Mycotoxins 101

For beef producers, mycotoxins are often a hidden problem. They are invisible, colourless and odourless. They are difficult to detect and often cause significant damage before they are identified and managed.

The source of mycotoxins most relevant to beef cattle production are fungi, including mold, that can be present in the grasses and cereals that cattle consume as feed. These fungi have the capability to produce mycotoxins when they are stressed. They do this as a defensive mechanism, with the mycotoxins meant to protect the fungi from external threats.

Virtually all feeds that comprise beef cattle rations are potential sources of mycotoxins. This includes green pastures, cereal swaths, standing corn for winter grazing, cured and ensiled grass, cereal forages, crop co-products (straw, distillers’ grains, grain screenings, oilseed meals) and commercial feeds.

It is important to note that the fungi or mold itself is not toxic to animals. The damage is done by the defensive mycotoxins, which are secondary metabolites that the fungi produce.

More than 400 mycotoxins have been identified, but only a few are regularly found in grains and seeds used for animal feed.

A few top examples of the types of mycotoxins that can be produced are:

Vomitoxin– also known as deoxynivalenol (DON), which occurs predominantly in cereal grains such as wheat, barley, corn, oats, and rye, and less often in canary seed and forage grasses. The occurrence of DON in Canada is associated primarily with Fusarium Head Blight caused by the pathogen Fusarium graminearum. Other mycotoxins which may be associated with DON are T2 and HT2, which are even more toxic than DON.

Zearalenone– Also produced by Fusarium, this less common mycotoxin is an estrogen-like compound that generally doesn’t have an effect on feeder cattle but can cause reproductive issues in cows.

Alkaloids – various types related to ergot including ergovaline, ergocornine, ergocristine, ergometrine, ergosine and ergotamine, which can contaminate cereal grains and cereal forages as well as cool season grasses. Claviceps purpurea is the fungus that causes ergot and produces these mycotoxins in purplish-black ergot bodies in the heads of the grasses or cereal grains.

Threat to Beef Cattle

The risk of mycotoxins being present at high concentrations  in cattle feed can fluctuate substantially in any given year, based on conditions such as warm moist conditions during flowering as well as environmental conditions during grain handling and storage.

In general, the risk is higher when moisture levels and temperatures are higher during the flowering stage – conditions also favorable for higher risk of pathogens and mold in feed.

The most common causes of mycotoxin issues that Canadian producers encounter are fungal diseases such as fusarium and ergot, as well as environmental, handling and storage issues that contribute to moldy feed.

Fusarium

Fusarium has been a rising threat to feed crops particularly in Western Canada but also in Eastern Canada. Warm, moist weather promotes spore germination on the infected crop residue that is spread by the wind to infect florets at the flowering stage of the cereal crop.  In areas where fusarium is present, these mycotoxins typically present a threat to cereal grains and cereal forages fed to livestock. The threat of fusarium contamination tends to be seasonal. In addition to feed quality and feed intake issues, fusarium mycotoxins contribute to gastrointestinal irritation and immune suppression. 

Even kernels infected with fusarium can appear normal (top left). Photo credit: Innovad

Ergot

Ergot has traditionally been more common in Eastern Canada but is now also rising in occurrence in Western Canada. Produced by Claviceps purpurea, ergot alkaloids can contaminate cereal grains and cereal forages as well as cool season grasses after they flower. In addition to feed intake issues, ergot mycotoxins can lead to “classic ergotism” – vasoconstriction leading to lameness and eventually gangrene (sloughed hooves, tails, ears.) They also contribute to undesirable metabolic effects such as increased body temperature, heart rate and respiratory rate. Ergot can also lead to abortion, weak calves, and a complete lack of milk production.

Other sources

In addition, there are multiple fungal classes present in crop production and beef production areas across Canada which can impact crops, feed grains and forages and lead to mycotoxins.

Conditions leading to moldy feed

Problems related to handling and storage of feedstuffs that can lead to mold development are another major threat. An open flap on silage can allow infiltration and  feed spoilage. There’s also a risk of spread due to air contamination when spores and fungus growing on mold are released into the air. Another common issue is wet grain in storage bins that are not properly monitored and managed.

Summary – the big threats

Typically the main mycotoxins of concern are tricothecenes (T2 and HT2, which are commonly found with DON), and ergot alkaloids. Moldy feed is also a major feed quality issue undermining health and performance, independent of whether or not mycotoxins are produced by the mold.

Exposure to mycotoxins can have a wide variety of effects on cattle health and performance, ranging from mild to moderate to severe.

Mycotoxins can result in lower feed intake, gastrointestinal irritation, compromised nutrition, lower weight gains and even weight loss. They can lead to gut health and respiratory problems, including secondary infections, as well as reproductive issues. They can also cause immune suppression, making animals more vulnerable to other threats and reducing the effectiveness of antibiotics. They can reduce fertility of both bulls and cows, lead to weak calves and at high concentrations can lead to abortion in pregnant cows and major health deterioration of animals including death.

Ergot in particular can cause vasoconstriction, which results in less blood to the extremities and can cause ears, tails and feet to fall off. Ergot is particularly damaging to reproductive function as it blocks release of the hormone prolactin which is needed to maintain pregnancy as well as for milk production. For bulls, ergot-contaminated feed reduces sperm production although overall reproductive effects are not as severe as for cows.

While typically the effects are mild to moderate and often hidden, many producers may not realize the degree to which mycotoxins are reducing the productivity of their herds and leaving the animals more vulnerable to sickness and stress.

Producers may notice times when cattle back off feed consumption or when weight gains drop, for no apparent reason, without realizing the issue is mycotoxins. Similarly producers may notice times when cattle get mild symptoms such as runny noses or show an energy drop off, again often not realizing the underlying issue is mycotoxins.

Even when the impacts are perceived as mild the related lost productivity costs can add up quickly. Experts say the mere presence of mold or other fungi can impair digestibility up to 15 percent, even when mycotoxins are not present.

When mycotoxins are also present, that reduction in feed digestibility can rise much higher.

A big challenge for producers in dealing with the threat of mycotoxins is that they are a hidden problem. The presence of fungi or mould is a noticeable indicator of a possible threat, but the mycotoxins themselves are invisible, colourless and odourless, and may be present regardless of whether or not fungi or mould are visible.

Eyeballs and experience don’t cut it when it comes down to knowing the quality of your feed. Testing for mycotoxins is the only way to know for sure.

The best options for producers are to simply not give moldy feed to animals, to follow all best practices and precautions (see next section below) and to consider testing feed samples on a regular basis particularly when risk conditions are high (i.e. when moisture levels and temperatures are higher during flowering and when storage conditions allow moisture levels beyond recommended ranges.) If the purplish black ergot bodies are noticed in cereal grain, testing the feed would be recommended.

When getting testing done, it’s important to recognize that mycotoxins can be present in various degrees. Some kernels will have very high levels of toxicity while others will be lower. Therefore, getting a representative sample of feeds is VERY important. When gathering samples from feed grown on farm, it is important to take samples from different areas and mix them. Check with advisors and / or the test company you are dealing with for information on best sampling protocols. For example, a protocol may call for: taking five sub-samples of 250 grams each from different areas, then mixing them together in a pail, then taking 250 grams from the pail as the sample used for mycotoxin analysis.

For those purchasing feed, make sure to ask about mycotoxins with your supplier. Many feed mills have procedures in place to sample from multiple locations and both identify and address any issues before feed is supplied. It’s good to ask about the feed mills mycotoxin testing procedures if feeding screenings, pellets or millrun as these feeds have a higher risk of contamination. 

Reducing the risk boils down to four factors – awareness, feed testing, additional best practices to ensure feed quality and best practices to keep animals healthy. 

Awareness – Monitor and address risk conditions. Awareness is about understanding and monitoring for risk factors, which can fluctuate season to season and year to year. When conditions are conducive to Fusarium, ergot and other sources of fungi and mold development – typically when temperatures and moisture conditions are high during flowering – greater precautions are required.

For producers growing their own feed, also consider disease monitoring from the year before as risk conditions and pathogen presence can carry over from one year to the next. For grasses used for feed, which may be infected, it’s best to mow them sooner rather than later to avoid conditions that would allow mold to develop and grow. When storing all feedstuffs, the key is to cover and store appropriately to keep moisture and oxygen levels in check. To reduce or prevent production of mycotoxins in corn, drying should take place as soon as possible after harvest. It is important to avoid damage to the kernels before and during drying, and during storage.

It’s also important to monitor livestock for early symptoms of mycotoxin related issues. Unexplained drop-offs in feed intake or weight gain, a rise in gastrointestinal issues, when these and other issues seem to happen for no apparent reason the cause could be mycotoxins and you should test your feed to see if mycotoxin contamination may be the problem.

Feed testing – Do it regularly. It’s important to remember that mold and mycotoxins are not the same thing. Mycotoxins may still be present even if no mold is visible. It is difficult to correlate mold or grain damage with the presence of mycotoxins. The only way to know for sure is feed testing for mycotoxin identification.

Regular feed testing is now advised as a standard part of good management that provides a valuable insurance policy and peace of mind.

While accurate rapid tests exist for the presence and levels of mycotoxins and others, one current challenge is the lack of a rapid test to quantify the level of specific ergot alkaloids. The Canadian feed industry has implemented approaches to help address the ergot issue by pre-screening incoming ingredients and limiting the use of certain risk materials in years where higher levels of ergot are suspected or known.

Feed quality – Follow best practices. Ensuring feed quality also means following best practices:

• Practice regular feed testing – remember visual appraisal is unreliable
• Never feed moldy feed to pregnant animals
• Purchase cereal by-products (cereal screenings and distillers’ grains are higher risk) from reputable feed sources and test for mycotoxins prior to feeding if you are unsure
• Remember forages can be contaminated too
• Source quality “clean feed” from trusted sources (feed mills, feed suppliers, etc., who have strong quality control measures in place)

Keep animals healthy – Multifactorial approach. Doing all you can to support healthy animals also helps make them less vulnerable to mycotoxins. Make sure to follow best practices for:

• Herd health (vaccinations, parasite control, routine monitoring)
• Biosecurity
• Clean, safe environment
• Nutritional status & feeding management
• Reduce stress (animal care and welfare best practices)
• Gut health

Use industry resources and trusted advisors to support your approaches in all of these areas.

Summary note – Do your homework. With all feed technology options there are a range of preventative sources with varying quality and efficacy. Do your homework and rely on trusted advisors to ensure you are using options based on sound science and proven results.

Digging Deeper on the Big Questions

What are the top challenges mycotoxins present?

 Mycotoxins pose a variety of challenges. To name the top ones:

• Animals given mycotoxin-infected feed can experience many health problems, some of which are severe
• Feed management strategies (such as testing, cleaning or diluting feed) can cost the producer time and money
• Although more than 400 mycotoxins are known, commercial testing is only available for a few of the most common
• Infection can degrade market quality of grain, causing significant financial loss for a producer growing crops for feed
• In extreme cases, infected feed may need to be thrown out and replaced.

In 2015, the United Nations Food and Agriculture Organization (FAO) prepared an assessment of mycotoxin contamination in feed and estimated its cost to the industry in North America.

“It has been estimated (Miller, Personal communication), for example, that annual losses in the USA and Canada, arising from the impact of mycotoxins on the feed and livestock industries, are of the order of $5 billion.” – FAO, 2015

Mycotoxin contamination is difficult to trace and measure, and field data and research into the effects of mycotoxins in cattle can be variable and contradictory. Mycotoxins rarely occur in isolation, yet the combined effects of different types of mycotoxins are not well-known.

If feed ingredients are contaminated with mycotoxins, degree of toxicity can be difficult to determine. Total mixed rations (TMR) using multiple ingredients can make it even more difficult to determine the extent of toxicity and pinpoint the cause. With other manufacturing processes, such as distillers’ grains, toxins can quickly add up to unsafe concentrations.

Further research is needed to fully understand how to control mycotoxins, and to determine what concentrations are ‘safe’ in feed for cattle.

Mycotoxins affect animals in a variety of ways, depending on their age and stage of life, the extent of mycotoxin exposure and the length of time the animal has ingested a certain mycotoxin. 

Eliminating the threat of mycotoxins is nearly impossible. However, producers can take preventative steps to reduce the possibility of mycotoxin contamination of their feed sources. If mycotoxins are detected in feed grains, certain strategies can be followed to make the feed source safer for cattle.

Cattle, being ruminants, are somewhat resistant to mycotoxins because microbes in the rumen can naturally detoxify a consistently low concentration of mycotoxins over time. However, if sudden high concentrations of mycotoxins are present in the feed, the negative impact on animal health can be severe. 

Where are mycotoxins found in Canada?

In recent years, Canadian producers have seen increased occurrence of mycotoxin contamination from fungi such as Claviceps purpurea and Fusarium graminearum.

In 2005, widespread ergot mycotoxin contamination was noted in Manitoba, followed by similar outbreaks in 2008 and 2011 across Saskatchewan, Manitoba and Alberta. Claviceps purpurea is more often found in the western Prairies. Cattle have a lower tolerance for ergot alkaloids than they do for  the mycotoxins that result from Fusarium.

Fusarium has traditionally been found in Eastern Canada and the Midwest United States, but a severe outbreak in 1993 made the disease more prevalent in Manitoba and Eastern Saskatchewan. Since 1999, Fusarium has continued to spread into Western Saskatchewan, Alberta and Northern British Columbia. 

What causes mycotoxins?

Mold growth, and the subsequent potential production of mycotoxins, is typically the result of plant exposure during flowering and tends to be worse when conditions produce a wet, cool spring. Drought can also stress plants and make them more susceptible to fungi such as Claviceps purpurea and Fusarium graminearum.

Ergot bodies produced by Claviceps purpurea can also drop from infected plants onto the soil. These ergot bodies then germinate in the spring and release spores which enter the plants at the flowering stage.

The complex ecology of mold growth, and subsequent mycotoxin production, can produce a staggering variety of toxins. These molds multiply in the field, and mycotoxins can also be ‘imported’ within the feed itself. Left undetected, many of these mycotoxins can make their way into feed sources for cattle at dangerous concentrations.

While the mycotoxins resulting from Claviceps purpurea and Fusarium contamination pose significant challenges for producers, the diseases caused by these mycotoxins have different characteristics.

What are the mycotoxin-specific best practices?

The effect that mycotoxin-contaminated feed can have on cattle depends on what type of mycotoxin is present, the age and production stage of the animal, the amount that the animal has ingested and how long the animal has been consuming contaminated feed. Calves born after exposure to mycotoxins may be permanently set back, although generally cattle should rapidly recover once the mycotoxins are removed from the diet. Reproductive functions such as milk production might not recover until the next pregnancy.

Here are some best practices to employ when you suspect mycotoxins in your field or feed.

Identify Crop Disease

Identify crop diseases early, especially those from Claviceps and Fusarium that produce mycotoxins.  Each crop disease will express differently, so get to know what to look for in your field. Catching the disease early can help to reduce the chance of mycotoxins entering the feed. More complete information can be found in the sections on ergot and Fusarium mycotoxins below.

Symptoms of Mycotoxin poisoning

Watch for symptoms of mycotoxin poisoning in cattle. Paying close attention to your livestock is key. One of the difficulties is that cattle with mycotoxin exposure express symptoms that are wide and variable, and those same symptoms can also relate to other problems. Younger animals, such as calves just weaned and starting on feed, or heifers at breeding, are more susceptible to poisoning because of their immature immune systems and must be watched carefully for signs of distress.

Some problems from ingesting mycotoxins are reversible, while others can be very serious, even leading to death.

Here are some general signs that your cattle could have mycotoxin poisoning. Trust your experience – if you feel ‘something is not right’, it probably isn’t. Take immediate action if an animal exhibits any of these symptoms (symptoms are most often seen in the winter months):

• animals consume less feed; a feed reduction greater than 30% should be investigated
• a decrease in growth or performance, or a failure to thrive
• animal seems to be frequently sick, which may indicate immune suppression
• animal does not respond to antibiotics
• animal has convulsions, muscle spasms, temporary paralysis (not typically seen in Western Canada)
• gangrene or lameness is present, especially in the animal’s ears, tail and feet
• animal has a fever, or has intermittent bloody diarrhea
• there are blisters, reddening, or ulcers in the mouth
• abortion and premature births occur, or reduced lactation
• fertility issues such as weak testicular development and low sperm count in bulls.

Actions to Take if You Suspect a Mycotoxin Infection

>> If you suspect mycotoxins in the feed, remove the feed immediately, and do not feed it until it’s been properly tested in a lab or diluted or cleaned to acceptable levels. >> If you suspect mycotoxin poisoning in your herd, consult your veterinarian immediately.

Feed Sources

Know the source of your feed ingredients. Some feed processing procedures can concentrate or increase mycotoxins in the feed (e.g.  grain screenings distillers’ grains). This can take a contaminated feed source from ‘safe’ levels to ‘high risk’ levels quickly. While most livestock feed manufacturers will screen for mycotoxins, it’s important to ask where the crop ingredients originated from, and whether it is from an area known to have high levels of mold growth, plant stress or mycotoxin contamination. Make sure you alert your whole team to be on the lookout for this problem. Keep your veterinarian, nutritionist and feed company reps in the loop.

Testing

If you suspect an infected crop or contaminated feed, get a lab test to confirm the extent of the problem. Allow several days for the lab to complete the test. If you operate in a high-risk area or have had issues in the past frequent testing may be a good prevention strategy.

For a list of labs in your province, consult the Canadian Grain Commission, your local agriculture specialist or search online. Costs will vary depending on the test required, so check with the lab.

Getting a Good Sample to Send to the Lab Mycotoxins are rarely evenly distributed, so getting a representative sample can be challenging. The accuracy of your lab results will depend on the quality of the sample you submit. Here are suggested steps for getting a good sample. More than 90% of the variability that is seen in the lab is due to sample collection. HARVESTED GRAIN take 15 to 20 samples during loading and unloading, or 1 to 4 spots in the grain bin aim for a sample of 1,000 to 2,500 grams clean the sample to remove weed seeds, rocks and other material - mix these samples in a container and collect a final sample of about 500 grams from the mixture (or the required amount for the lab you are using) send to the lab in a Ziploc bag with your name and paperwork attached FIELD SAMPLES close to harvest time, combine a swath from a typical section of the field, or collect an average of 5 to 10 plants from various locations throughout your field by cutting off the plant about 4 to 5 inches above the ground chop the samples into smaller pieces, and mix all the samples from the 5 to 10 plants together fill one-half to two-thirds of a bread bag (or a large Ziploc bag) and squeeze all the air out of it freeze the sample, label the sample and attach the required paperwork Mycotoxins are stable so it is not imperative to ship the sample to the lab immediately

Handling

Prevention

Ergot-related mycotoxins: How do they occur?

The major ergot fungus is Claviceps purpurea which produces sclerotia (commonly called ‘ergot bodies) in several grass species. Ergot is present in cereals and grains throughout the world, but is most typically found in rye, triticale, wheat, barley, oats and some perennial or wild grasses. Although Claviceps purpurea is not found in corn, other mycotoxin-producing fungi can contaminate corn and can cause problems when fed to livestock.

Once mature, the ergot sclerotia (the hard, purplish black body of the fungus) becomes detached from the host plant, drops to the ground and can remain dormant in the soil until favorable growth conditions occur.

Ergot contamination of cereals can occur in two stages. During the first stage, the sclerotia germinates and produces fruiting bodies resembling a tiny mushroom. These bodies produce thread-like spores that are wind-blown to the host plant. The plant’s florets must be open to be infected. Cool, damp weather during the flowering period can prolong the flowering stage, and make a plant more susceptible to infection, and thus the spread of disease.

Once a plant’s florets are infected, within about 5 days, a secondary spore growth occurs in the plant head along with a second chance at spreading the disease. These spores are encased in a sticky liquid referred to as ‘honey-dew’. This liquid can be spread by rain splash or insects that spread the spores further throughout the crop.

As the infected plant grows, the sclerotia matures and hardens into elongated, dark or black kernels (ergot bodies) that resemble mouse droppings. Left to mature, these ergot bodies will detach from the plant head and drop to the soil, starting the cycle over again.

If these ergot bodies are harvested along with the grain, however, the ergot bodies can enter the feed system. These dark ergot bodies contain toxins called ergot alkaloids. When consumed, these alkaloids can be harmful to cattle, causing irritability and more severe conditions such as gangrene of the ears, tail and feet. Young or pregnant animals are more susceptible to ergot poisoning.

What to do if you suspect ergot poisoning in cattle?

Ergot poisoning can be very serious. It can take between two and six weeks after an animal ingests ergot-infected feed to start showing symptoms of ergot-poisoning. Some symptoms such as gangrene, once manifested in an animal, are irreversible. Therefore, preventative measures are essential.

Symptoms of ergot poisoning

If you suspect ergot poisoning in your herd, remove the feed immediately and call your veterinarian. Here’s what to look for:

• Convulsions, muscle spasms, temporary paralysis
• Lameness, usually observed in the hind legs first
• Gangrene especially in an animal’s ears, tail and feetFever
  • The time for gangrene to appear will be influenced by the concentration of ergot in the feed and the ambient air temperature. Under extreme cold or heat, increased feed consumption and the combined vasoactive effects of cold, heat and ergot result in clinical manifestation at lower concentrations.
• Abortion and premature births
• Reduced milk production (usually persists for the entire lactation period)
• Animals consuming less feed, and generally failing to thrive.

Identifying ergot in a crop or harvested grain

Ergot can appear in seed heads of annual crops used for green feed, swath grazing or bale grazing, and can persist for up to a year (or longer) in stored grain or in the field. Ergot toxins can also be more highly concentrated in distillers’ grains, screenings and screening pellets. 

Dark or black elongated ergot bodies grow in place of the kernel. Ergot kernels can vary greatly in size, and can be much larger, the same size, or smaller than healthy kernels. A visual test will show the presence of the sclerotia, but a lab test is needed to determine the concentration of the alkaloid toxins. Ergot bodies may have different concentrations of alkaloids, and these concentrations can vary from crop to crop. For a visual reference of ergot, read our blog.

Management strategies for ergot-infected feed

The only way to know for sure if mycotoxins are present in feed, and to evaluate the risk of toxicity, is to have feed analyzed in a lab. An individual ergot body can have high or low levels of toxins, so testing is the only sure way to determine the concentration of the mycotoxins. See the Best Practices section above for details on lab testing.

It may be possible to clean infected feed by separating it from healthy grain by size, colour or by gravity cleaners. However, this process can be slow and/or expensive. For more on this, read our ergot blog.

If you are attempting to improve contaminated feed by diluting it with clean feed, or you are wondering what is ‘safe’ to feed your animal, be aware that ergot poisoning may occur at concentrations lower than those stated in previous guidelines.

There is much debate in the industry about the guidelines, and the bottom line is that it is not clearly known what concentrations  of ergot alkaloids are acceptable for feed. It can vary depending on the species of animal you are feeding. More research needs to be done to further answer this question.

The Canadian Food Inspection Agency (CFIA) publishes acceptable ‘action levels’ (allowed amounts) in feed by type of mycotoxin and commodity. These mycotoxin regulations for Canada can be found on the CFIA website. Again, these guidelines are to be used with caution because many in the industry believe that these recommendations are outdated and they are currently under revision.

Check with your lab, your vet or other feed experts on what is the most current research on offering contaminated feed to your animals. However, with this kind of uncertainty, you may not want to take the chance. In the end, it may be more economical to buy new feed if you discover heavy contamination in your feed, and dispose of any infected feed.

Prevention strategies for ergot in the field

Ergot can be difficult to spot until the disease is well underway. By the time the ergot bodies are visible, it is too late to stop the impact on the crop. Therefore, if you are growing crops for feed, it’s best to take preventative measures to try to minimize fungal disease before it takes hold on the farm. Once ergot infects a field, it is difficult to eradicate.

The following management practices can help reduce the chance of the disease gaining hold in a crop:

• grazing animals on pasture is safer, as it is difficult for ergot to take hold when the plant is eaten before it heads out
• if you graze animals on pasture with grass that has already headed out, check for ergot infection before allowing your animals to graze
• mow grasses in neighbouring fields, roadways or ditches
• plant seed that is free of disease, or choose a seed variety with a higher resistance to disease
• use practices that keep soil and crops healthy, such as tillage practices that may reduce infestations
• rotate crops away from infected crops to avoid carry-over of mold and sclerotia

Canadian Research on Ergot and Fusarium Mycotoxins: What Does the Science Say?

Because of the ability of cattle to detoxify DON, most Fusarium-related mycotoxins have traditionally been regarded as a less severe problem as compared to ergot-related mycotoxins. In Canada, most of the research on the impact of feeding ergot-infected feed has been done with swine and not cattle. Canadian standards are available for feeding cattle a ‘safe’ concentration of ergot alkaloids and Fusarium-related mycotoxins, but many livestock specialists feel they are outdated and lack Canadian relevance associated with temperature, moisture conditions and crop types.

The complexity of this issue means more research is needed for clear guidelines moving forward.