Poly(oxy-1,2-ethanediyl), .alpha.-[3-[(carboxymethyl)methylamino]-2-hydroxypropyl]-.omega.-(4-nonylphenoxy)-, sodium salt (1:1)

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July-August 1978

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: No data on batchno. and limited info on composition. Limited reported study according to standard/guideline (max score can be 2).

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

observation 24 h after patch removal and not also after 48 h

Principles of method if other than guideline:

During the induction phase it has been stated that 0.5 ml test agent was emulsified with 0.05 ml Freund's adjuvant. This should read 0.05 ml test agent plus 0.05 ml Freund's adjuvant.

GLP compliance:

no

Remarks:

pre-GLP

Type of study:

guinea pig maximisation test

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Porcellus Animals Ltd., UK
- Age at study initiation: no info
- Weight at study initiation: 300-400 g
- Housing: 5 to a cage
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: no info


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no info
- Humidity (%): no info
- Air changes (per hr): no info
- Photoperiod (hrs dark / hrs light): no info


IN-LIFE DATES: no info

Route:

intradermal and epicutaneous

Vehicle:

water

Concentration / amount:

Intradermal induction: 0.1 ml test compound 10% (v/v)
Topical induction: 10% v/v on patch
Topical challenge: 10% v/v on patch

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

Intradermal induction: 0.1 ml test compound 10% (v/v)
Topical induction: 10% v/v on patch
Topical challenge: 10% v/v on patch

No. of animals per dose:

10 in test group
5 in control group

Details on study design:

RANGE FINDING TESTS: using 2 guinea pigs the following levels were tested for irritation: 2, 5, 10 and 20% v/v. The test compound was moderately irritant at 20%. Therefore 10% v/v was chosen as challenge concentration.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (1st intradermal, 2nd topical)
- Exposure period: single injection plus topical application for 48 h (6 days after injection)
- Test groups: test compound
- Control group: Freund's adjuvant only
- Site: 4x6 cm across the scapular region
- Concentrations: 10% v/v (injection), 10% v/v (topical)


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after last induction
- Exposure period: 24 h
- Test groups: 10% v/v
- Control group: 10% v/v
- Site: right flank
- Concentrations: 10% v/v
- Evaluation (hr after challenge): 24 h after patch removal


OTHER:

Challenge controls:

yes

Positive control substance(s):

no

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10% v/v at challenge

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10% v/v at challenge. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

At a non-irritant concentration of 10% v/v in water, the test compound was not a sensitiser.

Executive summary:

A study was performed to assess the contact sensitisation potential of the test material in the Dunkin-Hartley guinea pig. The study, a Guinea Pig Maximization Test, was essentially performed in compliance with the requirements of OECD 406. Ten test and five control animals were used for the main study. Based on the results of a sighting test using 2 guinea pigs, the concentration of the test compound for the induction and challenge phases were selected as follows: 10% v/v in water. This concentration was not-irritating, the next higher tested concentration of 20% v/v was moderately irritating. No reactions were observed in both test and control group. The test material, TL 856, was therefore considered a non-sensitiser to guinea pig skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The potential of the test item nonylphenol ethoxylate, sarcosine derivative (CAS no 75627-31-5)to induce delayed contact hypersensitivity have been evaluated in one in vitro skin sensitization study and one in vitro protein binding assay. The current state of the art understanding of the process that lead to skin sensitization and allergic skin reactions was recently published by the OECD series on testing and assessment No 168. This publication gives scientific evidence for skin sensitization is initiated by covalent binding to proteins. Although there is no OECD validated method to support this adverse outcome pathway, a non-GLP in vitro test was performed in order to support the negative in vivo test. This strategy was chosen in order to avoid repeating animal tests. In this protein binding assay, the nonylphenol ethoxylate, sarcosine derivate(CAS no 75627-31-5)showed no reactivity towards the synthetic peptide Ac-NKKCDLF at any of the tested concentrations at neither pH 7.4 nor pH 10.0. This indicates no potential to react with endogenous proteins within the skin to induce sensitizing effects under the assay conditions up to a concentration of 8 mM.

Migrated from Short description of key information:
The potential of nonylphenol ethoxylate, sarcosine derivative (CAS no 75627-31-5) to induce delayed contact hypersensitivity was evaluated in a Guinea Pig Maximization Test essentially performed in compliance with the requirements of OECD 406. The test was performed pre-GLP in a test with ten test and five control animals in the main study. Based on the results of a sighting test using 2 guinea pigs, the concentration of the test compound for the induction and challenge phases were selected as follows: 10% v/v in water. This concentration was not-irritating, the next higher tested concentration of 20% v/v was moderately irritating. No reactions were observed in both test and control group. The test material was therefore considered a non-sensitiser to guinea pig skin.

Justification for selection of skin sensitisation endpoint:
There is one in vivo skin sensitisation study available, performed on a product which contains nonylphenol ethoxylate, sarcosine derivative (CAS no 75627-31-5). The test was performed in 1978 and has validity rating 4 based on no data on batch number and limited info on composition. The report describes the test in a limited way, but it is performed according to the standards/guidelines. The test gave no indications on sensitising properties, and this result together with the newly performed in vitro protein binding test strongly supports the substance to be classified as not sensitising.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

There are no guidelines for an animal test for respiratory sensitisation, however in general respiratory sensitisers are also skin sensitisers. Nonylphenol ethoxylate, sarcosine derivate(CAS no 75627-31-5)was not found to be a skin sensitiser in the OECD 406 study, supported by the in vitro protein binding assay. This indicates that the substance is unlikely to possess any significant potential for respiratory sensitisation. Nonylphenol ethoxylate, sarcosine derivate (CAS no 75627-31-5) is produced within a ventilated factory with risk management measures in place to limit the exposure. Its use is limited to industrial settings and does not include formation of aerosols, particles or droplets of inhalable size. Exposure to humans via the inhalation route is therefore considered to be unlikely. Based on the non-skin sensitizing profile of the substance, it is not considered justified on animal welfare grounds to perform a respiratory sensitization study.

Justification for classification or non-classification

Skin

Nonylphenol ethoxylate, sarcosine derivate(CAS no 75627-31-5) was not found to be a skin sensitiser when tested according to the OECD 406 nor in the in vitro protein binding assay. There are therefore no indications that the substance should be classified according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011), nor the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

 

Inhalation

Nonylphenol ethoxylate, sarcosine derivate(CAS no 75627-31-5) was not found to be a skin sensitiser which indicates that it is unlikely to possess any significant potential for respiratory sensitisation.