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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
reproductive toxicity, other
Remarks:
QSAR model,Estrogen Receptor Binding method, relevant for reproductive toxicity endpoints in fish and mammals.
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
QSAR prediction:Accepted Estrogen Receptor Binding QSAR method for chemicals properties assessment.. This method is relevant for reproductive toxicity endpoints in fish and mammals.

Data source

Referenceopen allclose all

Reference Type:
other: QSAR model
Title:
Unnamed
Year:
2015
Reference Type:
publication
Title:
A conceptual framework for predicting toxicity of reactive chemicals: Models for soft electrophilicity
Author:
Schultz, T.W., Carlson. R.E., Cronin, M.T.D., Hermens, J.L.M., Johnson, R., O'Brien, P.J., Roberts, D.W., Siraki, A., Wallace, K.D. and Veith, G.D.
Year:
2006
Bibliographic source:
SAR QSAR in Environmental Research 17: 413-428.

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: QSAR Toolbox Version 3.3.5.17
Principles of method if other than guideline:
This grouping method contains simple categories for estrogen receptor (ER) binding. This method is relevant for reproductive toxicity endpoints in fish and mammals.
GLP compliance:
no
Remarks:
not applicable. QSAR model,Estrogen Receptor Binding method, relevant for reproductive toxicity endpoints in fish and mammals.
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
disodium 2-methylpropan-1-ol [(2-methylpropoxy)methanethioyl]sulfanide hydroxide
EC Number:
904-290-8
Cas Number:
25306-75-6
Molecular formula:
C5H10OS2.Na
IUPAC Name:
disodium 2-methylpropan-1-ol [(2-methylpropoxy)methanethioyl]sulfanide hydroxide
Details on test material:
- Name of test material (as cited in study report):sodium O-isobutyl dithiocarbonate
SMILES : O(C(CC)C)C(S([Na]))=S
CHEM : Carbonodithioic acid, o-(2-methylpropyl) ester, sodium salt
CAS Num: 25306-75-6
MOL FOR: C5 H9 O1 S2 Na1
MOL WT : 172.24
Log Kow: 1.78 (used)
Wat Sol: 663 mg/L (measured)

Test animals

Species:
other: fish (trout) and mammals.
Strain:
other: QSAR model
Sex:
not specified

Administration / exposure

Route of administration:
other: QSAR model
Vehicle:
other: QSAR model
Details on exposure:
Estrogen receptor (ER) binding is a molecular initiating event much like protein binding that leads to a series of adverse outcomes, which are typically considered reproductive and development hazards. It is an endpoint where several comprehensive databases exist, which has lead to the development of several approaches for using (Q)SARs to predict ER-binding and possible endocrine disruption .
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Estrogen receptor (ER) binding is a molecular initiating event much like protein binding that leads to a series of adverse outcomes, which are typically considered reproductive and development hazards. It is an endpoint where several comprehensive databases exist, which has lead to the development of several approaches for using (Q)SARs to predict ER-binding and possible endocrine disruption .
Doses / concentrations
Remarks:
Doses / Concentrations:

Basis:
other: QSAR model
Control animals:
not specified

Examinations

Parental animals: Observations and examinations:
Estrogen receptor (ER) binding is a molecular initiating event much like protein binding that leads to a series of adverse outcomes, which are typically considered reproductive and development hazards. It is an endpoint where several comprehensive databases exist, which has lead to the development of several approaches for using (Q)SARs to predict ER-binding and possible endocrine disruption .

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Description (incidence and severity):
QSAR model
Body weight and weight changes:
no effects observed
Description (incidence and severity):
QSAR model
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
QSAR model
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
QSAR model
Other effects:
no effects observed
Description (incidence and severity):
Test substance intake: QSAR model

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Description (incidence and severity):
QSAR model
Reproductive function: sperm measures:
no effects observed
Description (incidence and severity):
QSAR model
Reproductive performance:
no effects observed
Description (incidence and severity):
QSAR model

Details on results (P0)

Sodium O-isobutyl dithiocarbonate have a molecular weight of less than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Sodium O-isobutyl dithiocarbonate (SIBX) does not cause reproductive toxicity.

1.1. CAS number: 25306-75-6
1.2. Chemical name(s):
carbonodithioic acid, o-(2-methylpropyl) ester, sodium salt
sodium o-isobutyl dithiocarbonate
sodium o-(2-methylpropyl) carbonodithioate
carbonic acid, dithio-, o-isobutyl ester, sodium salt
sodium isobutyl xanthate
1.3. Structure codes:
a. SMILES: CC(C)COC(=S)S{-}.[Na]{+}
1.4. Profiling results:
-DNA binding by OECD -No alert found
-Est rogen Receptor Binding-Non binder, non cyclic structure
-OECD HPV Chemical Categories-Not categorized
-Protein binding by OECD-No alert found

Effect levels (P0)

Dose descriptor:
other: Relative ERBA (Estrogen Receptor Binding Affinity)
Effect level:
< -3 other: Log RBA(Relative Binding Affinities )
Based on:
other: Estrogen receptor (ER) binding
Sex:
not specified
Basis for effect level:
other: see 'Remark'
Remarks on result:
other: Generation: QSAR model (migrated information)

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Description (incidence and severity):
QSAR model
Mortality / viability:
no mortality observed
Description (incidence and severity):
QSAR model
Body weight and weight changes:
no effects observed
Description (incidence and severity):
QSAR model
Sexual maturation:
no effects observed
Description (incidence and severity):
QSAR model
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
QSAR model
Gross pathological findings:
no effects observed
Description (incidence and severity):
QSAR model
Histopathological findings:
no effects observed
Description (incidence and severity):
QSAR model

Details on results (F1)

Sodium O-isobutyl dithiocarbonate have a molecular weight of less than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Sodium O-isobutyl dithiocarbonate (SIBX) does not cause reproductive toxicity.

1.1. CAS number: 25306-75-6
1.2. Chemical name(s):
carbonodithioic acid, o-(2-methylpropyl) ester, sodium salt
sodium o-isobutyl dithiocarbonate
sodium o-(2-methylpropyl) carbonodithioate
carbonic acid, dithio-, o-isobutyl ester, sodium salt
sodium isobutyl xanthate
1.3. Structure codes:
a. SMILES: CC(C)COC(=S)S{-}.[Na]{+}
1.4. Profiling results:
-DNA binding by OECD -No alert found
-Est rogen Receptor Binding-Non binder, non cyclic structure
-OECD HPV Chemical Categories-Not categorized
-Protein binding by OECD-No alert found

Effect levels (F1)

Remarks on result:
other: no effects observed

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

This grouping method contains simple categories for estrogen receptor (ER) binding. This method is relevant for reproductive toxicity endpoints in fish and mammals.

 

Non-binder, impaired OH or NH2 group

Non-binder without OH or NH2 group

Non-binder, non-cyclic structure

Non-binder, MW > 500

Non-binder, non-cyclic structure– chemicals without cycles and MW =<500

Non-ER binder due to non-cyclic molecular structure.

 

Estrogen receptor (ER) binding is a molecular initiating event much like protein binding that leads to a series of adverse outcomes, which are typically considered reproductive and development hazards. It is an endpoint where several comprehensive databases exist, which has lead to the development of several approaches for using (Q)SARs to predict ER-binding and possible endocrine disruption .

Popular among these are the “four phase” assessment that includes Comparative Molecular Field Analysis (CoMFA) and the Common Reactivity Pattern Approach (COREPA)

Since the RE-binding is a receptor mediated event, particular organic functional groups, size and shape are critical to binding potency.

Sodium O-isobutyl dithiocarbonate have a molecular weight of less than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Sodium O-isobutyl dithiocarbonate (SIBX) does not cause reproductive toxicity.

Applicant's summary and conclusion

Conclusions:
Non-ER binder due to non-cyclic molecular structure. Sodium O-isobutyl dithiocarbonate have a molecular weight of less than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Sodium O-isobutyl dithiocarbonate (SIBX) does not cause reproductive toxicity.
Executive summary:

Sodium O-isobutyl dithiocarbonate have a molecular weight of less than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Sodium O-isobutyl dithiocarbonate (SIBX) does not cause reproductive toxicity.

1.1. CAS number: 25306-75-6

1.2. Chemical name(s):

carbonodithioic acid, o-(2-methylpropyl) ester, sodium salt

sodium o-isobutyl dithiocarbonate

sodium o-(2-methylpropyl) carbonodithioate

carbonic acid, dithio-, o-isobutyl ester, sodium salt

sodium isobutyl xanthate

1.3. Structure codes:

a. SMILES: CC(C)COC(=S)S{-}.[Na]{+}

1.4. Profiling results:

-DNA binding by OECD -No alert found

-Est rogen Receptor Binding-Non binder, non cyclic structure

-OECD HPV Chemical Categories-Not categorized

-Protein binding by OECD-No alert found