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Genetic toxicity in vitro

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Principles of method if other than guideline:
Model name: A7O, A7N, AN7 and AN8 from FDA Genetic toxicity set Model version: MC4PC version 2.4.1.5
Type of assay:
other: (Q)SAR
Genotoxicity:
negative
Additional information on results:
The tested molecule does not contain any confirmed alerts and is assumed to be inactive.
Remarks on result:
no mutagenic potential (based on QSAR/QSPR prediction)

Predicted value (comments):

c:\multicase\mc4pc\fda genetox 2011\job110612.txt

 

 VERSION 2.400

 

 

 

*******************************************************************************

 Now Processing... Sodium Ethyl Xantate                      (Molecule #    1)

*******************************************************************************

 A7O- Mutagenicity - Mammal In vitro CHO V79 hgprt loci - RCA     # 617 2.40

 ------------------------------------------------------------------------------

 MC calculated Water Solubility is: 0.38 [in log(mol/m**3)]

 MC calculated Log(Octanol/Water) Partition Coef.is: 1.17

 Molecule satisfies the rule of 5 (bioavailable)

 MC Calculated Human Intestinal Absorption is: 92.3%

** WARNING ** The following functionalities are UNKNOWN to me:

      *** SH -CS -O -

       *** CS -O -CH2-

 

MULTICASE-3 Prediction

----------------------

** The molecule does not contain any known biophore

    However,

 The UNKNOWN fragment : CS -O -

 is similar to the biophore : CS -N -

    The molecule might therefore be active and should be tested experimentally

 

 CONCLUSIONS:

 ------------

 ** The projected Mutagenicity activity is  10.0    CASE units **

 ** The compound is presumed to be INACTIVE **

 ** The probability that this molecule is Mutagenicity is   24% **-

 ** The results are INCONCLUSIVE

 

 RCA CONCLUSIONS:

 -------------------------

 RCA Expert Call: Negative Coverage: 2w

HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH

 

 

 

*******************************************************************************

 Now Processing... Sodium Ethyl Xantate

*******************************************************************************

 A7N- Mutagenicity - Mammal In vitro ML5178y tk loci Ct - RCA     # 806 2.40

 ------------------------------------------------------------------------------

 MC calculated Water Solubility is: 0.38 [in log(mol/m**3)]

 MC calculated Log(Octanol/Water) Partition Coef.is: 1.17

 Molecule satisfies the rule of 5 (bioavailable)

 MC Calculated Human Intestinal Absorption is: 92.3%

** WARNING ** The following functionalities are UNKNOWN to me:

      *** SH -CS -O -

       *** CS -O -CH2-

 

MULTICASE-3 Prediction

----------------------

** The molecule does not contain any known biophore

    However,

 The UNKNOWN fragment : CS -O -

 is similar to the biophore : CS -N -

    The molecule might therefore be active and should be tested experimentally

 

 CONCLUSIONS:

 ------------

 ** The projected Mutagenicity activity is  10.0    CASE units **

 ** The compound is presumed to be INACTIVE **

 ** The probability that this molecule is Mutagenicity is   25% **-

 ** The results are INCONCLUSIVE

 

 RCA CONCLUSIONS:

 -------------------------

 RCA Expert Call: Negative Coverage: 2w

HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH

 

 

 

*******************************************************************************

 Now Processing... Sodium Ethyl Xantate

*******************************************************************************

 AN7- Mutagenicity - Mammal In vitro ML5178y tk loci A  - RCA     # 565 2.40

 ------------------------------------------------------------------------------

 MC calculated Water Solubility is: 0.38 [in log(mol/m**3)]

 MC calculated Log(Octanol/Water) Partition Coef.is: 1.17

 Molecule satisfies the rule of 5 (bioavailable)

 MC Calculated Human Intestinal Absorption is: 92.3%

** WARNING ** The following functionalities are UNKNOWN to me:

      *** SH -CS -O -

       *** CS -O -CH2-

 

MULTICASE-3 Prediction

----------------------

** The molecule does not contain any known biophore

 ** The results are QUESTIONABLE due to the

               presence of UNKNOWN functionalities **

 

 CONCLUSIONS:

 ------------

 ** The projected Mutagenicity activity is  10.0    CASE units **

 ** The compound is presumed to be INACTIVE **

 ** The probability that this molecule is Mutagenicity is   22% **-

 

  RCA CONCLUSIONS:

 -------------------------

 RCA Expert Call: Negative Coverage: 2w

HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH

 

 

 

*******************************************************************************

 Now Processing... Sodium Ethyl Xantate

*******************************************************************************

 AN8- Mutagenicity - Mammal In vitro ML5178y tk loci B  - RCA     # 563 2.40

 ------------------------------------------------------------------------------

 MC calculated Water Solubility is: 0.38 [in log(mol/m**3)]

 MC calculated Log(Octanol/Water) Partition Coef.is: 1.17

 Molecule satisfies the rule of 5 (bioavailable)

 MC Calculated Human Intestinal Absorption is: 92.3%

** WARNING ** The following functionalities are UNKNOWN to me:

      *** SH -CS -O -

       *** CS -O -CH2-

 

MULTICASE-3 Prediction

----------------------

** The molecule does not contain any known biophore

    However,

 The UNKNOWN fragment : CS -O -

 is similar to the biophore : CS -N -

    The molecule might therefore be active and should be tested experimentally

 

 CONCLUSIONS:

 ------------

 ** The projected Mutagenicity activity is  10.0    CASE units **

 ** The compound is presumed to be INACTIVE **

 ** The probability that this molecule is Mutagenicity is   22% **-

 ** The results are INCONCLUSIVE

 

 RCA CONCLUSIONS:

 -------------------------

 RCA Expert Call: Negative Coverage: 2w

HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH

The Test is Done.

 

Conclusions:
Interpretation of results (migrated information):negativeThe tested molecule does not contain any confirmed alerts and is assumed to be inactive.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

No studies were available for assessing the genotoxicity of sodium ethyl xanthate or other xanthates.

The results should be considered together with the results of test with the 3 assays from FDA genetic toxicity set, designed from the FDA archives and openly published results of genetic toxicity tests date for:

Bacterial gene mutation in vitro

    • The Microbial composite (Sal_Ecoli_Bac) (A7A,3644 records)
    • TheSalmonella typhimurium5 strains (A7B, 3535 records)
    • The E.coli composite (A7C, 527 records)
    • The E.coli WP strains (A7D, 280 records)

Mammalian gene mutationin vitro

    • The Mammalianin vitroCHO V79 hgprt loci (A7O, 617 records)
    • The Mammalianin vitroML5178y tk loci Ct (A7N, 806 records)
    • The Mammalianin vitroML5178y tk loci A (AN7, 565 records)
    • The Mammalianin vitroML5178y tk loci B (AN8, 563 records)

The Chromosomal aberrationsin vitro

    • The Chromosomal Absin vitrocomposite (A7U, 1385 records)
    • The Chromosomal Absin vitroCHO cells (A7V, 686 records)
    • The Chromosomal Absin vitrocells (A7W, 744 records)
    • The Chromosomal Absin vitroHuLym (A7X, 187 records)
    • The Chromosome Absin vitroUndefined cells (A8H, 280 records)

 

The results of tests with the FDA GeneTOX sets are summarized in the following tables.

 

Important notice:The RCA method expert call is a computer-generated output that is considered, along with other available information, in formulating the final conclusion.The Final Conclusion is a conclusion made by the reviewer, taking into account all the available evidence, including thein-silicoand available experimental results.

Table 1. Ames test

Compound

A7A

A7B

A7C

A7D

RCA Method Expert Call (Overall)

Review expert

O-ethyl dithiocarbonic acid

-

-

-

-

-*

-

 

Table 2. Mammalian gene mutationin vitro

Compound

A7O

A7N

AN7

AN8

RCA Method Expert Call (Overall)

Review expert

O-ethyl dithiocarbonic acid

-

-

-

-

-*

-

 

Table 3. The Chromosomal aberrationsin vitro

Compound

A7U

A7V

A7W

A7X

A8H

RCA Method Expert Call (Overall)

Review expert

O-ethyl dithiocarbonic acid

-

-

-

-

-

-*

-

 

 

Table4.  Summary of results and overall conclusions for the genotoxicity tests

Compound

Ames

MAin vitro 

CAin vitro

FINAL CONCLUSION

RCAMethod Expert Call

 

Review

Expert

RCAMethod Expert Call

 

Review

Expert

RCAMethod Expert Call

 

Review

Expert

 

O-ethyl dithiocarbonic acid

-*

-

-*

-

-*

-

-

AMES= bacterial mutation assay; MA = mammalian; CA = chromosomal aberration;

+ positive; (+) potentially positive; - negative; (-) potentially negative. ? –inconclusive * possible structural coverage problems

 

The RCA paradigm, implemented in the RCA decision support system, requires the following criteria for a chemical to be designated as POSITIVE:

1.     To be active in more than one test assay within a test battery

2.     To be active in a test assay, there must be two or more structurally similar fragments across the modules of the test assay.

Tables 1 - 4 reveal these conditions were not met by test compound in FDA Genetic Toxicity Set. The unknown structural features, which were detected in all test batteries, are typical for xantate moieties.

The xantates were not reported a genetoxic in publicly available sources and no component of this product present at levels greater than or equal to 0.1% is identified as probable, possible or confirmed human carcinogen by. The tested substance was reported in NICNAS Priority existing chemical assessment report (1995, Vol.6, 66p) and it was not listed there as genetic toxicant for humans. The Final conclusion is that the tested chemical is considered to be nonthreatening to humans from this evaluation.

 

The tested molecule does not contain any confirmed alerts and is assumed to be inactive.

The probability that the prediction is accurate is 80%.

 

Other (Q)SAR predictions of:

Lazar Toxicity Predictions: Mutagenicity-Salmonella typhimurium (CPDB) and

 

Tox Predictfor:(http://apps.ideaconsult.net:8080/ToxPredict)

The above QSAR software models indicate that sodium ethyl xanthate (CAS# 140-90-9) and other xanthates are inactive as a mutagenic substance and does not contain alert structures according to Benigni/Bossa rules.


Justification for selection of genetic toxicity endpoint
The Final conclusion is that the tested chemical is considered to be nonthreatening to humans from this evaluation.

Justification for classification or non-classification