quarta-feira, 12 de outubro de 2011

Exposure to Aircraft Bleed-air Contaminants Among Airline Workers - Health Care



PORTUGUÊS  ENGLISH (scroll down)

Boeing Settles Toxic Cabin air Case

Boeing concorda com causa judicial sobre toxicidade de ar de cabine

Gerenciamento de exposição aos contaminantes de ar de sangria de aeronaves entre trabalhadores de empresa aérea

Um guia para provedores de serviço de saúde

Robert Harrison, MD, MPH1
Judith Murawski, MSc, CIH2
Eileen McNeely, PhD3
Judie Guerriero, RN, MPH1
Donald Milton, MD, DrPh4

1University of California, San Francisco
  2Association of Flight Attendants
   3Harvard School of Public Health
    4University of Massachusetts Lowell

Financiamento para este projeto foi fornecido pela Administração Federal de Aviação (FAA)
Gabinete de Medicina Aerospacial e é parte de um projeto colaborativo entre o Consórcio Ocupacional de Pesquisa de Saúde na Aviação (OHRCA) e o Centro de Excelência de pesquisa de Ambiente de Cabine de Aeronaves de Linhas Aéreas (ACER)/ Embora a agência FAA de Medicina Aerospacial tenha patrocinado o projeto, ela nem endossa nem rejeita as descobertas desta pesquisa.

O ar externo fornecido para a cabine de passageiros e pilotos em avião comercial ("ar de sangria") pode  às vezes estar contaminado com bio-óleo* do motor e/ou fluido hidráulico. Como um resultado desta contaminação, trabalhadores em empresa aérea e passageiros podem desenvolver efeitos crônicos e/ou agudos de saúde e buscar atenção de provedores de serviços de saúde.
* bio-óleo [pyrolized oil]
Óleo convertido a partir de biomassa sólida para um bio-óleo líquido.
A produção de bio-óleo a partir de biomassa é baseada no processo rápido de pirólise, a qual é composta de cinco áreas maiores de processamento: secagem e manuseio de alimentação, pirólise, combustão de carvão, recuperação do produto e geração de vapor. A figura abaixo é um diagrama de bloco do fluxo de um processo rápido de pirólise.
Na seção de manuseio de alimentação, a biomassa é reduzida em tamanho para menos de 1 a 5 mm e secada para 5 a 10% de umidade. Ela é depois enviada para pirólise onde ela é aquecida para 400 a 500°C em uma atmosfera deficiente de Oxigênio para degradar a biomassa dentro de uma mistura de gases, bio-óleos e carvão. O carvão é removido usando ciclones de alta energia e é queimado para alimentar a reação de pirólise. Para maximizar o rendimento de bio-óleos, a reação é rapidamente  apagada através de intercâmbio de calor ou injeção direta de líquido (por exemplo: água, bio-óleos reciclados). Os bio-óleos estão presentes no vapor de gas como aerosóis e requerem esfregadores e/o precipitadores eletrostáticos molhados para captura eficiente. Após estarem limpos, alguns dos gases limpos da pirólise são reciclados para fluidizar o leito e os gases remanescentes são queimados pelo processo de aquecimento. Onde viável, calor é recuperado dos gases de pirólise para gerar vapor para produção de eletricidade.


Este documento fornece informação acerca de efeitos de saúde que podem resultar após exposição a contaminantes de ar de sangria de aeronave, e faz recomendações a respeito de métodos de tratamento. A informação neste documento é grandemente baseada em informação que foi publicada na literatura médica e científica, e também conta com experiência clínica de um dos autores (Robert Harrison, MD, MPH) que diagnosticou e tratou trabalhadores de empresa de linhas aéreas com exposição ao ar de sangria contaminado. Uma discussão mais detalhada sobre a toxidade de aditivos de óleo de tricressylphosphate do motor pode ser encontrada no Anexo 1. Para mais informação, links da web para fontes adicionais e referências detalhadas estão fornecidas no final do docmento.

Durante o voo, ar comprimido em alta temperatura é sangrado dos motores e, após ser resfriado, é fornecido para a cabine [de passageiros] e [de pilotos]. No solo, aviões de linhas aéreas frequentemente contam com um compressor menor localizado na cauda da aeronave chamado Unidade Auxiliar de Força (APU).

Bio-óleo do motor ou fluido hidraulico podem contaminar o ar nestes compressores como um resultado de falhas mecânicas, irregularidades de manutenção, e projetos defeituosos (ASHRAE, 2006; van Netten, 2000; BAe Systems 2000) (Tabela 1). O mais recente estudo deste assunto no Conselho Nacional de Pesquisa (NRC) concluiu que, sob certas condições de falhas, tais tóxicos como bio-óleos do motor e fluidos hidráulicos podem vazar para dentro da cabine da aeronave e para sistemas de suprimento de ar da cabine dos pilotos, e que estes tóxicos podem estar associados com efeitos de saúde (NRC, 2002). O relatório do NRC caracterizou a necessidade de definir a toxicidade destes contaminantes em voo e investigar a relação entre exposição e doença como uma alta prioridade.

Tabela 1. Mecanismo para Contaminação de Air de Sangria de Aeronave

Tipo de Falhas
Exemplo
Falhas Mecânicas
Selos de óleo que também separam o “lado molhado” do ar do compressor de ar, do “lado seco”, pode vazar ou falhar
Irregularidades de Manutenção
Trabalhadores podem  encher demais os reservatórios de óleo/fluido hidráulico ou espirrar óleo/fluido hidráulico quando abastecendo o reservatório
Projetos Defeituosos
Alguns selos de óleo podem ser menos efetivos, operações transientes e alta temperatura do motor, a tomada de entrada de suprimento de ar pode estar no fluxo de fluido hidráulico que goteja através das portas de alívio de resíduos e é carregada em direção a cauda da aeronave

Os agentes tóxicos em voo para os quais passageiros e tripulantes da aeronave podem ser expostos quando o ar de suprimento estiver contaminado com bio-óleo do motor/fluido hidráulico formam uma mistura complexa, incluindo de 1 a 5% de tricresylphosphates (TCPs) (adicionado aos óleos do motor da aeronave e pelo menos um fluido hidráulico) e N-phenil-L-naphthylamine (PAN) (Bobb, 2003). Se a temperatura do sistema de suprimento de ar estiver alta o suficiente, então bio-óleo/ fluido hidráulico pode também gerar monóxido de Carbono (CO) (van Netten, 2000).


Toxicidade de Esteres Organofosfatos

Tricresil Fosfatos (TCP)

Muitos organofosfatos exercem suas toxicidades agudas pela supressão da acetilcolinesterase, a qual pode causar falha respiratória devido paralisação neurosmucular.
Todavia, organosfosfatos tais como TCP são também capazes de induzir uma condição retardada de neuropatia neurodegenerativa conhecida como neuropatia organofosfato induzida retardada (OPIDN), a qual afeta ambos os nervos centrais e periferais de pássaros e mamíferos [9].

A relação entre a estrutura química de muitos fosfatos triaril puro e potêncialidade em causar OPIDN tem sido extensivamente estudada e as atividades relativas neurotóxicas destas substâncias são bem conhecidas. Tem sido reconhecido por pelo menos 40 anos que substituintes alcil nas posições orto dos anéis aromáticos são responsáveis pela atividade neurotóxica de TCP. Material sintetizado de somente m-cresol e p-cresol não causa OPIDN [4], mas a possibilidade de toxicidade crônica desta mistura isomérica não pode ser rejeitada.

De todos os 10 possíveis isômeros TCP, os isômeros mono-o-crescil são considerados os mais tóxicos; 10 vezes mais tóxicos que os isômeros tri-o-cresil e 2 vezes mais tóxicos que os isômeros di-o.
Portanto a toxicidade de TCP é relacionada com o conteúdo isômero o-cresil com os isômeros m- e p-cresil tendo baixa toxidade [10].
Ésteres Triacil Fosfatos

Fluidos hidráulicos de aviação são conhecidos por conter ésteres fosfatos como retardadores de fogo [11].
Eles incluem trifenil fosfato e triacil fosfatos [12]. Há critérios profissionais  Australianos de exposição (TWA) para trifenil fosfato (3 mg/m3) e tributil fosfato (2,2 mg/m3), mas não para tris(2-etilhexil) fosfato e triisobutil fosfato [13]. Triisobutil fosfato é considerado ser de baixa toxicidade, não mostrando sinais de neurotoxicidade em altos níveis de dosagem quando dado oralmente para frangos.
Todavia, ele está listado pela Comissão Alemã para Investigação de Riscos no Local de Trabalho (MAKKommission) como uma substância sensível à pele baseada em exposição da derme em coelhos [14, 15].

Embora, não tenha havido relatórios de sensibilidade à pele humana associados à fabricação e manuseio da substância [14]. Similarmente, tris(2-etilhexil) fosfato é considerado ser de baixa toxicidade e não sensível à pele [16]. É também usado como um plastificador [selante] retardante de fogo para fiação PVC automotiva [17].

Toxicidade de Aditivos Aminas

Como previamente relatado óleos de motores à jato em aeronave ADF contêm amina anti-oxidantes [18] e tem havido algumas considerações expressadas sobre os efeitos potenciais de saúde destas substâncias [1, 3]. Fenil-a-naftalamina (PAN) e a substância isomérica, N-fenil-b-naftalamina, tem sido encontradas por produzir um aumento na incidência de cânceres de pulmão e rins segundo administração subcutânea de ratos. Uma alta incidência de várias formas de câncer foi também encontrada entre trabalhadores expostos a óleo anti-ferrugem contendo PAN [19].

ENGLISH

MANAGEMENT OF EXPOSURE TO AIRCRAFT BLEED-AIR

CONTAMINANTS AMONG AIRLINE WORKERS

A GUIDE FOR HEALTH CARE PROVIDERS

Robert Harrison, MD, MPH1
Judith Murawski, MSc, CIH2
Eileen McNeely, PhD3
Judie Guerriero, RN, MPH1
Donald Milton, MD, DrPh4

1University of California, San Francisco
 2Association of Flight Attendants
  3Harvard School of Public Health
   4University of Massachusetts Lowell

Funding for this project has been provided by the Federal Aviation Administration (FAA)
Office of Aerospace Medicine and is part of a collaborative project between the Occupational Health Research Consortium in Aviation (OHRCA) and the Airliner Cabin Environment research (ACER) Center of Excellence. Although the FAA Office of erospace Medicine has sponsored the project, it neither endorses nor rejects the findings of this research.

The outside air supplied to the cabin/flight deck on commercial aircraft ("bleed air") may
sometimes be contaminated with pyrolyzed engine oil and/or hydraulic fluid. As a result
of this contamination, airline workers and passengers may develop acute and/or chronic
health effects and seek attention from health care providers. This document provides
information about the health effects that may result after exposure to aircraft bleed air
contaminants, and makes recommendations regarding treatment methods. The
information in this document is largely based on information that has been published in
the medical and scientific literature, and also relies on the clinical experience of one of
the authors (Robert Harrison, MD, MPH) who has diagnosed and treated airline workers
with contaminated bleed air exposure. A more detailed discussion on the toxicity of
tricresylphosphate engine oil additives can be found in Attachment 1. For more
information, web links to additional resources and detailed references are provided at
the end of the document.

A EXPOSURE TO PYROLYZED ENGINE OILS AND HYDRAULIC FLUIDS

During flight, high-temperature compressed air is bled off the engines and, after being
cooled, is supplied to the cabin and flight deck. On the ground, airlines often rely on a
smaller compressor located in the aircraft tail called the auxiliary power unit (APU).
Pyrolyzed engine oil or hydraulic fluid may contaminate the air in these compressors as
a result of mechanical failures, maintenance irregularities, and faulty designs (ASHRAE,
2006; van Netten, 2000; BAe Systems 2000) (Table 1). The most recent National
Research Council (NRC) study of this subject concluded that, under certain failure
conditions, toxicants such as pyrolyzed engine oils and hydraulic fluids may leak into the
aircraft cabin and flight deck air supply systems, and that these toxicants may be
associated with health effects (NRC, 2002). The NRC report characterized the need to
define the toxicity of these airborne contaminants and investigate the relationship
between exposure and reported ill health as a high priority.

 
The airborne toxicants to which aircraft crewmembers and passengers may be exposed
when the air supply is contaminated with pyrolyzed engine oil/hydraulic fluid form a
complex mixture, including 1-5% tricresylphosphates (TCPs) (added to aircraft engine
oils and at least one hydraulic fluid) and N-phenyl-L-naphthylamine (PAN) (Bobb, 2003).
If the air supply system temperature is high enough, then the pyrolyzed engine
oil/hydraulic fluid may also generate carbon monoxide (CO) (van Netten, 2000).

Toxicity of Organophosphate Esters

Tricresyl Phosphates

Most organophosphates exert their acute toxicity by the suppression of acetylcholinesterase, which can cause respiratory failure due to neuromuscular block.

However, organophosphates such as TCP are also able to induce a delayed neurodegenerative condition known as organophosphate-induced delayed neuropathy
(OPIDN), which affects both the central and peripheral nerves of birds and mammals [9].

The relationship between the chemical structure of many pure triaryl phosphates and
potency in causing OPIDN has been extensively studied and the relative neurotoxic
activities of these compounds are well known. It has been recognised for at least forty years that alkyl substituents at the ortho positions of the aromatic rings are responsible for
the neurotoxic activity of TCP. Material synthesised from only m–cresol and p-cresol does not cause OPIDN [4] but the possibility of chronic toxicity of this isomeric mix cannot be dismissed.

Of all the 10 possible TCP isomers the mono-o-cresyl isomers are regarded as the most
toxic; 10 times more toxic than the tri-o-cresyl isomers and 2 times more toxic than the di-o isomers.

Hence the toxicity of TCP is related to the o-cresyl isomer content with the m- and p-cresyl isomers having low toxicity [10].

Trialkyl Phosphate Esters

Aviation hydraulic fluids are known to contain phosphate esters as fire retardants [11].
They include triphenyl phosphate and trialkyl phosphates [12]. There are Australian
occupational exposure standards (TWA) for triphenyl phosphate (3 mg/m3 ) and tributyl
phosphate (2.2 mg/m 3 ) but not for tris(2-ethylhexyl) phosphate and triisobutyl phosphate
[13]. Triisobutyl phosphate is considered to be of low toxicity, showing no signs of
neurotoxicity at high dose levels when given orally to chickens. Nevertheless, it is listed by
the German Commission for the Investigation of Hazards in the Workplace (MAKKommission)
as a skin sensitising substance based on dermal exposure to rabbits [14,15].

However, there have been no reports of human skin sensitisation associated with the
manufacture and handling of the compound [14]. Similarly, tris(2-ethylhexyl) phosphate is
considered to be of low toxicity and not skin sensitising [16]. It is also used as a fire
retardant plasticiser for automotive PVC wiring [17].

Toxicity of Amine Additives

As previously reported jet engine oils used in the ADF aircraft contain amine anti-oxidants
[18] and there has been some concern expressed over the potential health effects of these
compounds [1,3]. Phenyl-α-naphthylamine (PAN) and the isomeric compound, N-phenyl-
β-naphthylamine, have been found to produce an increase in the incidence of lung and
kidney cancers following subcutaneous administration to mice. A high incidence of
various forms of cancer was also found amongst workers exposed to antirust oil containing PAN [19].

Scrap from AVweb

REFERENCES
1. Senate Rural and Regional Affairs and Transport References Committee,(1999) Report “Air Safety and Cabin Air Quality in the BAe 146 Aircraft”.
2. House of Lords (UK), (2000) Select Committee on Science and Technology, Air Travel and Health.
3. Winder, C and Balouet, J-C. (2002) “The toxicity of commercial jet oils” Environ. Res. A, 89, 146-164.
4. Mackerer, C.R., Barth, M.L., Krueger, A.J., Chawla, B. and Roy, T.A., (1999)
“Comparison of Neurotoxic Effects and Potential Risks from Oral Administration or Ingestion of Tricresyl Phosphate and Jet Engine Oil containing TricresylPhosphate”, Journal of Toxicology and Environmental Health, Part A, 56, 293.
5. Singh, B. (2004) Institute of Aviation Medicine, Royal Australian Air Force, VMED 1856/1/3/1/MED Pt 1 (6).
6. Singh, B. (2004) Institute of Aviation Medicine, Royal Australian Air Force, Private Communications.
7. Kelso, A.G., Charlesworth, J.M. and McVea, G.G. (1988) “Contamination of Environmental Control Systems in Hercules Aircraft”, DSTO Report , MRL-R-1116.
8. SIMTARS (2002) “Smoke in F-111C & G Model Aircraft Cockpits, Preliminary Investigations”.
9. Fowler, M.J., Flaskos, J., McLean, W.G. and Hargreaves, A. J. (2001) “Effects of Neuropathic and Non-neuropathic Isomers of Tricresyl Phosphate and their Microsomal Activation on the Production of Axon-like Processes by Differentiating Mouse N2a Neuroblastoma Cells”, Journal of Neurochemistry, 76, (3), 671.
10. Henschler, D. (1958) “Die Trikresylphosphatvergiftung”, Klinische Wochenschrift, 36,
663.
11. US Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry (1977) “Toxicological Profile for Hydraulic Fluids.”
12. Healy C.E., Nair RS, Ribelin W.E. and Bechtel C.L. (1992) “Subchronic rat inhalation study with Skydrol 500B-4 fire-resistant hydraulic fluid.” Am Ind Hyg Assoc J. 53(3) 175-80.
13. National Occupational Health and Safety Commission http://www.worksafe.gov.au
DSTO-RR-030315
14. Berufsgenossenschaft der chemischen industrie, (2000) Toxicological Evaluation, No. 112 “Triisobutyl phosphate” CAS No 126-71-6.
15. Jenseit W., Bunke D., Rheinberger U., Kalberlah, Zerrin A. and Moll S. (2004) “Research, development statistical and analytical work to develop appropriate environmental indicators related to chemicals”, Interim report, July, Institute forApplied Ecology, Germany
16. van Esch G.J. (2000) Environmental Health Criteria 218 “Flame retardants: tris(2-butoxyethyl) phosphate, tris(2-ethylhexyl)phosphate and tetrakis(hydroxymethyl)phosphonium salts”, World Heath Organisation, Geneva.
17. Plasticisers Information Centre , www.plasticisers.org
18. Kibby J., Hanhela P.J., DeNola G and Mazurek W. (2005) “Analysis of Jet Engine Oils” DSTO Report DSTO-RR-0292.
19. Wang H-W., Wang D. and Dzeng R.W. (1984) “Carcinogenicity of N-phenyl-1 naphthylamine and N-phenyl-2-naphthylamine in rat.” Cancer Research 44 (7) 3098-3100.
20. Kristensen, S. “Mobil Jet Oil II – Overview of Available Scientific Background Information”. Submission No. 12 of Reference 1 (NICNAS).

REFERENCES
Hanhela, PJ; Kibby, J; DeNola, G; et al (2005) "Organophosphate and amine contamination of cockpit air on the Hawk, F-111, and Hercules C-130 aircraft" Australian Government Department of Defense, DSTO-RR-0303.

Henschler, D (1958) "Tricresyl phosphate poisoning. Experimental clarification of problems of etiology and pathogenesis" (Die Trikresylphosphatvergiftung Experimentelle Klarung von Problemen der Atiologie und Pathogenese) Klinische Wochenschrift, Vol. 26(14): 663-674.

Jamal, GA; Hansen, S; Julu, POO (2002) "Low level exposures to organophosphorus esters may cause neurotoxicity" Toxicol, 181-182: 23-33.

Mackerer, CR; Barth, ML; Krueger, AJ; et al (1999) "Comparison of neurotoxic effects and potential risks from oral administration and ingestion of tricresyl phosphate and jet engine containing tricresyl phosphate." J Tox Environ Health, Part A, 56: 293-328 NRC (2002) “The Airliner Cabin Environment and the Health of Passengers and Crew” Committee on Air Quality in Passenger Cabins of Commercial Aircraft. Board of Environmental Studies and Toxicology, Division of Earth and Life Sciences. US National Research Council, National Academy Press, Washington DC.

PCA (2000) "Air Safety and Cabin Air Quality in the BAe146 Aircraft." Parliament of the
Commonwealth of Australia, Prepared by the Senate Rural and Regional Affairs and
Transport Legislation Committee. Printed by the Senate Printing Unit, Department of the
Senate, Parliament House, Canberra, Australia.

SAE (1997) Aerospace Information Report 1539: "Environmental Control System Contamination." Rev. A. First issued Jan 1981; revised Oct 1997. Society of Automotive
Engineers International, Warrendale, PA.

SHK (2001) Board of Accident Investigation Report RL 2001: 41e "Incident onboard
aircraft SE-DRE during flight between Stockholm and Malmo, M country, Sweden, on 12
November 1999." Statens haverikommission, Stockholm, Sweden.

Singh, B (2004) “Inflight smoke and fumes” Aviation Safety Spotlight, 3:10-13.

Spengler, JS; Ludwig, S; Weker RA (2004) "Ozone exposures during trans-continental and trans-Pacific flights" Indoor Air (14 Suppl) 7:67-73.

van Netten, C and Leung, V (2001) “Hydraulic fluid and jet engine oil: pyrolysis and
aircraft air quality.” Arch Environ Health, Vol 56(2): 181-186

ATTACHMENT 1

TOXICITY OF TRICRESYLPHOSPHATE ENGINE OIL ADDITIVES

Tricreslyphosphates (TCPs) are added to most synthetic jet engine oils and at least one
hydraulic fluid1 primarily because of their anti-wear properties. According to a sample of
Material Safety Data Sheets of commonly used products2, the total concentration of TCPs varies between 1 and 5%.

The inhalation toxicity of pyrolyzed and aerosolized aircraft engine oil during commercial
airline flights is a subject that has received increasing attention over the past 10 years, not only in the US (NRC, 2002; SAE, 1997), but internationally (SHK, 2001; PCA, 2000).

The TCP additives are by no means the only toxic component of these oils, but it is important for HCPs to understand the inhalation toxicity of TCPs because it has been a
source of misunderstanding and debate. The levels or nature of airborne TCPs during an
air supply contamination event have not been characterized on commercial aircraft, although a recent study on military aircraft identified total TCP levels between 0.5 and 49
ug/m3 (Hanhela, 2005). Interestingly, TCP concentrations did not correlate with visible
smoke/fume or odor detection.

The three cresyl groups in a given molecule of TCP can attach to the phosphate in different configurations; these are called isomers. In total, there are ten TCP isomers
(Table 1), including a tri-ortho isomer (TOCP), two di-ortho isomers (DOCP), three mono-ortho isomers (MOCP), and four meta/para isomers. The relative amounts of these different isomers can vary between brands and batches of aviation engine oil, but
some combination of some or all of these isomers will be present in a given sample.

Although engine oil manufacturers consider the specific isomeric blend to be proprietary, it is known that the ortho isomers make up about 0.3% of the TCP and the vast majority
(99.97%) of the ortho isomers are MOCP and DOCP, while there is very little TOCP (PCA, 2000). Little is known about the relative amounts of the remaining meta and para
isomers.

Table 1: DESCRIPTION OF THE TEN ISOMERS OF TCP

Category of isomer Description of isomers

Tri-ortho: TOCP (1) o-o-o

Di-ortho: DOCP (2) o-o-m; o-o-p

Mono-ortho: MOCP (3) o-m-p; o-m-m; o-p-p

Meta and/or para (4) m-m-m; p-p-p; m-m-p; m-p-p

Probably because of some highly publicized TOCP mass poisonings resulting from adulteration of a popular alcoholic drink called "Ginger Jake" (1929) and a large batch of
cooking oil (1959), this single isomer has received the most attention, and it is the only
isomer for which an exposure limit exists (e.g., OSHA PEL: 0.1 mg/m3). These mass 1 Most engine oils used in the aviation industry do contain TCPs while most hydraulic fluids
contain tributylphosphates. One aviation engine oil that does not contain TCPs is Turbonycoil 600 manufactured by NYCO, SA. One hydraulic fluid that does contain TCPs is Chevron Hyjet
IV-A-plus (van Netten, 2001).

2 Referred to current Material Safety Data Sheets for Mobil Jet Oil II, Mobil Jet Oil 254, Mobil Jet Oil 291, BP/Exxon 2380, Royco 808, and Chevron Hyjet IV-A-plus. poisonings involving TOCP highlighted the risk of peripheral neuropathy and paralysis, which has been confirmed in laboratory studies involving animals that ingested TOCP or
absorbed it through their skin.

Peripheral neuropathy associated with dermal or oral TOCP exposure is of little relevance to the concerns raised over exposure to aerosolized engine oil on aircraft, in part because of the relative formulation and toxicity of the different TCP isomers in a given batch of engine oil. Specifically: (1) There is little, if any, TOCP in the engine oil
formulations; (2) The mono- and di-ortho isomers of TCP are five and ten times more toxic than TOCP, respectively, but are still only present at low concentrations such that
peripheral neuropathy should not be the primary endpoint of interest (PCA, 2000;

Mackerer, 1999; Henschler, 1958); (3) The ortho isomers have been implicated in chronic neurotoxicty in addition to peripheral neuropathy; and (4) The meta and para
isomers of TCP dominate commercial engine oil formulations and are not expected to cause peripheral neuropathy. However, evidence of potential for chronic symptoms of
neurotoxicity associated with acute exposures or chronic, low-level exposures has been
suggested for organophosphates in general (Jamal, 2002) and TCPs on the aircraft in particular (Singh, 2004). The ortho content of TCP has been successfully reduced in the last few decades but the toxicity of meta and para isomers are still of toxicological concern.

The majority of published research on the toxicity of engine oils has assessed symptoms of peripheral neuropathy among laboratory animals that either ingest the oil or absorb it
through their skin. However, aircraft occupants are primarily exposed via inhalation with
the potential for limited dermal exposure. There is no evidence that ground-based dermal/oral research data can be applied to inhalation exposures that are often incurred in a reduced oxygen environment. Inhalation toxicity testing in a controlled laboratory
setting, with post-mortem brain analysis of exposed animals may be necessary to confirm the observations of chronic neurotoxicity among exposed aircraft occupants.