Registration Dossier

Administrative data

Description of key information

Skin Irritation:

The Primary Irritation Index for 4-Nonylphenol, ethoxylated (Nonoxynol -2) was 2.0 after 24, 72 hours.

Based on the scores, 4-Nonylphenol, ethoxylated (Nonoxynol -2) was moderately irritating to rabbit skin.

Eye Irritation:

The Primary Irritation Index for 4-Nonylphenol, ethoxylated (Nonoxynol -2) was 3.7 after 24hours.

Based on the scores, 4-Nonylphenol, ethoxylated (Nonoxynol -2) was considered to be minimal irritant 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:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
data is from peer reviewed journals
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Primary skin irritation test was carried out to assess the irritation potential of 4-Nonylphenol, ethoxylated in rabbits
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: 4-Nonylphenol, ethoxylated
- Molecular formula: C17H28O2
- Molecular weight: 264.406 g/mol
- Smiles notation: CCCCCCCCCc1ccc(OCCOCCO)cc1
- Substance type: Organic
- Physical state: Liquid
Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
no data available
Type of coverage:
occlusive
Preparation of test site:
clipped
Remarks:
intact and abraded skin
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5 ml undiluteed test chemical
Duration of treatment / exposure:
single exposure
Observation period:
24,72 hours
Number of animals:
6
Details on study design:
SCORING SYSTEM: The sites were individually examined at 24 h and scored separately for erythema and edema at 24 and 72 hours. The mean scores for 24- and 72-hours gradings were averaged to determine the Primary Irritation Index (PII).
Other effects / acceptance of results:
no data available
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
2
Max. score:
8
Reversibility:
not specified
Remarks on result:
probability of moderate irritation
Irritant / corrosive response data:
Moderately irritating

Table 1: Primary Skin Irritation

Nonoxynol

Concentration (%)

No. of rabbits

Protocola

PII or Gradeb

Comment

2

100

6

B

2.0

Moderately irritating

 

a- as described in the method

b- PII max = 8.00, Grade max = 10

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The Primary Irritation Index for 4-Nonylphenol, ethoxylated (Nonoxynol -2) was 2.0 after 24, 72 hours.
Based on the scores, 4-Nonylphenol, ethoxylated (Nonoxynol -2) was moderately irritating to rabbit skin.
Executive summary:

A Primary skin irritation test was carried out to assess the irritation potential of4-Nonylphenol, ethoxylated (Nonoxynol -2) in rabbits.

0.5 ml of undiluted test chemical was applied under occlusion to the clipped, intact and abraded skin of 6 rabbits and observed for signs of irritation.The sites were individually examined at 24 h and scored separately for erythema and edema at 24 and 72 hours. The mean scores for 24- and 72-hours gradings were averaged to determine the Primary Irritation Index (PII).

The Primary Irritation Index for 4-Nonylphenol, ethoxylated (Nonoxynol -2) was 2.0 after 24, 72 hours.

Based on the scores, 4-Nonylphenol, ethoxylated (Nonoxynol -2) was moderately irritating to rabbit skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
data is from peer reviewed journals
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Primary eye irritation test was carried out to assess the irritation potential of 4-Nonylphenol, ethoxylated in rabbits
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: 4-Nonylphenol, ethoxylated
- Molecular formula: C17H28O2
- Molecular weight: 264.406 g/mol
- Smiles notation: CCCCCCCCCc1ccc(OCCOCCO)cc1
- Substance type: Organic
- Physical state: Liquid
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
sex: male and female
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
Single dose of 0.005, 0.02, 0.10, or 0.5 ml of undiluted Nonoxynol 2
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
within 1 h unstained and at 24 h after fluorescein staining
1, 2, 3, 4 and 7 days post –instillation
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
6 (males and females)
Details on study design:
TEST SITE
- Area of exposure: conjunctival sac
REMOVAL OF TEST SUBSTANCE
- Washing (if done): unwashed

SCORING SYSTEM: According to Draize method

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein:
Fluorescein staining was performed 1 hour after observation
Other effects / acceptance of results:
no data available
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24 h
Score:
3.7
Max. score:
120
Reversibility:
not specified
Remarks on result:
probability of mild irritation
Irritant / corrosive response data:
Minimal irritant

Table 1: Primary Eye Irritation

Nonoxynol

Concentration (%)

No. of rabbits

Wash (Y/N)

Average Score* (Draize)

Comment

1 day

 

2 days

 

3 days

 

4 days

 

7 days

 

2

100

6 (M+F)

N

3.7

0.0

0.0

-

-

Minimally Irritating

 

*- Maximum score = 120

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
The Primary Irritation Index for 4-Nonylphenol, ethoxylated (Nonoxynol -2) was 3.7 after 24hours.
Based on the scores, 4-Nonylphenol, ethoxylated (Nonoxynol -2) was considered to be minimal irritant to rabbit eyes.
Executive summary:

A Primary eye irritation test was carried out to assess the irritation potential of 4-Nonylphenol, ethoxylated (Nonoxynol -2) in rabbits.

Single dose of 0.005,0.02, 0.10, or 0.5 ml of undiluted Nonoxynol 2 was instilled into the conjunctival sac of 6 (male and female) rabbits. The treated eyes remained unwashed throughout the test. The eyes were examined within 1 h unstained and at 24 h after fluorescein staining. The rabbits were observed for signs of irritation at 1, 2, 3, 4 and 7 days post –instillation of the test chemical. Thereactions observed were scored according Draize method.

The Primary Irritation Index for4-Nonylphenol, ethoxylated (Nonoxynol -2) was 3.7 after 24hours.

Based on the scores, 4-Nonylphenol, ethoxylated (Nonoxynol -2) was considered to be minimal irritant 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, ethoxylated has 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.

A Primary skin irritation test was carried out (JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY, Volume 2, Number 7, 1983) to assess the irritation potential of 4-Nonylphenol, ethoxylated (Nonoxynol -2) in rabbits. 0.5 ml of undiluted test chemical was applied under occlusion to the clipped, intact and abraded skin of 6 rabbits and observed for signs of irritation.The sites were individually examined at 24 h and scored separately for erythema and edema at 24 and 72 hours. The mean scores for 24 - and 72-hours gradings were averaged to determine the Primary Irritation Index (PII).The Primary Irritation Index for 4-Nonylphenol, ethoxylated (Nonoxynol -2) was 2.0 after 24, 72 hours. Based on the scores, 4-Nonylphenol, ethoxylated (Nonoxynol -2) was moderately irritating to rabbit skin.

This study is supported by the human data summarized in International Journal of Toxicology, 18(Suppl. 1): I ; 1-31, 1999.

4-Nonylphenol, ethoxylated (Nonoxynol -2)(5% in mineral oil) was assessed for skin irritation/sensitization potential.In the study, the subjects were free of interfering systemic or dermatologic disorders, visible skin diseases, active atopic dermatitis, or psoriasis. The experimental procedure was a Jordan-King modification of the Draize Repeat Insult Patch Test. 110 volunteers (9 males, 101 females; 19 to 61 years old) were initially part of the study of which eight withdrew from the study.0.2 ml Nonoxynol -2 (5% in mineral oil) was under occlusive patches, to the scapular region of the back three times per week for 3 weeks (9 induction applications). Patches were removed, and sites were evaluated at 48-hour intervals. The induction phase was followed by a 14-day non-treatment period. During the challenge phase, initiated at week 6, two consecutive 48-hour patches were applied to new sites in the scapular region of the back. Challenge reactions were scored after 48 and 96 hours. During induction and challenge phases, reactions were scored according to the following scale: 0 (no reaction) to 4 (bullae or extensive erosions involving at least 50% of the test area).

Isolated evidence of faint to moderate erythema was observed in three subjects during the induction phase. Three subjects also had reactions during the challenge phase.

Based on these observations,4-Nonylphenol, ethoxylated (Nonoxynol -2) can be considered to be irritating to skin.

A similar study was conducted using 111 volunteers (15 males, 96 females; 18 to 64 years old) of which eight withdrew from the study.0.2 ml Nonoxynol -2 (10% in mineral oil) was applied to the volunteers as mentioned above. During the induction phase, isolated evidence of slight to moderate erythema was observed in 15 subjects, and, in an additional subject, strong, infiltrated erythema was observed after removal of the last induction patch.Based on these observations,4-Nonylphenol, ethoxylated (Nonoxynol -2) can be considered to be irritating to skin.

These results are supported by estimated studies by various models.

Skin irritation effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for 4-Nonylphenol, ethoxylated. Based on estimation, Severe skin irritation effects were known when 4-Nonylphenol, ethoxylated was exposed to rabbit skin. Hence, 4-Nonylphenol, ethoxylated can be considered to be severely irritating to rabbit skin.

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, ethoxylated. 4-Nonylphenol, ethoxylated was estimated to be irritating to the skin of New Zealand White rabbits.

Based on the available data for the target substance, 4-Nonylphenol, ethoxylated can be considered as irritating to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Category 2”.

Eye Irritation:

In different studies,4-Nonylphenol, ethoxylatedhas 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 chemical and for the structurally similar read across substances, Poly(oxy-1,2-ethanediyl),alpha-(nonylphenyl)-omega-hydroxy- (CAS: 9016-45-9) and 2-Butoxyethanol(butyl cellosolve) [CAS: 111-76-2].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

A Primary eye irritation test was carried out (JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY, Volume 2, Number 7, 1983) to assess the irritation potential of 4-Nonylphenol, ethoxylated (Nonoxynol -2) in rabbits.Single dose of 0.005, 0.02, 0.10, or 0.5 ml of undiluted Nonoxynol 2 was instilled into the conjunctival sac of 6 (male and female) rabbits. The treated eyes remained unwashed throughout the test. The eyes were examined within 1 h unstained and at 24 h after fluorescein staining. The rabbits were observed for signs of irritation at 1, 2, 3, 4 and 7 days post –instillation of the test chemical. Thereactions observed were scored according Draize method.The Primary Irritation Index for4-Nonylphenol, ethoxylated (Nonoxynol -2) was 3.7 after 24hours.

Based on the scores, 4-Nonylphenol, ethoxylated (Nonoxynol -2) was considered to be minimal irritant to rabbit eyes.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for4-Nonylphenol, ethoxylated. 4-Nonylphenol, ethoxylated was estimated to be irritating to the eyes of SPF-Albino-Himalayan rabbits.

The experimental and estimated results indicate the possibility of 4-Nonylphenol, ethoxylated being irritating to eyes.

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 chemicalPoly(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.

These studies are also supported by the experimental study summarized in ECETOC Technical Report no. 48 (2), 1998; for thestructurally similar read across substance, 2-Butoxyethanol(butyl cellosolve) [CAS: 111-76 -2]. The study was carried out according to OECD 405 “EYE IRRITATION” Guidelines.0.1 ml of butyl cellosolve was instilled into the conjunctival sac of 3 New Zealand White rabbits. Observations were made after 1 hour, 4 hours and then 1, 2, 3,7,14 and 21 days after instillation of test chemical. The scoring was done according to the Draize method. Conjunctival redness, chemosis and redness was observed even after 21 days of observation in all the treated animals. The MMAS (Maximum Modified Average Score) of butyl cellosolve was 68.7 after 2 days of observation.

Based on the classification of chemicals according to MMAS scores, butyl cellosolve can be considered to be severely irritating to rabbit eyes.

Based on the available data for the target and read across substances and applying the weight of evidence approach, 4-Nonylphenol, 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 “Category 2”.

Justification for classification or non-classification

Available studies for4-Nonylphenol, ethoxylated suggests that it is irritating to eyes and skin.

Hence,4-Nonylphenol, ethoxylated can be classified under the category “Category 2” as per CLP regulation.