes were also evaluated the get additional information for study
interpretation, no test item-related changes were seen in those animals.There
were test item-related differences on the offspring body weights or body
weight gains in the Mid and High dose groups (300 and 1000 mg/kg bw/day,
respectively) when compared to the control values. The difference in the
Mid dose group was not considered as an adverse effect of treatment
since the values were well within the historic control range, and hence
the pup growth was considered to be normal. The measured values of
growth and weight were clearly outside the historical control range in
case of the High dose group pups, the changes observed in this dose
group were considered as a test item related adverse effect (however,
significantly lower maternal body weight gain and lower food intake by
these lactating dams i.e. maternal toxicity, is considered to be an
important factor in, or the direct cause of, the High dose pup effects).
No indication of an endocrine disruptor effect was observed in the study
based on collected oestrus cycle data, anogenital distance measurement,
nipple retention, thyroid hormone measurement, thyroid weight and
histopathology and external reproductive organs analysis. Based on the
results of this study, the systemic NOAEL for parental toxicity was 300
mg/kg bw/day. The NOAEL for reproductive effects of the parental
generation was 1000 mg/kg bw/day (based on the lack of relevant
findings). The NOAEL for pups’ (F1 generation) development and survival
was 1000 mg/kg bw/day (based on the lack of evidence of a direct effect
on the pups at 1000 mg/kg bw/day, where treatment related reduced pup
growth and body weight were seen, but were attributed as most probably
due to maternal toxicity (~20% lower dam body weight gain and ~20%
reduced food intake, associated with local gastric irritation in the
lactating dams). No treatment related effect on pup growth was seen at
A key 90 -day
study was available for the registered substance in which 40 albino rats
(20 males, 20 females) were fed with 1% of various test items mixed into
the diet. In the same study, various members of the Sulfosuccinates
Diester Group were tested (Plank et al, 1969). After 84 days
hematological values, blood chemical values, urinalysis values were
measured for all animals. Tissues were examined pathologically at the
conclusion of the 90-days test period. Organ to body weight and organ to
brain weight ratios were calculated. No significant differences in
clinical blood chemistry studies and absolute organ weights have been
detected, except a slight increase in SGPT (serum glutamic pyruvic
transaminase) and SAP (serum alkaline phosphatase). Body weights, organ
to body weight ratios, hematologic studies and urinalysis were not
different between test and control animals. No deaths or abnormal
behavioral reactions occurred; no gross pathological findings were
noted. Administration of category members at 1% in the diet (10000 ppm
equivalent to ca.750 mg act. ingr./kg body weight/day on average basis)
for 90 days in rats did not result in any relevant changes in the
subchronic toxicity study. The NOAEL was therefore considered to be
worst case 750 mg/kg bw/day. The validity of the study was supported by
additional audits on the raw data and histopathological
evaluation. Although deficiencies were detected compared to current
standards, the study was concluded to be valid and reliable.
consideration of the observations in the OECD 422 study, in
particular the reduced body weight and food consumption in High dose
(1000 mg/kg bw/day) males and females, the experimental parental NOAEL
was 300 mg/kg bw by daily oral gavage administration. The clinical
pathology and histopathological changes related to the liver were
adaptive, therefore not adverse. The gross and histological changes in
the non-glandular stomach (forestomach) are considered to be due to
repeated rritation, and not relevant for humans.
1. Humans do
not have non-glandular stomach (forestomach).
was only seen at 1 site in these animals, no other tissues are involved.
3. There was
a clear dose-response: it was only observed at the highest dose, not at
the mid and low dose, so there is a clear threshold.
4. This high
oral exposure volume is not applicable in humans; and humans do not have
the same stomach anatomy (no forestomach in humans).
studies are negative (Ames, Micronucleus, Mammalian genotoxicty).
6. It was
only observed with gavage dosing. No other routes were tested, but the
gavage is giving a bolus dose, which is considered excessive.
The reduced body
weight and food consumption in the High dose (1000 mg/kg bw/day) males
and females were considered to be due to the stomach lesions.
Therefore,the NOAEL of 300 mg/kg bw is rather a local NOAEL for rodents
under the oral gavage conditions.As there is a NOAEL of 750 mg/kg bw
from the 90-day dietary toxicity study, the NOAEL of 300 mg/kg bw/day is
considered as a conservative departure point for systemic DNELs. A
justification for calculation of DNELs is attached.
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.
Deze website maakt gebruik van cookies om het surfen zo aangenaam mogelijk te maken.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again