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EC number: 812-724-1
CAS number: 106705-37-7
No histological changes
for uterus, ovaries, testes and prostate after the administration of up
to and including 4800 ppm strontium chloride hexahydrate were observed
in a sub-chronic oral repeated dose toxicity study OECD 408 (Kroes,
1977). The authors reported a NOAEL of 4800 ppm, which is equivalent to
a strontium concentration of 157.7 mg/kg bw.
In accordance with
regulation 1907/2006 (EC), Annex IX, Section 8.7.3, Column 1, an
extended one generation reproductive toxicity study shall be proposed,
only in case the available repeated dose toxicity studies (e.g. 28-day
or 90-day studies) indicate adverse effects on reproductive organs or
tissues or reveal other concerns in relation with reproductive toxicity.
Sufficient weight of evidence is available to demonstrate an absence of
reproductive toxicity and that testing on vertebrate animals in an
extended one- generation reproductive toxicity study (OECD 443) with
strontium neodecanoate shall be omitted.
In a modified
three-generation reproductive toxicity study, male and female
Sprague-Dawley rats were administered neodecanoic acid at 0, 100, 500
and 1500 ppm (approximately 0, 5, 25 and 75 mg/kg-bw/day, respectively)
in the diet. No adverse effects were observed on survival, appearance,
behaviour, body-weight gain and food consumption in the parental, F1 or
F2 generations. The reproductive performance of the parents was not
affected. No treatment-related gross or microscopic pathological
findings were observed at any of the dietary levels.
is not expected to show effects on fertility, since the two moieties
strontium and neodecanoic acid have not shown fertility toxicity in a
range of test systems. For further information on the toxicity of the
individual moieties, please refer to the relevant sections in the IUCLID
Information on the
individual moieties strontium and neodecanoic acid will be used for the
hazard assessment and, when applicable, for the risk characterisation of
strontium neodecanoate. For the purpose of hazard assessment of
strontium neodecanoate, the point of departure for the most sensitive
endpoint of each moiety will be used for the DNEL derivation. In case of
neodecanoic acid in strontium neodecanoate, the NOAEL of 250 mg/kg
bw/day for the developmental toxicity will be used. In case of strontium
the NOAEL of 9.9 mg Sr/kg bw/day for the repeated dose toxicity will be
used. The NOAEL of 9.9 mg Sr/kg bw/day for repeated dose toxicity (90 d
study, based on increased relative thyroid weights in male rats) is
lower than the NOAEL of 34.5 mg Sr/kg bw/day (developmental toxicity
Based on the outcome of
a prenatal developmental toxicity assay: Strontium chloride
hexahydrate did induce adverse developmental effects in a GLP OECD TG414
studie performed in pregnant Wistar rats from gestation day 6 (GD6) to
gestation day 19 (GD19) administered by oral gavage at dose levels of
105, 420, and 1681 mg SrCl2.6H2O/kg bw/d
(Nextreat, 2021). These developmental effects were seen in the absence
of maternal toxicity effects.
No mortality or clinical signs in the dams were observed under the
conditions of this study.
Based on the results of thyroid hormones analysis, thyroid weights,
histopathological evaluation of thyroids and the measurement of
anogenital distance of fetuses, no endocrine disruptor effect was
observed in the study.
Treatment at 1681 mg SrCl2.6H2O/kg bw/day was
associated with maternal toxicity effects, such as reduced body weight
and reduced body weight gain and reduced food consumption of the dams,
as well as with developmental toxicity effects, such as increased number
of dead fetuses, increased post implantation loss, increased
intrauterine mortality and growth retardation of the fetuses.
Consequently, this led also to a reduced litter weight and reduced
gravid uterine weight.
In addition, the test item at this dose level caused ossification
disturbances on the whole skeletal system in the fetuses, which was
expressed as: incomplete ossification of the whole skull, unossified
sternebrae, wavy and marked wavy ribs, unossified thoracic, lumbar and
sacral vertebrae, unossified metacarpal and metatarsal bones, unossified
pubis and/or ischium, misshapen, bent and/or short scapula, bent and/or
short clavicula, humerus, radius, ulna, femur, tibia and fibula.
Treatment at 420 mg SrCl2.6H2O/kg bw/day no
evidence of adverse maternal effect was observed, but was associated
with developmental toxicity effects, such as increased number of dead
fetuses and post implantation loss. In addition, the test item at this
dose level caused skeletal variations in the fetuses such as incomplete
ossification of the skull, wavy and marked wavy ribs, and skeletal
malformations, identified as bent and/or short scapula, humerus, femur,
tibia and fibula.
No adverse maternal or developmental toxicity effect was observed at 105
mg SrCl2.6H2O/kg bw/day.
LOAELmaternal toxicity: 1681 mg SrCl2.6H2O/kg
NOAELmaternal toxicity: 420 mg SrCl2.6H2O/kg
LOAELdevelopmental toxicity: 420 mg SrCl2.6H2O/kg
NOAELdevelopmental toxicity: 105 mg SrCl2.6H2O/kg
LOAELmaternal toxicity: 552.4 mg Sr/kg bw/day
NOAELmaternal toxicity: 138.1 mg Sr/kg bw/day
LOAELdevelopmental toxicity: 138.1 mg Sr/kg bw/day
NOAELdevelopmental toxicity: 34.5 mg Sr/kg bw/day
toxicity study, pregnant rats, n=22 per dose, were treated by oral
gavage to 50, 250, 600 or 800 mg/kg/day neoheptanoic acid, a substance
similar in structure to neodecanoic acid, during gestation days 6-15. On
gestation day 21, the dams were euthanized and the pups were examined
for signs of developmental toxicity. Under the conditions of the
experimental methods, the test material produced maternal toxicity at
dose levels of 600 and 800 mg/kg with maternal lethality at 800
mg/kg. The test material was severely embryotoxic at 800 mg/kg with less
than 20% of embryos surviving. Offspring of the 800 mg/kg group had
reduced body weight, reduced crown-rump distance, displayed variations
signifying delayed development, and a significant percentage (25%) were
malformed. In the 600 mg/kg group, there was an increase number of dams
with 3 or more resorptions. Offspring of the 600 mg/kg group displayed
significant incidences of major (hydrocephalus) and minor (knobby or
angular ribs, extra lumbar vertebrae) malformations but showed few signs
of delayed development and were not runted. There was no statistically
significant evidence of maternal toxicity at dose levels of 50 or 250
mg/kg. There was a slight, but not statistically significant, increase
in embryonic resorption noted for the 250 mg/kg group. There was no
statistically significant evidence of developmental toxicity at doses
for 50 or 250 mg/kg. The NOAEL for maternal toxicity is 250 mg/kg and
the NOAEL for developmental toxicity is 250 mg/kg.
In a reliable prenatal
developmental toxicity study conducted with strontium chloride
hexahydrate, adverse developmental effects were reported in the absence
of maternal toxicity. In addition, adverse effects were reported in a
developmental toxicity study conducted with neoheptanoic acid. However,
the study performed with neoheptanoic acid is of limited quality due to
major restrictions in study design. Nevertheless, strontium is the
moiety of concern.
Thus, final conclusion
on classification and labelling can be made.
For further information
on the toxicity of the individual moieties, please refer to the relevant
sections in the IUCLID and CSR.
No adverse effects were observed in a sub-chronic repeated dose toxicity study with strontium chloride and prenatal developmental toxicity study conducted with strontium chloride hexahydrate as well as in a modified three-generation study performed with neodecanoic acid. Thus, strontium neodecanoate in all probability has also no potential to impair sexual function or fertility. Therefore, no classification is required for fertility.
Based on the outcome of a prenatal developmental toxicity study according to the OECD 414 guideline (Nextreat, 2021), clear evidence was shown of adverse effects on development induced by strontium chloride hexahydrate in the absence of maternal toxic effects. These adverse effects were: skeletal malformations (bent and/or short scapula, humerus, femur, tibia, and fibula), next to increased number of dead fetuses and post implantation loss, and skeletal variations (incomplete ossification of the skull, wavy and marked wavy ribs). A clear dose-response was observed.
LOAEL developmental = 420 mg SrCl2.6H2O/kg bw/d (138.1 mg Sr/kg bw/d)
NOAEL developmental = 105 mg SrCl2.6H2O/kg bw/d (34.5 mg Sr/kg bw/d)
LOAEL maternal = 1681 mg SrCl2.6H2O/kg bw/d (552.4 mg Sr/kg bw/d) based on decreased body weight and body weight gain, decreased food consumption of the dams
NOAEL maternal = 420 mg SrCl2.6H2O/kg bw/d (138.1 mg Sr/kg bw/d)
Based on the information from the key OECD TG 414 study (Nextreat, 2021), the hazard classification for SrCl2.6H2O and Sr is re-evaluated and updated. According to the Guidance on the application of CLP criteria, and the clear adverse effects on the development of the offspring, with a clear dose-response relationship, and in the absence of maternal toxicity, the substance SrCl2.6H2O and Sr meet the criteria laid down in Annex I Section 126.96.36.199.1 for classification as toxic to reproduction category 1B 'Presumed human reproductive toxicant' (evidence for classification is from animal data).
Label elements in accordance with table 3.7.3 of Annex I: 188.8.131.52:
GHS Pictograms: GHS08: Health Hazard
Signal word: Danger
Hazard statement: H360D May damage the unborn child
Classification for strontium neodecanoate
Reproductive toxicity classification of strontium neodecanoate is based on the presence of strontium which is classified for reproductive toxicity (see CLP Article 6(3) and Annex I, 3.7.3). Generic concentration limits triggering classification (Annex I Table 3.7.2) Category 1B: ≥0.3%. Therefore,
Classification strontium neodecanoate: 1B
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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