The Neuropsychological Toxicology Unit  
Sarah established the Neuropsychological Toxicology Unit (NTU) in 2004, which was initially based in the Research Department of Clinical, Educational and Health Psychology, University College London. It is the only unit of its kind in the UK . The NTU studies the impact of toxins on psychological function. It promotes understanding and recognition of the ways in which toxic substances affect human behaviour, cognition and emotion. The NTU currently undertakes clinical work and multi-disciplinary research.  

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Agriculture

Retrospective, cross-sectional study of sheep farmers exposed to sheep dip In June 2000 the UK Department of Environment Food and Rural Affairs, Health & Safety Executive and the Department of Health agreed to fund a programme of research to address a number of strategic research questions which had been identified for further study by the Committee on Toxicity of Chemicals in Food. UK scientists were invited to submit proposals by a process of competitive tender. Proposals were peer-reviewed by independent scientists and Sarah Mackenzie Ross was successful in winning a major research award from DEFRA (circa £700,000) and was the Principal Investigator/Grant Holder for DEFRA project VM02302. The study began in August 2004 and ended in 2008.

Study Aims
The purpose of the study was to determine whether low level exposure to organophosphates causes disabling neurological or psychiatric disease in a small sub-group of exposed persons?

Previous studies have examined farm workers who are fit enough to be in employment and have not considered the possibility that there may be a group of people who have reduced their workload or retired on ill health grounds. Failure to include these individuals in research studies may mean that the risk of developing ill health following exposure to hazardous chemicals has been underestimated.

Study participants 160 working farmers and farmers who have retired on ill health grounds (RIHG), who have a history of exposure to sheep dip, were examined. 80 rural police workers (working and retired on IHG), who do not have a history of exposure to organophosphate pesticides were recruited to act as a comparison group. Study participants were recruited from the south west and north of England and all underwent neuropsychological and adult mental health assessment which involved tests of memory and problem-solving ability and an interview about work history, emotional state and physical health. Participants were examined in their own homes.

Image courtesy of www.rsc.org

The study explored factors which may render some individuals more vulnerable to the effects of organophosphates than others such as exposure history, past medical and psychiatric history and biological factors, such as PON1 status. PON1 is an enzyme which plays a major role in the breakdown and detoxification of pesticides. Professor Clem Furlong, Professor of Genome Sciences and Medicine, University of Washington, undertook this analysis.

International collaboration - Professor Clem Furlong
Paraoxonase (PON1) is a liver and plasma enzyme that metabolizes oxidized lipids and plays a major role in the metabolism and detoxification of insecticides.

Costa and Furlong have determined that a polymorphism of position 192 in the coding sequence of the gene significantly affects the catalytic efficiency of PON1 and that polymorphisms in the noncoding promoter region of the gene impact plasma levels of PON1 expression. There are large interindividual differences in the amount of PON1 protein in sera that are stable over time. Costa & Furlong stress the importance of measuring PON1 status (polymorphisms and PON1 levels) to determine individual susceptibility to environmentally-induced disease.

PON1 polymorphisms play an important role in determining susceptibility to OP toxicity. Over the past 15 years, a series of studies in rodents has demonstrated the relevance of PON1 in modulating OP toxicity. More recently, Cherry et al (2002) and Mackness et al (2003) found that farmers who report ill health following exposure to sheep dip have a higher proportion of the PON1-192 polymorphism than controls.

Given these recent findings, measurement of PON1 status is an essential component of any research which seeks to explore factors that may render some individuals more vulnerable to the effects of OPs than others.

Please click here for more details of Professor Furlong's work.

Progress to date
This study was completed in 2008 and a report was sent to DEFRA who arranged for it to be independently peer reviewed. The full report is now available on the DEFRA website.

In addition, the study findings have been independently peer reviewed and accepted for publication by the scientific journal ‘Neurotoxicology and Teratology'. The paper has been published online at http://dx.doi.org/10.1016/j.ntt.2010.03.04

Doctoral Thesis
Between 1998 and 2002 Sarah Mackenzie Ross examined a number of agricultural workers who complained of chronic ill health following exposure to organophosphate pesticides (sheep dip in particular). All of the agricultural workers were involved in litigation. A range of cognitive and emotional problems were identified in agricultural workers. Exposure history varied enormously amongst individuals who seemed to have similar jobs and many appeared to have a history of undiagnosed acute poisoning. Sarah Mackenzie Ross was awarded a Doctoral Degree from the University of Edinburgh for this work. A copy of her Doctoral Thesis is held in the University Library.

Click here for a summary of these findings which were also peer reviewed and published in the following scientific journal:

S J Mackenzie Ross, J S Clark , V Harrison, K M Abraham (2007). Cognitive impairment following exposure to organophosphate pesticides: A pilot study. Journal of Occupational Health & Safety: Australia & New Zealand 23 (2): 133-142

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Aviation

Between 2005 and 2008 Sarah Mackenzie Ross examined a number of commercial airline pilots who complain of ill health following reported exposure to engine oil fumes.

S J Mackenzie Ross (2008). Cognitive function following exposure to contaminated air on commercial aircraft. A case series of 27 airline pilots seen for clinical purposes. Journal of Nutritional & Environmental Medicine, 17 (2): 111-126 .

S J Mackenzie Ross, A C Harper, J Burdon (2006). Ill health following reported exposure to contaminated air on commercial aircraft: psychosomatic disorder or neurological injury? Journal of Occupational Health & Safety: Australia & New Zealand 22 (6): 521-528

Sarah Mackenzie Ross collated the results of neuropsychological testing from 27 pilots seen between 2005 and 2006 and wrote a report for the UK Department of Transport and a UK Government Scientific Advisory Committee, called the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT)

Click here to see a summary of the report submitted to COT. Click here to see an expanded summary of her findings.

Retrospective Study of 1500 pilots 2007-2009 The NTU undertook a survey of 15OO UK commercial airline pilots in 2007 and 2008. The Independent Pilot Association is assisted the NTU with this work, by contacting their members and inviting them to take part in this research. Study Aims The purpose of the study was to determine the prevalence and nature of ill health in commercial airline pilots and any association that might exist with work history and/or exposure to engine oil fumes.

Progress to date
This work has now been completed and the results are being written up for publication in a scientific journal.

Future Research Plans - Large Scale international study of pilots
Sarah Mackenzie Ross is assembling a multi-disciplinary research team (comprising epidemiology, medicine, psychology and brain imaging) to undertake a large scale, international cross sectional study of health and neuropsychological functioning in commercial airline pilots.

The COT committee recommended that the Department of Transport (DfT) commission a cross sectional, international neuropsychological study. We are waiting to hear if the DfT will make funds available for this work.

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Liver Failure Unit

The NTU undertook a research project in 2006/2007 looking at the impact of liver disease on cognitive function and mood. The NTU has been collaborating with the Liver Failure Group at the Institute of Hepatology at UCL.

Dr Rajiv Jalan and his team asked us to undertake a study looking at the impact of early stage cirrhosis on cognitive functioning and quality of life.

A Clinical Psychologist in Training, carried out the research and submitted these findings in June 2007 as part fulfilment of a doctoral degree in clinical psychology.

Click here for further information about the Liver Failure Group

Forthcoming papers

Cognitive function in patients with early stages of hepatic encephalopathy

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