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EC number: 202-718-1 | CAS number: 98-97-5
- 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
Description of key information
The skin sensitization potential of Pyrazine-2-carboxylic acid (CAS No: 98 -97 -5) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. Pyrazine-2-carboxylic acid (CAS No: 98 -97 -5) was estimated to be not sensitising to the skin of Pirbright White guinea pigs. Based on the estimated result Pyrazine-2-carboxylic acid (CAS No: 98 -97 -5) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Pirbright White guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation
- Remarks:
- in vivo
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
- Justification for type of information:
- Data is from OECD QSAR Toolbox 3.3 and the QMRF report has been attached.
- Qualifier:
- according to guideline
- Guideline:
- other: Prediction
- Principles of method if other than guideline:
- Prediction was done using OECD QSAR Toolbox version 3.3.
- GLP compliance:
- not specified
- Type of study:
- other: estimated data
- Justification for non-LLNA method:
- No data
- Specific details on test material used for the study:
- - Name of test material: Pyrazine-2-carboxylic acid
- Molecular formula: C5H4N2O2
- Molecular weight: 124.099 g/mol
- Substance type: organic
- Physical state: solid
- Smiles: c1ncc(C(=O)O)nc1
- InChI: 1S/C5H4N2O2/c8-5(9)4-3-6-1-2-7-4/h1-3H,(H,8,9) - Species:
- guinea pig
- Strain:
- Pirbright-Hartley
- Sex:
- male/female
- Details on test animals and environmental conditions:
- No data
- Route:
- epicutaneous, occlusive
- Vehicle:
- physiological saline
- Concentration / amount:
- 50 % of a 0.5 % aqueous solution
- Day(s)/duration:
- 6 hours
- Adequacy of induction:
- not specified
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- physiological saline
- Concentration / amount:
- 50 %
- Day(s)/duration:
- on day 30
- Adequacy of challenge:
- not specified
- No. of animals per dose:
- 5 animals in treatment group. 10 animals in a control group.
- Details on study design:
- No data
- Challenge controls:
- No data
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 50%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- none
- Remarks on result:
- no indication of skin sensitisation
- Cellular proliferation data / Observations:
- No skin reaction were detectable at 24 and 48 hours after epidermal challenge. No systemic toxicity was observed.
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information
- Conclusions:
- Pyrazine-2-carboxylic acid (CAS No: 98 -97 -5) was estimated to be not sensitising to the skin of Pirbright White guinea pigs.
- Executive summary:
The skin sensitization potential of Pyrazine-2-carboxylic acid (CAS No: 98 -97 -5) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.
Pyrazine-2-carboxylic acid (CAS No: 98 -97 -5) was estimated to be not sensitising to the skin of Pirbright White guinea pigs.
Based on the estimated result Pyrazine-2-carboxylic acid (CAS No: 98 -97 -5) can be considered to be not sensitizing to Pirbright White guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.
Data is from OECD QSAR Toolbox 3.3 and the QMRF report has been attached.
Reference
The
prediction was based on dataset comprised from the following
descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 6 nearest neighbours
Domain logical expression:Result: In Domain
((((((((((("a"
or "b" or "c" or "d" )
and ("e"
and (
not "f")
)
)
and ("g"
and (
not "h")
)
)
and ("i"
and (
not "j")
)
)
and ("k"
and (
not "l")
)
)
and ("m"
and (
not "n")
)
)
and "o" )
and ("p"
and (
not "q")
)
)
and ("r"
and (
not "s")
)
)
and "t" )
and ("u"
and "v" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as Aryl OR Carboxylic acid OR
Pyrazine by Organic Functional groups ONLY
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as Aryl OR Carboxylic acid OR
Overlapping groups OR Pyrazine by Organic Functional groups (nested) ONLY
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as Acid, aromatic attach [-COOH] OR
Alcohol, olefinic attach [-OH] OR Aromatic Carbon [C] OR Aromatic
Nitrogen OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one
aromatic attach [-C(=O)-] OR Miscellaneous sulfide (=S) or oxide (=O) OR
Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as Aromatic compound OR Carbonic
acid derivative by Organic functional groups, Norbert Haider (checkmol)
ONLY
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OASIS v.1.3
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as AN2 OR AN2 >> Nucleophilic
addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >>
Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >>
alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2
>> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR Michael
addition OR Michael addition >> Quinone type compounds OR Michael
addition >> Quinone type compounds >> Quinone methides OR Radical OR
Radical >> ROS formation after GSH depletion OR Radical >> ROS formation
after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation
after metabolically formed carbenium ion species OR SN1 >> Alkylation
after metabolically formed carbenium ion species >> Polycyclic Aromatic
Hydrocarbon Derivatives OR SN2 OR SN2 >> Alkylation, direct acting
epoxides and related after P450-mediated metabolic activation OR SN2 >>
Alkylation, direct acting epoxides and related after P450-mediated
metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR
SN2 >> Direct acting epoxides formed after metabolic activation OR SN2
>> Direct acting epoxides formed after metabolic activation >> Quinoline
Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at
an activated carbon atom >> Quinoline Derivatives by DNA binding by
OASIS v.1.3
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OECD
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as Michael addition OR Michael
addition >> P450 Mediated Activation to Quinones and Quinone-type
Chemicals OR Michael addition >> P450 Mediated Activation to Quinones
and Quinone-type Chemicals >> Arenes OR Michael addition >> P450
Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic
(PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR
Michael addition >> Polarised Alkenes-Michael addition OR Michael
addition >> Polarised Alkenes-Michael addition >> Alpha, beta-
unsaturated amides OR Michael addition >> Polarised Alkenes-Michael
addition >> Alpha, beta- unsaturated esters OR SN1 OR SN1 >> Iminium Ion
Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines
by DNA binding by OECD
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Non binder, without OH or NH2
group by Estrogen Receptor Binding
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Non binder, impaired OH or NH2
group OR Non binder, MW>500 OR Non binder, non cyclic structure by
Estrogen Receptor Binding
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as No alert found by Protein
binding by OASIS v1.3
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as Acylation OR Acylation >> Ester
aminolysis OR Acylation >> Ester aminolysis >> Amides OR Michael
Addition OR Michael Addition >> Michael addition on conjugated systems
with electron withdrawing group OR Michael Addition >> Michael addition
on conjugated systems with electron withdrawing group >>
alpha,beta-Carbonyl compounds with polarized double bonds OR Michael
Addition >> Michael addition on conjugated systems with electron
withdrawing group >> Cyanoalkenes OR Michael Addition >> Polarised
Alkenes OR Michael Addition >> Polarised Alkenes >> Polarised Alkene -
alkenyl pyridines, pyrazines, pyrimidines or triazines OR Nucleophilic
addition OR Nucleophilic addition >> Addition to carbon-hetero double
bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds
>> Ketones by Protein binding by OASIS v1.3
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as (!Undefined)Group All Lipid
Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4
g/kg AND Group All Melting Point > 200 C AND Group CN Melting Point >
180 C by Skin irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as (!Undefined)Group C Surface
Tension > 62 mN/m OR (!Undefined)Group CNS Surface Tension > 62 mN/m OR
Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group C Aqueous
Solubility < 0.0001 g/L OR Group C Melting Point > 55 C OR Group C
Vapour Pressure < 0.0001 Pa OR Group CN Aqueous Solubility < 0.1 g/L OR
Group CN log Kow > 4.5 OR Group CNS Melting Point > 50 C by Skin
irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "p"
Referential
boundary: The
target chemical should be classified as Non-Metals by Groups of elements
Domain
logical expression index: "q"
Referential
boundary: The
target chemical should be classified as Alkali Earth OR Metalloids by
Groups of elements
Domain
logical expression index: "r"
Referential
boundary: The
target chemical should be classified as Group 14 - Carbon C AND Group 15
- Nitrogen N AND Group 16 - Oxygen O by Chemical elements
Domain
logical expression index: "s"
Referential
boundary: The
target chemical should be classified as Group 15 - Phosphorus P by
Chemical elements
Domain
logical expression index: "t"
Referential
boundary: The
target chemical should be classified as Reactive unspecified by Acute
aquatic toxicity MOA by OASIS ONLY
Domain
logical expression index: "u"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -0.452
Domain
logical expression index: "v"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 1.15
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Additional information:
Various studieshas been investigated for the test chemicalPyrazine-2-carboxylic acid (CAS No: 98 -97 -5)to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs and humans for target chemicalPyrazine-2-carboxylic acid (CAS No: 98 -97 -5) and its structurally similar read across substancesNiacinamide (CAS No: -98-92-0) and Nicotinic acid (CAS no: 59-67-6).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;
The skin sensitization potential of Pyrazine-2-carboxylic acid (CAS No: 98 -97 -5) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. Pyrazine-2-carboxylic acid (CAS No: 98 -97 -5) was estimated to be not sensitising to the skin of Pirbright White guinea pigs. Based on the estimated result Pyrazine-2-carboxylic acid (CAS No: 98 -97 -5) can be considered to be not sensitizing to Pirbright White guinea pigs.
According to Danish QSAR database , the skin sensitization effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for Pyrazine-2-carboxylic acid (CAS No: 98 -97 -5). Based on estimation, no skin sensitization reactions were observed in guinea pigs and humans. Therefore, Pyrazine-2-carboxylic acid (CAS No: 98 -97 -5) was considered to be not sensitizing.
The Cosmetic Ingredients Review (CIR, 2005) conductedskin sensitization study for structurally similar read across substance Niacinamide(CAS No: -98-92-0) in guinea pigsto determine its sensitization potential.The preliminary irritation tests were performed in 8 guinea pigs to determine concentrations suitable for sensitization test [injection challenge concentration (ICC) and application challenge concentration(ACC)]. The concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC) and the highest concentration which caused no irritation was selected as the application challenge concentration ( ACC).As a result of the preliminary studies, the concentration selected for skin sensitization test were 5% forICC and 20% for ACC.During the induction phase,the total dose was administered on one occasion as 4 intradermal injections, each 2.5 times the ICC (2.5X5%). Fourteen days later each animal was challenged intradermally in one flank and topically in the other with 0.1 ml aliquots of test substance at the respective ICC and ACC (5%and 20% respectively). Twenty-four hours later the reactions were observed.Reactions were examined under a constant and artificial day light.In the absence of sensitization reactions at first challenge the induction and challenge procedures were repeated, andapparent sensitization reactions confirmed 7 days later by a second and confirmatory challenge with controls included.At 24 hours after the first challenge(A1)and at the second(B1)and confirmatory challenge(B2)with 5% and 20% niacinamide none of the rabbits showed positive results. Thus, it can be concluded that theNiacinamide(CAS No: -98-92-0)was considered to be not sensitizing onguinea pigs.
The above results were supported by Skin irritation study reported by European Food Safety Authority (EFSA, 2012) and OECD (Organization for Economic Cooperation and Development, 2002) for same read across substance Niacinamide(CAS No: -98-92-0)according to the OECD Guideline 406 (Skin Sensitization). During induction test, 50% in saline (0.9% NaCl)was applied on day 1, 8 and 15. Following 15 days rest period, animals were challenged at concentration of 50% Nicotinamide in saline. Skin reactions were evaluated after 24 and 48 hours (day 31 and 32). Also clinical signs and body weights were observed on day 2 and weekly thereafter. None of the animals exposed to the Nicotinamide showed any clinical signs, change in body weight and cutaneous sensitizing properties. Therefore the chemicalNiacinamide (CAS no: 98-92-0)was to be non-sensitizing.
The OECD SIDS(1993) carried outSkin sensitizationstudy inPirbright white guinea pigsfor anotherstructurally similar read across substanceNicotinic acid (CAS no: 59-67-6) according to OECD guideline 406.During this test, the guinea pigs were exposed to theNicotinic acid and were observed for skin reactions. As no skin sensitizing effects were observed in treated animals, the chemical Nicotinic acid (CAS no: 59-67-6)was considered to be not sensitizing to thePirbright white guineapigs in Guinea pig maximization test.
Thus on the basis of available data for thetarget chemicalPyrazine-2-carboxylic acid (CAS No: 98 -97 -5) and its structurally similar read across substancesNiacinamide (CAS No: -98-92-0)andNicotinic acid (CAS no: 59-67-6),it can be concluded thatchemical Pyrazine-2-carboxylic acid (CAS No: 98 -97 -5) is unable to cause skin sensitization and considered as non skin sensitizer.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.
Justification for classification or non-classification
The skin sensitization potential of test substance Pyrazine-2-carboxylic acid (CAS No: 98 -97 -5) and its structurally similar read across substances Niacinamide (CAS No: -98-92-0)andNicotinic acid (CAS no: 59-67-6) were observed in various studies. From the results obtained from these studies it is concluded that the chemical Pyrazine-2-carboxylic acid (CAS No: 98 -97 -5) is not likely to cause skin sensitization and hence can be classified as non skin sensitizer.
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