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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
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 journal.

Data source

Reference
Reference Type:
publication
Title:
SKIN SENSITIZATION STUDY OF TEST MATERIAL
Author:
Hon-Wing Leung et. al.,
Year:
1998
Bibliographic source:
Journal of Toxicology: Cutaneous and Ocular Toxicology 1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Human Repeat Insult Patch Test was conducted on an exclusive panel of 200 male and female volunteers to assess the skin sensitization potential of test chemical.
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Not applicable

Test material

Constituent 1
Chemical structure
Reference substance name:
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
EC Number:
500-038-2
EC Name:
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
Cas Number:
25322-68-3
Molecular formula:
(C2-H4-O)mult-H2-O
IUPAC Name:
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
Details on test material:
- Name of test material (IUPAC name): Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
- Molecular formula: (C2H4O)multH2O
- Molecular weight: 44.0526 g/mol
- Substance type: Organic

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Remarks:
albino
Sex:
male/female
Details on test animals and environmental conditions:
- Age at study initiation: Young adult Hartley albino guinea pigs
- Weight at study initiation: 306-528 g

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
not specified
Concentration / amount:
Intradermal application:
0.1 ml of 50% (v/v) Freund's Complete Adjuvant (FCA) water emulsion, the test material, and the test material in FCA/water emulsion.

Topical application: 0.3 ml –applied to saturation
Day(s)/duration:
48 hours
Adequacy of induction:
other: The concentration that produced only local necrosis (i.e., no extensive necrosis or ulceration) was used for the intradermal induction. The highest concentration that produced only mild irritation was appropriate for the topical induction.
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
not specified
Concentration / amount:
75%
Day(s)/duration:
48 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 guinea pigs/ group
Details on study design:
RANGE FINDING TESTS: Range-finding studies were conducted to select appropriate concentrations of test chemical for the intradermal and topical procedures. Animals were inspected 24 and 48 h after dosing for signs of inflammation, necrosis, and ulceration. The concentration that produced only local necrosis (i.e., no extensive necrosis or ulceration) was used for the intradermal induction. The highest concentration that produced only mild irritation was appropriate for the topical induction, and the highest concentration that did not produce irritation was used for the topical challenge.

MAIN STUDY
A. INDUCTION EXPOSURE: INTRADERMAL
- No. of exposures:1
- Exposure period: 9 days
- Test groups:10 guinea pigs
- Control group:10 guinea pigs
- Site: each guinea pig received 0.1 ml intradermal induction injections into two sites each of the clipped shoulder skin.
- Frequency of applications: not specified
- Duration: 5-9 days
-Concentrations: 0.1 ml of 50% (v/v) Freund's Complete Adjuvant (FCA) water emulsion, the test material, and the test material in FCA/water emulsion.


A.II. INDUCTION EXPOSURE: TOPICAL
- No. of exposures: 1
- Exposure period: 48 hours
- Test groups: 10 guinea pigs
- Control group: 10 guinea pigs
- Site: not specified
- Frequency of applications: not specified
- Duration: 48 hours
- Concentrations:0.3 ml –applied to saturation


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 12-16 days later
- Exposure period:24 hours
- Test groups: 10 guinea pigs
- Control group: 10 guinea pigs
- Site: a previously untreated site (right flank)
- Concentrations: 75%
- Evaluation (hr after challenge): 24-48 h after removal of the occlusive dressings

OTHER: If the test article was nonirritating, 10% (w/w) sodium lauryl sulfate in petrolatum might be massaged into the skin to produce a mild inflammatory response.
Challenge controls:
Vehicle control animals were similarly treated with distilled water.
Positive control substance(s):
yes
Remarks:
Positive control animals were similarly treated with 5 % formaldehyde.

Results and discussion

In vivo (non-LLNA)

Results
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
The severity indices in the test group were comparable to those produced in the irritation control groups, suggesting that sensitization had not been induced.
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

Twenty nine of the 30 animals (97%) challenged with 5% formaldehyde (positive control) showed clear skin responses, while all the irritation control animals were free of skin responses, confirming the validity of this skin sensitization test.

Applicant's summary and conclusion

Interpretation of results:
other: not sensitizing
Conclusions:
The test material was considered to be not sensitizing on skin of guinea pigs in a Guinea pig maximisation test described by Magnusson and Kligman.
Executive summary:

A Guinea pig maximisation test was conducted to evaluate the allergic contact sensitization potential of test chemical.

 

Range-finding studies were conducted to select appropriate concentrations of test chemical for the intradermal and topical procedures. Animals were inspected 24 and 48 h after dosing for signs of inflammation, necrosis, and ulceration. The concentration that produced only local necrosis (i.e., no extensive necrosis or ulceration) was used for the intradermal induction. The highest concentration that produced only mild irritation was appropriate for the topical induction, and the highest concentration that did not produce irritation was used for the topical challenge.

 

In the definitive sensitization test, groups of 10 male and 10 female guinea pigs each received 0.1 ml intradermal induction injections into two sites each of the clipped shoulder skin as follows: 50% (v/v) Freund's Complete Adjuvant (FCA) water emulsion, the test material, and the test material in FCA/water emulsion. Topical inductions were conducted 5-9 days later. If the test article was nonirritating, 10% (w/w) sodium lauryl sulfate in petrolatum might be massaged into the skin to produce a mild inflammatory response. The test material was applied to saturation (0.3 ml) to a 2 x 4 cm filter paper that was then placed on the test site and secured with tape. The patches were left in place for about 48 h, after which they were removed and the skin wiped free of any excess test material.

 

Topical challenge was undertaken 12-16 days later by applying 2 x 2 cm filter paper squares soaked in the appropriate concentration of the test material to a previously untreated site (right flank). Patches were left in place for 24 h, and the sites inspected for signs of irritation 24-48 h after removal of the occlusive dressings.

 

Positive control and vehicle control animals were similarly treated with 5 % formaldehyde and distilled water, respectively. Irritation control animals received the same challenge procedures as in the definitive sensitization study, but did not undergo the preceding intradermal and topical induction procedures.

 

These naive animals allowed differentiation between primary skin irritation due to the test material and those produced by a hypersensitivity reaction.

 

In general, scores of 1 or greater were considered clearly indicative of sensitization. Scores of 0.5 were considered equivocal, although a high percentage of 0.5 scores with no response in irritation control animals would be considered suggestive of sensitization. The percentage of animals reacting, rather than the intensity of reactions, was the criterion for assessing sensitization potency.

 

The Twenty nine of the 30 animals (97%) challenged with 5% formaldehyde (positive control) showed clear skin responses, while all the irritation control animals were free of skin responses, confirming the validity of this skin sensitization test.

 

The severity indices in the test group were comparable to those produced in the irritation control groups, suggesting that sensitization had not been induced. 

 

Since the test chemical did not cause skin sensitization in treated group, the chemical was considered to be not sensitizing to the skin of guinea pigs in a Guinea pig maximisation test described by Magnusson and Kligman.