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Description of key information

Acute toxicity:
- oral: LD50 >5000 mg/kg bw (OECD 401; Analogy CAS CAS 57-10-3, CAS 57-11-4);
- inhalative: LC50 >0.1521 mg/L (IHT; Analogy CAS 124-07-2);
- dermal: LD50 > 2000 mg/kg bw (Analogy CAS 57-11-4);

Key value for chemical safety assessment

Additional information

Oral

Due to the lack of reliable data with bw fatty acids (hydrogenated tallow, distn. residues) on acute oral toxicity, studies with two of the main constituents, C16 fatty acid (palmitic acid) and C18 fatty acid (stearic acid), are used for hazard assessment. Since fatty acids (hydrogenated tallow, distn. residues), palmitic acid, and stearic acid belong to the same category based on similar structural and toxicological properties, this approach can be regarded as scientifically justified. Thus, read-across is performed based on a category approach (for details refer to IUCLID chapter 13).

 

Acute oral toxicity of palmitic acid was evaluated in a study performed according to OECD guideline 401, where in a limit test five male and five female Wistar rats received an oral application of 10 mL of 5000 mg/kg bw palmitic acid in DMSO (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.

Acute oral toxicity of stearic acid was evaluated in a study performed in accordance to OECD guideline 401, where in a limit test five male and five female Wistar rats received 10 mL/kg bw stearic acid in DMSO at concentration of 5000 mg/kg bw by gavage (Kästner, 1981). Clinical signs including ruffled fur, strong salivation and much diminished activity appeared approximately 20 minutes after dosing, but subsided within 24 hours after dosing. Since only one male died on day 13 after dosing, the LD50 for stearic acid was found to be >5000 mg/kg bw.

 

Due to the similar structural and toxicological properties of the members within the category including fatty acids (hydrogenated tallow, distn. residues) and two of its main constituents palmitic acid and stearic acid, the LD50 for bw fatty acids (hydrogenated tallow, distn. residues) can be set as >5000 mg/kg bw.

 

Inhalation

Inhalation of fatty acids as vapour is not expected due to the low vapour pressure of < 1 mmHg. Therefore, only very limited data on acute inhalative toxicity of fatty acids is available.

However, the identified uses include spraying tasks where exposure to an aerosol of fatty acids can occur like use in cleaning agents.  

The only available data on acute inhalation toxicity of fatty acids are data of a published inhalation risk test with C8 fatty acid (octanoic acid; Smyth, 1962). No mortality of rats was reported after a 4-hour exposure to a saturated atmosphere which corresponds to a value of >0.1521 mg/L air based on QSAR calculation (Danish EPA Database, 2004).

Although not reported in this study, respiratory irritation/corrosion as primary effect is expected for fatty acids with a chain length ≤C12 due to the corrosive/irritation properties of the short- and mid-chain fatty acids C6 – C12, respectively.

In more detail, C8 fatty acids show corrosive properties to the skin at concentrations >70%. C9 fatty acid (at a concentration of >50%) and C10 fatty acid is irritating to skin and eyes, respectively. C12 fatty acid is not irritating to skin but is found to be irritating to eyes when applied with a concentration >70%.

Members of the category with a chain length >C12 are only causing negligible effects when applied to the skin or eyes. Their respiratory uptake would therefore not lead to irritation, but they would be included in the pulmonary surfactant of the respiratory tract which is mainly composed of large portions of phospholipids based on long chain fatty acids.

Since in industrial and professional applications inhalation exposure is controlled by ventilation systems, personal protective equipment, and measuring devices, the inhalation exposure can be considered to be sufficiently controlled.

Thus, it can be concluded that acute inhalation of fatty acids can cause irritation of the respiratory tract leading to classification and therefore no further testing shall be performed due to animal welfare reasons.

 

Dermal

Limited data is available on acute dermal toxicity of fatty acids since C8 fatty acid show corrosive properties at concentrations >70%, C9 (at a concentration of >50%) and C10 fatty acids are irritating to skin, respectively. The consequence after dermal application of these substances would therefore be irritation/corrosion as the primary effect. All other members of the category with longer chain length are only causing negligible effects when applied to the skin.

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 IUCLID chapter 7.1).

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 C18 fatty acid (stearic acid) found in a in limit test performed according to internal company standards (Jones, 1979). Three male and three female New Zealand White rabbits received a dermal application of 2000 mg/kg bw stearic acid to 25% of the total body surface under occlusion for 24 hours. As result, slight diarrhoea was noted in one female animal on day 3 after treatment. All other animals appeared normal throughout the observation period. Laboured breathing on day 6 was noted in one male, which died the next day. Although the pathological examination revealed severe consolidation of the lungs, this finding was not considered to be substance related. Irritating effects were noted on the skin of all animals which were described as ranging from slight to severe. Four animals showed slight and moderate desquamation. Slight oedema and eschar formation were also noted in some animals during the first week of observation. However, these observed effects can be attributed to the severe conditions used for application which are not in line with current guidelines. However, a LD50 of >2000 mg/kg bw was found for stearic acid.

Although the dermal absorption of C18 fatty acid6 (stearic acid) with 0.00026 mg/cm2is lower compared to fatty acids with shorter chain lengths (e.g. C12 fatty acid: 0.005 mg/cm2), even single or repeated oral uptake of C12 fatty acid does not lead to systemic effects due to the physiological function within the body.

Moreover, dermal exposure can be considered to be sufficiently controlled in industrial and professional applications since the employees are wearing gloves and protective clothing. Thus, no acute dermal toxicity by fatty acids is expected and no further testing shall be performed due to animal welfare reasons.

Justification for classification or non-classification

According to DSD (67/548/EEC) or CLP (1272/2008/EC) classification criteria for acute toxicity, fatty acids (hydrogenated tallow, distn. residues) do not fulfill the criteria for classification and thus a non-classification is warranted for this endpoint.