Fatty acids, soya, conjugated

Endpoint summary

Description of key information

Skin
Animal data:
Skin irritation (OECD 404): not irritating; CAS# 57-10-3, C16 (Kästner, 1988)
Skin irritation (4h, occlusive, rabbit, reading: 20 h and 44h): not irritating; CAS# 112-80-1, C18:1 (Bio-Toxicology Laboratories, 1973)
Skin irritation (24h, occlusive, rabbit, reading: 48 h): not irritating; CAS# 112-80-1, C18:1 (USFHSA, 1973)
 
in vitro data: 
Human skin model (OECD 439; EPISKIN-SM): not irritating; CAS# 61789-45-5 (Verbaan, 2012)
 
Human data:
Skin irritation (closed epicutanous test): not irritating; CAS# 57-10-3, C16 (Matthies, 1988)
Skin irritation (repeated occlusive patch test, 1M): not irritating CAS# 57-10-3, C16; CAS# 112-80-1, C18:1; irritating CAS# 60-33-3, C18:2 (Stillman et al., 1975)
Eye
Animal data: 
Eye irritation (OECD 405): not irritating; CAS# 57-10-3, C16 (Kästner, 1988)
Eye irritation (rabbit, 0.1 mL, reading: 24, 48 and 72 h): not irritating; CAS# 112-80-1, C18:1 (USFHSA, 1974)
Eye irritation (OECD 405): not irritating; CAS# 112-86-7, C22:1 (Sterzel and Pittermann, 1992)

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

Skin

No data on skin irritation are available for fatty acids, soybean oil, conjugated. Therefore, skin irritation effects are predicted from adequate and reliable data for source substances by read-across to the target substance within the group applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular,the source substances structurally closest to the target substanceare chosen forread-across, with due regard to the requirements of adequacy and reliability of the available data.Reliable studies with the main constituents (> 10%) C16 fatty acid (palmitic acid) and C18:1 fatty acid (oleic acid) are used for hazard assessment. Furthermore, since fatty acids, soybean oil, conjugated consists mainly of long-chain unsaturated C18 fatty acids, read-across from fatty acids, dehydrated castor-oil was also performed.

 

Skin irritation by palmitic acid (CAS# 57-10-3) was evaluated in a study performed under GLP according to OECD Guideline 404 with the exception, that the test was performed under occlusive conditions (Kästner, 1988). Four Himalayan rabbits received an application of 0.5 g palmitic acid to the shaved skin under occlusion for 4 hours. The readings 24, 48, and 72 hours after application did not reveal any signs of irritation, thus resulting in mean scores of 0 for erythema and edema, respectively. As a consequence, the test was terminated after the 72 h reading. Based on the results, palmitic acid can be regarded as not irritating to skin.

In a study with human subjects, palmitic acid and 19 other substances were investigated with a closed epicutaneous test. 10 µL of palmitic acid at a concentration of 50% were applied to the back of the volunteers for 24 hours using a Large Finn Chamber (Matthies, 1988). The reactions were scored for edema, erythema, scaling and fissures 1, 6, 24, 48, 72 and 144 hours after application. As result, for all readings the score 0 was found. In another study with human subjects, 12.8% and 25.6% (w/v) palmitic acid was applied daily under occlusive patches to human skin until detectable erythema appeared (Stillman et al., 1975). Only one single subject showed erythema after six days of repeated application of 12.8% palmitic acid.

Based on the available studies in animals and humans, palmitic acid is considered to be not skin irritating.

 

In a skin irritation study with oleic acid (CAS# 112-80-1) 0.5 mL of the test substance was applied under occlusive conditions for 4 h to the abraded and intact skin of 6 rabbits (Bio-Toxicology Laboratories, 1973). Reading was performed upon removal of test substance and 20 and 44 h after patch removal. All animals showed very slight erythema (barely perceptible; score 1) on the intact and abraded skin sites upon removal of the occlusive patch. Within 20 h this reaction was reversible on all intact sites and on 5 abraded sites. At the 44 h reading time point no more erythema or eschar formation were observed in any of the animals. No edema formation was noted at the three reading time points. The mean score for erythema and edema, on the basis of only the 20 and 44 h time points and restricted to the results obtained from intact skin, was 0.

In a single insult occlusive patch test, 6 albino rabbits were administered a 0.5 mL dose of oleic acid for 24 hours to abraded and intact skin sites (USFHSA, 1973). Slight erythema of both intact and abraded skin (score of 1) in all six animals was observed directly after patch removal. By the 48 hour reading, erythema was no longer present. No edema was observed in any animal at any reading during the study.

A primary irritation index (PDII) of 0.5 was reported by Briggs et al. (1976), who tested 75% oleic acid to a method specified in the Regulation for the Enforcement of the Federal Hazardous Substances Act.

1 M oleic acid (~28% w/v), which was applied daily under occlusive patches to human skin until detectable erythema appeared, produced no irritation in any of the panellists within 10 days (Stillman et al., 1975).

Thus, based on this available data, oleic acid is considered to have no skin irritation potential.

 

For linoleic acid (CAS# 60-33-3), which is one of the main constituents of fatty acids, soybean oil, conjugated only limited data are available.

In an unpublished report by Eastman Kodak Co. (1979) (as cited in Cragg, 2000) the occlusive application of linoleic acid to the depilated abdominal skin of guinea pigs for 24 hours resulted in slight skin irritation. A primary irritation index of 1.64 was reported by Briggs et al. (1976), who tested 53% linoleic acid to a method specified in the Regulation for the Enforcement of the Federal Hazardous Substances Act. In a guinea pig maximization test linoleic acid was one of the tested substances which itself caused a clear skin irritation at the topical induction concentration (100%), when applied for 48 h (Kreiling et al., 2008). The test concentration used for topical challenge (50%) was too high and induced non-specific, i.e. irritative, skin reactions in test and control animals after application for 24 h under occlusive conditions.

1 M linoleic acid (~28% w/v), which was applied daily under occlusive patches to human skin until detectable erythema appeared, produced irritation in 7 panellists by the tenth day (Stillman et al., 1975). The first reaction was observed on day 4.

Taking all data together for linoleic acid, there is not sufficient information to make a final decision on the hazard assessment. However, the above mentioned tests with linoleic acid were conducted under more rigorous test conditions (≥ 24 h, occlusive applications, repeated exposure) than in the standard test (OECD guideline 404) for hazard assessment required under the REACH Annex VIII provisions.

 

The skin irritation potential of fatty acids, dehydrated castor-oil (UVCB consisting mainly of unsaturated C18 fatty acids) was determined in vitro on a human three dimensional epidermal model (EPISKIN Small ModelTM) according to OECD Guideline 439 (Verbaan, 2012). The undiluted test substance (25 µL) was applied topically for 15 minutes on the skin tissues. Phosphate buffered saline (PBS) and 5% (aq) SDS served as negative and positive control, respectively. The test was performed in triplicates for the treatment and control groups. After exposure and a 42 h post-incubation period, the cytotoxic (irritancy) effect was determined by measuring photometrically the enzymatic conversion of MTT into a blue formazan salt. The positive control had a mean cell viability of 5% and met the acceptability criteria. The absolute mean OD570 of the negative control tissues were within the laboratory historical control data range. The standard deviation value of the percentage viability of three tissues treated identically was less than 12%, indicating that the test system functioned properly. The relative mean tissue viability obtained after 15 minutes treatment with fatty acids, dehydrated castor-oil compared to the negative control tissues was 106%. Since the mean relative tissue viability for fatty acids, dehydrated castor-oil was above 50%, the substance is considered to be non-irritant in the Human Skin Model Test.

In conclusion, the main constituents palmitic acid and oleic acid are regarded as not irritating to skin. Furthermore fatty acids, dehydrated castor-oil, which consists like the target substance fatty acids, soybean oil, conjugated mainly of unsaturated C18 fatty acids showed no skin irritation potential in vitro. Therefore, by means of read-across based on a weight of evidence approach the substance fatty acids, soybean oil, conjugated is not irritating to skin.

Eye

No data on eye irritation are available for fatty acids, soybean oil, conjugated. Therefore, eye irritation effects are predicted from adequate and reliable data for source substances by read-across to the target substance within the group applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, the source substances structurally closest to the target substanceare chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Thus, reliable studies with theC16 fatty acid (palmitic acid), C18:1 fatty acid (oleic acid) and C22:1 (erucic acid) are used for hazard assessment.

 

Eye irritation by palmitic acid (CAS# 57-10-3) was analysed in a study performed in accordance with GLP and according to OECD Guideline 405 (Kästner, 1988). 0.1 g of palmitic was instilled into the right eyes of four Himalayan rabbits, while the untreated left eyes served as control. The reactions were examined 1, 6, 24, 48, and 72 h after administration and resulted in mean scores of 0, 0, 0.3 and 0 for corneal opacity, iris, conjunctival redness and chemosis, respectively. Since all signs subsided on day three after instillation, the study was terminated on that day due to animal welfare reasons. Based on these findings, palmitic acid is considered to be not irritating to eyes.

Palmitic acid was also found to be not irritating to eyes in a study performed according to National Guidelines since no signs of irritation were noted (Briggs, 1976).

 

A single application of 0.1 mL oleic acid (CAS# 112-80-1) was added to one eye of each of six albino rabbits (USFHSA, 1974). The other eye of each rabbit was left untreated and served as control. The eyes were examined at 24, 48 and 72 h after treatment, and scored for corneal opacity, iris lesions, conjunctival redness, chemosis, and discharge. The test material produced mild conjunctival redness (score of 1) and chemosis (score of 1) in one animal at the 24 h-reading and these symptoms were not reduced by the end of the observation period at 72 h. Discharge (score of 1) was also observed in this animal at the 48 and 72 h reading time points. Minor conjunctival redness (score of 1) was observed in four other animals at the 24 h-reading only. No signs of irritation were observed in one animal. The overall mean scores were 0, 0, 0.4 and 0.17 for corneal opacity, iris, conjunctival redness and chemosis, respectively. Thus, oleic acid is not regarded as eye irritant.

Briggs et al. (1976) reported mild conjunctival redness with complete clearing within 72 h for a mixture containing 75% oleic acid and 7.4% linolenic acid.

No or minimal conjunctival irritation was observed in the eyes of 6 albino rabbits treated with 0.1 mL oleic acid as commercially supplied using the Draize Method (Elder, 1987).

 

The eye irritation potential of erucic acid (CAS# 112-86-7) was determined according to OECD Guideline 405 under GLP (Sterzel and Pittermann, 1992). The undiluted test substance was instilled into the right eye of three Himalayan rabbits, while the untreated eye of each animal served as control. The test substance was washed out 24 h after application. Mild conjunctival redness was observed in one animal at the 1 h reading time point and disappeared completely within 24 h. No irritation effects of the two additional animals were noted at the 24, 48 and 72 h reading time points. Therefore, erucic acid is not considered as eye irritant.

 

In conclusion, palmitic acid, oleic acid and erucic acid are not irritating to the eye based on the available animal data. By means of read-across based on similar structural and toxicological properties of fatty acids, soybean oil, conjugated, palmitic acid, oleic acid and erucic acid, the same result is expected for fatty acids, soybean oil, conjugated. Thus, fatty acids, soybean oil, conjugated is considered to be not irritating to eyes.

 

References:

Briggs, G.B. et al. (1976). Safety studies on a series of fatty acids. Am Ind Hyg Assoc J. 37(4):251-253. Testing laboratory: International Bio-Research, Miamiville, Ohio, USA.

Cragg, 2000. Aliphatic Catboxylic Acids, Unsaturated. E. Bingham, B. Cohrssen, C.H. Powell (ed.), Patty’s Toxicology.

Elder (1987) Final Report on the Safety Assessment of Oleic Acid, Lauric Acid, Palmitic Acid, Myristic Acid, and Stearic Acid, Journal of the American College of Toxicology, 6(3): 321-401.

Justification for selection of skin irritation / corrosion endpoint:
Hazard assessment is conducted by means of reas-across based on a category approach. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of eye irritation endpoint:
Hazard assessment is conducted by means of reas-across based on a category approach. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

By means of read-across based on a category approach, the available data on skin and eye irritation/corrosion does not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

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