Hazardous Chemical Use in Animal Research

Introduction/Purpose

This website has been prepared by University of Maryland, Baltimore (UMB) Environmental Health and Safety (EHS) office to assist researchers in determining reporting requirements for the use of hazardous drugs and chemicals in research involving animals and to aid in preparation of documents for submission to the UMB Institutional Animal Care and Use Committee (IACUC).

An additional resource can be found in the spreadsheet entitled IACUC EHS Chemical Index, which summarizes the hazard determinations for various drugs and chemicals that have been used in animals. The list is reviewed with information available as of the last update, is not an exhaustive list of all hazardous chemicals, and may be subject to change. Use this list to determine whether a chemical Hazardous Agent Addendum (HAA) should be prepared, but be aware that further considerations must be taken into account, such as route of administration, dosage, frequency of exposure, and use of appropriate engineering controls and PPE.

Note that researchers should always know the hazards associated with all chemicals in use in their workspace and should use engineering controls and personal protective equipment to minimize risk.

Chemical Hazard Levels

Chemical Hazard Levels (CL) have been established for the purpose of guiding minimum requirements for engineering controls and use of personal protective equipment (PPE) for researchers and animal husbandry staff using or exposed to potentially hazardous chemicals. These levels have been assigned based on prior review of chemicals proposed for use on campus and may be amended due to changes in hazard classification and/or usage. Refer to the IACUC EHS Chemical Level spreadsheet to determine the appropriate CL level for review.

The hazard levels increase from CL0 to CL1 to CL2 and the requirements at each subsequent level are additive.

The three levels are:

Chemical Level 0 (CL0): This level is assigned to chemicals that have not been identified as hazardous by the reportable drugs/chemicals standards listed below. Additional information will not be requested for review by the EHS office.

Chemical Level 1 (CL1): This level is assigned to chemicals that have been identified as hazardous by the reportable drugs/chemicals standards listed below. The chemical may be toxic or hazardous to humans during preparation and administration to animals, but not after. After administration, neither the animal nor the bedding is considered hazardous and standard PPE worn in the animal facilities is appropriate for Veterinary Resources staff.

Chemical Level 2 (CL2): This level is assigned to chemicals that have been identified as hazardous by the reportable drugs/chemicals standards listed below AND the chemical may be toxic or hazardous to humans during preparation, administration AND in bedding after administration. Additional PPE may be required for researchers and Veterinary Resources staff. Additional cage- and door-level labeling is required during the hazard phase of the chemicals used.

 

*See notes below for further information on each section*

Chemical Hazard Level

CL0

CL1

CL2

1. Additional information required by EHS

No

Yes

Yes

2. PPE for researchers

Standard

Standard

May have additional requirements

3. PPE for Veterinary Resources Staff

Standard

Standard

May have additional requirements

4. Cage- and door-level labeling

No

No

Yes

5. Notification to VR Staff prior to use

No

No

Yes

6. Use of fume hood or biosafety cabinet during preparation and/or administration

No

Yes

Yes

7. EHS training required for use of Hazardous Chemicals

Yes

Yes

Yes

 

1. Additional information required by EHS

EHS does not request further information for CL0 level chemicals to be used in animal research; however, all standard requirements for PPE in labs and animal care areas should be followed. If CL1 and/or CL2 chemicals are proposed for use in animal research, further information will be requested in your IACUC protocol. It is recommended that you contact EHS at 410-706-7055 to discuss your usage of CL2 chemicals before submission of your IACUC protocol.

2. and 3. Personal Protective Equipment (PPE)

The standard/minimum PPE to be worn in research and animal care areas include a laboratory coat and gloves, with additional laboratory safety eyewear when the potential for sprays or splashes may exist. When dry hazardous chemicals must be weighed outside the fume hood, an additional dust mask should be worn. Additional PPE such as dust masks, face shields, shoe covers, or rubber boots may be required due to facility level requirements or species-specific PPE.

4. Cage- and door-level labeling

In addition to standard cage cards, all cages containing animals exposed to CL2 hazardous chemicals must also be marked with an Orange Health Hazard cage card, appropriately filled out for agent used, dosage, and date of administration. These Orange Health Hazard cage cards are available by the biosafety cabinets and from Veterinary Resources staff. The Orange Health Hazard cage card may be removed after the hazard phase of the chemical has passed (to be determined by EHS). Door-level labeling and signage will be maintained by Veterinary Resources staff, however it is the responsibility of the Principal Investigator/Researcher to notify VR Staff prior to use of CL2 chemicals.

5. Notification to Veterinary Resources (VR) staff prior to use

VR maintains a list of approved chemicals to be used in the animal care areas, but must be notified prior to use of CL2 level chemicals in the animal facility.  Provide an estimate on number of animals, cages required, and duration of the experiment in order to ensure that appropriate housing, cage-level labels, and door-level signage are maintained during the hazard phase of the chemical. 

Please send this information to either E. Douglas Allen (edallen@som.umaryland.edu) or Dawn Hull (dhull@som.umaryland.edu) at your earliest convenience or no less than 48 hours prior to the tentative start date.

6. Preparation and Administration of Hazardous Chemicals

Preparation of hazardous chemicals that are respiratory hazards or select carcinogens should be performed in a fume hood or exhaust-connected biosafety cabinet. Administration may be performed in a biosafety cabinet (exhaust-connected or not) if the chemical is in a non-volatile diluent (examples include water, saline, or sesame oil), but otherwise should be performed in a fume hood or exhaust-connected biosafety cabinet.

7. EHS Training required for use of Hazardous Chemicals

In addition to CITI training administrated by the OAWA and participation in the Laboratory Animal Exposure Risk Assessment Program (LAERAP), all personnel that work with hazardous chemicals must complete and maintain annual training on Laboratory Chemical Safety and Hazardous Waste. 

Reportable Drugs/Chemicals

If your material will be administered to any live laboratory animal and falls into any of the categories below, a Hazardous Agent Use Addendum (HAA) — Chemicals, Toxins, Hazardous Drugs must be submitted with your IACUC protocol for review:

  1. Identified on the IACUC EHS Chemical Index  spreadsheet as requiring an HAA
  2. Defined as a Carcinogen:
    1. On the materials Safety Data Sheet (SDS);
    2. By OSHA (“select carcinogens”);
    3. By the National Toxicology Program (NTP) (“known to be human carcinogen” or “reasonably anticipated to be human carcinogen”), with 13th edition list;
    4. By IARC (Group 1: Carcinogenic to Humans; Group 2A: Probably Carcinogenic to Humans; Group 2B: Possibly Carcinogenic to Humans; Group 3: data not classifiable for carcinogenicity in humans), with IARC lastest classifications;
  3. Listed as an antineoplastic drug by NIOSH or on the list of proposed NIOSH additions 
  4. Any chemical that is listed as being a reproductive toxin, mutagen, teratogen, or displays acute toxicity with an animal LD50 (oral) < 500mg/kg, LD50 (dermal)< 200mg/kg, or LD50 (inhalation) < 200ppm/hr or <2000mg/m3/hr

Chemicals with Unknown or Limited Toxicological Data

For compounds with limited hazard information available or where there may be a potential increase in hazard associated with a chemical due to the delivery method (i.e., Nanoparticle encapsulation), a note should appear in the protocol addressing potential risk and the use of engineering controls (biosafety cabinet or hood) and standard personal protective equipment (PPE; lab coat, gloves, safety eyewear, dust mask, etc.).

Exemptions

Drugs or compounds that are routinely administered to animals and exempt from reporting in the Hazardous Agents Identification table may include various analgesic, anesthetic, antibiotic, or euthanasia agents, which are identified in the UMB IACUC Guidelines at http://www.medschool.umaryland.edu/iacuc/Guidelines/.

Formaldehyde and Related Chemicals

Note that formaldehyde (as well as paraformaldehyde and formalin) does not need to be accompanied by a chemical HAA form submitted to the IACUC if used in animals post-euthanasia; however, researchers should be aware and follow the guidelines of OSHA’s Standard on Toxic and Hazardous Substances: Formaldehyde (29CFR 1910.1048; https://www.osha.gov/pls/oshaweb/owadisp.show_document?p_id=10075&p_table=STANDARDS) and notify EHS if the work proposed may expose workers to formaldehyde above permissible limits, so EHS can monitor exposure and ensure use of appropriate controls.

If formaldehyde and its related derivatives will be used in live animals (i.e., vital perfusion), then a chemical HAA form will be required.

References

References used to prepare this document, which can and should be used in preparation for protocol submission:

FDA pregnancy categories (note that this labeling system was updated in 2015, but still appears on the NIOSH 2014 list)

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Labeling/ucm093307.htm

Category A: Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).

Category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

Category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

(From https://www.drugs.com/pregnancy-categories.html)

 

OSHA list of Highly Hazardous Chemicals, Toxins, and Reactives:

https://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=10647

 EPA P-listed wastes that must be disposed of through EHS:

https://www.epa.gov/hw/defining-hazardous-waste-listed-characteristic-and-mixed-radiological-wastes

If you have questions about whether a Hazardous Agent Use Addendum is required for the use of a chemical, or would like to discuss recommendations on work practices and PPE required, please contact the EHS Research Safety Specialist at 410-706-7055 or x67055 from a campus phone.