Registration Dossier

Administrative data

Description of key information

Not irritating to skin or eye irritating, based on animal test data.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Information is available on skin and eye irritation potential of the following members of this category:

Test substance identity

Route

Skin

Eye

Hex-1-ene

Alkenes, C6-8

Alkenes, C6-8, branched, C7 rich

Oct-1-ene

Alkenes, C8-10, branched, C9 rich

 

Dec-1-ene

Dodec-1-ene

Alkenes, C10/11/12/13

 

Alkenes C11/13/14

Alkenes, C11-13, C12 rich

 

Alkenes, C11-15

 

Alkenes, 12-14 α

Tetradec-1-ene

 

Hydrocarbons, C14-30, olefin-rich

Hexadec-1-ene

Alkenes, C16-18

Octadec-1-ene

 

Alkenes, C18-24, ethylene polymn. By-product

 

Alkenes, 20-24

Alkenes, 20-24 α

 

 

 

Thirty five guideline or near-guideline rabbit skin irritation studies have been conducted on 16 category members, ranging from hex-1-ene to alkenes, C20-24. In general, the studies show that these higher olefins are not skin irritants. There are a few studies that are exceptions, and this may be due to differences in laboratory methods i.e. use of occluded or semi-occluded conditions; duration of exposure (4 or 24 hours).

Twenty-two eye rabbit irritation studies have been conducted on 16 category members, ranging from hex-1-ene to alkenes, C20-24. It can be concluded from all of these studies that higher olefins are not irritating to the rabbit eye.

Based on a weight of evidence analysis of these findings, no classification for skin or eye irritation potential is necessary according to the CLP regulation.

Details of these studies are summarised below.

Skin Irritation

Information is available from four studies that have investigated the skin irritation potential of 1-hexene and the related substance alpha olefin C6.

In the first study (Price, 1985), young adult white rabbits (3/sex) were exposed dermally to 0.5 millilitres of test substance (99.4% pure) applied to 2 cm x 2 cm area of body surface area under semi-occlusion for 4 hours. Animals then were observed for 7 days. Irritation was scored based on OECD guidelines, on a scale of 0 to 4. The application of 1 -hexene resulted in no skin reactions, with a mean irritation score of 0 for erythema and oedema at all time points. In this study, 1-hexene was not a dermal irritant and no classification is necessary according to the CLP regulation.

In a second study using 1-hexene (Cagen, 1982), young adult white rabbits (3 males, 2 females) were exposed dermally to 0.5 ml of test substance applied to a 4 inch x 4 inch area of body surface for 24 hours under occlusion. Animals were then observed for 3 days. Irritation was scored based on Draize criteria, on a scale of 0 to 4. The application of 1-hexene resulted in skin irritation, with a Primary Irritation Index of 0.975. The mean score (24-72 hours) for erythema was 0.35 for intact and abraded skin; the mean score (24-72 hours) for oedema was 0.64 for intact skin and 0.65 for abraded skin. In this study, reactions obtained with 1 -hexene were insufficient to lead to classification as a skin irritant under the CLP regulation.

In one study (Monrose, 1973), six rabbits were exposed dermally to 0.5 millilitres 1-hexene (alpha olefin C6) undiluted under occlusion. The test substance was applied to four shaved areas (unspecified size and location) per rabbit; two abraded and two intact test sites. Following 24 hour exposure, each test site was evaluated for erythema and oedema at 24 and 72 hours post-application using the Draize method of scoring. No signs of oedema were observed on any intact or abraded test sites. Mild erythema was observed at both 24 and 72 hours on both intact and abraded sites.  The mean score (24 -72 hours) for erythema was 1.0 for intact skin and 1.08 for abraded skin; for oedema, the mean scores (24-72) for intact and abraded skin was 0.0. A Draize score of 1.0 was reported for alpha olefin C6 classifying it as a mild dermal irritant by the study authors; this Draize score falls below the threshold for classification under CLP, hence alpha olefin C6 is not classified as possessing a potential for cause skin irritation under the CLP regulation.

In the final study, 1-hexene (0.5 mL) was applied to clipped rabbit skin for 24 hours under occlusion (Rinehart, 1967). Skin reactions to the test chemical were observed at 24 and 72 hours post application and evaluated on the basis of erythema and oedema. The study author reported that dermal application of 1-hexene to the shaved skin of rabbits produced very slight to well-defined, but not severe, erythema with a Primary Irritation Index of 1. At 24 hours, the intact and abraded skin average erythema scores were 1.2 and 1.5, respectively. At 72 hours, the intact and abraded skin average erythema scores were 0.7 and 0.8, respectively. Oedema scores averaged 0.0 for both intact and abraded skin for both the 24 and 72 observation periods. The author concluded that 1-hexane was not an irritant to the rabbit skin. According to the CLP regulation, a Draize score of 1 also is considered not irritating.

Information is available from one study that has investigated the skin irritation potential of Alkenes, C6-8.

In a dermal irritation study (Rees, 1996), 3 New Zealand White Rabbits were exposed dermally to 0.5 mL of alkenes, C6-8 (SHOP C68 Internal Olefin) applied to 3 x 2 cm area of skin under semi-occlusion for 4 hours. Animals then were observed at 1, 24, 48, and 72 hours and 7, 10, and 13 days post-exposure. Irritation was scored using the method of Draize. All animals had very slight to slight erythema, which sometimes extended beyond the test site, and occasionally very slight oedema for the first 72 hours post-exposure (mean erythema score = 1.55; mean oedema score = 0.66; average for 24, 48 and 72 hours). The study authors concluded that under the study conditions, SHOP C68 internal olefin was slightly irritating to rabbit skin, but the result does not lead to classification as a skin irritant under the CLP regulation.

Information is available from one study that has investigated the skin irritation potential of Alkenes, C6-8, branched, C7 rich.

 

In a skin irritation study (Moreno, 1978), eight New Zealand White rabbits were exposed dermally to Alkenes C6-8, branched, C7 rich (MRD-ECH-78-36) applied under occlusive conditions for 24 hours. Prior to test chemical administration, the abdomen of all rabbits was clipped free of hair. The clipped area of all animals was abraded such that the abrasions were deep enough to penetrate the stratum corneum, but not deep enough to cause bleeding. The test material was applied at a concentration of 200 or 3160 mg/kg dermally to the prepared sites of the animals. At 24 hours the wrapping was removed and the treated sites were wiped, not washed before evaluation. Dermal evaluations were recorded daily for 14 days using the Draize (1959) method of skin evaluation. Additionally rabbits were observed at 1, 2, 3, and 4 hours post dosing and daily thereafter for 14 days for overt signs of toxicity and mortality. All animals were sacrificed on day 14 and necropsied. Animals treated with 200 mg/kg test material showed slight to well defined erythema and oedema during the first few days of observation (mean erythema score = 1.88; mean oedema score = 0.75). These signs appeared to diminish and were clear during observation on day 14. In animals treated with 3160 mg/kg test material, moderate to severe erythema and oedema was observed for the first few days of observation (mean erythema score = 2.38; mean oedema score = 1.50). Though these signs diminished slightly by day 14, complete reversibility was not noted. Based on these results, the study authors concluded that the test material was not irritating to rabbit skin at 200 mg/kg, but is irritating at 3160 mg/kg, under occlusion. The latter results support classification under the CLP regulation.

Information is available from four studies that have investigated the skin irritation potential of 1-octene and the related substance alpha olefin C8.

In the first study (Driscoll, 1996), 5 male and 1 female New Zealand White rabbits were exposed dermally to 0.5 millilitre of 1-Octene (Gulftene 8) applied under semi-occlusion for 4 hours. Animals then were observed for 14 days and irritation was scored by the Draize method. The test material application produced a primary irritation index of 3.42 calculated according to US EPA FIFRA guidelines, and mean scores (24, 48 and 72 hours) of 1.9 for erythema/eschar formation and 1.1 for oedema according to EU scoring methods. Compound-induced corrosion was not reported. 1-Octene was not irritating to skin, and no classification is necessary.

In a second study (Morris, 1992), six white rabbits (3/sex) were exposed dermally to 0.5 millilitres of 1-Octene (Neodene 8 alpha olefin) applied under occlusion for 4 hours. Animals were observed at 1/2 to 1 hour, 24, 48, 72 hours and 7 days post-exposure. Irritation was scored by the method of Draize. All six animals exhibited erythema (average score 2.00) and oedema (average score 2.67) 1 hour post-exposure. Mean erythema and oedema scores (averaged over 24, 48, and 72 hours) were 2.28 and 1.83, respectively. Irritation persisted through 72 hours in all treated animals, while on day 7 only one of the six treated animals was free of irritation. Based on these results, 1-octene is considered a skin irritant according to the CLP regulation.

 In another study (Angevine, 1983), young adult white rabbits (3/sex) were exposed dermally to 0.5 millilitres of 1-octene (Neodene 8) applied to 4 in x 4 in body surface area under occlusion for 24 hours.  Animals were then observed for 7 days. Irritation was scored based on Draize, on a scale of 0 to 4. The application of 1-octene resulted in skin irritation, with a Primary Irritation Index of 3.38. The mean score for erythema (recorded at 24 and 72 hours) was 1.08 for intact skin and 1.21 for abraded skin; the mean score for oedema (recorded at the same time points) was 2.08 for intact skin and 2.38 for abraded skin. In this study, 1-octene meets criteria for classification as a skin irritant.

In a final study (Monrose, 1973), six New Zealand White rabbits were exposed dermally to 0.5 millilitre of 1-octene (C8 alpha olefin) for 24 hours; the type of wrapping used (occluded or semi-occluded) was not reported. Animals were observed for 3 days and irritation was scored by the Draize method. Based on observations at 24 and 72 hours, the study authors calculated an average Draize score of 1.8. Mean scores of 1.5 for erythema (intact and abraded skin) and 0.25 and 0.33 (intact and abraded skin, respectively) for oedema were determined over the 24 to 72 hour period. The authors concluded that 1-octene was considered a mild, but not primary, irritant to the white rabbit. Based on these results, 1-octene does not meet criteria for classification according to the CLP regulation.

Information is available from three studies that have investigated the skin irritation potential of 1-decene and the related substance alpha olefin C10.

In the first irritation study (Driscoll, 1996), young adult New Zealand white rabbits (five males/one female) were exposed dermally to 0.5 millilitres of 1-decene (Gulftene 10), applied to 2.5 centimetres x 2.5 centimetres of body surface area under semi-occlusion for 4 hours. Animals then were observed for 14 days. Irritation was scored based on OECD guidelines (Draize), on a scale of 0 to 4. The application of 1-decene resulted in reversible, mild skin reactions, with a mean irritation score of 2.0 for erythema and 1.7 for oedema averaged over 24, 48, and 72 hours. In this study, 1-decene was a mild dermal irritant but the magnitude of the response did not trigger classification under the CLP regulation.

In a second study (Morris, 1992), six young adult rabbits (gender unspecified) were exposed dermally to 0.5 millilitres of undiluted 1-decene (Neodene 10 alpha olefin), applied to 1 by 1 inch section of skin under occlusion for 4 hours. Animals were then observed for 7 days. Irritation was scored by the Draize method. Severe dermal irritation was observed in all animals 1 hour post-exposure (erythema: average score 2.17; oedema: average score 3.33) through 72 hours post-exposure (erythema: 3.0; oedema: 2.5). By day 7, two animals were irritation free and the remaining animals exhibited slight to moderate irritation. Mean erythema and oedema scores (24 to 72 hour averages) were 2.72 and 2.5, respectively. Based on the reported mean irritation scores, 1-decene meets criteria for classification as a skin irritant according to the CLP regulation.

In the final study (Rinehart, 1967), Six male rabbits clipped free of fur were exposed dermally to 0.5 millilitre of 1-decene (C10 alpha olefins) for 24 hours after which the treatment patches were removed. It is not clear whether exposure involved occluded or semi-occluded conditions. Skin reactions to the test chemical were observed at 24 and 72 hours post application and evaluated on the basis of erythema and oedema. At 24 hours, the intact and abraded skin average erythema scores were 0.7 and 0.7, respectively. At 72 hours, the intact and abraded skin average erythema scores were 1.0 and 1.2, respectively. Oedema scores averaged 0.0 for both intact and abraded skin for both the 24 and 72 observation periods. The study author reported that dermal application of 1-decene to the shaved skin of rabbits produced very slight to well-defined, but not severe, erythema with a Primary Dermal Irritation Index of 0.9. The level of response was insufficient to result in classification under the CLP regulation.

Information is available from four studies that have investigated the skin irritation potential of 1-dodecene and the related substance alpha olefin C12.

In the first dermal irritation study (Driscoll, 1996), young adult white rabbits (five males/one female) were exposed dermally to 0.5 millilitres of 1-dodecene (Gulftene 12), purity unknown, applied to 2.5 centimetres x 2.5 centimetres of body surface area under semi-occlusion for 4 hours. Animals then were observed for 14 days. Irritation was scored based on OECD guidelines (Draize), on a scale of 0 to 4. The application of 1-dodecene resulted in reversible skin reactions, with a mean irritation score of 2.2 for erythema and 2.4 for oedema averaged over 24, 48, and 72 hours. In this study, 1-dodecene is a dermal irritant according to the CLP regulation.

In the second study (Merkel, 2002), 2 male and 1 female New Zealand White rabbit was exposed dermally to 0.5 mL of 1-dodecene, applied to a 6 cm2 section of shaved skin under semi-occlusion for 4 hours. After 4 hours, the site was gently cleaned and irritation was scored according to the Draize scoring system at 1, 24, 48, and 72 hours and 7 and 10 days. The test conditions complied with the guideline requirements for this study type.  An hour after patch removal, all three sites had well-defined erythema and very slight to moderate oedema. Mean erythema scores at 1, 24, 48, 72 hours and 7 and 10 days were 2.0, 1.7, 1.3, 1.3, 0.3, and 0.0, respectively. Mean oedema scores were 1.7, 1.0, 0.7, 0.7, 0.0, and 0.0, respectively. The mean erythema was 1.44 averaged over 72 hours (24, 48, and 72 hours); the mean oedema was 0.78 averaged over 72 hours (24, 48, and 72 hours). After 1 hour, the incidence and severity of erythema and oedema decreased progressively. On day 10 all animals were free of dermal irritation. Based on a Primary Dermal Irritation Index of 2.6, the study authors concluded that 1-dodecene is moderately irritating to the rabbit skin; however, no classification is necessary according to the CLP regulation.

In a third study (Morris, 1992), 6 rabbits (3/sex) were exposed dermally to 0.5 millilitres of 1-dodecene (Neodene 12 alpha olefin) applied under occlusion for 4 hours. Animals were observed for skin irritation effects and scored using the Draize method of skin irritation scoring at 0.5-1, 24, 48, 72 hours, and 7 days post exposure. Severe irritation was observed in all animals 1 hour post exposure through 72 hours. By day 7, 5 animals exhibited moderate dermal irritation and one animal had only slight irritation. Mean erythema scores at 0.5 to 1 hour, 24 hours, 48 hours, 72 hours, and 7 days were 2.00, 2.83, 3.00, 3.00, and 1.83, respectively; oedema scores for the same observation periods were 3.33, 2.17, 1.50, 2.00, and 1.50, respectively. The mean erythema was 2.94 averaged over 72 hours (24, 48, and 72 hours); the mean oedema was 1.89 averaged over 72 hours (24, 48, and 72 hours). A Primary Dermal Irritation Index (PDII) was calculated for the test chemical using the mean of the average total scores for erythema and oedema for readings from 1-72 hours. Based on a PDII of 5.0, 1-dodecene was classified Toxicity Category II for dermal administration. Based on these results, 1-dodecene is a skin irritant according to the CLP regulation.

In a final study (Carter, 1976), six New Zealand white rabbits were exposed dermally with 0.5 millilitre of 1-dodecene (Alpha Olefin C12) applied neat for 24 hours under semi-occlusion. Of the four clipped skin areas treated, two areas were abraded prior to treatment. The treated areas were covered with gauze to keep the material in contact with the skin for 24 hours. Animals were observed for erythema and oedema at 24 and 72 hours post exposure. The mean score (24 -72 hours) for erythema was 0.0 for intact skin and 0.25 for abraded skin; the mean score (24-72 hours) for oedema was 0.0 for intact and abraded skin. The authors calculated a PDII of 0.13 based on erythema and oedema response at the 24 and 72 hour observation period. The results seen do not result in classification according to the CLP regulation.

Information is available from one study that has investigated the skin irritation potential of Alkenes, C10/C11/C12/C13.

In a dermal irritation study (Price, 1985), New Zealand white rabbits (3/sex) were exposed dermally to 0.5 mL of Alkenes, C10/C11/C12/C13 (SHOP olefins 103) applied to a 2 x 2 cm area of skin under semi-occlusion for 4 hours. Animals then were observed up to 16 days. Irritation was scored by the method of Draize. The application of SHOP olefins 103 resulted in inflammation and superficial necrosis in two rabbits, with a mean irritation score of 1.69 for erythema and 0.50 for oedema. Alkenes, C10/11/12/13 was “mildly irritating” to skin but the magnitude of the response does not lead to classification under the CLP regulation.

Information is available from one study that has investigated the skin irritation potential of Alkenes, C11/C13/C14.

In a dermal irritation study (Rees, 1996), 3 female New Zealand White Rabbits were exposed dermally to 0.5 mL of alkenes, C11/13/14 (SHOP C134 Internal Olefin) applied under semi-occlusion for 4 hours. Animals then were observed for 1, 24, 48, and 72 hours after removal of the dressing, as well as on days 7, 10, and 13. Irritation was scored by the method of Draize criteria. Very slight or slight erythema (mean 24, 48 and 72 hours = 1.44) was observed after the bandages were removed and the site was washed. Less frequent observations of very slight oedema (mean 24, 48 and 72 hours = 0.55) also were noted. On day 7, very slight oedema in one animal was noted; loss of elasticity was noted in another animal, and two animals showed exfoliation. On day 10, all test sites showed exfoliation. Additionally, loss of elasticity and poor hair growth persisted in one animal. Skin sites were observed to be normal by day 13. Based on these study results, alkenes, C11/13/14 were considered to be slightly irritating to rabbit skin by the study authors but the level of response would not result in classification according to the CLP regulation.

Information is available from one study that has investigated the skin irritation potential of alkenes, C12-14 alpha.

In one dermal irritation study (Monrose and Carter, 1973), 6 New Zealand white rabbits (sex not specified) were exposed dermally to 0.5 millilitre of C12-14 Alpha Olefin for 24 hours under “open” conditions. Animals were then observed at 24 and 72 hours post exposure and irritation was scored by the Draize method. The test material application produced a primary irritation index of 1.6 calculated using the Draize scoring system. Based on these scores the authors concluded that the test material is a mild irritant when applied dermally to rabbit skin. The mean score for erythema over a 72 -hour period was 0.53, regardless of whether skin was intact or abraded. The mean score for oedema over a 72 -hour period was 0.83, regardless of whether skin was intact or abraded. According to the CLP regulation, C12 -14 Alpha Olefin is not a skin irritant.

Information is available from three studies that have investigated the skin irritation potential of 1-tetradecene and the related substance alpha olefin C14.

In the first study (Merkel, 2002), young adult New Zealand rabbits (two males and one female) were exposed dermally to 0.5 millilitre of undiluted 1-tetradecene (Amodrill 1410) applied to 6 square centimetre section of skin under semi-occlusion for 4 hours. Animals were then observed for 3 days. Irritation was scored by the Draize method. All three rabbits exhibited well-defined erythema 1 hour following patch removal. Very slight oedema was evident in one rabbit 24 hours post exposure and all animals were free of dermal irritation by 72 hours post exposure. No signs of gross toxicity, adverse pharmacological effects or abnormal behaviour were reported. The mean erythema was 0.56 averaged over 72 hours (24, 48, and 72 hours); the mean oedema was 0.22 averaged over 72 hours (24, 48, and 72 hours). Based on a Primary Dermal Irritation Index of 1.1, the study author considered 1-tetradecene was considered to be slightly irritating to the skin of rabbits; however, according to the CLP regulation, the test material would not be considered irritating.

In a second study (Driscoll, 1996), six (five male and one female) young adult New Zealand white rabbits were exposed dermally to 0.5 millilitres of undiluted 1-tetradecene (Gulftene 14), applied to a 2.5 by 2.5 centimetre area under semi-occlusion for 4 hours. Animals then were observed for 14 days. Irritation was scored by the Draize method. By 24 hours all sites had well-defined erythema and slight oedema. The irritation began to recede by 48 hours with desquamation observed beginning at 72 hours. The test material application produced a primary dermal irritation index of 2.79, and mean scores of 1.3 for erythema/eschar formation and 1.1 for oedema between 24 and 72 hours after application. According to the CLP regulation, 1-tetradecene is not a skin irritant.

In the final study (Morris, 1992), six young adult rabbits (gender unspecified) were exposed dermally to 0.5 millilitre of undiluted 1-tetradecene (Neodene 14 alpha olefin) applied to a 1 by 1 inch section of skin under occlusion for 4 hours. Animals were then observed for 7 days. Irritation was scored by the Draize method. Severe skin irritation was observed in all animals 1 hour post-exposure (erythema: average score 2.0; oedema: average score 3.0) through 72 hours post-exposure (erythema: 2.0; oedema: 2.0). By day 7, two animals were free of irritation and the remaining 4 had slight to moderate irritation. Mean erythema and oedema scores (averaged over 24, 48, and 72 hours) were 2.00 and 2.28, respectively). Based on the reported mean irritation scores, 1-tetradecene meets the criteria for classification as a skin irritant in accordance with the CLP regulation.

Information is available from one study that has investigated the skin irritation potential of Hydrocarbons, C14-30, olefins rich.

In a dermal irritation study (Springer, 1977), 6 albino rabbits were exposed dermally to 0.5 mL of hydrocarbons, C14-30, olefin rich (ethyl compound 100-606) applied at two test sites (intact and abraded skin) under occlusion for 24 hours. Animals then were observed for 72 hours. Irritation was scored by the Draize method. Results, measured immediately post-exposure and again at 72 hours post-exposure, were reported according to a simple numerical scoring system based on Draize, where the degree of erythema and oedema was assessed visually on a scale from 0 to 4. No rabbits experienced oedema or erythema at the site of intact skin exposure. Results showed that the material would be classified as practically non-irritating according to the Draize scoring system. The test substance was not a skin irritant according to the CLP regulation

Information is available from four studies that have investigated the skin irritation potential of 1-hexadecene and the related substance alpha olefin C16.

In the first irritation study (Driscoll, 1996), six New Zealand White rabbits were exposed dermally to 0.5 millilitres of 1-hexadecene (Gulftene 16) applied under semi-occlusion for four hours. Animals were observed for 30 minutes post exposure period, 24 hours, 48 hours and 72 hours. Irritation was scored by the method of Draize. In this study, 1-hexadecene is a moderate dermal irritant to the skin based on the primary irritant index score of 2.46 (U.S. FIFRA guidelines). No corrosive effects were noted. The mean score (24 -72 hours) for erythema/eschar was 1.3 and the mean score for oedema over the same period was 0.9. According to the CLP regulation, the test substance does not require classification as a skin irritant.

In the second study (Hoekstra and Phillips, 1963), albino guinea pigs were exposed dermally to 0.5 and 0.6 mL of 1-hexadecene (n-hexadecene) applied to unshaved area of skin; it was not stated whether exposure was occluded or semi-occluded. Skin exposures occurred days 1, 3, 5, and 7 for a total of 4 treatments. Skin evaluations were conducted every other day for 20 days following the first treatment. Scoring was done on a scale of 0-8. Based on animal response, the study authors concluded that application of the 1-hexadecene produced severe skin damage with a relative skin effect of 8 (maximal damage) in exposed guinea pigs. The non-guideline nature of this study (sub-acute exposure regime, use of guinea pig rather than rabbit) precludes its use for the purposes of classification.

In a third study in rabbits (Product Safety Labs, 2002), 2 male and 1 female New Zealand albino rabbit was exposed dermally to 0.5 mL of 1-hexadecene (alpha olefin C16) applied under occlusion for 4 hours. The mean erythema was 0.44 averaged over 72 hours (24, 48, and 72 hours); the mean oedema was 0.00 averaged over 72 hours (24, 48, and 72 hours). The response obtained does not lead to classification under the CLP regulation.

In a final study (Morris and Goble, 1992), young New Zealand White rabbits (3/sex) were exposed dermally to 0.5 millilitres of 1-hexadecene (Neodene 16 Alpha Olefin) applied under occlusion for four hours. Animals then were observed at 30 minutes, 1 hour, 24 hour, 48 hour and 72 hours after application. Irritation was scored by the method of Draize. The mean erythema was 1.94 averaged over 72 hours (24, 48, and 72 hours); the mean oedema was 0.94 averaged over the same period. In this study, 1-hexadecene is found to be mildly irritating to the skin based on the mean Primary Irritation Index score of 3.2 (based on erythema and oedema formation). Not classification for skin irritation is required under the CLP regulation.

Information is available from one study that has investigated the skin irritation potential of alkenes, C16-18.

In a dermal irritation study (Morris, 1995), young adult white rabbits (two males, one female) were exposed dermally to 0.5 mL of alkenes, C16-18 (C16/18 isomerized alpha olefins) applied to 6.25 cm2 of the body under semi-occlusion for 4 hours. Animals then were observed for 14 days. Irritation was scored by the method of Draize (1959). The test material produced well-defined erythema and very slight to slight oedema, which had all cleared by day 14 of observation. The 24, 48 and -72 hour average erythema score was 1.56; and the average oedema score was 0.22 over the same time period. In this study, results for alkenes, C16-18 do not support classification under the CLP regulation.

Information is available from three studies that have investigated the skin irritation potential of 1-octadecene and the related substance alpha olefin C18.

In the first irritation study (Driscoll, 1996), six New Zealand White rabbits were exposed dermally to 0.5 millilitre of 1-octadecene (GULFTENE 18) applied under semi-occlusion for 4 hours. Animals were observed for 3 days. Irritation was scored by the Draize method. 1-octadecene was found to produce a primary irritation index of 2.29, calculated according to US EPA FIFRA data reporting guidelines. The test substance did not cause corrosion. Mean scores (24 -72 hours) of 1.5 for erythema/eschar formation and 0.9 for oedema were obtained indicating the 1-octadecene is not irritating according to the CLP regulation.

In a second study (Price, 1985), young adult white rabbits (3/sex) were exposed dermally to 0.5 millilitres of 1-octadecene (SHOP Alpha Olefin C18), 97.2% pure, applied to 2 centimetres x 2 centimetres of body surface area under semi-occlusion for 4 hours. Animals then were observed for 7 days. Irritation was scored based on OECD guidelines, on a scale of 0 to 4. There were no skin reactions to 1-octadecene when the application patch was removed at 4 hours after dosing. However, at the 24-hour observation all rabbits had slight inflammation of the treated site. Inflammation persisted and increased at 72 hours post-dosing. Minimal erythema was still apparent in five of the six rabbits at 7 days. Reactions were all cleared by day 16. However, the skins of all animals were dry and flaking. The application of 1-octadecene resulted in inflammation and minimal erythema, with mean (24, 48 and 72 hr) irritation scores of 1.22 for erythema and 0.14 for oedema. Based on these results, 1-octadecene does not require classification according to the CLP regulation.

In the final study (Morris, 1992), six white rabbits (3/gender) were exposed dermally to 0.5 millilitres of 1-octadecene (Neodene 18 alpha olefin) applied under occlusion for 4 hours via dorsal skin patches. Animals were observed at 1/2 to 1 hour, 24, 48, 72 hours and 7 days post-exposure. Irritation was scored by the method of Draize. Severe irritation was observed in all animals 1 hour post-exposure (average erythema score was 2.17; average oedema score was 2.00). Mean erythema and oedema scores (averaged over 24, 48, and 72 hours) were 2.17 and 0.94, respectively. Based on the reported mean erythema and oedema scores, 1-octadecene was not considered a skin irritant according to the CLP regulation.

Information is available from two studies that have investigated the skin irritation potential of Alkenes, C20-24.

In a dermal irritation study (Driscoll, 1998), young adult New Zealand white rabbits (six males) were exposed dermally to 0.5 mL of alkenes C20 -24, purity unknown, applied to 2.5 centimetres x 2.5 centimetres of body surface area under semi-occlusion for 4 hours. Animals were then observed for 72 hours. Irritation was scored based on Draize (1977). The application of C20 -24 alkenes resulted in no skin reactions, with a mean irritation score of 0 for erythema and 0 for oedema averaged over 24 and 72 hours. In this study, C20 -24 alkenes is not a dermal irritant based on CLP regulation criteria.

In a second study (Sanders, 2008), New Zealand White rabbits (2 male and 1 female) were exposed dermally to 0.5 millilitres of alkenes, C20-24 (ENORDET O241) applied under semi-occlusion for 4 hours. Animals were then observed for 3 days. Irritation was scored by the method of Draize. The mean erythema score at the 24-hour observation was 1.0, which indicated a very slight erythema. The mean erythema score at the 48 and 72-hour observation points was 0.0. The mean oedema score at the 24, 48, and 72-hour observation points was 0.0. The test material produced a primary irritation index of 0.5. In this study, alkenes, C20-24 is not considered a dermal irritant based on EU classification criteria. 

Information is available from one study that has investigated the skin irritation potential of Alkenes, C20-24 alpha.

In one study (Morris, 1992), six white rabbits (3/gender) were exposed dermally to 0.5 millilitre of alkenes, C20-24 alpha (Neodene 20-24 alpha olefin) under occlusion for 4 hours. Animals then were observed for 7 days. Irritation was scored by the method of Draize. All six animals exhibited erythema (average score 1.83) and oedema (average score 2.17) 1 hour post-exposure. Although moderate irritation persisted through 72 hours, by day 7, four of the six animals were free of irritation and the remaining two animals had only slight irritation indicating a reversible trend. Desquamation was the only change noted in the colour and/or texture of the skin. Mean erythema and oedema scores (averaged over 24, 48, and 72 hours) were 1.94 and 0.72, respectively. The reported mean erythema and oedema scores for alkenes, C20-24 alpha does not meet the criteria for classification as a skin irritant according to the CLP regulation.

Eye Irritation

Information is available from three studies that have investigated the eye irritation potential of 1-hexene and the related substance alpha olefin C6.

In the first study (Cagen, 1982), 0.1 millilitre of 1-hexene (Neodene 6), undiluted, was instilled into the conjunctival sac of the right eyes of six male and three female New Zealand White rabbits. Three males had their eyes washed 30 seconds post-exposure. Animals were then observed for 8 days. Irritation was scored by the method of Draize. Mild irritation was noted 1 hour post-exposure in both washed and unwashed eyes. Irritation persisted to day 3 of the observation period, but was not noted on day 8 post-exposure. In this study, 1-hexene is not classified as an eye irritant based on CLP criteria.

 

In a second study (Monrose, 1973), 0.1 millilitres undiluted 1-hexene (alpha olefin C6) was instilled into the conjunctival sac of a single eye in each of six rabbits; the other eye served as a control. Observations of the cornea, iris, and conjunctiva were made 24, 48, and 72 hours post-dose application and scored on a scale of 1 -6 (scoring criteria not provided). Mean scores were reported for each time interval. Minimal irritation of the conjunctiva was observed in one animal at 24 hours but was completely resolved by 48 hours. There were no other observations of ocular irritation recorded. 1-Hexene was not an eye irritant in the rabbit and no classification is required.

In the final study (Rinehart, 1967), 1-hexene (0.1millilitre) was instilled into one eye of six male rabbits while the other eye served as a control. The treated eyes were not washed and were observed at 24, 48 and 72 hours. Instillation of 1-hexene in the eyes produced mild, transient redness of the conjunctival tissue in one animal only. No effects on the cornea or iris were observed. Based on this test results, the author concluded that 1-hexene is not irritating to rabbit eye. No classification is required under the CLP regulation.

Information is available from one study that has investigated the eye irritation potential of Alkenes, C6-8.

In a study (Rees, 1996), 0.1 mL of alkenes, C6-8 (SHOP C68 internal olefin) was instilled into the conjunctival sac of the right eye in 3 New Zealand White rabbits. Animals then were observed at 1, 24, 48, and 72 hours. Irritation was scored by the guidelines. Initial instillation of the test compound caused very slight initial pain response. All animals had very slight to slight conjunctivitis within an hour of treatment, but one animal showed persistent response at 48 hours. At 72 hours, all animals’ eyes appeared normal. In this study, alkenes, C6-8 was not irritating to the eye and no classification is necessary. 

Information is available from one study that has investigated the eye irritation potential of Alkenes, C6-8, branched, C7 rich.

In one study (Moreno, 1978), six white rabbits were treated with 0.1 mL of alkenes, C6-8, branched, C7 rich (MRD-78-36) which was instilled into the conjunctival sac of one eye. The treated eyes were held shut for a few minutes to ensure adequate distribution of the test material. The untreated eye served as control. All animals were observed for overt signs of toxicity and for irritation of the cornea, iris, and conjunctiva at 1 and 4 hours, and on days 1, 2, 3, 4 and 7. Fluorescein was used in examining ocular irritation on days 7, 10 and 14. Ocular irritation was scored using the Draize system of eye irritation (1959). No overt signs of toxicity were noted in any of the animals. Slight to moderate irritation was noted during the 1st and 4th hour following instillation. Slight irritation continued to be seen on day 2 in two rabbits. Based on these results, the study authors concluded that the test material is not irritating when instilled into rabbit eyes. The results indicate that no classification of alkenes, C6-8, branched, C7 rich is necessary under the CLP regulation.

Information is available from two studies that have investigated the eye irritation potential of 1-octene and the related substance alpha olefin C8.

In one study (Angevine, 1983), 0.1 millilitre of 1-octene (Neodene 8), undiluted, was instilled into the conjunctival sac of the right eyes of six male and three female New Zealand White rabbits. Three males had their eyes washed 30 seconds post-exposure. Animals were then observed for 7 days. Irritation was scored by the method of Draize. Mild irritation was noted 1 hour post-exposure in both washed and unwashed eyes. Irritation persisted to day 1 of the observation period, but was not noted on day 2 post-exposure. In this study, 1-octene was not classified as an eye irritant based on EU classification criteria.

 In a second study (Monrose, 1973), 0.1 millilitres of 1-octene (Alpha Olefin C8) was instilled once into the conjunctival sac of one eye in six white rabbits. The eye was not washed and the other eye acted as a control. Animals then were observed for 24, 48 and 72 hours. One animal exhibited minimal conjunctival irritation which cleared by the 48 hour reading. Since no other irritation was observed in the 48 and 72 hour readings, a day 7 observation was not made. 1-Octene does not require classification according to CLP criteria.

Information is available from two studies that have investigated the eye irritation potential of alkenes, C8-10 branched, C9 rich.

In one study (Paynter, 1962), six male and female (animal number per sex not specified) albino rabbits were instilled with 0.1 mL of alkenes, C8-10 branched, C9 rich (MRD-62-28 nonene) in the conjunctival sac of the left eye. The untreated eye served as control. Following treatment, the eyes were held shut for 30 seconds. The animals were observed for signs of systemic toxicity and eye irritation at 1, 4, 24, hours and 2, 3, 4, and 7 days. Signs of eye irritation were scored using the Draize method. On the seventh day, animal eyes were examined using the sodium fluorescein solution to detect the presence of corneal damage. Following eye examination, animals were weighed and the study was terminated.  Irritation was confined to the conjunctivae with visible signs of slight to moderate redness accompanied by slight discharge in two animals. In two of the animals the irritation had subsided at the 4 hour observation period, and in the remaining animals the irritation had completely subsided by 24 hours.  Examination on the seventh day using fluorescein solution confirmed the absence of any corneal damage. Based on the study outcome, it may be concluded that alkenes, C8-10 branched, C9 rich are not irritating when instilled into rabbit eyes and no classification is necessary.

Information is available from one study that has investigated the eye irritation potential of 1-decene and the related substance alpha olefin C10.

In one study (Rinehart, 1967), 0.1 millilitres of 1-decene, undiluted, was instilled into one eye of six male albino rabbits. All rabbit eyes remained unwashed.  Animals were then observed for 72 hours. Irritation was scored by the method of Draize. Mild irritation was noted 24 and 48 hours post-exposure in two rabbits and one rabbit, respectively. Irritation had disappeared by day 3 of the observation period. In this study, 1-decene is not an eye irritant based on criteria given in the CLP regulation.

Information is available from one study that has investigated the eye irritation potential of alkenes, C11/13/14.

In one study (Rees, 1996), three New Zealand White rabbits (sex not specified) were instilled with 0.1mL of alkenes, C11/13/14 (SHOP 134) in the right eye. The left eye served as control. Following test chemical instillation, the animals were observed for overt signs of toxicity for several minutes and were checked twice during the first hour after treatment and at regular intervals throughout the day and daily to ensure that the treated eyes did not exhibit infection or cause distress. Ocular irritation was scored at 1, 24, 48, and 72 hours after treatment using a method similar to the Draize (1959) eye irritation scoring system. Very slight to slight conjunctivitis was observed in all animals one hour after exposure. Very slight conjunctival redness persisted in one animal and was observed at the 24- and 48-hour examinations. Iritis was observed in one animal at the 1-hour examination. At the 72-hour examination, there were no signs of ocular irritation. None of the animals exhibited a pain response to administration of the test material. Based on these results, alkenes C11/13/14 was non-irritating to the rabbit eye and no classification is necessary.

Information is available from one study that has investigated the eye irritation potential of alkenes, C11-13, C12 rich.

In one study (Scala, 1961), 0.1 mL of alkenes, C11-13, C12 rich (tetrapropylene) was instilled into the conjunctival sac of left eyes of rabbits (9/sex) for 30 seconds in unwashed eyes (6 animals) and for four seconds in washed eyes (3 animals, 20 mL of water). Animals then were observed for seven days. Irritation was scored by the method of Draize (1959). Application of alkenes, C11-13, C12 rich produced very slight irritation in the washed eyes and in four of the unwashed eyes, and the other two animals showed no sign of irritation. In two of the washed eyes, significant irritation was noted at one hour, including slight or moderate erythema, slight oedema and discharge (scores of 6 and 10 for the two animals). The treated eyes of all animals appeared normal after 24 hours, and there was no evidence of corneal damage for any animal. In this study, alkenes, C11-13, C12 rich was not an eye irritant and the results do not lead to classification under the CLP regulation.

Information is available from one study that has investigated the eye irritation potential of alkenes, C11-15.

In one study (Cassidy and Clark, 1977), 0.2 mL of alkenes, C11-15 (Internal Olefin 114 LP11) was instilled into the conjunctival sac of one eye of four New Zealand white rabbits (eyes were not washed). Animals then were observed for 1 to 2 hours, then 1, 2, 3, and 7 days, thence every four days until irritation was not observed. Irritation was scored by the method of Draize using a scale of 0 to 4. Eyes were observed for response of conjunctiva (redness, chemosis and discharge), corneal opacity and iris damage. Mean response of 1.0 and 0.8 were reported for redness after 1 to 2 hours and 1 day, respectively. In this study, alkenes, C11-15 was not irritating to the eye and no classification is necessary.  

Information is available from one study that has investigated the eye irritation potential of 1-dodecene.

In one study (Carter, 1976), six New-Zealand white rabbits were instilled with 0.1 millilitre of neat 1 -dodecene (C12 alpha olefin) in one eye, while the other eye served as control. Observations for damage and irritation were made at the end of days 1, 2, 3, and 7 after treatment. Based on study results, the test chemical did not cause any irritation in the eyes of the treated animals.

Information is available from two studies that have investigated the eye irritation potential of alkenes, C12-14 alpha.

In one study (Rinehart, 1967), C12 -16 alpha olefin blend was instilled into male albino rabbit eyes at 0.1 millilitres. After instillation, the upper and lower lids were held shut briefly to avoid loss of the test material. The exposed eyes were not washed after treatment and were examined at 24, 48, and 72 hours post treatment. In addition to the untreated eye serving as a control, six rabbits treated with 5% ivory soap solution also served as a control. All C12-16 alpha olefin-treated animals had mild transient redness of the conjunctivae. There were no effects to the cornea or the iris. Results were less severe than the 5% Ivory Soap solution treatment group. Based on the study results, the study author concluded that alkenes, C12-16 was not irritating to the eye. The results do not lead to classification under the CLP regulation.

In a second study (Monrose and Carter, 1973), 6 white rabbits (sex not specified) were instilled with 0.1 millilitre of C12-14 Alpha Olefin for 7 days. Animals were observed at 24, 48, and 72 hours and at 7 days post exposure. Irritation appears to have been scored according to the Draize scoring system for eye irritation. The test material application produced minimal conjunctival irritation in 2 of the 6 treated animals at the 24 hour observation period, but the irritation had cleared at the 48 hour reading. The authors concluded that C12-14 alpha olefin was not irritating when instilled into rabbit eyes. No classification is necessary based on findings from this study.

Information is available from one study that has investigated the eye irritation potential of hydrocarbons, C14-30, olefin rich.

In one study (Springer, 1977), six rabbits (sex and strain not specified) were instilled with 0.1 millilitre of hydrocarbons, C14-30, olefin rich (Ethyl Compound 100-606) in the right eye. The left eye served as control. The treated animals were observed for any signs of injury to the cornea, iris and bulbar and palpebral conjunctivae at 24, 48, and 72 hours after treatment. The Draize method (1959) of eye irritation scoring was used. Five of the six rabbits experienced mild conjunctivitis, which disappeared after two days. No other signs of irritation were noted. Based on visual assessment, the test material was classified as practically non-irritating to rabbit eyes and was not an ocular irritant according to criteria in the CLP regulation.

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

In one study (Rinehart, 1967), 0.1 millilitre of 1-hexadecene was instilled into the conjunctival sac of six male albino rabbits. Treated eyes were not washed during exposure. The animals were observed at 24, 48 and 72 hours after exposure. Irritation was scored by the Draize method. In this study, 1-hexadecene was not an eye irritant based on a 24 hour average redness Draize score of 0.7.

Information is available from one study that has investigated the eye irritation potential of alkenes, C16-18.

In one study (Morris, 1995), 0.1mL of alkenes, C16-18 (C16/18 isomerized alpha olefin), undiluted, was instilled into the conjunctival sac of the right eyes of young adult New Zealand White rabbits (one male, two female) for 24 hours and then rinsed. Animals were then observed for 72 hours. Irritation was scored by the method of Draize. Conjunctival irritation was noted 1 hour post-exposure and persisted to day 1 of the observation period, but no irritation was noted on day 2 post-exposure. In this study, alkenes, C16-18 are not classified as irritating to the eye based on EU classification criteria.

Information is available from two studies that have investigated the eye irritation potential of alkenes, C18-24, ethylene polymerization by product.

In the first study (Fletcher, 1977), 0.1 millilitre of alkenes, C18-24, ethylene polymerization by product (Compound 100 -527) was instilled into the conjunctival sac of the right eye of six New Zealand white rabbits for 24 hours. Eyes were not washed after instillation. Animals then were observed for 72 hours. Irritation was scored by the method of Draize. The eyes of all six exposed rabbits responded with mild conjunctivitis. No corneal opacity occurred in any rabbits. These effects were reversible after two days. In this study, alkenes, C18-24, ethylene polymerization by product was not an eye irritant based on the low mean score and lack of other effects.

In the second study (Fletcher, 1977), 0.1 millilitres of alkenes, C18-24, ethylene polymerization by product (Compound 100 -494) was instilled into the conjunctival sac of the right eye of six New Zealand white rabbits for 24 hours. Eyes were not washed after instillation. Animals then were observed for 72 hours. Irritation was scored by the method of Draize. The eyes of all six exposed rabbits responded with mild conjunctivitis. No corneal opacity occurred in any rabbits. These effects were reversible after two days. In this study, alkenes, C18-24, ethylene polymerization by product was not an eye irritant to the eye based on the low mean score and lack of other effects. No classification is necessary.

Information is available from two studies that have investigated the eye irritation potential of alkenes, C20-24.

In the first study (Driscoll, 1998), C20-C24 alkenes, branched and linear, was instilled into rabbit eyes with a single 0.1 mL volume in the conjunctival sac of the right eye. Irritation was assessed in both unwashed and washed eyes. Results were reported according to the numerical scoring system based on Draize (1977); irritation scores were weighted and averaged to calculate a Draize score. For both unwashed and washed rabbit eyes, conjunctival redness was observed at the 1 hour observation period. All treated eyes appeared normal at the 24-hour observation. This resulted in a Draize score of 0.0 which indicates that the test substance is not irritating to rabbit eye.

In the second study (Sanders, 2008), 0.1 millilitres of alkenes, C20-24 (ENORDET O241) was instilled into the conjunctival sac of the right eye in male, New Zealand white rabbits and the animals observed for 3 days. Irritation was scored based on a modified Kay and Calandra classification system. No corneal or iridial effects were noted, however, moderate conjunctival irritation was noted in all treated eyes 1 hour after treatment. Minimal conjunctival irritation was noted in all treated eyes when observed at the 24 hour point. The group mean score was 8.0 at 1 hour, 2.0 at 24 hours, and 0.0 at both 48 and 72 hours. In this study, alkenes, C20-24 was considered a minimal eye irritant based on the modified Kay and Calandra classification system, however no classification is triggered under EU CLP criteria.


Justification for selection of skin irritation / corrosion endpoint:
Thirty five guideline or near-guideline rabbit skin irritation studies have been conducted on 16 category members, ranging from C6 to C20-24. In general, the studies show that these higher olefins are not skin irritants. There are a few studies that are exceptions, and this may be due to differences in laboratory methods i.e. use of occluded or semi-occluded conditions; duration of exposure (4 or 24 hours). A weight of evidence analysis of these findings indicates that members of this category are not irritating to skin

Justification for selection of eye irritation endpoint:
Twenty-two eye rabbit irritation studies have been conducted on 16 category members, ranging from C6 to C20-24. It can be concluded from all of these studies that higher olefins are not irritating to the rabbit eye.

Justification for classification or non-classification

Thirty five guideline or near-guideline rabbit skin irritation studies have been conducted on 16 category members, ranging from C6 C20-24. In general, the studies show that these higher olefins are not skin irritants. There are a few studies that are exceptions, and this may be due to differences in laboratory methods i.e. use of occluded or semi-occluded conditions; duration of exposure (4 or 24 hours). Based on a weight of evidence analysis of these findings, no classification for skin irritation potential is necessary according to the CLP regulation.

Twenty-two eye rabbit irritation studies have been conducted on 16 category members, ranging from C6 to C20-24. It can be concluded from all of these studies that higher olefins are not irritating to the rabbit eye. No classification for eye irritation potential is necessary according to the CLP regulation.