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EC number: 222-883-3 | CAS number: 3648-18-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2018-2020
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Cross-referenceopen allclose all
Reference
- Endpoint:
- immunotoxicity: acute oral
- Remarks:
- Part of the OECD 414 study on the read across substance Dioctyltin oxide.
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2017-2019
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Justification for type of information:
- READ ACROSS
Hydrolysis under stomach condition (pH 1.2) of Diotyltin dilaurate into Dioctyltin oxide and lauric acid (cp. Section basic toxicokinetics: Nasshan, In vitro metabolism study)
Study for justification of read across is link via cross reference.
DIOCTYLTIN DILAURATE
Furthermore another study with dioctyltin dilaurate shows additional information regarding the immune toxicity. - Reason / purpose for cross-reference:
- reference to other study
- Reason / purpose for cross-reference:
- other: Hydrolysis under stomach condition (pH 1.2)
- Reason / purpose for cross-reference:
- other: Main study (OECD 414, rat)
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPP 85-7 (Immunotoxicity)
- Deviations:
- not applicable
- Principles of method if other than guideline:
- see attached report: study performed as port of an OECD 414 study
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Crl:WI(Han)
- Sex:
- female
- Route of administration:
- oral: feed
- Vehicle:
- other: in diet
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 72 h
- Frequency of treatment:
- in diet
- Dose / conc.:
- 0 mg/kg diet
- Remarks:
- 0 mg/kg bw/day
- Dose / conc.:
- 5 mg/kg diet
- Remarks:
- 0-4 mg/kg bw/day
- Dose / conc.:
- 25 mg/kg diet
- Remarks:
- 1.8 mg/kg bw/day
- Dose / conc.:
- 200 mg/kg diet
- Remarks:
- 11.8 mg/kg bw/day
- No. of animals per sex per dose:
- 5 in control, low and mid dise, 4 in high dose group
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale:
Subpart of OECD 414 study in rat, test substance Dioctyltin oxide. So rationale for dose selection is the main study. Dose selection form outcome of former studies with Dioctyltin oxide ((Waalkens-Berendsen, OECD 422, DOTO)
- Rationale for selecting satellite groups:
Determination of immunotoxicity as maternal toxicity
- Post-exposure recovery period in satellite groups:
Not planed, but time of last exposure to necropsy showed recovery of the immune system of test animals
- Rationale for animal assignment (if not random):
Subpart of OECD 414 study in rat, test substance Dioctyltin oxide
- Other:
Immunophenotyping:
Immunophenotyping was performed on Immunotoxicity animals from blood samples (0.5mL in EDTA) during the predose phase and on Gestation Days 7 (24 hours after first dose), 8 (48 hours after first dose), 9 (72 hours after first dose) and 10 (prior to necropsy)
Cytokine Measurement:
Blood samples (0.5 mL in serum separator tubes) were collected from Immunotoxicity cohort animals during the predose phase and on Gestation Days 7 (24 hours after first dose), 8 (48 hours after first dose), 9 (72 hours after first dose) and 10 (prior to necropsy) - Observations and clinical examinations performed and frequency:
- Immunophenotyping:
Immunophenotyping was performed on Immunotoxicity animals from blood samples (0.5mL in EDTA) during the predose phase and on Gestation Days 7 (24 hours after first dose), 8 (48 hours after first dose), 9 (72 hours after first dose) and 10 (prior to necropsy)
Cytokine Measurement:
Blood samples (0.5 mL in serum separator tubes) were collected from Immunotoxicity cohort animals during the predose phase and on Gestation Days 7 (24 hours after first dose), 8 (48 hours after first dose), 9 (72 hours after first dose) and 10 (prior to necropsy) - Positive control:
- not required
- Clinical signs:
- not specified
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- In the moin OECD 414 study no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- In the moin OECD 414 study no effects observed
- Food efficiency:
- no effects observed
- Description (incidence and severity):
- In the moin OECD 414 study no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Description (incidence and severity):
- not reported at the moment, if findings, report in endpoint of main OECD study
- Clinical biochemistry findings:
- not examined
- Description (incidence and severity):
- not reported at the moment, if findings, report in endpoint of main OECD study
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not specified
- Immunological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- see section specific immunotoxic examinations
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- 4ß percent of thymus decrease in high dose group
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Description (incidence and severity):
- not reported at the moment, if findings, report in endpoint of main OECD study
- Histopathological findings: neoplastic:
- not examined
- Description (incidence and severity):
- not reported at the moment, if findings, report in endpoint of main OECD study
- Other effects:
- not examined
- Description (incidence and severity):
- not reported at the moment, if findings, report in endpoint of main OECD study
- Details on results:
- not reported at the moment, if findings, report in endpoint of main OECD study
- Cell viabilities:
- effects observed, treatment-related
- Description (incidence and severity):
- Blood
At gestation Day 9, activated B lymphocyte numbers (CD3-/CD45RA+/CD25+) were markedly higher than the control group animals (approximately 3 to 4 times for the majority of the animals) at the 11.8mg/kg/day dose level.
Other observed differences, were limited to several lymphocyte sub-populations and tended to be slight to moderate in nature. On gestation Day 9, moderate increases were noted for CD3+/CD8+/CD25+, CD3+/CD25+ and CD3+/CD4+/CD25+ cell counts in animals dosed 11.8mg/kg/day. When compared to the control group results, the aforementioned populations were +85%, +60% and +50% greater, respectively.
At gestation Days 8 and 10, all groups administered Dioctyltin Oxide, displayed slightly lower numbers and relative percentages of NK cells (CD3-/CD161a+) when compared to the control group, although results within the treated groups were relatively unchanged when compared to other sampling days. No other changes of note were observed on Days 8 and 10.
Cytokines
Results for serum concentrations of IL-2 varied from day to day, with almost all animals, across all groups including controls, displaying quantifiable results on Days 8 and 10, but no animals recording results above the lower limit of quantitation (LLOQ) on Day 10. No test article-related effect could be determined, as the frequency and magnitude of quantifiable IL-2 were similar across all groups, and comparable to the results observed during the pre-dose phase. Quantifiable results, where observed were either slightly above the LLOQ value, or at least within 3 times the LLOQ value. - Humoral immunity examinations:
- not examined
- Specific cell-mediated immunity:
- not specified
- Non-specific cell-mediated immunity:
- not specified
- Other functional activity assays:
- not examined
- Other findings:
- not specified
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- ca. 11.8 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- immunology
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 1.8 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- immunology
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 11.8 mg/kg bw/day (nominal)
- System:
- immune system
- Organ:
- thymus
- other: immune system
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- no
- Conclusions:
- The LOAEL for acute immune toxicity for Dioctyltin oxide was determined to be 11.8 mg / kg bw7day thus a NOAEL of 1.8 mg/kg bw7day results.
Reference
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Objective of study:
- metabolism
- other: Hydrolysis under stomach conditions
- Qualifier:
- no guideline required
- GLP compliance:
- no
- Specific details on test material used for the study:
- Dioctyltin dilaurate
- Radiolabelling:
- no
- Metabolites identified:
- yes
- Details on metabolites:
- dimeric Distannoxane
- Bioaccessibility (or Bioavailability) testing results:
- There is no bioavailability of the dimeric Distannoxane based on a molecular mass of > 1000 DA
- Conclusions:
- DOTL in-vitro metabolism can be monitored using 119Sn-NMR Spectroscopy. Under the simulated gastric conditions (0.1 M HCl/pH 1.2/37°C) the tin resonance at -155 ppm characteristic to DOTL (Annex 1) disappeared completely indicating that DOTL has been used up within 0.5-4.0 hour of the experiment. Main products of the hydrolysis (Annex 2 and 3) are DOTLC, (DOTCL)2O and a DOTO complex. (DOTCL)2O was detected as two sharp peaks at -92 ppm and -145 ppm
Increasing the exposure time from 30 min. to 4 hours slightly increased the amount of DOTLC and decreased the amount of the DOTO complex (Annex 2 and 3).
Formation of the dialkytin mono-chloro carboxylates is described in literature 2). This type of hydrolytic behavior at low pH is consistent with the results obtained on hydrolysis of dialkyltinmecaptides4-6). The dialkyltin mono-chloro esters are formed under the same conditions rapidly and equilibrated with the initial dialkyltin mecaptides.
A broad signal at about 150 ppm was assigned to the DOTO complex. On one hand, the DOTO reference material results in a comparable chemical shift with a broad signal (Annex 6), on the other hand, DOTO is not known to be soluble in hexane. Therefore, the DOTO complex term in this study describes a hexane-extractable solution of DOTO in DOTLC or DOTL.
Alkyltincarboxylates are known for their rich structural variety which includes different ways of coordinating the carboxyl groups and tin atoms and their ability to form bridged chemical structures2,3). Additionally, bulky alkyl groups (such as octyl groups) on a tin atom of the dialkyltin oxides are known to form more soluble cyclic trimers as opposed to dialkyltin oxide polymers7).
Addition of a DOTC excess resulted in an instant reaction of the DOTO complex to DOTLC.
In order to check if any non-extractable by hexane tin compounds were formed as a result of DOTL in-vitro metabolism and remained in the aqueous phase, that phase was analyzed for a total tin content using AAS. The total tin content of the aqueous phase was found to be < 10 ppm (trace quantity).
In a hydrolysis study of Dioctyltin dilaurate with 0.1 M Hydrogenchloride (4h, 37 ^C) was identified a distannoxane as hydrolysis product. In an similar experiment with Dioctyltin dichloride also was identified a distannoxane as hydrolysis.
Based on 119Sn-NMR data and data from mass spectroskopy, the distannoxane is minimum monomeric with a mass > 1000 Da.
So even if formed by both substances (source and target) under low pH conditions this substance cannot pass the
membranes of the gastrointestinal tract and thus is toxicological not of relevance
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 020
- Report date:
- 2020
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Version / remarks:
- This study was designed to meet the requirements of the OECD test guideline 414
(adopted 25 June 2018)
- GLP compliance:
- yes
Test material
- Reference substance name:
- Dioctyltin dilaurate
- EC Number:
- 222-883-3
- EC Name:
- Dioctyltin dilaurate
- Cas Number:
- 3648-18-8
- Molecular formula:
- C40-H80-O4-Sn
- IUPAC Name:
- dioctyltin dilaurate
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- Lot number : VP19-120
Test animals
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- Crl:WI(Han) from Charles River Laboratories, Margate, UK
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: Ground Purina Mills Certified Rodent Diet 5002
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg diet
- Remarks:
- ppm
- Dose / conc.:
- 20 mg/kg diet
- Remarks:
- ppm
- Dose / conc.:
- 80 mg/kg diet
- Remarks:
- ppm
- Dose / conc.:
- 500 mg/kg diet
- Remarks:
- ppm
- No. of animals per sex per dose:
- 20 females
- Control animals:
- yes, concurrent vehicle
Examinations
- Blood sampling:
- Blood for toxicokinetic evaluations was collected prior to the initiation of dosing on
GD 6, approximately 24 (±1) hours after the initiation of dosing, and at necropsy on
GD 21 - Fetal examinations:
- The progress and outcome of pregnancy were evaluated, and
fetuses were examined for malformations and variations and fetal anogenital distances
were recorded
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Test article-related unscheduled deaths occurred for animals provided with 500 ppm
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Adverse test article-related reductions in body weights were evident for animals
provided with 500 ppm - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Adverse test article-related reductions in food consumption were evident for animals
provided with 500 ppm, compared with controls - Endocrine findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Adverse test article-related reductions in thyroxine (T4) and increases in thyroid
stimulating hormone (TSH) were evident for animals provided with 500 ppm,
compared with controls.
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Description (incidence and severity):
- No Aborts observed.
- Total litter losses by resorption:
- effects observed, treatment-related
- Description (incidence and severity):
- Two females (Animals R0307 and R0313) provided with 500 ppm had total in utero
litter losses - Dead fetuses:
- effects observed, treatment-related
- Description (incidence and severity):
- Adverse test article-related lower gravid uterus weights, and weight changes were
evident for females provided with 500 ppm, compared with controls. A higher
incidence of dead fetuses and lower fetal weights were also evident following
maternal exposure of 500 ppm, compared with controls, and considered adverse.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 0.8 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- maternal abnormalities
Results (fetuses)
- Anogenital distance of all rodent fetuses:
- effects observed, treatment-related
- Description (incidence and severity):
- An adverse test article-related effect on anogenital distance was noted for male fetuses
maternally exposed with 500 ppm.
No effect on anogenital distance was evident for female fetuses maternally exposed
with 500 ppm or fetuses of either sex maternally exposed with 20 or 80 ppm. - External malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- Adverse test article-related fetal malformations and variations were observed
following maternal exposure of 500 ppm.
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 3.9 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- skeletal malformations
- Remarks on result:
- other: incomplete ossification of cervical arches
Fetal abnormalities
- Abnormalities:
- effects observed, treatment-related
- Localisation:
- external: limb
- external: paw
- external: anogenital distance
- other: polydactyly
- Description (incidence and severity):
- Adverse test article-related fetal malformations and variations were observed
following maternal exposure of 500 ppm.
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- Ad libitum dietary administration of control article (vehicle) or 20, 80, or 500 ppm
Dioctyltin dilaurate (equivalent to nominal dose levels 0, 0.8, 3.9, or 25.4 mg/kg/day,
respectively) to the pregnant rat from GD 6 through 21 resulted in adverse test
article-related effects for animals provided with 500 or 80 ppm, and adversely
affected the developing fetuses following maternal exposure of 500 ppm.
Based on the finding of this study, the no observed adverse effect level (NOAEL) for
maternal toxicity is 20 ppm.
Fetuses were not adversely affected by maternal exposure to 80 ppm; as such, the
NOAEL for embryo-fetal development is 80 ppm
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