This page is dedicated to the
lactational transfer of drugs and toxic chemicals
to human breast milk.
This page is dedicated to the
lactational transfer of drugs and toxic chemicals
to human breast milk.
Breast Feeding--Best
Bet for Babies
Contaminants have been found in human milk. Should I wean my baby?
La Leche League: FAQ Abstracts of selected publications.
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ABSTRACTS
RUNNING TITLE: TOXIC CHEMICALS IN BREAST MILK
Key words: occupational exposure, infant, breast milk, toxic chemicals, toxicokinetics
Byczkowski,J.Z., Gearhart,J.M., & Fisher, J.W.: "Occupational" exposure of infants to toxic chemicals via breast milk. Nutrition, 10, 43-48, 1994.
The transfer of toxic chemicals to breast milk represents an important, although not widely recognized, chemical exposure route for the infant. For an increasing number of nursing mothers who resume their professional activities after giving birth, the obvious benefits of breast-feeding must be evaluated versus the risk of the lactational transfer of occupational chemicals to the infant. In this article, we review qualitative and quantitative data on occupational chemicals that may contaminate the breast milk of lactating women in the work force, and we discuss the possible use of physiologically based pharmacokinetic models to aid in the assessment of risk for infants whose mothers are occupationally exposed to chemicals. (Supported in part by the US Department of the Air Force Contract #F33615 90-C 0532)
The opinions or conclusions expressed herein do not necessarily reflect those of USAF.
RUNNING TITLE: PBPK MODEL FOR LACTATIONAL TRANSFER OF PCE
Key words: PCE, tetrachloroethylene, perchloroethylene, PBPK, physiologically based pharmacokinetic model, GC, gas chromatography, PC, partition coefficient, rat, closed chamber, inhalation exposure
Byczkowski,J.Z., Kinkead,E.R., Leahy,H.F., Randall,G.M., & J.W. Fisher: Computer simulation of lactational transfer of tetrachloroethylene in rats using a physiologically based model. Toxicol. Appl. Pharmacol., 125: 228 - 236, 1994.
Abstract
A physiologically based pharmacokinetic (PBPK) model describing transfer of inhaled tetrachloroethylene (PCE) into breast milk with the consequent exposure of the nursing pups was developed and validated in lactating rats. The PBPK model was based on partition coefficients (PCs), which were determined by the equilibration of tissues with known concentrations of PCE vapor. The blood/air and milk/blood PCs for the dam were 33.5 and 12.0; liver/blood and fat/blood PCs for the dam were 1.9 and 42.4; and slowly perfused tissues/blood and richly perfused tissues/blood PCs for the dam were 0.9 and 1.7, respectively. The blood/air PC for the pup was 24.3, and solid tissues/blood PC for the pup was 4.5. Metabolic constants were determined by a gas uptake method. The pseudo maximal velocity of PCE metabolism in the dam was low, 0.03 mg/kg/hr, and the apparent Michaelis-Menten constant was 0.3 mg/L. The lactating Sprague-Dawley females were exposed to PCE vapor for 2 hr with concentrations ranging from 20 ppm to 1000 ppm PCE. The dams were returned to the pups after exposure and the pups received PCE via breast milk while they nursed. PCE concentrations in the air, blood, milk, and tissues were determined by gas chromatography and compared to PBPK model predictions. Nursing resulted in a peak pup blood PCE concentration of 0.9 mg/L and a peak pup solid tissue PCE concentration of 8 mg/kg. The PBPK lactation model adequately described the distribution of inhaled PCE in maternal blood and milk, as well as in the nursed pup's gastrointestinal tract, blood, and solid tissues. It is concluded that the predictions based on PBPK modeling for disposition of PCE in lactating rats and their pups were in good agreement with the experimental data. <http://members.aol.com/januszb/pbpk.htm
RUNNING TITLE: DEVELOPMENT OF PBPK MODEL FOR PCE IN BREAST MILK
Key words: Tetrachloroethylene, Perchloroethylene, Breast Milk, Rat, Human Infant
Byczkowski,J.Z., & Fisher,J.W.: Lactational transfer of tetrachloroethylene in rats. Risk Analysis, 14: 339 - 349, 1994.
Abstract
Tetrachloroethylene is a commonly used organic solvent and a suspected human carcinogen, reportedly transferred to human breast milk following inhalation exposure. Transfer of tetrachloroethylene to milk may represent a threat to the nursing infant. A physiologically based pharmacokinetic model was developed to quantitatively assess the transfer of inhaled tetrachloroethylene into breast milk and the consequent exposure of the nursing infant. The model was validated in lactating rats. Lactating Sprague-Dawley females were exposed via inhalation to tetrachloroethylene at concentrations ranging from 20 ppm to 1000 ppm, and then returned to their nursing, 10 to 11-day old pups. Tetrachloroethylene concentrations in the air, blood, milk, and tissue were determined by gas chromatography and compared to model predictions. The model described the distribution of inhaled tetrachloroethylene in maternal blood and milk, as well as the nursed pup's gastrointestinal tract, blood, and tissue. Several computer simulations of tetrachloroethylene distribution kinetics in exhaled air, blood, and milk of exposed human subjects were run and compared with limited human data available from the literature. It is concluded that the physiologically based pharmacokinetic model successfully described the concentration of tetrachloroethylene in both lactating rats and humans. Although, predictions versus observation were good, the model slightly underpredicted the peak whole pup tetrachloroethylene concentration, and underpredicted systemic clearance of tetrachloroethylene from the pup.<http://members.aol.com/januszb/pbpk.htm
RUNNING TITLE: CANCER RISK AND PBPK MODEL FOR PCE IN BREAST MILK
Key words: Physiologically based pharmacokinetic model; Tetrachloroethylene; Cancer risk assessment; Breast-fed infant; Toxicology
Byczkowski,J.Z., & Fisher,J.W.: A computer program linking physiologically based pharmacokinetic model with cancer risk assessment for breast fed infants. Computer Meth. Progr. Biomed. 46: 155 - 163, 1995
Abstract
The risk assessment process predicts the chances of adverse health effects that the toxicant possibly can do to the target organism under expected conditions of exposure. Regulators chose among several mathematical approaches to estimate the risk, but in each case it is necessary to link the dosemetrics of the toxicant with its predicted health effect. In this paper, a computer program is described that allows to link a physiologically based pharmacokinetic (PBPK) model for tetrachloroethylene (PCE) in the lactating mother with the estimate of extra cancer risk for breast-fed infants, according to the U.S. Environmental Protection Agency (EPA) methodology. When inhaled by a lactating woman, PCE may partition into breast milk and may be transferred to the breast-fed infant. We have developed and validated experimentally a PBPK model for lactational transfer of PCE in rats, including a quantitative description of a milk compartment and the nursing pup. Subsequently, the model has been scaled to describe human physiology, and was validated with literature data for human cases of PCE exposure. Finally, we linked the dosage predictions of the PBPK model with equations used by EPA to estimate the cancer risk from PCE. The model predictions are in good agreement with both the measured values and those reported in the literature for exposure to PCE. This comparison confirms the usefulness of PBPK modeling in risk assessments.< http://members.aol.com/januszb/pbpk.htm
RUNNING TITLE: PHARMACOKINETIC MODEL OF PCE IN BREAST MILK
Key words: physiologically-based pharmacokinetic model, cancer risk assessment, tetrachloroethylene, breast milk, nursing infants
Byczkowski,J.Z.: Linked PBPK model and cancer risk assessment for breast fed infants. Drug Inf. J. 30: 401-412, 1996.
Abstract:
In this paper, a step-by-step process is described that allowed a
physiologically-based pharmacokinetic (PK) model for
tetrachloroethylene (PCE) for lactating mothers to be linked with the estimate
of extra cancer risk in breast-fed infants, according
to the United States Environmental Protection Agency (EPA) method. If inhaled
by a lactating woman, PCE may partition to breast milk and may be transferred
to the breast-fed infant. A PK model for lactational transfer of PCE in rats,
including a quantitative description of milk compartment and the nursing
pup, has been scaled to describe human physiology, and was validated with
human literature data for PCE exposure cases. The model predictions were
in good agreement with both the measured values and those reported in the
literature. Further, the model has been applied to scenarios of occupationally
and nonoccupationally exposed mothers, simulating PCE concentrations in breast
milk and the infant exposure. Finally, the dosage predictions were linked
with equations used by EPA to estimate the cancer risk
from PCE. Comparison of the predictions with those from the literature confirms
the usefulness of PK modeling in risk assessments.<
Link to this article
(you will need an Acrobat to read *.pdf file)
Codes of a PBPK Model
for Lactational Tansfer of PCE
RUNNING TITLE: PHARMACOKINETIC MODEL OF METHYLMERCURY IN BREAST MILK
Key words: physiologically-based pharmacokinetic model, methylmercury, MeHg, breast milk, nursing infants
Byczkowski,J.Z., Lipscomb,J.C.: Application of PBPK Model for Assessment of the Lactational Transfer of MeHg to Nursing Infant.Society for Risk Analysis 1999 Annual Meeting, Atlanta, GA, 1999, Final Program P1.17, p. 47 (1999)
Abstract:
Exposure of developing humans and animals to high concentrations of methylmercury (MeHg) may have catastrophic results to their central nervous system. Due to outbreaks of MeHg poisoning that occurred in Minimata Bay, Japan, and in Iraq, the developmental toxicity produced by MeHg has been well-documented in human subjects. While several pharmacokinetic models have been developed to address the transplacental transfer of MeHg in humans and animals, to date there was no report in the peer-reviewed literature about the construction of a functional physiologically based pharmacokinetic (PBPK) model for MeHg lactational transfer in humans. The goal of the present study was to develop a PBPK model which could be applied to the assessment of lactational transfer of MeHg from mother to the nursing infant. The PBPK model was based on information published by Gearhart et al. (1995) describing MeHg kinetics in the pregnant woman and fetus. An additional module was developed to describe the breast milk compartment, with subsequent delivery of MeHg with milk to the nursing infant. It was assumed that the concentration of MeHg in maternal blood plasma rapidly equilibrates with the aqueous phase of breast milk. The PBPK model for lactational transfer of MeHg was initially calibrated with experimental data from rats. Then, it was allometrically scaled to humans, and finally verified with the available data from mothers and their nursing infants. The model predicts kinetics of MeHg excretion with milk and the daily intake by infant, depending on current and previous maternal exposures to MeHg. There is close agreement between the data of Amin-Zaki et al. (1976) and predictions of concentrations of MeHg in breast milk and infants’ blood produced by this model. < http://www.riskworld.com/Abstract/1999/SRAam99/ab9ab047.htm >
Codes of a PBPK Model
for Lactational Tansfer of Methylmercury
RUNNING TITLE: PHARMACOKINETIC MODEL OF METHYLMERCURY IN BREAST MILK
Key words: physiologically-based pharmacokinetic model, methylmercury, MeHg, breast milk, nursing infants
Byczkowski, J.Z., and Lipscomb, J.C.: Physiologically Based Pharmacokinetic Modeling of the Lactational Transfer of Methylmercury. Risk Anal. 21: 869-882, 2001.
Abstract:
The developmental neurotoxicity of methylmercury (MeHg) in the human has been described following catastrophic events in Minamata Bay, Japan and in Iraq and following the exposure to lower doses elsewhere in the world. The most common route of MeHg exposure in humans is through the intake of contaminated food, especially fish. While the precautions against the ingestion of potentially-contaminated food during pregnancy are well-recognized, precautions against the ingestion of MeHg during lactation are not so uniformly recognized. However, the continued development of the central nervous system during the early postnatal period serves to prolong the period during which this critical system is susceptible to the toxic insult of MeHg. Because no direct method is available to quantitatively assess the lactational transfer of MeHg to the human, we sought to develop a computer-aided simulation method. An available gestational physiologically based pharmacokinetic (PBPK) model was refined and expanded to include parameters and algorithms specific for the elimination of MeHg in breast milk. The predictions of the completed model were compared with experimental data obtained from rodents, and the model parameters were allometrically scaled to humans. Finally, the model was validated by comparing its predictions against the available clinical data for MeHg distribution and elimination in mothers and their nursing infants. This model incorporates current and previous maternal exposures to MeHg to accurately predict the kinetics of MeHg excretion in breast milk and the daily intake by the nursing infant. This model may be used to quantify MeHg intake by the nursing infant, under different rates of maternal MeHg ingestion. < Codes of a PBPK Model for Lactational Tansfer of Methylmercury
List of
relevant publications:
1. Giroux D, Lapointe G, Baril M. Toxicological index and the presence in the workplace of chemical hazards for workers who breast-feed infants. Am Ind Hyg Assoc J 1992;53:471
2. Wolff MS. Occupationally derived chemicals in breast milk. Am J Ind Med 1983;4:259
3. Jensen AA, Slorach SA. Chemical Contaminants in Human Milk. Boca Raton, FL: CRC Press Inc., 1991
4. White GJ, White MK. Breastfeeding and drugs in human milk. Vet Hum Toxicol 1980;22:1
5. Jensen AA Chemical contaminants in human milk. Resid Rev 1983;89:1
6. World Health Organization. Contemporary patterns of breast-feeding, report on the WHO collaborative study on breast-feeding. Geneva: WHO, 1981
7. Auerbach KG, Guss E. Maternal employment and breastfeeding. AJDC 1984;138:958
8. Janbu T, Koss KS, Thoresen M, Wesche J. Blood velocities to the female breast during lactation and following oxytocin injections. J Develop Physiol 1985;7:373
9. Fleishaker JC, Desai N, McNamara PJ. Factor affecting the milk-to-plasma drug concentration ratio in lactating women: physical interactions with protein and fat. J Pharm Sci 1987;76:189
10. Berlin CM. The excretion of drugs in human milk. In: Schwarz RH, Yaffe SJ, eds. Drug and chemical risk to the fetus and newborn. New York; Alan R. Liss 1980:115
11. Butte NF, Wills C, Jean CA, O'Brian-Smith E, Garza C. Feeding patterns of exclusively breast-fed infants during the first four month of life. Early Human Dev 1985;12:291
12. Cone MV, Baldauf MF, Opresko DM, Uziel MS. Chemicals identified in human breast milk, a literature search. EPA 560/5 83 009, Washington, DC: EPA, 1983
13. Committee on Drugs, American Academy of Pediatrics. Transfer of drugs and other chemicals into human milk. Pediatrics 1989;84:924
14. Keith HL, Walters DB. National Toxicology Program's chemical solubility database. Boca Raton, FL: Lewis Publishers, 1992
15. American Conference of Governmental Industrial Hygienists. 1991 1992 Threshold limit values for chemical substances and physical agents and biological exposure indices. Cincinati, OH: ACGIH, 1991
16. Poitrast BJ, Keller WC, Elves RG. A guide to the estimation of the hazard presented by chemicals in human milk. USAFOEHL Report No. 85 185CO111LCE, USAF Occupational and Environmental Health Laboratory Aerospace Medical Division. Brooks Air Force Base, TX: US Natl Technical Inform Service, 1985
17. Rabinowitz M, Leviton A, Needleman H. Lead in milk and infant blood: A dose-response model. Arch Environm Hlth 1985;40:283
18. Amin-Zaki L, Majeed MA, Greenwood MR, Elhassani SB, Clarkson TW, Doherty RA. Methylmercury poisoning in the Iraqi suckling infant: A longitudinal study over five years. J Appl Toxicol 1981;1:210
19. Bhattacharyya MH. Bioavailability of orally administered cadmium and lead to the mother, fetus, and neonate during pregnancy and lactation: an overview. Sci Total Environm 1983;28:327
20. Juszkiewicz T. Environmental toxicology of fetal and postnatal threats. Materials of 20th Meeting of Polish Gynecological Soc. in Warsaw. [in Polish].Ginekologia Polska 1979;2(Suppl):14
21. Juszkiewicz T, Radomanski T, Szprengier T, Szkoda J, Zmudzki J. Toxic elements in bovine and human milk. [in Polish]. Przeglad Lekarski 1983;40:525
22. Kanja LW, Skaare JU, Ojwang SBO, Maitai CK. A comparison of organochlorine residues in maternal adipose tissue, materneal blood, cord blood, and human milk from mother/infant pairs. Arch Environ Contam Toxicol 1992;22:21
23. Gallenberg LA, Vodicnik MJ. Transfer of persistent chemicals in milk. Drug Metabol Rev 1989;21:277
24. Yakushiji T, Watanabe I, Kuwabara K, Yoshida S, Koyama K, Hara I, Kunita N. Long-term studies of the excretion of polychlorinated biphenyls (PCBs) through the mother's milk of an occupationally exposed worker. Arch Environm Contam Toxicol 1978;7:493
25. Bangell PC, Ellenberger HA. Obstructive jaundice due to a chlorinated hydrocarbon in breast milk. Can Med Assoc J 1977;117:1047
26. Novikov KI, Kolodina LN, Lipovskii SM, Badalova LV. Specificity of lactation in workers of the chemical (rubber) industry. [in Russian].Gigiena Truda Prof Zabolev 1979;23(#2):45
27. Taskinen H, Anttila A. Linbohm ML, Sallmen M, Hemminki K. Spontaneous abortions and congenital malformations among the wives of men occupationally exposed to organic solvents. Scand J Work Environ Health 1989;15:345
28. Vanuni SO. On some indices of a chemical composition of breast milk of working mothers and women living in the area of synthetic rubber factory. [in Russian].Zhurnal Experiment Klin Mediciny 1972;13:111
29. Vanuni SO. A comparative characteristics of individual and total amino acids in breast milk of working mothers and women living in villages at different distances around a synthetic chloroprene rubber plant. [in Russian].Zhurnal Experiment Klin Mediciny 1974;14:96
30. Vozovaya MA, Malyarova LK, Enikeeva RM. Contents of methylene chloride in biological tissues during pregnancy and lactation in female workers of a rubber-technology plant. [in Russian].Gigiena Truda Prof. Zabol. 1974;18(#4):42
31. Cote CJ, Kenepp NB, Reed SB, Strobel GE. Trace concentrations of halothane in human breast milk. Br J Anaesth 1976;48:541
32. Wilson JT, Brown RD, Cherek DR, Dailey JW, Hilman B, Jobe PC, Manno BR, Manno JE, Radetzki HM, Stewart JJ. Drug excretion in human breast milk: principles, pharmacokinetics and projected consequences. Clin Pharmacokinetics 1980;5:1
33. Gonzales MJ, Rico MC, Hernandez LM, Baluja G. Mercury in human hair: a study of residents in Madrid, Spain. Arch Environm Health 1985;40,225
34. Juszkiewicz T, Sikorski R, Niewiadomska A, Radomanski T. Traces of polychlorinated biphenyls in the adipose tissue and the human breast milk. [in Polish].Ginekologia Polska 1979;50:917
35. Wischnik A, Manth SM, Lloyd J, Bullingham R, Thompson JS. The excretion of ketorolac tromethamine into breast milk after multiple oral dosing. Eur J Clin Pharmacol 1989;36:521
36. Wilson JT, Brown RD, Hinson JL, Dailey JW. Pharmacokinetic pitfalls in the estimation of the breast milk/plasma ratio for drugs. Ann Rev Pharmacol Toxicol 1985;25:667
37. Travis CC, Arms AD. Bioconcentration of organics in beef, milk, and vegetation. Environ Sci Technol 1988;22:271
38. Travis CC, Hattemer-Frey HA, Arms AD. Relationship between dietary intake of organic chemicals and their concentrations in human adipose tissue and breast milk. Arch Environm Contam Toxicol 1988;17:473
39. Poitrast BJ, Keller WC, Elves RG. Estimation of chemical hazards in breast milk. Aviat Space Environ Med 1988; 59:A87
40. Shelley ML, Andersen ME, Fisher JW. An inhalation distribution model for the lactating mother and nursing child. Toxicol Lett 1988;43:23
41. Shelley ML, Anderson ME, Fisher JW. A risk assessment approach for nursing infants exposed to volatile organics through the mother's occupational inhalation exposure. Appl Ind Hyg 1989;4:21
42. Gargas ML, Burgess RJ, Voisard DE, Cason GH, Andersen ME.Partition coefficients of low-molecular weight volatile chemicals in various liquids and tissues. Toxicol Appl Pharmacol 1989;89:87
43. Ramsey JC, Andersen ME. A physiologically based description of the inhalation pharmacokinetics of styrene in rats and humans. Toxicol Appl Pharmacol 1984;73:159
44. Ward RC, Travis CC, Hetrick DM, Andersen ME, Gargas ML. Pharmacokinetics of tetrachloroethylene. Toxicol Appl Pharmacol 1988;93:108
45. Fisher JW, Whittaker TA, Taylor DH, Clewell III HJ, Andersen ME Physiologically based pharmacokinetic modeling of the lactating rat and nursing pup: A multiroute exposure model for trichloroethylene and its metabolite, trichloroacetic acid. Toxicol Appl Pharmacol 1990;102:497
46. Byczkowski JZ, Kinkead ER, Greene RJ, Bankston LA, Fisher JW. Physiologically-based modeling of the lactational transfer of tetrachloroethylene. Toxicologist 1993;13:354 (1385)
47. Leo A, Hanch C, Elkins D. Partition coefficients and their uses. Chem Rev 71;71: 5
48. West CE, Horton BJ. Transfer of polycyclic hydrocarbons from diet to milk in rats, rabbits and sheep. Life Science 1976;19:1543
49. Byczkowski,J.Z., & Fisher,J.W.: Lactational transfer of tetrachloroethylene in rats. Risk Analysis, 14: 339 349, 1994.
50. Byczkowski,J.Z., Kinkead,E.R., Leahy,H.F., Randall,G.M., & J.W. Fisher: Computer simulation of lactational transfer of tetrachloroethylene in rats using a physiologically based model. Toxicol. Appl. Pharmacol., 125: 228 236, 1994.
51. Byczkowski,J.Z., & Fisher,J.W.: A computer program linking physiologically based pharmacokinetic model with cancer risk assessment for breast fed infants. Computer Meth. Progr. Biomed. 46: 155 163, 1995.
52. Byczkowski,J.Z.: Linked PBPK model and cancer risk assessment for breast fed infants. Drug Inf. J. 30: 401-412, 1996.
53. Byczkowski,J.Z., & Fisher,J.W.: Tetrachloroethylene: exposure and risk assessment in breast fed infants. 1993 Toxic Hazards Res. Unit Ann. Rep. No. AL/OE TR 1994-0119, pp. 67-81, 1994.
54. Byczkowski,J.Z., & Fisher,J.W.: Application of physiologically based pharmacokinetic model to cancer risk assessment for breast fed infants. 1994 Toxic Hazards Res. Unit Ann. Rep. No. AL/OE TR 1995-0135, 1995.
55. Byczkowski,J.Z., & Fisher,J.W.: Lactational transfer of tetrachloroethylene in rats. Conference on the Risk Assessment Paradigm After Ten Years: Policy and Practice Then, Now, and in the Future. WPAFB Dayton, OH., Biographies and Papers EPA/630/R 93 039 March 1993.
56. Byczkowski,J.Z., & Fisher,J.W.: Quantitative Approach to assess risk from lactational transfer of tetrachloroethylene to breast fed infants. Society for Risk Analysis Annual Meeting, Savannah, GA, Program and Abstracts E 10, 1993.
57. Byczkowski,J.Z., & Fisher,J.W.: Tetrachloroethylene exposure assessment of breast fed infants. 33rd Annual Meeting of the Society of Toxicology, Dallas, TX, Toxicologist 14: 86 (45) 1994.
58. Byczkowski,J.Z.: Linked PBPK model and cancer risk assessment for breast fed infants. Drug Information Association 30th Annual Meeting, Washington, DC, Abstracts Presentations, CM/PH, p. 69 (1994).
59. Byczkowski,J.Z., & Fisher,J.W.: Cancer risk assessment for breast-fed infants: a PBPK model. Conference on Risk Assessment Issues for Sensitive Human Populations, Wright Patterson AFB, OH. Registration and Abstract Booklet, p. 70, 1995.
60. Byczkowski,J.Z., & Fisher,J.W.: Computer simulation of tetrachloroethylene exposure and cancer risk assessment for breast-fed infants. 104 Annual Meeting of the Ohio Acad. Sci., Westerville, OH. Oh. J. Sci. 95, A-47, 1995.
61. Byczkowski,J.Z., Gearhart,J.M., & Fisher,J.W.: "Occupational" exposure of infant to toxic chemicals via breast milk. Nutrition, 10, 43-48, 1994.
62. Byczkowski, J.Z.: Model for Lactational Transfer. Library of Published Models, URL: http://members.aol.com/januszb/pbpk.htm
63. Clewell,R.A., Gearhart,J.M.: "Pharmacokinetics of Toxic Chemicals in Breast Milk: Use of PBPK Models to Predict Infant Exposure" Environmental Health Perspectives 110: (Number 6), A333-A337, June 2002. Available on line, URL: http://ehp.niehs.nih.gov/members/2002/110pA333-A337clewell/clewell-full.html
64. Byczkowski,J.Z. in: "EXPLORATION OF PERINATAL PHARMACOKINETIC ISSUES. Final Report" EPA/630/R-01/004, Prepared for: Risk Assessment Forum, Office of Research and Development, U.S. Environmental Protection Agency, Washington, D.C. Prepared by: Versar, Inc., May 10, 2001. Available on line, URL: http://cfpub.epa.gov/ncea/raf/recordisplay.cfm?deid=29420
65. Byczkowski, J.Z.: Methyl Mercury Toxicity: Pharmacokinetics And Toxicodynamic Aspects. In: Annual Reviews in Food and Nutrition: Toxic and Pathological Aspects (Preedy,V.R. and Watson,R., Eds.). CRC Press LLC, Boca Raton, FL in press, 2004.
LIST OF
CHEMICALS
A list of occupational chemical agents known to contaminate the breast milk of lactating women
This searchable list is an example of the approach, designed to guide the industrial hygienist or occupational physician in his decision to reassign the breast-feeding mother to another work assignment or to recommend the stoppage of breast-feeding (according to: Byczkowski,J.Z., Gearhart,J.M., & Fisher, J.W.: "Occupational" exposure of infant to toxic chemicals via breast milk. Nutrition, 10, 43-48, 1994).
The information on this list you may search for: Chemical Name, Chemical Abstracts Number (CAS No.), NIOSH Registry Number (NIOSH No.) or Molecular Weight (M.W.) using "FIND" function of your browser.
KEY:
Chemical Name
CAS No.
NIOSH No.
M.W.
TLV - TWA (Threshold Limit Values as listed by ACGIH, 1991)
Milk
Notes:
sw=solubility in water,
logKow=log partition
coefficient octanol/water
(- negative value=better
soluble in water then in octanol),
M/P=milk/plasma partition coefficient
Chemical Name: 1,1,2-Trichloro-1,2,2-trifluoroethane
CAS No.: 76-13-1
NIOSH No.: KJ4000000
M.W.: 187
TLV - TWA: 1000 ppm; 7670 mg/m3
Milk: Detected in human milk
Chemical Name: Acetone
CAS No.: 67-64-1
NIOSH No.: AL3150000
M.W.: 58
TLV - TWA: 750 ppm; 1780 mg/m3
Milk: Detected in human milk
Notes: sw>100mg/ml, logKow-0.24
Chemical Name: Antimony
CAS No.: 7440-36-0
NIOSH No.: CC4025000
M.W.: 122
TLV - TWA: 0.5 mg/m3
Milk: Excreted in human milk
Chemical Name: Antimony oxide (3+)
CAS No.: 1309-64-4
NIOSH No.: CC5650000
M.W.: 292
TLV - TWA: 0.5 mg/m3 as Sb
Milk: Excreted in human milk
Notes: sw<1mg/ml
Chemical Name: Benzene
CAS No.: 71-43-2
NIOSH No.: CY1400000
M.W.: 78
TLV - TWA: 10 ppm; 32 mg/m3
Milk: Detected in human milk
Notes: sw1-5mg/ml, logKow 1.95, M/P1.2
Chemical Name: Butanol-1
CAS No.: 71-36-3
NIOSH No.: ED1400000
M.W.: 74
TLV - TWA: 50 ppm; 152 mg/m3
Milk: Detected in human milk
Notes: sw>100mg/ml, logKow 0.88
Chemical Name: Butanol-2 (sec-butyl alcohol)
CAS No.: 78-92-2
NIOSH No.: ED1750000
M.W.: 74
TLV - TWA: 100 ppm; 303 mg/m3
Milk: Detected in human milk
Notes: sw>100mg/ml
Chemical Name: Butanone-2 (Methyl ethyl ketone)
CAS No.: 78-93-3
NIOSH No.: EL6475000
M.W.: 72
TLV - TWA: 200 ppm; 590 mg/m3
Milk: Detected in human milk
Notes: logKow 0.28
Chemical Name: Cadmium (metal)
CAS No.: 7440-43-9
NIOSH No.: EU9800000
M.W.: 112
TLV - TWA: 0.05 mg/m3
Milk: Excreted in animal milk
Chemical Name: Cobalt (metal)
CAS No.: 7440-48-4
NIOSH No.: GF8750000
M.W.: 59
TLV - TWA: 0.05 mg/m3
Milk: Excreted in animal milk
Chemical Name: Cobalt chloride (2+)
CAS No.: 7646-79-9
NIOSH No.: GF9800000
M.W.: 238
TLV - TWA: 0.05 mg/m3 as Co
Milk: Excreted in human milk
Chemical Name: Copper (2+ sulfate)
CAS No.: 7758-99-8
NIOSH No.: GL8900000
M.W.: 250
TLV - TWA: 1 mg/m3 as Cu
Milk: Excreted in human milk
Chemical Name: Copper (metalic)
CAS No.: 7440-50-8
NIOSH No.: GL5325000
M.W.: 64
TLV - TWA: 0.2 mg/m3 (fume); 1 mg/m3 (dust & mists)
Milk: Excreted in animal milk
Chemical Name: Copper sulfate (anhydrous)
CAS No.: 7758-98-7
NIOSH No.: GL8800000
M.W.: 160
TLV - TWA: 1 mg/m3 as Cu
Milk: Excreted in human milk
Notes: ws 199mg/ml
Chemical Name: Cyclohexane
CAS No.: 110-82-7
NIOSH No.: GU6300000
M.W.: 84
TLV - TWA: 300 ppm; 1030 mg/m3
Milk: Detected in human milk
Notes: sw<1mg/ml
Chemical Name: Dichlorodifluoromethane
CAS No.: 75-71-8
NIOSH No.: PA8200000
M.W.: 121
TLV - TWA: 1000 ppm; 4950 mg/m3
Milk: Detected in human milk
Chemical Name: Ethyl alcohol
CAS No.: 64-17-5
NIOSH No.: KD630000
M.W.: 46
TLV - TWA: 1000 ppm; 1880 mg/m3
Milk: Excreted in human milk
Notes: sw>100mg/ml, log Kow-0.32
Chemical Name: Ethyl benzene
CAS No.: 100-41-4
NIOSH No.: DA0700000
M.W.: 103
TLV - TWA: 100 ppm; 434 mg/m3
Milk: Detected in human milk
Notes: sw<1mg/ml
Chemical Name: Fluorotrichloromethane (Trichlorofluoromethane)
CAS No.: 75-69-4
NIOSH No.: PB6125000
M.W.: 137
TLV - TWA: 1000 ppm; 5620 mg/m3
Milk: Detected in human milk
Chemical Name: Isopropyl alcohol
CAS No.: 67-63-0
NIOSH No.: NI8050000
M.W.: 60
TLV - TWA: 400 ppm; 983 mg/m3
Milk: Detected in human milk
Notes: sw>100mg/ml
Chemical Name: Lead (inorganic)
CAS No.: 7439-92-1
NIOSH No.: OF7525000
M.W.: 207
TLV - TWA: 0.15 mg/m3
Milk: Excreted in animal milk
Chemical Name: Lead chromate (oxide)
CAS No.: 18454-12-1
NIOSH No.: OF9800000
M.W.: 546
TLV - TWA: 0.05 mg/m3 as Pb; 0.012 mg/m3 as Cr
Milk: Excreted in animal milk
Chemical Name: Lead dioxide
CAS No.: 1309-60-0
NIOSH No.: DG0700000
M.W.: 239
TLV - TWA: 0.15 mg/m3 as Pb
Milk: Excreted in animal milk
Chemical Name: Lead tetraoxide
CAS No.: 1314-41-6
NIOSH No.: DG5425000
M.W.: 686
TLV - TWA: 0.15 mg/m3 as Pb
Milk: Excreted in animal milk
Chemical Name: Manganese
CAS No.: 7439-96-5
NIOSH No.: OO9275000
M.W.: 55
TLV - TWA: 5 mg/m3 (dust and compounds); 1 mg/m3 (fumes)
Milk: Excreted in animal milk
Chemical Name: Mercury (metal)
CAS No.: 7439-97-6
NIOSH No.: OV4550000
M.W.: 201
TLV - TWA: 0.1 mg/m3 (compounds); 0.01 mg/m3 (alkyl); 0.05 mg/m3 (vapor)
Milk: Excreted in human milk
Chemical Name: Mercury oxide (2+)
CAS No.: 21908-53-2
NIOSH No.: OW8750000
M.W.: 217
TLV - TWA: 0.1 mg/m3 as Hg
Milk: Excreted in animal milk
Chemical Name: Methylene chloride
CAS No.: 75-09-2
NIOSH No.: PA8050000
M.W.: 85
TLV - TWA: 50 ppm; 174 mg/m3
Milk: Excreted in human milk
Notes: sw10-15mg/ml
Chemical Name: Naphthenic acid lead salt (Cyclohexanecarboxylic acid lead salt)
CAS No.: 61790-14-5
NIOSH No.: QK9150000
M.W.: 1579
TLV - TWA: 0.15 mg/m3 as Pb
Milk: Excreted in animal milk
Chemical Name: Phenyl mercuric acetate
CAS No.: 62-38-4
NIOSH No.: OV6475000
M.W.: 337
TLV - TWA: 0.1 mg/m3 as Hg
Milk: Excreted in animal milk
Chemical Name: Styrene
CAS No.: 100-42-5
NIOSH No.: WL3675000
M.W.: 104
TLV - TWA: 50 ppm; 213 mg/m3
Milk: Detected in human milk
Notes: sw<1mg/ml
Chemical Name: Tetrachloroethylene (Perchloroethylene)
CAS No.: 127-18-4
NIOSH No.: KX3850000
M.W.: 166
TLV - TWA: 50 ppm; 339 mg/m3
Milk: Excreted in human milk
Notes: A case of exposure through breast milk described:
Exposed mother, milk level 1 mg/dL, jaundice in infant,
M/P3.3, sw 0.15mg/ml, logKow2.88
Chemical Name: Toluene
CAS No.: 108-88-3
NIOSH No.: XS5250000
M.W.: 92
TLV - TWA: 100 ppm; 375 mg/m3
Milk: Detected in human milk
Notes: sw<1mg/ml, log Kow2.71
Chemical Name: Xylene
CAS No.: 1330-20-7
NIOSH No.: ZE2100000
M.W.: 106
TLV - TWA: 100 ppm; 434 mg/m3
Milk: Detected in human milk
Notes: sw<1mg/ml, log Kow3.15
Chemical Name: Zinc (metal)
CAS No.: 7440-66-6
NIOSH No.: ZG8600000
M.W.: 65
TLV - TWA: 1 mg/m3 (fume)
Milk: Excreted in animal milk
Notes: sw<1mg/ml
Chemical Name: Zinc chloride
CAS No.: 7646-85-7
NIOSH No.: ZH1400000
M.W.: 136
TLV - TWA: 1 mg/m3 (fume)
Milk: Excreted in animal milk
Notes: sw3620mg/ml
Chemical Name: Zinc oxide
CAS No.: 1314-13-2
NIOSH No.: ZH4810000
M.W.: 81
TLV - TWA: 5 mg/m3 (fume); 10 mg/m3 (dust)
Milk: Excreted in animal milk
Notes: sw<1mg/ml
SOME
DRUGS
Some drugs and chemicals that can leach to human breast milk:
These are just examples. While breastfeeding always ask your doctor and/or read specific instruction before taking any medication. If you think that you may be exposed to any chemical at work, ask your occupational physician or safety officer.
Examples According to US FDA:
Bromocriptine (Parlodel): A drug for Parkinson's disease, it also decreases a woman's milk supply.
Most Chemotherapy Drugs for Cancer: Since they kill cells in the mother's body, they may harm the baby as well.
Ergotamine (for migraine headaches): Causes vomiting, diarrhea, convulsions in infants.
Lithium (for manic-depressive illness): Excreted in human milk.
Methotrexate (for arthritis): Can suppress the baby's immune system.
Drugs of Abuse: Some drugs, such as cocaine and PCP, can intoxicate the baby. Others, such as amphetamines, heroin and marijuana, can cause a variety of symptoms, including irritability, poor sleeping patterns, tremors, and vomiting. Babies become addicted to these drugs.
Tobacco Smoke: Nursing mothers should avoid smoking. Nicotine can cause vomiting, diarrhea and restlessness for the baby, as well as decreased milk production for the mother. Maternal smoking or passive smoke may increase the risk of sudden infant death syndrome (SIDS) and may increase respiratory and ear infections.
LINKS TO
DRUGS
Acetaminophen (Anacin, Panadol, Tylenol)
Alcohol: Several Drinks on Anniversary Dangerous to Baby?
Alcohol: How does consumption of alcohol affect the nursing baby?
Antigens: Maternal antigen avoidance during lactation
Breast Implants: U.S. Food and Drug Administration Documents
Carcinogens: found in breast milk of smokers
Chlorinated hydrocarbon residues in breast milk of Canadian women (1986)
Temporal trends of OC in breast milk of Canadian Women
Coumarin Anticoagulants - oral
Dioxin in Breast Milk Raises New Health Concerns
Dioxin and PCBs: The Royal College of General Practitioners
DIOXINS AND POLYCHLORINATED BIPHENYLS IN FOODS AND HUMAN MILK
Dioxins and PCBs in human milk - 1992-1993 data
Divalproex Sodium - RxList Monographs
Doxepin Hydrochloride - RxList Monographs
Herbal Medicines and Breastfeeding
Inderal/Lopresor/Tenormin and Breastfeeding
Isoflavones in Human Breast Milk and Other Biological Fluids After Soy Consumption
Lead: Dangers of Lead Still Linger
LEAD: CONCENTRATION IN BREAST MILK OF NURSING MOTHERS LIVING IN RIYADH
Leptin in Breast Milk--Obesity Factor?
Leptin: Obesity Hormone Found In Human Breast Milk
Leptin: Human breast milk contains obesity hormone
Marijuana: Is Occasional Marijuana Use OK?
Mercury In Fish: Cause for Concern?
Mercury and Lead: Exposure to toxic elements via breast milk.
Radioactive Iodide Sodium: PhD proposal by Turner
LINKS
WWW sites dealing with drugs and chemicals in human breast milk:
Introduction to hormone disrupting chemicals
Pediatric Pharmacotherapy, Volume 2, Number 4
Microbial contaminants in human milk
La Leche League International--Breastfeeding Information, Breast milk
Breastfeeding solutions - Web links and Medela, Inc.
Breast Feeding--Best Bet for Babies
BCadvisor
A Breast Cancer support group
REFERENCES
RELEVANT BOOKS AND OTHER REFERENCES:
You may search using "FIND" function of your browser.
New Book (2001):
Drugs During Pregnancy and Lactation, Handbook of prescription drugs and comparative risk assessment
Edited by: Christof Schaefer, Leo Baeck-strasse 21, D-14165 Berlin, Germany
With important contributions from:
Hanneke Garbis, Pat McElhatton, Paul Peters, Minke Reuvers, Elisabeth Robert, Margreet Rost van Tonningen, Tony Scially.
Published by: ELSEVIER, 2001.<http://www.elsevier.nl/locate/isbn/0-444-50763-9>
Description:
The care of pregnant women presents one of the paradoxes of modern medicine. Women usually require little medical intervention during an (uneventful) pregnancy. Conversely, those at high risk of damage to their own health or that of their unborn require the help of appropriate medicinal technology, including drugs. Accordingly, there are two classes of pregnant women, the larger group requires support but not much intervention, while the other needs the full range of diagnostic and therapeutic measures applied in any other branch of medicine.
This book presents the current state of knowledge about drugs in pregnancy. In each chapter information is presented separately for two different aspects of the problem seeking a drug appropriate for prescription during pregnancy, and assessing the risk of a drug when exposure has already taken place.
Practising clinicians who prescribe medicinal products to women who are, or who may become, pregnant, will find this volume an invaluable reference.
Contents:
1. General commentary to drug therapy and drug risks in pregnancy (P. Peters, C. Schaefer).
2. Specific drug therapies during pregnancy.
Analgesics and antiphlogistics (M. Reuvers).
Antiallergic drugs and desensitization (M.R. van Tonningen).
Antiasthmatic and cough medication (H. Garbis).
Antiemetics and hyperemesis gravidarum (T. Scially, M.R. van Tonningen).
Antiepileptics (E. Robert, M. Reuvers, C. Schaefer).
Antiinfective agents (H. Garbis, M. Reuvers, M.R. van Tonningen).
Anticoagulant and fibrinolytic drugs (M. Reuvers).
Vitamins, minerals and trace elements (C. Schaefer, P. Peters).
Diagnostic agents (E. Robert, M. Reuvers).
Dermatological medications and local therapeutics (C. Schaefer, P. Peters).
Diuretics (C. Schaefer, P. Peters).
Heart and circulatory system drugs (P. McElhatton).
Hormones (T. Scially, M.R. van Tonningen).
Gastrointestinal and antilipidemic agents and spasmolytics (M.R. van Tonningen).
Antineoplastic, immunosuppressive and immunomodulating agents (E. Robert, M. Reuvers, H. Garbis, C. Schaefer).
General and local anesthetics and muscle relaxants (T. Scially, M.R. van Tonningen).
Psychotropic, sedative-hypnotic and Parkinson drugs (H. Garbis).
Vaccines and immunoglobulins (E. Robert, M. Reuvers).
Uterine contraction agents, tocolytics, vaginal therapeutics and local contraceptives (T. Scially, M.R. van Tonningen).
Poisons and overdoses (P. McElhatton, H. Garbis, C. Schaefer).
Recreational drugs (C. Schaefer).
Industrial chemicals and environmental contaminants (P. McElhatton, H. Garbis, C. Schaefer).
3. General commentary to drug therapy and drug risks during lactation (C. Schaefer).
4. Specific drug therapies during lactation (C. Schaefer).
Analgesics, antiphlogistics, and anesthetics.
Antiallergics, antiasthmatics and antitussives.
Antiinfectives.
Cardiovascular drugs and diuretics.
Hormones and hormone antagonists.
Gastrointestinal drugs.
Antiepileptics.
Psychoactive and Parkinson's drugs.
Anticoagulants and fibronolytics.
Dermatological drugs and local therapeutics.
X-ray studies, diagnostics and radionuclides.
Immunosuppressives, immune modulators and antineoplastics.
Alternative medications, vitamins, minerals and others.
Immunization and breastfeeding.
Infections during breastfeeding.
Recreational drugs.
Plant toxins.
Industrial chemicals and environmental contaminants.
<>
OTHER BOOKS:
To order any of these books, go to Amazon.com
Bookstore
Doctors
Guide to Medication During Pregnancy and Lactation
Environmental
Toxicology and Pharmacology of Human Development
Drugs
in Breast Milk. Ed by John T. Wilson
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To read abstract of any of these journal articles or to order the reprint,
go to MEDLINE (Free Evaluated
MEDLINE), type authors name and select the Article
of interest and /or Related Articles. /Last update as of 1997/
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Anderson PO. Drug use during breast-feeding.Clin Pharm 1991 Aug;10(8):594-624
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Cooper DS. Antithyroid drugs: to breast-feed or not to breast-feed. Am J
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Wong SH. Monitoring of drugs in breast milk. Ann Clin Lab Sci 1985 Mar;15(2):100-105.
Black RF. Transmission of HIV-1 in the breast-feeding process. J Am Diet Assoc 1996 Mar;96(3):267-274.
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Frederick IB, Auerbach KG. Maternal-infant separation and breast-feeding. The return to work or school. J Reprod Med 1985 Jul;30(7):523-526.
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Azuno Y, Kaku K, Fujita N, Okubo M, Kaneko T and Matsumoto N. Mitoxantrone and etoposide in breast milk Am. J. Hematol. 1995, 48:131-132.
Moretti ME, Ito S and Koren G. Disposition of maternal ketoconazole in breast milk Am. J. Obstet. Gynecol. 1995, 173:1625-1626.
Ito S, Moretti M, Liau M and Koren G. Initiation and duration of breast-feeding in women receiving antiepileptics Am. J. Obstet. Gynecol. 1995, 172:881-886.
Breyer-Pfaff U, Nill K, Entenmann A and Gaertner HJ. Secretion of amitriptyline and metabolites into breast milk Am. J. Psychiatry 1995, 152:812-813.
Gladen BC and Rogan WJ. DDE and shortened duration of lactation in a northern Mexican town Am. J. Public Health 1995, 85:504-508.
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Anderson KL, Moats WA, Rushing JE, Wesen DP and Papich MG. Potential for oxytetracycline administration by three routes to cause milk residues in lactating cows, as detected by radioimmunoassay (Charm II) and high-performance liquid chromatography test methods Am. J. Vet. Res. 1995, 56:70-77.
Oskarsson A, Hallon IP and Sundberg J. Exposure to toxic elements via breast milk Analyst 1995, 120:765-770.
Hallon IP, Jorhem L and Oskarsson A. Placental and lactational transfer of lead in rats: A study on the lactational process and effects on offspring Arch. Toxicol. 1995, 69:596-602.
Nordenholl K, Dock L and Vahter M. Lactational exposure to methylmercury in the hamster Arch. Toxicol. 1995, 69:235-241.
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Buist A and Janson H. Effect of exposure to dothiepin and northiaden in breast milk on child development Br. J. Psychiatry 1995, 167:370-373.
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Howard PC, Consolo MC, Dooley KL and Beland FA. Metabolism of 1-nitropyrene in mice: Transport across the placenta and mammary tissues Chem. Biol. Interact. 1995, 95:309-325.
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