arizole

SECTION 2: Hazards identification

RISK SAFETY » Explosive when dry. » Keep away from combustible material. » Contact with combustible material » Do not breathe gas/fumes/vapour/spray. may cause fire. » Flammable. » Wear suitable protective clothing. » May form explosive peroxides. » Use only in well ventilated areas. » Irritating to skin. » Keep container in a well ventilated place. » May cause SENSITISATION by skin » To clean the floor and all objects contaminated by this contact. material use water and detergent. » Toxic to aquatic organisms. » Keep container tightly closed. » HARMFUL- May cause lung damage if » Keep away from food drink and animal feeding stuffs. swallowed. » Vapours may cause drowsiness and dizziness. » Take off immediately all contaminated clothing. » Ingestion may produce health damage*. » If swallowed IMMEDIATELY contact Doctor or Poisons » Inhalation may produce serious Information Centre. (show this container or label). health damage*. » This material and its container must be disposed of as » Cumulative effects may result hazardous waste. following exposure*. » In case of accident by inhalation: remove casualty to » May produce discomfort of the fresh air and keep at rest. respiratory system*. » Limited evidence of a carcinogenic effect*. * (limited evidence).

Potential Acute Health Effects

SWALLOWED » Swallowing of the liquid may cause aspiration of vomit into the lungs with the risk of haemorrhaging, pulmonary oedema, progressing to chemical pneumonitis; serious consequences may result. Signs and symptoms of chemical (aspiration) pneumonitis may include coughing, gasping, choking, burning of the mouth, difficult breathing, and bluish coloured skin (cyanosis). » Accidental ingestion of the material may be damaging to the health of the individual. » Terpenes and their oxygen-containing counterparts, the terpenoids, produce a variety of physiological effects. monoterpenes, for example, produce a haemorrhagic gastritis characterised by stomach pain and bleeding and vomiting. Systemic effects of pine oils include weakness and central nervous depression, excitement, loss of balance, headache, with hypothermia and respiratory failure. » Central nervous system (CNS) depression may include nonspecific discomfort, symptoms of giddiness, headache, dizziness, nausea, anaesthetic effects, slowed reaction time, slurred speech and may progress to unconsciousness. Serious poisonings may result in respiratory depression and may be fatal. » Taken internally the essential oils exert a mild irritant effect on the mucous membranes of the mouth and digestive tract which induces a feeling of warmth and increases salivation. Excessive oral doses irritate the gastro-intestinal tract and may cause nausea, vomiting and diarrhoea. Occasional irritation of the urinary tract and aggravation of pre-existing inflammatory conditions have been reported. Other effects include dysuria, haematuria, unconsciousness and shallow respiration. Complications arising from ingestion of volatile oils include anuria, pulmonary oedema, and bronchial pneumonia. Central nervous system depression may lead to stupor and possible respiratory failure whilst central system stimulation may lead to excitement and convulsions. Pathologic findings include renal degeneration and intense congestion and oedema in the lungs, brain and gastric mucosa. Excretion takes place through the lungs, skin and kidneys. Most essential oils are reported to be ecbolic but abortions cannot be induced at safe doses. EYE » Although the liquid is not thought to be an irritant (as classified by EC Directives), direct contact with the eye may produce transient discomfort characterised by tearing or conjunctival redness (as with windburn). SKIN » Evidence exists, or practical experience predicts, that the material either produces inflammation of the skin in a substantial number of individuals following direct contact, and/or produces significant inflammation when applied to the healthy intact skin of animals, for up to four hours, such inflammation being present twenty-four hours or more after the end of the exposure period. Skin irritation may also be present after prolonged or repeated exposure; this may result in a form of contact dermatitis (nonallergic). The dermatitis is often characterised by skin redness (erythema) and swelling (oedema) which may progress to blistering (vesiculation), scaling and thickening of the epidermis. At the microscopic level there may be intercellular oedema of the spongy layer of the skin (spongiosis) and intracellular oedema of the epidermis. » 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. » When applied to intact skin essential oils have an irritant and rubefacient action, causing first a sensation of warmth and smarting followed by mild local anesthesia. They have been used as counter-irritants and cutaneous stimulants in the treatment of chronic inflammatory conditions and to relieve neuralgia and rheumatic pain. Care should be taken to avoid blistering. These oils may also produce sensitisation. » It is likely that older pine oils become irritants from the build up of peroxides of delta- 3-carene and limonene etc. » Entry into the blood-stream through, for example, cuts, abrasions, puncture wounds 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. » Application of d-limonene produced moderate irritation to both intact and abraded skin. High purity d-limonene does not cause significant allergic reaction in guinea pigs; d-limonene, exposed to air for 2-months, sensitised the animals and it is surmised that allergenic compounds are formed after prolonged air contact. In human patch testing, weak or moderate reactions (erythema, swelling) have been observed. Positive eczematous responses to purified limonene were observed in 5 of 16 previously sensitised to oil of turpentine. In one study, a 39-year old male immersed one hand in a jar of solvent, ensuring that inhalation exposure was minimal. After only few minutes of exposure, the subject experienced painful itching and burning. Itching decreased after the exposure but burning continued for 10 minutes. Swelling disappeared after 100 minutes. Six hours post-exposure, a purpuric eruption was observed; this persisted for several weeks. Blood concentrations during skin exposure were low compared to those during inhalation exposure. INHALED » Inhalation of vapours may cause drowsiness and dizziness. This may be accompanied by narcosis, reduced alertness, loss of reflexes, lack of coordination and vertigo. » Inhalation of aerosols (mists, fumes), generated by the material during the course of normal handling, may produce serious damage to the health of the individual. » Limited evidence or practical experience suggests that the material may produce irritation of the respiratory system, in a significant number of individuals, following inhalation. In contrast to most organs, the lung is able to respond to a chemical insult by first removing or neutralising the irritant and then repairing the damage. The repair process, which initially evolved to protect mammalian lungs from foreign matter and antigens, may however, produce further lung damage resulting in the impairment of gas exchange, the primary function of the lungs. Respiratory tract irritation often results in an inflammatory

Response

involving the recruitment and activation of many cell types, mainly derived from the vascular system. » Inhalation hazard is increased at higher temperatures. » Acute effects from inhalation of high concentrations of vapour are pulmonary irritation, including coughing, with nausea; central nervous system depression - characterised by headache and dizziness, increased reaction time, fatigue and loss of co- ordination. » Central nervous system (CNS) depression may include nonspecific discomfort, symptoms of giddiness, headache, dizziness, nausea, anaesthetic effects, slowed reaction time, slurred speech and may progress to unconsciousness. Serious poisonings may result in respiratory depression and may be fatal. » Inhalation of essential oil volatiles may produce dizziness, rapid, shallow breathing, tachycardia, bronchial irritation and unconsciousness or convulsions. Complications include anuria, pulmonary oedema and bronchial pneumonia.

Potential chronic health

Practical experience shows that skin contact with the material is capable either of inducing a sensitisation reaction in a substantial number of individuals, and/or of producing a positive response in experimental animals. On the basis, primarily, of animal experiments, concern has been expressed by at least one classification body that the material may produce carcinogenic or mutagenic effects; in respect of the available information, however, there presently exists inadequate data for making a satisfactory assessment. Limited evidence suggests that repeated or long-term occupational exposure mayproduce cumulative health effects involving organs or biochemical systems. In the presence of air, a number of common flavour and fragrance chemicals can form peroxides surprisingly fast. Antioxidants can in most cases minimise the oxidation. Fragrance terpenes are generally easily oxidised in air. Non-oxidised limonene, linalool and caryophyllene turned out to be very weak sensitizers, however after oxidation limonene hydroperoxide and linalool hydroperoxide are strong sensitizers. Of the patients tested 2.6% showed positive reaction to oxidised limonene, 1.3% to oxidised linalool, 1.1% to linalool hydroperoxide, 0.5% to oxidised caryophyllene, while testing with caryophyllene oxide and oxidised myrcene resulted in few positive patch tests. 2/3 of the patients reacting positive to oxidised terpenes had fragrance related contact allergy and/or positive history for adverse reactions to fragrances. As well as the hydroperoxides produced by linalol, limonene and delta-3-carene other oxidation and resinification effects progressively causes other fairly major changes in essential oil quality over time. Autoxidation of fragrance terpenes contributes greatly to fragrance allergy, which emphasizes the need of testing with compounds that patients are actually exposed to and not only with the ingredients originally applied in commercial formulations. Hydroperoxides of d-limonene are potent contact allergens when studied in guinea pigs. They may result when d- limonene is unstabilised against oxidation, or upon prolonged standing at room temperature and/ or upon exposure to light, or when stabiliser levels diminish. The two major hydroperoxides in auto-oxidised d-limonene,are cis- and trans- limonene-2- hydroperoxide (2- hydroperoxy-p-mentha-6,8-diene). In photo-oxidised d-limonene, they represent a minor fraction. Hydroperoxides may bind to proteins of the skin to make antigens either via a radical mechanism or after reactions to give epoxides. The cross- reactivity between the epoxide limonene-1,2-oxide, a potent contact allergen, and the hydroperoxides is NOT significant, indicating different mechanisms of sensitisation. d-Limonene was considered to be weakly carcinogenic for the mouse fore-stomach epithelium, but not tumour producing. In 13-week and 2-year gavage-studies, male rats showed a range of compound-related kidney lesions including exacerbation of age- related nephropathy, mineralisation in the renal medulla, hyperplasia of the transitional epithelium overlying the renal papilla and proliferation of the renal tubular epithelium. Neoplasms were believed to be caused by progression to tubular cell hyperplasia to tubular cell adenomas and, with increasing size, to adenocarcinomas or carcinomas. The similarity of the nephrotoxicity caused by trichloroethylene and N-(4'-fluoro-4-biphenyl)acetamide, tris(2,3-dibromopropyl)phosphate in rats and the species specific nature of the response suggests that degeneration and necrosis of convoluted tubules may be associated with the accumulation of alpha-2u- globin (a2u-G). Since a2u-G is a species and gender-specific protein that is causal for both the cytotoxic and carcinogenic response in male rats, extrapolation of d-limonene carcinogenicity data from rat studies to other species (including humans) is probably not warranted. Humans do not synthesise a2u-G; they do however produce other related low molecular weight proteins capable of binding chemicals that cause a2u-G nephropathy in rats but this does not necessarily connote human risk. The Risk Assessment Forum of the USA EPA concluded; • Male renal rat tumours arising as a result of a process involving a2u-G accumulation do not contribute to the qualitative weight-of-evidence that the chemical poses a human carcinogenic hazard. Such tumours are included in dose-response extrapolations for the estimation of human carcinogenic risk. • If the chemical induces a2u-G accumulation in male rats, the associated nephropathy is not to be used as an end- point for determining non-carcinogenic hazard. Essential oils and isolates derived from the Pinacea family, including Pinus and Abies genera, should only be used when the level of peroxides is kept to the lowest practicable level, for instance by adding antioxidants at the time of production. Such products should have a peroxide value of less than 10 millimoles peroxide per liter. Based on the published literature mentioning sensitising properties when containing peroxides (Food and Chemical Toxicology 11,1053(1973); 16,843(1978); 16, 853(1978). Pine oil is also a weak allergen. (SAX).