Reaction mass of 1-chloro-3-[(Z)-octadec-9-en-1-yloxy]propan-2-ol and alpha-(Z)-octadec-9-en-1-yl-omega-hydroxy-di[oxy[(chloromethyl)-1,2-ethanediyl]] and alpha-(Z)-octadec-9-en-1-yl-omega-hydroxy-tri[oxy[(chloromethyl)-1,2-ethanediyl]]

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01 October 1992 - 02 November 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented study performed according to a method similar to OECD Guideline 406 with some minor deviations: the vehicle choice was not justified, no precise details were given on used patch materials

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

the vehicle choice was not justified, no precise details were given on used patch materials

GLP compliance:

no

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

reaction mass of 1-chloro-3-[(Z)-octadec-9-en-1-yloxy]propan-2-ol and alpha-(Z)-octadec-9-en-1-yl-omega-hydroxy-di[oxy[(chloromethyl)-1,2-ethanediyl]] and alpha-(Z)-octadec-9-en-1-yl-omega-hydroxy-tri[oxy[(chloromethyl)-1,2-ethanediyl]]

Cas Number:

108726-95-0

Molecular formula:

C21H41O2Cl C24H46O3Cl2 C27H51O4Cl3

IUPAC Name:

reaction mass of 1-chloro-3-[(Z)-octadec-9-en-1-yloxy]propan-2-ol and alpha-(Z)-octadec-9-en-1-yl-omega-hydroxy-di[oxy[(chloromethyl)-1,2-ethanediyl]] and alpha-(Z)-octadec-9-en-1-yl-omega-hydroxy-tri[oxy[(chloromethyl)-1,2-ethanediyl]]

Test material form:

other: liquid

Details on test material:

- Physical state: brown liquid
- Lot/batch No.: op600
- Date received: 29 May 1992
- Storage condition of test material: at room temperature

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Lebeau, 78950 Gambais, France
- Weight at study initiation: 346 +/- 19g ( males) and 331 +/- 20g (females)
- Housing: individually in polypropylene cages (48*27*20 cm) covered by sawdust (SICSA, Alfortville, France)
- Diet: complete pelleted diet "Cobayes entretien référence 106" (UAR, Villemoisson-sur-Orge, France), ad libitum
- Water: Water filtered on a 22 µm membrane (Millipore, Vélizy, France)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 50 +/- 20%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 06 October 1992 To: 02 November 2012

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

paraffin oil

Remarks:

Lot No 6909 (Gifrer, Decines, France)

Induction 2

Concentration / amount:

RANGE FINDING TEST:
- Intradermal induction exposure: 1, 10, 25 and 50% w/w in paraffin oil
- Topical induction exposure: 75% in paraffin oil and undiluted

MAIN TEST:
- Intradermal induction exposure: 50 % w/w in paraffin oil; mixture of 50% w/w in paraffin oil in Freund's Complete Adjuvant (FCA) plus distilled water in the ratio 1:1
- Topical induction exposure: undiluted test item
- Topical challenge exposure: undiluted test item

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

paraffin oil

Remarks:

Lot No 6909 (Gifrer, Decines, France)

Challenge 2

Concentration / amount:

RANGE FINDING TEST:
- Intradermal induction exposure: 1, 10, 25 and 50% w/w in paraffin oil
- Topical induction exposure: 75% in paraffin oil and undiluted

MAIN TEST:
- Intradermal induction exposure: 50 % w/w in paraffin oil; mixture of 50% w/w in paraffin oil in Freund's Complete Adjuvant (FCA) plus distilled water in the ratio 1:1
- Topical induction exposure: undiluted test item
- Topical challenge exposure: undiluted test item

No. of animals per dose:

10 animals/sex in the treated group; 5 animals/sex in the control group

Details on study design:

RANGE FINDING TESTS:
- Intradermal induction exposure: different concentrations were tested (1, 10, 25 and 50%) in order to select one that does not cause ulceration or necrosis.

MAIN STUDY
A. INDUCTION EXPOSURE: INTRADERMAL
- No. of exposures: One
- Day of induction: Day 1
- Test groups: 3 intradermally injection of 0.1 mL each of:
¤ a mixture of 1:1 (v/v) of FCA and 0.9% NaCl,
¤ test material diluted to 50% in paraffin oil,
¤ a mixture of 1:1 (V/V) of test material diluted to 50 % in paraffin oil and a mixture of 1:1 (v/v) of FCA and 0.9% NaCl
- Control group: 3 intradermally injection of 0.1 mL each of:
¤ a mixture of 1:1 (v/v) of FCA and 0.9% NaCl,
¤ paraffin oil,
¤ 50 % of paraffin oil in a mixture of 1:1 (v/v) of FCA and distilled water
- Site: Both sides of the spinal column, at the scapular level

Before the topical induction exposure, a local irritation was created on Day 7 by applying dermallyt 0.5 mL of sodium lauryl sulfate 10% (v/v) in paraffin oil in the scapular area.


B. INDUCTION EXPOSURE: TOPICAL
- No. of exposures: One
- Day of induction: Day 8
- Exposure period: 48 hr
- Test group: 0.5 mL of the undiluted test material was applied under an occlusive patch (4*2 cm)
- Control group: 0.5 mL of paraffin oil under an occlusive patch (4*2 cm)
- Site: Same as intradermal injection area
- Frequency of applications: Single application


C. CHALLENGE EXPOSURE: TOPICAL
- No. of exposures: One
- Day(s) of challenge: Day 22
- Exposure period: 24 hr
- Test and control groups: 0.5 mL of:
¤ the undiluted test material under an occlusive patch (2*2 cm) on the right flank
¤ paraffin oil under an occlusive patch (2*2 cm) on the left flank
- Site: dorso-lumbar region
- Evaluation (hr after challenge): 24 and 48 hr

OTHER:
- Animals were observed once daily for mortality and clinical signs
- Body weight: animals were weighed on Day -1, 1, 8, 15 and 25
- Pathology: On completion of the observation period, all animals were sacrificed by C02 asphyxiation. No macroscopic post-mortem examination was performed in any animals. For all animals, skin samples of the challenged application sites were preserved in 10 % buffered formalin. No microscopic examination was performed

Challenge controls:

A dry gauze (2 x 2 cm) moistened with 0.5 mL of undiluted test material applied on the right flank of the dorso-lumbar region of each animal via an occlusive patch.

Positive control substance(s):

no

Results and discussion

Positive control results:

N/A

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50% (w/w) in paraffin oil

No. with + reactions:

3

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: 50% (w/w) in paraffin oil. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: None.

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0

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: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.

Results 3

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50% (w/w) in paraffin oil

No. with + reactions:

3

Total no. in group:

10

Clinical observations:

Dryness of the skin in 5 animals

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50% (w/w) in paraffin oil. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: Dryness of the skin in 5 animals.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0

No. with + reactions:

7

Total no. in group:

10

Clinical observations:

None

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: None.

Any other information on results incl. tables

Table 7.4.1/2 Main test results

Group	Sex	Erythema score	Hours after challenge
			24 hr		48 hr
			LF	RF	LF	RF
Control	Males	0 1	- -	5/5 0	- -	2/5 3/5
	Females	0 1 2	- - -	5/5 0 0	- - -	1/5 1/5 3/5
Treated group	Males	0 1	10/10 0	9/10 1/10	10/10 0	8/10 2/10
	Females	0 1 2	10/10 0 0	8/10 2/10 0	10/10 0 0	9/10 0 1/10

LF: left flank    RF: right flank

- : untreated flank

 

Cutaneous reactions:

- Necrosis was observed on the site of intradermal injection in animals treated with the test item on Day 10.

- A very slight erythema (grade 1) was observed on the right flank (treated with the test item) in 7/10 animals in the control group at the 48 hr reading. No dermal reactions were observed in the other control animals.

- In the treated group, a very slight erythema (grade 1) was observed on the right flank (treated with the test item) in 3/20 animals at the 24 hr reading. A very slight and slight erythema were observed on the right flank (treated with the test item) in 2/20 and 1/20 animals, respectively, at the 48 hr reading.

- As the dermal reactions observed on the right flank (treated with the test item) of the test item-treated animals were of the same severity as those recorded in the control animals, they were not attributed to delayed contact hypersensitivity.

 

 

Others:

- No unscheduled deaths occurred during the study.

- No clinical signs indicative of systemic toxicity were observed in any animals.

- Body weight of the animals was unaffected by the test item treatment.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under these test conditions, the test material is not classified as skin sensitiser according to the Annex VI to the Directive 67/548/EEC and to the CLP Regulation (EC) N° (1272 -2008).

Executive summary:

In a non-GLP Magnusson & Kligman maximisation study (GPMT) performed according to a method equivalent to OECD Guideline 406, 20 Dunkin Hartley guinea pigs were induced with three pairs of intradermal injections (0.1 mL each) of FCA in 0.9% NaCl (1:1), the test material 50 % (w/w) in paraffin oil, and the test material 50 % (w/w) in paraffin oil in a 1:1 preparation of FCA in 0.9% NaCl, on Day 1 on three different sites on each side of the spinal column at the scapular level. The control group of 10 animals (5/sex) was intradermally induced with 0.1 mL of FCA in 0.9% NaCl (1:1), paraffin oil and paraffin oil in a preparation of FCA in 0.9% NaCl (1:1). After 7 days, 0.5 mL of sodium lauryl sulphate was applied to the skin to induce an inflammatory reaction. On Day 8, the same area was topically induced with undiluted test material under an occlusive patch for 48 hr for the treated group, and with paraffin oil only in the control group. After a 11 day resting period, a challenge occlusive patch of undiluted test material were applied for 48 hr to the dorso-lumbar region of each animal.

No mortality and no clinical signs of systemic toxicity were observed during the study. A very slight erythema (grade 1) was observed on the right flank (treated with the test item) in 7/10 animals in the control group at the 48 hr reading. In the treated group, a very slight erythema (grade 1) was observed on the right flank (treated with the test item) in 3/20 animals at the 24 hr reading. A very slight and slight erythema were observed on the right flank (treated with the test item) in 2/20 and 1/20 animals, respectively, at the 48 hr reading.

As the dermal reactions observed on the right flank (treated with the test item) of the test item-treated animals were of the same severity as those recorded in the control animals, they were not attributed to delayed contact hypersensitivity.

 

 

Under these test conditions, the test material is not classified as skin sensitiser according to the Annex VI to the Directive 67/548/EEC and to the CLP Regulation (EC) N° (1272 -2008).