4,4'-[(1,10-dioxodecane-1,10-diyl)bis(oxy)]bis(2,2,6,6-tetramethylpiperidine-1-oxidanyl)

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4100 (Skin Sensitisation)

Deviations:

yes

Remarks:

Deviations did not affect the outcome of the study.

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

A guinea pig maximisation study was available, therefore a LLNA method was not necessary.

Test material

Test material information

Constituent 1

Reference substance name:

1,10-bis(2,2,6,6-tetramethyl-1-piperidinyloxy)-1,10-dioxodecane

EC Number:

417-440-8

EC Name:

1,10-bis(2,2,6,6-tetramethyl-1-piperidinyloxy)-1,10-dioxodecane

Cas Number:

2516-92-9

Molecular formula:

C28 H50 N2 O6

IUPAC Name:

bis(1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl) decanedioate

Details on test material:

Identification code (lab) = TKA 40075

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Remarks:

albino

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc., Houston, Texas
- Females (if applicable) nulliparous and non-pregnant: not specified
- Microbiological status of animals, when known: not known
- Age at study initiation:
- Weight at study initiation:
Males (285-340g); Females (290-320g) (at time of testing)
- Housing:
Cage Type: Suspended, wire bottom, stamless steel
Housing: One per cage
Transfer to Clean Cages: Weekly
Litter Pan Lining: Paper
Litter Pan Lining Change: Three times weekly
Food: Purina Gumea Pig Chow; available ad libitum
Water Type: Tap; available ad libitum
Water System: Automatic
- Acclimation period: At least five days
- Indication of any skin lesions: not specified

- IN-LIFE DATES: From: June 17, 1992 To: July 11, 1992

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

propylene glycol

Concentration / amount:

For the test animals, the first pair of injections (one on each side of the spine column and approximately 3.5 cm apart), consistmg of Freund's Complete Adjuvant diluted to 50% v/v in 0.9% saline, was made at the anterior edge of the exposure area.
The second pair of injections, consisting of 2% w/v test material in propylene glycol vehicle, was made approxunately 0.5 cm behind the first pair of injections.
The third pair of injections, consisting of a 50:50 mixture of Freund's Complete Adjuvant (diluted to 50% v/v in 0.9% salme) and 2% w/v test material in vehicle, was made approximately 1.0 cm behind the second pair.

Day(s)/duration:

on day 0

Adequacy of induction:

other: an intermediate dose of 2% w/v test material in propylene glycol was selected for the intradermal induction.

Induction 2

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

a 2 x 4 cm patch of filter paper with 0.5 ml of 25% w/w test material m petrolamm was placed over the exposure areas to cover the three paks of injection sites of each test group animal.

Day(s)/duration:

On day 7

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Challenge

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

25% w/w test material m petrolatum for topical applications

Day(s)/duration:

on day 21

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

15

Details on study design:

RANGE FINDING TESTS:
Six healthy, short-haured, albino guinea pigs (3 males and 3 females) were released from quarantine for pre-testing. The animals were clipped prior to dosing. One male and one female received intradermal injections at different sites of 0.1 ml each of 1%, 2%, 4% and 5% w/v test material in propylene glycol (vehicle), as well as two 0.1 ml injections per animal of vehicle only. Observations were made at 24 and 48 hours after injection. Of the remaining four animals, one male and one female received 0.5 ml applications of 5% and 15% w/w test material in petrolatum, and one male and one female received 0.5 ml of 20% and 25% w/w test material m petrolatum. Observations were made at 48 hours after application. Significant irritation was seen with all
intradermal doses screened, including vehicle alone, and an intermediate dose of 2% w/v test material in propylene glycol was selected for the intradermal induction. No irritation was observed after any of the extemal cutaneous doses screened. The highest dose, 25%, was selected for cutaneous application on Day 7 and at challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 21 days
- Test groups: 1
- Control group: 1
- Site:
All injections were within a 2 X 4 cm area of the 4 x 6 cm exposure are
- Frequency of applications: at day 0 and 7.
- Duration: 21 days
- Concentrations:
For the test animals, the first pair of injections (one on each side of the spine column and approximately 3.5 cm apart), consistmg of Freund's Complete Adjuvant diluted to 50% v/v in 0.9% saline, was made at the anterior edge of the exposure area.
The second pair of injections, consisting of 2% w/v test material in propylene glycol vehicle, was made approxunately 0.5 cm behind the first pair of injections.
The third pair of injections, consisting of a 50:50 mixture of Freund's Complete Adjuvant (diluted to 50% v/v in 0.9% salme) and 2% w/v test material in vehicle, was made approximately 1.0 cm behind the second pair.
On Day 7, a 2 x 4 cm patch of filter paper with 0.5 ml of 25% w/w test material in petrolatum was placed over the exposure areas to cover the three pairs of injection sites of each test group animal. The patch was then occluded with an unpermeable plastic adhesive tape and secured in place with an elastic adhesive tape wound around the torso of the animal. A patch of filter paper with 0.5 ml of petrolatum only was placed over the exposure areas of the control group animals. The wrappings and patches were removed after 48 hours.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 3
- Exposure period: 1 day
- Test groups: 1
- Control group: 1
- Site: a 5 x 5 cm area was clipped on both the left and right flanks of each anunal.
- Concentrations:
A 2 x 2 cm patch of filter paper with 0.5 ml of 25% w/w test material in petrolatum was applied topically to the right flank of each test animal in a manner identical to the Day 7 treatment. A 2 x 2 cm patch of filter paper with 0.5 ml of petrolatum was applied to the left flank of each test animal for a control site. A 2 x 2 cm patch of filter paper with 0.5 ml of petrolatum only was applied topically to the right flank of the control ammals. A 2 x 2 cm patch of dry filter paper was applied to the left flank of each control animal for an untreated control site.
- Evaluation (hr after challenge):
On Day 22 (24 hours after challenge), the wrappings and patches were removed. On Day23 (24 hours after unwrapping), the test sites were observed for sldn reactions, and again on Day 24 (44 hours after unwrapping).

Challenge controls:

A 2 x 2 cm patch of filter paper with 0.5 ml of petrolatum only was applied topically to the right flank of the control ammals. A 2 x 2 cm patch of dry filter paper was applied to the left flank of each control animal for an untreated control site.

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

Treatment (25% w/w test material in petrolatum)

No. with + reactions:

3

Total no. in group:

20

Results 2

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

Treatment (25% w/w test material in petrolatum)

No. with + reactions:

1

Total no. in group:

20

Results 3

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

Control (no test material)

No. with + reactions:

1

Total no. in group:

20

Results 4

Reading:

2nd reading

Hours after challenge:

72

Group:

negative control

Dose level:

Control (no test material)

No. with + reactions:

0

Total no. in group:

20

Results 5

Group:

positive control

Remarks on result:

not measured/tested

Any other information on results incl. tables

Maximum concentration not causing irritating effects in preliminary test: 25 %

Signs of irritation during induction: Moderate erythema (2-3 grade), slight oedema (1-2 grade).

The test material, GUlO-415, appeared to produce a sensitizing reaction in three of twenty, or 15%, of the test animals. However, one of the ten controls, 10%, received a similar skin reaction score. The test material is therefore rated as a weak sensitizer in albino guinea pigs.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

No classificaiton of GU 10-415 is needed based on the guinea pig maximisation test.

Executive summary:

A maximization test for topically applied test materials was conducted on 30 short-haired male and female albino guinea pigs to determine if the test article labeled GU10-415, produced a sensitizing reaction.

Twenty guinea pigs each received three pairs of intradermal injections (adjuvant, a 2% w/v solution of the test material, and a mixture of adjuvant and 2% w/v solution of test material) followed one week later by a single topical application of the test material at 25% w/w in. petrolatum. Two weeks after the topical application, the animals were challenged with a second topical application of the test material at 25% w/w petrolatum at a virgin test site. Ten additional animals served as a control group. Control animals were treated at the same time periods and locations but with the vehicle used in place of the 2% w/v solution of test material. The percentage of animals exhibiting erythema and/or edema after the challenge treatment was used to assign the test material a sensitization potency rating.

The test material, GU10-415, appeared to produce a sensitizing reaction in three of twenty, or 15%, of the test animals. However, one of the ten controls, 10%, received a similar skin reaction score. According to the CLP guidelines, GU10 -415 does not have to be classified as a skin sensitizer.