Fatty acids, soya, conjugated

Endpoint summary

Description of key information

Oral (OECD 401), rat: LD50 > 5000 mg/kg bw; CAS# 57-10-3, C16 (Gloxhuber and Kästner, 1981)
Oral (OECD 401), rat: LD50 > 2000 mg/kg bw; CAS# 112-80-1, C18:1 (Reijnders and Daamen, 1988)
Oral (OECD 401), rat: LD50 > 5000 mg/kg bw; CAS# 112-80-1, C18:1 (Gloxhuber and Kästner, 1981)
Oral (EU method B.1), rat: LD50 > 5000 mg/kg bw; CAS# 112-80-1, C18:1 (Potokar, 1984)
Inhalation, IRT, rat, 8h: LC50 > 1.3682 mg/L air; CAS# 142-62-1, C6 (Smyth et al., 1954)
Dermal (OECD 402, limit test), rat: LD50 > 2000 mg/kg bw ; CAS# 112-05-0, C9 (van Otterdijk, 2001)
Dermal (OECD 402, limit test), rat: LD50 > 2000 mg/kg bw; CAS# 111-20-6, C10d (Yu, 1999)
Dermal (OECD 402, limit test), rat: LD50 > 2000 mg/kg bw; CAS# 334-48-5, C10 (TalviOja, 2006)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2 due to read-across) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common functional group, common precursors/breakdown products and similarities in acute toxicity properties. Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2 due to read-across) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common functional group, common precursors/breakdown products and similarities in acute toxicity properties. Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Oral

No data on acute oral toxicity are available for fatty acids, soybean oil, conjugated.Therefore, acute oral toxicity is 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, studies with the constituents C16 fatty acid (palmitic acid) and C18:1 fatty acid (oleic acid) are used for hazard assessment.

 

Acute oral toxicity of palmitic acid (CAS# 57-10-3) was evaluated in a limit test performed according to OECD Guideline 401, in which 5 male and 5 female Wistar rats received an oral application of 5000 mg/kg bw palmitic acid in DMSO (Gloxhuber and Kästner, 1981). Clinical signs appeared approximately 20 minutes after dosing including slightly diminished activity and ruffled fur, which completely subsided within 24 hours after dosing. While one female died on day 12 after dosing, all males survived the 14 day observation period. Pathological examination revealed a swelling of the gastric mucosa. Based on the results, the LD50 for palmitic acid was found to be > 5000 mg/kg bw.

An oral LD50 > 10000 mg/kg bw in rats was reported for palmitic acid by Briggs et al. (1976).

 

The acute toxicity via the oral route of oleic acid (CAS# 112-80-1) has been investigated in rats in three studies.

In a limit test performed according to GLP and OECD Guideline 401 5 male and 5 female Wistar rats received a single oral application of 2000 mg/kg bw oleic acid (Reijnders and Daamen, 1988). Since no mortality was noted during the 14-day observation period, the LD50 was set as > 2000 mg/kg bw. No signs of systemic toxicity were noted and macroscopic examination of animals at termination did not reveal any abnormalities that were considered to be treatment-related.

A LD50 of > 5000 mg/kg bw for oleic acid was found in another limit test performed according to GLP and OECD Guideline 401 (Gloxhuber and Kästner, 1981). The test substance was applied via gavage to groups of 5 male and 5 female Wistar rats. All animals survived the 14-day observation period. No clinical signs and no abnormal findings were observed at the macroscopic examination.

A further acute oral toxicity test with oleic acid was performed in accordance with EU method B.1 and under GLP conditions (Potokar, 1984). 5 male and 5 female Wistar rats received a single oral application of 5000 mg/kg bw oleic acid. Except for ruffled fur within 10 min to 1 hour after dosing, no further symptoms were noted. The body weights were not affected by treatment and gross pathology did not reveal any treatment-related findings. Based on these results a LD50 of > 5000 mg/kg bw was established for oleic acid.

In summary, the oral LD50 value for oleic acid is > 2000 mg/kg bw.

 

In general, all available studies studying the acute oral toxicity of fatty acids category members resulted in LD50 values > 2000 mg/kg bw, indicating no hazard for acute oral toxicity.

 

Due to the similar structural and toxicological properties of the members within the category including fatty acids, soybean oil, conjugated and two of its main constituents, in particular palmitic acid and oleic acid, the LD50 for fatty acids, soybean oil, conjugated is considered to be > 2000 mg/kg bw.

Inhalation

Only very limited data on acute inhalative toxicity of fatty acids is available. The only available data on acute inhalation toxicity of fatty acids are data of a published inhalation risk test with C6 fatty acid (hexanoic acid). Hexanoic acid (CAS# 142-62-1) has the highest vapour pressure among the members of the fatty acids category. No mortality of rats was reported after an 8-hour exposure to a saturated atmosphere which corresponds to a value of >1.3682 mg hexanoic acid/L air based on QSAR calculation (Danish EPA Database, 2004). However, due to limited information this study is regarded insufficient for assessment.

In general, inhalation of fatty acids as vapour is not expected due to the low vapour pressure of ≤ 0.06 hPa. In addition, exposure to particles of inhalable size can be excluded under normal conditions of use. In case of respiratory uptake long chain fatty acids (>C12) will not cause adverse local or systemic effects but will be absorbed in the lungs and undergo normal metabolism. The likelihood of persistence in the lungs is considered non-existent.

Therefore testing is not justified for the inhalation route in accordance EC 1907/2006, Annex VIII, Column 2, Section 8.5 and due to animal welfare reasons. Data for the most relevant routes of human exposure (oral and dermal route) are provided for fatty acids.

Dermal

No data on acute dermal toxicity is available for fatty acids, soybean oil, conjugated. Therefore acute dermal health 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.

A general prerequisite for systemic toxicity after dermal application is the permeability of the skin for the applied substance. Although the dermal penetration of fatty acids is very variable, in general they do not have significant systemic bioavailability (for details see discussion on toxicokinetics).

Thus, no acute dermal toxicity by fatty acids is expected as it could be demonstrated by a LD50 value of > 2000 mg/kg bw for C9 fatty acid nonanoic acid, C10 fatty acid (decanoic acid) and C10 dicarboxylic fatty acid (sebacic acid).

The acute dermal toxicity of nonanoic acid (CAS# 112-05-1) was examined in Wistar rats according to OECD Guideline 402 and under GLP conditions (van Otterdijk, 2001). The animals were treated with an occlusive patch for 24 hours. All animals survived the 14-day observation period following the application of 2000 mg/kg bw. Clinical signs of toxicity were hunched posture on the treatment day and the following three days. Skin reactions due to the corrosive properties of nonanoic acid were noted in all treated animals and consisted of general erythema, scales and scabs of the treated skin, generally of slight to moderate grade. In 6 of 10 animals, skin reactions persisted until the end of the observation period on day 15. Body weights were not affected, and there were no abnormalities at necropsy after sacrifice on day 15.

After the semiocclusive application of sebacic acid (CAS# 111-20-6) on the skin of Sprague-Dawley rats for 24 hours according to OECD Guideline 402 and under GLP condition, a LD50 of >2000 mg/kg bw was observed (Yu, 1999). No mortality occurred during the 14-day observation period and no clinical signs or body weight abnormalities were noted till the end of the study. Additionally, no macroscopic findings were evident.

The acute dermal toxicity of decanoic acid (CAS# 334-48-5) was investigated in a limit test according to OECD guideline 402 and in compliance with GLP (TalviOja, 2006). In this study, 5 male and 5 female HanRCC: WIST rats were treated with the test substance at a dose of 2000 mg/kg bw. The test substance was dissolved in polyethylene glycol at a concentration of 250 mg/mL and applied onto the clipped skin of the test animals (8 mL/kg bw) for 24 h under semiocclusive conditions. After exposure, residual test substance was removed and animals were observed for a period of 14 days. No deaths occurred and the body weight of all animals was within the normal range except of one female rat which lost 2.3% of body weight during the first week after treatment. This female rat showed recovery during the last week of observation. 4/5 males and 3/5 females were found slightly or moderately sedated on day 2 of the study after patch removal. Furthermore, at this time point 3 males and 2 females showed deep respiration and 3 males and 1 female revealed hunched posture. From day 3 on no further clinical signs were recorded in any of the treated rats. After removal of the dressing, slight to moderate erythema was noted in all animals. The local effects developed into slight to moderate scaling in all animals and slight scabs were observed in all animals except one female. Scaling and/or scabs were reversible within day 5 and 13 in the animals. At necropsy, no findings were noted. Therefore, the LD50 in male and female rats is > 2000 mg/kg bw.

The dermal absorption of C9 fatty acid (nonanoic acid) with 0.014 mg/cm², of C10 fatty acid (decanoic acid) with 0.009 mg/cm² and of C10 dicarboxylic fatty acid (sebacic acid) with 0.01 mg/cm² is greater compared to fatty acids with longer chain lengths (e.g. C12 fatty acid: 0.005 mg/cm², C22 fatty acid: 0.00005 mg/cm² or C18:1 fatty acid: 0.00033 mg/cm²) and can therefore be considered as “worst case assumption” for acute dermal absorption and consequently for the toxicity of fatty acids.

 

This is being supported by Opdyke et al. (1978, 1979 and 1981 as cited in Cragg, 2001), who reported in a short summary, that the acute dermal LD50 in rabbits for octanoic acid (CAS# 124-07-2), nonanoic acid (CAS# 112-05-0), decanoic acid (CAS# 334-48-5) and stearic acid (CAS# 57-11-4) exceeded 5000 mg/kg bw. In addition, the topical application of commercial grade oleic acid to the skin of guinea pigs at a concentration of 3000 mg/kg bw produced no deaths (CIR, 1987).

In conclusion, based on available data on various representative substances within the fatty acids category, no acute dermal toxicity for members of the fatty acids category are expected.

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, S.T. 2001. Aliphatic Carboxylic Acids, Saturated. Patty’s Toxicology

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

QSAR; Danish EPA Database, 2004: http://130.226.165.14/

Justification for selection of acute toxicity – oral endpoint
Hazard assessment is conducted by means of read-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 acute toxicity – inhalation endpoint
No study required since exposure of humans via inhalation is unlikely taking into account the physico-chemical properties of the substance and the lack of exposure to particles of inhalable size under normal conditions of use. Moreover, in case of respiratory uptake long chain fatty acids (>C12) will not cause adverse local or systemic effects but will be absorbed in the lungs and undergo normal metabolism. The likelihood of persistence in the lungs is considered non-existent.
There is one study (inhalation risk test) available, in which no mortality occurred after an 8-hour exposure to a saturated atmosphere with the reference substance hexanoic acid. However, this study alone is regarded insufficient for assessment (Klimisch score 4).

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of read-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

Based on available data on acute oral and dermal toxicity, fatty acids do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC.

No information on acute inhalation toxicity is available.