1. LEAD Valya Dessaure, Ph.D. student Walden University PH 8165-1
Instructor: Dr. Shana Morrell
Spring Quarter, 2009

2. Goals Upon viewing this presentation, viewers will: Know what lead is
Learn about laws regarding lead
Know common exposure routes
Learn the symptoms of lead poisoning
Learn about the risks to children, pregnant women, and adolescents
The goals of this training are that participants will:
Know what lead is
Be familiar with the US laws to decrease lead exposure
Be aware of the PH law regarding prenatal providers and lead screening
Be knowledgeable of how a person is exposed to lead, sources of lead, how lead enters the body, the symptoms of lead poisoning, the organs that lead affects
Be knowledgeable in how lead affects children, pregnant women, and adolescents

3. What is Lead? Naturally occurring soft, blue gray metal
Present in all parts of the environment
Has many industrial uses
Very resilient
Agency for Toxic Substances and Disease Registry. (2007). Case Studies in Environmental Medicine retrieved from
Lead is a metal which occurs naturally in the environment. It is very resilient and stable and does not breakdown in the environment. Lead is normally present in the earth’s crust.

4. Lead Poisoning
In the mid 1970’s- 78% of children between the ages of 1-5 had elevated BLL
In the mid that number decreased to less then 5%
Between a little more then 2% of children between the ages of 1-5 had an elevated BLL
Centers for Disease Control and Prevention. (2005). Blood lead levels-United States, MMWR, 54,
The United States has had great success in reducing the number of people who have been affected by and exposed to lead. The number of children with elevated blood lead levels has decreased by more then 75% in the past thirty years.
Lead poisoning continues to be a problem that needs to be addressed. Because it is preventable those that work with children and pregnant women need to continue to be aware of lead poisoning, to assess and educate those populations we work with.
The statistics on the slide demonstrate the success the US has made in decreasing the number of children affected by lead.

5. Action Level The CDC action level is 10 mcg/dl.
There are six classes of lead exposure.
Bellinger, David C. (2003). Lead. Pediatrics, 113,
Center for Disease Control (2005) Lead Poisoning Prevention Program retrieved from
The CDC (2005) has determined that a blood lead level greater then or equal to 10 mcg/dl requires public health action. Bellinger (2004) cautions against using this number as a “threshold”, he feels there are other variables, such as age at exposure, length of exposure, age at assessment etc. which should also be considered.
There are six classes of lead exposure based on one’s blood lead level. One’s blood lead level and class will determine what follow-up screening, environmental assessment, education, and/or treatment are needed. The blood lead levels range from <9 for a class 1 to >70 for class 6. Recommended actions for a class 2 elevated lead are: lead education and referrals with diagnostic testing within three months and follow-up testing in two to three months. If there are a large number of children with a blood lead level of mcg/dl this should trigger a community-wide lead prevention program. For a class 6 elevated lead level the recommend actions are the child is considered a medical emergency requiring hospitalization for immediate chelation.

6. New York State (exc. NYC) Statistics
Year
State
Population
<72
Months
Old
Number of
Children
Tested
Total
Confirmed
Cases
EBBL’s
as % of
Number of Confirmed Children By Highest Blood Lead Level (mcg/dl) at or Following Confirmation
10-14
Mcg/dl
15-19
20-24
25-44
45-69
>=70
1997
1,555,068
206,547
13,026
6.31%
7,810
2,967
1,165
1,009 66 9
1998
1,504,741
194,784
10,664
5.47%
6,435
2,520
915
715 71 8
1999
1,469,922
181,768
8,281
4.56%
5,123
1,844
663
592 49 10
2000
New York
1,500,961
181,036
6,171
3.41%
3,854
1,308
521
427 52
2001
(Excl. NYC)
1,503,096
183,201
5,166
2.82%
3,229
1,122
403
368 37 7
2002
179,769
4,493
2.50%
2,842
946
356
309 36 4
2003
160,825
3,767
2.34%
2,286
845
318
285 28 5
2004
133,721
3,218
2.41%
1,963
697
280
254 22 2
2005
193,523
3,012
1.56%
1,954
607
218
211 16 6
2006
198,050
3,098
1,878
692
249
247 29 3
As can be seen from the chart, New York state has made great strides in decreasing the number of children with elevated BLL. The number of children tested has decreased slightly from 206,547 thousand in 1997 to 198,050 in The number of children under the age of 6 years old with elevated BLL’s in 2006 is about ¼ of the number it was in The number of children with elevated BLL dropped from 13,036 in 1997 to 3,098 in 2006 (CDC, 2009).
CDC Surveillance Data retrieved from /

7. Laws Banning leaded gasoline Mandated lead screening in children
Banning the use of lead paint
Limits on smokestack emissions of lead
Center for Disease Control (2005) Lead Poisoning Prevention Program retrieved from
There are laws which have decreased the incidence of lead poisoning in the Unites States. They include banning the use of lead paint for residential use in 1978, banning most uses of leaded gasoline in 1986, and placing limits on smokestack emissions of lead. There are also state mandates to screen for lead in children. The state of New York has implemented laws for assessing women receiving prenatal care.

8. NYS Public Health Law
Prenatal providers in NYS are required by Public Health Law 67 to provide lead screening and follow-up of pregnant women.
New York State Department of Health. (2008) . NYS Regulations for Lead Poisoning Prevention and Control - NYCRR Title X, Part 67
Prenatal providers in NYS are required by Public Health Law 67 to provide lead screening and follow-up of pregnant women. They are required to :
provide anticipatory guidance on lead poisoning prevention during pregnancy
assess all pregnant women at their first prenatal visit and provide testing for all those at risk
for women with an elevated BLL risk reduction and nutritional counseling must be provided
if an occupational exposure is the suspected reason for the elevated BLL a referral must be made to an occupational health service
provide information at the postpartum visit re: prevention of children’s lead poisoning prevention (NYSDOH, 2008)

9. How Lead Enters the Body
Ingestion
Inhalation
Dermal contact
Lead is excreted though the kidneys and liver
Agency for Toxic Substances and Disease Registry. (2007). Case Studies in Environmental Medicine.
Lead enters the human body via ingestion and inhalation and is excreted through the kidneys and liver. According to the ATSDR (2005) most inhaled lead is absorbed by the body and 20-70% of ingested lead is absorbed. Children absorb more lead then adults. Ingestion is the primary route of exposure for children and children absorb between 40-50% of ingested lead, while adults 10%. Dermal contact (through the skin) is rare in the US.

10. Everyone is Affected by Lead
Children
Women
Men
Children between the ages of six months and six years are most susceptible to lead poisoning for two primary reasons: they place their hands near or in their mouths frequently and their brains are still developing. Immigrant children, children of color, poor children and children living in urban and industrialized areas are more susceptible.
Pregnant women are also of great concern because of the risk to the fetus. Lead that has been stored in a woman’s bones can move during pregnancy and into her bloodstream and cause damage to her body and to her unborn baby. The lead moving from the bones to the bloodstream will cause an increase in the woman’s blood lead level. Men are of concern because of occupational exposure and exposure that may occur as a result of hobbies (making stained glass, fishing lures, exposure to lead shot).
Between ,522 adults were reported to New York state’s adult Heavy Metals Registry with a BLL > 10 mcg/dl. 10,021 of those reported were men and 8,276 of those reported had an unknown reason for exposure (unknown means it was not a work or non-work exposure)(NYSDOH,2006).

11. Sources of Lead Herbal medicines Lead-based paint
Food and candy from other countries
Food containers
Pets
Lead-based paint
Lead in water
Leaded gas
Work
Toys
Before 1960 lead paint was used in 70 % of homes being built. If a home is in poor, deteriorating condition lead can be released into the air. If renovation is occurring and lead based paint is sanded dust is created which can be inhaled. The dust can also settle in the soil and be disturbed when children play outdoors. Plants can also absorb lead from the soil. Ingestion of lead can occur If these plants are then used for food products (Edwards, 2008).
Some old water pipes may have lead in them which can leach into the water supply. According to the CDC (2003) 10-20% of lead exposure in children occurs from drinking water. A study conducted by Bryant (2004) found that more then 57% of the public school buildings in Philadelphia had water lead levels above the EPA’s acceptable levels between 2000 and 2001.
Herbal medicines are not monitored by the FDA and may contain unacceptable levels of lead. The same is true for food and candy from other countries.
Some persons are exposed to lead and lead dust as a result of the work they do. If people who are exposed at work wear those clothes home they may expose their family members to lead dust on their clothes.
Pets can get lead dust from soil on their fur and expose humans. Pets can get ill from lead also.
Doumouchtsis (2006) reports on a pregnant woman who was diagnosed with lead poisoning after her cats were exposed to lead during home renovations became ill and one died.
Some countries do not have bans on leaded gasoline and immigrants and refugees may have been exposed while in those countries.
Recent recalls of toys has brought attention to lead in toys and the use of lead-based paints on some toys. Children are also at risk if they are exposed to antique toys or collectibles which may contain lead.
Agency for Toxic Substances and Disease Registry. (2007). Case Studies in Environmental Medicine.
Bryant, S.D. (2004). Lead-contaminated drinking waters in the public schools of Philadelphia. Journal of Toxicology. Clinical Toxicology, 42,
Doumouchtsis, S.K., Martin, N.S., Robins, J.B. (2006). ‘Veterinary’ Diagnosis of lead poisoning in pregnancy. British Medical Journal, 333,
Edwards, Marilyn. (2008) Lead Poisoning: a public health issue. Primary Health Care, 18,

12. Pica
Eating non-food substances.
Poor nutrition
Mineral deficiencies.
Hamilton, Shawn, Rothenberg, Stephen J., Khan, Fuad A., Manalo, Mario, Norris, Keith C. (2001). Neonatal lead poisoning from maternal pica behavior during pregnancy. Journal of the National Medical Association, 93,
Pica is a disorder in which a person eats non-food substances. Two causes of pica are poor nutrition and mineral deficiencies. Eating clay dirt is a source of lead ingestion and has been seen in black women from the Southeast and migrant Mexicans.
Hamilton (2001) reports on a 25 year old pregnant Hispanic female who ingested pieces of a clay pot on a daily basis. She had been told by her family and friends that she could get the needed minerals from a clay pot. She proceeded to break clay pottery into small pieces and eat pieces a few times each day. She had an uneventful pregnancy with complaints of occasional headaches, dizziness and forgetfulness. When presenting to the hospital for delivery she enrolled in a lead screening survey and was found to have an BLL of Her infant had a cord BLL of and required a double-volume transfusion and chelation therapy with good results

13. Stored Lead Blood Soft Tissues Bones Teeth
Riess, Matthias L., Halm, Josiah K. (2007). Lead Poisoning in an Adult: Lead Mobilization by Pregnancy?. Journal of
General Internal medicine, 22,
Lead that is absorbed in the body and not excreted may be stored in the blood, soft tissues, bones and teeth. Lead can remain in bones and teeth for many years. More than 95% of lead that is absorbed by the body is stored in bone and teeth. 2% of absorbed lead is stored in the blood.

14. Effects of Lead Peripheral nervous system Central nervous system
Gastrointestinal system
Joints
Muscles
Kidneys
Blood system
Cardiovascular system
Agency for Toxic Substances and Disease Registry. (2007). Case Studies in Environmental Medicine.
Lead affects a number of systems. It can affect the neurological system, the GI and GU systems, the musculo-skeletal system, and the vascular system.
The neurological effects for an adult who was exposed as a child can be different then the effects for an adult who was exposed as an adult. Exposed adults can tolerate higher BLL’s then children who’s brains are developing.

15. Effects on Major Organs
Kidney disease
High blood pressure
Nerve damage
Gout
Encephalopathy
Cognitive deficiencies
Death
Agency for Toxic Substances and Disease Registry. (2007). Case Studies in Environmental Medicine.
Lead stored in major organs can cause: kidney disease possibly leading to renal failure, high blood pressure, nerve damage, coma, convulsions, gout, encephalopathy, cognitive deficiencies and even death.

16. Symptoms of Lead Poisoning
Fatigue
Dizziness
Headache
Nausea
Vomiting
Abdominal pain
Bone & joint pain
Agency for Toxic Substances and Disease Registry. (2007). Case Studies in Environmental Medicine.
These are some of the usual symptoms of lead poisoning. It is important to remember that it is possible to have an elevated blood lead level (BLL) and have no symptoms. A BLL measures only the amount of lead a person currently has in their bloodstream or has been exposed to continually. It does not tell if or how much lead is stored in a person’s bones.

17. Pregnancy & Lead Poisoning
Elevated BLL in a pregnant woman can cause:
-High BP during the pregnancy
-Increased chance of miscarriage
-Learning problems in their children
-Premature labor
-Anemia
Sowers, Maryfran, Jannausch, Mary, Scholl, Theresa, Li, Wenjie, Kemp, Francis W., Bogden, John D. (2002). Blood
Lead Concentrations and Pregnancy Outcomes. Archives of Environmental Health, 57,
As noted, pregnant women are of particular concern in regards to elevated BLL. Elevated BLL in pregnant women can cause: high blood pressure, miscarriage, premature labor, anemia, and learning problems in the baby when it gets older.

18. Pregnancy & Lead Poisoning (con’t)
Lead can cross the placental barrier (Sowers, 2002).
Stress can cause stored lead to shifts (Johnson, 2001).
Poor calcium intake can cause elevated BLL (Johnson, 2001).
Johnson, Mary Ann. (2001). High calcium intake blunts pregnancy-induced increases in maternal blood lead. Nutrition reviews, 59,
Sowers, Maryfran, Jannausch, Mary, Scholl, Theresa, Li, Wenjie, Kemp, Francis W., Bogden, John D. (2002). Blood Lead Concentrations and Pregnancy Outcomes. Archives of Environmental Health, 57,
Lead can easily cross the placental barrier during pregnancy and go from a pregnant woman to her fetus and effect the fetus (Sowers, 2002). Pregnancy is naturally stressful to a woman’s body and during times of stress the lead that has been stored for many years in a woman’s bones can move into her bloodstream. Pregnant women with poor calcium intake also have an increased risk of having elevated blood lead levels and can release lead stored in the bones into the bloodstream and organs. Research by Johnson (2001) found that pregnant women who increased their calcium to 2500 mg/day which is twice the recommended dosage would decrease the amount of lead in their blood. Before a pregnant woman takes any supplements or medications she should talk to her medical provider.

19. Pregnancy & Lead Poisoning (con’t)
When a baby is born its blood lead level will often be similar to or higher then it’s mothers (Hamilton 2001).
Lead has its greatest effect when the baby is in the womb and during the first 3 years of the child’s life.
Lead can be passed to the infant when the mother breastfeeds (Zentner, 2006).
Hamilton, Shawn, Rothenberg, Stephen J., Khan, Fuad A., Manalo, Mario, Norris, Keith C. (2001). Neonatal lead poisoning from maternal pica behavior during pregnancy. Journal of the National Medical Association, 93,
Riess, Matthias L., Halm, Josiah K. (2007). Lead Poisoning in an Adult: Lead Mobilization by Pregnancy?. Journal of General Internal medicine, 22,
Zentner, Luz Estela, Rondo, Patricia H.C. Mastroeni, Silmara S.B.S. (2006). Lead Contamination and Anthropometry. Journal of Tropical Pediatrics, 52,
Riess (2007) reports on a case study of a 22 year-old African-American woman with complaints of sharp mid-abdominal pain for two weeks nausea and vomiting for two days, pain in both knees, headaches, finger tingling and increased irritability. The young lady had lead poisoning at the ages of 6 and 15. At the age of 15 hospitalization was required due to an elevated BLL which caused seizures and kidney failure. Her BLL was 145 mcg/dl. She was treated with chelation treatments for three weeks. 8 months earlier she had been pregnant and miscarried due to the complications of gonorrhea. When she presented to the emergency room with her current complaints her blood pressure was significantly elevated as was her heart rate. Her BLL was 81 mcg/dl and she received chelation treatments for three weeks. 5 months later her BLL had decreased to 57 mcg/dl and her symptoms were resolved. This case is a good example of how lead can move during pregnancy and how lead can effect multiple organs.
Although lead can be passed to the infant via breastfeeding it is usually better for the baby then bottle feeding. .

20. Impact on Children
Lead exposure during early childhood can cause problems with:
learning
attention (Braun, 2006)
fine motor skills
social skills
impulse control (Bellinger, 2003)
Bellinger, David C. (2003). Lead. Pediatrics, 113,
Braun, Joe M., Kahn, Robert S., Froehlich, Tanya, Auinger, Peggy, Lanphear, Bruce. (2006). Exposures to
Environmental Toxicants and Attention Deficit Hyperactivity Disorder in U.S. Children. Environmental Health
Perspectives, 114,
Children that are exposed to lead during the first few years of their lives may have problems with: their ability to learn, attention deficits, fine motor skills, social and behavior skills and impulse control. Central nervous system involvement occurs more in children then in adults. The effects on the central nervous system appear not to reversible in children (Bellinger, 2003).
A study conducted by Braun (2006) found that 290,000 children were diagnosed with attention deficit hyperactivity disorder which was linked to lead exposure.

21. Immigrant Children & Lead
Recent immigrants.
Refugees and adoptees
Children with extended visits to foreign countries.
Tehranifar, Parisa, Leighton, Jessica, Auchincloss, Amy, H., Faciano, Andrew, Alper, Howard, Paykin, Andrea, et al. (2008). Immigration and Risk of Childhood Lead Poisoning: Findings From a Case-Control Study of New York City Children. American Journal of Public Health, 98,
It is very important that children who are recent immigrants to the US have BLL screening done. A study conducted by Tehranifer (2008) in New York City found that immigrant children should have BLL screening. It is important to remember that other countries do not have the laws pertaining to leaded gasoline, leaded paint etc. that the US has. Therefore children from other countries are at greater risk for exposure to lead. This includes children who have recently immigrated to the US, refugees, adoptees, and children who have had a prolonged visit (more then 2 months) to a foreign country. Children who had recently lived in a foreign country were 11 times more likely to have an elevated BLL then US born children with no history of living in a foreign country.

22. Adolescents & Lead Poisoning
Adolescents with previous lead exposure;
-Antisocial acts
-Behavioral problems
-marijuana use
Dietrich, Kim N., Douglas, Ris M,. Succopa, Paul A., Berger, Omer G., Bornschein, Robert L.,. (2001). Early exposure to Lead and Juvenile Delinquency. Neurotoxicology and Teratology, 23,
A study conducted by Dietrich (2001) found that adolescents who had been exposed to lead both before they were born and after they were born were more likely to demonstrate delinquent and anti-social behavior. These adolescents were also at greater risk to use marijuana.

23. Treatment Determine the source of the lead exposure if possible.
Remove or contain the exposure.
Chelation
Erickson, Lori, Thompson, Teri. (2005). A Review of a Preventable Poison: Pediatric lead Poisoning. Journal for Specialists in pediatric Nursing, 10,
The degree of treatment a person requires is dependent on the BLL. The first priority of treatment is to determine the source of the lead exposure. Once that source is determined either the source needs to be removed or the person with the elevated BLL needs to be removed from the source. Chelation which is treatment with either oral or IV meds are recommended for class IV and above. The meds used in chelation bind with the lead so it is excreted from the body.

24. Healthy People 2010
Eliminate elevated blood lead levels in children by 2010.
Healthy People (2000). Eliminate blood lead levels in children retrieved from
The goal of the federal government is to not only reduce blood lead levels in children by 2010 but to eliminate elevated blood lead levels. Lead poisoning is a totally preventable disease. In order for this goal to be met, exposure to lead has to be reduced for all populations, especially those populations at risk.

25. The Future
The more we educate ourselves and assess and educate our clients and patients, the closer we will get to achieving the goal of HP 2010.
Healthy People (2000). Eliminate blood lead levels in children retrieved from
In order to meet the Healthy People 2010 goal it is necessary to try to prevent all children’s exposure to lead. Unfortunately, there are still children in the United States with elevated BLL’s. Because of these children’s continued exposure lead elimination is a goal for Healthy People 2020 goal.
The local and state health department are great resources for questions and concerns about lead.

26. References
Agency for Toxic Substances and Disease Registry. (2007). Case Studies in Environmental Medicine.
Bellinger, David C. (2003). Lead. Pediatrics, 113,
Braun, Joe M., Kahn, Robert S., Froehlich, Tanya, Auinger, Peggy, Lanphear, Bruce. (2006). Exposures to Environmental Toxicants and Attention Deficit Hyperactivity Disorder in U.S. Children. Environmental Health Perspectives, 114,
Brown, Mary Jean. (2008). Childgood Lead Poisoning Prevention: Getting the Job Done by Journal of Environmental Health, 70,
Bryant, S.D. (2004). Lead-contaminated drinking waters in the public schools of Philadelphia. Journal of Toxicology. Clinical Toxicology, 42,
Center for Disease Control (2005) Lead Poisoning Prevention Program retrieved from
Centers for Disease Control and Prevention. (2005). Blood lead levels-United States, MMWR, 54,
Cleveland, Lisa M., Minter, Monica L., Cobb, Kathleen A., Scott, Anthony A., German, Victor F. (2008). Lead Hazards for Pregnant women and Children. American Journal of Nursing, 108,
Dietrich, Kim N., Douglas, Ris M,. Succopa, Paul A., Berger, Omer G., Bornschein, Robert L.,. (2001). Early exposure to Lead and Juvenile Delinquency. Neurotoxicology and Teratology, 23,
Doumouchtsis, S.K., Martin, N.S., Robins, J.B. (2006). ‘Veterinary’ Diagnosis of lead poisoning in pregnancy. British Medical Journal, 333,
Edwards, Marilyn. (2008) Lead Poisoning: a public health issue. Primary Health Care, 18,
Erickson, Lori, Thompson, Teri. (2005). A Review of a Preventable Poison: Pediatric lead Poisoning. Journal for Specialists in pediatric Nursing, 10,

27. References (con’t)
Fletcher, Alicia M., Gelberg, Kitty H., Marshall, Elizabeth G. (1999). Reasons for testing and exposure sources among women of childbearing age with moderate blood lead levels. Journal of Community Health, 24,
Healthy People (2000). Eliminate blood lead levels in children retrieved from
Hamilton, Shawn, Rothenberg, Stephen J., Khan, Fuad A., Manalo, Mario, Norris, Keith C. (2001). Neonatal lead poisoning from maternal pica behavior during pregnancy. Journal of the National Medical Association, 93,
Johnson, Mary Ann. (2001). High calcium intake blunts pregnancy-induced increases in maternal blood lead. Nutrition reviews, 59,
New York State Department of Health. (2006). NYS Heavy Metals Registry retrieved from
New York State Department of Health. (2008) . NYS Regulations for Lead Poisoning Prevention and Control - NYCRR Title X, Part 67 retrieved from
Riess, Matthias L., Halm, Josiah K. (2007). Lead Poisoning in an Adult: Lead Mobilization by Pregnancy?. Journal of General Internal medicine, 22,
Sowers, Maryfran, Jannausch, Mary, Scholl, Theresa, Li, Wenjie, Kemp, Francis W., Bogden, John D. (2002). Blood Lead Concentrations and Pregnancy Outcomes. Archives of Environmental Health, 57,
Tehranifar, Parisa, Leighton, Jessica, Auchincloss, Amy, H., Faciano, Andrew, Alper, Howard, Paykin, Andrea, et al. (2008). Immigration and Risk of Childhood Lead Poisoning: Findings From a Case-Control Study of New York City Children. American Journal of Public Health, 98,
Zentner, Luz Estela, Rondo, Patricia H.C. Mastroeni, Silmara S.B.S. (2006). Lead Contamination and Anthropometry. Journal of Tropical Pediatrics, 52,

28. Bibliography for Further Reading
Ang, H. H., Lee, E.L., Matsumoto, K. (2003). Analysis of lead content in herbal preparations in Malaysia. Human & Experimental Toxicology, 22,
Bellinger, David C. (2007). Children’s Cognitive Health: The Influence of Environmental Chemical Exposures. Alternative Therapies in Health and Medicine, 13,
Jusko, Todd A., Henderson Jr., Charles R., Lanphear, Bruce P., Cory-Slechta, Deborah A., Parsons, Patrick J., Canfield, Richard L. (2008). Blood Lead Concentrations<10 µg/dl and Child Intelligence at 6 Years of Age. Environmental health Perspectives, 116,
Kranz, Brenda D., Simon, David L., Leonardi, Bianca G. (2004). The behavior and routes of lead exposure in pregrasping infants. Journal of Exposure Analysis and Environmental Epidemiology, 14,
Levin, Ronnie, Brown, Mary Jean, Kashtock, Michael E., Jacobs, David J., Whelan, Elizabeth A., et al. (2008). Lead Exposure in U.S. Children, 2008: Implications for Prevention. Environmental Health Perspectives, 116,
Zhichang, Lewis, Zheng, Shi, Zheng, Wei. (2007). Early Lead Exposure increases the leakage of the blood-cerebrospinal fluid barrier, in vitro. Human & Experimental Toxicology, 26,