Evaluatie van het PX-10
rapport van het ministerie
van Defensie
RIVM Briefrapport 609037001/2010
VERTROUWELIJK

Dit is een uitgave van:
Rijksinstituut voor Volksgezondheid
en Milieu
Postbus 1 | 3720 ba Bilthoven
www.rivm.nl

Evaluatie van het PX-10
rapport van het ministerie
van Defensie
RIVM Briefrapport 609037001/2010
VERTROUWELIJK

RIVM Briefrapport 609037001

Inhoud

Colofon—5
1

Inleiding—8

2

Conclusie—9
Appendix 1: Rapportage IRAS—11

Pagina 3 van 25

RIVM Briefrapport 609037001

Colofon

© RIVM 2010
Delen uit deze publicatie mogen worden overgenomen op voorwaarde
van bronvermelding: 'Rijksinstituut voor Volksgezondheid en Milieu
(RIVM), de titel van de publicatie en het jaar van uitgave'.

N.J.C. van Belle
N. Janssen
Contact:
N.J.C. van Belle
IMG
Jurgen.van.Belle@RIVM.nl

Dit onderzoek werd verricht in opdracht van Ministerie van Defensie, in
het kader van Andere Overheden

Pagina 5 van 25

RIVM Briefrapport 609037001

Pagina 6 van 25

RIVM Briefrapport 609037001

Rapport in het kort

Evaluatie van het PX-10 rapport van het ministerie van Defensie
In 2008 is het ministerie van Defensie aansprakelijk gesteld voor de
gezondheidsschade die een ex-militair zou hebben opgelopen als gevolg
van zijn werkzaamheden binnen de Koninklijke Marine, en in het
bijzonder door het werken met het onderhoudsmiddel “PX-10”. Daarna
heeft het ministerie literatuuronderzoek uitgevoerd naar de mate
waarin Defensiemedewerkers aan dit onderhoudsmiddel van (hand)
vuurwapens zijn blootgesteld. Dit onderzoek is onlangs beoordeeld door
het RIVM. Het RIVM heeft daarbij de hulp ingeschakeld van het Instute
for Risk Assessment Sciences (IRAS). Dit instituut heeft specifieke
kennis op het gebied van arbeidsepidemiologie.
Het RIVM en het IRAS concluderen dat het onderzoek van Defensie naar
behoren is uitgevoerd. Wel schatten beide instituten de mate van
blootstelling aan benzeen, een ingrediënt van PX-10, tien keer lager in
dan Defensie. Ook geven de onderzoeksinstituten een aantal
aanvullingen op de opsomming van mogelijk te verwachten
gezondheidseffecten, voornamelijk op het gebied van bepaalde vormen
van lymfeklierkanker. Om de mogelijke blootstelling beter in te schatten
en vervolgens de mogelijke effecten te kunnen relateren aan de
klachten is nader onderzoek noodzakelijk. Defensie heeft het
onderhoudsmiddel PX-10 tot 1995 gebruikt.
PX-10, Wapenonderhoud, Benzeen

Pagina 7 van 25

RIVM Briefrapport 609037001

1

Inleiding

In 2008 is het ministerie van Defensie aansprakelijk gesteld voor de
gezondheidsschade die een ex-militair van de Koninklijke Marine (KM)
zou hebben opgelopen als gevolg van zijn werkzaamheden binnen de
KM en in het bijzonder door het werken met het onderhoudsmiddel “PX10”.
Mede omdat dit onderhoudsmiddel “PX-10” in elk geval gedurende
meerdere jaren benzeen, tolueen en xyleen bevatte, en daarnaast
veelvuldig binnen de Defensieorganisatie werd gebruikt, heeft het
ministerie van Defensie een onderzoek ingesteld naar “de
samenstelling, het gebruik en de gezondheidseffecten van PX-10 op
defensiepersoneel”. Het doel van dit onderzoek is om zo objectief
mogelijk te kunnen beoordelen of en in welke mate, (oud-)
defensiemedewerkers extra gezondheidsrisico’s hebben gelopen door
het werken met het onderhoudsmiddel PX-10.
Het onderzoek bestaat uit 2 delen:
1) een door het ministerie van Defensie zelf uitgevoerd onderzoek
naar de samenstelling, het gebruik, de gezondheidseffecten van
PX-10 op defensiepersoneel en de nog openstaande vragen
welke aan het RIVM moeten worden voorgelegd voor nader
onderzoek.
2) Een extern onderzoek, uitbesteed aan het RIVM, waarin onder
andere gevraagd wordt een oordeel te geven over de
rapportage over het door het ministerie van Defensie zelf
uitgevoerde onderzoek.
Het ministerie van Defensie heeft het RIVM gevraagd het tweede deel
van het onderzoek uit te voeren omdat het instituut een aanzienlijke
kennis op het gebied van de epidemiologie en de toxicologie heeft.
Omdat bij dit onderzoek ook specifieke kennis op het gebied van
arbeidsepidemiologie noodzakelijk is, heeft het RIVM samenwerking
gezocht en gevonden bij het IRAS (Institute for Risk Assessment
Sciences) van de Universiteit Utrecht. In verband met de ingewikkelde
problemen rondom de blootstellingschattingen (van de samenstelling
van PX-10 door de jaren heen is niet veel bekend) heeft het IRAS op
zijn beurt intensief samengewerkt met het IOM (Institute of
Occupational Medicine) uit het Verenigd Koninkrijk. Het voorliggende
rapport is het resultaat van de samenwerking tussen IRAS en IOM,
onder begeleiding van het RIVM.
Het externe RIVM/IRAS/IOM onderzoek betreft een drietal
deelprojecten:
1. Het beoordelen van een door het ministerie van Defensie
opgesteld rapport over de stand van zaken met betrekking tot
PX-10 ten aanzien van:
a. aannames die worden gedaan resp. conclusies die
worden getrokken ten aanzien van exacte samenstelling
van het product PX-10
b. de conclusies uit de door het ministerie van Defensie
uitgevoerde literatuurstudie naar gezondheidsrisico’s
van bestanddelen van PX-10
c. de beschreven risicoscenario’s voor hoog en laag risico.
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RIVM Briefrapport 609037001

2.

3.

Het (doen) uitvoeren van onderzoek waarmee de
gezondheidsrisico’s voor een hoog risicoscenario respectievelijk
een laag risico scenario ingeschat kunnen worden voor in het
verleden aan PX-10 blootgesteld defensiepersoneel. Dit
onderzoek omvat zowel blootstellingsschattingen als
gezondheidsrisicoschattingen
Het (doen) ontwikkelen van een methodiek om voor overige
blootstellingscenario’s de relatieve risico’s van de blootstelling
aan PX-10 in te kunnen schatten. De methodiek zal zodanig
vormgegeven worden dat zij, na voldoende training, zelfstandig
uitgevoerd kan worden door deskundigen (arbeidshygiënisten)
van de defensie organisatie. Omdat in dit stadium nog niet
duidelijk is hoe een stand alone tool voor de inschatting van
blootstelling / gezondheidrisico’s bij verschillende scenario’s
vorm gegeven kan worden en wat de vormgeving zal kosten
valt deze specifieke deelvraag niet binnen de opdracht. Op basis
van gebruikerswensen kan, wanneer de methodiek voor de
twee reeds beschreven risicoscenario's is ontwikkeld, alsnog,
indien gewenst, een aanvullende offerte opgesteld worden voor
het ontwikkelen van deze stand alone tool.

Dit briefrapport beschrijft de resultaten van het eerste deelproject.
Hierin is het door het ministerie van Defensie samengestelde rapport
aangaande PX10 geëvalueerd door een team van wetenschappers van
het IRAS en het IOM. In de evaluatie zijn de aannames en conclusies
van het rapport getoetst ten opzichte van de huidige wetenschappelijke
kennis omtrent PX10 en haar mogelijke bestandsdelen. Het door het
IRAS en IOM opgestelde evaluatierapport is opgenomen in bijlage 1.
Het rapport van het ministerie van Defensie gaat in op de volgende
vragen:
1. Kan meer duidelijkheid worden verkregen over de samenstelling
van PX-10 door de jaren heen.
2. Kan meer duidelijkheid worden verkregen over het gebruik van
PX-10 door de jaren heen.
3. Kan meer duidelijkheid worden gegeven over de extra
gezondheidsrisico’s die (oud)defensie medewerkers mogelijk
hebben gelopen door het werken met PX-10.
4. Welke vragen moeten aan de civiele wetenschappelijk
organisatie worden voorgelegd om nog openstaande vragen te
kunnen beantwoorden.
In de evaluatie van het rapport ligt de nadruk op de nauwkeurigheid
van de aannames en conclusies met betrekking tot de samenstelling,
gebruik en gezondheidseffecten van PX-10.

2

Conclusie

De conclusie van de evaluatie is dat het rapport van het ministerie van
Defensie in het algemeen in overeenstemming is met de huidige
wetenschappelijke literatuur. Echter, het door het IRAS en IOM
ingeschatte benzeengehalte van PX-10 ligt ongeveer een factor 10 lager
dan de inschatting van het ministerie van Defensie. Ten aanzien van
het gebruik van PX-10 is gebleken dat het lastig is om daar in deze fase
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RIVM Briefrapport 609037001

van het onderzoek uitspraken over te doen. Hier zal in aanvullende
focusgroepbijeenkomsten aandacht aan besteed worden. Daarnaast
geeft het evaluatierapport een aantal aanvullingen op de beschrijving
van de gezondheidseffecten van PX-10, waaronder bepaalde vormen
van kanker in relatie tot blootstelling aan benzeen (met name van de
lymfeklieren) en effecten op de reproductie in relatie tot blootstelling
aan oplosmiddelen. Om de door defensie gebruikte scenario’s van hoge
en lage blootstelling, gebaseerd op informatie over het gebruik van PX10, te kunnen evalueren zijn eveneens aanvullende
focusgroepbijeenkomsten nodig. Deze aanvullende bijeenkomsten zijn
voorzien in de 2de fase van het onderzoek. Deze tweede fase zal
aansluitend door het IRAS in samenwerking met het RIVM worden
uitgevoerd.

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RIVM Briefrapport 609037001

Appendix 1: Rapportage IRAS

Evaluation of the internal report on PX-10 by
the ministry of Defence

Roel Vermeulen
Dick Heederik
Lutzen Portengen
Jelle van Vlaanderen
Martie van Tongeren
Alastair Robertson
Kaspar Schmid
John Cherrie

Institute for Risk Assessment Sciences, Utrecht University,
The Netherlands
Institute of Occupational Medicine, Edinburgh, United
Kingdom

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RIVM Briefrapport 609037001

1. Introduction
In 2008 the Ministry of Defence received a claim of an ex-military
person regarding serious health complaints due to the use of PX-10.
Subsequently, this claim has received attention by the national
government, the military union and the media. As PX-10, at least for
part of the time, contained benzene and other organic solvents the
suggestion has been that the Ministry of Defence, although aware of the
potential health effects, has not acted adequately in eliminating or
reducing the exposure or in providing appropriate personal protection to
their employees. In response, the Ministry of Defence has agreed to
further investigate the use of PX-10, its contents and the potential
associated health effects with the goal to objectively assess the
potential health risks that (ex-) military personnel might have had due
to the historical use of PX-10. As part of this investigation the Ministry
of Defence has produced an internal report in which four main questions
were addressed (Neuteboom et al. 2009):
1.

What was the composition of PX-10 over time?

2.

How was PX-10 used over time?

3.

What is known about the possible (additional) health effects
that defence personnel might have had due to the use of PX10?

4.

Which questions need to be answered by scientific
organisations in order to answer open questions?

In this evaluation of the internal report of the Ministry of Defence we
will focus on the accuracy of the assumptions and conclusions made
with regard to the composition, use and related health effects of PX-10.

2. What was the composition of PX-10 over
time?
The report states that the main components of PX-10 were white spirit
(85 – 95%), mineral oils (1-12%) and additives (1.5 – 6%). The
conclusion that white spirit is likely the main constituent of PX-10
seems consistent with the physical properties described for PX-10.
Several historical safety data sheets of PX-10 by the Dutch ministry of
defence are available. Table 1 shows the information available for the
different years based on the safety data sheets. These sources describe
roughly the composition of PX-10 after 1987, and in the transition time
around the year 1984-1985. However, older documents are less explicit
and cannot be dated exactly. The wording of the main content changed
over the years from “turpentine” to “naphta”.

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RIVM Briefrapport 609037001

Table 1.
Year
<1985
1984-1985

>1987

Sources of information about the content of PX-10
PX-10 content description
Turpentine* 93% (max .20% aromatic) mineral oil
1 % additives 6 %
Turpentine* 85 - 95% (max. 20% aromatic),
mineral oil 3 - 12%, fatty esters 0,5 - 1,5%
additives 1,5 - 2,5%
Naphta 90% (max. 1% aromatic of which
0.0005% benzene), mineral oil 7%, fatty esters
1%, other components 2%.

* Turpentine is a translation of the Dutch word ‘Terpentine’ which is used for
several solvent mixtures among which white spirit
(1) Defensie Materieel Organisatie. AVIB 8030-07; Water Displacing Fluid (PX10/-). 1985
(2) Defensie Materieel Organisatie. AVIB 8030-07/B; Water Displacing Fluid (PX10/-). 1985
(3) Defensie Materieel Organisatie. C:03/0, PX-10 Water Displacing Fluid. <1985
(4) Defensie Materieel Organisatie. AVIB 8030-07/C; PX-10 Water Displacing
Fluid. 1987

White spirit with high aromatic content is mentioned as "carcinogenic"
in the Map Book of Chemistry in 2009 (24th edition). This type of white
spirit with the CAS No 8052-41-3 was used in early times. The
percentage was lowered over time in parallel to the reduction of
benzene. More recently produced white spirit has a much lower
aromatic content and is therefore sometimes also called “aliphatic white
spirit”.
The exact composition of PX-10 remains unclear, especially for the time
before 1985 and needs to be deduced from the physical properties of
the substance: In a document from the UK Ministry of Defence (MOD
Def Stan 68-11) PX-10 is described as a water displacing fluid which
must consist of protective and surface active materials dissolved in a
volatile solvent. This standard defines PX-10 in terms of its properties
rather than its composition, including flash point, copper corrosion,
weight loss between 46 and 50 hours, water displacing properties,
emulsifying properties and stability. The minimum flash point should be
32oC. On the grounds of cost, it seems likely that the solvent will be a
boiling point mixture. Some flash points for typical boiling point
mixtures are given in Table 2. The minimum flash point of white spirit
was defined in BS245:1976 as 32oC. This information is consistent with
PX-10 being white spirit or perhaps turpentine-based.
Table 2.

Flash points for selected solvent mixtures

Solvent

Flash point (oC)

Petrol

<-40

Naphtha

-30
Pagina 13 van 25

References

(1) (2)
(3)
(4)

RIVM Briefrapport 609037001

white spirit (BSI)

32

Turpentine

35

Kerosene jet fuel

60

Diesel fuel

52-96

As the report by the Ministry of Defence indicates white spirit is likely to
have contained benzene in the past, as well as toluene and xylene. On
page 15 of the report estimates are derived for the possible contents of
benzene in PX-10 and how this will have changed over time (Table 3).
The estimates are based on the worst case scenario that PX-10
contained 95% of white spirit (see Table 1).
Table 3. Benzene contents of PX-10 as estimated by the Ministry of
Defence
Solvent

Benzene

Period before 1981

1% [0.2 -2.0%]

Period 1981 to 1985

0.5% [0.2 – 1.0%]

Period 1985 - 1995

<0.1%

After 1995

0%

White spirit is also known as Stoddard Solvent and mineral spirit.
Traditional white spirit is produced by fractional distillation of naphtha
and kerosene streams of crude oil fractionation. The boiling point range
is 130 to 220OC. It contained 25% aromatics, predominantly in the C7C12 range. There are a number of definitions for white spirit. BSI (1976)
defines two types; type A has <25% aromatics and type B has 25-50%
aromatic content. The flash point is defined as 32OC.
CEFIC (1989) defines three types of white spirit:
Type 1: Naphtha (petroleum), hydrodesulfurized, heavy
Type 2: Naphtha (petroleum), solvent-refined, heavy
Type 3: Naphtha (petroleum), hydrotreated, heavy.
Types 1 and 2 have boiling ranges from 90-230OC and type 3 has a
boiling range of 65-230OC. Straight run white spirit (type 0) has not
been treated beyond the process of distillation. Types 1, 2 and 3 white
spirit are further divided into 3 grades based on flash points (see Table
4).
Table 4.

Flash points for different grades of white spirit

Grade

Flash point (OC)

Boiling point (OC)

low flash

21-30

130-144

regular flash

31-54

145-174

high flash

>55

175-200

The flash point in PX-10 corresponds to regular flash white spirit.
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RIVM Briefrapport 609037001

Traditional white spirit contained less than 0.1% benzene, with some
companies now claiming levels in the order of 40ppm (0.004%) and
less.
IPCS (1996) quoted publications from the 1970s which reported a
benzene content of white spirits of between 0.001 and 0.1%. NIOSH
(1977) noted that benzene was typically present in white spirit at
around 0.1%. Amoruso et al (2008) reported that the specification for
benzene content in mineral spirits is usually <0.1%, but in practice
benzene levels are typically below 0.005% (<50 ppm) due to the
refining

and

distillation

techniques.

CLH

(2009)

reviewed

the

composition of white spirit and quoted values from the 1980s and
1990s in the range from <0.001% to 0.1%. Amoruso et al (2008)
quote a 1977 study conducted by Battelle Columbus Laboratories on
behalf of the U.S. Consumer Product Safety Commission (CPSC) as
stating that typical levels of benzene in mineral spirits were in the
range of 0.01% to 0.03% (100 to 300 ppm) (quoting Hillman and
Simpson, 1978). McKee et al (2007) noted that levels of benzene in
mineral spirits have been below approximately 50 ppm since the late
1970s, dropping from 100-200 ppm in 1975. Carpenter et al. (1975)
reported that the sample of Stoddard solvent that was used in their
toxicological studies contained 0.1% (1000 ppm) benzene and this is
widely quoted as evidence of the likely benzene content of white spirit.
As evidence for the carcinogenicity of benzene became accepted, its use
became increasing restricted. Since 1976 in Europe, a solvent that
contained more than 0.1% benzene had to be classified as a
carcinogen.
There appears to be little worthwhile information on benzene in white
spirit from before the 1970s. Various papers in the 1950s, 60s and
1970s refer to the use of PX10, white spirit and other solvents (e.g.
Elgar, 1973, Ellis, 1957, Stroud and Rhoades, 1953) but none that have
been traced so far contain any reference to benzene content of white
spirit.
In summary, the benzene content of white spirit would almost certainly
have been very much lower than 1% even before the 1970s. The
boiling point of regular white spirit is 145-220oC is substantially
different from the boiling point of benzene (80oC) and therefore,
fractional distillation would have resulted in efficient separation of
benzene

from

the

white

spirit

mixture,

whose

main

aromatic

components have 9 or 10 carbon atoms.
Based on our information, a preliminary estimate for the benzene
content of white spirit is presented in Table 5. These estimates are

Pagina 15 van 25

RIVM Briefrapport 609037001

about a 10-fold lower than the estimates given in the Ministry of
Defence report.
Table 5. Preliminary estimates of benzene in white spirit
Period
before 1970

% Benzene in white spirit
Best estimate

Upper limit

0.1

0.2

1970-1980

0.03

0.1

1980 onwards

0.01

0.03

Toluene and xylene have higher boiling points than benzene and are
present in higher concentrations than benzene. Concentrations of
toluene and xylene in white spirit were reported by IPCS (1996) (Table
6).

Pagina 16 van 25

RIVM Briefrapport 609037001

Table 6. Toluene and xylene content of white spirit (in % volume).
Solvent
Northern Europe
(Varnoline,
Henriksen,
1980))
0.005
1.1

% by volume
Russia
(Henriksen,
1980)

Toluene
0.2
Xylene (o,p &
4.14
m)
* C8 aromatics, includes ethyl benzene.

USA (Carpenter
et al, 1975)

0.4
1.4*

Clearly the contents of toluene and benzene will vary according to the
aromatic content of the white spirit, with low aromatic white spirit
having a lower content than traditional white spirit.
Data published by ICPS (1996) indicates that C9 and C10 aromatic
hydrocarbons account for over 60% the aromatic content of white
spirit. C11 and C12 aromatics are also likely to be present at
concentrations of around 1% and 0.1% by volume.
As previously indicated the most likely alternative to white spirit, based
on the minimum flashpoint definition of PX-10, seems to be turpentine.
Turpentine is obtained by the distillation of resin from trees, mainly
pine trees. It has similar solvent properties as white spirit and is used
for thinning oil-based paints, for producing varnishes, and as a raw
material for the chemical industry. Its industrial use as a solvent in
industrialized nations has largely been replaced by the much cheaper
turpentine substitutes distilled from crude oil.
The exact composition of turpentine depends on the species from which
it is derived. Broadly, turpentine consists of i) terpenes: 45-75% apinene (1), 5-30% b-pinene (2), 2-40% 3-carene (3), ii) other
turpentines such as limonene and camphene, and iii) their oxidation
products, such as alcohols and aldehydes. Terpenes are a group of
hydrocarbons which can be regarded as oligomers of isoprene, 2methyl-1,3-butadiene (Swedish Chemical Agency 1994). There is no
information on benzene being present in turpentine in the literature
indicating that benzene in turpentine is unlikely to be a significant
hazard.

3. How was PX-10 used over time?
The report described the use of PX-10 by the military. It is possible that
PX-10 was already used in the 1950s. It is likely that use was minimal
after the 1980s. The report describes several scenarios (high and low
exposure scenarios) which were based on documents and interviews
with (ex-)military personnel. Without additional focus group meetings it

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RIVM Briefrapport 609037001

is not possible to comment on the use-scenarios described. This will
need to be addressed in a later stage of the research project.

4. What is known about the possible
(additional) health effects that defence
personnel might have had due to the use of PX10?
The main constituents of PX-10 have been identified as i) white spirit
(which may include variable amounts of benzene, toluene and xylene),
ii) mineral oils possibly containing polycyclic aromatic hydrocarbons;
and iii) additives
White spirit
As indicated there is no data available that pertains specifically to the
health effects of white spirit. Although it is possible that the different
constituents of white spirit could work synergistically or antagonistically
there is little data to support this assumption. It seems therefore
reasonable to assume that the effects are additive and as such the
focus of the health evaluation can be made on the individual
constituents.
Benzene
Exposure to benzene can be by inhalation or dermal contact. However,
given the high volatility benzene tends to evaporate off the skin more
rapidly than it can be absorbed. In non-immersion situations it can be
assumed that less than one percent is taken up through the skin (EPA,
2002).

This can

however

change

dramatically

when

hands

are

immersed in benzene or when occlusion occurs. Therefore, the
significance of dermal exposure cannot be determined at this time as
information is lacking regarding the exact patterns of dermal exposure.
Health effects related to benzene exposure that are mentioned in the
internal report are haematological effects (myeloiddysplastic syndrome,
aplastic anaemia, and acute myelogenous leukaemia), immunological
and lymphoreticular effects and neurological effects.
It is generally accepted that benzene causes a reduction in the number
of circulating erythrocytes, leukocytes and thrombocytes, generally
referred to as pancytopenia. Continued exposure can result in aplastic
anaemia and leukaemia. As indicated in the report benzene has been
causally related to acute non-lymphocytic leukaemia (ANLL; which is
primarily comprised of acute myelogenous leukaemia (AML)). However,
in a recent re-evaluation of the IARC of benzene, the working group
concluded that in addition to ANLL there is also limited evidence that
benzene

causes

Pagina 18 van 25

acute

lymphocytic

leukaemia

(ALL),

chronic

RIVM Briefrapport 609037001

lymphocytic leukaemia (CLL), non-Hodgkin lymphoma (NHL), and
multiple myeloma (MM) in humans (Baan et al., 2009). A recent metaanalysis of occupational cohort studies published prior to 2009 provided
strong evidence for an association between occupational benzene
exposure and increased risk of MM, ALL and CLL (Vlaanderen et al.,
2010). The association between benzene and NHL is less convincing but
this might well be explained by the heterogeneity in the association for
particular subgroups of this disease. For instance, two recent casecontrol studies reported a stronger association with benzene with
follicular lymphoma (FL) than for diffuse large B-cell lymphoma (DLBCL)
(Cocco et al., 2010; Wong et al., 2009). This together with the
substantial experimental and molecular epidemiological evidence that
benzene exposure alters key components of the immune system
relevant for lymphomagenesis (e.g. CD4+ T cell level; CD4+Tcell/CD8+
T cell ratio) (Lan et al., 2004), provide support that benzene is likely to
be causally related to one or more subtypes of lymphoma.
As mentioned in the report there is indeed evidence that more recent
exposure to benzene is more important for AML. This observation
however cannot be extended necessarily to lymphomas given the
different pathogenesis and the lack of epidemiological data supporting
or refuting this notion.
Limited studies suggest that benzene may cause effects on the
peripheral nerves and/or spinal cord. Symptoms included an increased
incidence of headaches, fatigue, difficulty sleeping and memory loss
among workers with significant exposures (EPA, 2002).
Furthermore, prolonged or repeated contact with benzene can cause
redness, dryness, cracking (dermatitis) due to the defatting action of
benzene.
Toluene
The health effects associated with toluene exposure mentioned in the
report are neurological effects (most seriously chronic encephalopathy).
Numerous studies of rotogravure printers, painters and rubberizedmatting workers with long-term exposure to toluene are inconclusive
about the potential of toluene to cause central nervous system (CNS)
damage (Baslo and Aksoy, 1982; Snyder, 2000; Filley et al., 2004).
Most studies do not have good exposure data, several indicate alcohol
consumption as a confounder and few have used the neurobehavioural
tests recommended by the World Health Organization. Some studies
reported changes such as memory loss, sleep disturbances, loss of
ability to concentrate, or incoordination, while others report no effects.
Recent studies using sensitive neurobehavioural tests have shown
altered scores for exposed workers but whether or not these results
actually indicate CNS damage is not clear. Other studies have shown no
change in neurobehavioural performance for workers with long-term
exposure to toluene.
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RIVM Briefrapport 609037001

A review of several studies on toluene and its effects on colour vision
concluded that the evidence is inconclusive as to whether long-term
exposure to toluene results in a persistent impairment of colour vision
(ATSDR, 2000). Similarly, the evidence of hearing loss due to toluene
exposure is limited. Hearing loss has been observed in workers in some
studies following long-term exposure to toluene and noise and in
animals exposed to very high concentrations of toluene.
Several

occupational

studies

have

reported

on

the

reproductive

outcomes among women exposed to toluene. Studies on spontaneous
abortion provided the most convincing evidence for an association with
toluene.

However,

the potential for

bias and multiple chemical

exposures suggests that the results from these studies should be
interpreted cautiously (Health Council, 2008). Few data are available
regarding the effects of toluene on human male reproduction. In the
report of the Dutch Health council it was concluded that the available
data give weak indications for an association between paternal
exposure to toluene and spontaneous abortion (Health Council, 2008).
In the EU toluene is classified as toxic to reproduction Category 3
(substances which cause concern for humans owing to possible
developmental toxic effects). This requires use of the risk phrase R63,
(possible risk of harm to the unborn child) (RAIS, 1994).
Repeated or prolonged contact with toluene may cause dermatitis (red,
itchy, dry skin) because of its defatting action.
Xylene
The health effects associated with xylene exposure mentioned in the
report are neurological effects (chronic encephalopathy). Indeed longterm xylene exposure may cause harmful effects on the nervous
system, but there is not enough information available to draw firm
conclusions. Symptoms such as headaches, irritability, depression,
insomnia,

agitation,

extreme

tiredness,

tremors,

and

impaired

concentration and short-term memory have been reported following
long-term occupational exposure to xylene and other solvents (ATSDR,
2007). Unfortunately, there is very little information available which
isolates xylene from other solvent exposures in the examination of
these effects.
Xylene has been linked to reproductive effects in some but not all
studies. The Health Council concluded in their report that the available
data indicate a weak association between maternal exposure to xylene
and spontaneous abortion (Health Council, 2009).
Besides possible neurological effects chronic health effects after
prolonged exposure to xylene are dermatitis (dryness and cracking).
Mineral oils
Untreated and mildly treated mineral oils are known to be human
carcinogens based on sufficient evidence of carcinogenicity in humans
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RIVM Briefrapport 609037001

that indicates that exposure to these types of mineral oils causes
cancer. The carcinogenicity of exposure to mineral oils has been
evaluated in numerous studies in a variety of occupations including
metal working, jute processing, mule spinning, newspaper press
operation, and other newspaper work (NTP, 2009). Exposure to mineral
oils was consistently and strongly associated with an increased risk of
squamous cell cancers of the scrotum and skin.
Mineral oils are a complex mixture of different oils that can contain
PAHs. It is likely that the described health effects such as skin cancer
can be ascribed to the PAHs present in mineral oils. Besides skin cancer
PAHs have been linked to lung and bladder cancer (Baan et al., 2009).
It is unclear why the latter two are not mentioned in the report.
However, these cancers have been observed in populations with high
occupational exposures to PAHs. Given the low content of mineral oils in
PX-10 and the low contents of PAHs in mineral oils it can be expected
that PAH exposures would have been low. Given the low volatility of
mineral oils the most important exposure route will have been dermal.
Additives or other compounds
Besides the aforementioned major constituents PX10 contained fatty
esters (0.5 – 1.5%) and unknown additives (max 6%). As it is unknown
which fatty esters were used it is difficult to assess the potential health
effects. However, health effects associated with fatty acids are
generally minimal with the exception potentially for glycol ether fatty
acid esters which have been associated with reproductive effects. Other
compounds or additives are not specified and as such no meaningful
health risk assessment can be performed.
In summary the described health effects in the report seems reasonably
accurate with the exception of the cancer sites related to benzene
exposure and the possible reproductive effects associated with solvent
exposure.

5. Which questions need to be answered by
scientific organisations in order to answer open
questions?
The report identifies two main questions. The first is related to the use
and possible exposures associated with the use of PX-10. The second
question is related to the estimation of the risk of developing a serious
health complaint due to the use of PX-10.
Although, there is uncertainty around the composition of PX-10
exposure can be reconstructed assuming likely concentration ranges of
the different constituents. Together with more detailed information on
the likely use scenarios exposure distributions can be estimated using
for instance probabilistic mass balance models. Given the nature of the
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RIVM Briefrapport 609037001

exposure these models will need to incorporate both dermal and
inhalation exposure.
The health risk of most concern related to use of PX-10 are mostly
related to potential benzene exposure and hemato- and lymphopoetic
cancers. Although, solvent exposures have been linked to neurological
effects the scientific literature is not consistent. This is certainly true
regarding the specific constituents and the dose-response relationships.
As such it seems that the risk estimation should focus on benzene
exposure and hemato- and lymphopoetic cancers. However, if the
nature of the current claims is such that other health endpoints should
be considered this can be explored further but would probably not lead
to a quantitative assessment of risk associated with the use of PX-10.

6. Summary conclusion
The

internal

report

of

the

Ministry

of

Defence

regarding

the

composition, use and associated health effects of PX-10 seems largely
consistent with the current scientific literature. However, we note that
the estimation of the benzene contents of PX-10 might have been too
high. In addition, we noted several additional possible health effects
associated with the different constituents of PX-10.

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RIVM Briefrapport 609037001

7. References
Amoruso MA, Gamble JF, McKee RH, Rohde AM and Jaques A (2008).
Review of the Toxicology of Mineral Spirits; Int J Toxicol 27; 97-165.
Agency for Toxic Substances and Disease Registry (ATSDR) (2000).
Toxicological profile for toluene. US department of Health and Human
Services. Atlanta, US
Agency for Toxic Substances and Disease Registry (ATSDR) (2007).
Toxicological profile for xylene. US department of Health and Human
Services. Atlanta, US
Baan R, Grosse, Straif K, Secretan B, El Ghissassi F, Bouvard V (2009).
A review of human carcinogens — Part F: chemical agents and related
occupations. Lancet Oncol 10(12):1143-1144.
Baslo A and Aksoy M (1982). Neurological abnormalities in chronic
benzene poisoning. A study of six patients with aplastic anemia and two
with preleukemia. Environ Res 27, 457-65.
British Standards Institution (1976). Specification for mineral solvents
(white spirit and related hydrocarbon solvents) for paints and other
purposes. BS 245:1976. London (BSI).
Carpenter CP, Kinkead ER, Geary Jr, DL, Sullivan LJ, King JM (1975).
Petroleum Hydrocarbon Toxicity Studies III. Animal and Human
Respoinse to Vapors of Stoddard Solvent. Toxicology and Applied
Pharmacology. 32; 282-297.
Chemical maps (Safety Information on chemical substances). Original
title: "Chemiekaarten : gegevens voor veilig werken met chemicaliën".
2009, (Sdu Uitgevers, TNO)
CEFIC (1989) Data submitted to EEC-Commission Working Group on
Classification and Labelling of Dangerous Substances. Bruxelles,
European Chemical Industry Council, Hydrocarbon Solvent Sector Group
(Working Paper No XI/748/86-Add 20 and No XI/748/86-Add 28).
CLH (2009). Proposal for Harmonised Classification and Labelling of
White
Spirit.
http://echa.europa.eu/doc/consultations/cl/clh_dk_axrep_white_spirits.
pdf
Cocco P, t’Mannetje A, Fadda D, Melis M, Becker N, De Sanjose S et al.
(2010). Occupational exposure to solvents and risk of lymphoma
subtypes. Occupational Environmental Medicine. In press.
European Chemicals Bureau (ECB) Classification and Labelling, Annex I
of Directive 67/548/EEC.
Elgar DJ (1973). Temporary Corrosion
Methods and Materials 20 (10) 17-19.

Protectives.

Anticorrosion

Elkins HE Pagnotto LD (1955). Benzene Contents of Petroleum Spirits.
AMA Archives of Industrial Health 1955, 51-54.

Pagina 23 van 25

RIVM Briefrapport 609037001

Ellis EG (1957). Lubricant Specifications. Industrial lubrication and
Tribology, 9 (3), 27-35.
Filley, CM., Halliday, W, Kleinschmidt-DeMasters, B.K., 2004. The
effects of toluene
on the central nervous system. J. Neuropathol. Exp. Neurol. 63, 1–12.
Health Council of The Netherlands (2008). Occupational exposure to
organic solvents: effects on human reproduction. The Hague.
Henriksen, HR (1977). [Analysis of the occupational use of white spirit.]
Copenhagen, Polyteknisk Forlag.
Hillman, M., and G. Simpson (1978). CPSC-C-78–0091, task 4, subtask
4.01, 4.02, and 4.03. Analysis of technical and economic feasibility of a
ban on consumer products containing 0.1 percent or more benzene.
December 22, 1978.
International Programme on Chemical Safety (1996). Environmental
Health Criteria 187 White Spirit (Stoddard Solvent), World Health
Organisation, Geneva. (IPCS)
Lan Q., Zhang L., Li G, Vermeulen R, Weinberg RS, Dosemeci M et al.
(2004). Hematotoxicity in workers exposed to low levels of benzene.
Science 306(5702):1774-1776.
McKee, R. H., A. M. Rohde (Medeiros), and W. C. Daughtrey (2007).
Benzene levels in hydrocarbon solvents—response to author’s reply.
(Letter to the editor.) J. Occup. Environ. Hyg. 4:D60-D62.
National Institute of Occupational Safety and Health (1977). Criteria for
a recommended standard…Occupational Exposure limit for refined
petroleum spirits. Cincinnati. DHEW (NIOSH) Publication Number 1977192 (NIOSH)
Report on Carcinogens, Eleventh Edition (2009); U.S. Department of
Health and Human Services, Public Health Service, National Toxicology
Program
Neuteboom MJW, Gerretsen HA, Leenstra T, Sijbranda T (2009). PX-10:
Internal progress report. Original title "PX-10: Intern Onderzoek".
Dutch ministry of defence, Soesterberg.
Risk Assessment Information System (RAIS) (1994). Toxicity summary
for toluene. Chemical Hazard Evaluation and Communication Group,
Biomedical and Environmental Information Analysis Section, Health and
Safety Research Division.
Snyder, R (2000). Overview of the toxicology of benzene. J Toxicol
Environ Health A 61, 339-46.
Stroud EG, Rhoades-Brown JE (1953). Note on the protection of mild
steel by films of lanolin. Journal of Applied Chemistry 3 (6), 287 – 288.
Swedish Chemical Agency (1994).
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http://apps.kemi.se/flodessok/floden/kemamne_Eng/terpentin_eng.ht
m
Vlaanderen J, Lan Q, Kromhout H, Rothman N, Vermeulen R
Occupational benzene exposure and the risk of lymphoma subtypes: a
meta-analysis of cohort studies incorporating three quality dimensions.
Accepted. 2010.
Wong O, Harris F, Armstring TW, Hua F (2009). A hospital-based casecontrol study of non-Hodgkin lymphoid neoplasms in Shanghai: Analysis
of environmental and occupational risk factors by subtypes of the WHO
classification. Chem Biol. Interact.

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Evaluatie van het PX-10
rapport van het ministerie
van Defensie
RIVM Briefrapport 609037001/2010
VERTROUWELIJK

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