Department of Rehabilitation, Warsaw Division of Physical Medicine, Military Medical Institute, Jan Kochanowski University, Kielce, Poland
Received date: December 28, 2016; Accepted date: March 15, 2017; Published date: March 20, 2017
Citation: Kulinski W (2017) Severe Nervous System Damage in Long-Term Professional Exposure to Phthalates. J Clin Toxicol 7:342. doi: 10.4172/2161-0495.1000342
Copyright: © 2017 Kuliński W. 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
This paper presents a case of a 37-year-old male patient who suffered from very severe nervous system damage with tetraparesis after having used a paint thinner containing diisononyl phthalate at work for more than ten years. Brain MRI revealed scattered focal lesions in both cerebral hemispheres, typical of cytotoxic oedema. A follow-up examination conducted after 2 years showed persistent lesions and more severe cortical atrophies. Decreased cognitive function and operating memory disturbances were also observed in the patient. His mental processes display features of sluggishness and lack flexibility. Clinical presentation of the patient indicates severe nervous system damage in long-term contact with phthalates.
Phthalates; Nervous system damage
In 2005 the European Parliament (Directive 2005/EC) banned manufacturing and distribution of toys and cosmetics for children containing certain phthalates. However, there are no legal regulations concerning the use of phthalates in products for adults. There is no obligation to list these substances among ingredients on the packaging. Consequently, consumers do not know whether a given product contains phthalates or not. These compounds are easily absorbed into the body and after a prolonged exposure may cause a number of health problems [6-10].
To present diagnostic difficulties and problems in treatment of a patient with nervous system damage in phthalate poisoning.
A 37-year-old male patient with tetraparesis and speech disturbances (aphasia), having scattered lesions of unknown aetiology in the central nervous system, was admitted to the Department of Rehabilitation of the Military Medical Institute in Warsaw in August 2011 to undergo rehabilitation.
The patient worked for 17 years as a steel fixer. He received engines equipment parts to repair. Before disassembling and grinding this equipment was cleaned by washing in liquid which contained 5% phthalates. He did not use protective gloves or face masks. He was doing these several times during the day for over 17 years. He worked alone at the position.
First manifestations of the disease were observed in November 2010 when speech disturbances and limb strength decreases appeared. At the time the patient was diagnosed and treated at the Department of Neurology and Department of Oncology of the Regional Hospital and then at the Nervous System Cancer Department at the Cancer Centre in Warsaw. Numerous lesions in both cerebral hemispheres were found in the patient during the stay. Stereotactic biopsy of suspicious brain lesion in the frontal lobe was performed. Brain biopsy demonstrated severe astroglial cells vascular response and perivascular lymphocytic infiltrates. The cancer cells were not detected.
As regards the aetiology, tests for bacteria, fungi, toxoplasmosis, toxocariasis, and cysticercosis gave negative results. Other diseases were excluded: vasculitis, sarcoidosis, granulomatosis with polyangiitis, and tuberculosis. Carotid and vertebral arteries were patent with smooth wall outlines and the blood flow was normal. Treatment with steroids resulted in very severe complications: sepsis, steroid-induced diabetes and respiratory failure in bilateral pneumonia, which required the use of a ventilator. The patient was treated for many months at various hospital departments.
On admission to the Department of Rehabilitation, 10 months after first manifestations of the disease appeared, the following was observed: moon face and muscle atrophies, especially in forearms, arms, and shins (typical of Cushing's syndrome). Neurological examination revealed abnormalities; the patient was oriented to time and person, had speech disturbances (aphasia), slight horizontal-rotational nystagmus when looking to the left, anisocoria (R>L), central paresis of nerve VII on the right, and slurred speech. He suffered from tetraparesis with decreased muscle tone in the upper limbs: the score of the left limb was 3 points and of the right limb-2 points on Lovett scale. As regards the lower limbs, there was abnormal flexion in the hip and knee joints as well as abnormal plantar flexion and extension of the feet. The score was 1 point on Lovett scale on both sides and there were weak reflexes in the triceps on the left. There were no other tendon and periosteal reflexes, no plantar reflexes, and Babinski's sign was observed on the right. The patient was immobilised and required help in the activities of daily living.
Accessory investigations included magnetic resonance imaging conducted on 21 March 2011 (Figure 1).
The scan revealed abnormal focal lesions in both cerebral hemispheres with intensified and coalescent lesions in the left frontal lobe. The lesions were hyperintense on T2-weighted and FLAIR images. Diffusion-weighted imaging showed that central parts of the lesions were hypointense while the oedema around the lesions was hyperintense, which is typical of cytotoxic oedema. There was a biopsy scar in the left frontal lobe.
Laboratory data reveal no significant changes, except for abnormalities observed in the period of severe complications.
Taking into consideration the history which indicates that the patient worked for more than ten years in equipment repair where he used a cleaning and maintenance fluid with which he came into direct contact through the skin and airway system for several hours every day, samples of the fluid used by the patient were tested. The laboratory test was conducted at the Department of Forensic Toxicology of the Institute of Forensic Research in Cracow. As a result of chemical and toxicological examination of the material received in the form of colourless liquid, the following substances were found: ethyl alcohol (concentration-95.7%) and compounds used as additives (so-called plasticisers) in the process of plastic manufacturing, mainly Diisononyl Phthalate (DINP).
This chemical substance is not classified as dangerous, according to Annex I to Directive 67/548/EEC.
In 2011 and 2012, during the stays at the Department of Rehabilitation of the Military Medical Institute, each stay lasting several weeks, the patient underwent comprehensive physical therapy and rehabilitation adjusted to his needs and abilities. It included low frequency magnetic field therapy, laser therapy, muscle electric stimulation, massage, individual rehabilitation, occupational therapy, and neurophysiological therapy. The aim of physical therapy was to achieve independence, active sitting, strengthening of the trunk and limb muscles, vertical positioning in a vertical stander, and improved cardiovascular and respiratory performance.
Speech disturbances affected mostly language and had the form of amnesic aphasia. According to the Goodglass and Kaplan scale score, intensity of the deficits was 3. Therapy concerned language functions and the improvement of communication skills.
A follow-up MRI scan of the head (Figures 2 and 3) revealed:
The examination conducted in three planes using SE and TSE sequences, T1-, T2-weighted and FLAIR images, and DWI+ADC as well as T1-weighted images with intravenous contrast administration revealed status post stereotactic biopsy in the left frontal area. Single hyperintense focal lesions of a vascular character were found in the white matter of both cerebral hemispheres on T2-weighted and FLAIR images. No new lesions were found. There were cortical atrophies.
Out-patient physical therapy and rehabilitation has been continued up to now. Between November 2010 and October 2015 the patient did not come into contact with phthalates.
The patient's condition was assessed by a follow-up examination on 7th October 2013.
The patient was verbally responsive and oriented, there were no meningeal signs, and there was slight facial nerve damage. The patient moved with support on both sides. He spoke more slowly and his cognitive functions were visibly slower. The functions of visual analyser were partially disturbed. Muscle strength disturbances were observed. Limb movements were slower and the spatial movement organisation was disturbed. Disturbances of working (short-time) and visual memory were visible and results of tests assessing semantic memory were low. The patient's mental processes displayed features of sluggishness and lacked flexibility. When attempting to walk without the support, the patient was very unsure and suffered from dizziness.
The patient's condition was assessed by a follow-up examination on 15th October 2015
The patient was verbally responsive and oriented, there were no meningeal signs, and there was slight facial nerve damage. He spoke more slowly and his cognitive functions were visibly slower. The functions of visual analyser were partially disturbed. Muscle strength disturbances were observed. Limb movements were slower and the spatial movement organisation was disturbed. Disturbances of working (short-time) and visual memory were visible and results of tests assessing semantic memory were low. The patient's mental processes displayed features of sluggishness and lacked flexibility.
The abnormalities identified during physical examination and history-taking are connected with prolonged toxic central nervous system damage caused by phthalates contained in the fluid which the patient used for many years in his professional work. However, phthalates are present all around us. They are used in the production of creams, body lotions, moisturising lotions, nail polish, hairspray, and perfumes. Thanks to them the product effectively adheres to the body, remaining on the skin over a longer period of time, and its scent is long-lasting. Phthalates prevent stiffness and peeling off of the product and enhance its flexibility, transparency, and durability.
These compounds penetrate the body through the oral cavity, airway system, and skin.
A group of scientists from Rochester conducted studies which indicate that these chemicals may be responsible for disturbances in the development of sexual organs in boys as well as for reducing pregnancy duration. Studies conducted by Prof. Sharpe from Edinburgh confirm that phthalates may have a negative influence on the production of the male hormone testosterone .
Many studies have associated exposure to chemicals with neurological impairments (cognitive, motor and sensory impairment) and/or neurodegenerative disease. The increase in many diseases including neurological disorders, have been attributed to greater exposure to exogenous toxic chemicals. It’s reported that exists connection between exposure to lipophilic chemicals (including phthalates) and neurological impairment, neurodevelopmental disorders and neurodegenerative diseases [13-16]. It’s also well known that lipophilc chemicals (inkl. phthalates) if absorbed can remain in the body for days or weeks or longer  and can penetrate the blod-brain barrier .
The observations described in this paper, concerning a 37-year-old male patient, show that during almost 3 years following the occurrence of first manifestations of the disease, after preventing the patient from having further contact with phthalates and despite complications having such dramatic course, it was possible to improve the health status of the patient. The patient moves with difficulty, but unassisted; however, central nervous system damage is so extensive that examinations indicate abnormalities, mental processes lack flexibility, and MRI of the brain reveals cortical atrophies.
Phthalates may cause severe nervous system damage.
It is in the interests of people all over the world to act on the urgent need to start interdisciplinary studies concerning the influence of phthalates on the human body and promote healthy behaviour in this respect.