9-Octadecenoic acid (Z)-, zinc salt, basic

Endpoint summary

Description of key information

Minimal absorption via oral, dermal or inhalation routes of exposure is expected based on the experimental data and the physico-chemical properties of the substance. Distribution will be through blood to tissues and organs although absorption will be minimal. No significant level of metabolism is expected and the substance is expected to be excreted unchanged in the dissociated form in the faeces. The substance will not bioaccumulate.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

The toxicokinetic profile of the test material was predicted using the physical chemical properties of the substance, the data obtained from acute and repeated-dose toxicity studies, as well as information gained from genotoxicity assays.

 

Physico-chemical properties

 

The test item is a UVCB with a waxy solid form and the molecular weight of the most abundant basic structure is 1972 g/moL. However, in an acidic environment the substance converts to the neutral salt with a MW of 630 g/moL. The substance is poorly water soluble (8.48 x 10E-04 g/L) and has a low vapour pressure of 1.0 x 10E-03 Pa at 25 °C. The substance dissociates in aqueous media to give zinc-containing constituents that are not expected to bioaccumulate on the grounds of molecular weight (> 5000 to 2034 g/moL). The dissociated organic acid constituent of the UVCB (molecular weight 282.46) has a very high estimated octanol/water partition coefficient, Log Pow of 7.73 (which is > 4, the bioaccumulation limit).

Absorption

Oral Route

The physico-chemical properties described above indicate that the test material has a molecular size (molecular weight significantly >500) greater than that which may be expected to be easily absorbed within the mammalian gastrointestinal tract, should that material be ingested. The substance has a low water solubility and is highly lipophilic whilst the dissociated acid has a Log Pow of 7.73, hence the substance may be expected not to cross gastrointestinal epithelial barriers, and the high molecular weight may also significantly restrict absorption. The test item may participate in micellar transport into the hepatic portal system along with other lipophilic substances (e.g., dietary fats). However, an acute oral gavage toxicity study identified no evidence of toxicity (LD50 >5000 mg/kg bw) and a combined repeat dose and reproduction screening toxicology study using the oral route gave a NOAEL of 1000 mg/kg bw/day. The lack of adverse findings following oral dosing may be due to limited gastrointestinal absorption of the test material after dosing, or a very low index of inherent toxicity for this substance, and/or its metabolite(s).

Dermal Route

Regarding the dermal absorption of the UVCB substance, its rate of uptake into the stratum corneum and its rate of transfer between the stratum corneum and the epidermis are likely to be slow considering both the high molecular weight (>500 g/moL) of most components and the Log Pow of 7.73 for the free acid . Moreover, it is assumed that the dermal uptake of the test item is also limited based on its low water solubility (8.48 x 10E-04 g/L) [References 1,2]. These assumptions were supported by the absence of observed systemic effects following dermal application of test material in an acute toxicity study at up to 2000 mg/kg bw and the absence of irritant effects to the skin.

Inhalation Route

The potential for inhalation toxicity was not studied directly in a toxicology study using the inhalation route. However, the low vapour pressure of the substance (1.0 x 10E-03 Pa) indicates a very low propensity to enter atmospheric air in a respirable form. Thus, respiratory absorption under normal use and handling of this material is expected to be inconsequential. The substance is used as a component in lubricant additives, lubricants and greases, and as a consequence there is little potential for exposure via the production of aerosols. In any case, absorption across the respiratory epithelium is likely to be low, because of the physicochemical properties discussed previously.

Distribution

Systemic distribution of the test item can be predicted from the physico-chemical properties of this substance. The high Log Pow and poor water solubility suggests that this substance, upon systemic absorption, may be transported through the circulatory system in association with a carrier molecule such as a lipoprotein or other macromolecule. The lipophilic character but high Log Pow of 7.73 of the dissociated acid plus high molecular weight of other components suggests that a major proportion of the substance will not readily traverse cellular barriers or distribute into fatty tissues. There is no evidence of systemic toxicity and/or histopathological changes from the repeated dose study, indicative of cumulative toxicity, as may be manifested by an accumulation of test item or metabolites in tissues.

Metabolism

Acute and repeated-dose toxicity testing provided no evidence that the UVCB substance was metabolised into toxic metabolites. Data from a bacterial mutagenicity test, a mammalian cell gene mutation assay and a chromosomal aberration in mammalian cells, in which the test item was subjected to rat hepatic microsomal enzyme systems, did not show any evidence of genotoxic activity from the substance or from any potential metabolites. Furthermore, the in vitro toxicity of the substance to mammalian cells was equivalent in the presence and absence of metabolic enzymes. This may be taken to indicate the absence of any significant level of metabolism.

Excretion

 

The substance is not expected to be absorbed to any significant degree and there is no evidence of metabolism by metabolic activation systems in vitro. Consequently, the substance is expected to be excreted unchanged as the dissociated form in the faeces with perhaps trace amounts in the urine.

References

 

[1] Derivation of assessment factors for human health risk assessment. ECETOC Technical Repot No. 86. ISBN-0773-6347-86, Brussels, February 2003, page 13, paragraph 1.

 

[2] Guidance document on dermal absorption. European Commission Sanco/222/2000 rev. 7. Page 7, paragraph 2.