Leaching of the plasticizer di(2-ethylhexyl)phthalate (DEHP) from plastic containers and the question of human exposure

AbstractMost medical devices utilized in blood storage and transfusion, as well as in many medical and surgical procedures, are manufactured with polyvinylchloride (PVC) plastic containing the plasticizer di(2-ethylhexyl)phthalate (DEHP). During exposure of blood to the plastic surface, the DEHP is leached into the plasma where it is converted to mono(2-ethylhexyl)phthalate (MEHP) by a plasma enzyme in vivo or ex vivo during storage in plastic containers. The toxic effects of MEHP when infused into rats were investigated. The amount of MEHP infused was based on MEHP levels found in a variety of stored blood products (>6 ug/mL in red cell concentrates) and values actually measured during exchange transfusion (5 ug/mL) and cardiopulmonary bypass surgery (2.7 ug/mL). When the circulating level of MEHP in the rat's blood was >125 ug/mL, a greater than 50% decrease in heart rate and blood pressure was observed. This represents a margin of safety of only 25 fold higher than levels measured in humans during exchange transfusions. Although DEHP and MEHP have low oral toxicity, acute exposure by infusion may have lethal effects.

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The effect of the plasticizer di(2-ethylhexyl)phthalate on red cell deformability

Blood ◽

10.1182/blood.v70.1.319.bloodjournal701319 ◽

1987 ◽

Vol 70 (1) ◽

pp. 319-323

Author(s):

RS Labow ◽

RT Card ◽

G Rock

Keyword(s):

Storage Period ◽

Osmotic Fragility ◽

Osmotic Gradient ◽

Red Cell ◽

Cell Deformability ◽

Red Cell Deformability ◽

Plastic Bag ◽

Elongation Index ◽

Plastic Containers ◽

Ethylhexyl Phthalate

Red cell concentrates (RCC) are stored for 35 to 42 days in plastic containers manufactured with the liquid plasticizer di(2- ethylhexyl)phthalate (DEHP). DEHP leaches from the polyvinylchloride (PVC) plastic bag, then binds to and stabilizes the RC membrane. This study was undertaken to determine the deformability of the RC membrane using an osmotic gradient ektacytometer and to relate these measurements to the concentration of DEHP in the stored RCC. Pooled RCC was aliquoted into PL146 (PVC), PL732 (polyolefin), and PL732 (with added DEHP) bags with samples removed weekly for analysis of osmotic fragility, deformability, and DEHP concentration. The adenosine triphosphate (ATP) content was also measured. The increase in osmotic fragility during storage was greater when RCC was stored without DEHP. In addition, there was a decrease in the maximum elongation index (El max) when there was decreased DEHP in the storage bag. The osmolarity (Omax) at which El max occurred, as well as the Omin, the osmolarity at which minimum elongation (El min) occurred was higher in the PL732 container than in the PL146 or in the PL732 to which DEHP had been added. These changes could be reversed by addition of DEHP at the beginning of the storage period, showing a direct correlation between DEHP concentration during storage and RC membrane flexibility. By a better understanding of the mechanism of DEHP protection, it might be possible to substitute a less toxic stabilizing compound.

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The effect of the plasticizer di-2-ethylhexyl phthalate on the survival of stored RBCs

Blood ◽

10.1182/blood.v71.2.448.448 ◽

1988 ◽

Vol 71 (2) ◽

pp. 448-452 ◽

Cited By ~ 66

Author(s):

JP AuBuchon ◽

TN Estep ◽

RJ Davey

Keyword(s):

Whole Blood ◽

Red Cells ◽

Refrigerated Storage ◽

Plasticized Pvc ◽

Normal Human ◽

Plastic Containers ◽

Ethylhexyl Phthalate ◽

Citrate Phosphate

Abstract Recent in vitro studies have shown that di-2-ethylhexyl-phthalate (DEHP) inhibits the deterioration of RBCs during refrigerated storage in containers that use this compound as a plasticizer. The experiments described in this report were designed to assess whether this in vitro protective effect of DEHP would result in a prolonged in vivo survival of RBCs infused into normal human recipients. Whole blood collected from ten normal donors was stored for 35 days in citrate-phosphate- dextrose-adenine (CPDA-1) anticoagulant contained in polyvinylchloride (PVC) bags plasticized with DEHP or a trimellitate compound that is known to have low leachability. Aliquots of RBCs from each container were then labeled with chromium-51 and were reinfused into the original donors. For blood stored in DEHP-plasticized PVC bags, 24% more red cells survived in vivo 24 hours after reinfusion than was observed when the blood had been stored in trimellitate-plasticized bags (P less than .001). Whole blood stored in glass bottles showed a similar improvement in in vivo survival when DEHP was added in weekly increments to mimic the accumulation of this plasticizer seen during storage in plastic containers. Survival of packed red cells stored in the presence of DEHP increased by 14% compared with storage in trimellitate-plasticized bags (P less than .05). In agreement with previous studies, hemolysis and microvesicle formation were also reduced in the presence of DEHP. These results suggest that proposed new storage systems lacking DEHP should be carefully evaluated to determine whether adequate post-transfusion survival of RBCs may be achieved.

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Di(2-ethylhexyl)phthalate (DEHP)

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-9.2.89 ◽

2004 ◽

Vol 9 (2) ◽

pp. 89-95

Author(s):

Arthur A. Strauss

Keyword(s):

Health Care Professionals ◽

Human Exposure ◽

Medical Literature ◽

High Risk Population ◽

Potential Toxicity ◽

Human Carcinogen ◽

Chemical Agents ◽

The Status ◽

Ethylhexyl Phthalate ◽

Oily Liquid

Di(2-ethylhexyl) phthalate or DEHP is a colorless, oily liquid and notably, with respect to clinical concerns, is soluble in blood and body fluids containing lipoproteins. Despite being listed as a possible human carcinogen in the 1980's, more recent concerns have focused on its potential toxicity as a result of leaching from medical devices into patients via intravenous or enteral routes. Initial discussion of this problem was reported in the medical literature over 20 years ago. This article provides an update on the status of DEHP as a potential reproductive toxin and the potential implications for high-risk population groups (most notably neonates). The use of the precautionary principle for a guidepost in relating human exposure effects to chemical agents, including DEHP, has become a topic relevant to all health care professionals and is discussed herein.

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Occupational Hazards and Risks Associated with Phthalates among Slovakian Firefighters

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17072483 ◽

2020 ◽

Vol 17 (7) ◽

pp. 2483

Author(s):

Branislav Kolena ◽

Ida Petrovičová ◽

Miroslava Šidlovská ◽

Henrieta Hlisníková ◽

Lenka Bystričanová ◽

...

Keyword(s):

Vital Capacity ◽

Plastic Material ◽

Positive Association ◽

Shape Index ◽

Forced Expiratory Volume ◽

Negative Association ◽

Body Structure ◽

Hip Circumference ◽

Plastic Containers ◽

Ethylhexyl Phthalate

Despite increasing attention to the occupational risk of firefighters, little is known about phthalate exposure. In our study, we detected mono-isobutyl phthalate (MiBP), mono-n-buthyl phthalate (MnBP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MECPP), and mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP) in each urine sample. We detected positive association between MnBP, MiBP, mono-2-ethylhexyl phthalate (MEHP), 5OH-MEHP, 5oxo-MEHP, 5cx-MECPP, mono-isononyl phthalate (MiNP), the sum of low (∑LMWP) and high molecular-weight phthalates (∑HMWP). and Tiffeneau–Pinelli index (the ratio of forced expiratory volume in 1/ forced vital capacity; FEV1/FVC; p = 0.001−0.04) and the percent predicted value (%PV) of FEV1/FVC (p = 0.005−0.05) and negative association between MiNP and peak expiratory flow (PEF; r = −0.31; p = 0.084). We observed a positive association between phthalate metabolites (MnBP, 5OH-MEHP, 5oxo-MEHP, 5cx-MECPP, 2cx-MMHP, ∑LMWP, and ∑HMWP) and waist-to-hip ratio (WHR; p = 0.003−0.09) and body shape index (ABSI; p = 0.039−0.09) and a negative association between MnBP, ∑LMWP, and hip circumference (p = 0.005−0.02). We detected association between concentrations of 5OH-MEHP, 5cx-MECPP, 5oxo-MEHP, and MnBP and consumption of food heating in plastic material in microwave (p = 0.02−0.04) and between probands who ate margarines and vegetable fat packed in plastic containers and concentration of MMP (p = 0.03). Results of multivariate regression indicated that exposure to phthalates could be linked with changing body structure, which subsequently affects values of pulmonary functions in firefighters.

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Impact of di-(2-ethylhexyl) phthalate on the uterus of adult Wistar rats

Human & Experimental Toxicology ◽

10.1177/0960327116657601 ◽

2016 ◽

Vol 36 (6) ◽

pp. 565-572 ◽

Cited By ~ 10

Author(s):

DB Somasundaram ◽

K Manokaran ◽

BC Selvanesan ◽

RS Bhaskaran

Keyword(s):

Body Weight ◽

Human Exposure ◽

Wistar Rats ◽

Healthy Adult ◽

Ovarian Hormones ◽

The Body ◽

Female Rats ◽

Adult Rats ◽

Structural Abnormalities ◽

Ethylhexyl Phthalate

Di-(2-ethylhexyl) phthalate (DEHP) is the most common plasticizer used in polyvinyl chloride-based plastics. DEHP is not covalently bound to the plastics and is easily released to the environment, resulting in human exposure. In this study, the adult rats were exposed to DEHP and its effects on the uterus was evaluated. Healthy adult female rats were treated with DEHP orally (with dose level 0, 1, 10, and 100 mg/kg body weight/day) for 30 days. No significant changes in the body weight and wet uterine weight were observed. Ovarian hormones and their receptor levels in the uterus were increased. Histological studies exhibited the structural abnormalities such as decrease in diameter, thinning of the layers and disruption in the glandular epithelium.

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The effect of the plasticizer di(2-ethylhexyl)phthalate on red cell deformability

Blood ◽

10.1182/blood.v70.1.319.319 ◽

1987 ◽

Vol 70 (1) ◽

pp. 319-323 ◽

Cited By ~ 24

Author(s):

RS Labow ◽

RT Card ◽

G Rock

Keyword(s):

Storage Period ◽

Osmotic Fragility ◽

Osmotic Gradient ◽

Red Cell ◽

Cell Deformability ◽

Red Cell Deformability ◽

Plastic Bag ◽

Elongation Index ◽

Plastic Containers ◽

Ethylhexyl Phthalate

Abstract Red cell concentrates (RCC) are stored for 35 to 42 days in plastic containers manufactured with the liquid plasticizer di(2- ethylhexyl)phthalate (DEHP). DEHP leaches from the polyvinylchloride (PVC) plastic bag, then binds to and stabilizes the RC membrane. This study was undertaken to determine the deformability of the RC membrane using an osmotic gradient ektacytometer and to relate these measurements to the concentration of DEHP in the stored RCC. Pooled RCC was aliquoted into PL146 (PVC), PL732 (polyolefin), and PL732 (with added DEHP) bags with samples removed weekly for analysis of osmotic fragility, deformability, and DEHP concentration. The adenosine triphosphate (ATP) content was also measured. The increase in osmotic fragility during storage was greater when RCC was stored without DEHP. In addition, there was a decrease in the maximum elongation index (El max) when there was decreased DEHP in the storage bag. The osmolarity (Omax) at which El max occurred, as well as the Omin, the osmolarity at which minimum elongation (El min) occurred was higher in the PL732 container than in the PL146 or in the PL732 to which DEHP had been added. These changes could be reversed by addition of DEHP at the beginning of the storage period, showing a direct correlation between DEHP concentration during storage and RC membrane flexibility. By a better understanding of the mechanism of DEHP protection, it might be possible to substitute a less toxic stabilizing compound.

Download Full-text

The effect of the plasticizer di-2-ethylhexyl phthalate on the survival of stored RBCs

Blood ◽

10.1182/blood.v71.2.448.bloodjournal712448 ◽

1988 ◽

Vol 71 (2) ◽

pp. 448-452 ◽

Cited By ~ 1

Author(s):

JP AuBuchon ◽

TN Estep ◽

RJ Davey

Keyword(s):

Whole Blood ◽

Red Cells ◽

Refrigerated Storage ◽

Plasticized Pvc ◽

Normal Human ◽

Plastic Containers ◽

Ethylhexyl Phthalate ◽

Citrate Phosphate

Recent in vitro studies have shown that di-2-ethylhexyl-phthalate (DEHP) inhibits the deterioration of RBCs during refrigerated storage in containers that use this compound as a plasticizer. The experiments described in this report were designed to assess whether this in vitro protective effect of DEHP would result in a prolonged in vivo survival of RBCs infused into normal human recipients. Whole blood collected from ten normal donors was stored for 35 days in citrate-phosphate- dextrose-adenine (CPDA-1) anticoagulant contained in polyvinylchloride (PVC) bags plasticized with DEHP or a trimellitate compound that is known to have low leachability. Aliquots of RBCs from each container were then labeled with chromium-51 and were reinfused into the original donors. For blood stored in DEHP-plasticized PVC bags, 24% more red cells survived in vivo 24 hours after reinfusion than was observed when the blood had been stored in trimellitate-plasticized bags (P less than .001). Whole blood stored in glass bottles showed a similar improvement in in vivo survival when DEHP was added in weekly increments to mimic the accumulation of this plasticizer seen during storage in plastic containers. Survival of packed red cells stored in the presence of DEHP increased by 14% compared with storage in trimellitate-plasticized bags (P less than .05). In agreement with previous studies, hemolysis and microvesicle formation were also reduced in the presence of DEHP. These results suggest that proposed new storage systems lacking DEHP should be carefully evaluated to determine whether adequate post-transfusion survival of RBCs may be achieved.

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