Caffeine Anhydrous: Cambridge Commodities

Caffeine Anhydrous
Cambridge Commodities Chemwatch Hazard Alert Code: 3

Part Number: P0301 Issue Date: 02/10/2024
Version No: 2.6 Print Date: 13/10/2024
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 Caffeine Anhydrous
Chemical Name caffeine
Synonyms Not Available
Proper shipping name ALKALOIDS, SOLID, N.O.S. (contains caffeine); ALKALOID SALTS, SOLID, N.O.S. (contains caffeine)
Chemical formula Not Applicable

Other means of
P0301
identification
1.2. Relevant identified uses of the substance or mixture and uses advised against
Relevant identified uses Use according to manufacturer's directions.
Uses advised against No specific uses advised against are identified.
1.3. Details of the manufacturer or 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 enquiries@cambridgecommodities.com
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
2019/720 and UK SI H302 - Acute Toxicity (Oral) Category 4
2020/1567 [1]
Legend: 1. Classified by Chemwatch; 2. Classification drawn from GB-CLP Regulation, UK SI 2019/720 and UK SI 2020/1567
2.2. Label elements
Product code: P0301 Version No: 2.6 Page 1 of 21

S.REACH.GB.EN Lancaster Way Business Park
Safety Data Sheet (Conforms to Annex II of REACH (1907/2006) - Regulation 2020/878) Ely, Cambridgeshire, CB6 3NX, UK.
Chemwatch: 9-724537 +44 (0) 1353 667258
Issue Date: 02/10/2024 info@c-c-l.com
Print Date: 13/10/2024 www.c-c-l.com
Hazard pictogram(s)
Signal word Warning
Hazard statement(s)
H302 Harmful if swallowed.
Supplementary statement(s)
Not Applicable
Precautionary statement(s) Prevention

P264 Wash all exposed external body areas thoroughly after handling.
P270 Do not eat, drink or smoke when using this product.
Precautionary statement(s) Response

P301+P312 IF SWALLOWED: Call a POISON CENTER/doctor/physician/first aider if you feel unwell.
P330 Rinse mouth.
Precautionary statement(s) Storage

Not Applicable
Precautionary statement(s) Disposal

P501 Dispose of contents/container to authorised hazardous or special waste collection point in accordance with any local regulation.
Material contains caffeine.
2.3. Other hazards

Inhalation may produce health damage*.
Cumulative effects may result following exposure*.
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, Nanoform Particle
Name SCL / M-Factor
3.Index No [weight] UK SI 2019/720 and UK SI 2020/1567 Characteristics
4.REACH No
SCL: Not Available

1. 58-08-2
Acute M factor:
2.200-362-1
100 caffeine Acute Toxicity (Oral) Category 4; H302 [2] Not Available Not Available
3.613-086-00-5
4.Not Available Chronic M factor:
10
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

Eye Contact If this product comes in contact with the eyes:

Chemwatch: 9-724537 +44 (0) 1353 667258
Immediately hold eyelids apart and flush the eye continuously with running water.
Ensure complete irrigation of the eye by keeping eyelids apart and away from eye and moving the eyelids by occasionally
lifting the upper and lower lids.
Continue flushing until advised to stop by the Poisons Information Centre or a doctor, or for at least 15 minutes.
Transport to hospital or doctor without delay.
Removal of contact lenses after an eye injury should only be undertaken by skilled personnel.
If skin or hair contact occurs:

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.
IF SWALLOWED, REFER FOR MEDICAL ATTENTION, WHERE POSSIBLE, WITHOUT DELAY.
For advice, contact a Poisons Information Centre or a doctor.
Urgent hospital treatment is likely to be needed.
In the mean time, qualified first-aid personnel should treat the patient following observation and employing supportive
measures as indicated by the patient's condition.
If the services of a medical officer or medical doctor are readily available, the patient should be placed in his/her care and a
copy of the SDS should be provided. Further action will be the responsibility of the medical specialist.
If medical attention is not available on the worksite or surroundings send the patient to a hospital together with a copy of the
Ingestion SDS.
Where medical attention is not immediately available or where the patient is more than 15 minutes from a hospital or
unless instructed otherwise:
INDUCE vomiting with fingers down the back of the throat, ONLY IF CONSCIOUS. Lean patient forward or place on left side
(head-down position, if possible) to maintain open airway and prevent aspiration.
NOTE: Wear a protective glove when inducing vomiting by mechanical means.
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
for stimulants:
Treatment and Management.
A specific antidote does not exist for acute stimulant intoxication. Activated charcoal should be prescribed in a case of acute overdose. Otherwise the treatment
should target specific signs and symptoms such as hypertension, agitation, seizures, and hyperthermia. Rapid supportive treatment may reduce mortality.
Supportive therapy
Acute intoxication usually presents with increased sensitivity to sensorial stimuli and paranoia. As such, decreasing the patient's level of stimulation (keep voice
low, dim lights, minimise touch) and working with the patient's paranoid state (reduce eye contact, respect personal space, do not approach from behind) is
important.
As in all cases of suspected poisoning, follow the ABCDEs of emergency medicine (airway, breathing, circulation, disability, exposure), then the ABCDEs of
toxicology (antidotes, basics, change absorption, change distribution, change elimination).
Decontamination with gastric lavage may be appropriate in cases of recent ingestion.
Monitor vital signs and hydrate with intravenous fluids.
Withdrawal related insomnia may be treated with trazodone (75-200 mg), hydroxyzine (25-50 mg), or diphenhydramine (50-100 mg) at bedtime.
Benzodiazepines should be avoided unless the patient is also in detox from alcohol/benzodiazepines/opiates.
Neuroleptics may be used for the symptomatic treatment of psychosis.
Physical restraints may be required in certain cases.
Common withdrawal symptoms may include dysphoria, anxiety, and irritability, decreased energy (manifested as reported fatigue, psychomotor retardation and
hypersomnia), hyperphagia, decreased concentration, and paranoia. The withdrawal symptoms are uncomfortable but not life threatening; consequently, no
current recommendations for a stimulant-detoxification regimen are available.
Stimulant withdrawal dysphoria is common and does not in itself represent an indication for an antidepressant. However, a thorough assessment (including
consideration of an antidepressant) is recommended for persistent (longer than a week) depressive symptoms at a level of moderate or severe or associated with
suicidal ideation/attempts.
Medscape
Treat symptomatically.
for caffeine intoxication:
If caffeine has been ingested within 4 hours in amounts over 15 mg/kg, removal from the stomach by Ipecac syrup or gastric lavage is recommended. Activated
charcoal is probably useful within the first 4 hours. Magnesium sulfate cathartic may be useful.
SECTION 5 Firefighting measures
5.1. Extinguishing media

Foam.

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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 full body protective clothing with breathing apparatus.
Prevent, by any means available, spillage from entering drains or water course.
Use fire fighting procedures suitable for surrounding 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.
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
Fire/Explosion Hazard 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)
,
nitrogen oxides (NOx)
,
other pyrolysis products typical of burning organic material.
SECTION 6 Accidental release measures
6.1. Personal precautions, protective equipment and emergency procedures

See section 8
6.2. Environmental precautions

Chemwatch: 9-724537 +44 (0) 1353 667258
See section 12
6.3. Methods and material for containment and cleaning up

Clean up waste regularly and abnormal 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 Vacuum up or sweep up. NOTE: Vacuum cleaner must be fitted with an exhaust micro filter (H-Class HEPA type) (consider
explosion-proof machines designed to be grounded during storage and use). H-Class HEPA filtered industrial vacuum
cleaners should NOT be used on wet materials or surfaces.
Dampen with water to prevent dusting before sweeping.
Place in suitable containers for disposal.
Clear area of personnel and move upwind.
Alert Fire Brigade and tell them location and nature of hazard.
Wear full body protective clothing with breathing apparatus.
Prevent, by any means available, spillage from entering drains or water course.
Stop leak if safe to do so.
Contain spill with sand, earth or vermiculite.
Major Spills
Collect recoverable product into labelled containers for recycling.
Neutralise/decontaminate residue (see Section 13 for specific agent).
Collect solid residues and seal in labelled drums for disposal.
Wash area and prevent runoff into drains.
After clean up operations, decontaminate and launder all protective clothing and equipment before storing and re-using.
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

Safe handling NOTE : Do NOT pipette by mouth. Only trained personnel should be allowed to handle or use this product.
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.
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.
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.

Chemwatch: 9-724537 +44 (0) 1353 667258
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
Store in original containers.
Keep containers securely sealed.
Store in a cool, dry, well-ventilated area.
Other information
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.
7.2. Conditions for safe storage, including any incompatibilities

Glass container is suitable for laboratory quantities
Lined metal can, lined metal pail/ can.
Plastic pail.
Polyliner drum.
Packing as recommended by manufacturer.
Check all containers are clearly labelled and free from leaks.
For low viscosity materials
Drums and jerricans must be of the non-removable head type.
Where a can is to be used as an inner package, the can must have a screwed enclosure.
For materials with a viscosity of at least 2680 cSt. (23 deg. C) and solids (between 15 C deg. and 40 deg C.):
Removable head packaging;
Suitable container
Cans with friction closures and
low pressure tubes and cartridges
may be used.
-
Where combination packages are used, and the inner packages are of glass, there must be sufficient inert cushioning material in
contact with inner and outer packages *.
-
In addition, where inner packagings are glass and contain liquids of packing group I and II there must be sufficient inert
absorbent to absorb any spillage *.
-
* unless the outer packaging is a close fitting moulded plastic box and the substances are not incompatible with the plastic.
Avoid strong acids, bases.
Storage incompatibility
Avoid reaction with oxidising agents
Hazard categories in
accordance with
Not Available
Regulation (EC) No
2012/18/EU (Seveso III)
Qualifying quantity
(tonnes) of dangerous
substances as referred to Not Available
in Article 3(10) for the
application of
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
0.087 mg/L (Water (Fresh))
0.87 mg/L (Water - Intermittent release)
Dermal 25.17 mg/kg bw/day (Systemic, Chronic) 0.009 mg/L (Water (Marine))
caffeine
Inhalation 44.37 mg/m³ (Systemic, Chronic) 0.4 mg/kg sediment dw (Sediment (Fresh Water))
0.029 mg/kg soil dw (Soil)
10 mg/L (STP)
* Values for General Population
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

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Not Applicable
Ingredient Original IDLH Revised IDLH
caffeine Not Available Not Available
Occupational Exposure Banding
Ingredient Occupational Exposure Band Rating Occupational Exposure Band Limit

caffeine 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

8.2.1. Appropriate For potent pharmacological agents:
engineering controls Powders
To prevent contamination and overexposure, no open handling of powder should be allowed.
Powder handling operations are to be done in a powders weighing hood, a glove box, or other equivalent ventilated
containment system.
In situations where these ventilated containment hoods have not been installed, a non-ventilated enclosed containment hood
should be used.
Pending changes resulting from additional air monitoring data, up to 300 mg can be handled outside of an enclosure
provided that no grinding, crushing or other dust-generating process occurs.
An air-purifying respirator should be worn by all personnel in the immediate area in cases where non-ventilated containment
is used, where significant amounts of material (e.g., more than 2 grams) are used, or where the material may become
airborne (as through grinding, etc.).
Powder should be put into solution or a closed or covered container after handling.
If using a ventilated enclosure that has not been validated, wear a half-mask respirator equipped with HEPA cartridges until
the enclosure is validated for use.
Solutions Handling:
Solutions can be handled outside a containment system or without local exhaust ventilation during procedures with no
potential for aerosolisation. If the procedures have a potential for aerosolisation, an air-purifying respirator is to be worn by all
personnel in the immediate area.
Solutions used for procedures where aerosolisation may occur (e.g., vortexing, pumping) are to be handled within a
containment system or with local exhaust ventilation.
In situations where this is not feasible (may include animal dosing), an air-purifying respirator is to be worn by all personnel in
the immediate area. If using a ventilated enclosure that has not been validated, wear a half-mask respirator equipped with
HEPA cartridges until the enclosure is validated for use.
Ensure gloves are protective against solvents in use.
Air should be supplied by an independent system.
Engineering controls are used to remove a hazard or place a barrier between the worker and the hazard. Well-designed
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 usually required. If risk of overexposure exists, wear approved respirator. Correct fit is essential to
obtain adequate protection. Supplied-air type respirator may be required in special circumstances. Correct fit is essential to
ensure adequate protection.
An approved self contained breathing apparatus (SCBA) may be required in some situations.
Provide adequate ventilation in warehouse or closed storage area. Air contaminants generated in the workplace possess varying
"escape" velocities which, in turn, determine the "capture velocities" of fresh circulating air required to effectively remove the
contaminant.
Type of Contaminant: Air Speed:

0.25-0.5 m/s (50-
solvent, vapours, degreasing etc., evaporating from tank (in still air).
100 f/min.)
aerosols, fumes from pouring operations, intermittent container filling, low speed conveyer transfers, 0.5-1 m/s (100-
welding, spray drift, plating acid fumes, pickling (released at low velocity into zone of active generation) 200 f/min.)
direct spray, spray painting in shallow booths, drum filling, conveyer loading, crusher dusts, gas 1-2.5 m/s (200-
discharge (active generation into zone of rapid air motion) 500 f/min.)
grinding, abrasive blasting, tumbling, high speed wheel generated dusts (released at high initial velocity 2.5-10 m/s (500-
into zone of very high rapid air motion). 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

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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 1-2 m/s (200-400 f/min) for extraction of solvents generated in a tank 2
meters 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. Individual protection

measures, such as
personal protective
equipment
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
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.
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.
Hands/feet protection
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.
Wear chemical protective gloves, e.g. PVC.
Wear safety footwear or safety gumboots, e.g. Rubber
Body protection See Other protection below
Handle extremely poisonous natural toxins in closed systems such as glove bags or other enclosures, to avoid accidental
contact. Workers should wear complete disposable clothing including shoe covers, gloves and mask with an independent air
supply.
Other protection Overalls.
Eyewash unit.
Barrier cream.
Skin cleansing cream.

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Respiratory protection
Type -P Filter of sufficient capacity. (AS/NZS 1716 & 1715, EN 143:2000 & 149:2001, 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
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.
Class P2 particulate filters are used for protection against mechanically and thermally generated particulates or both.
P2 is a respiratory filter rating under various international standards, Filters at least 94% of airborne particles
Suitable for:
· Relatively small particles generated by mechanical processes eg. grinding, cutting, sanding, drilling, sawing.
· Sub-micron thermally generated particles e.g. welding fumes, fertilizer and bushfire smoke.
· Biologically active airborne particles under specified infection control applications e.g. viruses, bacteria, COVID-19, SARS
The use of a disposable filtering facepiece respirator is required when working with toxins in solution if there is a concern for aerosol generation.
8.2.3. Environmental exposure controls

See section 12
SECTION 9 Physical and chemical properties
9.1. Information on basic physical and chemical properties

Appearance Not Available
Relative density (Water =

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

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 (1%) Not Available

Chemwatch: 9-724537 +44 (0) 1353 667258
Vapour density (Air = 1) Not Available VOC g/L Not Available
Heat of Combustion (kJ/g) Not Available Ignition Distance (cm) Not Available
Flame Height (cm) Not Available Flame Duration (s) Not Available
Enclosed Space Ignition

Enclosed Space Ignition
Not Available Deflagration Density Not Available
Time Equivalent (s/m3)
(g/m3)
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

Inhalation of dusts, generated by the material, during the course of normal handling, may be harmful.
The material is not thought to produce respiratory irritation (as classified by EC Directives using animal models). Nevertheless
inhalation of dusts, or fumes, especially for prolonged periods, may produce respiratory discomfort and occasionally, distress.
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.
Inhalation of caffeine dusts or aerosols may produce nose and throat irritation, coughing and chest discomfort. The material may
act as a stimulant following massive inhalations.
Toxic effects may result from the accidental ingestion of the material; animal experiments indicate that ingestion of less than 40
gram may be fatal or may produce serious damage to the health of the individual.
Adenosine has a depressive action on the brain, heart, kidneys and other organs, and is believed to mediate its effects via four
receptors. It is also involved in the sensation of pain, movement, and sleep.
Adverse effects associated with the administration of central nervous system stimulants include shortness of breath, coughing,
spasm of the bronchi and spasm of the throat (larynx). Muscular involvement may produce symptoms ranging from twitching to
spasticity or seizures. Headache, dizziness and confusion may also result, as can a very high fever or a sensation of warmth.
Other symptoms may include nausea, vomiting, diarrhea and difficulty in urination. Cardiovascular involvement may cause
changes in blood pressure, an increased heart rate or heart rhythm disturbances. Haemorrhagic (bleeding) stroke and heart
attack may occur. There may also be low blood sodium levels. Due to excessive dopaminergic discharge, dyskinesias
(involuntary movements) may be present.
Ingestion The material may produce biochemical inhibition of the enzyme, phosphodiesterase. Several families of drug (including
xanthines, papaverine, bipyridines, imidazolines, imidazolones, dihydropyridazinones, dihydroquinilones, pyrrolidinones) produce
this effect.
Vasodilators given orally or by injection may produce dose dependent and transient flushing of the face, and skin, together with a
sensation of heat, a pounding in the head, swelling in the ankles, headache, low blood pressure, palpitations, dizziness and
fatigue. High doses may cause skin damage, abdominal cramps, diarrhoea, nausea, vomiting, loss of appetite, general
unwellness, jaundice, cause ulcers and impair liver function. It may cause a mild diabetes. These effects depend on the dosage
and generally subside after withdrawal of the drug.
Xanthine derivatives may produce nausea, vomiting, anorexia, stomach pain, vomiting of blood and diarrhoea. Protein in the
urine, increased amounts of urine output, and increased excretion of renal tubular cells and red blood cells may also occur.
Low doses of caffeine are safe although mildly stimulatory. Acute poisoning is characterised by nausea and vomiting, loss of
appetite, vomiting blood, gastrointestinal upset, increased urination and dehydration.
Skin Contact Skin contact is not thought to produce harmful health effects (as classified under EC Directives using animal models). Systemic
harm, however, has been identified following exposure of animals by at least one other route and 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

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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.
Although the material is not thought to be an irritant (as classified by EC Directives), direct contact with the eye may cause
Eye
transient discomfort characterised by tearing or conjunctival redness (as with windburn). Slight abrasive damage may also result.
Ample evidence exists that this material directly causes reduced fertility
In general, vasodilators dilate or prevent constriction of the blood vessels, which allow greater blood flow to various organs in the
body. Many vasodilators bind to receptors on endothelial cells of the blood vessel, which stimulate calcium release. Calcium
activates the enzyme nitric oxide synthase (NO synthase) and converts L-arginine into NO. It leaves the endothelial cell via
diffusion and enters vascular smooth muscle cells. NO activates GTP and converts it into cGMP. cGMP then stimulates myosin-
light chain phosphatase, which removes a single phosphate from myosin and actin filaments. The dephosphorylation of myosin
and actin filaments allows vascular smooth muscle relaxation.
Direct-acting vasodilating agents enter the vascular smooth muscle cell to cause vasodilatation. For long term treatment of
hypertension, the use of these drugs as monotherapy is accompanied by activation of the sympathetic nervous system and the
renin-angiotensin-aldosterone system. These counteracting mechanisms limit the antihypertensive efficacy of these drugs, and
Chronic
cause adverse effects such as tachycardia and fluid retention. These adverse effects require treatment with beta-blockers and
diuretics. However, there is still an important role for intravenous vasodilator therapy in hypertensive emergencies. In the
treatment of chronic heart failure, vasodilator therapy has been an important advance. Combination therapy with hydralazine and
nitrates is efficacious in improving survival, but ACE inhibitors have an incremental benefit on survival over this combination.
Undertreatment and/or non-compliance, using vasodilation therapies, can cause severe hypertension, and this can lead to
catastrophic events such as stroke, hypertensive emergency, aortic dissection, and many other preventable diseases
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.
TOXICITY IRRITATION
Caffeine Anhydrous
Not Available Not Available
TOXICITY IRRITATION
dermal (rat) LD50: >2000 mg/kg[1] Eye (Rodent - rabbit): 100mg

caffeine
Inhalation (Rat) LC50: ~4.94 mg/l4h[1] Eye: no adverse effect observed (not irritating)[1]
Oral (Mouse) LD50; 127 mg/kg[2] Skin: no adverse effect observed (not irritating)[1]
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
Oral (woman) TDLo: 96 mg/kg/1d-I Tumorigenic - Carcinogenic by RTECS criteria.

Methylxanthine overdose may result in hyperventilation, respiratory alkalosis, and respiratory arrest.
Methylated xanthines (methylxanthines), which include caffeine, aminophylline, IBMX, paraxanthine, pentoxifylline, theobromine, and theophylline, affect not
airways but stimulate heart rate, force of contraction, and cardiac arrhythmias at high concentrations. In high doses, they can lead to convulsions that are res
CAFFEINE
anticonvulsants. Methylxanthines induce acid and pepsin secretions in the gastrointestinal tract. Methylxanthines are metabolized by cytochrome P450 in the
The substance is classified by IARC as Group 3:
NOT classifiable as to its carcinogenicity to humans.
Evidence of carcinogenicity may be inadequate or limited in animal testing.
Caffeine Anhydrous & For adenosine and adenosine receptor (AR) ligands.
CAFFEINE There are several conditions in which chronic adenosine overproduction can be harmful, leading to increased inflammation, fibrosis, cytokine release, brain d
depletion, and kidney damage It is well known that adenosine is beneficial, adopting the role of guardian angel when present at physiological levels or when
acute situations. However, it must be re membered that there are instances in which its chronic overproduction is pathological. In particularly, over-production
with ischaemia, neurodegenerative diseases, fibrosis, hepatic steatosis, colitis,asthma, diabetes and cancer, Indeed, A2A, A2B and A3 receptor antagonists m
specific/unique place in different clinical applications
However, there are conditions in which chronic adenosine overproduction can be harmful, leading to increased inflammation, fibrosis, cytokine release, brain
depletion, and kidney damage .
One limitation of AR agonists for human therapeutics is that their target GPCRs might be subject to agonist-induced desensitization as shown for all four ARs
However, in other cases, depending on multiple pharmacological factors, a prolonged agonist exposure did not lead to in vivo desensitization of the desired e
a full A3 receptor agonist. Two possible approaches to circumvent GPCR desensitization are the use of partial agonists in cases where the desired effect is m
as in A1 antiarrhythmic activity and the use of positive allosteric modulators (PAMs) . Partial agonists are also known to display tissue or organ selectivity, be
differential receptor expression level . Thus, when spare receptors are present, i.e., overexpression or high level of endogenous expression, a partial agonist
efficacious in tissues where there is a receptor reserve and activation of only a fraction of the receptors suffices
The negative actions of long-lasting increases in the extracellular adenosine concentration lead to overactivation of membrane receptors, thus opening the w
clinical development of specific antagonists. First of all, starting with the CNS injuries, A2A selective antagonists may have a role in the therapy of ischaemia
careful attention to administration time and to the dose of A2A receptor antagonist has to be considered for a novel therapeutic strategy. Parkinson's disease
neurodegenerative diseases such as Huntington's disease (HD) and Alzheimer's (AD), major depression, schizophrenia, epilepsy, acute and chronic stress, r
syndrome (RLS) and memory fear are pathologies for which A2A selective inhibitors could became new drugs.
The elegant evidence regarding the modulation of heterotetrameric structure of the A2A/D2 receptor complex and the similarity between A2A receptor agonis
antagonist effect on the affinity and intrinsic efficacy of dopamine-2 (D2) receptor ligands offers a novel model that can provide new clues about how to adjus
use of these drugs.
In multiple sclerosis (MS), an autoimmune disease of central origin, both A2A and A2B receptor antagonists attenuated the increased inflammation and then
development of its pathology. Hence, the blockade of these receptors might be a strategy for the development of new drugs for MS therapy.
Understanding the effect of A2B receptor modulation in intestinal inflammation, glucose and lipid regulation is necessary to clarify whether this subtype is pro
injurious in both colitis, diabetes and atherosclerosis, respectively, with the aim of adequately recognizing its therapeutic potential.

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Furthermore, A2B and A3 receptor antagonists may represent a starting point for the development of novel drugs to hamper remodelling occurring after tissu
and for the therapy of consequent fibrotic diseases arising in the lung, kidney and heart.
Pioneering research on tumours and hypoxia also opens the way for the use of A2A receptor antagonists in the therapy of cancer. Due to their immunosuppr
and tumour tolerant behaviour, now both A2A an A2B receptors are considered important and promising targets for the development of a novel class of antitu
able to weaken the hypoxia-adenosine mediated signalling pathways. It is important to note that existing A2A receptor antagonists tested in human clinical st
have already demonstrated their safety profile. However, in the future, it will be important to consider the development of new A2A receptor blockers unable t
blood-brain-barrier (BBB), thus avoiding the occurrence of potential neurological side effects in cancer patients with non-cerebral tumours. This task may be
important advances in the structure-based design of A2A receptor antagonists that take advantage of the molecular basis of this adenosine subtype
Pathological role of adenosine in cerebral ischaemia
In the CNS, both neurons and glial cells produce adenosine and express adenosine receptors that affect several homeostatic functions ranging from sleep to
learning, memory and cerebral blood circulation. The principal adenosine receptor subtypes located in the CNS are A1 and A2A receptors, which are crucial
of neurotransmitter release, neuronal excitability, synaptic plasticity, vasodilatation and neuroinflammation.
In general, the role of A1 receptors emerges as neuroprotective being an inhibitor of excitatory transmission, while that of the A2A receptor is detrimental, eve
evidence has been obtained showing that its activation has beneficial effects.
The molecular bases of the adverse effects of A2A receptor stimulation are attributed to its modulation of neuronal glutamate release, potentiation of NMDA-m
effects, central inflammatory processes, glial reactivity, blood–brain barrier (BBB) permeability and infiltration of peripheral immune cells, which are associate
excitotoxicity and the pathogenesis of several brain disease. Studies related to the involvement of A2A receptors. in ischaemia, found that its antagonism pro
against ischaemic insult. It has been demonstrated that after ischaemia, excitotoxicity is the first phenomenon occurring in the brain in the first 4 hours, when
receptor is responsible for the increase in glutamate levels, through both the release of glutamate from glutamatergic terminals and the inhibition of the glutam
transporter (GLT-1) in astrocytes. Indeed, it has been shown that A2A receptor blockade protects against excitotoxicity. Furthermore, A2A receptor activation
affinity of agonists for A1 receptors in A1-A2A receptor heteromers, which exert a presynaptic control of striatal glutamate release, resulting in the finetuning o
modulatory effect on striatal glutamatergic neurotransmission.
At the intracellular level, the inhibition of p38 MAPK in microglia and JNK in oligodendrocytes may be responsible for the protective effect mediated by A2A re
antagonists in ischaemia. However, it is also known that later, hours and days after insult, there is a massive infiltration of blood cells and neuroinflammation
inhibited by activation of A2A receptors located on blood cells. Accordingly, the chronic administration of an A2A receptor antagonist for 7 days after transient
ischaemia failed to protect the brain, suggesting that A2A receptor antagonists should be administered for a limited time window of about 4 hours after stroke
important to mention that chronic enhanced levels of adenosine may lead to seizures, through A2A receptor activation and neurotrophins, suggesting that in
receptor antagonists could be useful clinically
Interestingly, certain evidence adds a new pathological aspect to adenosine overproduction related to the development of pain behaviour. This effect seems t
activation A2B receptors on myeloid cells, which are able to transactivate nociceptors of sensory neurons, and induce hypersensitive neurons and chronic pa
pathway involving IL-6. Hence, the A2B receptor may play a major role in chronic pain by promoting immune-neuronal interactions
Pathological role of adenosine in neurodegenerative diseases
There is a well-established allosteric relationship between striatal A2A receptors and dopamine D2 receptors, supported by evidence that A2 receptor activat
responsible for the decreased affinity of agonist binding to D2 receptors.
Interestingly, the well-known epidemiological consideration that caffeine protects against PD has been confirmed in an animal model of Parkinson's disease (
attributed to A2A receptor antagonism
A2A receptors and D2 receptor heteroceptor complexes have been detected in cellular models and in the striatum.
As the receptors show antagonistic interactions at both membrane and intracellular signalling levels, dopamine depletion may be responsible for an overactiv
receptors and the consequent symptoms of PD .
Therefore, antagonists of A2A receptors are beneficial for the improvement in motor function in different animal models of PD, as they attenuate the inhibition
A2A receptors on the effects of D2 receptors in the gabaergic striato-pallidal neurons. One model suggest that high concentrations of A2A receptor antagonis
same effects as A2A receptor agonists, thus reducing D2 receptor-mediated activity in neurons; these findings could be important from a clinical point of view
of A2A receptor antagonists is being considered for therapy.
The use of A2A receptor antagonists has been found useful in other pathologies involving neuronal dysfunction including Huntington s (HD) and Alzheimer s
as well as major depression and schizophrenia, epilepsy, acute and chronic stress, restless legs syndrome (RLS) and memory fear. It has also been shown t
receptor antagonists block working memory deficits at early stages of HD model
Pathological role of adenosine in autoimmune diseases
Immune cells express all adenosine receptors, which means adenosine can affect inflammatory and immune events. In particular, it was found that adenosin
immune function by exerting inhibitory effects on neutrophils, lymphocytes monocytes/macrophages and dendritic cells. Therefore, a possible area of investig
therapeutic strategies through adenosine receptor modulation is the study of adenosine s role in the immunopathogenesis of multiple sclerosis (MS).
Surprisingly, even though the A2A receptor is recognized as a major mediator of anti-inflammatory responses, it has been reported that the pharmacological
subtype attenuates experimental autoimmune encephalomyelitis (EAE) pathology in CD73 KO mice (EAE is an animal model for MS). However, to explain th
effects of A2A receptor antagonists in EAE, it has been suggested that although the A2A receptor present on lymphocytes is anti-inflammatory, that expresse
plays a pro-inflammatory role and appears to be essential for EAE development. However, an A2A receptor agonist worsened experimental autoimmune neu
inhibitory effect of T-cell proliferation and IL-2 secretion .
Pathological role of adenosine in inflammatory conditions
Inflammation is a hallmark of important diseases such as cardiovascular, metabolic, intestinal and pulmonary disorders.
As for the detrimental signalling of adenosine in inflammatory conditions, focus is placed on A2B receptors as mediators of the effects of autacoids because t
activated by µM concentrations of adenosine, occurring in inflammation, hypoxia and cell injury (autacoids act like brief duration local hormones).. In particula
expression of A2B receptors is increased in hypoxia in response to hypoxia-inducible factors (HIFs). Indeed, it has been demonstrated that A2B receptors ha
inflammatory environment typically present in asthma, chronic obstructive pulmonary disease (COPD), kidney pathologies and inflammatory bowel diseases.
receptors expressed in the human lung, mast cells and in macrophages enriched with lipids, known as foam cells (FC), play a role in the regulation of the infl
present in pulmonary and atherosclerotic diseases.
Adenosine is responsible for the production of VEGF, IL-6 and IL-8 through interaction with all four adenosine receptors in inflamed tissues, in which the leve
autacoids are increased. However, the A2B and A3 receptor subtypes are mainly involved in the modulatory effects of adenosine on wound healing processe
angiogenesis and fibrosis. The A2B receptor plays a significant role in the chronic phase of wound healing after tissue injury and increases the adverse signa
responsible for the continuous tissue remodelling and fibrosis occurring n chronic inflammatory conditions
Pulmonary fibrosis is a harmful lung disease with limited therapeutic options. Adenosine has a role as a proinflammatory messenger in different chronic pulm
inflammatory conditions, such as asthma and COPD. It has been reported that increased extracellular adenosine concentrations, by inducing the production
17, are associated with the progression of experimental pulmonary fibrosis. It has been hypothesized that adenosine may induce IL-17 expression through its
subtype in chronic lung injury, thus contributing to lung fibrosis. Furthermore, adenosine promotes the differentiation of alternatively activated macrophages, a
subtype that has been shown to contribute to pulmonary fibrosis, stimulated by Th2 cytokines (IL-4 and IL-13) . In addition, it has been reported that A2B rec
regulated in lung tissue from idiopathic pulmonary fibrosis patients. Therefore, it is important to verify and understand the association between extracellular a
and the progression of pulmonary fibrosis to develop new drugs for this pathology based on the structures of adenosine ligands binding to A2B receptors. As
adenosine in asthma and COPD, it is interesting to note that A2B receptor signalling promotes the production of Th2-type cytokines and the recruitment and

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eosinophils. Furthermore, the secretion of IL-4 by human mast cells is mediated through A2B receptors and this increases IgE production by B cells and as a
triggers allergic inflammation.
Pathological role of adenosine in diabetes
It is well recognized that adenosine regulates insulin secretion, glucose homeostasis and lipid metabolism, by stimulation its receptors. The stimulation of A1
receptor subtypes seems to promote an antidiabetic phenotype even though it has been shown that blockade of A1 receptor activation offers protection from
oxidative stress and secretion of proinflammatory cytokines, thus improving insulin release and effect. The protective effect of the A2B receptor is challenged
studies reporting the beneficial effects of A2B receptor antagonists. It was firstly reported that A2B receptor antagonists behave as hypoglycaemic agents in r
hepatic glucose production induced by adenosine. Furthermore, it was found that A2B receptor activation increases glucose production by affecting glycogen
gluconeogenesis in the rat liver. Following this line, A2B receptor antagonists were shown to counteract the reduction in insulin levels induced by a non-selec
receptor agonist in pancreatic cells and plasma from rats, even though this effect is not mediated through A2B receptor activation. A2B receptor antagonists w
demonstrated to reduce the levels of IL-6 and other cytokines affecting glucose and fat metabolism in a diabetic mouse model, thus improving insulin resistan
Interestingly, it has been found that high glucose levels and experimental diabetes increase the concentrations of adenosine in plasma. This increase correla
marker of renal fibrosis in diabetic rats. Furthermore, the expression of profibrotic cell activation markers alpha-smooth muscle actin and fibronectin was incre
stimulation of A3 receptors. Therefore, before establishing a role for A2B receptor agonists or A2B/A3 receptor antagonists in diabetic therapy, when looking
it is important to accurately examine the experimental conditions associated with glucose and insulin regulation including the method used for inhibiting the re
(pharmacological vs. genetic) and the cell types or model system used.
Pathological role of adenosine in cancer
Adenosine plays a role in promoting cancer development by evoking immunosuppressive effects and directly affecting the growth, metastasis and angiogene
cells. Within tumor microenvironment, extracellular adenosine reaches elevated concentrations and by activating the adenosine receptor subtypes A2A and A
effector T cell functions, induces immunosuppression, and stimulates angiogenesis Extracellular adenosine production is finely regulated by many enzymes,
critically impaired in pathological conditions, such as inflammatory disorders or cancer. The classical pathway of extracellular adenosine production is based
reactions mediated by two ectonucleotidases, specifically extracellular adenosine triphosphate is first hydrolyzed by CD39 into adenosine monophosphate (A
dephosphorylated into adenosine by CD73.
There is a strong relationship between cancer, hypoxia and adenosine metabolism resulting in increased levels of the autacoids in hypoxic tumours. This effe
a consequence of specific alterations in the enzymes involved in adenosine production, for example, the overexpression of CD-73 and the down-regulation o
kinase (ADK) are both increased by hypoxia.
Indeed, clinical studies have reported that the expression of CD73 is associated with a poor prognosis in different types of cancer including breast, ovarian, p
and leukemia. The effects of CD73 on cancer development have been attributed to the immunosuppressive effects of A2A and A2B receptor stimulation.
In particular, adenosine induces an immune-tolerant microenvironment around tumours affecting the functions of immune and inflammatory cells like T- and n
(NK) cells, macrophages and dendritic and myeloid-derived suppressor cells (MDSC). Treg cells express high levels of CD39 resulting in an increased produ
adenosine, which then inhibits the antitumour immune response; this effect of adenosine is mediated through inhibition of NK effector lymphocytes that lose t
recognize neoplastic cells. This effect was initially attributed to A3 receptor activation, but is now thought to be mediated by A2A receptors.
The adenosine machinery also mediates its effects directly in tumour cells by affecting their proliferation and cell death through recruitment of different recept
particular, opposite effects on cell growth and motility have been observed, with A1, A2A and A2B receptors being promoters whilst A3 receptors are inhibitor
proliferation.
Nevertheless, it has been reported that A2B receptors have a prometastatic and prosurvival effect and that stimulation of A1, A2A and A3 receptors increases
growth, neovascularization, angiogenesis and macrophage infiltration in CD73 KO mice.
An overexpression of A3 receptors has been reported in different tumours including colon, breast, hepatocellular and mesothelioma. Furthermore, an up-regu
receptors has also been observed in colorectal cancer. Therefore, ii can be concluded that the important effects adenosine exerts on the progression and dev
cancer depend on the subtype of adenosine receptor expressed in each tumour.
Pathological overproduction: the bad side of adenosine: Pier Andrea Borea et al:: British Journal of Pharmacology (2017) 174 pp 1945–1960
https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.13763#:~:text=The%20molecular%20bases%20of%20the,peripheral%20immune%20cells%2C%
For phosphodiesterase inhibitors
Phosphodiesterase (PDE) inhibitors are a heterogenic class of drugs that target various isoforms of PDE enzymes. Normally, the PDE decreases cAMP or cG
cells by catalyzing the hydrolysis of these second messengers. By inhibiting this step, PDE inhibitors actually increase cAMP and/or cGMP concentrations. T
classified according to their target isoforms as nonspecific, PDE5, PDE4, and PDE3 inhibitors, each of which has a different clinical use.
The cardiac and vascular effects of cAMP-dependent PDE inhibitors cause cardiac stimulation, which increases cardiac output, and reduced systemic vascu
which tends to lower arterial pressure. Because cardiac output increases and systemic vascular resistance decreases, the change in arterial pressure depen
relative effects of the PDE inhibitor on the heart versus the vasculature.
Activators of PDEs appear to relieve the influence of autoinhibitory domains located within the enzyme structure. Side-effects of treatment with PDEIs, often
the nature of inhibition. For example, the use of PDE-III-specific agents have a tendency to produce tachycardia (elevated heart-rates, typically exceeding 10
minute). PDE-IV, the primary isozyme located in inflammatory cells associated with bronchial asthma have been targeted by PDE-IV-specific inhibitors; atopic
also treated with this family of inhibitors. Some PDE-IV-specific agents (such as rolipram) produce central nervous system side-effects. Type-V inhibitors (typ
dipyridamole) have been used as vasodilators of the coronary circulation, increasing blood flow to a weakened heart, in part, because they inhibit thrombo-em
been shown that increased cAMP and cGMP levels reduce platelet aggregation, reducing the size of clots). cGMP-PDE-specific agents (those mimicking the
and thus acting as substrates for several isozymes, in a specific manner) are generally targeted towards angina, hypertension, congestive heart failure, ather
peripheral vascular disease, stroke, bronchitis, asthma, glaucoma and irritable bowel syndrome. One of these, a synthetic vasodilator, Sildenafil (Viagra) was
produce unexpected side-effects, namely formation and maintenance of penile erection. The effect of this drug on the corpus cavernosal smooth muscle of th
established; PDE-V has been identified as the primary isoenzyme associated with relaxation of the arteries of the this muscle. A side-effect of Viagra treatme
substrate binding to PDE-VI, the predominant PDE found in the retina. Patients occasionally complain about altered colour perception and/or increased sens
(photophobia). This "blue haze" showed a dose-related effect, probably restricted to the blue-green part of the spectrum. Cardiovascular effects have also be
Viagra especially amongst patients receiving nitric oxide donators (e.g nitroglycerin, isosorbide mononitrate and pentaerythritol) for hypertension and heart d
drugs produce a synergistic effect resulting in unexpectedly high levels of cGMP; this often results in a catastrophic drop in systemic blood pressure (due to v
producing a continuum of symptoms ranging from mild dizziness or light-headedness, fainting upon standing, or even a heart attack or stroke.
Common side effects include:
Nonspecific phosphodiesterase inhibitors
Cardiotoxicity: tachycardia that may degenerate into arrhythmias and hypotension in severe cases
Neurotoxicity: dosage-dependent
At low levels: dizziness, lightheadedness, headache, tremor, agitation, irritability, insomnia, psychotic symptoms
At high levels: seizures
Gastrointestinal (GI) upset: severe, refractory nausea and vomiting, diarrhea, abdominal pain
Phosphodiesterase type 5 inhibitors
Headaches, cutaneous flushing
Lightheadedness
Sildenafil: visual deficits (blue-tinted vision, or cyanopia) due to PDE-6 inhibition in the retina
Runny nose, nasal congestion

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Exanthema
Dyspepsia
Rarely: myocardial infarction, stroke, hearing loss, optic neuropathy
GI upset (nausea, abdominal pain)
Weight loss
Mental disorders: sleep disturbances, anxiety, depression
PDE5 is found in the corpus cavernosum of the penis and in vascular smooth muscle. This enzyme is responsible for breaking down cGMP that forms in resp
increased nitric oxide (NO). Increased intracellular cGMP inhibits calcium entry into the cell, thereby decreasing intracellular calcium concentrations and caus
muscle relaxation.
NO also activates K+ channels, which leads to hyperpolarization and relaxation. Finally, NO acting through cGMP can stimulate a cGMP-dependent protein k
activates myosin light chain phosphatase, the enzyme that dephosphorylates myosin light chains, which leads to relaxation. Therefore, inhibitors of cGMP-de
phosphodiesterase, increase intracellular cGMP, enhance smooth muscle relaxation and vasodilation, and cause penile erection.
Tachycardia, ventricular arrhythmias (most common and severe side effect, so not recommended for chronic use)
Headaches
Hypotension
Intracellular concentrations of cAMP play an important second messenger role in regulating cardiac muscle contraction. Activation of the sympathetic nervou
releases the neurotransmitter norepinephrine and increases circulating catecholamines (epinephrine and norepinephrine). These catecholamines bind prima
adrenoceptors in the heart that are coupled to Gs-proteins. This activates adenylyl cyclase to form cAMP from ATP. Increased cAMP, through its coupling wit
intracellular messengers, increases contractility (inotropy), heart rate (chronotropy) and conduction velocity (dromotropy). Cyclic-AMP is broken down by an e
cAMP-dependent phosphodiesterase (PDE). The isoform of this enzyme that is targeted by currently used clinical drugs is the type 3 form (PDE3). Inhibition
prevents cAMP breakdown and thereby increases its intracellular concentration. This increases cardiac inotropy, chronotropy and dromotropy. PDE3 inhibitor
thought of as a backdoor approach to cardiac stimulation, whereas beta-agonists go through the front door to produce the same cardiac effects.
PDE3 inhibitors also decrease platelet aggregation by increasing platelet cAMP.
Goitrogenic:
Goitrogens are substances that suppress the function of the thyroid gland by interfering with iodine uptake, which can, as a result, cause an enlargement of t
goitre).
Goitrogens include:
- Vitexin, a flavonoid, which inhibits thyroid peroxidase, contributing to goitre
- Thiocyanate and perchlorate, which decrease iodide uptake by competitive inhibition and consequently increase release of TSH from the pituitary gland
- Lithium, which inhibits thyroid hormone release
- Certain foods, such as soy and millet (containing vitexins) and vegetables in the genus Brassica (which includes broccoli, Brussels sprouts, cabbage, caulif
horseradish).
- Caffeine (found in coffee, tea, cola and chocolate), which acts on thyroid function as a suppressant.
Derivatives of xanthine (known collectively as xanthines) are a group of alkaloids commonly used for their effects as mild stimulants and as bronchodilators,
treatment of asthma or influenza symptoms.In contrast to other, more potent stimulants like sympathomimetic amines, xanthines mainly act to oppose the ac
adenosine, and increase alertness in the central nervous system.
In in vitro pharmacological studies, xanthines act :
as competitive nonselective phosphodiesterase inhibitors which raise intracellular cyclic adenosine monophosphate (cAMP) - cAMP is a second messeng
intracellular signal transduction, such as transferring into cells the effects of hormones like glucagon and adrenaline, which cannot pass through the plasm
It is also involved in the activation of protein kinases
to activate protein kinase A (PKA) - PKA targeting is largely known to control cell growth in many cancer types in vitro and in vivo; remarkably, targeting P
site-selective cAMP analogs or antisense approaches has clearly shown antitumor activity in cancer patients
to inhibit TNF-alpha (using anti-inflammatory drugs to inhibit cytokines, in particular TNF-alpha, has been successful in several clinical trials for treating rh
arthritis) and
to inhibit leukotriene synthesis
to reduce inflammation and innate immunity and are nonselective adenosine receptor antagonists which inhibit sleepiness-inducing adenosine.
Different analogues show varying potency at the numerous subtypes, and a wide range of synthetic xanthines (some nonmethylated) have been developed s
compounds with greater selectivity for phosphodiesterase enzyme or adenosine receptor subtypes.
People with the rare genetic disorders, specifically xanthinuria and Lesch-Nyhan syndrome, lack sufficient xanthine oxidase and cannot convert xanthine to u
Neuroactive agents may produce tachyphylaxis whereby a high-intensity prolonged stimulus or often-repeated stimulus may bring about a diminished respon
as desensitization)
Headaches, tension and nervousness are characteristics of excessive caffeine consumption. Over long periods agitation, psychosis, heartburn and hyperven
occur.
For G-protein inhibitors:/ antagonists/ modulators.
G protein-coupled receptors (GPCRs) are essential cell membrane signaling molecules and represent the most important class of drug targets. Some signali
downstream of a GPCR may be responsible for drug adverse effects, while others mediate therapeutic efficacy. Biased ligands preferentially activate only a s
GPCR signaling pathways. They hold great potential to become next-generation GPCR drugs with less side effects due to their potential to exclusively activa
signaling pathways.
GPCR ligands include odorants, tastants, and neurotransmitters, and vary in size and properties. Dramatic chemical diversity may occur even among ligands
receptor. Chemical variability of antagonists significantly correlates with the binding site hydrophobicity and anti-correlates with the number of hydrogen bond
binding site. The number of disulfide bridges in the extracellular region of a receptor anti-correlates with the range of molecular weights of its antagonists, hig
role of the entrance pathway in determining the size selectivity for GPCR antagonists.
The number of protein targets included in the cross-pharmacology profile of the different GPCRs changes significantly upon varying the ligand similarity and
criteria. However, with the exception of muscarinic receptors, aminergic GPCRs distinguish themselves from the rest of the members in the family by their re
levels of pharmacological similarity among them.
GPCRs are classified under the GRAFS system (Metabotropic Glutamate, Rhodopsin, Adhesion, Frizzled/taste2/Smoothened and Secretin), with therapies h
developed for about 30 GPCRs from the glutamate, rhodopsin and secretin families.
GPCR signaling requires significant conformational changes within the trans-membrane TM domain, triggered by agonist binding, and is often coupled to inte
the extracellular domains or loops.It is becoming clear that many binding sites and mechanisms exist for positive and negative allosteric regulation, and for b
pathways, likely in greater numbers than seen in most other protein systems.
When GPCRs are exposed to a neutral agonist, such as morphine on mu-opioid receptor, an occupied receptor can generate several signal waves (non-bias
GPCR signaling, the ability of a molecule to selectively activate one pathway without affecting another pathway is called biased agonism. Biased signaling oc
signaling proteins, including G proteins, GRKs, beta-arrestins, and even at levels of the allosteric binding site. Since GPCR activation-induced two distinct sig
protein-dependent signaling followed by beta-arrestin-dependent signaling opens a new promising therapeutic future in the world of GPCRs. This is true sinc

Chemwatch: 9-724537 +44 (0) 1353 667258
such molecules dramatically lowers the adverse effects by turning off unwanted signals. For example, the analgesic effect of morphine (neutral agonist) throu
activation of u-receptors is accompanied by several side effects, including constipation, respiratory depression, tolerance, nausea, and sedation
Despite the long history and obvious desirability of developing drugs targeting GPCRs, there are several problems associated with their development. For ex
muscarinic M1 receptor is a well-validated target for agonists that could alleviate cognitive decline during neurodegeneration .
Muscarinic acetylcholine receptors (MRs, or mAChRs), which are more sensitive to muscarine than to nicotine, are a group of class A GPCRs comprising five
subtypes, named as muscarinic M1, M2, M3, M4, and M5 receptors (M1R-M5R) M1R, M3R, and M5R are coupled to the Gq/11 family of G proteins, whereas
are coupled to the Gi/o family of G proteins.
However, the orthosteric binding site of M1 is virtually identical to those of the related receptors M2,M3, M4, and M5 as they all bind the native ligand acetylc
activation of M2 and M3 in particular gives rise to dose-limiting side effects (gastrointestinal [GI] disturbances, cardiovascular effects).
Atropine and other anticholinergic agents exert their bronchodilator effects through the blockade of MRs in the airways. As a tertiary ammonium derivative, at
nonselective antagonist with similar affinity for all of the MR subtypes The half-life of atropine for M3R residence is 3.5 hours. Although extensively used in th
is rarely used at the present time because it is well absorbed into the systemic circulation and penetrates the blood–brain barrier, leading to multiple systemic
including tachycardia.
Several long-acting muscarinic antagonists (LAMAs) are under investigation or are available for the treatment of obstructive airway diseases. LAMAs are con
safe drugs at recommended dosages. However, because MRs are expressed not only in the lungs, but also in the heart and the digestive and urinary tracts,
different MR subtypes in these organs by LAMA treatment can cause diverse, unwanted physiologic effects. For example, these agents can initially block pre
on cholinergic airway nerves that normally reduce the release of the bronchoconstricting neurotransmitter acetylcholine, thus resulting in cough and paradoxi
bronchoconstriction. Side effects including cardiovascular morbidity and mortality of inhaled LAMA agents in asthma need to be further studied and defined.
Another potential source of side effects when targeting other receptors could arise due to signaling through multiple different pathways
There are multiple signaling pathways for GPCRs, and it is sometimes possible to bias the signaling of a given GPCR through either a specific G protein or th
arrestin which could reduce the side effects of some drugs
Targeting G protein alpha-subunits has the potential for pleiotropic effects and could result in multiple side effects.
Particular targets of concern include ion channels such as the G protein-activated inward rectifier K+ channel (GIRK) and the N-type voltage-gated calcium c
gamma activates GIRK channels in neurons and in atria, leading to a hyperpolarization-induced decrease in action potential firing. Therefore, when consider
Gbeta-gamma inhibitors in cardiac or immune therapy, interfering with the regulation of action potentials would have highly undesirable side effects, such as
However, empirical data using prototypical Gbeta-gamma blockers indicate that these pathways are unaffected by Gbeta-gamma inhibitors, and animals trea
show no signs of arrhythmias or alterations in heart rate.
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 Information on other hazards
11.2.1. Endocrine disrupting properties

No evidence of endocrine disrupting properties were found in the current literature.
11.2.2. Other information

See Section 11.1
SECTION 12 Ecological information
12.1. Toxicity
Endpoint Test Duration (hr) Species Value Source

Caffeine Anhydrous Not Not Not
Not Available Not Available
Available Available Available
Endpoint Test Duration (hr) Species Value Source

EC50 72h Algae or other aquatic plants >100mg/l 2
caffeine EC50 48h Crustacea 177.8mg/l 4
LC50 96h Fish ~87mg/l 2
NOEC(ECx) 24h Fish 0.003mg/l 4
Legend: Extracted from 1. IUCLID Toxicity Data 2. Europe ECHA Registered Substances - Ecotoxicological Information - Aquatic Toxicity
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
Harmful to aquatic organisms, may cause long-term adverse effects in the aquatic environment.
Do NOT allow product to come in contact with surface waters or to intertidal areas below the mean high water mark. Do not contaminate water when cleaning
equipment or disposing of equipment wash-waters.
Wastes resulting from use of the product must be disposed of on site or at approved waste sites.

Chemwatch: 9-724537 +44 (0) 1353 667258
Environmental Fate: Based on the distribution modeling, caffeine is primarily partitioned in water compartment. Although there is no available data on the
biodegradation of caffeine, it is presumed that caffeine can undergo biodegradation as exhibited by its structurally analogous compound theophylline.
Terrestrial Fate: When released in soil, caffeine is considered highly mobile based on its low soil adsorption coefficient. In addition, caffeine does not volatilize from
moist and dry soil to the atmosphere. Limited data available suggest that caffeine can possibly undergo biodegradation in soil.
Aquatic Fate: Available data shows that when caffeine is released in water, it will not undergo volatilization to the atmosphere and will not adsorb to sediment and
suspended organic matter. Limited data available suggest that caffeine can be biodegraded in water under aerobic conditions.
Atmospheric Fate: When released in air, caffeine tends to adhere onto air particulates thus may reduce the rate of hydroxyl radical oxidation.
Ecotoxicity:
There is no available data on the chronic effect of caffeine. But based on EU risk assessment procedure, the PNEC aqua can be estimated to 0.087 mg/l by
applying an assessment factor of 1000 on most sensitive species (Leuciscus idus LC50, 96hr is 87 mg/l)
Fish LC50 (96h): Leuciscus idus 87 mg/l
Daphnia magna EC50 (48h): 182 mg/l
Algae ErC50 (72h), ErC10 (72h): Scenedesmus subspicatus >100 mg/l
DO NOT discharge into sewer or waterways.
12.2. Persistence and degradability

Ingredient Persistence: Water/Soil Persistence: Air
caffeine HIGH HIGH
12.3. Bioaccumulative potential

Ingredient Bioaccumulation
caffeine LOW (LogKOW = -0.07)
12.4. Mobility in soil

Ingredient Mobility
caffeine LOW (Log KOC = 10)
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 disrupting properties

No evidence of endocrine disrupting properties were found in the current literature.
12.7. Other adverse effects

No evidence of ozone depleting properties were found in the current literature.
SECTION 13 Disposal considerations
13.1. Waste treatment methods

Product / Packaging There is conflicting evidence as to which methods are most effective for the inactivation of non-proteinaceous biotoxins.
disposal The following disposal instructions have been developed to ensure all the non-proteinaceous biotoxin wastes are disposed in a
manner that is consistent and safe for all personnel involved.
Note: Additional instructions may apply to biotoxins regulated as "select agents"..A biotoxin is regulated as a select agent only if
the aggregate amount of the biotoxin under the control of a principal investigator exceeds a certain predefined amount.
For biotoxins containing non-proteinaceous biotoxins (includes biotoxin contaminated debris)
Solid waste:
(Debris includes disposable items such as gloves, labcoats, absorbent paper, plastic pipette tips and empty containers)
Do NOT add bleach or any other chemical to deactivate.
Place the contaminated items directly in a puncture-resistant bag, no larger than 40 litre in size (small trash can size) and
keep weight below 10 kg. The bag must be labeled with the contents – e.g. aflatoxin contaminated debris.
Do not use biohazard bags or anything marked with a biohazard symbol. You will be required to repackage the waste if there
are any biohazard symbols visible or covered.
Liquid waste:
Do NOT add bleach or any other chemical to deactivate.
Collect waste in glass or plastic containers with screw cap lids.
Label containers as to the contents – list all chemicals in the liquid waste including the biotoxin. Do NOT label with a
biohazard symbol. You will be required to repackage the waste if there are any biohazard symbols visible or covered.

Chemwatch: 9-724537 +44 (0) 1353 667258
For all wastes:

Submit a chemical waste pickup request form to the appropriate department/ administrator (before working with biotoxins
identify all agents responsible for administering work-flow) .
Indicate the maximum amount of toxin present in the waste on the form (this is to verify that quantities do not qualify for
regulation as select agents.
Some labs have found it useful to place a bag in a container that has a lid to minimise exposure. The container holding the bag
should be clearly marked so that janitorial/ custodial staff does not mistake it for regular trash.
When full, seal bag and confirm the label on the bag is accurate.
Submit a chemical waste pickup request form to the appropriate department/ administrator (before working with biotoxins
identify all agents responsible for administering work-flow)
Indicate the maximum amount of toxin present in the waste on the chemical waste form (this is to verify that quantities do not
qualify for regulation as select agents, e.g. tetrodotoxin < 100 mg.).
Handling of sharps:
Sharps are generally agreed to be the most hazardous items in the waste stream. A high degree of precaution must always be
taken with any sharp item, contaminated or not. All sharps (hypodermic, intravenous, or other medical needles and syringes;
Pasteur pipettes; scalpel or razor blades; blood vials; glass microscope slides and cover slips; and any other laboratory
glassware in contact with the biotoxin must be placed immediately upon disposal into a sharps disposal container.
Sharps disposal containers are closable, puncture resistant, leak-proof on the sides and bottoms, and available in (typically) 1-
litre, 8-litre, and 25-litre sizes
Sharps disposal containers are closable, puncture resistant, leak-proof on the sides and bottoms, and available in (typically) 1-
litre, 8-litre, and 25-litre sizes. When discarding sharps:
Place the item into the sharps disposal container, immediately following use.
Never empty the contents of the sharps disposal container into another container.
Never remove the lid from the container.
Never overfill a sharps disposal container; no materials should be sticking out the top.
Never force materials into a sharps disposal container
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
Disposal (if all else fails)
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
Marine Pollutant NO
HAZCHEM 2X
Land transport (ADR-RID)

14.1. UN number or ID
1544
number
14.2. UN proper shipping

ALKALOIDS, SOLID, N.O.S. (contains caffeine); ALKALOID SALTS, SOLID, N.O.S. (contains caffeine)
name
14.3. Transport hazard Class 6.1

class(es) Subsidiary Hazard Not Applicable
14.4. Packing group III

14.5. Environmental
Not Applicable
hazard
14.6. Special precautions

Hazard identification (Kemler) 60
for user
Classification code T2

Chemwatch: 9-724537 +44 (0) 1353 667258
Hazard Label 6.1
Special provisions 43 274

Limited quantity 5 kg
Tunnel Restriction Code E
Air transport (ICAO-IATA / DGR)

14.1. UN number 1544

Alkaloid salts, solid, n.o.s. * (contains caffeine); Alkaloids, solid, n.o.s. * (contains caffeine)
name
ICAO/IATA Class 6.1

14.3. Transport hazard
ICAO / IATA Subsidiary Hazard Not Applicable
class(es)
ERG Code 6L
14.5. Environmental
Not Applicable
hazard
Special provisions A3 A5 A6 A801
Cargo Only Packing Instructions 677
Cargo Only Maximum Qty / Pack 200 kg

Passenger and Cargo Packing Instructions 670
for user
Passenger and Cargo Maximum Qty / Pack 100 kg
Passenger and Cargo Limited Quantity Packing Instructions Y645
Passenger and Cargo Limited Maximum Qty / Pack 10 kg
Sea transport (IMDG-Code / GGVSee)


ALKALOIDS, SOLID, N.O.S. (contains caffeine); ALKALOIDS SALTS, SOLID, N.O.S. (contains caffeine)
name
14.3. Transport hazard IMDG Class 6.1

class(es) IMDG Subsidiary Hazard Not Applicable

14.5 Environmental hazard Not Applicable
EMS Number F-A , S-A

Special provisions 43 223 274
for user
Limited Quantities 5 kg
Inland waterways transport (ADN)

ALKALOIDS, SOLID, N.O.S. (contains caffeine); ALKALOID SALTS, SOLID, N.O.S. (contains caffeine)
name
14.3. Transport hazard

6.1 Not Applicable
class(es)
14.5. Environmental
Not Applicable
hazard
Classification code T2
Special provisions 43; 274; 802

Limited quantity 5 kg
for user
Equipment required PP, EP
Fire cones number 0
14.7.1. Transport in bulk according to Annex II of MARPOL and the IBC code

Chemwatch: 9-724537 +44 (0) 1353 667258
Not Applicable
14.7.2. Transport in bulk in accordance with MARPOL Annex V and the IMSBC Code
Product name Group
caffeine Not Available
14.7.3. Transport in bulk in accordance with the IGC Code

Product name Ship Type
caffeine Not Available
SECTION 15 Regulatory information
15.1. Safety, health and environmental regulations / legislation specific for the substance or mixture
caffeine is found on the following regulatory lists
FEI Equine Prohibited Substances List - Controlled Medication

FEI Equine Prohibited Substances List (EPSL)
Great Britain GB mandatory classification and labelling list (GB MCL)
International Agency for Research on Cancer (IARC) - Agents Classified by the IARC Monographs - Not Classified as Carcinogenic
Additional Regulatory Information

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.
Information according to 2012/18/EU (Seveso III):

Seveso Category Not Available
15.2. Chemical safety assessment

No Chemical Safety Assessment has been carried out for this substance/mixture by the supplier.
National Inventory Status

National Inventory Status
Australia - AIIC / Australia
Yes
Non-Industrial Use
Canada - DSL Yes
Canada - NDSL No (caffeine)

China - IECSC Yes
Europe - EINEC / ELINCS /

Yes
NLP
Japan - ENCS Yes
Korea - KECI Yes
New Zealand - NZIoC Yes
Philippines - PICCS Yes
USA - TSCA Yes

Taiwan - TCSI Yes
Mexico - INSQ Yes
Vietnam - NCI Yes
Russia - FBEPH Yes

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
registration.
SECTION 16 Other information
Revision Date 02/10/2024
Initial Date 05/03/2020

Chemwatch: 9-724537 +44 (0) 1353 667258
Full text Risk and Hazard codes
SDS Version Summary

Date of
Version Sections Updated
Update
Toxicological information - Acute Health (inhaled), Toxicological information - Acute Health (swallowed), First Aid
measures - Advice to Doctor, Physical and chemical properties - Appearance, Toxicological information - Chronic
1.6 02/10/2024 Health, Ecological Information - Environmental, First Aid measures - First Aid (inhaled), Exposure controls /
personal protection - Personal Protection (Respirator), Identification of the substance / mixture and of the
company / undertaking - Use
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
DNEL: Derived No-Effect Level
PNEC: Predicted no-effect concentration
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
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
Classification and procedure used to derive the classification for mixtures according to Regulation (EC) 1272/2008 [CLP]

Chemwatch: 9-724537 +44 (0) 1353 667258
Classification according to
regulation (EC) No
Classification Procedure
1272/2008 [CLP] and
amendments
Acute Toxicity (Oral)

On basis of test data
Category 4, H302
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Caffeine Anhydrous: Cambridge Commodities

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Caffeine Anhydrous

Cambridge Commodities Chemwatch Hazard Alert Code: 3

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

1.1. Product Identifier

Chemical formula Not Applicable

1.3. Details of the manufacturer or supplier of the safety data sheet

Website Not Available

1.4. Emergency telephone number

SECTION 2 Hazards identification

2.1. Classification of the substance or mixture

2.2. Label elements

Product code: P0301 Version No: 2.6 Page 1 of 21

Signal word Warning

Precautionary statement(s) Prevention

Precautionary statement(s) Response

P330 Rinse mouth.

Precautionary statement(s) Storage

Precautionary statement(s) Disposal

Material contains caffeine.

2.3. Other hazards

Cumulative effects may result following exposure*.

Limited evidence of a carcinogenic effect*.

SECTION 3 Composition / information on ingredients

SCL: Not Available

SECTION 4 First aid measures

4.1. Description of first aid measures

Product code: P0301 Version No: 2.6 Page 2 of 21

If skin or hair contact occurs:

If fumes or combustion products are inhaled remove from contaminated area.

SECTION 5 Firefighting measures

5.1. Extinguishing media

Product code: P0301 Version No: 2.6 Page 3 of 21

Dry chemical powder.

5.2. Special hazards arising from the substrate or mixture

5.3. Advice for firefighters

SECTION 6 Accidental release measures

6.1. Personal precautions, protective equipment and emergency procedures

6.2. Environmental precautions

Product code: P0301 Version No: 2.6 Page 4 of 21

6.3. Methods and material for containment and cleaning up

6.4. Reference to other sections

SECTION 7 Handling and storage

7.1. Precautions for safe handling

Product code: P0301 Version No: 2.6 Page 5 of 21

7.2. Conditions for safe storage, including any incompatibilities

7.3. Specific end use(s)

SECTION 8 Exposure controls / personal protection

8.1. Control parameters

* Values for General Population

Occupational Exposure Limits (OEL)

Source Ingredient Material name TWA STEL Peak Notes

Product code: P0301 Version No: 2.6 Page 6 of 21

Occupational Exposure Banding

Ingredient Occupational Exposure Band Rating Occupational Exposure Band Limit

8.2. Exposure controls

Type of Contaminant: Air Speed:

Within each range the appropriate value depends on: