Oct-2-ene

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1982-03-02 to 1982-05-14

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable with restrictions because although the study does not meet current OECD 406 guidelines, the study was well conducted and reported.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in Section 13.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

The induction dose was low and did not produce mild irritation

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The study was conducted in accordance with OECD and EU test guidelines applicable at the time of undertaking.

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

Cas Number:

111-66-0

Molecular formula:

C8H16

Details on test material:

- Name of test material (as cited in study report): NEODENE-8
- Substance type: C8 alpha olefin
- Physical state: Clear liquid

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Weight at study initiation: Average female-445 grams; Average male-518 grams
- Housing: Stainless steel caging-5 animals/cage
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 18 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0 to 21.1
- Humidity (%): 40 to 70

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol

Induction 2

Concentration / amount:

0.5 millilitres of 1% W/V in absolute ethanol

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol

Challenge 2

Concentration / amount:

0.5 millilitres of 1% W/V in absolute ethanol

No. of animals per dose:

10 animals; 5 males, 5 females

Details on study design:

RANGE FINDING TESTS: Preliminary tests used 6 animals at three different concentrations (one male, one female animal were used at each concentration) to determine the highest concentration at which no irritation occurs. Each animal was treated at two sites. Preliminary test concentrations were 100, 50 and 1% W/V of Neodene-8 Alpha Olefin.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours/application
- Test groups: 10:5 males and 5 females
- Control group: 10: 5 males and 5 females
- Site: back/trunk region
- Frequency of applications: once a week
- Duration: 3 weeks
- Concentrations: 0.5ml of 1% Neodene-8 in absolute ethanol


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Week 5 post induction
- Exposure period: 6 hours
- Test groups: 10: 5 males, 5 females
- Control group: 10: 5 males, 5 females
- Site: back/trunk region; one patch placed at the original treated site; another patch placed at a virgin site posterior to the original patch
- Concentrations: 0.5ml of 1% Neodene-8 in absolute ethanol
- Evaluation (hr after challenge): 24 and 48 hours post exposure


OTHER: In addition to the three groups used in the main study (Induction Exposure and Challenge Exposure), a fourth group termed "Irritation Control Group" was treated during the fifth week only along with the Challenge Group to determine the test materials sensitisation potential

Challenge controls:

Control group consisted of 10 animals (5 males; 5 females) treated with 0.5 millilitres of absolute ethanol.

Positive control substance(s):

yes

Remarks:

0.5ml of 0.1% W/V 2,4-dinitrochlorobenzene in diethyl ether

Results and discussion

Positive control results:

The positive control, 2,4-dinitrochlorobenzene, was found to be irritating (average score at week 1 was 2.00 and at week 5 was 1.78). Eschar and necrosis were evident in the positive control on both the treatment site and challenge site indicating a positive skin sensitising reaction.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

05ml of 1% W/V

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

None reported

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 05ml of 1% W/V. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None reported.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5ml of 1% W/V

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

None reported

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5ml of 1% W/V. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None reported.

Results 3

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Remarks on result:

other: scores for the vehicle control group were not provided. Control group showed little or no increase in skin irritation

Results 4

Reading:

2nd reading

Group:

positive control

Clinical observations:

Eschar and necrosis were evident in the positive control on both the treatment site and challenge site indicating a positive skin sensitising reaction.

Remarks on result:

other: The positive control, 2,4-dinitrochlorobenzene, was found to be irritating (average score at week 1 was 2.00 and at week 5 was 1.78).

Applicant's summary and conclusion

Interpretation of results:

other: Not sensitising

Conclusions:

Neodene-8 Alpha Olefin is not sensitising when applied dermally to albino Hartley guinea pigs.

Executive summary:

Hartley albino guinea pigs were used in this study to determine the skin sensitisation potential of Neodene-8 Alpha Olefin. Prior to main study initiation, a preliminary test was conducted during week three of the pre-trial period using 6 animals at three different concentrations (1 male, 1 female at each concentration) to determine the highest concentration at which no irritation occurs. Each animal was tested at two sites. Preliminary testing included 0.5ml of 100, 50, and 1% W/V Neodene-8 in absolute ethanol. Results of this preliminary test indicated that no irritation was present at the 1% W/V concentration while slight irritation occurred at the two higher concentrations. Hence the 1% W/V concentration was used to conduct the main sensitisation study.

Two days prior to main study initiation, the animals were examined for general health and suitability for testing. Animals certified to be healthy were weighed and randomly assigned to four treatment groups: vehicle control, positive control, test group and irritation control. Each treatment group consisted of 5 male and 5 female animals. Approximately 48 hours prior to each dose application, the animals were clipped free of hair from the back/trunk region. Approximately 18 -24 hours prior to dosing, the animals were depilated with NEET hair removal lotion and rinsed with warm water and dried. Each sensitising treatment consisted of dispensing an appropriate dose on a 1" x1" gauze pad which was prepared by attaching the corners of the gauze pad to a strip of aluminium foil while using a minimum of Blenderm surgical tape. This patch was then applied to the anterior central portion of the clipped area. The aluminium foil dressing was kept in place at the treated site using strips of Blenderm tape and occluded with saran wrap. The animals were then placed in a stainless steel wire restrainer for six hours before removal of the patch and any excess test material using moistened gauze pads. This process was repeated for two additional weeks for a three week total exposure period.

The challenge application was conducted in a similar manner except that at the time of this application, one patch was placed at the original site, while another patch was placed at a virgin site immediately posterior to the original patch. The treatment period was the same, i.e. six hours of exposure during week 5 of the main study (animals were allowed a two week recovery period prior to challenge dose application).

In addition to the challenge group, the study authors also included an "Irritation Control Group" (5 males and 5 females) which was treated only once during week 5 with the application of only one patch. All treated animals were scored for skin reactions approximately 24 and 42 hours after each treatment using the following scoring system:

Scoring Scale

No Reaction	0
Minimal erythema (barely perceptible with edges not defined)	+
Slight erythema (pale red/pink in colour and edges of area defined)	1
Moderate erythema (red in colour and edges well-defined)	2
Moderate erythema with slight oedema (red in colour, edges well-defined, raised less than 1millimetre)	3
Severe erythema with moderate oedema and cracking of skin (beet/crimson red in colour, raised 1 mm or more, cracking of skin)	4

 

All treated animals were scored for skin sensitisation approximately 24 and 48 hrs post exposure. The study authors reported that there were no changes in body weight during the course of the study and concluded that Neodene-8 Alpha Olefin treated group and the control group showed little or no increase in skin irritation. The positive control group performed as expected with treated animals exhibiting Eschar and necrosis on both the treatment site and challenge site indicating a positive skin sensitising reaction. Based on these results, the study authors concluded that Neodene-8 Alpha Olefin is not sensitising to albino Hartley guinea pigs when applied dermally.

This study was given a Klimisch score of 1 andis classified as reliable without restrictions because it closely followed OECD 406 guidelines and was GLP compliant.