4-Nonylphenol, branched, ethoxylated

Endpoint summary

Description of key information

Estimated LD50 was considered to be 1602 mg/kg when rats were treated with poly(oxy-1,2-ethanediyl),?-(4-nonylphenyl)-?-hydroxy-, branched orally.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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 predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: estimated

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched
- Molecular formula (if other than submission substance): C23H40O5
- Molecular weight (if other than submission substance): 396.63 g/mol
- Substance type: Organic
- Physical state: Liquid

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data avaialble

Route of administration:

other: Oral

Details on oral exposure:

No data avaialble

Doses:

1602 mg/kg

No. of animals per sex per dose:

No data avaialble

Control animals:

not specified

Details on study design:

No data avaialble

Statistics:

No data avaialble

Preliminary study:

No data avaialble

Sex:

not specified

Dose descriptor:

LD50

Effect level:

1 602 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % moratlity observed

Mortality:

No data avaialble

Clinical signs:

other: No data avaialble

Gross pathology:

No data avaialble

Other findings:

No data avaialble

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average 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 ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and "t" )  )

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 Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "g"

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 OR Strong binder, OH group OR Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "l"

Similarity boundary:Target: CCCC(C)CC(C)Cc1ccc(OCCOCCOCCOCCOCCO)cc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as 4,4'-Diethylaminoethoxyhexestrol (Hepatotoxicity) Alert OR Halobenzenes (Hepatotoxicity) Rank A OR Halobenzenes (Renal toxicity) Rank A OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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 >> Methylenedioxyphenyl OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as 1,3-Benzodioxoles (Nongenotox) OR Phtalate (or buthyl) diesters and monoesters (Nongenotox) OR Structural alert for nongenotoxic carcinogenicity by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.02

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.3

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

estimated LD50 was considered to be 1602 mg/kg when rats were treated with Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched orally.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, acute oral toxicity was estimated in rats for Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched orally. The LD50 was estimated to be 1602 mg/kg when rats were treated with Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched orally.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 602 mg/kg bw

Quality of whole database:

Data is from QSAR toolbox 3.4 (2017)

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

In different studies, Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched (CAS no 127087-87-0 ) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated studies in rodents, i.e. most commonly in rats and rabbit for Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched along with the study available on structurally similar read across substance Nonoxynol -9 (CAS no 26027-38-3). 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, acute oral toxicity was estimated in rats for Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched orally. The LD50 was estimated to be 1602 mg/kg when rats were treated with Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched orally.

In another study conducted by LONZA INC (OTS0558916, Consumer Prod Testing Co Inc, page no 1-15, 1996), acute oral toxicity was evaluated in male and female rats by using Carsonon N-10 (Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched) in the concentration of 5000 mg/kg bw orally. All the treated male and female rats were dead at 5000 mg/lg bw. Therefore, LD50 was considered to be < 5000 mg/kg bw when male and female rats were treated with Carsonon N-10 (Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched) orally.

In a above similar experimental study, another group of 3 male and 3 female rats were treated with Carsonon N-10 (Poly(oxy-1,2-ethanediyl), .alpha.-(4-nonylphenyl)-.omega.-hydroxy-, branched) in the concentration of 630, 1260, 2250, 3140 mg/kg (40 ml/kg top dose mechanically feasible) orally. 2 male and all female died at 2250 and 3140 mg/kg, 2 female died at 1260 mg/kg and 1 male died at 630 mg/kg. Therefore, LD50 was considered to be 1890 mg/kg bw (1330 - 2690) when male and female rats were treated with Carsonon N-10 (Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched) orally.

Also it is further supported experimental data by Cosmetic Ingredient Review (Journal of the American College of Toxicology, Volume 2, Number 7, 1983) and U.S. National Library of Medicine (ChemIDplus, Toxnet Database, 2017) on another structurally similar read across substance Nonoxynol -9 (CAS no 26027-38-3), male and female rabbits were treated with Nonoxynol -9 in the concentration of 100% orally by gavage. 50 % mortality observed in treated rabbits at 657.2 mg/kg bw. Somnolence (General Depressed Activity) and Acute Pulmonary Edema of Lungs, Thorax, or Respiration: was observed in treated rabbits. Therefore, LD50 was considered to be 657.2 mg/kg bw (265-1664.2 for male) and (296.8 -1452.2 for female ) when male and female rabbits were treated with Nonoxynol -9 orally.

Thus based on the above studies and predictions on Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched and its read across substances and considering the weight of evidence, it can be concluded that LD50 value is less than 2000 mg/kg bw. Thus comparing this value with the criteria of CLP regulation, Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched can be classified as “Category IV “of acute oral toxicity.

Justification for classification or non-classification

Based on the weight of evidence for target Poly (oxy-1,2-ethanediyl), .alpha.-(4-nonylphenyl)-.omega.-hydroxy-, branched (CAS no 127087-87-0 ) and its read across Nonoxynol -9 (CAS no 26027-38-3) is likely to be hazardous by oral route of exposure and as per criteria of CLP regulation comes under ‘Category IV’