Registration Dossier

Administrative data

Description of key information

No acute toxicity studies with fatty acids, tall-oil, manganese salts are available, thus the acute toxicity will be addressed with existing data on the assessment entities manganese and tallate.

Signs of acute oral or acute dermal toxicity are not expected for fatty acids, tall-oil, manganese salts, since the two assessment entities manganese and tallate do not show signs of acute oral or acute dermal toxicity in experimental testing (both LD50 > 2000mg/kg).

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Manganese

Acute toxicity: oral

Acute toxicity was determined in male and female Wistar rats. The LD50 -value was 2150 mg/kg, which was the highest dose tested. Three supporting studies were identified which studied the acute oral toxicity in rats and mice. The LD50 -values determined in these studies were > 2000 mg/kg.

 

Acute toxicity: dermal

Classification for the acute dermal toxicity is not considered necessary as the substance is not classified for acute oral toxicity and absorption through the skin is likely to be less than oral.

 

 

Tallate

Acute oral:

According to Regulation (EC) No 1907/2006 Annex V substances obtained from natural sources and not modified such as vegetable fats and oils as well as fatty acids from C6 to C24 and their potassium, sodium, calcium and magnesium salts are excluded from the obligation to register.

 

The substance subjected to registration is a mixture of different saturated and unsaturated C16 -C18 fatty acids. Based on this, the following endpoint is covered by publicly available data on fatty acids with the same or similar structure.

 

According to the HERA document on fatty acid salts “the available data for fatty acids provide a clear picture of low acute toxicity for this class of chemicals. All oral LD50values were greater than 2,000 mg/kg, with little mortality being observed even at the highest doses tested in the studies (IUCLID, 2000c, 2000e, 2000f, 2000g; Clayton & Clayton, 1982; CIR, 1987). The available data for the fatty acid salts also indicate that these are of low acute toxicity. For example, an acute oral LD50value of >5,000 mg/kg (highest dose tested) has been reported for sodium soap. This test was done according to GLP and OECD Guideline 401 (IUCLID, 2000f), while in another study also done to GLP and according to Directive 84/449/EEC, B.1, an LD50value of >2,000 mg/kg (highest dose tested) was reported for fatty acids, C16-18 and C18-unstad., sodium salts (IUCLID, 2000f)” (HERA, 2002).

“In an OECD TG 401 study, a group of five rats/sex was administered octadecanoic acid (as a 50% suspension in DMSO) at a dose of 5000 mg/kg bw. There was one death. Animals exhibited transient piloerection, excessive salivation, and diminished activity. At necropsy, the male animal that died exhibited a stomach full of test substance; surviving animals showed remnants of test substance in the stomach with swelling of the mucous membrane. The LD50 was > 5000 mg/kg bw” (OECD SIDS, 2014).

“International-BioResearch (1974, as referred to by CIR, 1987) determined the acute oral toxicity in groups of five male albino rats. Animals were administered by gavage lauric-, myristic-, palmitic- or stearic acid with increasing doses of up to 10,000 mg/kg bw and oleic acid up to 20,000 mg/kg bw. It was observed that for all these fatty acids the LD50value was above the maximum level tested. No mortality was observed in five albino rats gavaged with 5 g/kg bw oleic acid (commercially supplied); clinical signs were not reported during the 7-day post-exposure period (CTFA, 1978, as referred to in CIR, 1987)” (EFSA NDA Panel, 2017).

“Any toxic effects, such as excessive salivation, diarrhoea, central nervous system depression, loss of reflex actions or coma, shown at higher doses, decrease in severity with an increase in the chain length of the fatty acid (Pi-Sunyer et al., 1969). These reported effects are a result of the high doses administered and the fact that unlike humans rats don’t have a vomiting reflex. Therefore, these high dose effects are not considered relevant for human exposure” (HERA, 2002).

 

Acute dermal:

According to Regulation (EC) No 1907/2006 Annex V substances obtained from natural sources and not modified such as vegetable fats and oils as well as fatty acids from C6 to C24 and their potassium, sodium, calcium and magnesium salts are excluded from the obligation to register.

The substance subjected to registration is a mixture of different saturated and unsaturated C16 -C18 fatty acids. Based on this, the following endpoint is covered by publicly available data on fatty acids with the same or similar structure.

The HERA document on fatty acids salts concluded that “the available acute dermal toxicity data for the fatty acids (and their salts) provide a clear picture of low acute toxicity for this group of chemicals. All dermal LD50values were greater than >2,000 mg/kg (BIBRA, 1996; IUCLID, 2000e; Clayton & Clayton, 1982; CIR, 1982, 1987). In a dermal study in which concentrations of sodium stearate (C18) ranged between 10-25% in a 20% bath soap detergent form, the LD50was >3000 mg/kg (highest dose tested) (CIR, 1982). In a dermal study in guinea pigs, application of commercial grade oleic acid (3,000 mg/kg) produced no deaths and no signs of toxicity. The number of applications was not stated (CIR, 1987)” (HERA, 2002).

Acute toxicity of an abundantly available essential nutrient for animals and humans such as stearic acid would be grossly implausible and can therefore safely be excluded. Classification is not warranted.

 

Fatty acids, tall-oil, manganese salts

Signs of acute oral or acute dermal toxicity are not expected for fatty acids, tall-oil, manganese salts, since the two moieties manganese and fatty acids, tall-oil have not shown signs of acute oral toxicity in experimental testing (both LD50 > 2000mg/kg). Under the assumption that the moieties of fatty acids, tall-oil, manganese salts show their toxicological profile individually upon dissolution, the acute oral (systemic) toxicity of fatty acids, tall-oil, manganese salts can be calculated using the equation given in regulation (EC) 1272/2008, Annex I, Section 3.1.3.6.1.

Acute dermal toxicity is not expected to occur with fatty acids, tall-oil, manganese salts due to its poor percutaneous absorption and the lack of systemic acute toxicity as obtained in acute oral toxicity studies:

In the absence of measured data on dermal absorption, current guidance suggests the assignment of either 10 % or 100 % default dermal absorption rates. In contrast, the currently available scientific evidence on dermal absorption of metals yields substantially lower figures, which can be summarised briefly as follows:

Measured dermal absorption values for metals or metal compounds in studies corresponding to the most recent OECD test guidelines are typically 1 % or even less. Therefore, the use of a 10 % default absorption factor is not scientifically supported for metals. This is corroborated by conclusions from previous EU risk assessments (Ni, Cd, Zn) and current metal risk assessments under REACH, which have derived dermal absorption rates of 2 % or far less (but with considerable methodical deviations from existing OECD methods) from liquid media.

However, considering that under industrial circumstances many applications involve handling of dry powders, substances and materials, and since dissolution is a key prerequisite for any percutaneous absorption, a factor 10 lower default absorption factor may be assigned to such “dry” scenarios where handling of the product does not entail use of aqueous or other liquid media. This approach was taken in the in the EU RA on zinc. A reasoning for this is described in detail elsewhere (Cherrie and Robertson, 1995), based on the argument that dermal uptake is dependent on the concentration of the material on the skin surface rather than it’s mass.

The following default dermal absorption factors for metal cations are therefore proposed (reflective of full-shift exposure, i.e. 8 hours):

From exposure to liquid/wet media: 1.0 %

From dry (dust) exposure: 0.1 %

This approach is consistent with the methodology proposed in HERAG guidance for metals (HERAG fact sheet - assessment of occupational dermal exposure and dermal absorption for metals and inorganic metal compounds; EBRC Consulting GmbH / Hannover /Germany; August 2007).

A study for acute toxicity via inhalation was not conducted with fatty acids, tall-oil, manganese salts, since it is produced and placed on the market in a form in which no inhalation hazard is anticipated, thus acute toxic effects are not likely to occur during manufacture and handling of that substance. For further information on the toxicity of the individual moieties, please refer to the relevant sections in the IUCLID and CSR.

 

The calculated oral LD50 for fatty acids, tall-oil, manganese salts is > 2000mg/kg, hence the substance is not to be classified according to regulation (EC) 1272/2008 for acute oral and dermal toxicity as well as for specific target organ toxicity, single exposure (STOT SE).

 

Justification for classification or non-classification

Based on in vivo oral LD50 data on the moieties, acute toxicity estimates for fatty acids, tall-oil, manganese salts have been calculated resulting in LD50 values > 2000 mg/kg bw.

According to the criteria of REGULATION (EC) No 1272/2008 and its subsequent adaptions, fatty acids, tall-oil, manganese salts does neither have to be classified and has no obligatory labelling requirement for acute oral or dermal toxicity nor for specific target organ toxicity after single exposure (STOT SE).