Cranberry extract 25% Proanthocyanidins Cambridge Commodities Chemwatch Hazard Alert Code: 2 Part Number: P31139 Issue Date: 10/09/2020 Version No: 1.1.23.11 Print Date: 28/09/2021 Safety data sheet according to REACH Regulation (EC) No 1907/2006, as amended by UK REACH Regulations SI 2019/758 S.REACH.GB.EN

SECTION 1 Identification of the substance / mixture and of the company / undertaking

1.1. Product Identifier

Product name Cranberry extract 25% Proanthocyanidins Chemical Name Not Applicable

Synonyms Not Available Chemical formula Not Applicable Other means of P31139 identification

1.2. Relevant identified uses of the substance or mixture and uses advised against

A flavonoid. Many of the biological effects of flavonoids appear to be related to their ability to modulate a number of cell-signaling cascades. Flavonoids have been shown to exhibit antiallergic, antimicrobial, antiinflammatory, antithrombogenic, antidiabetic, anticancer, antitumorigenic, and antimutagenic and neuroprotective activities through different mechanisms of action in vitro and in animal modes.Flavonoids are regarded as vitamins that are important in the regulation of oxidative stress and act as antioxidants. Flavonoids potentially prevent cancer, heart disease, bone loss, and a number of other diseases Flavonoids are able to reduce plasma levels of low-density lipoproteins, inhibit platelet aggregation, and reduce cell proliferation. These properties result, inter alia, from their mechanisms of action: inhibiting the cell cycle, diminishing oxidative stress, improving detoxification enzymes, inducing apoptosis, and stimulating the immune system. The parent compound , flavanone, is involved in several enzymatic reactions to yield several different flavonoid sub-classes or types, e.g., flavones, flavonols, flavanonols (dihydroflavonols), isoflavones, and anthocyanins. Antioxidant activity Flavonoids are characterized by a molecular frame of two phenyl rings linked by a three carbon chain, making them good Relevant identified uses electron donators or acceptors. Their anti-oxidant capacity depends on this framework, the number and pattern of substitutions (primarily with hydroxyl groups), their ability to chelate with metal ions, and on their specific environment. Flavonoids can readily combine with free radicals, including reactive oxygen species (*ROS) by way of the hydroxyl groups on their structure, ultimately forming resonance-stabilized phenoxyl radicals.The antioxidant properties of flavonoids are related to their potential to prevent disorders associated with oxidative stress caused by free radicals and other reactive oxygen species (ROS). Flavonoids are phytamines with a common chemical structure and a broad range of activities, the most prominent being their radical scavenging ability. Reactive oxygen species (ROS) damage cells by different mechanisms. Direct cytotoxic effects include destruction of the cell membrane by causing radical chain reactions or induction of mutagenic changes in the nuclear and mitochondrial DNA. Indirect changes involve modification of intracellular signal transduction pathways that regulate inflammatory or proliferative activities. Hyperglycaemia results in the generation of free radicals, which may lead to disruption of cellular functions, oxidative damage to cell membranes and enhanced susceptibility to lipid peroxidation. Product code: P31139 Version No: 1.1.23.2 Page 1 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

Reactive oxygen species (ROS) refers to a diverse group of reactive, short-lived, oxygen-containing species, such as superoxide (O2• -), hydrogen peroxide (H2O2), hydroxyl radical (• OH), singlet oxygen (1O2), and lipid peroxyl radical (LOO• ). ROS serve as second messengers for cellular signaling . However, excessive production of ROS results in oxidative stress and damage to DNA, lipids, and protein that is involved in cancer as well as cardiovascular and neurodegenerative diseases It is believed that flavonoids could behave as antioxidants or pro-oxidants, depending on the concentration and the source of the free radicals. Structures essential to flavonoid's antioxidant activity: 3', 4' hydroxylation, the presence of a double bond between carbons 2 and 3, and a carbonyl group on carbon 4 . The hydrogen atom from an aromatic hydroxyl group can be donated to free radicals. Pro-oxidant activity: Although the ability of flavonoids to protect cells from oxidative stress has been well-documented, there is increasing evidence for their pro-oxidant property . The pro-oxidant activity of flavonoids may be related to their ability to undergo autoxidation catalyzed by transition metals to produce superoxide anions . In other reports, however, it was observed that the phenol rings of flavonoids are metabolized by peroxidase to form pro-oxidant phenoxyl radicals, which are sufficiently reactive to co-oxidize glutathione (GSH) or nicotinamide-adenine hydrogen (NADH) accompanied by extensive oxygen uptake and ROS formation . The structure- activity relationship study on pro-oxidant cytotoxicity of flavonoids shows that flavonoids with a phenol ring are generally more bioactive than the catechol ring-containing ones . Cytotoxicity induced by flavonoids is correlated with their electrochemical oxidation susceptibility and lipophilicity Anti-cancer activity: Plant flavonoids have been shown to decrease the risk of development of cancers and have been widely researched for chemoprevention. An epidemiological study in men has indicated the consumption of five flavonoids including apigenin, myricetin, quercetin, kaempferol, and luteolin decreases the incidence of all types of cancer, as well as the mortality from gastrointestinal and respiratory cancers One study also reported that, in both women and men, consuming a diet rich in flavonoids decreases the risk of cancers, more so in lung cancer, over a 24-year-long follow-up period. Flavonoids have been found to inhibit the proliferation of many cancer cells by arresting cell cycle progression either at the G1/S or G2/M checkpoint . The G1 cell cycle arrest is associated with inhibition of the cyclin dependent(CDK2) activity in melanoma and colorectal cancer cells. This arrest is achieved by up-regulation of the CDK inhibitors p27/kip1 and p21/waf1, or direct inhibition on the CDK2 activity Carcinogens activate cell survival pathways such as NF-kB and MAPK during the course of carcinogenesis; these pathways could be additional targets for flavonoids in anti-carcinogenesis Phyto-oestrogen activity: Flavonoids are naturally occurring phytoestrogens because they can bind to estrogen receptors (ERs) and activate their signaling pathways Flavonoids bind and activate ERs when estrogen is deficient. However, due to their relative weak estrogenic activity they may function as anti-estrogenic agents through competition with natural estrogens for binding to ERs Another mechanism of anti-estrogenic activity iinvolves inhibition of aromatase whose function is to aromatize androgens and produce estrogens . Additionally, one flavonoid, luteolin, reduces the ER expression level through inhibiting transcription of the ER gene or potentiating degradation of the ER protein. Finally, some alternative signaling mechanisms unrelated to ERs could also be involved . Although the interaction of estrogen agonists and antagonists with the ER is a primary event in estrogen action, mammalian cells contain a second binding site (type II site) for estrogen to control cell growth, which resides in endogenous proteins such as histone . Luteolin was found to bind to nuclear type II sites irreversibly and to compete for estradiol binding to these sites The etiology of breast, prostate, ovarian, and endometrial cancers is associated with estrogen activity. Flavonoids,are able to inhibit DNA synthesis and proliferation in mammary epithelial cells and breast cancer cells induced by estrogens, both in vitro and in vivo . Suppressing estrogen-induced cancer cell proliferation may contribute to flavonoids therapeutic and preventive activities against estrogen-associated cancer. Epidemiological studies suggest that dietary intake of flavonoids is inversely associated with risk of lung, prostate, stomach, and breast cancer in humans. Dietary intake of flavonols and flavones was found to be inversely associated with the risk of lung cancer. It should be noted that mixed bioactive compounds, such as different flavonoids that exist in foods, may impact each others’ biological effects. Lifestyle differences of the subjects in a study may interfere with the results. Furthermore, variations in epidemiological studies, including differences in questionnaire design, databases for flavonoid content in foods, and methods for data analysis, may substantially vary the outcomes of different studies. Thus, caution should be exercised when interpreting epidemiological study results Anti-inflammatory activity: Experiments with animals show that some flavonoids suppresses lipopolysaccharide (LPS) or bacteria-induced inflammation in vivo . LPS-induced-high mortality was effectively alleviated by luteolin, which is associated with reduction of LPS-stimulated TNFalpha release in serum and intercellular adhesion molecule-1 (ICAM-1) expression in the liver . Inflammation is one of the body's defense mechanisms that guard against infection and help heal injury. However, chronic inflammation may result in harmful diseases such as arthritis, chronic obstructive pulmonary disease, and cancer During

Product code: P31139 Version No: 1.1.23.2 Page 2 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

inflammation macrophages are activated by various molecules, including cytokines from the host and toxins from the pathogens. Lipopolysaccharide (LPS), an outer membrane component of Gram-negative bacteria, is a common endotoxin and inflammation trigger. The activated macrophages vigorously produce inflammatory molecules and free radicals (ROS and reactive nitrogen species, RNS), leading to recruitment of inflammatory cells, such as neutrophils and lymphocytes, to the infection site and clearance of the pathogens . Persistent production of these molecules during chronic inflammation can result in diseases such as cancer. Flavonoids exerts its anti-inflammatory effect through suppressing the production of these cytokines and their signal transduction pathway. Suppression of these pathways underlies the main mechanism of its inhibitory effect on both acute and chronic inflammation. The suppression of inflammatory cytokine-induced signaling is at least partly on the level of the receptor, because accumulation of lipid rafts, which is the critical step for receptor signaling, was blocked by luteolin. Based on the observations that some flavonoids with strong antioxidant activities are completely ineffective in suppressing LPS-stimulated TNFalpha production, it is assumed that the inhibitory action of flavonoids on proinflammatory cytokine production is not directly associated with their antioxidant properties Cytochrome P450 activity: In the liver, aglycones are metabolized by the cytochromes P450. The major metabolic reactions to which flavonoids are susceptible are aromatic hydroxylations and O-dealkylations, which are catalyzed by cytochromes P450. Cytochromes P450 are major metabolic enzymes involved in the biotransformation of xenobiotics including drugs.The major cytochromes P450 involved in the metabolism of flavonoid aglycones are CYP1A2, CYP3A4, and CYP2D6. Flavonoids can also act as inhibitors of these metabolic enzymes, causing clinically significant interactions. In one study flavonoids were mainly reversible inhibitors of CYP1A2 and CYP2A6, while the inhibition of CYP2C8 was of mixed type (reversible and irreversible). Drugs defined as inhibitors bind either to the active site or to an allosteric site of the enzyme.However, they can also bind to both; in these cases, the process is called “mixed inhibition” and can often be more potent than simple competitive or non-competitive inhibition. Inhibitors can be either substrates or non-substrates of the enzyme. Non-substrate inhibitors typically bind to an allosteric site of the enzyme. If the inhibitor is a substrate transformed by the enzyme, the substrate itself or its metabolites could contribute to the inhibition mechanism The dietary flavanoids naringenin, naringin, quercetin and rutin are all substrates for CYP1A2. CYP1A1 and CYP1B1 are two extrahepatic enzymes that have been implicated in carcinogenesis and cancer progression. Selective inhibition of CYP1A1 and CYP1B1 by dietary constituents, notably by certain flavonoids, is a widely accepted paradigm that supports the concept of dietary chemoprevention. In a study of six naturally occurring flavonoids (acacetin, diosmetin, eriodictyol, hesperetin, homoeriodictyol, and naringenin), flavonone homoeriodictyol selectively inhibited P450 1B1 (CYP1B1) with a relatively high IC50 of 0.24 uM. Hence, much emphasis has been on the inhibition of these enzymes to develop potential cancer preventative and therapeutic agents. The potential anti-cancer strategies targeting P450 inhibition were postulated as: (i) preventing the conversion of environmental procarcinogens to active carcinogens; (ii) preventing the conversion of hormonal precursors to carcinogenic hormone derivatives; and (iii) preventing the metabolic inactivation of anti-cancer drugs Cytochrome P450 enzymes are a large ubiquitous superfamily of enzymes, playing a significant physiological role in the detoxification of xenobiotics, and the biosynthesis of many endogenous compounds. P450 families 1, 2, and 3 contribute most extensively to the biotransformation of xenobiotics into more polar metabolites that are readily excreted. In humans and most mammals, P450 family 1 comprises three well-studied monooxygenases, 1A1, 1A2, and 1B1. Cytochrome P450 1A1, a well-known aryl hydrocarbon hydroxylase, is implicated in the metabolic activation of environmental procarcinogens such as polycyclic aromatic hydrocarbons (PAHs) and polyhalogenated aromatic hydrocarbons (PAHs). Human P450 1A1 is mainly expressed in extrahepatic tissues such as lung, gastrointestinal tract, placenta, and skin, and is present only at low levels in the liver. P450 1A1 is one of the most important enzymes involved in tumorigenesis initiated by environmental pollutants. A number of epidemiological studies have shown that genetic variants of human CYP1A1 gene are significantly associated with the susceptibilities to lung and breast cancers. Because of the significant role of P450 1A1 enzyme in human carcinogenesis, modulation of P450 1A1 activity has been considered as a potential target for cancer chemoprevention. Certain data suggest that dietary flavonoids exhibit three distinct modes of action with regard to cancer prevention, based on their hydroxyl and methoxy decoration: (1) inhibitors of CYP1 enzymatic activity, (2) CYP1 substrates and (3) substrates and inhibitors of CYP1 enzymes. The most potent inhibitors of CYP1 activity were the methoxylated flavones acacetin, diosmetin, eupatorin and the di-hydroxylated flavone chrysin, indicating that the 4'-OCH(3) group at the B ring and the 5,7-dihydroxy motif at the A ring play a prominent role the inhibition. Potent inhibition of CYP1B1 activity was also obtained for the poly-hydroxylated flavonols quercetin and myricetin The determined types of inhibition are important for the further assessment of flavonoid-drug interactions. If flavonoid is a reversible inhibitor, flavonoid-rich foods or dietary supplements could inhibit drug metabolism mediated by cytochromes P450 and dose adjustment if needed. If flavonoid is an irreversible inhibitor of cytochrome P450 enzyme, combinations with drugs that it can interact with should be avoided. Natural flavonoids with methoxy substitutions are metabolized by CYP1 enzymes to yield the corresponding demethylated

Product code: P31139 Version No: 1.1.23.2 Page 3 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

product.The antiproliferative activity of the hydroxylated flavonoids apigenin, luteolin, scutellarein, kaempferol and quercetin exposed to CYP1 recombinant enzymes and in the CYP1 expressing cell lines has been investigated. Apigenin was converted to luteolin and scutellarein, whereas kaempferol was metabolized only to quercetin by recombinant CYP1 enzymes. Luteolin metabolism yielded 6 hydroxyluteolin only by recombinant CYP1B1, whereas CYP1A1 and CYP1A2 were not capable of metabolizing this compound. Molecular modeling demonstrated that CYP1B1 favored the A ring orientation of apigenin and luteolin to the heme group compared with CYP1A1. Taken collectively, the data demonstrate that the metabolism of hydroxylated flavonoids by cytochrome P450 CYP1 enzymes, notably CYP1A1 and CYP1B1, can enhance their antiproliferative activity in breast cancer cells. In addition, this antiproliferative activity is attributed to the combined action of the parent compound and the corresponding CYP1 metabolites. As modulators of neutrophil oxidative burst activity: Polymorphonuclear neutrophils (PMNs) generate reactive oxygen species (ROS) during phagocytosis and in response to soluble agonists. This functional response, termed oxidative burst, contributes to host defense, but it can also result in collateral damage of host tissues. Neutrophil oxidative burst test (or chronic granulomatous disease (CGD) test) is a measure of neutrophil oxidation and is a useful assay in the diagnosis of chronic granulomatous disease and is also a useful means to determine the overall metabolic integrity of phagocytosing neutrophils. The relevance of the presence of a C2-C3 double bond for the inhibitory activity of flavonoids was demonstrated. Flavonoids apigenin, luteolin and quercetin and their structurally related flavanones, without the C2-C3 double bond, (+/-)- naringenin (+/-)-eriodictyol, (+/-)-taxifolin, respectively, were studied In general, the flavonoids with the C2-C3 double bound were more active than their flavanones, where the double bond lacks. The most pronounced effect of quercetin in comparison with (±)-taxifolin (64)] could be related to the less planar structure of (+/-)- taxifolin, due to the lack of the C2-C3 double bond, which results in a higher ability to undergo inactivation through the formation of strong hydrogen bonds with macromolecules Substituted flavonoids: Under natural conditions, flavonoids can be found as aglycones or as several sorts of glycosides, prenylated, acetylated, methylated and sulfated derivatives. each different substituent or pattern of substitution creates new derivatives with particular characteristics and properties. Flavonoids are well known for their many beneficial biological and pharmacological functions.Structural modifications, for example, sulfation, methylation, and glycosylation usually change their solubility, stability, and biological activities. The negatively- charged sulphated derivatives have greater water solubility, and the negative charge is very important in interactions with biological targets Several biological activities have been investigated for sulfated flavonoids, such as anticoagulant,antiplatelet aggregation, anti-inflammatory, immunomodulatory, and antitumor effects .Among them, the anticoagulant and antiplatelet aggregation activities are well studied. Heparin,a naturally-occurring anticoagulant, is a negatively-charged sulfated polysaccharide and the negative charge of sulfated flavonoids seems to allow them to bind to heparin receptors Other activity: Flavonoids are reported to be effective in the inhibition of the alpha-amylase and alpha-glucosidase activities, via the inhibition of glucose transporters. The capacity of inhibition is related to the number of hydroxyl groups on the B ring of the flavonoid backbone. The interaction is established by the formation of hydrogen bonding between hydroxyl groups of the ring A (in position R6 or R7) and the ring B (in position R4 'or R5') of the polyphenol ligands and the catalytic residues of the attachment site, and formation of a conjugated pi--system that maintains the interaction with the active site N-acetyltransferases (NAT) inhibition: Arylamine N-acetyltransferases (NAT) are important enzymes involved in the metabolic activation of aromatic and heterocyclic amines and inhibitors of NAT enzymes may be valuable as chemopreventive agents. Certain phytochemical exhibit marked NAT inhibition activity. Caffeic acid, ferulic acid, gallic acid and epigallocatechin gallate (EGCG) inhibited the isoform NAT1 but not NAT2, whereas scopuletin and curcumin inhibited NAT2 but not NAT1. Quercetin, kaempferol and other flavonoids, except epicatechin and silymarin, inhibited both enzymes. The kinetics of inhibition of NAT1 by caffeic acid, EGCG and quercetin were of the non-competitive type, whereas that of NAT2 by quercetin, curcumin and kaempferol was also of the non-competitive type. The most potent inhibitor was quercetin, which has the inhibitory constants for NAT1 and NAT2 of 48.6 +/- 17.3 and 10.0 +/- 1.8 microM, respectively. In plants and organisms: Flavonoids (specifically flavanoids such as the catechins) are "the most common group of polyphenolic compounds in the human diet. Flavonoids are widely distributed in plants, fulfilling many functions. Flavonoids are the most important plant pigments for flower coloration, producing yellow or red/blue pigmentation in petals designed to attract pollinator animals. In higher plants, flavonoids are involved in UV filtration, symbiotic nitrogen fixation and floral pigmentation. They may also act as chemical messengers, physiological regulators, and cell cycle inhibitors. Flavonoids secreted by the root of their host plant help Rhizobia in the infection stage of their symbiotic relationship with legumes like peas, beans, clover, and soy. Rhizobia living in soil are able to sense the flavonoids and this triggers the secretion of Nod factors, which in turn are recognized by the host plant and can lead to

Product code: P31139 Version No: 1.1.23.2 Page 4 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

root hair deformation and several cellular responses such as ion fluxes and the formation of a root nodule. In addition, some flavonoids have inhibitory activity against organisms that cause plant diseases, e.g. Fusarium oxysporum. Benzopyrans (also called chromenes), bicyclic heterocyclic systems consisting of a benzene ring fused to a heterocyclic pyran ring, constitute a privileged structure (capable of binding to multiple receptors with high affinity) in medicinal chemistry. Benzopyran derivatives (chromones and flavones) are potentially useful anti-inflammatory agents due to their ability to inhibit protein kinase dependant signal transduction pathways. Furthermore, some natural benzopyran derivatives showed inhibitory activity of prostaglandin E2 (PGE2) production. Benzopyran derivatives are also an attractive template for the identification of potential anticancer agents. The presence of a halogen allows these reagents to be used as substrates in various coupling reactions, including Suzuki- Miyaura cross-coupling reactions. The pharmacological activities and mechanisms of action of natural phenylpropanoid glycosides (PPGs) extracted from a variety of plants such as antitumor, antivirus, anti-inflammation, antibacteria, antiartherosclerosis, anti-platelet-aggregation, antihypertension, antifatigue, analgesia, hepatoprotection, immunosuppression, protection of sex and learning behavior, protection of neurodegeneration, reverse transformation of tumor cells, inhibition of telomerase and shortening telomere length in tumor cells, effects on enzymes and cytokines, antioxidation, free radical scavenging and fast repair of oxidative damaged DNA, have been reported in the literature. Phenylpropanoids (PPs) belong to the largest group of secondary metabolites produced by plants, mainly, in response to biotic or abiotic stresses such as infections, wounding, UV irradiation, exposure to ozone, pollutants, and other hostile environmental conditions. It is thought that the molecular basis for the protective action of phenylpropanoids in plants is their antioxidant and free radical scavenging properties. These numerous phenolic compounds are major biologically active components of human diet, spices, aromas, wines, beer, essential oils,propolis, and traditional medicine. Phenylpropanoids are ingredients of essential oils including those derived from anis, cinnamon bark, and clove They are often used for fragrances and aromatherapy. Significant correlation (54-86%) between antiplatelet potency and PPs content in the oils was found, the key role for this moiety in the control of haemostasis was suggested. As a confirmation of the importance of PP moieties in defining this kind of biological activity, traditional Chinese medicine preparations, identified as remedies to prevent blood stasis and thrombus formation were analyzed for their structure/effect relationships. The PPs isoeugenol, ferulic acid, elemicin, myristicin, ethyl gallate, and dihydroxyacetophenone were recognized as essential platelet protecting compounds. Many of these substances share both the shikimic acid biosynthetic pathway and a common PP backbone. It is thought that some beneficial health effects of PPs such as reducing the risk of cancer,osteoporosis and cardiovascular diseases may depend on their action as estrogen agonists/antagonists via estrogen receptors Estrogen receptor, a nuclear steroid receptor, binds estrogens and regulates the transcription of estrogen-responsive genes by interacting directly with DNA at estrogen response elements (ERE) of their promoters. PPs may act as nonsteroidal anti-inflammatory drug (NSAID)-like compounds. The COX-2 gene expression was dramatically inhibited by the synthesized dimer of ferulic acid. Phenylpropanoid glycosides (aka phenylethanoid glycosides, PPGs) originate from the shikimic acid-phenylpropanoid pathway and include simple monosaccharides,consisting of hydroxycinnamic acid and hydroxyphenylethyl (methoxyphenol) moieties bonded to a central beta-glucopyranose by ester and glycosidic linkages, respectively,and more complex di-and trisaccharides with one or two additional sugars linked to the core glucose. Members of this compound class have shown a wide range of biological activity,including inhibition of plant pathogenic bacteria and fungi, antioxidant activity, tumour cell suppression, feeding stimulation of specialist herbivores and deterrence of generalist insects. Plant-derived PPGs were found to be effective in the selective inhibition of both tyrosinase activity and melanin synthesis in cultivated melanocytes without cytotoxic effects. The PPGs with antioxidant activities, such as acteoside and martynoside, exhibited antiproliferative, cytotoxic, antimetastatic and immunomodulatory properties Phenylpropanoids fulfill numerous physiological functions, essential for plant growth and development, as well as plant– environment interactions. The phenylpropanoid pathway is one of the most frequently investigated metabolic routes, among secondary metabolite. Phenylpropanoid metabolism generates an enormous array of secondary metabolites, based on the few intermediates of the shikimate pathway). The shikimate pathway is a source of phenylalanine and the entry point leading to the biosynthesis of phenylpropanoids. The so-called central phenylpropanoid pathway is defined by three enzymatic activities: (i) the phenylalanine deamination by phenylalanine ammonia-lyase (PAL) to the trans-cinnamic acid, (ii) the trans-cinnamic acid hydroxylation to the 4-coumarate, as a resulting from cinnamic acid 4-hydroxylase (C4H) activity, and finally (iii) the 4-coumarate conversion to the 4-coumaroyl-CoA by 4-coumarate-CoA ligase (4CL). The cooperating enzymes from the phenylpropanoid pathway were proposed to be organized into complexes called metabolons. The term “metabolon” encompasses multienzymatic complexes bound to the cellular structural elements – membranes. Most metabolon models are based on a dynamic, non-covalent aggregation of components on the endoplasmic reticulum (ER) surface. Organization of enzymes in metabolons is, at the cellular level, a way to optimize biosynthesis. It provides: (i) direct transport of intermediates between successive enzymes, hence increasing local concentration of the substrate around the

Product code: P31139 Version No: 1.1.23.2 Page 5 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

enzyme active center, (ii) minimization of highly biologically active and potentially toxic intermediates within the cell, as well as (iii) coordination of reactions leading to different branches of pathways with shared enzymes or intermediates. In the phenylpropanoid pathway, intracellular interactions between biosynthetic enzymes were shown for the central phenylpropanoid pathway – where PAL and C4H colocalize in the ER. as well as for particular branches leading to the formation of (iso)flavonoids, monolignols, and anthocyanins. Anthocyanidins and anthocyanosides, of which they are part, are used (as plant extracts) in the treatment of visual disorders. Clinical applications include: · Alteration to the micro-circulation · Alteration of peripheral venous circulation (treatment of chronic venous insufficiency and hemorroids) · Gastric and duodenal injury · Visual disorders due to impaired photosensitivity in diabetic retinopathy. Anthocyanidin polyphenols are highly biologically active polyphenol component present in red grape skin and red wine and may have significant effects on cardiovascular risk factors (CRFs) Red wine polyphenol extracts may increase human endothelial nitric oxide synthase (eNOS) promotor and enzyme activity. Polyphenols such as resveratrol, phenolic acids, anthocyanins, and flavonoids in grapes and grape skin possess potent antioxidant properties, and may decrease LDL cholesterol oxidation and platelet aggregation, and promote cardioprotective and vasoprotective properties including antiatherosclerotic, antiarrhythmic, and vasorelaxation actions. The potential and possible mechanism is through an inhibition of oxidation of LDL and other favorable effects on the cellular redox state, an improvement of endothelial function, lowering of blood pressure, inhibition of platelet aggregation, reducing inflammation, and activating novel proteins that prevent cell senescence (e.g., Sirtuin 1). Uses advised against Not Applicable

1.3. Details of the supplier of the safety data sheet

Registered company name Cambridge Commodities Address Lancaster Way Business Park, Ely, Cambridgeshire Cambridgeshire CB6 3NX United Kingdom Telephone +44 1353 667258 Fax Not Available Website Not Available Email [email protected]

1.4. Emergency telephone number

Association / Organisation Not Available Emergency telephone Not Available numbers Other emergency Not Available telephone numbers

SECTION 2 Hazards identification

2.1. Classification of the substance or mixture

Classified according to GB-CLP Regulation, UK SI H335 - Specific Target Organ Toxicity - Single Exposure (Respiratory Tract Irritation) Category 3, H315 - Skin Corrosion/Irritation 2019/720 and UK SI Category 2, H319 - Serious Eye Damage/Eye Irritation Category 2 2020/1567 [1]

Legend: 1. Classified by Chemwatch; 2. Classification drawn from GB-CLP Regulation, UK SI 2019/720 and UK SI 2020/1567

Product code: P31139 Version No: 1.1.23.2 Page 6 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

2.2. Label elements

Hazard pictogram(s)

Signal word Warning

Hazard statement(s)

H335 May cause respiratory irritation. H315 Causes skin irritation. H319 Causes serious eye irritation.

Supplementary statement(s) Not Applicable

Precautionary statement(s) Prevention

P271 Use only outdoors or in a well-ventilated area. P261 Avoid breathing dust/fumes. P280 Wear protective gloves, protective clothing, eye protection and face protection. P264 Wash all exposed external body areas thoroughly after handling.

Precautionary statement(s) Response

P305+P351+P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. P312 Call a POISON CENTER/doctor/physician/first aider/if you feel unwell. P337+P313 If eye irritation persists: Get medical advice/attention. P302+P352 IF ON SKIN: Wash with plenty of water. P304+P340 IF INHALED: Remove person to fresh air and keep comfortable for breathing. P332+P313 If skin irritation occurs: Get medical advice/attention. P362+P364 Take off contaminated clothing and wash it before reuse.

Precautionary statement(s) Storage

P405 Store locked up. P403+P233 Store in a well-ventilated place. Keep container tightly closed.

Precautionary statement(s) Disposal

P501 Dispose of contents/container to authorised hazardous or special waste collection point in accordance with any local regulation.

2.3. Other hazards Cumulative effects may result following exposure*.

Product code: P31139 Version No: 1.1.23.2 Page 7 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

Limited evidence of a carcinogenic effect*.

REACh - Art.57-59: The mixture does not contain Substances of Very High Concern (SVHC) at the SDS print date.

SECTION 3 Composition / information on ingredients

3.1.Substances See 'Composition on ingredients' in Section 3.2

3.2.Mixtures

1.CAS No 2.EC No Classified according to GB-CLP Regulation, UK SI 2019/720 Nanoform Particle %[weight] Name 3.Index No and UK SI 2020/1567 Characteristics 4.REACH No 1.9050-36-6 2.232-940-4 8 maltodextrin Not Applicable Not Available 3.Not Available 4.Not Available 1.91770-88-6 Vaccinium 2.294-875-8 67 macrocarpon Not Applicable Not Available 3.Not Available (cranberry) extract 4.Not Available

1.4852-22-6 Skin Corrosion/Irritation Category 2, Serious Eye Damage/Eye 2.Not Available Irritation Category 2, Specific Target Organ Toxicity - Single 25 procyanidin Not Available 3.Not Available Exposure (Respiratory Tract Irritation) Category 3; H315, H319, 4.Not Available H335 [1]

Legend: 1. Classified by Chemwatch; 2. Classification drawn from GB-CLP Regulation, UK SI 2019/720 and UK SI 2020/1567; 3. Classification drawn from C&L; * EU IOELVs available; [e] Substance identified as having endocrine disrupting properties

SECTION 4 First aid measures

4.1. Description of first aid measures

If this product comes in contact with the eyes: Wash out immediately with fresh running water. Ensure complete irrigation of the eye by keeping eyelids apart and away from eye and moving the eyelids by occasionally Eye Contact lifting the upper and lower lids. Seek medical attention without delay; if pain persists or recurs seek medical attention. Removal of contact lenses after an eye injury should only be undertaken by skilled personnel. If skin contact occurs: Immediately remove all contaminated clothing, including footwear. Skin Contact Flush skin and hair with running water (and soap if available). Seek medical attention in event of irritation. If fumes or combustion products are inhaled remove from contaminated area. Lay patient down. Keep warm and rested. Prostheses such as false teeth, which may block airway, should be removed, where possible, prior to initiating first aid Inhalation procedures. Apply artificial respiration if not breathing, preferably with a demand valve resuscitator, bag-valve mask device, or pocket mask as trained. Perform CPR if necessary. Transport to hospital, or doctor, without delay.

Product code: P31139 Version No: 1.1.23.2 Page 8 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

Immediately give a glass of water. Ingestion First aid is not generally required. If in doubt, contact a Poisons Information Centre or a doctor.

4.2 Most important symptoms and effects, both acute and delayed See Section 11

4.3. Indication of any immediate medical attention and special treatment needed Treat symptomatically.

SECTION 5 Firefighting measures

5.1. Extinguishing media Foam. Dry chemical powder. BCF (where regulations permit). Carbon dioxide. Water spray or fog - Large fires only.

5.2. Special hazards arising from the substrate or mixture

Avoid contamination with oxidising agents i.e. nitrates, oxidising acids, chlorine bleaches, pool chlorine etc. as ignition may Fire Incompatibility result

5.3. Advice for firefighters

Alert Fire Brigade and tell them location and nature of hazard. Wear breathing apparatus plus protective gloves. Prevent, by any means available, spillage from entering drains or water courses. Use water delivered as a fine spray to control fire and cool adjacent area. Fire Fighting DO NOT approach containers suspected to be hot. Cool fire exposed containers with water spray from a protected location. If safe to do so, remove containers from path of fire. Equipment should be thoroughly decontaminated after use. For starch/ air mixtures Starch is a class St1 dust at normal moisture level: Minimum Ignition Temperature (MIE): >30 mJ at normal moisture level Pmax 9.5 Bar Kst 170 bar.m/s Layer Ignition Temperature: >450 deg C Autoignition Temperature: 170 deg C (above this temperature starch will self-heat)

Dust Explosion Hazard Class 1

Fire/Explosion Hazard Dusts fall into one of three Kst* classes. Class 1 dusts; Kst 1-200 m3/sec; Class 2 dusts; 201-299 m3/sec. Class 3 dusts; Kst 300 or more. Most agricultural dusts (grains, flour etc.) are Class 1; pharmaceuticals and other speciality chemicals are typically Class 1 or 2; most unoxidised metallic dusts are Class 3. The higher the Kst, the more energetically the dust will burn and the greater is the explosion risk and the greater is the speed of the explosion.. Standard test conditions, used to derive the Kst, are representative of industrial conditions, but do not represent and absolute worst case. Increased levels of turbulence increase the speed of the explosion dramatically.

* Kst - a normalised expression of the burning dust pressure rise rate over time. Dusts with Minimum Ignition Energies (MIEs) ranging between 20 and 100 mJ may be sensitive to ignition. They require that: · plant is grounded

Product code: P31139 Version No: 1.1.23.2 Page 9 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

· personnel might also need to be grounded · the use of high resistivity materials (such as plastics) should be restricted or avoided during handling or in packaging The majority of ignition accidents occur within or below this range. The MIE of a dust/air mix depends on the particle size the water content and the temperature of the dust. The finer and the dryer the dust the lower the MIE. Higher temperatures cause lower MIE and an increased risk of dust explosion. Quoted values for MIE generally are only representative. Characteristics may change depending upon the process and conditions of use or any changes made to the dust during use, including further grinding or mixing with other products. In order to obtain more specific data for dust, as used, it is recommended that further characterisation testing.is performed. Combustible solid which burns but propagates flame with difficulty; it is estimated that most organic dusts are combustible (circa 70%) - according to the circumstances under which the combustion process occurs, such materials may cause fires and / or dust explosions. Organic powders when finely divided over a range of concentrations regardless of particulate size or shape and suspended in air or some other oxidizing medium may form explosive dust-air mixtures and result in a fire or dust explosion (including secondary explosions). Avoid generating dust, particularly clouds of dust in a confined or unventilated space as dusts may form an explosive mixture with air, and any source of ignition, i.e. flame or spark, will cause fire or explosion. Dust clouds generated by the fine grinding of the solid are a particular hazard; accumulations of fine dust (420 micron or less) may burn rapidly and fiercely if ignited - particles exceeding this limit will generally not form flammable dust clouds; once initiated, however, larger particles up to 1400 microns diameter will contribute to the propagation of an explosion. In the same way as gases and vapours, dusts in the form of a cloud are only ignitable over a range of concentrations; in principle, the concepts of lower explosive limit (LEL) and upper explosive limit (UEL) are applicable to dust clouds but only the LEL is of practical use; - this is because of the inherent difficulty of achieving homogeneous dust clouds at high temperatures (for dusts the LEL is often called the "Minimum Explosible Concentration", MEC). When processed with flammable liquids/vapors/mists,ignitable (hybrid) mixtures may be formed with combustible dusts. Ignitable mixtures will increase the rate of explosion pressure rise and the Minimum Ignition Energy (the minimum amount of energy required to ignite dust clouds - MIE) will be lower than the pure dust in air mixture. The Lower Explosive Limit (LEL) of the vapour/dust mixture will be lower than the individual LELs for the vapors/mists or dusts. A dust explosion may release of large quantities of gaseous products; this in turn creates a subsequent pressure rise of explosive force capable of damaging plant and buildings and injuring people. Usually the initial or primary explosion takes place in a confined space such as plant or machinery, and can be of sufficient force to damage or rupture the plant. If the shock wave from the primary explosion enters the surrounding area, it will disturb any settled dust layers, forming a second dust cloud, and often initiate a much larger secondary explosion. All large scale explosions have resulted from chain reactions of this type. Dry dust can be charged electrostatically by turbulence, pneumatic transport, pouring, in exhaust ducts and during transport. Build-up of electrostatic charge may be prevented by bonding and grounding. Powder handling equipment such as dust collectors, dryers and mills may require additional protection measures such as explosion venting. All movable parts coming in contact with this material should have a speed of less than 1-meter/sec. A sudden release of statically charged materials from storage or process equipment, particularly at elevated temperatures and/ or pressure, may result in ignition especially in the absence of an apparent ignition source. One important effect of the particulate nature of powders is that the surface area and surface structure (and often moisture content) can vary widely from sample to sample, depending of how the powder was manufactured and handled; this means that it is virtually impossible to use flammability data published in the literature for dusts (in contrast to that published for gases and vapours). Autoignition temperatures are often quoted for dust clouds (minimum ignition temperature (MIT)) and dust layers (layer ignition temperature (LIT)); LIT generally falls as the thickness of the layer increases. Combustion products include: , carbon monoxide (CO) , carbon dioxide (CO2) , other pyrolysis products typical of burning organic material. May emit poisonous fumes. May emit corrosive fumes.

Product code: P31139 Version No: 1.1.23.2 Page 10 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

SECTION 6 Accidental release measures

6.1. Personal precautions, protective equipment and emergency procedures See section 8

6.2. Environmental precautions See section 12

6.3. Methods and material for containment and cleaning up

Clean up all spills immediately. Avoid breathing dust and contact with skin and eyes. Wear protective clothing, gloves, safety glasses and dust respirator. Use dry clean up procedures and avoid generating dust. Minor Spills Sweep up, shovel up or Vacuum up (consider explosion-proof machines designed to be grounded during storage and use). Place spilled material in clean, dry, sealable, labelled container.

Moderate hazard. CAUTION: Advise personnel in area. Alert Emergency Services and tell them location and nature of hazard. Control personal contact by wearing protective clothing. Prevent, by any means available, spillage from entering drains or water courses. Major Spills Recover product wherever possible. IF DRY: Use dry clean up procedures and avoid generating dust. Collect residues and place in sealed plastic bags or other containers for disposal. IF WET: Vacuum/shovel up and place in labelled containers for disposal. ALWAYS: Wash area down with large amounts of water and prevent runoff into drains. If contamination of drains or waterways occurs, advise Emergency Services.

6.4. Reference to other sections Personal Protective Equipment advice is contained in Section 8 of the SDS.

SECTION 7 Handling and storage

7.1. Precautions for safe handling

Avoid all personal contact, including inhalation. Wear protective clothing when risk of exposure occurs. Use in a well-ventilated area. Prevent concentration in hollows and sumps. DO NOT enter confined spaces until atmosphere has been checked. DO NOT allow material to contact humans, exposed food or food utensils. Avoid contact with incompatible materials. When handling, DO NOT eat, drink or smoke. Safe handling Keep containers securely sealed when not in use. Avoid physical damage to containers. Always wash hands with soap and water after handling. Work clothes should be laundered separately. Launder contaminated clothing before re-use. Use good occupational work practice. Observe manufacturer's storage and handling recommendations contained within this SDS. Atmosphere should be regularly checked against established exposure standards to ensure safe working conditions are maintained.

Product code: P31139 Version No: 1.1.23.2 Page 11 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

Organic powders when finely divided over a range of concentrations regardless of particulate size or shape and suspended in air or some other oxidizing medium may form explosive dust-air mixtures and result in a fire or dust explosion (including secondary explosions) Minimise airborne dust and eliminate all ignition sources. Keep away from heat, hot surfaces, sparks, and flame. Establish good housekeeping practices. Remove dust accumulations on a regular basis by vacuuming or gentle sweeping to avoid creating dust clouds. Use continuous suction at points of dust generation to capture and minimise the accumulation of dusts. Particular attention should be given to overhead and hidden horizontal surfaces to minimise the probability of a "secondary" explosion. According to NFPA Standard 654, dust layers 1/32 in.(0.8 mm) thick can be sufficient to warrant immediate cleaning of the area. Do not use air hoses for cleaning. Minimise dry sweeping to avoid generation of dust clouds. Vacuum dust-accumulating surfaces and remove to a chemical disposal area. Vacuums with explosion-proof motors should be used. Control sources of static electricity. Dusts or their packages may accumulate static charges, and static discharge can be a source of ignition. Solids handling systems must be designed in accordance with applicable standards (e.g. NFPA including 654 and 77) and other national guidance. Do not empty directly into flammable solvents or in the presence of flammable vapors. The operator, the packaging container and all equipment must be grounded with electrical bonding and grounding systems. Plastic bags and plastics cannot be grounded, and antistatic bags do not completely protect against development of static charges. Empty containers may contain residual dust which has the potential to accumulate following settling. Such dusts may explode in the presence of an appropriate ignition source. Do NOT cut, drill, grind or weld such containers. In addition ensure such activity is not performed near full, partially empty or empty containers without appropriate workplace safety authorisation or permit. Fire and explosion See section 5 protection Phenylpropanoids are labile and after unsealing the container, they should be stored refrigerated or frozen under an inert gas such as nitrogen/argon. Phenylpropanoids are easily oxidised in the liquid state and should be used them within a short period of time after preparation. As long as no special remark is mentioned in the catalogues or labels, they can be stored at room temperature. Solids can be stored longer than liquid compounds or solutions. Compounds with phenolic hydroxy groups can gradually change colour from brown to black while being stored. Compounds with aldehyde groups are also apt to be oxidized to carboxylic acids. Store in original containers. Keep containers securely sealed. Other information Store in a cool, dry area protected from environmental extremes. Store away from incompatible materials and foodstuff containers. Protect containers against physical damage and check regularly for leaks. Observe manufacturer's storage and handling recommendations contained within this SDS. For major quantities: Consider storage in bunded areas - ensure storage areas are isolated from sources of community water (including stormwater, ground water, lakes and streams}. Ensure that accidental discharge to air or water is the subject of a contingency disaster management plan; this may require consultation with local authorities.

7.2. Conditions for safe storage, including any incompatibilities

Polyethylene or polypropylene container. Suitable container Check all containers are clearly labelled and free from leaks. Polyphenols: · are generally easily oxidised (and hence act as antioxidants which quench free radicals in animals); oxidation products can be characterised using ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) in the TEAC Trolox equivalent antioxidant Storage incompatibility capacity) assay. · also characteristically possess a significant binding affinity for proteins, which can lead to the formation of soluble and

Product code: P31139 Version No: 1.1.23.2 Page 12 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

insoluble protein-polyphenol complexes (thought to produce astringency) and particular amine-containing organics (e.g. particular alkaloid natural products) · engage in reactions related to both their core phenolic structures, their linkages, and types of glycosides they form: standard phenolic reactions include ionization (which contributes to solubility and complexation), oxidations to ortho- and para-quinones (which contributes to antioxidant characteristics), and underlying aromatic transformations related to the presence of the phenolic hydroxyl reactions related to their linkages include nucleophilic additions, and oxidative and hydrolytic bond cleavages. · form particular, characteristic metal complexes Reducing sugar-based material. Autooxidation of reducing sugars may produce up to 3000 ppm carbon monoxide under moderately alkaline conditions. High pH aqueous solutions of saccharides (aldoses, ketoses) or polysaccharides based on these sugars may generate hazardous atmospheres in confined spaces. Reducing sugars contain an aldehyde or free hemiacetal in the open-chain form. Sugars with ketone groups in their open chain form are capable of isomerising via a series of tautomeric shifts to produce an aldehyde group in solution. Therefore, ketone- bearing sugars like fructose are considered reducing sugars but it is the isomer containing an aldehyde group which is reducing since ketones cannot be oxidized without decomposition of the sugar. Many disaccharides, like lactose and maltose, also have a reducing form, as one of the two units may have an open-chain form with an aldehyde group. However, sucrose and trehalose, in which the anomeric carbons of the two units are linked together, are non-reducing disaccharides since neither of the rings is capable of opening. In glucose polymers such as starch and starch-derivatives like glucose syrup, maltodextrin and dextrin the macromolecule begins with a reducing sugar, a free aldehyde. More hydrolysed starch contains more reducing sugars. The percentage of reducing sugars present in these starch derivatives is called dextrose equivalent (DE). Dilute solutions of all sugars are subject to fermentation, either by yeast or by other microorganisms or enzymes derived from these, producing gases which can pressurise and burst sealed containers. Some microorganisms will produce hydrogen or methane, adding a fire and explosion hazard. Anthocyanins are thought to be subject to physiochemical degradation in vivo and in vitro. Structure, pH, temperature, light, oxygen, metal ions, intramolecular association, and intermolecular association with other compounds (copigments, sugars, proteins, degradation products, etc.) are generally known to affect the colour and stability of anthocyanins. Anthocyanins are generally degraded at higher pHs. B-ring hydroxylation status and pH have been shown to mediate the degradation of anthocyanins to their phenolic acid and aldehyde constituents. (Significant portions of ingested anthocyanins are likely to degrade to phenolic acids and aldehyde in vivo, following consumption. This characteristic confounds scientific isolation of specific anthocyanin mechanisms in vivo). Phenylpropanoids are labile and after unsealing the container, they should be stored refrigerated or frozen under an inert gas such as nitrogen/argon. Phenylpropanoids are easily oxidised in the liquid state and should be used them within a short period of time after preparation. As long as no special remark is mentioned in the catalogues or labels, they can be stored at room temperature. Solids can be stored longer than liquid compounds or solutions. Compounds with phenolic hydroxy groups can gradually change colour from brown to black while being stored. Compounds with aldehyde groups are also apt to be oxidized to carboxylic acids. Avoid reaction with oxidising agents

7.3. Specific end use(s) See section 1.2

SECTION 8 Exposure controls / personal protection

8.1. Control parameters

DNELs PNECs Ingredient Exposure Pattern Worker Compartment Not Available Not Available Not Available

* Values for General Population

Product code: P31139 Version No: 1.1.23.2 Page 13 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

Occupational Exposure Limits (OEL)

INGREDIENT DATA

Source Ingredient Material name TWA STEL Peak Notes Not Available Not Available Not Available Not Available Not Available Not Available Not Available

Not Applicable

Emergency Limits

Ingredient TEEL-1 TEEL-2 TEEL-3 Cranberry extract 25% Not Available Not Available Not Available Proanthocyanidins

Ingredient Original IDLH Revised IDLH maltodextrin Not Available Not Available Vaccinium macrocarpon Not Available Not Available (cranberry) extract procyanidin Not Available Not Available

Occupational Exposure Banding

Ingredient Occupational Exposure Band Rating Occupational Exposure Band Limit

procyanidin E ≤ 0.01 mg/m³ Notes: Occupational exposure banding is a process of assigning chemicals into specific categories or bands based on a chemical's potency and the adverse health outcomes associated with exposure. The output of this process is an occupational exposure band (OEB), which corresponds to a range of exposure concentrations that are expected to protect worker health.

8.2. Exposure controls

Assess operations based upon available dust explosion information to determine the suitability of preventative or protective systems as precautionary measures against possible dust explosions. If prevention is not possible, consider protection by use of containment, venting or suppression of dust handling equipment. Where explosion venting is considered to be the most appropriate method of protection, vent areas should preferably be calculated based on Kst rather than an St value. If nitrogen purging is considered as the protective system, it must operate with an oxygen level below the limiting oxygen concentration. The system should include an oxygen monitoring and shut-down facility in the event of excessive oxygen being detected.

The maximum surface temperature of enclosures potentially exposed to this material should be based on values obtained by taking 2/3 of the minimum ignition temperature (MIE) of the dust cloud. The effect of dust layers should be reviewed.

An isolated (insulated) human body can readily produce electrostatic discharges in excess of 50 mJ, but have been recorded up to 100 mJ. 8.2.1. Appropriate Engineering controls are used to remove a hazard or place a barrier between the worker and the hazard. Well-designed engineering controls engineering controls can be highly effective in protecting workers and will typically be independent of worker interactions to provide this high level of protection. The basic types of engineering controls are: Process controls which involve changing the way a job activity or process is done to reduce the risk. Enclosure and/or isolation of emission source which keeps a selected hazard "physically" away from the worker and ventilation that strategically "adds" and "removes" air in the work environment. Ventilation can remove or dilute an air contaminant if designed properly. The design of a ventilation system must match the particular process and chemical or contaminant in use. Employers may need to use multiple types of controls to prevent employee overexposure.

Local exhaust ventilation is required where solids are handled as powders or crystals; even when particulates are relatively large, a certain proportion will be powdered by mutual friction.

Product code: P31139 Version No: 1.1.23.2 Page 14 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

Exhaust ventilation should be designed to prevent accumulation and recirculation of particulates in the workplace. If in spite of local exhaust an adverse concentration of the substance in air could occur, respiratory protection should be considered. Such protection might consist of: (a): particle dust respirators, if necessary, combined with an absorption cartridge; (b): filter respirators with absorption cartridge or canister of the right type; (c): fresh-air hoods or masks Build-up of electrostatic charge on the dust particle, may be prevented by bonding and grounding. Powder handling equipment such as dust collectors, dryers and mills may require additional protection measures such as explosion venting. Air contaminants generated in the workplace possess varying "escape" velocities which, in turn, determine the "capture velocities" of fresh circulating air required to efficiently remove the contaminant.

Type of Contaminant: Air Speed: direct spray, spray painting in shallow booths, drum filling, conveyer loading, crusher dusts, gas 1-2.5 m/s (200-500 discharge (active generation into zone of rapid air motion) f/min.) grinding, abrasive blasting, tumbling, high speed wheel generated dusts (released at high initial 2.5-10 m/s velocity into zone of very high rapid air motion). (500-2000 f/min.)

Within each range the appropriate value depends on:

Lower end of the range Upper end of the range 1: Room air currents minimal or favourable to capture 1: Disturbing room air currents

2: Contaminants of low toxicity or of nuisance value only 2: Contaminants of high toxicity 3: Intermittent, low production. 3: High production, heavy use 4: Large hood or large air mass in motion 4: Small hood-local control only

Simple theory shows that air velocity falls rapidly with distance away from the opening of a simple extraction pipe. Velocity generally decreases with the square of distance from the extraction point (in simple cases). Therefore the air speed at the extraction point should be adjusted, accordingly, after reference to distance from the contaminating source. The air velocity at the extraction fan, for example, should be a minimum of 4-10 m/s (800-2000 f/min) for extraction of crusher dusts generated 2 metres distant from the extraction point. Other mechanical considerations, producing performance deficits within the extraction apparatus, make it essential that theoretical air velocities are multiplied by factors of 10 or more when extraction systems are installed or used.

8.2.2. Personal protection

Safety glasses with side shields. Chemical goggles. Contact lenses may pose a special hazard; soft contact lenses may absorb and concentrate irritants. A written policy document, describing the wearing of lenses or restrictions on use, should be created for each workplace or task. This should Eye and face protection include a review of lens absorption and adsorption for the class of chemicals in use and an account of injury experience. Medical and first-aid personnel should be trained in their removal and suitable equipment should be readily available. In the event of chemical exposure, begin eye irrigation immediately and remove contact lens as soon as practicable. Lens should be removed at the first signs of eye redness or irritation - lens should be removed in a clean environment only after workers have washed hands thoroughly. [CDC NIOSH Current Intelligence Bulletin 59], [AS/NZS 1336 or national equivalent]

Skin protection See Hand protection below The selection of suitable gloves does not only depend on the material, but also on further marks of quality which vary from manufacturer to manufacturer. Where the chemical is a preparation of several substances, the resistance of the glove material can not be calculated in advance and has therefore to be checked prior to the application. The exact break through time for substances has to be obtained from the manufacturer of the protective gloves and has to be Hands/feet protection observed when making a final choice. Personal hygiene is a key element of effective hand care. Gloves must only be worn on clean hands. After using gloves, hands should be washed and dried thoroughly. Application of a non-perfumed moisturiser is recommended.

Product code: P31139 Version No: 1.1.23.2 Page 15 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

Suitability and durability of glove type is dependent on usage. Important factors in the selection of gloves include: · frequency and duration of contact, · chemical resistance of glove material, · glove thickness and · dexterity Select gloves tested to a relevant standard (e.g. Europe EN 374, US F739, AS/NZS 2161.1 or national equivalent). · When prolonged or frequently repeated contact may occur, a glove with a protection class of 5 or higher (breakthrough time greater than 240 minutes according to EN 374, AS/NZS 2161.10.1 or national equivalent) is recommended. · When only brief contact is expected, a glove with a protection class of 3 or higher (breakthrough time greater than 60 minutes according to EN 374, AS/NZS 2161.10.1 or national equivalent) is recommended. · Some glove polymer types are less affected by movement and this should be taken into account when considering gloves for long-term use. · Contaminated gloves should be replaced. As defined in ASTM F-739-96 in any application, gloves are rated as: · Excellent when breakthrough time > 480 min · Good when breakthrough time > 20 min · Fair when breakthrough time < 20 min · Poor when glove material degrades For general applications, gloves with a thickness typically greater than 0.35 mm, are recommended. It should be emphasised that glove thickness is not necessarily a good predictor of glove resistance to a specific chemical, as the permeation efficiency of the glove will be dependent on the exact composition of the glove material. Therefore, glove selection should also be based on consideration of the task requirements and knowledge of breakthrough times. Glove thickness may also vary depending on the glove manufacturer, the glove type and the glove model. Therefore, the manufacturers’ technical data should always be taken into account to ensure selection of the most appropriate glove for the task. Note: Depending on the activity being conducted, gloves of varying thickness may be required for specific tasks. For example: · Thinner gloves (down to 0.1 mm or less) may be required where a high degree of manual dexterity is needed. However, these gloves are only likely to give short duration protection and would normally be just for single use applications, then disposed of. · Thicker gloves (up to 3 mm or more) may be required where there is a mechanical (as well as a chemical) risk i.e. where there is abrasion or puncture potential Gloves must only be worn on clean hands. After using gloves, hands should be washed and dried thoroughly. Application of a non-perfumed moisturiser is recommended. Experience indicates that the following polymers are suitable as glove materials for protection against undissolved, dry solids, where abrasive particles are not present. polychloroprene. nitrile rubber. butyl rubber. fluorocaoutchouc. polyvinyl chloride. Gloves should be examined for wear and/ or degradation constantly. Body protection See Other protection below Overalls. P.V.C apron. Other protection Barrier cream. Skin cleansing cream. Eye wash unit.

Respiratory protection Particulate. (AS/NZS 1716 & 1715, EN 143:2000 & 149:001, ANSI Z88 or national equivalent)

Required Minimum Protection Factor Half-Face Respirator Full-Face Respirator Powered Air Respirator

P1 - PAPR-P1 up to 10 x ES Air-line* - -

up to 50 x ES Air-line** P2 PAPR-P2

Product code: P31139 Version No: 1.1.23.2 Page 16 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

up to 100 x ES - P3 - Air-line* - 100+ x ES - Air-line** PAPR-P3

* - Negative pressure demand ** - Continuous flow A(All classes) = Organic vapours, B AUS or B1 = Acid gasses, B2 = Acid gas or hydrogen cyanide(HCN), B3 = Acid gas or hydrogen cyanide(HCN), E = Sulfur dioxide(SO2), G = Agricultural chemicals, K = Ammonia(NH3), Hg = Mercury, NO = Oxides of nitrogen, MB = Methyl bromide, AX = Low boiling point organic compounds(below 65 degC)

· Respirators may be necessary when engineering and administrative controls do not adequately prevent exposures. · The decision to use respiratory protection should be based on professional judgment that takes into account toxicity information, exposure measurement data, and frequency and likelihood of the worker's exposure - ensure users are not subject to high thermal loads which may result in heat stress or distress due to personal protective equipment (powered, positive flow, full face apparatus may be an option). · Published occupational exposure limits, where they exist, will assist in determining the adequacy of the selected respiratory protection. These may be government mandated or vendor recommended. · Certified respirators will be useful for protecting workers from inhalation of particulates when properly selected and fit tested as part of a complete respiratory protection program. · Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU) · Use approved positive flow mask if significant quantities of dust becomes airborne. · Try to avoid creating dust conditions.

8.2.3. Environmental exposure controls See section 12

SECTION 9 Physical and chemical properties

9.1. Information on basic physical and chemical properties

A flavonoid derivative (also known as a bioflavonoid). Flavonoids share on of the following benzopyran structures: 2-phenylchromen-4-one, 3-phenylchromen-4-one or 4-phenylcoumarin. Chemically, flavonoids have the general structure of a 15-carbon skeleton, which consists of two phenyl rings (A and B) and heterocyclic ring (C). This carbon structure can be abbreviated C6-C3-C6. Ring A usually shows a phloroglucinol substitution pattern Flavonoid are all ketone-containing compounds. The terms flavonoid and bioflavonoid have also been more loosely used to describe non-ketone polyhydroxy polyphenol compounds which are more specifically termed flavanoids. According to the IUPAC nomenclature, flavonoids can be classified into: · flavonoids or bioflavonoids · isoflavonoids, derived from 3-phenylchromen-4-one (3-phenyl-1,4-benzopyrone) structure · neoflavonoids, derived from 4-phenylcoumarin (4-phenyl-1,2-benzopyrone) structure Appearance Designated as an aromatic polyketide a compounds in which carbon chains are extended with malonyl-CoA onto phenylpropanoids. The polyketides are further categorised as: · Diarylheptanoids which are biosynthesized from two cinnamyl-CoA units and one malonyl-CoA. Their two aromatic rings are connected with an aliphatic seven-carbon chain. · Stilbenoids, chalconoids, flavonoids and isoflavonoids which are formed from a cinnamyl-CoA with three malonyl-CoA units. Chalconoids, flavonoids and isoflavonoids possess a C6-C3-C6 skeleton whereas stilbenoids have a C6-C2-C6skeleton which arises by decarboxylation during the biosynthesis. A phenylpropanoid derivative - a natural organic compound of plant origin biosynthesised via the shikimic acid pathway. Phenylalanine and tyrosine are their precursors. Phenylpropanoids comprise a group of compounds with side-chains of three carbons attached to a benzene ring. Phenylpropanoids are generally soluble in many organic solvents. They can be rather difficult to dissolve in non-polar solvents such as hexane but dissolve well in high polar solvents such as chloroform, methanol and DMSO. Compounds with carboxyl or

Product code: P31139 Version No: 1.1.23.2 Page 17 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

phenolic hydroxy groups are soluble in aqueous alkaline solutions. They can be further subdivided into groups described as: · Cinnamic acid and esters · Cinnamic acid derivatives · Cinnamaldehydes · Phenylpropenes · Coumarins Anthocyanins (also anthocyans from the Greek meaning "dark blue") are water-soluble vacuolar pigments that, depending on their pH, may appear red, purple, or blue Anthocyanins belong to a parent class of molecules called flavonoids synthesized via the phenylpropanoid pathway; they are odourless, but flavourful, contributing to taste as a moderately astringent sensation. Anthocyanins occur in all tissues of higher plants, including leaves, stems, roots, flowers, and fruits. Anthoxanthins are clear, white, to yellow counterparts of anthocyanins occurring in plants. Anthocyanins are derived from anthocyanidins by adding sugars. Anthocyanins fluoresce, enabling a tool for plant cell research to allow live cell imaging without a requirement for other fluorophores Anthocyanins are considered secondary metabolites as a food additive with E number E163 (INS number 163). Anthocyanins have an antioxidant role in plants against reactive oxygen species caused by abiotic stresses, such as overexposure to ultraviolet light and extreme temperatures. Tomato plants protect against cold stress with anthocyanins countering reactive oxygen species, leading to a lower rate of cell death in leaves. Although anthocyanins have antioxidant properties in vitro, this antioxidant effect is not conserved after the plant is consumed. Dietary anthocyanins and other flavonoids appear to have little or no direct antioxidant food value following digestion. Unlike controlled test-tube conditions, the fate of anthocyanins in vivo shows they are poorly conserved (less than 5%), with most of what is absorbed existing as chemically modified metabolites that are rapidly excreted. The increase in antioxidant capacity of blood seen after the consumption of anthocyanin-rich foods may not be caused directly by the anthocyanins, but instead may result from increased uric acid levels derived from metabolism of flavonoids. Anthocyanins have been used in organic solar cells because of their ability to convert light energy into electrical energy. The many benefits to using dye-sensitized solar cells instead of traditional pn junction silicon cells include lower purity requirements and abundance of component materials, such as titania, as well as the fact they can be produced on flexible substrates, making them amenable to roll-to-roll printing processes. Anthocyanin production can be engineered into genetically modified materials to enable their visual identification The absorbance pattern responsible for the red colour of anthocyanins may be complementary to that of green chlorophyll in photosynthetically active tissues Anthocyanins occur in all tissues of higher plants, including leaves, stems, roots, flowers, and fruits. Anthoxanthins are clear, white to yellow counterparts of anthocyanins occuring in plants. Anthocyanins are derived from anthocyanidins by adding sugars. Anthocyanins represent a large group of water-soluble plant pigments of the 2-phenylbenzophyrylium (flavylium) structure. Anthocyanins belong to the flavonoid family of plant molecules and consist of some 200 or more compounds, chemically combined to a sugar moiety (glucose, rhamnose, galactose, xylose, arabinose) of which the most common are pelargonidin, cyanidin, delphinidin, peonidin, petunidin and malvidin. The blue to red colour imparted by the anthocyanins depends largely upon the pH of the medium. The anthocyanins normally exist as glycosides (anthocyanosides); the aglycone component alone is extremely unstable.

Relative density (Water = Physical state Divided Solid|Powder Not Available 1) Partition coefficient Odour Not Available Not Available n-octanol / water Auto-ignition temperature Odour threshold Not Available Not Available (°C) Decomposition pH (as supplied) Not Available Not Available temperature

Melting point / freezing Not Available Viscosity (cSt) Not Available point (°C)

Initial boiling point and Not Available Molecular weight (g/mol) Not Available boiling range (°C)

Flash point (°C) Not Available Taste Not Available

Product code: P31139 Version No: 1.1.23.2 Page 18 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

Evaporation rate Not Available Explosive properties Not Available Flammability Not Available Oxidising properties Not Available Surface Tension (dyn/cm Upper Explosive Limit (%) Not Available Not Applicable or mN/m) Lower Explosive Limit (%) Not Available Volatile Component (%vol) Not Available Vapour pressure (kPa) Not Available Gas group Not Available Solubility in water Not Available pH as a solution (%) Not Available Vapour density (Air = 1) Not Available VOC g/L Not Available Nanoform Particle Nanoform Solubility Not Available Not Available Characteristics Particle Size Not Available

9.2. Other information Not Available

SECTION 10 Stability and reactivity

10.1.Reactivity See section 7.2 Unstable in the presence of incompatible materials. 10.2. Chemical stability Product is considered stable. Hazardous polymerisation will not occur. 10.3. Possibility of See section 7.2 hazardous reactions 10.4. Conditions to avoid See section 7.2 10.5. Incompatible See section 7.2 materials 10.6. Hazardous See section 5.3 decomposition products

SECTION 11 Toxicological information

11.1. Information on toxicological effects

The material can cause respiratory irritation in some persons. The body's response to such irritation can cause further lung damage. Persons with impaired respiratory function, airway diseases and conditions such as emphysema or chronic bronchitis, may incur further disability if excessive concentrations of particulate are inhaled. Inhaled If prior damage to the circulatory or nervous systems has occurred or if kidney damage has been sustained, proper screenings should be conducted on individuals who may be exposed to further risk if handling and use of the material result in excessive exposures.

Anthrocyanosides are rapidly absorbed and eliminated; in low oral doses, long term toxicity is not significant. Starch is generally of low toxicity. An abnormal craving for starch (amylophagia) during pregnancy has been recognized in certain Ingestion areas. The material has NOT been classified by EC Directives or other classification systems as "harmful by ingestion". This is because of the lack of corroborating animal or human evidence. This material can cause inflammation of the skin on contact in some persons. Skin Contact The material may accentuate any pre-existing dermatitis condition

Product code: P31139 Version No: 1.1.23.2 Page 19 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

Skin contact is not thought to have harmful health effects (as classified under EC Directives); the material may still produce health damage following entry through wounds, lesions or abrasions. Open cuts, abraded or irritated skin should not be exposed to this material Entry into the blood-stream, through, for example, cuts, abrasions or lesions, may produce systemic injury with harmful effects. Examine the skin prior to the use of the material and ensure that any external damage is suitably protected. Eye This material can cause eye irritation and damage in some persons. Long-term exposure to respiratory irritants may result in airways disease, involving difficulty breathing and related whole-body problems. Substance accumulation, in the human body, may occur and may cause some concern following repeated or long-term occupational exposure. Flavonoids, which are found in a range of foods and medicines, have been shown to cause leukaemia in infancy, but, if taken at high levels in the diet, they reduce the risk of breast and prostate cancer. Injected anthocyanosides has been reputed to cause a lowering of the incidence of gastric ulcer and increase capillary Chronic permeability. They have not been shown to cause cancer or mutations. Some workers may develop chronic occupational dermatitis (generally mild) through the handling of starch products. When starch is used as a lubricant in surgical gloves, small amounts, released into the patient during the course of surgery, have resulted in granulomas and peritonitis. Long term exposure to high dust concentrations may cause changes in lung function i.e. pneumoconiosis, caused by particles less than 0.5 micron penetrating and remaining in the lung. There has been some concern that this material can cause cancer or mutations but there is not enough data to make an assessment.

Cranberry extract 25% TOXICITY IRRITATION Proanthocyanidins Not Available Not Available

TOXICITY IRRITATION maltodextrin Not Available Not Available

Vaccinium macrocarpon TOXICITY IRRITATION (cranberry) extract Not Available Not Available

TOXICITY IRRITATION procyanidin Not Available Not Available

Legend: 1. Value obtained from Europe ECHA Registered Substances - Acute toxicity 2.* Value obtained from manufacturer's SDS. Unless otherwise specified data extracted from RTECS - Register of Toxic Effect of chemical Substances

Asthma-like symptoms may continue for months or even years after exposure to the material ends. This may be due to a non-allergic condition known as reactive airways dysfunction syndrome (RADS) which can occur after exposure to high levels of highly irritating compound. Main criteria for diagnosing RADS include the absence of previous airways disease in a non-atopic individual, with sudden onset of persistent asthma-like symptoms within minutes to hours of a documented exposure to the Cranberry extract 25% irritant. Other criteria for diagnosis of RADS include a reversible airflow pattern on lung function tests, moderate to severe Proanthocyanidins & bronchial hyperreactivity on methacholine challenge testing, and the lack of minimal lymphocytic inflammation, without PROCYANIDIN eosinophilia. RADS (or asthma) following an irritating inhalation is an infrequent disorder with rates related to the concentration of and duration of exposure to the irritating substance. On the other hand, industrial bronchitis is a disorder that occurs as a result of exposure due to high concentrations of irritating substance (often particles) and is completely reversible after exposure ceases. The disorder is characterized by difficulty breathing, cough and mucus production. MALTODEXTRIN & VACCINIUM MACROCARPON No significant acute toxicological data identified in literature search. (CRANBERRY) EXTRACT

Product code: P31139 Version No: 1.1.23.2 Page 20 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

& PROCYANIDIN

Acute Toxicity Carcinogenicity Skin Irritation/Corrosion Reproductivity Serious Eye STOT - Single Exposure Damage/Irritation Respiratory or Skin STOT - Repeated Exposure sensitisation Mutagenicity Aspiration Hazard

Legend: – Data either not available or does not fill the criteria for classification – Data available to make classification

11.2.1. Endocrine Disruption Properties Not Available

SECTION 12 Ecological information

12.1. Toxicity

Endpoint Test Duration (hr) Species Value Source Cranberry extract 25% Not Not Not Proanthocyanidins Not Available Not Available Available Available Available

Endpoint Test Duration (hr) Species Value Source maltodextrin Not Not Not Not Available Not Available Available Available Available

Endpoint Test Duration (hr) Species Value Source Vaccinium macrocarpon Not Not Not (cranberry) extract Not Available Not Available Available Available Available

Endpoint Test Duration (hr) Species Value Source procyanidin Not Not Not Not Available Not Available Available Available Available

Legend: Extracted from 1. IUCLID Toxicity Data 2. Europe ECHA Registered Substances - Ecotoxicological Information - Aquatic Toxicity 3. EPIWIN Suite V3.12 (QSAR) - Aquatic Toxicity Data (Estimated) 4. US EPA, Ecotox database - Aquatic Toxicity Data 5. ECETOC Aquatic Hazard Assessment Data 6. NITE (Japan) - Bioconcentration Data 7. METI (Japan) - Bioconcentration Data 8. Vendor Data

DO NOT discharge into sewer or waterways.

12.2. Persistence and degradability

Ingredient Persistence: Water/Soil Persistence: Air

No Data available for all ingredients No Data available for all ingredients

12.3. Bioaccumulative potential

Ingredient Bioaccumulation

Product code: P31139 Version No: 1.1.23.2 Page 21 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

Ingredient Bioaccumulation No Data available for all ingredients

12.4. Mobility in soil

Ingredient Mobility No Data available for all ingredients

12.5. Results of PBT and vPvB assessment

P B T Relevant available data Not Available Not Available Not Available PBT vPvB

PBT Criteria fulfilled? No vPvB No

12.6. Endocrine Disruption Properties Not Available

12.7. Other adverse effects Not Available

SECTION 13 Disposal considerations

13.1. Waste treatment methods

Legislation addressing waste disposal requirements may differ by country, state and/ or territory. Each user must refer to laws operating in their area. In some areas, certain wastes must be tracked. A Hierarchy of Controls seems to be common - the user should investigate: Reduction Reuse Recycling Product / Packaging Disposal (if all else fails) disposal This material may be recycled if unused, or if it has not been contaminated so as to make it unsuitable for its intended use. Shelf life considerations should also be applied in making decisions of this type. Note that properties of a material may change in use, and recycling or reuse may not always be appropriate. In most instances the supplier of the material should be consulted. DO NOT allow wash water from cleaning or process equipment to enter drains. It may be necessary to collect all wash water for treatment before disposal. In all cases disposal to sewer may be subject to local laws and regulations and these should be considered first. Where in doubt contact the responsible authority. Waste treatment options Not Available

Sewage disposal options Not Available

SECTION 14 Transport information

Labels Required

Product code: P31139 Version No: 1.1.23.2 Page 22 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

Marine Pollutant NO HAZCHEM Not Applicable

Land transport (ADR): NOT REGULATED FOR TRANSPORT OF DANGEROUS GOODS

14.1. UN number Not Applicable 14.2. UN proper shipping Not Applicable name

14.3. Transport hazard Class Not Applicable class(es) Subrisk Not Applicable

14.4. Packing group Not Applicable 14.5. Environmental Not Applicable hazard

Hazard identification (Kemler) Not Applicable Classification code Not Applicable

14.6. Special precautions Hazard Label Not Applicable for user Special provisions Not Applicable Limited quantity Not Applicable Tunnel Restriction Code Not Applicable

Air transport (ICAO-IATA / DGR): NOT REGULATED FOR TRANSPORT OF DANGEROUS GOODS

14.1. UN number Not Applicable 14.2. UN proper shipping Not Applicable name

ICAO/IATA Class Not Applicable 14.3. Transport hazard ICAO / IATA Subrisk Not Applicable class(es) ERG Code Not Applicable

14.4. Packing group Not Applicable 14.5. Environmental Not Applicable hazard

Special provisions Not Applicable Cargo Only Packing Instructions Not Applicable Cargo Only Maximum Qty / Pack Not Applicable 14.6. Special precautions Passenger and Cargo Packing Instructions Not Applicable for user Passenger and Cargo Maximum Qty / Pack Not Applicable

Passenger and Cargo Limited Quantity Packing Instructions Not Applicable Passenger and Cargo Limited Maximum Qty / Pack Not Applicable

Sea transport (IMDG-Code / GGVSee): NOT REGULATED FOR TRANSPORT OF DANGEROUS GOODS

14.1. UN number Not Applicable

Product code: P31139 Version No: 1.1.23.2 Page 23 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

14.2. UN proper shipping Not Applicable name

14.3. Transport hazard IMDG Class Not Applicable class(es) IMDG Subrisk Not Applicable

14.4. Packing group Not Applicable 14.5. Environmental Not Applicable hazard

EMS Number Not Applicable 14.6. Special precautions Special provisions Not Applicable for user Limited Quantities Not Applicable

Inland waterways transport (ADN): NOT REGULATED FOR TRANSPORT OF DANGEROUS GOODS

14.1. UN number Not Applicable 14.2. UN proper shipping Not Applicable name 14.3. Transport hazard Not Applicable Not Applicable class(es) 14.4. Packing group Not Applicable 14.5. Environmental Not Applicable hazard

Classification code Not Applicable Special provisions Not Applicable 14.6. Special precautions Limited quantity Not Applicable for user Equipment required Not Applicable Fire cones number Not Applicable

14.7. Transport in bulk according to Annex II of MARPOL and the IBC code Not Applicable 14.8. Transport in bulk in accordance with MARPOL Annex V and the IMSBC Code

Product name Group maltodextrin Not Available Vaccinium macrocarpon Not Available (cranberry) extract

procyanidin Not Available

14.9. Transport in bulk in accordance with the ICG Code

Product name Ship Type maltodextrin Not Available

Vaccinium macrocarpon Not Available (cranberry) extract

Product code: P31139 Version No: 1.1.23.2 Page 24 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

Product name Ship Type procyanidin Not Available

SECTION 15 Regulatory information

15.1. Safety, health and environmental regulations / legislation specific for the substance or mixture

maltodextrin is found on the following regulatory lists Europe EC Inventory European Union - European Inventory of Existing Commercial Chemical Substances (EINECS)

Vaccinium macrocarpon (cranberry) extract is found on the following regulatory lists Europe EC Inventory European Union - European Inventory of Existing Commercial Chemical Substances (EINECS)

procyanidin is found on the following regulatory lists Not Applicable

This safety data sheet is in compliance with the following EU legislation and its adaptations - as far as applicable - : Directives 98/24/EC, - 92/85/EEC, - 94/33/EC, - 2008/98/EC, - 2010/75/EU; Commission Regulation (EU) 2020/878; Regulation (EC) No 1272/2008 as updated through ATPs.

15.2. Chemical safety assessment No Chemical Safety Assessment has been carried out for this substance/mixture by the supplier.

ECHA SUMMARY Not Applicable National Inventory Status

National Inventory Status Australia - AIIC / Australia No (procyanidin) Non-Industrial Use Canada - DSL No (procyanidin) Canada - NDSL No (maltodextrin; Vaccinium macrocarpon (cranberry) extract; procyanidin) China - IECSC No (Vaccinium macrocarpon (cranberry) extract; procyanidin) Europe - EINEC / ELINCS / No (procyanidin) NLP Japan - ENCS No (maltodextrin; Vaccinium macrocarpon (cranberry) extract; procyanidin) Korea - KECI No (Vaccinium macrocarpon (cranberry) extract; procyanidin) New Zealand - NZIoC No (Vaccinium macrocarpon (cranberry) extract; procyanidin) Philippines - PICCS No (Vaccinium macrocarpon (cranberry) extract; procyanidin)

USA - TSCA No (Vaccinium macrocarpon (cranberry) extract; procyanidin) Taiwan - TCSI No (procyanidin)

Mexico - INSQ No (Vaccinium macrocarpon (cranberry) extract; procyanidin) Vietnam - NCI No (procyanidin)

Russia - FBEPH No (Vaccinium macrocarpon (cranberry) extract; procyanidin)

Yes = All CAS declared ingredients are on the inventory Legend: No = One or more of the CAS listed ingredients are not on the inventory. These ingredients may be exempt or will require

Product code: P31139 Version No: 1.1.23.2 Page 25 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

National Inventory Status registration.

SECTION 16 Other information

Revision Date 10/09/2020 Initial Date 10/09/2020

Full text Risk and Hazard codes

Other information Classification of the preparation and its individual components has drawn on official and authoritative sources as well as independent review by the Chemwatch Classification committee using available literature references.

The SDS is a Hazard Communication tool and should be used to assist in the Risk Assessment. Many factors determine whether the reported Hazards are Risks in the workplace or other settings. Risks may be determined by reference to Exposures Scenarios. Scale of use, frequency of use and current or available engineering controls must be considered.

For detailed advice on Personal Protective Equipment, refer to the following EU CEN Standards: EN 166 Personal eye-protection EN 340 Protective clothing EN 374 Protective gloves against chemicals and micro-organisms EN 13832 Footwear protecting against chemicals EN 133 Respiratory protective devices

Definitions and abbreviations PC－TWA: Permissible Concentration-Time Weighted Average PC－STEL: Permissible Concentration-Short Term Exposure Limit IARC: International Agency for Research on Cancer ACGIH: American Conference of Governmental Industrial Hygienists STEL: Short Term Exposure Limit TEEL: Temporary Emergency Exposure Limit。 IDLH: Immediately Dangerous to Life or Health Concentrations ES: Exposure Standard OSF: Odour Safety Factor NOAEL :No Observed Adverse Effect Level LOAEL: Lowest Observed Adverse Effect Level TLV: Threshold Limit Value LOD: Limit Of Detection OTV: Odour Threshold Value BCF: BioConcentration Factors BEI: Biological Exposure Index AIIC: Australian Inventory of Industrial Chemicals DSL: Domestic Substances List NDSL: Non-Domestic Substances List IECSC: Inventory of Existing Chemical Substance in China EINECS: European INventory of Existing Commercial chemical Substances ELINCS: European List of Notified Chemical Substances NLP: No-Longer Polymers ENCS: Existing and New Chemical Substances Inventory KECI: Korea Existing Chemicals Inventory Product code: P31139 Version No: 1.1.23.2 Page 26 of 27 S.REACH.GB.EN Lancaster Way Business Park Safety Data Sheet (Conforms to Regulation (EU) No 2020/878) Ely, Cambridgeshire, CB6 3NX, UK. Chemwatch: 9-775582 +44 (0) 1353 667258 Issue Date: 10/09/2020 [email protected] Print Date: 28/09/2021 www.c-c-l.com

NZIoC: New Zealand Inventory of Chemicals PICCS: Philippine Inventory of Chemicals and Chemical Substances TSCA: Toxic Substances Control Act TCSI: Taiwan Chemical Substance Inventory INSQ: Inventario Nacional de Sustancias Químicas NCI: National Chemical Inventory FBEPH: Russian Register of Potentially Hazardous Chemical and Biological Substances

Powered by AuthorITe, from Chemwatch.

Product code: P31139 Version No: 1.1.23.2 Page 27 of 27