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EC number: 259-515-6
CAS number: 55184-72-0
purpose of this OECD No. 422 study was to obtain information on the
possible toxic effects of Sodium 1,4-diisotridecyl sulphonatosuccinate
(CAS 55184-72-0, EC 259-515-6) test item following repeated (daily)
administration by oral gavage to Wistar (Crl:WI) rats at 3 dose levels.
A control group received the vehicle only (propylene glycol).
study also comprised a reproductive/developmental toxicity screening
test, intended to provide initial information on possible effects on
male and female reproductive performance such a gonadal function, mating
behaviour, conception, pregnancy, parturition and also on the
development of the F1 offspring from conception to Day 13 post-partum.
dose levels were selected by the Sponsor in consultation with the Study
Director based on the results of a Dose Range Finding (DRF) study. Based
on those results, 1000 mg/kg bw/day was selected as the High dose for
Dose formulation concentration
Dose formulation volume
Number of animals
measured during the study included twice a day mortality checking, daily
routine and weekly detailed observation of clinical signs, weekly body
weight and food consumption measurements and clinical pathology
evaluation (including haematology, coagulation, clinical chemistry and
urinalysis). Neurological assessment (Functional Observation Battery
(FOB) including measurements of the landing foot splay, grip strength as
well as locomotor activity measurement) was performed during the last
week of the treatment for each sex. In addition, the reproductive
performance, pregnancy, parturition and postpartum/lactation period were
monitored in the adult animals, and viability, clinical signs and
development were evaluated in their F1 offspring until PND13. At
termination (Day 28 for males, PPD (Post-partum Day) 14 for females),
necropsy with macroscopic examination was performed. Weights of selected
organs were recorded, and representative tissues/organs were sampled and
preserved in appropriate fixatives from the adult animals or F1 animals.
The thyroxine (T4) levels in the PND (Post-natal Day) 13 pups and
parental males were also determined.
the adult animals, a detailed histological examination was performed on
the selected list of retained organs of 5 animals/sex in the Control and
High dose groups, all found dead animals and all those male / female
mating pairs where no liveborn pups were achieved.
formulation were analysed for concentration and/or homogeneity on four
occasions during the study. Overall, the formulations were considered
adequate for the study.
summary, under the conditions of this study the daily administration of
Sodium 1,4-diisotridecyl sulphonatosuccinate (CAS 55184-72-0, EC
259-515-6) by oral gavage to Wistar rats at dose levels of 100, 300 or
1000 mg/kg bw/day (Low, Mid and High dose groups, respectively) did not
result in test item related mortality or clinical signs. Test
item related adverse effect was 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
changes were noted in the reproductive parameters during mating and
gestation, delivery and post-partum/lactation period until PPD14. The
number of implantation or liveborn pups, as well as the pre-natal,
post-natal or total mortality values were comparable with the control
values in all test item treated dose groups. No test item related
macroscopic findings were recorded for F1 pups at necropsy.
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. As the measured
values were clearly outside the historical control range iin case of the
High dose group, the changes observed in that dose group were considered
as a test item related adverse effect.
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
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 following No-Observed-Adverse-Effect Levels (NOAELs)
were considered: The NOAEL for systemic toxicity of the parental
generation: 300 mg/kg bw/day (based on body weight and food consumption
effects, and stomach microscopic findings).The NOAEL for reproductive
effects of the parental generation: 1000 mg/kg bw/day (based on the lack
of relevant findings). The NOAEL for pups’ (F1 generation) development
and survival: 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 300 mg/kg/day).
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