Fatty acids, tallow, zinc salts

Endpoint summary

Additional information

Justification for Read-across

There are no data on toxicological information available for fatty acids, tallow, zinc salts (CAS No. 68440-34-0). In order to fulfil the standard information requirements set out in Annexes VII - IX, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances and from surrogate substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human and environmental toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity and common physiological active moieties.

Fatty acids, tallow, zinc salts consist of approximately 10% zinc and 90% natural fatty acids, mainly of saturated C16 and C18 fatty acids and monounsaturated C18 fatty acid.

In the case of Fatty acids, tallow, zinc salts, read-across to Fatty acids, zinc salts and to inorganic zinc salts and zinc metal (as listed below) was used. Justification for both approaches is given below.

Fatty acids, zinc salts

The target substances Fatty acids, tallow, zinc salts and the source substances Fatty acids, C16-18, zinc salts (CAS No. 91051-01-3), zinc distearate (CAS No. 557-05-1), zinc bis[12-hydroxystearate] (CAS No. 35674-68-1) and zinc dicaprylate (CAS No. 557-09-5) are substances with a zinc moiety and a fatty acid moiety. The zinc content is considered to be similar. The fatty acid moiety is considered not being hazardous to humans and the environment. Fatty acids are natural constituents of the human body and the environment and essential components of a balanced nutrition for humans and animals. Fatty acids are generally judged as not representing a risk to human health (except the irritating/corrosive properties of short-chain fatty acids and the environment. Variability in the poorly soluble fatty acid moiety is not expected to have a relevant influence on the physiological activity of fatty acid zinc salts and therefore, read-across to another fatty acid zinc salts is justified without restrictions.

Inorganic zinc salts

A basic assumption for read-across made in this hazard assessment and throughout this CSR is that the biological activities of Fatty acids, tallow, zinc salts are expected to be mainly determined by ionic zinc, in case of dissociation. Since water solubility is the main determinant of bioavailability, read-across to source substances with higher water solubility and thus higher bioavailability of the zinc cation can be considered as worst-case for the target substance fatty acids, tallow, zinc salts.

This read-across approach is in accordance with the read-across approach applied in the course of the EU Risk assessments within the framework of EU Existing Chemicals Regulation (EEC) No 793/93 on substances zinc metal (CAS No. 7440-66-6), zinc oxide (CAS No. 1314-13-2), zinc chloride (CAS No. 7646-85-7), zinc sulphate (CAS No. 7733-02-0), trizinc bis(orthophosphate) (CAS No. 7779-90-0) and the structural analogue to Fatty acids, tallow, zinc salts being zinc distearate (CAS No. 557-05-1 / 91051-01-3).

For a comprehensive overview of the environmental fate properties and environmental and toxicological information of “Zinc” see the Chemical Safety Assessment of "Zinc" within the framework of Regulation (EC) No 1907/2006 in the technical dossier (see IUCLID Section 13).

 

Overview of source and target chemicals including CAS No./EC No.

Chemical Name	CAS No. / EC No.
Target substance
Fatty acids, tallow, zinc salts	68440-34-6 / 270-451-8
Source substances
Fatty acids, C14-18 and C16-18 unsatd., zinc salts	67701-12-6 / 266-936-9
Fatty acids, C16-18 and C18 unsatd., zinc salts	67701-13-7 / 266-937-4
Fatty acids, C16-18, zinc salts	91051-01-3 / 293-049-4
Zinc distearate	557-05-1 / 209-151-9
Zinc bis[12-hydroxystearate]	35674-68-1 / 252-669-5
Zinc dicaprylate	557-09-5 / 209-156-6
Zinc diacetate	557-34-6 / 209-170-2
Zinc dichloride*	7646-85-7 / 231-592-0
Zinc sulfate*	7733-02-0 / 231-793-3
Zinc nitrate*	7779-88-6 / 231-943-8
Zinc oxide*	1314-13-2 / 215-22-5
Zinc*#	7440-66-6 / 231-175-3

*) Surrogate substances (inorganic zinc salts)

#) The acceptance of zinc as surrogate refers to the cases where the specified CAS No. is given as test substance identity in the technical dossier with no further data on specification. In most cases this is presumably an ionic form, Zn²⁺.

A detailed read-across justification is provided in the technical dossier (see IUCLID Section 13).

Toxicokinetics, metabolism and distribution

Zinc compounds release, depending on their solubility, zinc cations which determine the biological activity of the respective zinc compounds. The fatty acid moiety of fatty acids, tallow, zinc salts is considered not being hazardous to humans in regard to local and systemic effects. Fatty acids are natural constituents of the human body and essential components of a balanced human nutrition.

 

Fatty acids

Absorption

After oral ingestion, short-chain or unsaturated fatty acids are in general more readily absorbed than long-chain, saturated fatty acids. Among common fatty acids, stearic acid (C18:0) is the most poorly absorbed. Thus, the absorption of palmitic (16:0), stearic (18:0), oleic (18:1) and linoleic (18:2) acid from vegetable oils has been shown to be 75, 62, 92 and 94%, respectively, in studies with human infants (IOM, 2005).

Absorption via the gastrointestinal tract occurs by micellar solubilisation followed by transport via the lymphatic system and esterification with glycerol (CIR, 1987; IOM, 2005). In contrast to the rapid uptake of fatty acids via the oral exposure route, fatty acids are in general poorly absorbed through skin due to their physicochemical properties.

 

Distribution

Fatty acids are distributed in the organism to different tissues where they are incorporated into cell membranes, used as energy source or stored as triglycerides in adipose tissue depots (Masoro, 1977).

 

Metabolism

Fatty acids are stepwise degraded within the mitochondrium matrix by ß(-)Oxidation. The released C2 units are cleaved as acyl-CoA which subsequently enters the citric acid cycle (CIR, 1987).

 

Excretion

In general, fatty acids are entirely catabolised by oxidative processes resulting in carbon dioxide and water as the principal excretion products. Small amounts of ketone bodies arising from the oxidation of fatty acids are excreted via the urine (IOM, 2005).

  

Zinc

Sufficient data is available on the soluble zinc compounds zinc chloride and zinc sulphate and on the slightly soluble zinc compounds ZnO and ZnCO3.

Absorption

Zinc is an essential trace element which is regulated and maintained in the various tissues mainly by the gastrointestinal absorption and secretion during high and low dietary zinc intake and because of the limited exchange of zinc between tissues, a constant supply of zinc is required to sustain the physiological requirements. The zinc absorption process in the intestines includes both passive diffusion and a carrier-mediated process. The absorption can be influenced by several factors such as ligands in the diet and the zinc status. Persons with adequate nutritional levels absorb 20-30% and animals absorb 40-50%. Persons that are zinc deficient absorb more, while persons with excessive zinc intake absorb less.

For the soluble zinc compounds, the available information suggests an oral absorption value of 20%. This value can be considered as the lower bound range at adequate nutritional levels. The oral absorption of the slightly soluble zinc oxide has been shown to be 60% of that of the soluble zinc compounds. This corresponds to approximately 12-18%. No oral absorption information is available for the remaining slightly soluble and insoluble zinc compounds (i.e., Zn(OH)2, Zn3(PO4)2, ZnCO3, Zn, ZnS). However, considering that these substances have lower water solubility than ZnO, it can be conservatively assumed that the oral absorption of these compounds is = 12%.

Animal data suggests that there is pulmonary absorption following inhalation exposure. Half-life values of 14 and 6.3 hours were reported for dissolution of zinc oxide. The absorption of inhaled zinc depends on the particle size and the deposition of these particles therefore data was provided on the particle size distribution of zinc aerosol from three different industry sectors. The particle size distribution data was evaluated by using a multiple path particle deposition (MPPDep) model. This model revealed that for zinc aerosols the largest part of the deposition is in the head region and much less in the tracheobronchial and pulmonary region. Although most of the material deposited in the head and tracheobronchial region is rapidly translocated to the gastrointestinal tract, a part will also be absorbed locally.

Based on data for local absorption of radionuclides in the different airway regions, it can be assumed that the local absorption of the soluble zinc compounds will be approximately 20% of the material deposited in the head region, 50% of the material deposited in the tracheobronchial region and 100% of the material deposited in the pulmonary region. For the slightly soluble and insoluble zinc compounds a negligible absorption can be assumed for materials deposited in the head and the tracheobronchial region. 100% of the deposited slightly or insoluble zinc compounds are assumed to be absorbed in the pulmonary tract. The deposited material will be cleared via the lung clearance mechanisms into the gastrointestinal tract where it will follow oral absorption kinetics. Therefore the inhalation absorption for the soluble zinc compounds is a maximum of 40% and for the slightly soluble and insoluble zinc compounds inhalation absorption is at a maximum of 20%. These values can be assumed as a reasonable worst case, because they are considered to cover existing differences between the different zinc industry sectors with respect to the type of exercise activities (and thus breathing rate) and particle size distribution.

The available information from in vivo as well as the in vitro studies suggests the dermal absorption of zinc compounds through intact skin to be less than 2%. In vitro studies that estimated dermal absorption values only on the basis of the zinc levels in the receptor medium without taking into account the zinc present in the stratum corneum appear to underestimate absorption values derived from in vivo studies. Such zinc trapped in the skin layers may become systemically available at a later stage. Quantitative data to evaluate the relevance of this skin depot are however lacking. Given the efficient homeostatic mechanisms of mammals to maintain the total body zinc and the physiologically required levels of zinc in the various tissues to be constant, the anticipated slow release of zinc from the skin is not expected to disturb the homeostatic zinc balance of the body. Considering the available information on dermal absorption, the default for dermal absorption of all zinc compounds (solutions or suspensions) is 2%. Based on the physical appearance, for dust exposure to zinc and zinc compounds a 10-fold lower default value of 0.2% is a reasonable assumption.

 

Distribution

Zinc appears to be distributed to all tissues and tissue fluids and it is a cofactor in more than 200 enzyme systems.

 

Metabolism

As described in EU RARs, zinc is primarily bound to organic ligands rather than existing free in solution as a cation (Gordon et al., 1981). It is found in diffusible and non-diffusible forms in the blood. About 66% of the diffusible form of zinc in the plasma is freely exchangeable and loosely bound to albumin (Cousins et al., 1985). A small amount of the non-diffusible form of zinc is tightly bound to a₂-macroglobulin in the plasma and is not freely exchangeable with other zinc ligands. Zinc is incorporated into and dissociated from a₂-macroglobulin only in the liver (Henkin et al., 1974).

 

Excretion

The excretion of zinc is primarily via faeces, but also via urine, saliva, hair loss, sweat and mothers-milk.

 

 

References

CIR (1987) Final report on the safety assessment of oleic acid, lauric acid, palmitic acid, myristic acid, stearic acid.J. of the Am.Coll. of Toxicol.6(3):321-401.

Cousins RJ (1985). Absorption, transport, and hepatic metabolism of copper and zinc, special reference to metallothionein and ceruplasmin. Physiol. Rev. 65, 238-309. [Cited from ATSDR, 1994].

Gordon EF, Gordon RC and Passal DB (1981). Zinc metabolism: Basic, clinical, and behavioral aspects. J. Pediatr. 99, 341-349.

Henkin RI (1974). Metal-albumin, amino acid interactions: Chemical and physiological interrelationships. In: Chemical and Physiological Inter Relationships in Protein-Metal Interactions Friedman M (ed.). Plenum Press, New York, NY, 299-328.

Institute of of the National Academies (IOM) (2005). Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). The National Academies Press. http://www.nap.edu/openbook.php?record_id=10490&page=R1

Masoro, E.J. (1977) Lipids and lipid metabolism. Ann. Rev. Physiol.39: 301-321.