G3ImE8w@ report no 94/51

This report is based on a paper given on behalf of the CONCAWE Health

Management Group to the Workshop on the Carcinogenicity of Coal and
Petroleum Derived Substances held a t the EC Joint Research Centre at lspra,
Italy, May 25-26, 1992.

R.J. Ellison

B.J. Simpson Technical Coordinator

Reproduction permined with due acknowledgement

O CONCAWE
Brussels
February 1994
 report no 94/51

ABSTRACT

Untreated lubricant base oils have been associated in the past with the
development of human skin cancer To give a better understanding of these
health effects, industry has conducted an extensive range of long-term dermal
carcinogenicity studies with the objective of identifying the influence of
different types of refinery processing and t o establish the important base oil
compositional factors The studies have led t o improved refining techniques
and t o the development of simple markers for control purposes based on a
standard analytical test.

However, with the increasing emphasis o n the regulatory classification and

labelling of petroleum products, i t is proposed that the same markers can be
effectively used for the classificatiorl of base oils.

The report describes the development of markers for the prediction of base oil
carcinogenicity and examines the relative merits of t w o particular candidates,
one based on dimethyl sulphoxide extraction by method IP 3 4 6 and the other
based on benzo(a)pyrene (Bap) concentration.

KEYWORDS
Animal, aromatic extract, base oil, benzo(alpyrene, carcinogens, classification,
dermal, DMSO extract, IP 3 4 6 test, ISPRA, labelling, lubricant base oils,
marker, mice, PAC, RAE, skin, tumour.

NOTE
Corrsiderable efforts have beerr made to assure the accuracy and reliabdiry of the
information contained in tlhs publication However, rreitlier CONCA WE nor any conlpany
participatirlg in CONCA WE can accept liabdity for any loss. damage or injury whatsoever
resulting from the use of this information

This repot! does not necessarrly represent the views of any company particrpatrng in
CONCA WE
(cxml~@w@ report no. 94/51

CONTENTS

1. INTRODUCTION
2. HEALTH ASPECTS OF MINERAL OlLS AND DEVELOPMENT
OF CONTROL MEASURES

3. PETROLEUM SUBSTANCES AND THE IP 346 METHOD

3.1 PETROLEUM SUBSTANCES

3.2 LUBRICANT BASE OlLS AND PAC CONTENT
3.3 IP 346 METHOD
3.4 RESIDUAL AROMATIC EXTRACTS

4. CARClNOGENlClTY MARKERS

4.1 SUPPORTING EVIDENCE

42 TUMOUR INCIDENCE CONSIDERED SIGNIFICANT
43 INFLUENCE OF STRAIN OF MOUSE ON TUMOUR
. RESPONSF
4.4 USE OF DATA FOR PREDICTINGCARCINOGENIC POTENCY
4.5 DMSO EXTRACT AND BAP MARKERS
4.6 CONFIRMATORY STUDIES
4.6.1 Using basestock blends
4.6.2 Additional data

5 CONCLUSIONS

6 REFERENCES
Table 1

Figures 1 to 5

Appendix: Supporting data for the IP 346 DMSO marker

 report no. 94/51

INTRODUCTION

llntreated lubricant base oils have been associated in the past with the
development of human skin cancer. To give a better understanding of these
health effects, industry has conducted an extensive range of long-term dermal
carcinogenicity studies with the objective of identifying the influence of
different types of refinery processing and to establish the important base oil
compositional factors. The studies have led to improved refining techniques
and to the development of simple markers for control purposes based on a
standard analytical test.

However, with the increasing emphasis on the regulatory classification and

labelling of petroleum products, it is proposed that the same markers can be
effectively used for the classification of base oils.

The report describes the development of markers for the prediction of base oil
carcinogenicity and examines the relative merits of two particular candidates,
one based on dimethyl sulphoxide extraction by method IP 346 and the other
on benzo1a)pyrene Bap) concentration.

Supporting experimental evidence for the study is a data base consisting of

over one hundred skin painting studies conducted by CONCAWE member
companies over a period of twenty years. This evidence is fully documented in
the Appendix to the report.

The report is based on a paper given to the Workshop on the Carcinogenicity

of Coal and Petroleum Derived Substances held at the EC Joint Research
Centre at lspra, Italy, May 25-26, 1992.
 report no. 94/51

HEALTH ASPECTS OF MINERAL OILS AND DEVELOPMENT OF

CONTROL MEASURES

Reports in the literature dating back to the early 1920s indicate that the use of
poorly or unrefined mineral oils under conditions of poor personal hygiene has
been associated with skin cancer in man. 1 The subject has been extensively
reviewed in the literature arid reference is made to the IARC study 7. and to the
CONCAWE Dossier on Aromatic Extracts. 3

Since the discovery that refinery processirlg can irifluence the carcinogenic
poteritial of lubricants, the oil industry has conducted a wide range of studies
to identify the factors involved. This has been one reason for the introduction
of more severe refining techniques, such as solvent refining and
hydrotreatment, and it is flow possible to produce lubricating oils that are
non-carcinogenic. As a result, older refining methods in Europe have been
largely discontinued.

The standard procedure for assessing carcinogenic potential is by long-term

animal skin painting studies. This involves applying test samples to the skin,
several times a week for the major portion of the life span of the test animals.
Such experiments may take two to three years to complete.

For industrial purposes, once the basic trends have been established, quicker
alternative ways of assessing carcinogenic potential are advaritageous for
routine use,.4 There is also the need to minimize continual animal testing.

By the mid 1980s, a number of CONCAWE member companies had developed

correlations between the results of animal studies and simple analytical
parameters and were using such techniques for a variety of purposes.
Recognising the importance of these developments, CONCAWE convened a
multi-disciplinary study to review the subject. Member companies submitted
data from their own records and altogether a data base of some 7 6 studies
was established.
The conclusions of this work were reported to the EC in 1988. 5 CONCAWE
recommerided that, in the absence of any appropriate long-term ariimal test
data, the carcinogenicity of lubricant base oils and distillate aromatic extracts
should be assessed based on the dimethyl sulphoxide (DMSOI extract as
determined by the IP 346 method. All substarices with a DMSO extract of
3% (mlm) or greater should be considered as Class 2 carciriogens.
Subsequently, this proposal and the supporting experimental data have been
reviewed by the TPC Working Group on the Classification and Labelling of
Dangerous Substances, initially at the Working Group Meeting or1 25-26 May
1992 held at the EC Joint Research Centre, Ispra, and later at following
meetings in Brussels.

With the voluntary acceptance of this standard by industry in many parts of

the world, the report describes the supporting evidence for the
recommendations.

The Appendix iricludes all the information known to CONCAWE at the end of
1992, including the studies published after the Ispra Workshop in the paper by
Chasey and McKee. 6
 report no. 9415 1

PETROLEUM SUBSTANCES AND THE IP 346 METHOD

PETROLEUM SUBSTANCES

Most petroleum substances come into the category described in the European
Inventory of Existing Commercial Chemical Substances (EINECS) as
"substances of unknown or variable composition". In the petroleum industry,
such substances are usually manufactured t o meet specified physical and
performance criteria, rather than a defined chemical composition. In
consequence, the assessment of potential carcinogenicity can be difficult if
based solely on the definitions given in EINECS.

LUBRICANT BASE OILS AND PAC CONTENT

It has been shown that the molecular species responsible for carcinogenic
potential of lubricant base oils are principally the three t o seven ring polycyclic
aromatic compounds (PACs). 1 in the simplest case, the aromatic rings may
consist of only hydrogen and carbon atoms and these compounds are termed
polycyclic aromatic hydrocarbons (PAH). More complex structures may contain
nitrogen, sulphur or oxygen atoms and as the number of rings increases, the
possible steric arrangements increase rapidly. The molecules may also have
side-chains of varying lengths, structures and complexity; such compounds are
referred to as alkylated PACs.

It has been shown that polycyclic aromatic C O ~ P O L J ~can

~ S be selectively
extracted from base oil streams by a dirnethyl sulphoxide (DMSO) solvent. 7
The oil industry has therefore used this approach for a procedure t o
characterize the PAC content. A standard method for the extraction has been
developed and is described in method IP 346. 8

IP 346 METHOD
The IP 3 4 6 method is a gravimetric procedure in which a sample of oil is
diluted with cyclohexane and extracted twice with DMSO. The sample is cut
so as to exclude material boiling below 300°C. The resulting extract includes
the three t o seven ring polycyclic aromatic hydrocarbons in the test sample,
but it is recognised that the method extracts other material as well. The
resulting DMSO extract is therefore higher in percentage terms than the PAC
content determined by a GLC analysis.

The IP 3 4 6 procedure is suitable for use with lubricant base oils and aromatic
extracts from vacuum distillates, but it is not suitable for use with substances
containing asphaltenes andlor resins such as some residual oils, residual fuels
and bitumen. With such oils, the asphaltenic components prevent the
separation of the DMSO extract.

In addition, the method is not suitable for use with used oils or formulated
products containing additives. With these materials, the dimethyl sulphoxide
may extract components from the additives as well as from the base oil, thus
rendering the results inconclusive.
 report no. 94/51

Experience has indicated that it is important to use a standardised method for

determining the DMSO extract. The composition of the fraction obtained by
DMSO extraction is dependent on the test procedure and different methods
have been showr~ to give significantly different extract levels. For the
correlations described later in this report, it is essential that only the IP 346
procedure is used.

RESIDUAL AROMATIC EXTRACTS

Typically, residual aromatic extracts have a boiling range from about 400°C to
above 650°C. Because of the high boiling range, the molecules extracted by
DMSO are likely to be highly alkylated or possess high molecular weight side
chains and are therefore markedly different from those extracted from distillate
aromatic extracts. There is little evidence to indicate that residual aromatic
extracts are carcinogenic and, for this reason, it is not appropriate to base the
classification on the DMSO extract. A high level of extract by IP 346 may not
necessarily indicate potential carcinogenicity.
~ ~ ~ ~ ~ w @
report no. 94/51

CARCINOGENICITY MARKERS

SUPPORTING EVIDENCE

At the time of the presentation to the EC lspra Workshop in May 1992, the
supporting data available for the evaluation of suitable markers consisted of
some 76 skin painting studies. Most of this information was supplied to
CONCAWE over the period 1981 to 1985 and came from individual studies
conducted by member companies in the previous 15 to 2 0 years.

As these studies were conducted independently by member companies and did

not form part of a co-ordinated programme, it was necessary to select
appropriate samples from the information received that had the required
manufacturing history, generic descriptions and analytical data. In particular, it
was necessary to ensure that the DMSO extract had been determined by the
IP 346 method, as other extraction procedures can give significantly different
results.

The samples selected for the evaluation programme are listed in the Appendix.
Table 1 gives a summary of the sample description, tumour incidence, DMSO
extract and benzo(a)pyrene content, Table 2 lists details of test protocols and
Table 3 lists the available analytical data on the test samples.

At the end of 1992, further information became available to CONCAWE with

the publication of the paper by Chasey and McKee. 5 Some of the studies
reported in this paper had already been included in the original CQNCAWE data
base, but others studies were new. The additional new data are listed in
Table 4 of the Appendix.

The presentation to the lspra Workshop in May 1992 was based on the
information contained in Tables 1 to 3 of the Appendix. With the publication of
the Chasey and McKee paper, the additional data listed in Table 4 has been
used to confirm previous conclusions and to assess the accuracy with which
potentially carcinogenic oils can be identified.

TUMOUR INCIDENCE CONSIDERED SIGNIFICANT.

For assessing the outcome of the dermal carcinogenicity studies, a sample has
been considered as potentially carcinogenic if 4% or more of the test animals
developed tumours. The 4% incidence rate was chosen as being above the
typical background level for the untreated controls. For a typical study, this
means that for a positive result, at least two of the 50 animals showed
evidence of tumour formation.

Discussions in the TPC Classification and Labelling working group and with
IARC have considered this 4% figure to be valid, although possibly severe.

INFLUENCE OF STRAIN OF MOlJSE ON TUMOUR RESPONSE

Information on the test protocols used by member companies is listed in

Table 2 of the Appendix. This shows that member companies have used two
different strains of mouse, the C3H variety and the CFI variety. It has been
found that those studies conducted with the C3H mouse strain often gave a
higher tumour response than those conducted with the CF1 mouse. This is
illustrated in Figure 1 which shows tumour response against DMSO extract for
each of the two strains. With the C3H mouse, tumour response rates in
 report no. 94/51

excess of 70% can be obtained from samples with a DMSO extract in the 5 to
10% (mlm) range, whereas with the CF1 mouse, tumour response rates for
similar samples are not in excess of 50%.

This finding adds a further degree of variability to the data base in addition to
those of test procedure, test duration, dosage rates, etc. The marker levels
discussed below have been developed on a worst case basis and the variability
in the data base adds to the strength and applicability of the markers
proposed.

4.4 USE OF DATA BASE FOR PREDICTING CARCINOGENIC POTENCY

The relationship between skin tumour formation and DMSO extract or Bap
content are shown as scatter diagrams in Figures 1 to 3. These plots readily
show the number of points above the passlfail limit of a 4% tumour incidence
rate and give a simple graphical basis for setting passlfail limits for possible
markers. However, because of the different protocols used in developing the
data, such diagrams do not give a sound basis for developing mathematical
relationships for the prediction of carcinogenic response (the number of
animals expected to develop tumours on the basis of the measured DMSO
extract).

4.5 DMSO EXTRACT AND BAP MARKERS

The relationship between tumour incidence and DMSO extract is shown in
Figure 2. This scatter diagram illustrates that, with one exception, all of the 26
samples with a DMSO extract greater than 3% gave rise to significant skin
tumour formation in animal studies. Only one sample with a DMSO extract of
less than 3% was positive. This so-called "false negative" sample was
CONCAWE Sample No. 90, a solvent-extracted oil.

The alternative marker studied was benzo(a)pyrene (Bap). Bap can be

considered as representative of the polycyclic aromatic hydrocarbons found in
lubricant base oils and it can be determined by a variety of techniques
including gas chromatography and high-performance liquid chromatography.
The Bap data in this paper have been determined by the method described by
Grimmer 9. IARC 10 have reported that there is sufficient evidence to indicate
that Bap is carcinogenic in animal studies.

However, the scatter diagram in Figure 3 shows that Bap content alone is not
sufficient for accurately discriminating between potentially carcinogenic and
non-carcinogenic lubricant base oils as there is no clear dividing line between
potentially carcinogenic and non-carcinogenic oils; with Bap contents between
0.03 and 0.3 mglkg, test results could either be positive or negative.

Figure 4 shows that the correlation between DMSO extract and Bap content is
poor.

4.6 CONFIRMATORY STUDIES

4.6.1 Using basestock blends

Six of the samples included in the above evaluations were blends of lubricating
oil basestocks where long-term dermal carcinogenicity studies had been
conducted on both the individual comporlents and the blends.
 report no. 94151

Three of the blends, CONCAWE Samples 108, 109 and 110, were based on
components that had given rise to a significant tumour response in the initial
studies. These were then cut back with a non-carcinogenic white oil so as to
give blends with calculated DMSO extract levels, t w o below 3% and one
above 3%. Samples 108 and l09 with DMSO extracts below 3% did not give
rise to any tumour formation on further testing, whereas Sample 110 with a
DMSO extract of 6.3% resulted in 10% tumours.

CONCAWE Samples 106 and 107 were made up from constituents that had all
previously tested negative and had DMSO extract levels of below 3%. Both of
these blends tested negative.

The final blend, CONCAWE Sample 95, had a DMSO extract of 13% and
tested positive.

These studies give further experimental support to the choice of 3% DMSO

extract as the control level for the marker, although it is not proposed that the
wse of the marker should be extended to cover such preparations.

4.6.2 Additional data

The additional data made available on the publication of the paper by Chasey
and McKee 5 gave the opportunity of further checking and confirming the
recommendations put to the lspra Workshop. Inclusion of the new data
increased the number of studies available from 52 to 104. Figure 5 shows the
new data superimposed on Figure 2.

On the basis of all the data available to CONCAWE at the end of 1992, the
accuracy with which the DMSO marker can discriminate between potentially
carcinogenic and non-carcinogenic base oils is quantified in Table 1. This
shows predictability based on DMSO marker levels set at 1 %, 2% and 3%.

If the marker level is set at l%, the marker can predict the onset of
tumorigenic activity, but it is accompanied by an unacceptably high level of
false-positives (16%).At 2%, one false negative is given in 104 samples and
at 3%, three false negatives are given.

In view of the comments concerning the severity of the tumour incidence level
considered positive by CONCAWE and the fact that two of the three false
negatives only gave rise to a tumour incidence of 5%, it is considered that a
DMSO extract marker set at 3% gives a satisfactory limit for classification
purposes.
 report no. 94/51

CONCLUSIONS

CONCAWE considers that the use of a marker based on the dimethyl

sulphoxide (DMSO) extract by method IP 346 offers a simple and effective
system for the prediction of the carcinogenic potential for lubricant base oils
and distillate aromatic extracts.

The scope of the IP 346 method does not allow the proposed marker to be
applied to products containing asphaltenes, such as residual fuel oils, or to
formulated products containing additives. Also, the marker is not applicable t o
gas oils or residual aromatic extracts.

The method by which the extract is determined must be IP 346, other

analytical methods are likely to give different results and should not be used
for classification purposes. The IP 346 procedure only requires equipment that
is routinely available in a manufacturing location.
 report no. 9415 1

REFERENCES

Medical Research Council (1968) The carcinogenic action of mineral oil -

a chemical and biological study. Special report series No 306. London:
HMSO
IARC (1984) Monographs on the evaluation of the carcinogenic risk of
chemicals to humans. Polynuclear aromatic hydrocarbons, Part 2, carbon
blacks, mineral oils (lubricant base oils and derived products) and some
nitroarenes. Vol 33, 87-168. Lyon: International Agency for Research on
Cancer

CONCAWE (1992) Aromatic Extracts. Product Dossier No 9211 01

Brussels: CONCAWE

Roy, T.A. et al (1988) Correlation of mutagenic and dermal carcinogenic

activities of mineral oils with polycyclic aromatic compound content.
FundApplied Toxicol 446-4476
CONCAWE ( 1 988) Classification of aromatic extracts and petroleum
distillates for Annex I of EEC Dangerous Substances Directive. Paper
submitted to Dr. K. Krisor (DG XI) for discussion in The Dangerous
Substances Directive TPC Working Group on 25th October. Brussels:
CONCAWE
Chasey, K.L. and McKee, R.H. (1993) Evaluation of the dermal
carcinogenicity of lubricant base oils by the mouse skin painting
bioassay and other proposed methods. J Applied to xi col^ 57-65

Van der Wiel, A. (1993) Selective determination of potentially hazardous

polycyclic aromatics in luboil fractions by the DMSO extraction method -
As development, evaluation and use. Report AMER 93.023 (External
version of internal KSLA report issued 1979). Shell Research B.V.,
KonIShell Lab. Amsterdam.

IP (1993) Determination of polycyclic aromatics in unused lubricating

base oils and asphaltene free petroleum fractions - dimethyl sulphoxide
extraction refractive index method. IP 346192. In: Standard methods for
analysis and testing of petroleum and related products Vol 2. Chichester:
John Wiley and Sons

Grimmer, G. et al (1981) Profile of the polycyclic aromatic hydrocarbons

from lubricating oils. Inventory by GCIMS-PAH in Environmental
Materials, Part l.Fresenius Z A n a l Chem 306, 347-355

IARC (1983) Monographs on the evaluation of the carcinogenic risk of

chemicals to humans. Polynuclear aromatic hydrocarbons, Part 1,
Chemical, environmental and experimental data. Vol 32, 21 1-224. Lyon:
international Agency for Research on Cancer
cxxW8w@ report no. 94/51

Table 1 : Accuracy of prediction using DMSO extract marker

Prediction DMSO extract marker level (% m/m)

1% 2% 3%

Correct positive predictions 37 36 34

Correct negative predictions, 51 57 64

False positive predictions 16 10 3

False negative predictions 0 1 3

 (cxmmBlw@ report no. 9415 1

% mice with tumours - CF1 mouse strain

% DMSO extract by IP 346 (mlm)

Oh mice with tumours - C3N mouse strain

1W

% DMSO extract by IP 3 4 6 (mlm)

Figure 1: Influence of strain of mouse on tumour response

(cxxiE~W@ report no. 94/51

% mice with tumors

% DMSO extract by IP 346 (mlm)

% mice with tumors

% DMSO extract by IP 346 (mlm)

Figure 2: Tumour formation as a function of DMSO extract by IP 346.

(LxNiG~w@ report no. 94/51

% mice with tumours

*
*
ENLARGED BELOW

Bap content (mglkg)

% mice with tumours

Bap content (mglkg)

Figure 3: Tumour formation as a function of Bap content

 report no. 94/51

Bap Content (mglkg)

% DMSO extract by IP 346 (mlm)

Figure 4: Relationship between DMSO extract and Bap Content

txxiYmw@ report no. 94/51

mice with tumours

1W
SO

80

70

60

50

40

30

20
ENLARGED BELOW
10

0
0 5 10 15 20 25 30 35 40

% DMSO extract by IP 3 4 6 (mlm)

% mice with tumours

% DMSO extract by IP 3 4 6 (mlm)

A New data from paper by Chasey and McKee

* Original data

Figure 5: Tumour formation as a function of DMSO extract:

Addition of new data, February 1993.
 report no. 94/51

APPENDIX

SUPPORTING DATA FOR THE lP346 DMSO MARKER

The tables listed below summarize the data submitted by member companies to
CONCAWE as pan of its investigations into the relationship between the chemical
composition of mineral oils and their ability to cause skin cancer in mice :

Table 1: Study data grouped according to refinery processing. The table includes
relevant data received by CONCAWE up to 31 112/91.

Table 2: Summary of test protocols giving information concerning date of test, strain of
mouse, dose, frequency of dosing and test duration for the studies listed in
Table 1.

Table 3: Physical and chemical properties for the test, samples listed in Table 1.

Table 4: Study data received since 31/12/91 from the paper by Chasey and McKee.

The CONCAWE paper on the DMSO extract marker given in May 1992 to the lspra
Workshop on the Carcinogenicity Classification of Complex Petroleum Substances was
based on the information given in Tables 1, 2 and 3 only.
(cxmNmlw@ report no. 94/51

L! L! L! L! L! L!
C U y L ! L ! = o u : C C C
zE ,c
g
m
2a c r c W E E c ,
fEtllE"f
m m m
ga ga ga
m m m = % % m
%6 b$;$;:;ii
za z a a a z a a a 333
GOmGaW@ report no. 94/51

' N z N W . - - - m N ' . 'r.00

r

X 9 9 9 9 9 9 1
X d o o o o o o o
m
0 ,. .-
m .
.-
9
0
9
@o(Tileaw@ report no. 94/51

G
2
Y
, c
". . . m P
Y O U
. . .Z& C- Z
mm mm mm
U U U
C c c
G
". -
E E
mm mm mm
".
a a a a 0
. (L a.
(ixmiE8W@ report no. 94/51
 Table 2 CONCAWE mineral ail skin painting data: Summarv of test conditions

I CONCAWE Generlc Descrl~tlon Date Animal Dose Frsqusnc~ Duratron % Tumours

(Stertl Strain No pi ltirnedwsskl (Note 1) 18m 24ml

Vacuum distillates (raw untreated or dewaxed only)

93 Vacuum distillate
62 Dewexed vacuum distillate

Acid Treated Oils

1 37 ) Acidlearth treated distillate 1971 CF1 27 250 Note 2 18 m

1971 CF1 50 250 Note 3 18 m

Solvent-extracted oils

Dewaxed. solvent extracted vacuum distillate C3H 40

Dewaxed, solvent extracted vacuum distillate C3H 40
Furfural extracted. solvent dewexed CF1 50
Solvent extracted. vacuum distillate C3H 40
Solvent extracted, solvent dawsxed, vacuum distillate CFl 50
Solvent extracted vacuum distiilate CF1 48
Dewaxed, solvent extracted vacuum distillate C3H 40
Dawaxed, solvent extracted vacuum distillate

/solvent-extracted, eerth treated

98 Liquid S 0 2 extracted. earth treated distillate (150 solvent palet 1971 / CFl 501 250 l 18 m
l 100 Liquid S 0 2 extracted. earth treated distillate 160 solvent palel
79 Furfurai extracted. earth treated distiilate 1600 solvent palel
l
 report no. 94/51

m m m m m r n u , m o o ~ n o o m 0 0 0 Ln 0 0 0
N N N N N N N N m m N m m N 0 DUI N m m m
N W NN N NN N N N
D

- 0 0 0 0 0 0 0 0 0
m r n ~ * m
' O O r . 0
~m -~ w ~m d
O O r . 0 0
m m ~ ~ n *
0
Ln
"

?iE
<
5
2
m
I I I I T L I I r r I r r
m m m m m m r n m u u m u u
u u u u u u u u u u u u u
-I"
m
-..-
L LLL m
U U UU U
I
".".L
0 0 0
.-,..
 Table 2 CONCAWE mineral oil skin painting data: Summary of test conditions

CONCAWE Genanc Descrtptwn Date Animal Dose Fmsuancy Duratton

No. Wan) Strain No pl ltimedwcekl [Note 11

Distillate sramatlc extracts - untreated

66 oistiilate aromatlc extract from furfural extraction of LMO distillate CF1 48 200 2 17 m
11 Raw solvent extract from vacuum distillate C3H 30 25 3 LT
l
l
l ~ i s t i l l a t earomatlc extracts - treated
Hydrotreated M M 0 aromattc extract CF1 48 200 2 18 m
Blend of hvdrotreated extracts CFl 50 200 2 18 m
Hvdrotreated M M 0 aromatlc extract CF1 48 200 2 18 m
Hvdrotreated aromatlc extract
Blend of hvdrotreated aromatcc extracts CF1 50 200 2 18 m
Hydrogenated solvent extract from vacuum distillate C3H 30 25 3 LT
Hvdrogenated solvent extract from vacuum distilstte C3H 30 25 3 LT
Hvdrogenatad solvent extract from vacuum distillate C3H 30 25 3 LT

Residual Oils

45 Solvent extracted residual ail CF1 48 ZOO 2 18 m

26 Hydrogenated (mild), dewaxed. deasphalted stmospher6c residium C3H 40 25 3 LT
105 Deasphalted and dewaxed cylinder ail 18 m
 report no. 94/51
COnGawe

E E E E E
m m
, " D m 3

:: ::
N N
8::::
N N N
CONCAWE mineral oil skin painting studies: Sample phvsical end chemrcal properlies

Table 3 Vacuum distillate [raw untreated or dewaxed oniyl

Aramat~cCarbon (Brandas1 ID%)

Relatwe densltv 15115OC
K. Viscos~wat 37.8"C lmm2lsl
K. Viscostty at 98.9OC lmrn2/sl
Sulphur content 1% m i m l

DMSO Extract: 1P346 1% m h l

DMSO Extract: Ref.lndex/2S0C

PCA Content lmglkgl

Fluorenthene
Pyrane
Chrvsane
Benzolbifluoranthene
Benzo(sipvrene
Benzo(atpvrenrr
Pervlene
Benzolg.h.~)perylene
1-2 Benzofiuorena
2-3 Benzofluorene
Benzo(a1anthracana
Benzalklfluoranthane
Indenoll.2.3)pvrene
D!benzoanthrscenes
C18H1OS

First ~ssued:12-10-32
Rav~sed: 10-02-93 Ravlsed format
(!Xmmaw@ report no. 94/51
 CONCAWE ANALYTICAL DATA BANK

Table 3 Solvent-extracted ails

Arornattc Carbon IBrandesI 1%)

Relative d e n s w l511 5°C
K. Viscosm at 37.S°C lmrn2Isl
K. Viscosatv at 98.9OC lmrn2Isl
Sulphur content 1% rnlmi

OMSO Extract: P 3 4 6 1% rnhl

OMSO Extract: R e f . l n d e ~ l 2 5 ~ C

PCA Content lrngikgl

Fluorsnthene
Pvrene
Chwsena
Benrolblfluoranthene
8enzolelpvrene
Benzolalpvrene
Pervlene
Benzolg,h,ilpervlene
1-2 Benzofluorene
2-3 Benzofluarene
Benralalanthracene
Benzalklfluoranthene
Indenoll.2.3)pvrene
Oibenzoanthrecenes
C18HlOS

First ~ssued:12-10-92
Rev~sed: 10-02-93 Rewsed format
 CONCAWE ANALYTICAL DATA BANK

Table 3 Solventsxtracted, earth treated

4romstlc Carbon IBrandesl (%l

M a t w e denstty 1511S°C
<. Viscos~tyat 37.S°C 1rnrn2k)
<. Viscosity at 98.9"C tmrn21s)
julphur content (% mlrn)

3MSO Extrsct: lP346 (% mlrn)

3MS0 Extract: R s f . l n d a ~ l 2 5 ~ C

>CA Content IrngRg)

Fluoranthene
Pyrena
Chrysene
Benzo(b1fluoranthena
Benzoielpyrens
Bsnzota)pyrene
Perylene
Bsnzolg.h,i)perylene
1-2 Benzofluorene
2-3 Bsnzofluorene
Bsnzola)anthracsne
Benzo(k1fluoranthene
Indeno(l,2,3)pyrena
Dibenzoanthracenes
C18HIOS

First essusd: 12-10-92

Rsvtsad: 10-02-93 Revistons marked 1.1
 10'0 IZI PZ'O 22'0 80'0> 9 1.0
aN (L) £0'0 aN Z'O> aN
L0'0> aN (L1 90'0 aN 9'0> aN
10'0 111 ON aN Z'O> aN
.L0'0 10'0 10'0 20'0 10'0 L0'0> £0'0
29'0 09'0 60'0 60'0 z 1.0 P0'0
OZ.0 OE'O 09'0 90'0 80'0 EWO
LO'O> aN 111 z0'0 aN 8'0 ON
10'0 (L1 *0'0 10'0
.
L'O> 10'0
..
10'0 10'0 LW0 90'0 20'0 1'0 20'0
.LW0 10'0 .L0'0 P 1'0 90'0 L'O EL'O
80'0 z0'0 .LW0 60'0 P0'0 1'0 90'0
.*v0 LO'O OE'O Z'LL 9 1'0 PL'O 92'0
OL'O PS0 Z9'0 90'0 80'0 LO'O
EL'O KYO OE'O 95'0 90'0 1'0 P0'0
58SL ZP55.L 9FSS'L P965'L 8E9S L 9895'1 PP8S L ZL6Y l
.8'L 16'0 L8'0 LL'O "P'O 61'0 8 1'0 LL'O
OZ' L EO'O L 1.0 ZYO OE'O 60'0 PS0 0'Z L
LL'E Z0'P LE'6 8E.5 56'9 LO'Z L 68'E
LE'OZ LP'OZ L.EE LZ'EE 5Y6Z PZ L ZL'8L
EL8'0 188'0 E98'0 LLVO OL8.0 898'0 688'0 OS8'0
YL 9.8 YOL L'O L 0'6 9'6 5'01 9'2
(W2WiE~~@ report no. 94/51

"g' ' m
2 "2 ;-.,-.r.' 0 . _ a I

.2
m
...
in ' 9 - m
0
2v
(LxI3m8w@ report no. 94/51
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(Ixml~8w@ report no. 94/51
(cXmKmW@ report no. 94/51

' ?mg Uo*oU2? 0 - '

------.-,-, *,...-,..,..
0 0 0 0 0 0 0 0 0 0 0 0 0
v v v v v v v v v v v v
o@@
.-.
(cimiW8w@ report no. 94/51

.
c!
Y 2 m
2 W
7
,
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.. m m ,
.r m
cxcxmmIw@ repon no. 94/51

Table 4: Summary of CONCAWE mineral oil skin painting data: Additional study data received since
31112191

Chssey Tumour response DMSO extrect

5 McKee iP 346 BoP Content Yeer of Crude
Sample No. Animals %T % mlm m g k study type
.p

Vacuum distillates - raw untreated I P

P

Solvent extracted distillates

l P
P
P
P
P
P
P
P
P
P
P
P
P
P
P

Solvent extracted end hydrotreated distillates

l
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P

continued..
(!xHMmw@ report no. 94/51

hasey Tumour response DMSO extracl

McKee IP 3 4 6 Bap Content Year of
ernpie No Animnis % mlm mdkg study

ydrotraoted distillates

istiilote aromatic extract8

I
- untreated

istiiiote aromatic extracts .hydrotreated

d i n e d vacuum residunis

94 0 50 0

First issued: 11-02-93

Notes: Crude type P denotes paraffinic, N denotes naphthenic