4-Nonylphenol, branched, ethoxylated

Endpoint summary

Description of key information

Skin Irritation:

The dermal irritation potential of 4-Nonylphenol, branched, ethoxylated was estimated using OECD QSAR toolbox v3.4 with ligPow as the primary descriptor.

4-Nonylphenol, branched, ethoxylated was estimated to be not irritating to the skin of New Zealand White rabbits.

Eye Irritation:

The Draize score after 7 days was 3.2. Under the test conditions, 4-Nonylphenol, branched, ethoxylated was moderate ocular irritant.

Hence, 4-Nonylphenol, branched, ethoxylated can be considered to be moderately irritating to rabbit eyes.

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 v3.4 and the QMRF report has been attached

Qualifier:

equivalent or similar to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): 4-Nonylphenol, branched, ethoxylated
- Molecular formula : C17H28O2
- Molecular weight : 264.409 g/mol
- Substance type: Organic
- Physical state: Liquid
SMILES:CCCC(C)CC(C)Cc1ccc(OCCOCCOCCOCCOCCO)cc1

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:

0.5 ml

Duration of treatment / exposure:

24 hours

Observation period:

7 days

Number of animals:

3

Details on study design:

The test was performed on abraded and shaved skin.

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

7 d

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no irritation was observed

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and "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 "aa" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Nonionic Surfactants by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alcohol AND Alkane, branched with tertiary carbon AND Alkyl arenes AND Aryl AND Ether by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alcohol AND Alkyl arenes AND Ether AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aromatic Carbon [C] AND Hydroxy, aliphatic attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxygen, aliphatic attach [-O-] AND Oxygen, one aromatic attach [-O-] AND Tertiary Carbon by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Alcohol AND Alkylarylether AND Aromatic compound AND Dialkylether AND Ether AND Hydroxy compound AND Primary alcohol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> Polarised Alkenes-Michael addition 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: "j"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Lysine peptide depletion

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Moderate reactive OR Moderate reactive >> Unsaturated carboxylic acid anhydrides by DPRA Lysine peptide depletion

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.4

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols OR 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 by OASIS v1.4

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N by Chemical elements

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Alcohol AND Alkyl arenes AND Ether AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Acetal OR Aryl OR Benzodioxole OR Benzyl OR Carboxylic acid ester OR Cycloalkane OR Isopropyl OR Terpenes by Organic Functional groups (nested)

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Diethylene Glycol Alkyl Ethers (Less susceptible) No Rank OR Ethyleneglycol alkylethers (Hemolytic anemia) Rank A OR Ethyleneglycol alkylethers (Testicular toxicity) Rank B by Repeated dose (HESS)

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group C Surface Tension > 62 mN/m AND Group All Melting Point > 200 C AND Group C Melting Point > 55 C AND Group C Molecular Weight > 350 g/mol AND Group C Vapour Pressure < 0.0001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as (N/A) by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Has superfragment AND OCCOR{*} by Superfragments ONLY

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0155

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.5

Interpretation of results:

other: not irritating

Conclusions:

Nonylphenol ethoxylates was estimated to be not irritating to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of Nonylphenol ethoxylates was estimated using OECD QSAR toolbox v3.4 using logPow as the primary desriptor.

Nonylphenol ethoxylates was estimated to be not irritating to the skin of New Zealand White rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

data is from NTRL reports

Qualifier:

equivalent or similar to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Primary Ocular irritation test was conducted in rabbits to evaluate the irritation potential of 4-Nonylphenol, branched, ethoxylated

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): 4-Nonylphenol, branched, ethoxylated
- Molecular formula: C17H28O2
- Molecular weight: 264.409 g/mol
- Substance type: Organic
SMILES: CCCC(C)CC(C)Cc1ccc(OCCOCCOCCOCCOCCO)cc1
- Physical state: Liquid

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
Sex: Male and Female
- Source: Summit View Farm, Belvidere, New Jersey
- Age at study initiation: No data available
- Weight at study initiation: 1.8 - 2.4 kg
- Fasting period before study: No data available
- Housing: No data available
- Diet (e.g. ad libitum): ad libitum with Wayne animal feeds used exclusively
- Water (e.g. ad libitum): ad libitum
- Acclimation period: No data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

single application

Observation period (in vivo):

24 hours to 7 days

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

6

Details on study design:

Details on study design

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No washing
SCORING SYSTEM: Draize method

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

7 d

Score:

3.2

Reversibility:

not specified

Remarks on result:

probability of moderate irritation

Irritant / corrosive response data:

Under the test conditions, 4-Nonylphenol, branched, ethoxylated was moderate ocular irritant.

 

Table 1:

Draize Scores

Group	Draize Scores
	Days
	1	2	3	4	7
No wash	21.8	20.3	11.7	5.7	3.2

 

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The Draize score after 7 days was 3.2.
Under the test conditions, 4-Nonylphenol, branched, ethoxylated was moderate ocular irritant.
Hence, 4-Nonylphenol, branched, ethoxylated can be considered to be moderately irritating to rabbit eyes.

Executive summary:

Primary Ocular irritation test was conducted in rabbits to evaluate the irritation potential of 4-Nonylphenol, branched, ethoxylated.

6 male and female rabbits weighing1.8 - 2.4 kg were used for the study. 0.1 ml single administration of4-Nonylphenol, branched, ethoxylated (Carsonon N-10, 5% Active in Distilled Water) was instilled into the rabbit eyes. The treated eyes were not washed for 24 hours and up to seven day observation. The effects observed were scored according to Draize method.

The Draize score after 7 days was 3.2.

Under the test conditions, 4-Nonylphenol, branched, ethoxylated was moderate ocular irritant.

Hence, 4-Nonylphenol, branched, ethoxylated can be considered to be moderately irritating to rabbit eyes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

In different studies,4-Nonylphenol, branched, ethoxylatedhas been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical .The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

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 for4-Nonylphenol, branched, ethoxylated. 4-Nonylphenol, branched, ethoxylated was estimated to be not irritating to the skin of New Zealand White rabbits.

2 studies for dermal irritation and corrosion were performed by Lonza INC (OTS0558916, submitted by LONZA INC.; last updated 1996) to evaluate the primary dermal irritation and corrosion potential of 4-Nonylphenol, branched, ethoxylated.

For the Primary Dermal Irritation study 6 male & female rabbits were used. 0.5 ml single application of Nonylphenol Ethoxylates ( Carsonon N-10, 5% Active in distilled water) under occluded patch was applied to abraded and non abraded skin of rabbits. The effects were observed at 24 and 72 hours and reactions were scored.

The Primary Dermal Irritation Index of Nonylphenol Ethoxylates was 0.0.

A Primary Dermal Corrosion assay was performed according to 49 CFR 173.240 (a)(l) Guidelines in 6 rabbits. 0.5 ml single application of Nonylphenol Ethoxylates ( Carsonon N-10, 100% Active) under occluded patch was applied to non abraded skin of rabbits. The effects were observed at 4 and 48 hours. Under the test conditions, 4 -Nonylphenol, branched, ethoxylated was not corrosive to rabbit skin.

Based on the above results, 4-Nonylphenol, branched, ethoxylated was concluded to be not irritating and not corrosive to skin.

The above results are also supported by 2 studies for dermal corrosion performed by Lonza INC (OTS0558917, submitted by Lonza INC, last updated 1996).

The biological corrosivity of 4-Nonylphenol, branched, ethoxylated was performed on 6 New Zealand White rabbits according to BTP -3-3-055-81, Biological Corrosivity, (The Code of Federal Regulations, Title 49, Chapter 1, Section 173.1200, Appendix A) Guidelines. The rabbits were clipped free of hair (dorsal and lateral areas of trunk).0.5 gm of test material moistened with water was applied directly onto exposed skin of each rabbit and was covered with gauze squares which were securely taped and wrapped. At the end of a four hour exposure period, the bandages were removed and the sample was washed from the skin. Dermal reactions, erythema, eschar formation, edema and necrosis were evaluated at 4 and 48 hours after exposure. Corrosion will be considered to have resulted if the substance in contact with rabbit skin has caused destruction or irreversible alteration of tissue. Tissue destruction is considered to have occurred, if at any of the readings, there is no alteration or necrosis. The overall scores after 4 and 48 hours were 0.0. None of the rabbits exhibited irreversible alteration of tissues.

Primary Dermal Corrosion assay was performed on 6 New Zealand White rabbits according to BTP -2-3-077-82, Primary Dermal Irritants (The Code of Federal Regulations, Title 16, Section 1500.41) Guidelines.The rabbits were clipped free of hair (dorsal and lateral areas of trunk), the exposed skin was further prepared by making epidermal abrasions over half of the shaved area. 0.5 gm of test material was applied directly onto exposed skin of each rabbit and was covered with gauze squares which were securely taped and wrapped. At the end of a 24 hour exposure period, the bandages were removed and the sample was washed from the skin. Dermal reactions, erythema, eschar formation, edema and necrosis were evaluated at 24 and 72 hours after exposure. According to the definitions in “The Code of Federal Regulations”, a material is considered a Primary Dermal Irritant if Primary Irritation Score is 5.0 or greater. No erythema or edema was observed in any rabbits. The Primary Dermal Irritation Score was 0.0.

Based on the above scores and observations, 4-Nonylphenol, branched, ethoxylated was concluded to be not irritating and not corrosive to skin.

On the basis of the available data for the target and applying the weight of evidence approach,4-Nonylphenol, branched, ethoxylated was not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”

 

Eye Irritation:

In different studies,4-Nonylphenol, branched, ethoxylatedhas been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical and for the structurally similar read across substance Poly(oxy-1,2-ethanediyl),alpha-(nonylphenyl)-omega-hydroxy- (CAS: 9016-45 -9).

Primary Ocular irritation test was conducted (OTS0558916, submitted by LONZA INC.; last updated 1996) in rabbits to evaluate the irritation potential of 4-Nonylphenol, branched, ethoxylated. 6 male and female rabbits weighing 1.8 - 2.4 kg were used for the study. 0.1 ml single administration of4-Nonylphenol, branched, ethoxylated (Carsonon N-10, 5% Active in Distilled Water) was instilled into the rabbit eyes. The treated eyes were not washed for 24 hours and up to seven day observation. The effects observed were scored according to Draize method. The Draize score after 7 days was 3.2.

Under the test conditions, 4-Nonylphenol, branched, ethoxylated was moderate ocular irritant.

This was further supported by 2 experimental studies performed by Union Carbide Corp (OTS0536114, submitted by Union Carbide Corp, last updated 1992) to evaluate the ocular irritation potential of the target chemical.

In the first study, 0.1 ml single administration of 4-Nonylphenol, branched, ethoxylated was instilled into the eyes of 6 rabbits. The treated eyes were washed with water after 20-30 seconds of exposure.Under the test conditions, 4-Nonylphenol, branched, ethoxylated was substantially - severely to irritating to eyes of rabbits.

In another study, 9 rabbits were used instead of 6 and same procedure was followed. Under the test conditions, 4-Nonylphenol, branched, ethoxylated was severely irritating to eyes of rabbits.

These studies are also supported by the experimental study summarized in International Journal of Toxicology, 18(Suppl. 1): I ; 1-31, 1999 for the structurally similar chemical Poly(oxy-1,2-ethanediyl),alpha-(nonylphenyl)-omega-hydroxy- (CAS: 9016-45-9).The test was performed according to the Draize method. 6 rabbits were used for the study and the eyes were not rinsed. The eye reactions were scored according the Draize method (scales 0 to 110). The average Draize scores on days 1 and 7 post-instillation were 28.8 and 16.0, respectively.

Based on the scores,Poly(oxy-1,2-ethanediyl),alpha-(nonylphenyl)-omega-hydroxy- [Nonoxynol-6] can be considered to be a severe ocular irritant.

Based on the available data for the target and read across substance and applying the weight of evidence approach, 4-Nonylphenol, branched, ethoxylated can be considered as irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Eye 2”.

Justification for classification or non-classification

Available studies for 4-Nonylphenol, branched, ethoxylated ndicates that it is not likely to cause irritation to skin but causes severe irritation to eyes.

Hence, 4-Nonylphenol, branched, ethoxylated can be considered as “Non Irritant” to skin, but “Irritant” to eyes.It can be classified under "Not Classified" for Skin Irritation and “Category 2” for Eye Irritation according to CLP criteria.