Oct-2-ene

Endpoint summary

Description of key information

An analogue read-across source, Neodene-8 Alpha Olefin is not sensitising when applied dermally to albino Hartley guinea pigs.

Dermal sensitization testing has been conducted on 11 members of the HOPA category, ranging from C6 to C20-24.

There was no evidence of dermal sensitization in any of these studies, and no classification is necessary according to the CLP regulation.

Read-across to Oct-2-ene is claimed as valid based on the justifications provided for both analogue and category approaches. Oct-2 -ene is not anticipated to be sensitising.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

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.

Reason / purpose for cross-reference:

read-across: supporting information

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.

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

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol

Concentration / amount:

0.5 millilitres of 1% W/V in absolute ethanol

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol

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

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.

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.

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.

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

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).

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. 

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Read-across between the target substance Oct-2-ene (EC 203-894-2 / CAS 111-67-1) and source substances Octene (EC 246-920-8 / CAS 25377-83-7) and Oct-1-ene (EC 203-893-7 / CAS 111-66-0 / alpha-C8) is based upon the similarity of the chemical structures and their respective physico-chemical properties. The ECHA Read-Across Assessment Framework (RAAF) states that substances with qualitatively similar properties can form the basis of read-across in circumstances where the source and target substances share such similar characteristics.

Octene, Oct-1-ene and Oct-2-ene are linear olefins, each with a carbon chain length of C8. Structurally, the difference between source and target substances is the position of the carbon-carbon double bond. For Oct-1-ene the double bond is at the terminal C1 position (hence, an alpha-olefin), whereas for Oct-2-ene the double bond is at the non-terminal C2 position (hence, an internal olefin). A comparison of the target and source substance properties shows that all substances would be expected to exhibit similar environmental fate, ecotoxicological and mammalian toxicological behaviours. The justification for read-across from source substances Octene and Oct-1-ene to target substance Oct-2-ene is detailed in section 13 (Document name: “Oct-2-ene Read Across Document HOPA”).

Further, Oct-2-ene and Oct-1-ene both fit within the boundaries of the chemical category of higher olefins. Studies conducted by the HOPA consortium on a large range of higher olefin category members (including Oct-1-ene) demonstrated sufficiently similar physico-chemical, environmental fate and toxicological properties to substantiate the basis for read-across. Therefore Oct-2-ene is expected to behave similarly. Justification for inclusion of Oct-2-ene within the boundaries of the higher olefins category, and the relevance of each category member as an analogue substance to Oct-2-ene, is provided in Section 13 (Document name: “HOPA Higher Olefins CJD with Category Matrix Report [rev 1 Sept 2016]”).

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across source

Species:

guinea pig

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol

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.

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.

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

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).

Interpretation of results:

other: Not sensitising

Conclusions:

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

Read-across to Oct-2-ene is claimed as valid basd on the justifications provided for both analogue and category approaches.

Executive summary:

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

Read-across to Oct-2-ene is claimed as valid based on the justifications provided for both analogue and category approaches. Oct-2 -ene is not anticipated to be sensitising.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Information is available from one study that has investigated the skin sensitisation potential of 1-Octene and the related substance alpha olefin C8.

In a skin sensitization study, 1-octene (Neodene 8 alpha olefin) was tested in Hartley albino guinea pigs (5 animals/sex) (Lam and Angevine, 1983). Animals were exposed to 0.5 millilitres test material, 2,4 -dinitrochlorobenzene (positive control), or ethanol (vehicle control) for 1 day/week for 6 hours/day for 3 weeks. For the three weekly initiating doses, a 1% solution of 1-octene in ethanol was used; the primary challenge dose was also 1% 1-octene in ethanol.  Reactions were scored with a numerical grade to indicate severity.  The positive control and vehicle control provided the appropriate response. Body weight gain was not affected by treatment. 1-octene caused little or no irritation after the initiation or challenge dose and did not induce a delayed contact hypersensitivity reaction under the conditions of the study.  It was concluded that 1-octene was not a dermal sensitizer.

Information is available from one study that has investigated the skin sensitisation potential of 1-hexene and the related substance alpha olefin C6.

In a skin sensitization study 1-hexene (Neodene 6 alpha olefin) was tested in Duncan Hartley guinea pigs (5 animals/sex) using a patch sensitisation method (Cagen and Lam, 1982). Animals were exposed to 0.5 millilitres test material, 2,4-dinitrochlorobenzene (positive control), or ethanol (vehicle control) for 1 day/week for 6 hours/day for 3 weeks. For the three weekly initiating doses, a 1% solution of 1-hexene in ethanol was used; the primary challenge dose was also 1% 1-hexene in ethanol.  Reactions were scored with a numerical grade to indicate severity.  The positive control and vehicle control provided the appropriate response. Body weight gain was not affected by treatment. 1-hexene caused little or no irritation after the initiation or challenge dose and did not induce a delayed contact hypersensitivity reaction under the conditions of the study.  It was concluded that 1-hexene was not a dermal sensitiser.

Information is available from one study that has investigated the skin sensitisation potential of 1-dodecene and the related substance alpha olefin C12.

In a skin sensitisation study 1-dodecene (Neodene 12 alpha) was evaluated in young Hartley albino guinea pigs (10 animals/sex) for dermal sensitisation potential using the method of Buehler (Morris, 1992). Animals were exposed to 0.3 millilitres test material for 1 day/week for 6 hours/day for 3 weeks. Following a 2 week rest period, animals received a challenge dose in the same manner as the initiating doses.  For the three weekly induction doses, a 10% W/V solution of 1-dodecene in acetone was used; the primary challenge dose was a 5% W/V solution of 1-dodecene in acetone.  Reactions were scored with a numerical grade to indicate severity. Challenge of the test material resulted in a 24 -hour severity score of 0.3 for both test and naive control animals. The 48-hour scores for test and naive control animals were 0.2 and 0.05, respectively. Historical laboratory data indicated that the positive control substance, 2,4-dinitrochlorobenzene produced the appropriate response as in previous studies. It was concluded that 1-dodecene was not a dermal sensitizer since the graded dermal responses were not significantly different between the test and control animals.

Information is available from one study that has investigated the skin sensitisation potential of 1-hexadecene and the related substance alpha olefin C16.

In a skin sensitization study, 1-hexadecene (Neodene 16) was evaluated in young adult Hartley guinea pigs for dermal sensitisation potential using the method of Buehler (Morris, 1992). Animals were exposed to 0.3 millilitres test material 1 day/week for 6 hours/day for 3 weeks. Following a 2 week rest period, animals received a challenge dose in the same manner as the initiating doses.  For the three weekly induction doses, a 10% W/V solution of 1 -hexadecene in acetone was used; the primary challenge dose was a 2.5% W/V solution of 1-hexadecene in acetone.  Reactions were scored with a numerical grade to indicate severity. Challenge of the test material resulted in a 24 -hour severity score of 0.1 and 0.3 for test and naive control animals, respectively. The 48-hour scores for test and naive control animals were 0.05 and 0.2, respectively. Historical laboratory data indicated that the positive control substance, 2,4-dinitrochlorobenzene produced the appropriate response as in previous studies. It was concluded that 1-hexadecene was not a dermal sensitizer since the graded dermal responses were not significantly different between the test and control animals.

Information is available from one study that has investigated the skin sensitisation potential of alkenes C20-24 alpha.

In one skin sensitisation study alkenes C20-24 ? (Neodene C20-24 alpha olefin) was tested for its potential to induce skin sensitisation (delayed contact hypersensitivity) in male and female Harlan albino guinea pigs using the Buehler method (Morris, 1992). Animals were exposed to 0.3 millilitres test material 1 day/week for 6 hours/day for 3 weeks. Following a 2 week rest period, animals received a challenge dose in the same manner as the initiating doses.  For the three weekly induction doses, a warmed, undiluted alkenes, C20-24 ? (specified as undiluted in acetone) was used; the primary challenge dose was a 5% W/V solution of alkenes, C20-24? in mineral oil.  Reactions were scored with a numerical grade to indicate severity. Historical laboratory data indicated that the positive control substance, 2,4-dinitrochlorobenzene, produced the appropriate response as in previous studies. Alkenes, C20-24? caused little or no irritation after the challenge dose and did not induce a delayed contact hypersensitivity reaction under the conditions of the study. In this study, alkenes, C20-24? is not a dermal sensitiser.

Migrated from Short description of key information:
Not a skin sensitiser, based on animal test data.

Justification for selection of skin sensitisation endpoint:
Dermal sensitization testing has been conducted on 11 members of the HOPA category ranging from C6 to C20-24. Information is also available for triecene, a chemically related non-category member. Testing was normally performed in the guinea pig, using both adjuvant and non-adjuvant based methods, however one human repeated insult patch test is also available (1-octadecene). These was no evidence of dermal sensitization in any of these studies.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Migrated from Short description of key information:
Not expected to cause respiratory sensitisation based on results of skin sensitisation testing and an absence of reactive chemical alerts.

Justification for classification or non-classification

Dermal sensitization testing has been conducted on 11 members of this category, ranging from C6 to C20-24. Information is also available for triecene, a chemically related non-category member. Testing was normally performed in the guinea pig, using both adjuvant and non-adjuvant based methods, however one human repeated insult patch test is also available (1-octadecene). There was no evidence of dermal sensitization in any of these studies, and no classification is necessary according to the CLP regulation.

Read-across of these results to Oct-2 -ene is claimed as valid based on the justifications provided for both analogue and category approaches. Oct-2 -ene is not anticipated to be sensitising.