What are we Waiting for?
Department of Environmental and Occupational Health, Faculty of Medicine, University of Montreal, Montreal (Quebec), Canada
- *Corresponding Author:
- Pierre Brochu
Department of Environmental and Occupational Health
Faculty of Medicine, University of Montreal, Montreal (Quebec), Canada
E-mail: [email protected]
Received date: July 23, 2013; Accepted date: July 24, 2013; Published date: July 26, 2013
Citation: Brochu P (2013) What are we Waiting for? J Clin Toxicol 3:e119. doi: 10.4172/2161-0495.1000e119
Copyright: © 2013 Brochu P. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Visit for more related articles at Journal of Clinical Toxicology
The very demanding metabolism of pregnant and lactating females should lead to higher intakes of environmental and occupational chemicals by their respiratory tract compared to their male counterparts, during similar exposure concentrations and conditions. Additional overall energy costs in pregnant females compared to non-gravid females range from 91 614 to 99 726 kcal over the complete gestational period and correspond to extra daily costs varying from 32 to 496 kcal/day [1-3]. In late pregnancy, approximately half of the increment of 302kcal/ day is required for a 3-kg fetus [4,5]. During the postpartum phase, the maternal breastfeeding requires extra daily energy costs of 106kcal/day for the metabolism of milk synthesis and from 477 to 539kcal/day for milk energy outputs [6-8]. Prior observations [9,10] indicate that energy expenditures in human are supplied by the combustion of postprandial (i.e., carbohydrates, proteins and/or fats) and/or endogen metabolic fuels (i.e. glycogen, glucose, 3-hydroxybutyric acid, acetoacetic acid and triacylglycerol) which requires about the same oxygen consumption rate (VO2) per unit of energy expended of 0.2057 ± 0.0018 and 0.2059 ± 0.0019 L of O2/kcal (mean ± S.D.) respectively . Each additional kcal of energy expended during pregnancy and the postpartum phase compared to baseline values for non-gravid and non-lactating females requires an extra average metabolic consumption of 0.206 liter of oxygen. Consequently, in order to be adequately oxygenated pregnant and lactating females inhale more air than their non-gravid and nonlactating counter parts. This explain the progressively increase of the minute ventilation rate (VE) observed in pregnant females at rest, as early as 7 or 8 weeks of gestation. The latter value peaks up at 50% above pre-gravid levels around the second trimester, primarily due to a 40% increase in the tidal volume and a 15% increase in the respiratory frequency. This increase of the respiratory drive compensates for a loss of functional residual capacity and the fetus oxygenation of about 8 mL O2 kg-1min-1 [5,12-18].
Pregnant and breastfeeding females usually avoid overstrain and overwork by increasing work efficiency and adjusting daily physical activities [3,5-7,19-24]. However, VE values during exercises involving lifting the body (e.g., walking on a treadmill) are expected to by greater during pregnancy [12,13,15,16,25-30]. In normal-weight subjects, daily inhalation rates were found to be higher by 18 to 41% throughout pregnancy and 23 to 39% during postpartum weeks compared to those for males . Highest 99th percentiles of 47.31m3/day and 0.647m3/ kg-day were determined in overweight/obese pregnant women 23 to less than 30 years old at the 36th week of gestation and under-weight lactating females aged 11 to less than 23 years at the 27th postpartum week respectively. Since the ratio of the physiological dead space to the tidal volume remains unchanged, the alveolar ventilation rate (VA) is about 70% higher at the end of gestation [14,16,17,25]. Higher cardiac outputs (Q) have also been measured in pregnant females . For instance, Q values were showed to increase by almost 50% and 22% from the non-pregnancy level to that at 8-11 and 29.6 weeks gestation respectively [33,34]. Higher VE, VA, Q values and others significant physiological modifications occurring during pregnancy may affect the toxicokinetics of inhaled xenobiotics [35,36]. For instance, the blood volume, renal blood flow, as well as glomerular filtration increase, whereas plasma proteins decrease. Higher tidal volume, VE and VO2 can result in increased pulmonary distribution of toxic gas and reduce in time to reach alveolar steady state. The higher volume of distribution may prolong half-lives of many chemicals. An overall decrease in hepatic xenobiotic biotransformation during pregnancy is also observed.
It is well known that women live longer than men and have a higher percentage of body fat . Lipophilic toxic chemicals absorbed into the body through air pollution are stored in fat tissue and may remain sequestered for years before being released into the general circulation [38-41]. For instance, lipophilic organochlorines stored in fats, such as dichlorodiphenyltrichloroethane and polychlorinated biphenyls are released at critical periods of life, notably during weight loss resulting from an energy-restricted diet or when hormonal change occurs during pregnancy, lactation and menopause [42-49]. Other chemicals absorbed through air pollution, such as lead, are stored in bone tissue. The mobilization of lead from bone tissue into the bloodstream has been observed during pregnancy, lactation and menopause; it also increases in calcium-deficient diets [50-71]. Lead released into the bloodstream is more pronounced in aging women than in their male counterparts [53,61,62,72-74].
Most chemicals found in the bloodstream of pregnant women may be transferred to the embryos or fetus by the umbilical cord after crossing the placenta during pregnancy, or transferred to newborns during breastfeeding in the postpartum phase . In fact, numerous epidemiological studies have confirmed links between air pollutants and adverse birth outcomes in humans, such as low birth weight, premature birth and infant mortality [76-89].
Exposure to toxic chemicals during a brief duration (˜6 h) immediately following fertilization in mice has been demonstrated to result in malformed fetuses [90,91]. During the first week after the fertilization, thus before the positive pregnancy test, chemicals in sufficient exposure concentrations could alter the normal development of zygote, morula or blastocyst . Perera et al.  have showed that prenatal exposure to carcinogens apparently results in differentially higher levels of procarcinogenic DNA damage in fetus. In certain individuals, it may disproportionately increase the probability of developing a cancer over their lifetime. Such data is relatively alarming considering that in 1982 already 42% of pregnancies were occurring in working women .
Overall, considering what precedes, physiological data in pregnant and lactating females should be taken into consideration for a scientifically-sound determination of indoor and outdoor hygienic standards for airborne toxic chemicals, as well as adequate non hazardous safe working conditions for all females, their fetus and breastfed newborn.
- Goldberg GR, Prentice AM, Coward WA, Davies HL, Murgatroyd PR, et al. (1993) Longitudinal assessment of energy expenditure in pregnancy by the doubly labeled water method. Am J Clin Nutr 57: 494-505.
- Kopp-Hoolihan LE, van Loan MD, Wong WW, King JC (1999) Longitudinal assessment of energy balance in well-nourished, pregnant women. Am J Clin Nutr 69: 697-704.
- Butte NF, Wong WW, Treuth MS, Ellis KJ, O'Brian Smith E (2004) Energy requirements during pregnancy based on total energy expenditure and energy deposition. Am J Clin Nutr 79: 1078-1087.
- Sparks JW, Girard JR, Battaglia FC (1980) An estimate of the caloric requirements of the human fetus. Biol Neonate 38: 113-119.
- Butte NF, Hopkinson JM, Mehta N, Moon JK, Smith EO (1999) Adjustments in energy expenditure and substrate utilization during late pregnancy and lactation. Am J Clin Nutr 69: 299-307.
- Goldberg GR, Prentice AM, Coward WA, Davies HL, Murgatroyd PR, et al. (1991) Longitudinal assessment of the components of energy balance in well-nourished lactating women. Am J Clin Nutr 54: 788-798.
- Butte NF, Wong WW, Hopkinson JM (2001) Energy requirements of lactating women derived from doubly labeled water and milk energy output. J Nutr 131: 53-58.
- IOM (Institute of Medicine) (2002) Appendix I: doubly labeled water data used to predict energy expenditure. In: Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). Food and Nutrition Board, National Academies Press, Washington.
- McLean JA, Tobin G (1987) Animal and human calorimetry. Cambridge University Press, Cambridge, USA.
- Elia M (1997) Tissue distribution and energetic in weight loss and undernutrition. In: Physiology Stress and malnutrition: Functional Correlates, Nutritional Intervention, Kenney JM, Tucker HN (eds), Lippincott-Raven Publishers, New York.
- Brochu P, Brodeur J, Krishnan K (2011) Derivation of physiological inhalation rates in children, adults, and elderly based on nighttime and daytime respiratory parameters. Inhal Toxicol 23: 74-94.
- Knuttgen HG, Emerson K Jr (1974) Physiological response to pregnancy at rest and during exercise. J Appl Physiol 36: 549-553.
- Edwards MJ, Metcalfe J, Dunham MJ, Paul MS (1981) Accelerated respiratory response to moderate exercise in late pregnancy. Respir Physiol 45: 229-241.
- Sady SP, Carpenter MW, Thompson PD, Sady MA, Haydon B, et al. (1989) Cardiovascular response to cycle exercise during and after pregnancy. J Appl Physiol 66: 336-341.
- Field SK, Bell SG, Cenaiko DF, Whitelaw WA (1991) Relationship between inspiratory effort and breathlessness in pregnancy. J Appl Physiol 71: 1897-1902.
- Pivarnik JM, Lee W, Miller JF, Werch J (1990) Alterations in plasma volume and protein during cycle exercise throughout pregnancy. Med Sci Sports Exerc 22: 751-755.
- Ciliberto CF, Marx GF (1998) Physiological changes associated with pregnancy. Anesthesia 9: 1-3.
- Wolfe LA, Kemp JG, Heenan AP, Preston RJ, Ohtake PJ (1998) Acid-base regulation and control of ventilation in human pregnancy. Can J Physiol Pharmacol 76: 815-827.
- Prentice AM, Goldberg GR, Davies HL, Murgatroyd PR, Scott W (1989) Energy-sparing adaptations in human pregnancy assessed by whole-body calorimetry. Br J Nutr 62: 5-22.
- Poppitt SD, Prentice AM, Jéquier E, Schutz Y, Whitehead RG (1993) Evidence of energy sparing in Gambian women during pregnancy: a longitudinal study using whole-body calorimetry. Am J Clin Nutr 57: 353-364.
- Poppitt SD, Prentice AM, Goldberg GR, Whitehead RG (1994) Energy-sparing strategies to protect human fetal growth. Am J Obstet Gynecol 171: 118-125.
- Prentice AM, Poppitt SD, Goldberg GR, Prentice A (1994a) Adaptive strategies regulating energy balance in human pregnancy. Oxf Rev Reprod Biol 17: 33-60.
- Prentice AM, Poppitt SD, Goldberg GR, Murgatroyd PR, Black AE, et al. (1994b) Energy balance in pregnancy and lactation. In: Allen L, King J, Lonnerdal B (eds), Nutrient regulation in pregnancy, lactation and infant growth, New York.
- Butte NF, Hopkinson JM, Ellis KJ, Wong WW, Smith EO (1997) Changes in fat-free mass and fat mass in postpartum women: a comparison of body composition models. Int J Obes Relat Metab Disord 21: 874-880.
- PROWSE CM, GAENSLER EA (1965) RESPIRATORY AND ACID-BASE CHANGES DURING PREGNANCY. Anesthesiology 26: 381-392.
- Pernoll ML, Metcalfe J, Kovach PA, Wachtel R, Dunham MJ (1975) Ventilation during rest and exercise in pregnancy and postpartum. Respir Physiol 25: 295-310.
- Artal R, Wiswell R, Romem Y, Dorey F (1986) Pulmonary responses to exercise in pregnancy. Am J Obstet Gynecol 154: 378-383.
- Clapp JF III (1990) Exercise in pregnancy: a brief clinical review. Fetal Medical Review 161: 1464-9.
- Heenan AP, Wolfe LA, Davies GA (2001) Maximal exercise testing in late gestation: maternal responses. Obstet Gynecol 97: 127-134.
- Hytten F, Chamberlain G (1991) Clinical Physiology in Obstetrics (2nd Eds), Boston, Blackwell Scientific, Mosby—Year Book, St. Louis, USA.
- Brochu P, Ducré-Robitaille J-F, Brodeur J (2006b) Physiological daily inhalation rates for free-living pregnant and lactating adolescents and women aged 11 to 55 years, using data from doubly labeled water measurements for use in health risk assessment. Hum Ecol Risk Assess 12: 702-735.
- van Oppen AC, Stigter RH, Bruinse HW (1996) Cardiac output in normal pregnancy: a critical review. Obstet Gynecol 87: 310-318.
- Spätling L, Fallenstein F, Huch A, Huch R, Rooth G (1992) The variability of cardiopulmonary adaptation to pregnancy at rest and during exercise. Br J Obstet Gynaecol 99 Suppl 8: 1-40.
- Khodiguian N, Jaque-Fortunato SV, Wiswell RA, Artal R (1996) A comparison of cross-sectional and longitudinal methods of assessing the influence of pregnancy on cardiac function during exercise. Semin Perinatol 20: 232-241.
- Ellenhorn MJ, Barceloux DG (1988) Medical Toxicology. Diagnosis and Treatment of Human Poisoning. Elsevier publishing company Inc, New York.
- Klaassen CD (2008) Casarett and Doull's Toxicology: The Basic science of Poisons. (7th edn), McGraw Companies, New York.
- Durnin JVGA, Passmore R (1967) Energy, Work and Leisure. Heinemann Educational Books Ltd, London.
- Wolff MS, Toniolo PG, Lee EW, Rivera M, Dubin N (1993) Blood levels of organochlorine residues and risk of breast cancer. J Natl Cancer Inst 85: 648-652.
- Liljegren G, Hardell L, Lindström G, Dahl P, Magnuson A (1998) Case-control study on breast cancer and adipose tissue concentrations of congener specific polychlorinated biphenyls, DDE and hexachlorobenzene. Eur J Cancer Prev 7: 135-140.
- Aronson KJ, Miller AB, Woolcott CG, Sterns EE, McCready DR, et al. (2000) Breast adipose tissue concentrations of polychlorinated biphenyls and other organochlorines and breast cancer risk. Cancer Epidemiol Biomarkers Prev 9: 55-63.
- Stellman SD, Djordjevic MV, Britton JA, Muscat JE, Citron ML, et al. (2000) Breast cancer risk in relation to adipose concentrations of organochlorine pesticides and polychlorinated biphenyls in Long Island, New York. Cancer Epidemiol Biomarkers Prev 9: 1241-1249.
- Dorgan JF, Brock JW, Rothman N, Needham LL, Miller R, et al. (1999) Serum organochlorine pesticides and PCBs and breast cancer risk: results from a prospective analysis (USA). Cancer Causes Control 10: 1-11.
- Moysich KB, Ambrosone CB, Vena JE, Shields PG, Mendola P, et al. (1998) Environmental organochlorine exposure and postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev 7: 181-188.
- Demers A, Ayotte P, Brisson J, Dodin S, Robert J, et al. (2000) Risk and aggressiveness of breast cancer in relation to plasma organochlorine concentrations. Cancer Epidemiol Biomarkers Prev 9: 161-166.
- Millikan R, DeVoto E, Duell EJ, Tse CK, Savitz DA, et al. (2000) Dichlorodiphenyldichloroethene, polychlorinated biphenyls, and breast cancer among African-American and white women in North Carolina. Cancer Epidemiol Biomarkers Prev 9: 1233-1240.
- Høyer AP, Jørgensen T, Grandjean P, Hartvig HB (2000) Repeated measurements of organochlorine exposure and breast cancer risk (Denmark). Cancer Causes Control 11: 177-184.
- Lucena RA, Allam MF, Costabeber IH, Villarejo ML, Navajas RF (2001) Breast cancer risk factors: PCB congeners. Eur J Cancer Prev 10: 117-119.
- Høyer AP, Gerdes AM, Jørgensen T, Rank F, Hartvig HB (2002) Organochlorines, p53 mutations in relation to breast cancer risk and survival. A Danish cohort-nested case-controls study. Breast Cancer Res Treat 71: 59-65.
- Pelletier C, Doucet E, Imbeault P, Tremblay A (2002) Associations between weight loss-induced changes in plasma organochlorine concentrations, serum T(3) concentration, and resting metabolic rate. Toxicol Sci 67: 46-51.
- Arnest JL, Mahaffey KR (1984) Blood lead levels for persons ages 6 months-74 years. United States 1976-1980 (Vital and Health Statistics, Series 11; data from the National Health survey.
- Drasch GA, Böhm J, Baur C (1987) Lead in human bones. Investigations on an occupationally non-exposed population in southern Bavaria (F.R.G.). I. Adults. Sci Total Environ 64: 303-315.
- Grandjean P (1988) Ancient skeletons as silent witnesses of lead exposures in the past. Crit Rev Toxicol 19: 11-21.
- Silbergeld EK, Schwartz J, Mahaffey K (1988) Lead and osteoporosis: mobilization of lead from bone in postmenopausal women. Environ Res 47: 79-94.
- Graziano JH, Popovac D, Factor-Litvak P, Shrout P, Kline J, et al. (1990) Determinants of elevated blood lead during pregnancy in a population surrounding a lead smelter in Kosovo, Yugoslavia. Environ Health Perspect 89: 95-100.
- Koren G, Chang N, Gonen R, Klein J, Weiner L, et al. (1990) Lead exposure among mothers and their newborns in Toronto. CMAJ 142: 1241-1244.
- Kostial K, DekaniÄ‡ D, Telisman S, Blanusa M, DuvanciÄ‡ S, et al. (1991) Dietary calcium and blood lead levels in women. Biol Trace Elem Res 28: 181-185.
- Landrigan PJ (1991) Strategies for epidemiologic studies of lead in bone in occupationally exposed populations. Environ Health Perspect 91: 81-86.
- Silbergeld EK (1991) Lead in bone: implications for toxicology during pregnancy and lactation. Environ Health Perspect 91: 63-70.
- O'Halloran K, Spickett JT (1992) The interaction of lead exposure and pregnancy. Asia Pac J Public Health 6: 35-39.
- Silbergeld EK, Sauk J, Somerman M, Todd A, McNeill F, et al. (1993) Lead in bone: storage site, exposure source, and target organ. Neurotoxicology 14: 225-236.
- Goldman RH, White R, Kales SN, Hu H (1994) Lead poisoning from mobilization of bone stores during thyrotoxicosis. Am J Ind Med 25: 417-424.
- Muldoon SB, Cauley JA, Kuller LH, Scott J, Rohay J (1994) Lifestyle and sociodemographic factors as determinants of blood lead levels in elderly women. Am J Epidemiol 139: 599-608.
- Farias P, Borja-Aburto VH, Rios C, Hertz-Picciotto I, Rojas-Lopez M, et al. (1996) Blood lead levels in pregnant women of high and low socioeconomic status in Mexico City. Environ Health Perspect 104: 1070-1074.
- Hernandez-Avila M, Gonzalez-Cossio T, Palazuelos E, Romieu I, Aro A, et al. (1996) Dietary and environmental determinants of blood and bone lead levels in lactating postpartum women living in Mexico City. Environ Health Perspect 104: 1076-1082.
- Rothenberg SJ, Karchmer S, Schnaas L, Perroni E, Zea F, et al. (1996) Maternal influences on cord blood lead levels. J Expo Anal Environ Epidemiol 6: 211-227.
- Goyer RA (1997) Toxic and essential metal interactions. Annu Rev Nutr 17: 37-50.
- Arnay-De-La-Rosa M, Gonzalez-Reimers E, Velasco-Vazquez J, Galindo-Martin L, Delgado-Ureta E, et al. (1998) Comparison of bone lead in pre-Hispanic, 18th century and modern population of Tenerife. Sci Total Environ 209: 107-111.
- Carbone R, Laforgia N, Crollo E, Mautone A, Iolascon A (1998) Maternal and neonatal lead exposure in southern Italy. Biol Neonate 73: 362-366.
- Cifuentes E, Villanueva J, Sanin LH (2000) Predictors of blood lead levels in agricultural villages practicing wastewater irrigation in Central Mexico. Int J Occup Environ Health 6: 177-182.
- Han S, Pfizenmaier DH, Garcia E, Eguez ML, Ling M, et al. (2000) Effects of lead exposure before pregnancy and dietary calcium during pregnancy on fetal development and lead accumulation. Environ Health Perspect 108: 527-531.
- Schell LM, Denham M, Stark AD, Gomez M, Ravenscroft J, et al. (2003) Maternal blood lead concentration, diet during pregnancy, and anthropometry predict neonatal blood lead in a socioeconomically disadvantaged population. Environ Health Perspect 111: 195-200.
- Chisolm JJ Jr (1987) Mobilization of lead by calcium disodium edetate. A reappraisal. Am J Dis Child 141: 1256-1257.
- Cory-Slechta DA (1990) Lead exposure during advanced age: alterations in kinetics and biochemical effects. Toxicol Appl Pharmacol 104: 67-78.
- Kosnett MJ (1992) Unanswered questions in metal chelation. J Toxicol Clin Toxicol 30: 529-547.
- Scialli AR (1992) A clinical guide to reproductive and developmental toxicology, CRC Press Inc., Florida, USA.
- Xu X, Ding H, Wang X (1995) Acute effects of total suspended particles and sulfur dioxides on preterm delivery: a community-based cohort study. Arch Environ Health 50: 407-415.
- Wang X, Ding H, Ryan L, Xu X (1997) Association between air pollution and low birth weight: a community-based study. Environ Health Perspect 105: 514-520.
- Woodruff TJ, Grillo J, Schoendorf KC (1997) The relationship between selected causes of postneonatal infant mortality and particulate air pollution in the United States. Environ Health Perspect 105: 608-612.
- Bobak M, Leon DA (1999) Pregnancy outcomes and outdoor air pollution: an ecological study in districts of the Czech Republic 1986-8. Occup Environ Med 56: 539-543.
- Dejmek J, Selevan SG, Benes I, Solanský I, Srám RJ (1999) Fetal growth and maternal exposure to particulate matter during pregnancy. Environ Health Perspect 107: 475-480.
- Ritz B, Yu F (1999) The effect of ambient carbon monoxide on low birth weight among children born in southern California between 1989 and 1993. Environ Health Perspect 107: 17-25.
- Loomis D, Castillejos M, Gold DR, McDonnell W, Borja-Aburto VH (1999) Air pollution and infant mortality in Mexico City. Epidemiology 10: 118-123.
- Bobak M (2000) Outdoor air pollution, low birth weight, and prematurity. Environ Health Perspect 108: 173-176.
- Ritz B, Yu F, Chapa G, Fruin S (2000) Effect of air pollution on preterm birth among children born in Southern California between 1989 and 1993. Epidemiology 11: 502-511.
- Rogers JF, Thompson SJ, Addy CL, McKeown RE, Cowen DJ, et al. (2000) Association of very low birth weight with exposures to environmental sulfur dioxide and total suspended particulates. Am J Epidemiol 151: 602-613.
- Bobak M, Richards M, Wadsworth M (2001) Air pollution and birth weight in Britain in 1946. Epidemiology 12: 358-359.
- Ha EH, Hong YC, Lee BE, Woo BH, Schwartz J, et al. (2001) Is air pollution a risk factor for low birth weight in Seoul? Epidemiology 12: 643-648.
- Maisonet M, Bush TJ, Correa A, Jaakkola JJ (2001) Relation between ambient air pollution and low birth weight in the Northeastern United States. Environ Health Perspect 109 Suppl 3: 351-356.
- Liu S, Krewski D, Shi Y, Chen Y, Burnett RT (2003) Association between gaseous ambient air pollutants and adverse pregnancy outcomes in Vancouver, Canada. Environ Health Perspect 111: 1773-1778.
- Generoso WM, Rutledge JC, Cain KT, Hughes LA, Braden PW (1987) Exposure of female mice to ethylene oxide within hours after mating leads to fetal malformation and death. Mutat Res 176: 269-274.
- Generoso WM, Rutledge JC, Cain KT, Hughes LA, Downing DJ (1988) Mutagen-induced fetal anomalies and death following treatment of females within hours after mating. Mutat Res 199: 175-181.
- Perera FP, Tang D, Tu YH, Cruz LA, Borjas M, et al. (2004) Biomarkers in maternal and newborn blood indicate heightened fetal susceptibility to procarcinogenic DNA damage. Environ Health Perspect 112: 1133-1136.
- Brix KA (1982) Environmental and occupational hazards to the fetus. J Reprod Med 27: 577-583.