Laboratory Safety Manual - Chapter 08: Reproductive Hazards

This chapter supplements previous chapters by giving specific extra precautions, postings, training, and protective equipment necessary when working with reproductive hazards. These include chemical, biological, or radiological substances that can affect the developing fetus, or the reproductive health of the male or female parents. This chapter also outlines the UNC conceptus protection policy for laboratory workers who are pregnant or contemplating pregnancy.

Title

Laboratory Safety Manual - Chapter 08: Reproductive Hazards

Purpose

This chapter supplements previous chapters by giving specific precautions, postings, training, and protective equipment necessary when working with reproductive hazards. These include chemical, biological, or radiological substances that can affect the developing fetus, or the reproductive health of the parents. This chapter also outlines the UNC conceptus protection policy for laboratory workers who are pregnant or contemplating pregnancy. 

Table of Contents

1. Introduction
2. Laboratory Safety Plans
3. Facility Requirements
4. Protective Clothing
5. Use of Primary Containment Equipment
6. Use and Decontamination of Analytical Instrumentation
7. Storage, Inventory, and Identification
8. Working Quantities
9. Laboratory Transport
10. Protection of Vacuum Lines
11. Packaging and Shipping
12. Decontamination
13. Disposal
14. Animal Experimentation
15. Reproductive Hazards and the Pregnant Employee
    1. Introduction
    2. Chemical and Radiological Reproductive Hazards
    3. Biological Reproductive Hazards
    4. Declared Pregnancy
    5. Conceptus Protection Program
    6. Action Levels
    7. Additional Resources

I. Introduction

Work with reproductive hazards requires special containment practices in addition to those described in Chapter 6 for toxic chemicals and in the Biological Safety Manual. Reproductive hazards are defined by the OSHA Laboratory Standard as substances that cause chromosomal damage (mutagens) and substances with lethal or teratogenic (malformation) effects on fetuses. These can include chemicals, biological materials, and radioactive materials. The University policy for protecting pregnant employees is provided later in the section titled “Reproductive Hazards and the Pregnant Employee.” Methods and references that can be used to identify chemical reproductive hazards include:

• OSHA Reproductive Hazard Standards;
• California Proposition 65 List;
• Safety Data Sheets (SDS) of the chemical.

II. Laboratory Safety Plans

Laboratories working with reproductive hazards must include standard operating procedures in the Laboratory Safety Plan describing the hazards of the compounds or agents, safety precautions, and emergency procedures in the event of a spill. Complete and submit a Laboratory Safety Plan online. In addition to the safety practices described for use of toxic materials, several other special safety precautions are necessary for reproductive toxins.

III. Facility Requirements

Establish a “designated area,” with access restricted to personnel who are aware of the hazards of the substances in use and the necessary precautions. A foot- or elbow-operated hand washing facility must be available within the work area. A hands-free eyewash facility and a shower facility other than emergency drench showers must be available unobstructed within 10 seconds (55 feet) of the hazard. 

Exhaust ventilation systems are designed to maintain negative pressure within the work area (inflow of air from the corridor into the work area). The exhaust air from the work area must discharge directly to the outdoors and clear of occupied buildings and air intakes. Exhaust air from the work area must not recirculate. The exhaust air from glove boxes should have a dedicated exhaust connection that discharges directly to the outdoors. Contact EHS to determine the need for and type of treatment for other primary containment equipment. Exhaust air treatment systems that remove toxic chemicals from the exhaust air by collection mechanisms such as filtration or absorption must operate in a manner that permits maintenance, to avoid direct contact with the collection medium. All exhaust air from primary containment equipment must discharge directly to the outdoors and disperse clear of occupied buildings and intakes. Exhaust systems for highly toxic substances must contain engineered fail-safe mechanisms to prevent loss of containment due to utility outages. 

The EHS Director (or designee) must approve the purchase and installation of any non ducted hoods, such as Biological Safety Cabinets and ductless (or filtered) chemical fume hoods. Approval will be granted only in exceptional cases. For more information, see the Laboratory Ventilation Policy. Contact EHS if you have any questions or are looking to purchase a non-ducted hood. 

IV. Protective Clothing

Refer to Chapter 5: Protective Clothing and Equipment

Wear a full-fastened laboratory coat or a disposable jump suit in any area where known or suspected reproductive toxicants are in use. The Principal Investigator is to provide clean protective clothing weekly. You must not wear your lab coat or other additional protective clothing outside of the work area. Wear appropriate gloves (Appendix 5-B) when handling reproductive toxicants. Double gloving is recommended when handling known or suspected reproductive toxicants. Discard disposable gloves after each use and immediately after known contact with a known or suspected reproductive toxicant. Following an obvious exposure, decontaminate or immediately discard all clothing known and/or suspected to be contaminated by highly toxic chemicals. Do not send contaminated clothing to be laundered until it has been decontaminated. 

V. Use of Primary Containment Equipment

Procedures involving volatile chemicals, and those involving solid or liquid chemicals that may result in the generation of aerosols, must occur in a chemical fume hood, biological safety cabinet, glove box, or other suitable containment equipment. Note that only limited quantities of volatile chemicals can be safely handled within a biological safety cabinet; this equipment often recirculates HEPA filtered air from the contained work surface back into the room and HEPA filters are not designed to capture particles greater than 0.3 microns. Examples of aerosol-producing procedures include:

• opening closed vessels;
• transfer operations;
• weighing;
• preparing feed mixtures;
• and the application, injection or intubation of a chemical into experimental animals.

Class II, type B biological safety cabinets are suitable for the conduct of tissue culture and other procedures involving reproductive toxicants with biological origins (e.g., toxins, viruses). The Principal Investigator is to obtain guidance from EHS on the selection and use of Class II biological safety cabinets. For more information on biological safety cabinets, refer to Chapter 16: Biological Safety Cabinets.

Primary containment equipment used for reproductive toxicants must display a label bearing the legend: "CAUTION – REPRODUCTIVE TOXIN, Authorized Personnel Only." The examples below in Figure 8.1, Figure 8.2, and Figure 8.3 are available on the EHS Safety Labels webpage for printing.

Figure 8.1. Label for storage areas or primary containment equipment where reproductive toxins are present.

A clean bench (Chapter 16, Section IV) is a laminar flow cabinet that provides a flow of filtered air over the work service and offers product protection, not personnel protection. Do not handle reproductive toxicants in them. Clean benches should have signage that is posted by the lab or EHS with the information that it does not provide personnel protection and cannot be used with the specific materials listed above (Figure 8.2).

 

Figure 8.2. Example posting for clean benches.

VI. Use and Decontamination of Analytical Instrumentation

Analytical instruments used with reproductive toxicants must be entirely contained within a chemical fume hood, biological safety cabinet, or alternative engineering controls that are approved for the intended operations. When this is impossible (e.g., the equipment is too large to fit within the standard work surface), capture the vapors or aerosols produced by these instruments through local exhaust ventilation at the site of their production. When you remove a sample from the analytical instrument, place it in a tightly sealed sample tube, or in a manner that otherwise safeguards the lab from contamination. After use with reproductive hazards, completely decontaminate equipment before using again. Contact EHS if you have additional questions about equipment decontamination.

Decontamination guidelines are as follows: 

• Safely remove, drain, or discharge chemicals from the equipment.
• Collect the chemicals for re-use or hazardous waste disposal.
  • If applicable, use an inert gas or liquid to purge the chemical residues.
  • In some cases, the rinsate might require disposal as hazardous waste.
• For equipment with non-permeable surfaces, decontaminate by scrubbing with warm, soapy water.
• For equipment that also might contain biological contamination, follow the soapy water wash by soaking with a 10% bleach solution with an appropriate contact time.  10 minutes is sufficient for most biological materials, but the laboratory is responsible for verifying the appropriate contact time for any biological agents. Contact EHS with questions about biological decontamination. 
  • If the equipment has a metal surface, ensure that it is rinsed or wiped down with water or an appropriate liquid afterward to prevent corrosion. 

Additional guidance on decontamination can be found below in Section XII. 

VII. Storage, Inventory and Identification

Store stock quantities of reproductive toxins in designated storage areas. Post these storage areas with signs bearing the legend: "CAUTION – REPRODUCTIVE TOXIN, Authorized Personnel Only" (Figure 8.1).

Label all storage vessels containing stock quantities with the following information: "CAUTION – REPRODUCTIVE TOXIN" (Figure 8.3 or similar). This smaller label, which does not include the “Authorized Personnel Only” statement necessary for containment equipment or storage areas, is available at EHS Safety Labels webpage.

VIII. Working Quantities

Keep quantities of reproductive toxicants handled in the work area to a minimum. Quantities should not normally exceed the amounts required for use in one week. Use the label depicted in Figure 8.3 (or similar) for storage vessels containing working quantities of reproductive toxins.

Figure 8.3.  Label for storage vessels that contain reproductive toxins.

IX. Laboratory Transport

Place storage vessels containing reproductive toxicants in an unbreakable outer container (e.g., rubber lab bottle carrier) before transporting them from storage areas to laboratory work areas. Place contaminated materials (e.g., pipettes, gloves, etc.) that need to be transferred from work areas to disposal areas in a closed plastic bag or other suitable impermeable and sealed primary container, and place the sealed primary container inside a durable outer container before transporting. Label the outer container with both the name of the substance and the hazard information from Figure 8.3.

X. Protection of Vacuum Lines

Each vacuum service, including water aspirators, must have protection via an absorbent or liquid trap and a HEPA filter to prevent entry of any reproductive toxicant into the system for biological materials. When using a volatile chemical and a vacuum line, use a separate vacuum pump connected to external exhaust or other device placed in a chemical fume hood. 

XI. Packaging and Shipping

Package reproductive toxins to withstand shocks, pressure changes, or other conditions that could result in leaks from ordinary handling procedures during transportation. Shipments must be in accordance with DOT and IATA regulations. These regulations state that you must receive specific training in order to ship a hazardous material. Refer to the Transporting Research Materials website for more information. Contact EHS with any questions or for other guidance on shipping and labeling. 

XII. Decontamination

Address any spills of chemical, biological, or radioactive materials associated with reproductive hazards immediately.  Depending on the material, they must be either:

1. inactivated using a procedure that decomposes the hazardous material; or
2. they must be absorbed by appropriate means, collected, and disposed of through EHS. 

After inactivating or absorbing the spilled material, the spill areas must be thoroughly cleaned with soap and water or proper disinfectant, while collecting all cleaning materials for disposal through EHS. Write these decontamination protocols into your Laboratory Safety Plan and update the protocols as necessary. Means for ensuring adequate clean up are required, such as wipe tests or fluorescence tests. 

XIII. Disposal

EHS must approve all plans for handling and ultimate disposal of contaminated wastes. Write these into the Laboratory Safety Plan, Schedule B, and fully describe the reproductive hazards in your waste stream when submitting an online hazardous materials pick up request through EHS. Refer to Chapter 12: Laboratory Waste Management Plan for additional guidance.

XIV. Animal Experimentation

In all circumstances, research and animal care personnel must wear the appropriate protective apparel or equipment required for the location when entering Division of Comparative Medicine (DCM) animal housing facilities or procedure rooms (refer to Chapter 14: Safe Handling of Laboratory Animals). As discussed in Chapter 5, comfort masks (e.g., surgical masks) are not respirators. The comfort masks provided in several DCM facilities do not protect you from airborne exposures; instead, they protect the laboratory animals from your exhalations. Personnel who anticipate exposure to airborne particulates contaminated with reproductive toxins outside of primary containment must wear an appropriate respirator of N95 or higher protection, rather than a comfort mask. Refer to the Respiratory Protection section of Chapter 5: Protective Clothing and Equipment, for a description of respirator types.

EHS must approve the selection and use of respirators, and wearers must participate in the Respiratory Protection Program.

Do not wear the comfort mask or respirator outside of the animal room or procedure room. For tight-fitting cartridge respirators, dispose of used filters and decontaminate the respirator housing daily.

XV. Reproductive Hazards and the Pregnant Employee

A. Introduction

Reproductive hazards are defined by the OSHA Laboratory Standard as physical, chemical, or biological substances that impact an individual's fertility and/or ability to have a healthy child. Examples of toxicity mechanisms include chromosomal damage (mutagens) and/or substances with lethal or teratogenic (malformation) effects on fetuses. Teratogens may affect the conceptus at any stage of its development, from fertilization to birth, although damage is most likely during the first 8 to 10 weeks of pregnancy. Mutagens can also affect conceptus development, or prevent fertilization entirely by damaging the egg or sperm. In addition, there are microbiological agents that can cause maternal morbidity, miscarriage, fetal death or birth defects.

Teratogens are chemical and physical agents that interfere with normal embryonic development. Teratogens differ from mutagens in that there must be a developing fetus. Reproductive toxicants may produce congenital malformations or death of the fetus without inducing damage to the pregnant woman. In general, you should consider carcinogenic, mutagenic and teratogenic chemicals hazards to reproductive health. Even though OSHA has established hazardous material exposure limits, a developing fetus can suffer adverse effects at lower doses than those considered safe for adults. Thus, you must keep exposures as low as reasonably achievable to minimize reproductive health hazards.

UNC is committed to providing additional protection for the conceptus, and establish specific procedures to protect pregnant employees. Control of employee exposures will occur without economic penalty or loss of job opportunity, including, if necessary, consideration for work assignment changes, consistent with University personnel policy. Assuring protection from exposures to radiation and/or chemicals for the conceptus requires full cooperation of the employee with the Department of Environment, Health and Safety (EHS). If you wish to take advantage of this policy, contact EHS as soon as possible after determining or contemplating pregnancy, to ensure implementation of these policies.

B. Chemical and Radiological Reproductive Hazards

Known chemical reproductive toxins can be found in the OSHA Reproductive Hazard Standards and California Proposition 65 List. These lists includes agents that cause fetal developmental toxicity, damage the male/female reproductive cells, or other difficulty with conception. Examples of known or suspected reproductive toxins commonly found in laboratories are listed below.

 

 

C. Biological Reproductive Hazards

Exposure to certain biological agents (e.g., bacteria, viruses, parasites, toxins) have been associated with miscarriages, fetal death or birth defects. Pregnant individuals experience immunological changes to facilitate gestation and may be more susceptible or sensitive to infection following exposure to certain pathogens. Maternal infections can be transmitted to their child during gestation, during labor/childbirth, or via breastfeeding; these transmission mechanisms are referred to as congenital, perinatal, and postnatal infections respectively. Occupational exposure to biological materials can occur via splashes or other contact with mucous membranes (e.g., inhalation), needlesticks/punctures with contaminated sharps, or ingestion.

The following biological agents are known to be reproductive hazards. 

• Cytomegalovirus (CMV). CMV is a known teratogen and congenital infection can cause mental retardation, cerebral palsy, epilepsy, vision and hearing problems especially during the first 20 weeks of fetal development.
• Hepatitis A, B, C. Prenatal infection can cause prematurity and psychomotor retardation.
• Human Immunodeficiency Virus (HIV). HIV can affect fertility. HIV can also be transmitted to the fetus.
• Human Parvovirus (Fifth Disease). Prenatal infection with human parvovirus can cause fetal edema and death. Intrauterine infection may cause fetal anaemia.
• Listeria monocytogenes. This bacterium is found in a variety of animals including mammals and birds so is of special concern to employees handling animals. Perinatal infections occur transplacentally and can result in abortion, stillbirth, meningitis, endocarditis, or septicemia.
• Rubella virus (German measles). Congenital rubella syndrome (CRS) may occur in infants born to women who had rubella during the first trimester. This can lead to fetal death, spontaneous abortions, congenital malformations of the eyes, ears and heart, mental retardation and/or poor childhood growth. The risk decreases with fetal development.
• Toxoplasma gondii (toxoplasmosis). Congenital cases can result in abortion and stillbirth. Live births may result in central nervous system disorders, hydrocephaly, or mental retardation. Transplacental infection is least likely during the first trimester, but these cases are the most severe. Cats can carry this disease and employees conducting experiments with cats may need to take additional precautions.
• Varicella virus (Chicken Pox). Congenital infection can cause limb atrophy, microcephaly, cortical atrophy, motor, sensory and eye problems. Infection during the first trimester can cause miscarriage, muscular atrophy, clubbed foot, CNS disease and cataracts in the fetus.

While the agents listed above include some of the most common microorganisms linked to reproductive hazards, this list is not exhaustive for all biological reproductive hazards. Once an employee has declared their pregnancy, EHS will evaluate the biological materials documented for an employee’s workspace based in relation to available data regarding biological reproductive hazards.  

D. Declared Pregnancy

If you wish the University to be involved in protecting your fetus, and exposures to the fetus kept below the 500 millirems limit if you are a radiation worker, you must declare your actual, suspected, or planned pregnancy to your supervisor and EHS in writing, or by e-mail. The University’s responsibility for conceptus protection begins only after receipt of this notice of pregnancy, or intended pregnancy, to your supervisor and EHS. The involvement of supervisors is an essential part of the University’s safety management. EHS urges every potentially pregnant employee to consider her supervisor’s safety responsibilities and freely involve the supervisor in all work-related situations.

EHS understands that employees may choose to maintain their pregnancy status as personally confidential for a time. Any employee may still receive safety information about pregnancy and chemical, biological, and radiological exposures at any time from EHS without declaring their pregnancy status.

E. Conceptus Protection Program

Following written or e-mail notice of pregnancy or intended pregnancy to the EHS Director, Biological Safety Officer (BSO), Chemical Hygiene Officer (CHO), or Radiation Safety Officer (RSO), EHS institutes a Conceptus Protection Program (CPP).  For contact information, please see the EHS directory. The CPP consists of three elements.

1. Confidential Conferences

Conferences include the employee, the individual's supervisor, and EHS specialists. The employee is provided a copy of this policy and other pertinent literature on protecting pregnant employees from chemical, biological and radiological exposures. Following the conference, EHS will send an assessment report to the employee and supervisor listing potential reproductive hazards within the employee's workspace and recommendations for work duties involving hazardous materials. In some cases, adjustments should be made to an employee's work duties, if practicable, to avoid higher risk operations.

An additional interview is available with an occupational health nurse or physician at the University Employee Occupational Health Clinic (UEOHC). This interview allows the employee to express concerns and to ask questions about reproductive and developmental health. A review of an occupational and reproductive health questionnaire facilitates collection of employee-specific information, assists the employee in formulating concerns about chemical and physical hazards, and provides structure and focus for the interview. A preconception planning stage is also available. Obstetric specialists are available for consultation or referral for any specific concerns.

2. EHS Review of Laboratory Safety

EHS will conduct a review of the laboratory or worksite safety plan to ensure that it provides appropriate guidance to protect workers and prevent occupational exposures. EHS inspects the workplace to ensure that adequate engineering controls, such as chemical fume hoods, are provided, and that safe handling procedures and the use of personal protective equipment are in place. Employees have the responsibility of adhering to University safety procedures described in the Laboratory (or worksite) Safety Plan, the Environment, Health and Safety Manual, Laboratory Safety Manual, Biological Safety Manual, and the Radiation Safety Manual.

3. Radiation and Chemical Exposure Monitoring

EHS will monitor employee exposures levels for radiation and any chemicals of concern, especially those with evidence of reproductive toxicity. The employee and principal investigator, or supervisor, shall receive a copy of the monitoring report. The goal is to keep all exposures as low as reasonably achievable.

EHS performs the personnel radiation monitoring through the Radiation Safety section. EHS assigns the radiation employee a monthly radiation badge and/or places her on a monthly bioassay program.

F. Action Levels

1. Radiation Exposures

Current investigational radiation dose limits for declared pregnant or planned pregnancy employees will direct the RSO in evaluating reported doses. The North Carolina Regulations for Protection Against Radiation has established a radiation dose limit of 500 millirems for the conceptus during the entire gestation period.

Action Level I:

Employees with exposures greater than 30 millirems in a month. The RSO or designee shall send a written description of the dose report statistics, including the dose history for the previous two monitoring periods, to the person involved with a copy to the Authorized User. EHS asks the individual and their supervisor to review his or her radiation safety procedures and work habits in an effort to maintain all doses as low as reasonably achievable. Health physics reviews and consultation are available.

Action Level II:

Greater than 40 millirems in a month. The RSO shall conduct a direct investigation of the situation, including an interview with the person involved. The RSO prepares a written investigation report, including trends over the past one year (as available) for that person. The RSO provides a copy of the report to the employee for review and signature. Conclusions drawn from the investigation provide a basis for confirming or modifying the dose and for establishing corrective actions to undertake.

When the occupational radiation dose of a declared radiation employee exceeds 50 millirems in a month since declaration, the employee may request:

1. Maternity leave (for those employees actually pregnant)
2. Other paid leave
3. Leave without pay
4. Reassignment within their work unit
5. Transfer

The supervisor should respond to requests in accordance with Human Resources personnel policies.

EHS and the Radiation Protection Section of the NC Department of Environment and Natural Resources accept doses reported from personnel monitoring badges generally as an uncorrected guide to any conceptus dose. If personnel monitoring results indicate the possibility of a conceptus dose in excess of the 500-millirem limit, a special investigation will result. The investigation will take into full consideration the type and energy of radiation involved, protective shielding that might have mitigated conceptus dose, and shielding afforded by the mother’s body. The employee and EHS will discuss the investigation results, and a written report provided.

2. Chemical Exposures

As stated earlier, the goal is to keep all exposures to both radiation and chemicals as low as reasonably achievable. The actions taken in response to a measured chemical exposure depend on the specific circumstances and chemicals involved. However, as a general rule, if any exposure measurements exceed 10% of the threshold limit value (TLV) or permissible exposure limit (PEL) action will be taken to prevent further exposure by instituting engineering controls, improved work practices, personal protective equipment (PPE), or job reassignment.

3. Biological Exposures

There are no action levels for microbiological agents. Many of the agents listed above can be safely handled at Biosafety Level 2 practices and containment. For biological agents with higher risk to the individual, certain manipulations may require enhanced practices (e.g., culturing HIV requires Biosafety Level 3 practices).

Common Biosafety Level 2 practices include:

• Wearing gloves, lab coats and eye protection,
• Conducting any aerosol generating procedures inside of a biological safety cabinet,
• Decontamination of surfaces,
• Frequent hand washing, and
• No eating, drinking, smoking or handling contacts in areas where infectious materials are handled.

Please refer to the UNC Biological Safety Manual for more detailed information. These practices are required to protect the employee; however, some procedures conducted in the laboratory may be higher risk for pregnant employees and should be evaluated by EHS. In addition, the risks to the fetus from exposure to these pathogens may warrant restriction from use during a pregnancy. While the Conceptus Protection Program is limited to the duration of an individuals pregnancy, workers should also be aware that some biological agents may pose greater risk to their child after birth (e.g., RSV), and should continue to utilize the safety controls and procedures available to them. EHS in consultation with the employee and their supervisor will determine when restriction or additional personal protective equipment is necessary.

G. Additional Resources

Some additional resources for understanding and managing the reproductive hazards in the laboratory can be found below.

• OSHA Reproductive Hazards Standards
• NIOSH “The Effects of Workplace Hazards on Female Reproductive Health” and “The Effects of Workplace Hazards on Male Reproductive Health”
• NIH Information regarding “Electric and Magnetic Fields” in relation to ionizing radiation which has the potential for cellular or DNA damage.
• A Call for Increased Focus on Reproductive Health within Lab Safety Culture. J. Am. Chem. Soc. 2021, 143, 32, 12422 – 12427.
• What to Expect When Expecting in Lab: A Review of Unique Risks and Resources for Pregnant Researchers in the Chemical Laboratory. Chem. Res. Toxicol. 2022, 35, 2, 163 – 198
• Pregnancy in the lab. Nat. Rev. Chem. 2022, 6, 163 – 164.
• Megli, C.J., Coyne, C.B. Infections at the maternal–fetal interface: an overview of pathogenesis and defence. Nat Rev Microbiol 20, 67–82 (2022). https://doi.org/10.1038/s41579-021-00610-y Silasi M, Cardenas I, Kwon JY, Racicot K, Aldo P, Mor G. Viral infections during pregnancy. Am J Reprod Immunol. 2015 Mar;73(3):199-213. doi: 10.1111/aji.12355. 
• Center for Disease Control & Prevention (CDC) - National Institute for Occupational Safety & Health (NIOSH). About Reproductive Health in the Workplace.
• Stanford University Libraries reproductive and developmental hazards resources

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