Reaction Product of Rosin, fumarated, Tall-Oil Rosin, Ca(OH)2 and MgO

Endpoint summary

Additional information

According to the REACH guidance document "Guidance on information requirements and chemical safety assessment, Chapter R.6: QSARs and grouping of chemicals", "A chemical category is a group of chemicals whose physico-chemical and human health and/or environmental toxicological properties and/or environmental fate properties are likely to be similar or follow a regular pattern as a result of structural similarity (or other similarity characteristic)". 

 

Rosins and rosin derivatives are candidates for the category approach as they are a family of UVCB substances that share a common precursor background prior to modification. This group consists of gum rosin, wood rosin and tall oil rosin comprising the "rosins" part of family, with hydrogenated rosin and polymerized rosin (also known as dimerized rosin or rosin oligomers) composing the rosin derivatives part. Gum, wood and tall oil rosin have been recognized as equivalent substances for decades by regulatory agencies world-wide, and wood and gum rosin share the same CAS #. While the method of production is different, the chemical composition of these UVCB is roughly equivalent. In fact, rosins display more variability based on the country of origin than by the method of production. As the basic chemical composition, physical/chemical properties and mammalian/ecotoxicity of the three rosins is very similar, the use of read-across between them is justified. 

 

Read-across of rosin derivatives to the rosins is also justified for similar reasons. Hydrogenated rosin is identical to the parent rosin except that the olefinic bonds have been reduced to aliphatic ones. The elimination of the olefinic character in the rosin acids reduces the reactivity of the molecules and greatly decreases the succeptibility to oxidation, and the formation of side-products. Thus, rosins can be considered a worst-case from a toxicological point of view for their hydrogenated counterparts. Polymerized rosin primarily consists of rosin acid dimers with a small trimer content. It is not possible to make molecules greater than trimers. Due to the steric hindrance of these molecules, they also have reduced reactivity compared to rosins, and their greater molecular weight would suggest decreased absorption from the gut or across the skin. Thus, rosins could also be considered to be a worst-case for their monomeric counterparts.

 

Therefore, when viewed in light of the guidance, it is clear that the formation of a category for rosins and rosin derivatives is valid under the REACH guidance.

 

Rosin (a UVCB) reacts with maleic anhydride (or maleic acid) and fumaric acid to form adducts. The initial reaction is a Diels-Alder reaction. Irrespective of starting material the eventual product is maleopimaric acid anhydride (an acid anhydride often referred to as maleopimaric acid. The reaction with fumaric acid is slower than that with maleic anhydride and the conversion from fumaropimaric acid to the maleopimaric acid anhydride is thought to be partial. Thus maleated rosin and fumarated rosin are treated as separate, but related substances and are considered sufficiently similar to allow ‘read across’ from one to the other. This category justification was considered acceptable by the US Environment Protection Agency their High Production Volume Challenge Program. The inclusion of adducts of hydrogenated rosin and formaldehyde treated rosin and the salts of adducts formed from rosin, hydrogenated rosin and formaldehyde treated rosin in this family is based on the grouping used for the rosin and rosin salts category.

TOXICOKINETICS OF ROSIN ADDUCTS

The toxicokinetics requirement for REACH is a toxicokinetics assessment, based on available information. This uses all available information, both from studies on analogues and the test substance, and includes physicochemical data as well as data from animal toxicity tests studies and any data that may be available the human health.

The ECHA Guidance is too sophisticated for use with the available data for rosin and chemically modified rosins. It assumes the availability of information not present when dealing with chemically modified rosins. The older guidance in the Technical Guidance Document (TGD) on risk assessment in support of Commission Directive 93/67/EEC on risk assessment for notified substances, Commission Regulation (EC No 1488/94 on risk assessment for existing substances and Directive 98/8/EC of the European Parliament and of the Council concerning the placement of biocidal products on the market (second edition, 2003), in Annex IVA gives guidance useful when evaluating the basic data available for chemically modified rosins.

Except for the miscible monovalent salts, the substances are rather insoluble solids with predicted low vapour pressures. However they are generally transported in liquid thus not permitting dust formation. Thus, inhalation is unlikely, and, should it occur, the substances are likely to behave as insoluble particulates.

The TGD notes that some clinical signs, such as hunched posture may be due to discomfort caused by irritation or simply the presence of a large volume of test substance in the stomach. It also notes that reduced feed intake could be due to lack of palatability. It states that oral absorption is aided by modest log P values, i.e. those between 0 and 4, and some solubility in both water and lipids. Molecular weights above 500 are likely to result in poor absorption. Highly lipophilic substances (log P >4), particularly those that are poorly water soluble (<1 mg/L) may be taken up by micellar solubilisation.

The rosin fumarated, Ca and Mg salt has relatively high molecular weights (~400). A partition coefficient of 2.8 (logPow) that has been determined is strongly variable, with the values obtained being highly method dependant. Thus they are of little help. The substance is unlikely to be absorbed by passive diffusion, but it might be taken up following micelle formation in the intestine. That the latter is unlikely has been investigated experimentally using an analogue, the glycerol ester of rosin (CAS 8050 -31 -5), which can be considered the most likely to behave similarly to dietary triglycerides and hence the most likely to be taken up by this mechanism. The principal glycerol esters consists of two or three molecules of a rosin acid esterified onto one molecule of glycerol (EPA, October 2007), molecular weight ~650 and ~942. Studies have been conducted the absorption and excretion of the glycerol ester of wood rosin (Ester Gum 8BG, CAS 8050 -31 -5) in Fischer 344 rats. These include studies on dietary administration of non-labelled glycerol ester of (Blair, 1995), a pharmacokinetic study on ester gum 8BG in rats using oral administration of glycerol [1,3-¹⁴C] labelled test substance (Noker, 1996) and a study on thein vitro metabolism of glycerol [1,3-¹⁴C] labelled test substance in human faecal extracts and simulated human gastric juice (Lin, 1996). Summaries forthe latter two studies are in the IUCLID 5 files for CAS 8050 -31 -5. The first study (Blair 1995) indicated that essentially complete excretion of the test substance (1.4 or 2.8% in food) occurred in faeces. The second study (Noker, 1996) identified that very little absorption of test substance took place following oral administration of 200 mg /kg bw glycerol [1,3-¹⁴C] labelled test substance. Both male and female rats were examined. Less than 1.1% of the radiolabel was found in urine and less than 1% in exhaled air. Examination of faecal radioactivity identified that two small peaks, identified as mono-esters, may have been absorbed, but ester gum (which consists overwhelmingly of the triester) underwent very little hydrolysis or degradation in the gastrointestinal tract. Studies on absorption and excretion in biliary cannulated rats indicated that very little radiolabel (1.6-2.9%) test substance was absorbed from the gastro intestinal tract and excreted in bile. The third study indicated that beverage grade glycerol ester of gum rosin is stable in the human gastrointestinal tract. As the glycerol ester of rosin is likely to be the chemically modified rosin most similar in properties to tri-glycerides (fats) and therefore most likely to be taken up by a micellar based process, this suggests that such uptake is likely to be minimal. 

Dermal uptake into the stratum corneum may be high if log P is >4. Skin sensitisation is a phenomenon that does not require absorption, but probably requires uptake into the stratum corneum, so is quite possible in the absence of uptake via the skin.

The available repeated dose toxicity studies suggest that any adverse effect seen may be due to the influence of the test substance on dietary uptake of nutrients, rather than a direct systemic toxic effect.

Given the probable lack of absorption, metabolism and excretion are unlikely. The first stage of metabolism of the adduct esters would probably be hydrolysis of the ester. Metabolism of maleopimaric acid, should it occur, is likely to be hydrolysis of the anhydride to the acid, which would probably be excreted unchanged or following conjugation with, for example, glucuronic acid.

 

EPA (2007). Screening level hazard characterisation of high production volume chemicals. Rosin esters category. Prepared by High Production Volume Chemicals Branch, Risk Assessment Division, OPPT, Environment Protection Agency, Washington, DC, USA.. October 2007, INTERIM.

Speijers, G J A (1996) Glycerol ester of wood rosin. WHO Food Additives Series, 37. Geneva: World Health Organisation.

 

Speijers, G J A (1996) Glycerol ester of wood rosin. WHO Food Additives Series, 37. Geneva: World Health Organisation.