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EC number: 215-578-1 | CAS number: 1333-07-9
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Additional information
All key studies for this endpoint addressing bacterial mutagenicity, mammalian mutagenicity and mammalian clastogenicity were all negative for either o/p-TSA itself or via cross-reading from both its individual constituents p-TSA and o-TSA. Furthermore, substance has no structural alerts for mutagenicity, and a large database of performed studies indicate that neither p-TSA nor o-TSA possess genotoxic properties.
Discussion:
o/p-TSA consists of a mixture of p-TSA and o-TSA. Both these substances show no structural alerts for mutagenicity, and a large database of performed studies indicate that p-TSA and o-TSA do not have genotoxic properties.
The table below lists all available data, including from literature:
Type of test |
Substance |
Test system |
Doses |
Results |
Reference |
Bacterial test |
|||||
Ames test (reverse mutation) |
o/p-TSA |
S. typhimuriumstrains TA98, TA100, TA1535, TA1537, TA1538;Saccharomyces cerevisiaeD4 |
1.0 µg to 1000 µg/plate |
No mutagenic effects observed (+/- S9). |
Proprietary: Litton Bionetics, 1978 (Ketjenflex 9R) |
Ames test (reverse mutation) |
o/p-TSA |
S. typhimuriumstrains TA98, TA100, TA1535, TA1537, TA1538;Saccharomyces cerevisiaeD4 |
0.5 µ to 250 µg/plate |
No mutagenic effects observed (+/- S9). |
Proprietary: Litton Bionetics, 1976 |
Ames test (reverse mutation) |
p-TSA |
S. typhimuriumstrains TA98, TA100, TA1535, TA1537, TA1538;Saccharomyces cerevisiaeD4 |
1, 10, 100, 500, 1000 µg/plate |
No mutagenic effects observed (+/- S9). |
Proprietary: Litton Bionetics, 1978 (o-TSA) |
Ames test (reverse mutation) |
p-TSA |
S. typhimuriumstrains TA98, TA100, TA1535, TA1537;Escherichia coliWP2 uvrA |
0, 312.5, 625, 1250, 2500, 5000 μg/plate |
No mutagenic effects (+/- S9). |
MHW, Japan; cited by OECD (1994) |
Ames test (reverse mutation) |
p-TSA |
S. typhimuriumstrains TA98, TA100, TA102 |
TA98 &100: 0, 33, 100, 333, 1000 and 2000 or 3333 µg/plate ; TA102: 0, 100, 333, 1000, 3333 and 10000 µg/plate |
No mutagenic effects observed (+/- S9). |
NTP, 2007 |
Ames test (reverse mutation) |
p-TSA |
S. typhimuriumstrains TA1530, TA1535, TA1538, TA98, and TA100 |
4 x 10-7 mol up to 4 x 10-2 mol/plate. |
No direct mutagenic effects were observed (only +S9). |
Poncelet et al. (1980) |
Ames test (reverse mutation) |
p-TSA |
S. typhimuriumstrains TA98, TA100, TA1535, TA1537 |
Up to 18000 μg/plate |
No mutagenic activity (+/- S9). Evaluations included testing in ZLM agar (similar condition Eckhardt, 1981) |
Herbold (1981) |
Ames test (reverse mutation) |
p-TSA |
S. typhimurium –TA98, TA100, TA1535, TA1537 and TA1538. |
Doses of up to 12 mg/plate were used. |
(+/- S9) The only positive (marginally) increase in revertants were found intester strain TA98, with S9 and only using ZLM agar, and not in VB agar. |
Eckhardt et al. (1980) |
Gene mutation assay |
o-TSA |
S. typhimuriumstrains TA98, TA100, TA1535, TA1537, TA1538;Saccharomyces cerevisiaeD4 |
Up to 1000 ug/plate |
Negative (+/- S9) |
Proprietary, Litton Bionetics, 20838, 1978 |
Ames test (reverse mutation) |
o-TSA |
S. typhimurium (TA98, TA100, TA1535, TA1537) E. coli (WP2uvr A) |
Up to 5000 ug/plate |
Negative (+/- S9) |
MHW, Japan: 1999 |
Ames test (reverse mutation) |
o-TSA |
S. typhimurium (TA1535, TA100, TA98, TA1537) |
Up to 1000 ug/plate |
Negative (+/- S9) |
Stolts et al.: 1977 |
Ames test (reverse mutation) |
o-TSA |
S. typhimurium (TA1530, TA1535, TA1537, TA1538, TA100, TA98) |
Up to 4 x 10-2 mol/plate |
Negative (+/- S9) |
Poncelet et al.: 1979 |
Ames test (reverse mutation) |
o-TSA |
S. typhimurium (TA1535, TA100, TA1538, TA98, TA1537) |
Up to 18000 ug/plate |
Weakly positive: TA98 (+ S9) |
Eckhardt et al.: 1980 |
Ames test (reverse mutation) |
o-TSA |
S. typhimurium (TA98, TA 100, TA 1535, TA1537) |
Up to 18000 ug/plate |
Negative (+S9) |
Herbold: 1981 |
Ames test (reverse mutation) |
o-TSA |
S. typhimurium (TA1535, TA1538, TA98, TA100) |
Up to 2500 ug/plate |
Negative (+S9) |
Ashby et al.: 1978 |
Non-bacterial in vitro test |
|||||
forward mutations (TK locus) |
p-TSA |
L5 178Y mouse lymphoma cells |
Up to 5000 µg/mL |
(+/- S9) An increased frequency of mutations was only observed at the highest, cytotoxic, dose level with metabolic activation, involving an increase in small colonies. |
Proprietary. Covance, 2000 |
Chromosomal aberration |
p-TSA |
CHL cells |
Without S9: 0, 0.33, 0.65, 1.30 mg/mL; with S9: 0, 0.43, 0.85, 1.70 mg/mL. |
No chromosomal aberrations (+/- S9). |
MHW, Japan; cited by OECD (1994) |
Chromosomal aberration |
p-TSA |
CHO-K1 cells |
Cells were treated with 14, 200, and 400 μg/mL p-TSA for 24 h. |
(- S9) Negative. |
Masubuchi (1978a abstr) |
Development of ouabain resistance |
p-TSA |
RSa human cell line |
900 and 1800 μg/mL [5.26 and 10.51 mM], for 24 h |
(- S9) No increase in ouabain resistance was observed inp-TSAtreated cells, relative to controls. |
Suzuki and Suzuki (1988) |
forward mutations (TK locus) |
o-TSA |
mouse lymphoma L5178Y cells |
Up to 1712 μg/mL |
Negative (+/- S9) |
Proprietary, TNO Triskelion, V20203/05, 2013 |
Chromosomal aberration test |
o-TSA |
CHL cells |
Up to 3000 ug/mL |
Negative (+/- S9) |
MHW, Japan:1999 |
Ouabain-resistant mutation assay |
o-TSA |
Human RSa cells |
Up to 1800 ug/mL |
Negative (-S9) |
Suzuki & Suzuki: 1988 |
Chromosomal aberration test |
o-TSA |
CHO-K1 cells |
Up to 400 ug/mL |
Negative (-S9) |
Masubuchi et al.: 1978 |
In vivotest |
|||||
Micronucleus assay |
p-TSA |
Mouse Crl:CD-1, adult, M and F |
Oral 187.5, 375, 750, 1500 mg/kg bw |
Negative |
Proprietary. Covance, 2002 |
Micronucleus assay |
p-TSA |
Mouse Crl:CD-1, adult, only males |
i.v. 80, 120, 160 mg/kg bw, |
Negative |
Proprietary. Covance, 2000 |
Micronucleus assay |
p-TSA |
Mouse, NMRI, adult, number n.p., M and F |
p-TSA administered both orally 2 x 855 mg/kg and i.p. 2 x 428 and 2 x 855 mg/kg |
Negative |
Eckhardt et al. (1980) |
Mammalian spot test |
o-TSA |
Mouse |
1000 mg/kg bw (oral) |
Inconclusive |
Fahrig: 1982 |
Micronucleus assay |
o-TSA |
Mouse |
1026 mg/kg bw (by gavage) |
Negative |
Eckhardt et al.: 1980 |
Micronucleus assay |
o-TSA |
Mouse |
Up to 1026 mg/kg bw (i.p.) |
Negative |
Eckhardt et al.: 1980 |
SLRL (Sex-linked recessive lethal) test |
p-TSA |
D. melanogaster(Berlin K [wild-type] and Basc strains) |
Conc. 2.5 mM in 5% sucrose solutions used as feed for 3 days. |
A small but statistically significant increase in the frequency of recessive lethal mutations was observed only in the first brood, corresponding to mature sperm. (about double the control frequency) |
Eckhardt et al. (1980) |
SLRL (Sex- linked recessive lethal) test |
p-TSA |
D. melanogaster(Oregon-K [wild type] and Basc strains) |
Adult flies injected abdominal with about 0.2 μL of a 5 mM solution (~0.170 μg) |
There were no or marginal positive effects observed in first brood under the test conditions. (frequency was about 2.5 times higher than of the control) |
Kramers (1977) |
References:
o/p-TSA
· Proprietary: Litton Bionetics (Jagannath, D. R. & Brusick, D.), 20838, 1978.(Ketjenflex 9R)
· Proprietary: Litton Bionetics (Brusick, D.), 2547, 1976.
o-TSA
· Proprietary: Litton Bionetics (Jagannath, D. R. & Brusick, D.), 20838, 1978.(o-TSA)
· Proprietary: TNO Triskelion, V20203/05, 2013
· Ashby, J. et al. (1978) Fd. Cosmet. Toxicol., 16, 95-103.
· Eckhardt, K. et al. (1980) Toxicology Letters, 7, 51-60.
· Fahrig, R. (1982) Mutat. Res., 103, 43-47.
· Herbold, B.A. (1981) Mutat. Res., 90, 365-372.
· Masubuchi, M. et al. (1978) Mutat. Res., 54, 242-243.
· MHW, Japan (1999) Ministry of Health and Welfare, Toxicity Testing Reports of Environmental Chemicals, 7, 125-160.
· Poncelet, F. et al. (1979) Fd. Cosmet. Toxcol., 17, 229-231.
· Stolts, D. R. et al. (1977) J. Environ. Pathol. Toxicol., 1, 139-146
· Suzuki, H. & Suzuki, N. (1988) Mutat. Res., 209, 13-16.
p-TSA:
· Covance, 2000, Proprietary: in vitro-Mouse Lymphoma, report# 21198-0-431-ICH
· Covance, 2000, Proprietary: in vivo-micronucleus, report# 21198-0-455OECD
· Covance, 2002, Proprietary: in vivo-micronucleus, report# 3464-0-455OECD
· Eckhardt K., M.T. King, E. Gocke, and D. Wild. 1980. Mutagenicity study of Remsen-Fahlberg saccharin and contaminants. Toxicol Lett 7:51-60
· Herbold B.A. 1981 . Studies to evaluate artificial sweeteners, especially Remsen-Fahlberg saccharin, and their possible impurities, for potential mutagenicity by the Salmonella mammalian liver microsome test. Mutat Res 90:365-372.
· Kramers P.G. 1977. Mutagenicity of saccharin in Drosophila: The possible role of contaminants. Mutat Res 56:163-167
· Litton Bionetics, 1978, Proprietary: in vitro-Ames, report# 20838
· Masubuchi, M., S. Nawai, M. Hirokado, and K. Hiraga. 1978a abstr. Lack of the cytogenetic effects of saccharin impurities on CHO-K1 cells. Mutat. Res. 54[2], 242-243.
· MHW, Japan; cited by OECD (1994) – Ames: Hatano Research Institute, Food and Drug Safety Center, Japan, Reverse Mutation Test of 4 -Methylbenzenesulfonamide on Bacteria (http://dra4.nihs.go.jp/mhlw_data/home/pdf/PDF70-55-3e.pdf)
· MHW, Japan; cited by OECD (1994) – CHL: Hatano Research Institute, Food and Drug Safety Center, Japan, In vitro Chromosomal Aberration Test of 4-Methylbenzenesulfonamide on Cultured Chinese Hamster Cells (http://dra4.nihs.go.jp/mhlw_data/home/pdf/PDF70-55-3f.pdf)
· NTP, 2007: The Salmonella Mutagenicity Test on p-Toluenesulfonamide, report A84238 (http://tools.niehs.nih.gov/ntp_tox)
· Poncelet F., M. Mercier, and J. Lederer. 1980. Saccharin: Para forms of some impurities are not mutagenic inSalmonella typhimurium. Food Cosmet
· Suzuki H., and N. Suzuki. 1988. Mutagenicity of saccharin in a human cell strain. Mutat Res 209:13-16.
Justification for selection of genetic toxicity endpoint
No one specific study is selected. All key studies for this endpoint addressing bacterial mutagenicity, mammalian mutagenicity and mammalian clastogenicity were all negative.
Short description of key information:
All key studies for this endpoint addressing bacterial mutagenicity, mammalian mutagenicity and mammalian clastogenicity were all negative for either o/p-TSA itself or via cross-reading from both its individual consituents p-TSA and o-TSA. Furthermore, substance has no structural alerts for mutagenicity, and a large database of performed studies indicate that neither p-TSA nor o-TSA possess genotoxic properties.
Endpoint Conclusion: No adverse effect observed (negative)
Justification for classification or non-classification
Both p-TSA and o-TSA have no structural alerts for mutagenicity, and available studies covering bacterial mutagenicity, mammalian mutagenicity and mammalian clastogenicity all indicate that p-TSA and o-TSA do not have genotoxic properties. Consequently their mixture o/p-TSA does not need to be classified either.
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