Tamxifen SOP

flashypumpkincenterSoftware and s/w Development

Dec 14, 2013 (4 years and 17 days ago)

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Working with Tamoxifen
(
C
26
H
29
NO
)


According to the Material Safety Data Sheet (MSDS) for Tamoxifen

(
(C
26
H
29
NO) CAS#10540
-
29
-
1
),

special
precautions must be taken when working with this chemical. The EPA guidelines for classification

(40 CFR Part

261.3
)

list the compound as
a carcinogen.

Below are some of the characteristics of Tamoxifen followed by
safety
procedures for the use of the compound
. Research staff must inform Laboratory Animal Care in advance of the
intended time of use to make arrangements for animal housing.


Tamoxifen is

an off
-
white odorless solid crystalline powder with a melting point of 140
-
144◦ C. Tamoxifen is a
possible human carcinogen which causes eye and skin irritation; may cause respiratory and digestive tract
irritation if swallowed causing reproductive and
fetal effect. The chemical, physical, and toxicological properties
have not been thoroughly investigated.


Descriptio
n of chemical work for Protocol
:

Insert description of the intended work


route of injection, dose, frequency etc.



Brief Safety Over
view:



The Principal Investigator is responsible for training employees using the material. The training should include a
discussion of the known and potential hazards and an explanation of the relevant policies, techniques and procedures
including the pro
per use of personal protective equipment and containment equipment (engineering controls).
Employees should be trained initially and then annually thereafter. Their knowledge, competence and practices
should be evaluated and documented.



Implement a saf
ety program and include this information in the chemical hygiene plan.



Limit access to authorized users.



Minimize the possibility of inadvertent ingestion or inhalation and direct skin or eye contact with the drug.



Properly label containers of the chemic
al and any secondary containers.



Develop SOP for delivery and storage of the chemical; the SOP should have a contingency for broken or leaking
bottles.



Transportation of the chemical within the facility should be performed using a sealed, non
-
breakable

secondary
container.


Tamoxifen Classifications:

Carcinogen

Target Organ Effect (Eyes, Liver, Kidney, Blood)

Teratogen

Reproductive hazard




Label Precautionary statements must include
:

Dangerous

/ Toxic

Harmful if swallowed

May cause cancer

Reproduc
tive hazard


Routes of Exposure and Toxicological Effects

Acute effects
:

Harmful if inhaled, causes respiratory tract irritation, harmful if absorbed through skin causes skin irritation and
eye irritation.


Chronic effects:

May affect genetic material
and may cause cancer tumorigenic. Research has suggested that the use of tamoxifen
during pregnancy can cause harm to the fetus and that tamoxifen may induce mutations.


Pharmacokinetics
:
(
None

available
)


Working with Tamoxifen
(
C
26
H
29
NO
)


Handling Instructions

Precautions

As with all
hazardous agents, principal investigators must develop and implement standard operating procedures
to minimize the potential for exposures. All personnel involved in the research protocol (conducting tasks with
the potential for occupational exposure e.g.

generation the stock solution, preparing doses, and administering
injections) must receive instruction and training. All training must include chemical & function
-
specific
information such as the
health and safety risks, emergency procedures, and the SOP
.
Personnel must be trained in
good technique for reconstitution and handling tamoxifen. Only trained personnel should prepare/administer the
solution.


Preparation of the stock solutions:

Prepare fresh stock only as needed.

The stock solution should be

in light
-
resistant container
.

The bottle must be
labeled with the name of the chemical and appropriate hazard information (as listed above) PRIOR to adding the
solution.


Small quantities (mg quantities) of tamoxifen may be weighed out on a draft
-
protect
ed balance; clean around
balance after use (
whether you think you’ve spilled anything or not
). Larger quantities (gram scale) of tamoxifen
must be conducted in a chemical fume hood.


Engineering controls:

Prepare all solutions in a
designated area

Personne
l will prepare
solutions (from dry powder)

and dilutions of the compounds for use in animals within a
certified chemical fume hood or a cytotoxic ducted Biosafety cabinet.

The work surface should be protected from
contamination by disposable, plastic
-
back
ed, absorbent paper. The work area is prepared by laying down the
absorbent paper with the absorbent material facing up and impervious backing against the bench. This orientation
will minimize splatter and
limit potential for contamination of work surfac
es in the event of a minor spill.

Tape
the edges of the absorbent material to prevent its movement in the fume hood.


Sharps:

Laboratory personnel must be instructed to use extreme caution when performing injections involving tamoxifen;
needle sticks ar
e one of the greatest exposure risks in the lab. Syringes used for tamoxifen injection must be
safety engineered (self
-
sheathing syringes, luer
-
lock syringes, etc.).
Large bore needles are recommended to
minimize pressure and possible formation of aeros
ols. Aerosols may also be reduced by using a venting needle
during preparation.
Needles used for tamoxifen injection will be disposed of in approved sharps containers
immediately following use and these containers must be
disposed of into biological waste

bins for incineration.


Personal Protective Equipment:

Personnel will wear

appropriate PPE to prevent potential exposure to the chemical. PPE will include
chemical
resistant gloves, lab coat and eye protection (goggles). A mask is recommended.
Do not
wear latex gloves
.
When working with high concentrations (i.e. stocks or powder) or for a prolonged period of time,
double gloving

can further reduce the risk of exposure, especially if the outer glove is replaced frequently.


Personal hygiene
:

Always was
h hands after removing gloves following use of tamoxifen. A
fter handling

tamoxifen and prior to
leaving the lab (to eat, use the lavatory or
at the end of day)
, w
ash hands, forearms, and face thoroughly.


Special Precautions for Storage
:

Store tamoxifen
in clearly labeled, tightly closed containers
within a

in a cool, dry, well
-
ventilated
designated
area

at or below eye level. Protect from direct sunlight or strong incandescent light and retained in the original
carton until time of use. Keep away from

heat/flame, sources of ignition and moisture. Empty containers pose a
fire risk. Store away from incompatibles which include strong oxidizing agents, strong acids, and strong bases


Working with Tamoxifen
(
C
26
H
29
NO
)


Clean up procedure for work area after preparation complete
:

Areas wh
ere tamoxifen is prepared and/or administered
must be cleaned and decontaminated with at least
soap
and water

(a 1:5 bleach
-
water solution is recommended)
immediately

following each task

and following
removal
of the absorbent bench paper.
Potentially cont
aminated areas include bench tops, biological safety cabinet
interiors,

equipment, personal protective equipment, intravenous bags and tubing.


Waste disposal consideration for stock solutions:

Re
-
useable g
lassware and other non
-
porous materials can be dec
ontaminated by soaking in household bleach for
24 hours.


All disposable but not overtly contaminated items used for reconstitution, administration or cleaning, including
lab ware, bench paper, personal protective equipment, should be placed in regulated
medical waste for
incineration.


Disposal of any left over stock will be via chemical hazardous waste disposal.
Surplus tamoxifen must be
disposed of as a hazardous chemical Safety Affairs 8
-
6114.

All material contaminated with the chemical and
residu
al chemical must

also

be disposed of as hazardous waste. Any

contaminated bench paper and paper towels
should be placed
into a container for hazardous waste, appropriately labeled for waste removal and placed in a
designated area for removal / disposal

by
Safety Affairs.


Exposure Response and First Aid Measures

Tamoxifen, in its powder form, can become airborne and may result in personal exposure and area contamination.
Avoid creating dust. Do not inhale or ingest. Avoid contact with eyes, skin, and clo
thing.


For any exposures, have personnel in the lab assist you with flushing, contacting Occupational Health and
printing copies of the MSDS. All exposures require follow up with Occupational Health. Wash contaminated
clothing before reusing. Do not

re
-
don contaminated clothing. Thoroughly clean shoes before reuse.


Skin

If you are splashed with a chemical on any area of your body, you must rinse that area with copious amounts of
tepid

water for no less than 15 minutes. Gently and thoroughly wash t
he contaminated skin with running water
and non
-
abrasive soap or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush.
Be particularly careful to clean folds, crevices, creases and groin. Cold water may be used. Cover the ir
ritated skin
with an emollient. In case of
serious skin contact, w
ash with a disinfectant soap and cover the contaminated skin
with an anti
-
bacterial cream.


If you are splashed in an area of your body which cannot be put under a drench hose and flooded
immediately


you must use an emergency shower.


Eyes

Check for and remove any contact lenses. Hold your eyelids open with your fingers as you rinse your eyes for a
full 15 minutes

(move eyes up and down and side to side to fully remove chemical). Have
your helper make sure
you continue to rinse your eyes for the
full 15 minutes
.


Inhalation

Remove from exposure to fresh air immediately. Allow the victim to rest in a well ventilated area. If breathing is
difficult, give oxygen.
Do NOT

use mouth
-
to mou
th resuscitation.


Ingestion

Do not induce vomiting unless directed by medical personnel. Examine the lips and mouth to ascertain whether
the tissues are damaged, a possible indication that the toxic material was ingested; the absence of such signs,
Working with Tamoxifen
(
C
26
H
29
NO
)

howeve
r, is not conclusive. Loosen tight clothing such as a collar, tie, belt or waistband. If the victim is not
breathing, perform mouth
-
to
-
mouth resuscitation.


Emergency Procedure for Chemical Spills and Accidental Releases

A
minor

spill is one where the ind
ividual responsible for the spill feels they are capable of handling the spill
safely without the use of respiratory protection or the assistance of specially trained emergency response
personnel. A
major

spill is any spill that requires emergency response

personnel and/or requires a respirator to
avoid inhalation of tamoxifen.


For minor spills:
(less than 10 mL and generating little aerosol)



If spill occurs, restrict access to the affected area.
Wear two pairs of nitrile gloves, a suitable mask, a
protec
tive gown and safety glasses. Clean spill from outside to inside to prevent spread of contaminated
area. Clean up spills using
soap and water
or
5% sodium hypochlorite
.



Limit the spread of a liquid spill by covering with a suitable material such as abs
orbent towels or
adsorbent granules. For powders, place wet paper towels over the spilled material to avoid aerosolizing
material. Do not sweep up dust. Do not inhale dust
.

Decontaminate with bleach solution and wash work
surfaces with soap and water.




Collect the absorbent/ adsorbent and other debris resulting from the spill and clean up and place in a leak
-
proof plastic container. Cytotoxic waste should be regarded as toxic and hazardous and clearly labeled
“Cytotoxic waste for incineration”.



Call
S
afety at 8
-
6114

for hazardous waste pick up. All spills must be reported to Safety Affairs.


Inside a chemical fume hood



Close the hood sash



Notify personnel in the lab



Assemble supplies and follow applicable instructions above


Outside a chemical fume h
ood in the lab



Do not panic



Alert personnel in the immediate area and then evacuate area




Post warning signs and control the area of the spill by restricting access



Assemble supplies a
llowing time for any material to settle and then follow the
applicable i
nstructions
above
-

Or



Follow major spill instructions and remain on site to speak to first responders (if required)



Outside laboratory containment (i.e. hallway)



Notify personnel in the area



Post warning signs and control the area of the spill by rest
ricting access



Assemble supplies and follow applicable instructions above
-

Or



Follow major spill instructions and remain on site to speak to first responders (if required)


For major spills:
(more than 10 mL or with considerable aerosol)



Call Safety Affa
irs @ 8
-
6114 (if there is no answer, call UT Police @ 8
-
4444.)
(Provide your name,
phone number, location, and amount of material spilled)


Animal Procedures

Any tamoxifen solutions will be transported to the animal facility in appropriately labeled secon
dary containment
with absorbent between the primary and secondary container.


PPE required

Standard LACU PPE must be worn (shoe covers, hair cover, eye protection, disposable mask, disposable gowns,
and nitrile gloves). No latex gloves should be used.

Working with Tamoxifen
(
C
26
H
29
NO
)


Containment of the animal and chemical during administration of the chemical

Animals must be injected with tamoxifen within a Biosafety cabinet or designated fume hood. Animal handler
must wear PPE as above with a 2
nd

pair of gloves (double
-
glove).
Needl
es, post
-
use, will be disposed of in sharps
container for incineration



do not recap or bend needles. Clean areas where tamoxifen has been handled using
water and placing paper towels on top. Dispose of waste as described above.


R
equirements for
l
abeli
ng cages
and c
age handling

All cages
MUST

be labeled “Tamoxifen”, with a cytotoxic label and treatments (injections) dates


Rooms housing animals injected with Tamoxifen must be clearly identified on the outside of the room.


A
ll bedding
is considered co
ntaminated

and requires special handling
; cage changes should be handled using
procedures that minimize aerosolization (Micro
-
isolator technique). Bedding should
ONLY

be changed in a
Biological Safety Cabinet or a dump station to minimize exposure.



Prot
ocol specific procedures:

Animals and cages are considered hazardous for a minimum of three days after each administration of Tamoxifen
,
therefore, t
he
first cage change

should b
e done no sooner than
3 days after the administration
.


In this study,
animals

will be injected

Route of injection, dose, frequency etc. This information is used to determine the
required cage change frequency and labeling.


After the final cage change (minimum of
3

days) there is no need for further special precautions to be taken

regarding the animals or the cages as long as the animals have not received any more
tamoxifen
.



Options:

A)
All cage changes will be performed by the PI or personnel working for the PI. LACU staff will not
perform cage changes.

B) LACU staff may perf
orm cage changes.


Animal Waste disposal

Animals and other waste contaminated with Tamoxifen will be treated as cytotoxic waste. All animal waste and
bedding
during the injection period and
three

days after injections cease
must be collected
as
Regulated
Medical
Waste

for incineration.
N
eedles/syringes should be disposed in a sharps container destined for incineration
as
Regulated Medical Waste.


UTHSC policy declares that chemical and biological hazards must be clearly identified as part of the IACUC
pro
tocol when working with Tamoxifen in animal studies. Any PI who plans to work with Tamoxifen in an
animal study, must complete the “hazard” section of the IACUC protocol and provide standard operating
procedures for its use.


The laboratory’s Chemical H
ygiene Plan must include special practices when working with hazardous chemicals
and the MSDS must be accessible. Also, all laboratory personnel must be familiar with safe handling practices
(i.e., training with proof of training) when working with these
chemicals. This must be incorporated into the
comprehensive chemical hygiene plan of the laboratory. If you have any questions regarding risk assessment,
SOP development or a comprehensive mandatory laboratory chemical hygiene plan, contact Francine Roger
s,
Institutional Biosafety Officer at 448
-
3537 or
frogers1@uthsc.edu
.


For any other questions or concerns, please contact


PI contact information:


Name: ________




Date: __________________

Office Phone: ______
________



E
-
mail:
___________

Cell phone: __________________
_____

Home phone:
____________