Recommendation from the Scientific Expert
Group on Occupational Exposure Limits for
cyclohexanone
SEG/SUM/17
1992
European Commission
Employment, Social Affairs and Inclusion
Recommendation from the Scientific Expert Group on Occupational Exposure Limits for cyclohexanone
Table of Contents
1
2
3
4
Occurrence/use .......................................................................................................................... 4
Health Significance..................................................................................................................... 4
Recommendation....................................................................................................................... 5
Bibliography ................................................................................................................................. 6
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1992
European Commission
Employment, Social Affairs and Inclusion
Recommendation from the Scientific Expert Group on Occupational Exposure Limits for cyclohexanone
Recommendation from the Scientific Expert Group
on Occupational Exposure Limits
for cyclohexanone
8 hour TWA:
10 ppm (40,8 mg/m3)
STEL (15 mins):
20 ppm (81,6 mg/m3)
Notation:
skin
Substance:
Cyclohexanone
Synonyms
:
cyclohexyl ketone
EINECSN0
:
203-631-1
EECN°
:
606-010-00-7
Classification: RIO
Xn; R20
CAS N°
:
108-94-1
MWt
:
98.15
Conversion factor (20°C, lOlkPa)
:
4.08 mg/m3 = l ppm
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1992
European Commission
Employment, Social Affairs and Inclusion
Recommendation from the Scientific Expert Group on Occupational Exposure Limits for cyclohexanone
1 Occurrence/use
Cyclohexanone is a colourless to pale yellow liquid with an odour suggestive of
peppermint and acetone. It has a MPt of -45°C, a BPt of 155°C and a vapour pressure of
0.69kPa at 25°C. It has a vapour density of 3.4 times that of air and is explosive over the
range 1.1 - 9.4%. The odour threshold is approximately 0.12 ppm (0.5 mg/mj).
The production rate of Cyclohexanone in the EEC is in excess of 10,000 tonnes per annum.
It is predominantly used in nylon manufacturing and as a solvent for lacquers, resins,
polymers, glues, dyes and other applications. Technical grade cyclohexanone may contain
other chemicals, such as cyclohexanol and phenol. Cyclohexanone may occur together
with other solvents, especially in glues and lacquers.
2 Health Significance
Cyclohexanone is readily absorbed by inhalation, skin contact and ingestion and has a low
acute toxicity by all routes of exposure (Gupta et al, 1979; Smyth et al, 1969; Deichmann et al,
1943; Savolainen, 1982).
The critical effect of cyclohexanone is irritation to the eyes and upper respiratory tract. There is
evidence that a 3-5 minute exposure to cyclohexanone is irritating to throat and
eyes in concentrations as low as 75 ppm (306 mg/rrr), but 25 ppm (102 mg/nr3) was
considered to be tolerable by most individuals over this short exposure period (Nelson et
al, 1943). Systemic toxicity has been demonstrated at higher exposure levels. Treon et al
(1943) reported that rabbits exposed to 190 ppm (775 mg/m ) cyclohexanone (6h/day,
5 days/week for 10 weeks) developed barely demonstrable degenerative changes in
the liver and kidney. Greener et al (1982) established a NOAEL of 100 mg/kg/day for
intravenous injection of cyclohexanone in rats.
There is no evidence of neurotoxic, allergic or immunotoxic effects of cyclohexanone within
the concentration range significant for occupational exposure.
Induction of chromosomal aberrations by cyclohexanone has been observed in vitro in
human lymphocytes (Collin, 1971) and in vivo in bone marrow of rats injected subcutaneously
with 100 mg/kg cyclohexanone (de Hondt et al, 1983), suggesting that it may be a potential
carcinogen. However, a 2 year study in which cyclohexanone was administered in the
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1992
European Commission
Employment, Social Affairs and Inclusion
Recommendation from the Scientific Expert Group on Occupational Exposure Limits for cyclohexanone
drinking water at doses of up to 25,000 ppm to mice, and 6,500 ppm to rats, did not
provide clear evidence for carcinogenicity (Lijinsky and Kovatch, 1986).
3 Recommendation
The studies of Treon et al (1943), indicating a LOAEL of 190 ppm (775 mg/m3) for systemic
effects in rabbits, and of Nelson et al (1943), indicating a NOAEL of 25 ppm (102 mg/m3) for
irritation to the throat and eyes of human volunteers, were considered to be the best
available bases for proposing a limit. An uncertainty factor of 2 was applied to allow for the
limitations of the Nelson study. The recommended 8-hour TWA is 10 ppm (40.8 mg/m·3). This
is not contradicted by the study of Greene* et al (1982), establishing a NOAEL for systemic effects
of
100 mg/kg/day by intravenous injection. A S ILL (15 minš) of 20 ppm (81.6 mg/m3) is
proposed to limit peaks in exposure which could result in irritation. A "skin" notation is also
recommended as dermal absorption could contribute substantially to the total body burden.
At the level recommended, no measurement difficulties are foreseen.
Studies are required to determine whether the potential conversion of cyclohexanone to
cyclohexanol is sufficient to result in testicular toxicity.
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European Commission
Employment, Social Affairs and Inclusion
Recommendation from the Scientific Expert Group on Occupational Exposure Limits for cyclohexanone
4 Bibliography
Principal reference
SEG/CDO/12A (1991). Criteria document for occupational exposure limit values.
Cyclohexanone. Prepared by Dept of Toxicology and Biology, Danish National
Institute of Occupational Health.
Key Studies
C oll in , J .P . (1 9 71 ). E ffect c ytog enet ique du c ycla mat e de s ou de , de la
cyclohexanone et du cyclohexanol. Diabètes 19, 215-221.
De ichm ann ,
W. B .
and
Le
Bl an ch ,
T .J .
(1 9 43 ).
Det erm in at ion
of
t he
a pp r ox imat e let hal dose w ith a bout six an im als. J. I n d. H yg. T ox icol .
25 ,4 15 -417.
G reene r , Y ., Ma rt is , L . a n d I nda c oche a-Re dmon d, N . (1 9 82 ). As s essment o f
t he t o x ic it y o f c ycl ohe xa n one a dm in i st er e d i nt raven ousl y t o Wis t ar and
G u n n r at s . J . T o x i c ol . E n v i r on . Hea l t h 1 0 , 3 8 5 -3 9 6 .
Gupt a ,
P .K . ,
L a w ren ce ,
W. H . ,
T u r ner ,
J .E .
and
Aut ian ,
J.
(1 979 ).
T ox icol ogic al a spe ct s of c yclohe xa none . T o x ic ol . A p pl . P h a rm ac ol . 4 9 ,
525 -533 .
de Hondt , H.A., Te mt am y, S.A. and Ab d-Az iz , K .B . (1 9 83 ). C h rom o somal
st udie s on l ab o rat o ry r at s (Ra tt us n o rv egi cu s ) e xp o sed t o a n o rg an ic
s olv ent (c yclohexanone ). E gypt . J. Genet . C yt ol . 12 , 3 1 -41 .
Lijinsky,
W.
and
K ov at ch,
R .M.
(1986 ).
Chronic
t oxicit y
st udy
of
c ycl ohe xan one in r at s an d m ice . J. N at i. C ance r I nst . 77 , 9 41 -949 .
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European Commission
Employment, Social Affairs and Inclusion
Recommendation from the Scientific Expert Group on Occupational Exposure Limits for cyclohexanone
Nels on , K . W. , E g e , J .F . , R o s s , M.Jr . , Wo o dma n , L .E . an d S ilv erm an , L . (1 943 ).
S e ns o r y res po nse t o c e rt ain i n d u st r ia l s o l v e nt v ap ou r s . J . I n d . H y g .
T o x icol . 25, 2 82 .
Sav ol a inen,
H.
(1982 ).
Neu rot oxicit y
of
indust rial
chem ic als
and
c o n t a m i n a n t s : As p e c t s o f b io c h e m ic al mechanisms and effects. Arch.
T o x icol . S up pl . 5 , 7 1 -83 .
S m yt h , H .F . , C a r pent er , C .P . , We il , C . S . , P oz z ani , U.C . ,S t ie gel , J.A . a nd
N ycum , J. S . (1 9 69 ). R a nge -findin g t o x icit y dat a : l ist VI I . Arne r . I nd. H yg .
Ass. J. 30 , 470 -476 .
T r e on, J .F ., Cr utch f iel d , W.E . J r a n d Kit zm ille r, K. V. (1 9 43 ). Th e p h y s iol ogi c al
resp onse
of
an im als
to
cyclohexane ,
m et hyl cyclohe xane
an d
de riv at iv es of t hese com pou nds. J. Ind. Hyg. Toxicol . 25 . 323-347 .
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