Methyl isonicotinate

Endpoint summary

Description of key information

Skin irritation:

The dermal irritation potential of Methyl isonicotinate (CAS NO: 2459-09-8) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The chemical Methyl isonicotinate (CAS NO: 2459-09-8) was estimated to be irritating to the skin of New Zealand White rabbits. Based on the estimated result Methyl isonicotinate (CAS NO: 2459-09-8) can be considered to be irritating to skin and can be classified under the category “Category 2”as per CLP regulation.

Eye irritation:

The ocular irritation potential of Methyl isonicotinate (CAS NO: 2459-09-8) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The chemical Methyl isonicotinate (CAS NO: 2459-09-8)was estimated to be irritating into the eyes of New Zealand White rabbits. Based on the estimated result Methyl isonicotinate (CAS NO: 2459-09-8) can be considered to be irritating to eye and can be classified under the category “Category 2”as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: 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 version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: Methyl Isonicotinate
- Molecular formula: C7H7NO2
- Molecular weight: 137.1373 g/mol
- Smiles notation: c1(C(=O)OC)ccncc1
- InChl: 1S/C7H7NO2/c1-10-7(9)6-2-4-8-5-3-6/h2-5H,1H3
- Substance type: Organic
- Physical state: Liquid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not fully reversible within:

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Severe skin irriation was observed in treated group.

Estimation method: Takes mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((((((("a" or "b" or "c" )  and "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 ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and "y" )  and ("z" and ( not "aa") )  )  and ("ab" and ( not "ac") )  )  and ("ad" and ( not "ae") )  )  and ("af" and "ag" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Esters (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Esters by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Esters by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Alkali Earth OR Alkaline Earth OR Halogens OR Metalloids OR Metals by Groups of elements

Domain logical expression index: "g"

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: "h"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid ester AND Pyridine by Organic Functional groups

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Pyrimidine OR Pyrrolidine OR Saturated heterocyclic amine OR Saturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid ester AND Pyridine by Organic Functional groups

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as tert-Butyl OR Unsaturated heterocyclic amine OR Unsaturated heterocyclic fragment OR Urea derivatives by Organic Functional groups

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 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 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

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 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Group All Melting Point > 200 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

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 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Aromatic amines OR Ketones OR Phenols by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Not classified by Oncologic Primary Classification

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Aromatic Amine Type Compounds by Oncologic Primary Classification

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes by Protein binding by OASIS v1.3

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Basic [0,10) AND No pKa value by Ionization at pH = 9

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Acidic [0,10) by Ionization at pH = 9

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Basic [90,100] AND No pKa value by Ionization at pH = 1

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as Basic [20,30) by Ionization at pH = 1

Domain logical expression index: "af"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.399

Domain logical expression index: "ag"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.72

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The chemical Methyl isonicotinate (CAS NO: 2459-09-8) was estimated to be irritating to the skin of New Zealand White rabbits. Based on the estimated result Methyl isonicotinate (CAS NO: 2459-09-8) can be considered to be irritating to skin.

Executive summary:

The dermal irritation potential of Methyl isonicotinate (CAS NO: 2459-09-8) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The chemical Methyl isonicotinate (CAS NO: 2459-09-8) was estimated to be irritating to the skin of New Zealand White rabbits. Based on the estimated result Methyl isonicotinate (CAS NO: 2459-09-8) can be considered to be irritating to skin and can be classified under the category “Category 2”as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

other information

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 version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: Methyl Isonicotinate
- Molecular formula: C7H7NO2
- Molecular weight: 137.1373 g/mol
- Smiles notation: c1(C(=O)OC)ccncc1
- InChl: 1S/C7H7NO2/c1-10-7(9)6-2-4-8-5-3-6/h2-5H,1H3
- Substance type: Organic
- Physical state: Liquid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

single application

Observation period (in vivo):

72 hours

Duration of post- treatment incubation (in vitro):

No data available

Number of animals or in vitro replicates:

3

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not fully reversible within:

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Severe eye irritation was observed in treated group.

Estimation method: Takes mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((((("a" or "b" or "c" )  and "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 ( not "p") )  )  and ("q" and ( not "r") )  )  and "s" )  and ("t" and ( not "u") )  )  and "v" )  and "w" )  and ("x" and "y" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Esters (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Esters by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Esters by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Thiophenes-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 >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Schiff base formers OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic amine  OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

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 by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR Group All Aqueous Solubility < 0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Aqueous Solubility < 0.0005 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 380 g/mol OR Group CHal log Kow > 4.5 OR Group CHal Melting Point > 65 C OR Group CHal Molecular Weight > 280 g/mol OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN Molecular Weight > 290 g/mol OR Group CNHal Aqueous Solubility < 0.004 g/L OR Group CNHal Aqueous Solubility < 0.1 g/L OR Group CNHal log Kow > 3.8 OR Group CNHal Molecular Weight > 370 g/mol OR Group CNS Aqueous Solubility < 0.006 g/l OR Group CNS log Kow > 1.5 OR Group CNS log Kow > 3.6 OR Group CNS Melting Point > 200 C OR Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Organic sulphonic salts by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Esters including acrylic and methacrylic esters by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Ketones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Ethylenglycolethers by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "t"

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: "u"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "v"

Similarity boundary:Target: COC(=O)c1ccncc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "w"

Similarity boundary:Target: COC(=O)c1ccncc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.551

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.681

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The chemical Methyl isonicotinate (CAS NO: 2459-09-8)was estimated to be irritating into the eyes of New Zealand White rabbits. Based on the estimated result Methyl isonicotinate (CAS NO: 2459-09-8) can be considered to be irritating to eye.

Executive summary:

The ocular irritation potential of Methyl isonicotinate (CAS NO: 2459-09-8) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The chemical Methyl isonicotinate (CAS NO: 2459-09-8) was estimated to be irritating into the eyes of New Zealand White rabbits. Based on the estimated result Methyl isonicotinate (CAS NO: 2459-09-8) can be considered to be irritating to eye and can be classified under the category “Category 2”as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Various studieshas been investigated for the test chemical Methyl isonicotinate (CAS NO: 2459-09-8) to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and guinea pigs for target chemical Methyl isonicotinate (CAS NO: 2459-09-8) and its structurally similar read across substances Methyl Nicotinate (CAS No: 93-60-7) and Methylbenzoate (CAS No: 93-58-3).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data which are summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemical Methyl isonicotinate (CAS NO: 2459-09-8).The test substanceMethyl isonicotinate (CAS NO: 2459-09-8) is estimated to be irritating to skin of Rabbits when applied dermally.

 

The Becker LC et, al., {International Journal of Toxicology, November/December 2012 vol. 31 no. 6 suppl 342S-372S} performed Skin irritation study of structurally similar read across substance Methylbenzoate (CAS No: 93-58-3) in 14 male New Zealand albino rabbits. In this study, the undiluted test material was applied to the clipped dorsum (0.5mL) and external surface of the outer ear (0.2mL) of each rabbits for 6 observation period. On the dorsum there were marked cellular reactions and dermal edema beginning on day 2 followed by dermal hemorrhage, desquamated crust, and thickening of the malpighian stratum beginning on day 5 were observed and on the inner ear, there was slight hyperkeratosis on day 6.  Since the test chemical was rated as grade 1, Methylbenzoate (CAS No: 93-58-3) was considered to be irritating to the clipped dorsum and external surface of the outer ear of male New Zealand albino rabbits.

 

The above results were further supported by dermal irritation study carried out byARTO LAHTI AND HOWARD I. MAIBACH {TOXICOLOGY AND APPLIED PHARMACOLOGY 76, 2, 19-224, (1984)}for read across chemical methyl nicotinate (CAS No: 93-60-7) on guinea pigs. Six groups of 5 Hartley guinea pigs were used.Hair on the back, abdomen, and flank was shaved with an electric razor; remaining short hair was removed with a depilatory cream. These procedures did not cause any visible changes in guinea pig skin. The test sites were marked with a plastic ring stamp, 17 mm in diameter. The following sites were selected: upper back, lower back, upper abdomen, lower abdomen, and flank. 20µl of 0.2% methyl nicotinate in absolute ethyl alcohol was applied to the shaved test sites for 15 minutes. After 15 minutes of exposure, the test chemical was washed away with a soft sponge and lukewarm water. The thickness of the ear was measured 5 min after the application and then every 10 min during the first hour, every 15 min during the second, and every 30 min during the third hour. Erythema reactions from methyl nicotinate appeared within 5 minutes of application. The reactivity in different test sites varied greatly, the upper back being the most sensitive part of the guinea pig body. The strength of the reactions varied from slight to intensive erythema without edema. Hence, methyl nicotinate can be considered to be irritating to guinea pig skin.

 

 

Based on the available data for the target substance Methyl isonicotinate (CAS NO: 2459-09-8) and its structurally similar read across substancesMethyl Nicotinate (CAS No: 93-60-7) andMethylbenzoate (CAS No: 93-58-3),it can be concluded thatchemical Methyl isonicotinate (CAS NO: 2459-09-8) is able to cause skin irritation and considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.

 

Eye irritation:

In different studies,test chemicalMethyl isonicotinate (CAS NO: 2459-09-8) has been investigated for potential for ocular irritation to a greater or lesser extent.The studies are based on in vivo experiments in rabbits for target chemicalMethyl isonicotinate (CAS NO: 2459-09-8) and its structurally similar read across substancesMethylbenzoate (CAS No: 93-58-3)andNicotinamide(CAS No: 98-92-0).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data which are summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for test chemical Methyl isonicotinate (CAS NO: 2459-09-8).The test substanceMethyl isonicotinate (CAS NO: 2459-09-8)is estimated to be irritating to eye of Rabbits.

 

The Becker LC et, al., {International Journal of Toxicology, November/December 2012 vol. 31 no. 6 suppl 342S-372S} performed an eye irritation study of structurally similar read across substance Methylbenzoate (CAS No: 93-58-3) In this study,neat (100%) methyl benzoate was applied to the center of the cornea while the lids were retracted. One minute later the lids were released. The eyes were examined 18–24 h later in strong diffuse daylight and then stained with fluorescein. Methyl benzoate was given a grade 1 (iritis and slight internal congestion) after 24 hours of observation. Based on this rating, methyl benzoate can be considered as an eye irritant.

 

The above results were further supported by ocular irritation study reported by United Nations Environmental Programme (UNEP) {IUCLID Dataset for 98-92-0, UNEP, last updated 2004} for read across chemical Nicotinamide(CAS No:98-92-0)in rabbits according to OECD 405 Guidelines. Single application of ca. 100 mg was instilled in the right eye of 3 female New Zealand White rabbits. The rabbits were observed for signs of irritation and scored at 1,24,48,72 hours and 7 days. Severe discharge and dulling of the normal lustre of the corneal surface of the rabbit eyes were observed. At 72 h effects are still seen in animal 3 and animal 3 was killed for humane reasons on day 7. Hence, nicotinamide was considered to be irritating to the eyes of New Zealand White rabbits. 

 

Based on the available data for the target substance Methyl isonicotinate (CAS NO: 2459-09-8) and its structurally similar read across substancesMethylbenzoate (CAS No: 93-58-3)andNicotinamide(CAS No: 98-92-0),it can be concluded thatchemical Methyl isonicotinate (CAS NO: 2459-09-8) is able to cause eye irritation and considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.

 

Justification for classification or non-classification

The skin and eye irritation potential of test chemicalMethyl isonicotinate (CAS NO: 2459-09-8) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicates that the test chemical Methyl isonicotinate (CAS NO: 2459-09-8)is likely to cause skin and eye irritation. HenceMethyl isonicotinate (CAS NO: 2459-09-8) can be classified under the category “Category 2” for skin and eye as per CLP.