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Effects and mechanisms of phthalates’ action on neurological processes and neural health: a literature review

Abstract

During the period of mass industrial production of plastic products, the quality of human health has decreased significantly, especially in children’s neurodevelopmental disorders. Phthalates are endocrine-disrupting chemicals that can induce neurological disorders. This review aims to compile evidence concerning the associations between neurological disorders, such as attention-deficit/hyperactivity disorder, autism spectrum disorder, decreased masculine behavior, and phthalate exposure. Phthalates dysregulate the hypothalamic–pituitary–gonadal, adrenal, and thyroid axis, which is crucial for the neurodevelopmental process. Phthalates interfere with nuclear receptors in various neural structures involved in controlling brain functions and the onset of neurological disorders at the intracellular level. It is critical to increase the current knowledge concerning phthalates’ toxicity mechanism to comprehend their harmful effect on human health.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

ADHD:

Attention deficit hyperactivity disorder

ASD:

Autism spectrum disorders

BBzP:

Benzylbutyl phthalate

CRH:

Corticotropin-releasing hormone

CBG:

Corticosteroid-binding globulin

DBP:

Dibutyl phthalate

DCHP:

Dicyclohexyl phthalate

DEHP:

Di(2-ethylhexyl) phthalate

DEP:

Diethyl phthalate

DiBP:

Di-iso-butyl phthalate

DiDP:

Di-iso-decyl phthalate

DiNP:

Di-iso-nonyl phthalate

DMP:

Dimethyl phthalate

DnBP:

Di-n-butyl phthalate

DnOP:

Di-n-octyl phthalate

ED:

Endocrine-disrupting chemical

ER:

Estrogen receptor

FSH:

Follicle-stimulating hormone

FT3:

Free triiodothyronine

FT4:

Free thyroxine

GnRH:

Gonadotropin-releasing hormone

GR:

Glucocorticoid receptor

HMWP:

High-molecular-weight phthalate

HPA:

Hypothalamic–pituitary–adrenal axis

HPG:

Hypothalamic–pituitary–gonadal axis

HPT:

Hypothalamic–pituitary–thyroid axis

LH:

Luteinizing hormone

LMWP:

Low molecular weight phthalates

MBP:

Monobutyl phthalate

MBzP:

Monobenzyl phthalate

MCPP:

Mono-(3-carboxypropyl) phthalate

MDI:

Mental developmental index

MEHHP:

Mono(2-ethyl-5-hydroxyhexyl) phthalate

MEHP:

Mono-(2-ethylhexyl) phthalate

MEP:

Monoethyl phthalate

MECPP:

Mono-(2-ethyl-5-carboxypentyl) phthalate

MEOHP:

Mono(2-ethyl-5-oxohexyl) phthalate

MiBP:

Mono-iso-butyl phthalate

MnBP:

Mono-n-butyl phthalate

NIS:

Natrium iodide symporter

NR:

Nuclear receptor

PDI:

Psychomotor developmental index

SHBG:

Sex hormone-binding globulin

T3:

Triiodothyronine

T4:

Thyroxine

TT3:

Total triiodothyronine

TT4:

Total thyroxine

TBG:

Thyroxine-binding globulin

TPO:

Thyroid peroxidase

TR:

Thyroid receptor

TRH:

Thyroid-releasing hormone

TSH:

Thyroid-stimulating hormone

TTR:

Transthyretin

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Acknowledgements

This study was supported by the project of the Ministry of Health of SR [2016/9-UKFN-1].

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Hlisníková, H., Petrovičová, I., Kolena, B. et al. Effects and mechanisms of phthalates’ action on neurological processes and neural health: a literature review. Pharmacol. Rep 73, 386–404 (2021). https://doi.org/10.1007/s43440-021-00215-5

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Keywords

  • Phthalate
  • Endocrine disruptor
  • Nervous system
  • Hormone
  • Nuclear receptor