Overview of known plastic packaging-associated chemicals and their hazards

Which hazardous chemicals are associated with plastic packaging?

The use of plastic packaging is increasing globally, causing environmental and human health concerns. In 2015 annual plastic production was 380Mt, of which about 40 per cent was used in packaging, with the majority being used in food packaging.

The 906 substances which are most likely to be associated with plastic packaging have been published on the Data Commons websiteAt least 148 of the 906 chemicals most likely to be associated with plastic packaging were identified as particularly hazardous based on several harmonized hazard data sources, and 35 of the chemicals listed are regarded as endocrine disrupting chemicals (EDCs), CHEM Trust reports.

2018 Study Highlights

  • Database of Chemicals associated with Plastic Packaging (CPPdb) is presented.
  • CPPdb contains chemicals used in manufacturing and/or present in final articles.
  • 906 chemicals identified as likely, 3377 chemicals as possibly associated.
  • Hazard data: CLP classifications, EDC, PBT, vPvB identifications explored.
  • Data gaps concerning both the use and toxicity of numerous substances identified.

Abstract

Global plastics production has reached 380 million metric tons in 2015, with around 40% used for packaging. Plastic packaging is diverse and made of multiple polymers and numerous additives, along with other components, such as adhesives or coatings. Further, packaging can contain residues from substances used during manufacturing, such as solvents, along with non-intentionally added substances (NIAS), such as impurities, oligomers, or degradation products. To characterize risks from chemicals potentially released during manufacturing, use, disposal, and/or recycling of packaging, comprehensive information on all chemicals involved is needed. Here, we present a database of Chemicals associated with Plastic Packaging (CPPdb), which includes chemicals used during manufacturing and/or present in final packaging articles. The CPPdb lists 906 chemicals likely associated with plastic packaging and 3377 substances that are possibly associated. Of the 906 chemicals likely associated with plastic packaging, 63 rank highest for human health hazards and 68 for environmental hazards according to the harmonized hazard classifications assigned by the European Chemicals Agency within the Classification, Labeling and Packaging (CLP) regulation implementing the United Nations’ Globally Harmonized System (GHS). Further, 7 of the 906 substances are classified in the European Union as persistent, bioaccumulative, and toxic (PBT), or very persistent, very bioaccumulative (vPvB), and 15 as endocrine disrupting chemicals (EDC). Thirty-four of the 906 chemicals are also recognized as EDC or potential EDC in the recent EDC report by the United Nations Environment Programme. The identified hazardous chemicals are used in plastics as monomers, intermediates, solvents, surfactants, plasticizers, stabilizers, biocides, flame retardants, accelerators, and colorants, among other functions. Our work was challenged by a lack of transparency and incompleteness of publicly available information on both the use and toxicity of numerous substances. The most hazardous chemicals identified here should be assessed in detail as potential candidates for substitution.

60 MiNueTs Toxic

UCSF Program on Reproductive Health and the Environment, 2017

Video published on 18 Apr 2019 by the UCSF Program on Reproductive Health and the Environment.

The University of California San Francisco (UCSF) Program on Reproductive Health and the Environment (PRHE)’s mission is to create a healthier environment for human reproduction and development through advancing scientific inquiry, clinical care and health policies that prevent exposures to harmful chemicals in our environment.

More Information

Adult and Prenatal Chemical Exposures

Breast Cancer Prevention Partners, with Tracey Woodruff, Ph.D., Mar 2019

  • How am I exposed to chemicals?
  • What are prenatal exposures?
  • How can I reduce my own personal exposures?
  • What more can I do to help make a change?

Featuring BCPP Science Advisory Panel member Tracey Woodruff, Ph.D., Director of the Program on Reproductive Health and the Environment, University of California, San Francisco, Professor in the Department of Obstetrics, Gynecology, and Reproductive Sciences and Philip R. Lee Institute for Health Policy Studies at UCSF

Effect of environmental and pharmaceutical exposures on fetal testis development and function

A systematic review of human experimental data, 2019

Abstract

BACKGROUND
Overall, the incidence of male reproductive disorders has increased in recent decades. Testicular development during fetal life is crucial for subsequent male reproductive function. Non-genomic factors such as environmental chemicals, pharmaceuticals and lifestyle have been proposed to impact on human fetal testicular development resulting in subsequent effects on male reproductive health. Whilst experimental studies using animal models have provided support for this hypothesis, more recently a number of experimental studies using human tissues and cells have begun to translate these findings to determine direct human relevance.

OBJECTIVE AND RATIONALE
The objective of this systematic review was to provide a comprehensive description of the evidence for effects of prenatal exposure(s) on human fetal testis development and function. We present the effects of environmental, pharmaceutical and lifestyle factors in experimental systems involving exposure of human fetal testis tissues and cells. Comparison is made with existing epidemiological data primarily derived from a recent meta-analysis.

SEARCH METHODS
For identification of experimental studies, PubMed and EMBASE were searched for articles published in English between 01/01/1966 and 13/07/2018 using search terms including ‘endocrine disruptor’, ‘human’, ‘fetal’, ‘testis’, ‘germ cells’, ‘testosterone’ and related search terms. Abstracts were screened for selection of full-text articles for further interrogation. Epidemiological studies involving exposure to the same agents were extracted from a recent systematic review and meta-analysis. Additional studies were identified through screening of bibliographies of full-texts of articles identified through the initial searches.

OUTCOMES
A total of 25 experimental studies and 44 epidemiological studies were included. Consistent effects of analgesic and phthalate exposure on human fetal germ cell development are demonstrated in experimental models, correlating with evidence from epidemiological studies and animal models. Furthermore, analgesic-induced reduction in fetal testosterone production, which predisposes to the development of male reproductive disorders, has been reported in studies involving human tissues, which also supports data from animal and epidemiological studies. However, whilst reduced testosterone production has been demonstrated in animal studies following exposure(s) to a variety of environmental chemicals including phthalates and bisphenol A, these effects are not reproduced in experimental approaches using human fetal testis tissues. Image credit academic.oup.

WIDER IMPLICATIONS
Direct experimental evidence for effects of prenatal exposure(s) on human fetal testis development and function exists. However, for many exposures the data is limited. The increasing use of human-relevant models systems in which to determine the effects of environmental exposure(s) (including mixed exposures) on development and function of human tissues should form an important part of the process for assessment of such exposures by regulatory bodies to take account of animal-human differences in susceptibility.

Prenatal and childhood exposure to phthalates and motor skills at age 11 years

Using Lipstick, Moisturizers During Pregnancy Linked To Motor Skill Deficiencies In Kids

2019 Study Highlights

  • Prenatal exposure to certain phthalates was associated with lower motor BOT-2 scores measured at 11 years of age among girls.
  • Postnatal exposure to certain phthalates was associated with lower motor proficiency among boys measured at 11 years of age.
  • The association between MEP measured at age 3 and motor performance at age 11 was different among girls and boys.

Abstract

Background
Previous reports suggest that prenatal phthalate exposure is associated with lower scores on measures of motor skills in infants and toddlers. Whether these associations persist into later childhood or preadolescence has not been studied.

Methods
In a follow up study of 209 inner-city mothers and their children the concentrations of mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), monomethyl phthalate (MEP), mono-carboxy-isooctyl phthalate (MCOP), and four di-2-ethylhexyl phthalate metabolites (ΣDEHP) were measured in spot urine sample collected from the women in late pregnancy and from their children at ages 3, 5, and 7 years. The Bruininks-Oseretsky Test of Motor Proficiency short form (BOT-2) was administered at child age 11 to assess gross and fine motor skills.

Results
The total number of children included in the study was 209. Of the 209 children, 116(55.5%) were girls and 93 were (45%) boys. Among girls, prenatal MnBP(b=−2.09; 95%CI: [−3.43, −0.75]), MBzP (b=−1.14; [95%CI: −2.13, −0.14]), and MiBP(b=−1.36; 95%CI: [−2.51, −0.21] and MEP(b=−1.23 [95%CI: −2.36, −0.11]) were associated with lower total BOT-2 composite score. MnBP (b= –1.43; 95% CI: [–2.44, –0.42]) was associated with lower fine motor scores and MiBP(b = –0.56; 95% CI: [–1.12, –0.01]) and MEP (b = –0.60; 95% CI: [–1.14, −0.06])was associated with lower gross motor scores. Among boys, prenatal MBzP (b = –0.79; 95% CI: [–1.40, −0.19]) was associated with lower fine motor composite score.

The associations between MEP measured at age 3 and the BOT-2 gross motor, fine motor and total motor score differed by sex. In boys, there was an inverse association between ΣDEHP metabolites measured in childhood at ages 3 (b = –1.30; 95% CI: [–2.34, −0.26]) and 7 years (b = –0.96; 95% CI: [–1.79, −0.13]), and BOT-2 fine motor composite scores.

Conclusions
Higher prenatal exposure to specific phthalates was associated with lower motor function among 11- year old girls while higher postnatal exposure to ΣDEHP metabolites was associated with lower scores among boys. As lower scores on measures of motor development have been associated with more problems in cognitive, socioemotional functioning and behavior, the findings of this study have implications related to overall child development.

Research communication. Press release. Image mamans.femmesdaujourdhui.be.

Do Harmful Chemicals in Health and Beauty Products Make Uterine Fibroids Grow ?

Phthalates exposure and uterine fibroid burden among women undergoing surgical treatment for fibroids: a preliminary study

A pilot study published in the journal Fertility and Sterility suggests that exposure to certain harmful chemicals called phthalates may lead to an increased burden of fibroids, uterine tumors that can cause heavy bleeding, pain, infertility, and other serious reproductive problems.

2019 Study Abstract

Objectives
To examine the association between phthalate exposure and two measures of uterine fibroid burden: diameter of largest fibroid and uterine volume.

Design
Pilot, cross-sectional study.

Setting
Academic medical center.

Patient(s)
Fifty-seven premenopausal women undergoing either hysterectomy or myomectomy for fibroids.

Intervention(s)
None.

Main Outcome Measure(s)
The diameter of the largest fibroid and uterine dimensions were abstracted from medical records. Spot urine samples were analyzed for 14 phthalate biomarkers using mass spectrometry. We estimated associations between fibroid outcomes and individual phthalate metabolites, sum of di(2-ethylhexyl) phthalate metabolites (∑DEHP), and a weighted sum of anti-androgenic phthalate metabolites (∑AA Phthalates) using linear regression, adjusting for age, race/ethnicity, and body mass index. Fibroid outcomes were also examined dichotomously (divided at the median) using logistic regression.

Results
Most women were of black ethnicity, overweight or obese, and college educated. In multivariable models, higher levels of mono-hydroxyisobutyl phthalate, monocarboxyoctyl phthalate, monocarboxynonyl phthalate, mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-hydroxyhexyl phthalate) (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), ∑DEHP, and ∑AA Phthalates were positively associated with uterine volume. Associations were most pronounced for individual DEHP metabolites (MEHHP, MEOHP, MECPP), ∑DEHP, and ∑AA Phthalates. For example, a doubling in ∑DEHP and ∑AA Phthalates was associated with 33.2% (95% confidence interval 6.6–66.5) and 26.8% (95% confidence interval 2.2–57.4) increase in uterine volume, respectively. There were few associations between phthalate biomarkers and fibroid size.

Conclusions
Exposure to some phthalate biomarkers was positively associated with uterine volume, which further supports the hypothesis that phthalate exposures may be associated with fibroid outcomes. Additional studies are needed to confirm these relationships.

The George Washington University press release.

Components of plastic : experimental studies in animals and relevance for human health

You are what you eat, and drink

Abstract

Components used in plastics, such as phthalates, bisphenol A (BPA), polybrominated diphenyl ethers (PBDE) and tetrabromobisphenol A (TBBPA), are detected in humans. In addition to their utility in plastics, an inadvertent characteristic of these chemicals is the ability to alter the endocrine system. Phthalates function as anti-androgens while the main action attributed to BPA is oestrogen-like activity. PBDE and TBBPA have been shown to disrupt thyroid hormone homeostasis while PBDEs also exhibit anti-androgen action. Experimental investigations in animals indicate a wide variety of effects associated with exposure to these compounds, causing concern regarding potential risk to human health. For example, the spectrum of effects following perinatal exposure of male rats to phthalates has remarkable similarities to the testicular dysgenesis syndrome in humans. Concentrations of BPA in the foetal mouse within the range of unconjugated BPA levels observed in human foetal blood have produced effects in animal experiments. Finally, thyroid hormones are essential for normal neurological development and reproductive function. Human body burdens of these chemicals are detected with high prevalence, and concentrations in young children, a group particularly sensitive to exogenous insults, are typically higher, indicating the need to decrease exposure to these compounds.

General Conclusions

Exposure of humans to pharmaceuticals is deliberate, with the intention of achieving a desired effect. Development and testing of medications involves a series of evaluations culminating in human clinical trials before marketing is approved. This is quite different from the situation with chemicals, whose presence in biota and humans is inadvertent. In the field of toxicology, information regarding potential human health effects is mainly derived from experimental studies and, when available, from epidemiological studies. Difficulties are not only encountered with extrapolation from animal models to humans, but epidemiological studies are also thwarted by drawbacks such as controlling for confounding factors. In particular, subjects are exposed to an assortment of chemicals on a daily basis and, often, lack of data regarding the extent of exposure at what may have been the critical time frame. One of the goals of toxicology is to identify effects in animal models with the aim to lower the risks of negatively impacting human health. Implicit in this task is that toxicological data, derived from animal studies indicating a potential for adverse effects, serve as a basis to limit exposure before effects appear or are confirmed in humans. The evidence from animal studies on single exposures to the chemicals discussed here suggests the potential for risk to human health. Moreover, data derived from co-exposure studies support the contention that the assortment of chemicals to which we are exposed on a daily basis increases the likelihood of health effects. The high prevalence of body burdens of these chemicals and simultaneous exposure to a number of substances, in conjunction with the fact that the highest concentrations have been demonstrated in the developing young, a sensitive subpopulation of society, indicate the need to decrease the exposure to these compounds.

Read the full study (free access) on NCBI PubMed, 2009 Jul 27.

What are you putting on your baby? Or on your genitals?

Sanitary pads and diapers contain higher phthalate contents than those in common commercial plastic products

2019 Study Highlights

  • Three VOCs and 4 phthalates were measured in commercial sanitary pads and diapers.
  • Air in the packages of sanitary pads and diapers contained as high as 5.9 ppb of VOCs.
  • Sanitary pads and diapers contained as high as 8,014.9 ppb of phthalates.
  • VOCs and phthalates contained in the commercial products considerably vary among the brands.

Abstract

Sanitary pads and diapers are made of synthetic plastic materials that can potentially be released while being used. This study measured the amounts of volatile organic compounds (VOCs) (methylene chloride, toluene, and xylene) and phthalates (DBP, DEHP, DEP, and BBP) contained in sanitary pads and diapers. In sanitary pads, 5,900- and 130-fold differences of VOC and phthalate concentrations were seen among the brands. In the diapers, 3- and 63-fold differences of VOC and phthalate concentrations were detected among the brands. VOC concentrations from the sanitary pads and diapers were similar to that of the residential air. However, phthalate concentrations of sanitary pads and diapers were significantly higher than those found in common commercial plastic products. As sanitary pads and diapers are in direct contact with external genitalia for an extended period, there is a probability that a considerable amount of VOCs or phthalates could be absorbed into the reproductive system.

 

Impact of endocrine disrupting chemicals exposure on fecundity as measured by time to pregnancy

A systematic review;, Environmental research, 2018 Dec

Abstract

BACKGROUND
Emerging scientific evidence suggests that exposure to environmental pollutants is associated with negative effects on fecundity as measured by time to pregnancy (TTP).

OBJECTIVES
To conduct a systematic review of the literature on the association between selected endocrine disrupting chemicals (EDCs), and fecundity as measured by TTP in humans. Compounds included in this review are: brominated flame retardants (BFRs) such as hexabromocyclododecane, tetrabromobiphenol A and polybrominated diphenyl ethers; organophosphates flame retardants (OPFRs); and phthalates.

METHODS
Scopus, MEDLINE via Ebscohost and EMBASE databases were searched for articles exploring the relationships between selected EDCs and fecundity as measured by time to pregnancy. We assessed the quality of included studies and evidence for causality was graded using the criteria developed by the World Cancer Research Fund.

RESULTS
14 studies of 191 full-text articles assessed for eligibility were included for qualitative synthesis. Five studies examined BFRs and 10 studies examined phthalates. Among the fourteen, one study assessed both BFRs and phthalates. There were no studies which investigated fecundity as measured by TTP on HBCD, TBBPA, or OPFRs. We recorded plausible fecundity outcomes as measured by TTP related to some of these EDCs. BFRs or phthalates increased TTP. However, results were inconsistent.

CONCLUSION
We recorded mostly weak associations between exposure to selected EDCs and fecundity. However, evidence was considered limited to conclude a causal relationship due to inconsistency of results. The health risks posed by these chemicals in exposed populations are only beginning to be recognized and prospective measurement of the environmental effects of the chemicals in large cohort studies are urgently needed to confirm these relationships and inform policies aimed at exposure prevention

Prenatal Exposure to Phthalate connected to ADHD in Children

Prenatal Phthalates, Maternal Thyroid Function, and Risk of Attention-Deficit Hyperactivity Disorder in the Norwegian Mother and Child Cohort

Introduction

There is growing concern that phthalate exposures, particularly during the prenatal period, may have an impact on child neurobehavioral development. Prenatal exposure to phthalates has been associated with both externalizing and internalizing  behaviors using validated behavioral screening instruments, as well as with deficits in executive function as measured by both parental report and performance-based assessments , although not all studies have found evidence of associations. Among the neurobehavioral domains identified in multiple studies are inattention , aggression, conduct problems, and emotional reactivity/regulation, as well as impairments in working memory. Sex differences in the associations of phthalates with neurobehavioral end points have often been noted, although some studies have found stronger associations among boys, whereas others have found stronger associations among girls. The constellation of phthalate-associated behaviors highlighted across studies has led many researchers to note overlap with symptoms of attention-deficit hyperactivity disorder (ADHD).

Despite the observed overlap in affected neurobehavioral domains, there is less consensus on the specific phthalate responsible for neurodisruptive effects, and no prior study has accounted for the correlation among phthalates by mutual adjustment. Some studies have reported significant associations with dibutyl phthalates and/or di-2-ethylhexyl phthalate (DEHP) ; others have highlighted butyl benzyl phthalate (BBzP). Moreover, as of now there have been no studies with biomarkers of exposure in the prenatal period and access to clinically confirmed neurobehavioral end points, such as ADHD diagnoses from a clinical provider. Rather, the bulk of the literature relies on parent-reported symptoms. Because the ages of the children examined have varied substantially across and within studies, relying solely on parental reports to identify nonnormative behavior may be problematic.

A number of mechanisms have been proposed to explain how phthalates may negatively affect brain development, although few have been thoroughly examined in humans or in animal models. One prominent concern is phthalate-induced maternal thyroid hormone disruption. Phthalates have been associated with changes in circulating thyroid hormone levels in adults and in pregnant women. The most consistent finding across studies has been an inverse association between metabolites of DEHP and thyroxine and/or free thyroxine. Maternal prenatal thyroid hormone is essential for fetal neurodevelopment, and clinically diagnosed thyroid hormone disorders (hyperthyroidism and hypothyroidism) in the perinatal period have been linked with ADHD in offspring. Additionally, both higher and lower levels of thyroid hormone concentrations, even within population reference ranges, have been associated with ADHD-like behaviors. Perinatal phthalate exposure has also been associated with preterm delivery, which is itself a risk factor for ADHD.

A true causal association of phthalate exposure with child neurodevelopment would have major public health significance. Phthalates are ubiquitous in consumer products, are components of many food processing and packaging materials, and can be found in both pharmaceuticals, and personal care products. Therefore, to address this critically important public health question, we undertook a prospective, nested case–control study in the Norwegian Mother and Child Study (MoBa) to examine the hypothesis that prenatal biomarkers of phthalate exposure are associated with clinical ADHD in offspring. We further considered whether any associations were mediated by maternal thyroid function or preterm delivery or were modified by child sex.

Objectives

We undertook an investigation into whether prenatal exposure to phthalates was associated with clinically confirmed ADHD in a population-based nested case–control study of the Norwegian Mother and Child Cohort (MoBa) between the years 2003 and 2008.

Methods

Phthalate metabolites were measured in maternal urine collected at midpregnancy. Cases of ADHD (n=297) were obtained through linkage between MoBa and the Norwegian National Patient Registry. A random sample of controls (n=553) from the MoBa population was obtained.

Results

In multivariable adjusted coexposure models, the sum of di-2-ethylhexyl phthalate metabolites (∑DEHP) was associated with a monotonically increasing risk of ADHD. Children of mothers in the highest quintile of ∑DEHP had almost three times the odds of an ADHD diagnosis as those in the lowest [OR=2.99 (95% CI: 1.47, 5.49)]. When ∑DEHP was modeled as a log-linear (natural log) term, for each log-unit increase in exposure, the odds of ADHD increased by 47% [OR=1.47 (95% CI: 1.09, 1.94)]. We detected no significant modification by sex or mediation by prenatal maternal thyroid function or by preterm delivery.

Conclusions

In this population-based case–control study of clinical ADHD, maternal urinary concentrations of DEHP were monotonically associated with increased risk of ADHD. Additional research is needed to evaluate potential mechanisms linking phthalates to ADHD.