p-tert-Butyl phenol H

3
Classification/MAK value: 0.08 ml/m (ppm)
3
0.5 mg/m
Peak limitation category II,2
Pregnancy risk group see Section
IIc
of the List of MAK and BAT Values
Classification dates from: 1981, 1995
Synonyms: 4-tert-butylphenol
4-(1,1-dimethylethyl)phenol
1-hydroxy-4-tert-butylbenzene
Chemical name (CAS): 4-(1,1-dimethylethyl)phenol
CAS number: 98-54-4
Structural formula: OH

H3C−C−CH3
CH3

Molecular formula: C10H14O

Molecular weight: 150.21
Melting point: 98°C
Boiling point: 236.5°C
Vapour pressure at 20°C: 175 hPa
3 3 3 3
1 ml/m (ppm) = 6.243 mg/m 1 mg/m = 0.160 ml/m (ppm)

1 Toxic Effects and Modes of Action

p-tert-Butyl phenol causes patchy depigmentation of the skin like that known from
vitiligo. This ability to cause depigmentation is also a property of many other phenols
(Kahn 1970). Comparative studies with a series of phenols and catechols revealed that
the para-substituted compounds have a greater effect than the meta-substituted and
6 p-tert-Butyl phenol Volume 11

ortho-substituted compounds (Bleehen et al. 1968). There are considerable differences in

sensitivity between species; exposed individual persons react very differently, apparently
as a result of genetic factors.
The occurrence of vitiligo is characterized by the following conditions and symptoms:
• contact with the substance for several months is necessary (at least 4–6 months),
• previous reddening or burns are not necessary,
• no previous or simultaneous allergic sensitization occurs,
• the effects appear first on those parts of the skin subjected to direct and intensive
exposure (hands and face)
• later the changes also spread diffusely to areas of skin without direct contact with the
substance; the spreading is mainly symmetrical; a haematogenic distribution is sug-
gested,
• the areas particularly affected are the skin around the sternum and between the shoul-
der blades, anal groove, genitals and armpits.
Other phenols induce depigmentation only after exposures producing severe irritation
or burns.
The depigmentation, which is particularly noticeable on sun-tanned skin, is reversible
at first and so long as it is only weak. When large areas of skin have been affected for
some time, the depigmentation may persist for many years with little or no change.
Morphological examination of the depigmented skin reveals a complete absence of
melanin granules, a reduction in the number of melanocytes and degenerative changes in
the other pigment cells. The biochemical mechanism is still unclear. A disturbance in the
enzymatic oxidation of tyrosine to dopa (dihydroxyphenylalanine) (Figure 1) and a
concomitant reduction in melanin production is suspected (Kahn 1970, Bleehen et al.
1968, Jimbow et al. 1974). The structural similarity of para-phenols to tyrosine and dopa
suggests a competitive displacement of substrates from the enzymes of melanin synthesis;
in vitro, p-tert-butyl phenol causes competitive inhibition of tyrosine hydroxylation and
dopa oxidation (McGuire and Hendee 1971). Destructive changes in melanocytes have
also been detected (Horio et al. 1977). Hydroquinone, a suspected metabolite of p-tert-
butyl phenol, not only inhibits the formation, melanization and degradation of the
melanosomes, it also breaks down the membrane structure of the melanocytes, which can
finally be destroyed completely (Jimbow et al. 1974).

H H H
C COOH C COOH C COOH
HO O
CH CH +1/2 O2 CH
H H H
NH2 tyrosinase NH2 tyrosinase
HO HO O NH2
tyrosine (DOPA oxidase)
DOPA dopaquinone

+ O2 autooxidation

dopachrom

melanin intermediates

Figure 1. Formation of melanin (Hamperl 1974).

Volume 11 p-tert-Butyl phenol 7

The depigmentation effect of hydroquinone has been known for over 60 years. Long-
term oral administration to black cats caused grey discoloration of the fur which was
reversible after termination of the treatment (Oettel 1936).
In addition to disturbances in the formation of pigment in the skin, p-tert-butyl phenol
can induce systemic damage in the liver and thyroid gland. Degenerative destruction of
hormone-forming thyroid cells, which can be detected by the formation of auto-anti-
bodies, results in diffuse goitre. A pathogenetic connection is suspected between chemi-
cally induced and also non-chemically induced vitiligo and thyroid gland diseases or the
immunological changes suggested in the literature to result from thyroid gland disorders
(Cuncliffe et al. 1968, Bor et al. 1969, Ochi and DeGroot 1969, Grunnet et al. 1970,
Lerner 1971, Bedi et al. 1974). Symptoms of disturbances in the autonomous nervous
system reported to result from this thyroid gland disorder include: headaches, drowsi-
ness, fatigue, sleep disorders, profuse sweating, thirst, shortness of breath. A functional
relationship between changes to the skin and thyroid gland is suspected, but not proved.
The occurrence in animal experiments of not better defined paralytic effects of p-tert-
butyl phenol has been described occasionally.
In long-term studies with oral administration of about 750 or 800 mg/kg body weight
for 51 and 20 weeks, p-tert-butyl phenol caused proliferative changes in the forestomach
epithelium in rats and hamsters. Evidence of tumour-promoting effects were found in the
forestomach after initiation with N-methyl-N'-nitro-N-nitrosoguanidine and subsequent
long-term administration of p-tert-butyl phenol. There are no data available on genotoxic
effects of p-tert-butyl phenol.
The metabolism of p-tert-butyl phenol has hardly been investigated. The phenolic
hydroxyl group, like that of other phenols, is probably coupled with sulfuric acid and
glucuronic acid (Williams 1959). The biological half-life of unchanged p-tert-butyl
phenol in man (exposed workers) is given as 4 hours (Ikeda et al. 1978).

2 Effects in Man

The first reports of adverse effects of p-tert-butyl phenol on the skin came from the shoe
and automobile industries where the use of glues (neoprene glue, polychloroprene glue),
which contained monomeric and polymeric p-tert-butyl phenol, led to contact dermatitis
and contact eczema. In addition there were soon reports of non-occupational allergies in
persons wearing shoes, watch straps and other clothing made using these glues (Table 1).
p-tert-Butyl phenol formaldehyde resin, formed by polycondensation of p-tert-butyl
phenol and formaldehyde (see Figure 2) and the free p-tert-butyl phenol which it con-
tained initially in considerable amounts (Calan and Cooke 1974, Malten 1973, Malten
1967) were both suspected of being the cause of the allergies. Formaldehyde alone was
found to be the allergen less often (Malten 1958, Brehm 1966/67, Suurmond and
Verspijck Mijnssen 1967, Beetz 1971). After removal of the excess monomeric p-tert-
butyl phenol from the glues there was a decrease in the number of cases of eczema, so
that above all the monomer had to be regarded as the cause of epidermal sensitization in
8 p-tert-Butyl phenol Volume 11

addition to the low-molecular weight intermediates formed in the condensation product

(see Figure 2) (Malten and van Aerssen 1962). Later investigations speak against mono-
meric p-tert-butyl phenol as the effective agent (Agatha and Schubert 1979). It was
demonstrated in volunteers that the agents responsible for inducing eczema are the
2-hydroxy-5-tert-butyl benzyl alcohol (see Figure 2: (I)) and a condensation product
(four p-tert-butyl phenols linked linearly by methylene bridges, see Figure 2: type III)
formed during the alkali-catalysed condensation of p-tert-butyl phenol with formalde-
hyde. The final macromolecular condensate, the p-tert-butyl phenol formaldehyde resin,
is considered too large to penetrate the skin (Malten 1973). Positive test results with both
the synthetic resin glue and the p-tert-butyl phenol (Malten 1958) and other p-phenols
(Horio et al. 1977) suggest cross-reactions between the two allergens, and with all
p-phenols, which, however, could not be confirmed (Malten 1973). Of 8 patients who
had reacted in a patch test to a p-tert-butyl phenol formaldehyde resin glue by producing
contact dermatitis, 3 produced reactions to p-tert-butyl phenol (Malten and Seutter
1985). All 8 patients reacted to 2-hydroxymethyl-p-tert-butyl phenol and 2,6-dihydroxy-
methyl-p-tert-butyl phenol, and 6 reacted to 2-hydroxymethyl-p-tert-butyl phenol bound
to 2-methyl-p-tert-butyl phenol in the C5 position. In another case, patch tests with
p-tert-butyl phenol yielded negative results, although p-tert-butyl phenol formaldehyde
resin yielded positive results (Kaniwa et al. 1994).

OH OH OH

CH2 CH2OH
O OH + HOH2C
(I)
+ H-C
H

H3C−C−CH3 H3C−C−CH3 H3C−C−CH3

CH3 CH3 CH3

OH OH OH
H H H H H
C O C C O C C OH + H2O (II)
H H H H H

H3C−C−CH3 H3C−C−CH3 H3C−C−CH3

CH3 CH3 CH3 n
methylene ether bridges

OH OH OH
H H H O
C C C OH + H2O + HC (III)
H
H H H

H3C−C−CH3 H3C−C−CH3 H3C−C−CH3

CH3 CH3 CH3 n
methylene bridges

Figure 2. Polycondensation of p-tert-butyl phenol formaldehyde (Malten 1973)

Volume 11 p-tert-Butyl phenol 9

In an epicutaneous test, 5 of 466 (1.0 %) male and 1 of 254 (0.4 %) female persons
reacted to p-tert-butyl phenol (concentration not specified) applied to the skin in petrola-
tum (Gründer et al. 1993). In another study, 10 of 1220 patients reacted to at least one
phenol formaldehyde resin in patch tests (Bruze et al. 1985). Of these 10 persons, two
were also tested with monomeric p-tert-butyl phenol and did not produce a reaction.
Cases of contact dermatitis with subsequent skin depigmentation are also known (see
Table 1) (Calnan and Cooke 1974, Malten 1975, Wozniak and Hamm 1977) in which the
leukoderma was not found in the area affected by the eczema but was systemic. This
indicates percutaneous absorption and systemic distribution of p-tert-butyl phenol
(Wozniak and Hamm 1977).
There are no usable findings on the extent of percutaneous absorption.
In 1962 Chumakov et al. reported for the first time the epidemic occurrence of skin
depigmentation in workers of a factory producing phenol formaldehyde resin in the
former USSR. 23 of 52 workers with different functions in the factory (2 chemists, 2
machine operators, 3 labourers and cleaning staff, 5 mechanics, 11 technicians/skilled
personnel) had the characteristic vitiligo-like skin changes, in some cases as little as one
year after the beginning of production; the changes appeared first on the exposed parts of
the body such as hands and feet, head and neck, but then also spread to non-exposed
areas such as back, breast, armpits, abdomen, genital region and anal groove. The
affected persons complained of headaches, drowsiness, profuse sweating, in particular an
increase in sweating on the palms of the hands and soles of the feet, hoarseness, throat
irritation, thirst, weight gain, loss of libido and other neurological and otolaryngological
disorders. Vegetative function impairment was seen, for example, as increases or changes
in red and white dermatographism. Among the workers with less than two years contact
with the substance, 15 % had depigmentation; after more than two years contact 40 % of
the exposed persons were affected (Chumakov et al. 1962, Babanov and Chumakov
1966).
Air analysis revealed average levels of the phenol vapour of 0.029 mg/l air with fluc-
tuations of 0.003–0.191 mg/l. Crushing of the resin produced dust concentrations of
12 mg/m3 air (Chumakov et al. 1962). Independent of the fact that these values do not
necessarily say anything about the exact p-tert-butyl phenol concentration in the air (see
Ebner et al. 1979), they seem to be very high.
In the same year (Okumura and Shirai 1962) and subsequent years similar reports
came from Japan for other alkylphenols and arylphenols (data from air and/or dust ana-
lyses are not available) (Hara and Uda 1966, Itoh et al. 1968) and America, where p-tert-
butyl phenol catechol induced leukoderma in 4 workers from the automobile industry
(Gellin et al. 1970), and p-tert-butyl phenol and p-tert-amyl phenol induced depigment-
ation in 12 hospital staff (Kahn 1970). p-tert-Butyl phenol (3 %) and p-tert-amyl phenol
(0.8 %) were contained as disinfectants in the cleaning agents (o-Syl, Ves-Phene) used by
the hospital staff, in addition to other phenols (4.1 % or 3.4 % o-benzylparachlorophenol,
3.9 % o-phenylphenol), all of which induced leukoderma to a greater or lesser extent. In
both cases the substances responsible could be identified in tests with persons and ani-
mals (see Table 2 and Table 5). Of 18 persons tested with 6 % p-tert-butyl phenol (12
hospital staff and 6 test persons) 16 persons were found to have depigmentation, 6 had
primary skin irritation and 7 (only hospital staff) allergic sensitization. In another case
10 p-tert-Butyl phenol Volume 11

p-tert-butyl phenol, contained in the cleaning agent o-Syl, was responsible for vitiligo on
the hands of a hospital employee (Odom and Stein 1973).

Table 1. Literature on contact dermatitis and contact eczema after exposure to p-tert-butyl phenol
formaldehyde resin

Author Year Number of cases Type and place of Country

total + depigm. exposure

Malten 1958 10 shoe industry Holland

(production)
Calnan and Harman 1959 3 shoe industry England
(production)
De Vries 1964 4 wearing of shoes Holland
Brehm 1966/ 12 shoe industry Federal Republic of
1967 (production) Germany
Engel 1966 32 automobile industry ?
Suurmond and 1967 8 wearing of shoes and Holland
Verspijck Mijnssen leather prostheses
Foussereau and 1970 5 shoe industry France
Benezra
Loechel 1971 6 shoe industry German Democratic
(production) Republic
1 shoe repair
Beetz 1971 12 shoe industry German Democratic
Republic
Calnan and Cooke 1974 not specified automobile industry England
11
Malten 1975 1 1 watch strap Holland
Adams 1975 16 p-tert-butyl phenol USA
formaldehyde resin
in 1 % petrolatum
Foussereau, Foussereau 1976a 1 automobile industry France
et al. 1976b
Foussereau, Foussereau 1976a 10 wearing of clothes France
et al. 1976b
Foussereau, Foussereau 1976a 9 wearing of shoes France
et al. 1976b
Mobacken and Hersle 1976 not specified shoe repair Sweden
Mobacken and Hersle 1976 not specified watch strap Sweden
Wozniak and Hamm 1977 1 1 shoe repair German Democratic
Republic
Moran and Martin- 1978 1 handicrafts Spain
Pascual
Volume 11 p-tert-Butyl phenol 11

In Europe there were further reports from Holland (Malten et al. 1971, Wieland 1979)
where in a factory producing and processing p-tert-butyl phenol, leukoderma with
subjective complaints like those known from the Russian reports (see Table 3) was
detected at first in 20 % of the persons investigated and later in 50 %. There is no infor-
mation on air analyses at the workplace.
The first occupationally-induced cases of vitiligo in the Federal Republic of Germany
were observed in a factory producing p-tert-butyl phenol and described in 1974 by
Rodermund and Wieland. Manual contact with the substance was unusual or only brief.
The employees were instructed to wash their hands thoroughly immediately after touch-
ing the substance. Contact with the heated product in the liquid phase caused burns and
reddening and sometimes the formation of blisters which healed without trace and in
particular without depigmentation. Symptoms such as headaches, fatigue and dizziness
were observed here too. Later the authors noted in several publications (Rodermund and
Wieland 1975a, Rodermund and Wieland 1975b, Rodermund et al. 1975a, Rodermund et
al. 1975b, Rodermund 1976), in addition to the vitiligo-like depigmentation, the devel-
opment of hepatosplenopathy and diffuse goitre as a result of exposure to p-tert-butyl
phenol. Disturbances in liver function with an increase in serum transaminases and
retention of sulphobromophthalein, spleen enlargement (in two cases) and scintigraphic
stage II diffuse goitre were detected in the first three cases observed (Rodermund and
Wieland 1975b).
Finally, among 30 exposed persons who were monitored, 10 were found to have
vitiligo-like depigmentation, 15 discrete changes in liver tests and 20 enlargement of the
thyroid gland (Wieland 1979), which caused the authors to suggest that exposure to
p-tert-butyl phenol is associated with a nosological triad: vitiligo, hepatosplenopathy and
diffuse goitre. The following effects were observed:
a) The depigmentation first occurred after several months of exposure and was distrib-
uted diffusely over the whole body without any preferred areas. In cases with less
marked depigmentation of small skin areas there was a clear tendency towards
regression.
b) The changes in the liver and spleen were slight increases in the transaminases, gluta-
mate dehydrogenase and SGT, slight delays in the elimination of sulphobromo-
phthalein, occasionally mild dysproteinaemia, in some cases storage irregularities in
the liver and/or storage in the spleen (scintigraphy); in the liver biopsy the cell nuclei
presented a non-uniform picture and there was cytoplasmic disaggregation and fine
and medium drop fatty cell degeneration (but not fatty liver).
The changes in the liver were more persistent, but did, however, also regress. The dis-
crete changes in laboratory values returned to normal most quickly.
c) The thyroid gland enlargements were without exception euthyroid goitre without an
increase in density or the formation of nodules, and in most cases clearly improved
after the end of exposure, sometimes returning almost to normal. The typical secon-
dary effects of thyroid enlargement such as cardiovascular disturbances, sweating,
vegetative lability, bulimia etc. were only observed in some cases.
Analytical data for concentrations in the air are not given.
 12
Table 2. Short-term studies with p-tert-butyl phenol in test persons

Number Substance/solvent Administration Duration Primary skin Allergic Depigmentation References

reactions sensitization

p-tert-Butyl phenol
5 hospital staff 6 % p-tert-butyl occlusion every 2nd day 4 persons: slight 3 persons with ? persons: from Kahn 1970
phenol in 70 % bandage for 2 weeks itching, slight additional days 10 to 24
ethanol erythema at the primary skin (repigmentation
application site reactions which from 6 months to
extended beyond > 1 year)
the bandage
not specified 3 % p-tert-butyl occlusion every 2nd day not specified not specified ? persons: from Kahn 1970
phenol in 70 % bandage for 2 weeks days 24 to 42
ethanol
5 control 6 % p-tert-butyl occlusion every 2nd day 5 persons: mild 0 persons 5 persons: from Kahn 1970
persons phenol in 70 % bandage for 2 weeks eczematous days 8 to ?
ethanol irritation (repigmentation
after 1 month)
? 5 control 1) 6 % p-tert-butyl no bandage 3 times a day not specified not specified 0 persons Kahn 1970
persons phenol in 70 % for 6 weeks:
ethanol 1) 2) and 3)
2) 6 % p-tert-butyl each for 2
phenol in a weeks
hydrophilic ointment
3) 6 % p-tert-butyl
phenol with sodium
lauryl sulfate

Volume 11
 Volume 11
Table 3. Reports of occupationally related cases of vitiligo after exposure to p-tert-butyl phenol

Number of Cases of Source of exposure Exposure First signs Primary skin Associated symptoms References
exposed vitiligo duration of depig- reactions
persons mentation

52 23 production of p-tert- 1–9 years > 1 year not specified headaches, general weakness, Chumakov et
(9  and butyl phenol and drowsiness, profuse sweating, thirst, al. 1962
14 ) p-tert-butyl phenol sleep disturbances, neurological and
formaldehyde resin otolaryngological disturbances
39 15 production of phenol not 6 months very mildly depigmentation mainly on sweaty areas Okumura and
derivatives specified inflammatory of the body; otherwise no adverse side- Shirai 1962,
skin irritation effects Malten et al.
1971
not 5 disinfectants 6 months 6 months 3 persons: 3 persons: contact allergy, Kahn 1970
specified containing p-tert- to ? pruritis and 3 persons: depigmentation on the hands
butyl phenol erythema and forearms,
1 person: depigmentation also on the
trunk,
2 persons: spontaneous repigmentation
within a year
about 25 at 5 at the production of not >4 without shortness of breath, fatigue; no abnormal Malten et al.
the beginning, phenols: p-tert-butyl, specified months– primary skin values in blood, liver and kidney 1971,

p-tert-Butyl phenol
beginning, later 25 p-octyl and, p-nonyl years irritation function tests Wieland
later 50 phenol 1979
30 10 production of > 6 months < 16 1 person: headaches, fatigue, dizziness Wieland
p-tert-butyl phenol to < 5 months dermatitis-like 20 persons: diffuse goitre, 1979,
years (only reddening of 15 persons: discrete changes in the liver Rodermund
short-term the skin of the and Wieland
daily skin hands 1975a, 1974
contact)

13
 14
Table 3. continued

Number of Cases of Source of exposure Exposure First signs Primary skin Associated symptoms References
exposed vitiligo duration of depig- reactions

p-tert-Butyl phenol
persons mentation

99 11 glues containing years (with about 4 reddening and at first: inflammatory reddening, no Calnan and
p-tert-butyl phenol skin years burning marked dermatitis Cooke 1974
(up to 10 % free contact) later: leukoderma after several years
p-tert-butyl phenol)
48 14 production and 6 to 36 < 1 year to without 11/14 persons investigated: Goldmann
processing of years > 5 years primary skin 1 person: unclear, subjective complaints, and Thiess
p-tert-butyl phenol (usually irritation other persons: no complaints, 1976
only ½ all persons: no effects found in the
hour/day) clinical examination
9/11 persons: mild to moderate
euthyreotic goitre,
9/11 persons: chronic liver damage
not 1 shoe manufacture years 2 ½ years inflammatory no goitre, no swelling of the lymph Wozniak
specified and repair with glues after reddening nodes, liver and spleen not palpable and Hamm
containing p-tert- occurrence 1977
butyl phenol of contact
eczema
198 54 production of p-tert- < 5 to 20 not not specified 6 persons: pathological liver function James et al.
butyl phenol years specified tests and liver biopsy 1977
2 persons: thyroid gland antibodies
(increase not statistically significant!)
about 34 10 resin boiling room: years > 10 without no subjective complaints Ebner et al.
p-tert-butyl phenol months to primary skin 5 persons: hepatopathy 1979
and formaldehyde 7 years irritation 1 person: diffuse goitre

Volume 11
polymerization
Volume 11 p-tert-Butyl phenol 15

The coupling of vitiligo, hepatosis and goitre after exposure to p-tert-butyl phenol
was confirmed in 1976 in another study (Goldman and Thiess 1976) in another large
chemical factory. In 12 occupational cases and 12 cases of vitiligo sui generis—with no
differences between the two forms—21 persons were shown by scintigraphy to have
euthyroid goitre in addition to the leukoderma and 18 persons shown to have chronic
liver damage. With the exception of one person who was employed in a toxicological
study of p-tert-butyl phenol with guinea pigs and complained of unclear symptoms after
just a few weeks contact with the substance, all the other persons investigated felt free of
symptoms. The slight to moderate euthyroid goitre could not be detected clinically, but
only in the scintigram as part of the classical radio-iodine test. The changes in the liver
were seen in increased values in the sulphobromophthalein tests (normal value 0.2) with
a highest value of 0.87. In the two groups, the occupational and non-occupational group
with a total of 24 cases of vitiligo, numerous routine immune tests for changes in the
thyroid gland yielded 8 positive results, mainly in the group with non-occupational
exposure (6 cases). Two clearly positive results of antiglobulin consumption tests indi-
cate an autoimmune disease, others a post-infectious process (haemolytic streptococci
and staphylococci) and support the hypothesis of an autoimmunological genesis of the
vitiligo. The authors consider that the localization of the vitiligo loci on the skin takes
place by visceral projection; they conclude that vitiligo after absorption of p-tert-butyl
phenol occurs only after previous internal damage to the organism and therefore repre-
sents one (dermatological) symptom among several symptoms resulting from intoxica-
tion. In this study, results of air analyses are also not mentioned although a MAK value
of 1 ppm is suggested.
In England (James et al. 1977) monitoring of the employees of a factory producing
p-tert-butyl phenol revealed among 198 workers 54 persons with vitiligo and showed that
the duration of exposure and above all its intensity were decisive for the triggering and
severity of the leukoderma. Of 9 persons with severe vitiligo 5 workers were exposed to
high concentrations (employed in crushing and filling, in closed rooms) and 4 to medium
concentrations (distillation, alkylation and monitoring of equipment), 2 of them, how-
ever, for less than 5 years. During distillation the workers were exposed to p-tert-butyl
phenol vapour, in the packing station to the dust. Measurement of the total dust
(background dust level) yielded values of 10 ppm with occasional peaks of 100 ppm.
Histologically the skin damage did not differ from genuine vitiligo, but the association
with an autoimmune disease found with genuine vitiligo was not detected (with the
exception of 2 of the 54 persons who had thyroid gland antibodies, a statistically non-
significant number; up to 6 % of the population of a normal doctor’s surgery have anti-
thyreoglobulin antibodies). Enlargement of the thyroid gland or liver were also not
found. However, for 6 of the 54 persons, those with marked vitiligo, the results of liver
function tests were abnormal. Liver biopsies, which were carried out in these patients
after normalization of liver function, revealed pathological changes in all cases; these
were moderate to severe fatty focal changes (in 6 persons), formation of collagenic septa
(in 4 persons) and fibrosis in the hepatic portal, probably developing into macronodular
cirrhosis (in 1 person), in some cases liver cell necrosis with slight lymphocytic infiltra-
tion (in 4 persons). As excessive alcohol consumption could be excluded, the authors
conclude that vitiligo is very probably accompanied by liver damage, that its occurrence
16 p-tert-Butyl phenol Volume 11

is dose-dependent and that it occurs systemically after inhalation of p-tert-butyl phenol

and/or its absorption through the skin.
In Austria (Ebner et al. 1979) 10 cases of vitiligo were found among 34 persons
exposed to p-tert-butyl phenol in a factory producing synthetic resin and varnishes. Of
these persons four also had an enlarged liver, one an enlarged spleen, and two increased
levels of liver function parameters in the blood. Of 4 persons without effects on the liver,
one was found to have a palpable enlargement of the thyroid gland (stage 1 diffuse
goitre,) and another anti-thyroid gland antibodies. The authors conclude that the slightly
pathological scintigraphic and blood findings do not allow a final conclusion. In none of
the 10 persons was the triad, vitiligo, hepatosplenopathy and goitre found. Assay of the
ambient air in this factory revealed great differences in the total dust levels of 0.48 to
1.80 mg/m3. The level of p-tert-butyl phenol, which fluctuated from 0.12 to 0.96 mg/m3,
did not increase in parallel with the total dust, which could only be explained in terms of
different storage times of the p-tert-butyl phenol used; it was demonstrated that because
of the hygroscopic properties of p-tert-butyl phenol, longer storage resulted in a reduc-
tion in the amount of dust produced.

3 Animal Experiments and in vitro Studies

3.1 Acute toxicity

The data available for the acute toxicity of p-tert-butyl phenol are shown in Table 4.

Table 4. LD50 values for p-tert-butyl phenol

Species Administration route LD50 References

rat oral 801 mg/kg (714–939) Toxicology Data Sheet 1980

(10 % in dimethylsulfoxide)
rat oral 1440 mg/kg (560–3500) Denine 1973
rat oral 3200 ml/kg (2480–4260) Smyth et al. 1969
rat oral 5660 mg/kg Industrial Hygiene Foundation
of America 1967
rabbit cutaneous 2520 ml/kg (930–8580) Smyth et al. 1969
rabbit cutaneous > 5000 mg/kg Denine 1973

Apart from erythema, oedema, fissures, scaling and necrosis of the skin, no other
effect and, in particular, no significant damage (no further details) to the thoracic or
abdominal organs of rabbits was observed after a 14-day follow-up period after dermal
occlusive application of p-tert-butyl phenol doses of 2000, 8000 and 16000 mg/kg body
weight for 24 hours (Klonne et al. 1988).
Volume 11 p-tert-Butyl phenol 17

Inhalation exposure for 6 hours to air saturated with p-tert-butyl phenol vapour (no
further details) led in Sprague-Dawley rats (5 of each sex) neither to recognisable
changes in body weights nor to clinical symptoms or abnormal findings in the pathologi-
cal examination (Klonne et al. 1988).
After aerosol exposure for 4 hours (aerodynamic diameter: 3.6 µm) to a p-tert-butyl
phenol concentration of 5600 mg/m3, 1 of 5 male rats and 1 of 5 female rats died within 2
days. Laboured breathing and irritation of the respiratory tract were observed in all
animals (Klonne et al. 1988).
The animal experiments listed in Table 5 clearly show the depigmentation effect of
p-tert-butyl phenol on the skin and hair after different routes of administration. In some
experiments dimethylsulfoxide and/or sodium lauryl sulfate were applied to the skin
beforehand to improve penetration. The experiments were all designed to identify the
leukoderma-inducing substance and provide no information on pathological changes in
the animal organism. There are no animal experiments available which provide such
information.

3.2 Effects on skin and mucous membranes

After dermal occlusive application of p-tert-butyl phenol doses of 500 mg/kg body
weight for 4 hours, 1 of 6 rabbits was found to have erythema and scaling, and another
rabbit oedema and necrosis. The skin damage healed within 17 days (Klonne et al.
1988).
From 2000 mg/kg body weight, erythema, oedema, fissures, scaling and necrosis were
observed in rabbits after dermal occlusive application of p-tert-butyl phenol for 24 hours;
14 days later some of these symptoms still persisted (Klonne et al. 1988).
Undiluted p-tert-butyl phenol applied occlusively to the skin for 24 hours has an
irritative effect on the intact or abraded skin of rabbits (Toxicology Data Sheet 1980,
Denine 1973). It causes marked irritation in the rabbit eye (Toxicology Data Sheet 1980,
Smyth et al. 1969, Klonne et al. 1988).
In guinea pigs, sensitizing properties of both free p-tert-butyl phenol and the low-
molecular weight formaldehyde resin were detected. In addition there was group-specific
cross-sensitization between the two substances (Malten 1967).

3.3 Subacute, subchronic and chronic toxicity

There are two studies available on the chronic toxicity of p-tert-butyl phenol (Hirose et
al. 1986, 1988). In one investigation, in which 15 male Syrian hamsters received a diet
containing 1.5 % p-tert-butyl phenol for 20 weeks (~800 mg/kg body weight), the relative
liver weights were increased by about 20 %. On the surface of the forestomach a
keratinous white coating was found and moderate to severe hyperplasia of the epithelium.
In 7 of 14 treated Syrian hamsters, there were papilloma-like changes in the forestomach
which were not observed in the control animals.
 18
Table 5. The depigmentation effect of p-tert-butyl phenol in animal studies

Species Dose Application site Administration Duration Findings References

(no., fur colour) solvent route

p-tert-Butyl phenol
mouse C57 0.01 M ptBP, subcutaneous 6 x per week after 12 weeks: beginning of Hara and Uda
(black ) 0.05 ml olive oil for 7 months depigmentation 1966, Hara and
Nakajima 1969
mouse C57 0.2 M ptBP, gavage 3 x per week diffuse areas of depigmentation Hara and
(black) 0.2 ml olive oil for 6 months Nakajima 1969,
Hara 1967
rabbit 10 mg/kg body i.m. daily for 6 after 20–24 days: focal greying on Chumakov et
(15, black) weight ptBP, weeks the flanks and back; 4 animals: al. 1962
peach-kernel oil spastic paralysis of the hind limbs;
decrease in leukocytes; pathology:
enlargement of the adrenal glands,
congestion in the internal organs
rabbit 7.5 mg/kg body subcutaneous daily for 6–8 after 10–14 days: brown coloration Chumakov et
(8, black) weight synthetic weeks of the hair, slow progression to al. 1962
phenol*, silver grey; 1 animal: paralysis of
water the hind limbs
rabbit 7.5 mg/kg body i.m. about 21 after 12–20 days: greying of the Babanov and
(8, black) weight ptBP, days hair without previously turning Chumakov
dog peach-kernel oil brown, (the same for both routes of 1966
(7, black) administration); 3 rabbits: still
depigmented 2 years after
termination of the treatment

Volume 11
 Volume 11
Table 5. continued
Species Dose Application site Administration Duration Findings References
(no., fur colour) solvent route
rabbit 7.5 mg/kg body with the diet about 21 after 12–20 days: greying of the Babanov and
(4, black) weight ptBP, days hair without previously turning Chumakov
dog peach-kernel oil brown, (the same for both routes of 1966
(1, black) administration); 3 rabbits: still
depigmented 2 years after
termination of the treatment
rabbit 7.5 mg/kg body ? 6 days per after 10–14 days: hair brown, Babanov and
(12, black) weight synthetic (injection) week for 6 progression slowly to silver grey; Chumakov
phenol*, weeks 6–8 months after termination of the 1966
water treatment: repigmentation
cat 7.0 mg/kg body oral 7 days/week no depigmentation, no deviation in Malten et al.
(black) weight ptBP, for 2 months hair colour 1971
milk
guinea pig 7.5 mg/kg body gavage 5 days per no clear depigmentation visible Malten et al.
(10, natural weight ptBP, week for 10 1971
colouring, i.e. aqueous months
brown/black emulsion
guinea pig, 6 % ptBP in shaved dorsal skin moistened cloth 2 weeks scaly irritation; but no loss of skin Kahn 1970

p-tert-Butyl phenol
Hartley () 70 % ethanol (occlusion test) pigmentation except on the scars
guinea pig 6 % ptBP, left ear (right ear painting 2 x per day, left ear: sensitive and erythem- Kahn 1970
DMSO (1 week as control: only 5 days per atous, swollen after 6 applications;
previously NLS) DMSO + NLS) week for 3 minimal depigmentation in a few
weeks animals; right ear: no findings
guinea pig 1 % ptBP, 0.2 ml areas of skin with intradermal once local necrosis, depigmentation and Kahn 1970
and without hair permanent hair loss at injection site

19
 20
Table 5. continued
Species Dose Application site Administration Duration Findings References
(no., fur colour) solvent route

p-tert-Butyl phenol
guinea pig 0.1 ml: shaved dorsal skin painting daily for 3 no depigmentation Gellin et al.
12  , black) 0.005 % ptBP (3 x 3 cm) weeks from 5 % skin irritation 1970
1.0 % ptBP from 10 % marked skin irritation
5.0 % ptBP
10.0 % ptBP,
acetone
guinea pig 0.1 ml: shaved dorsal skin painting daily for 3 1 % and 5 %: no depigmentation Gellin et al.
12  , black) 1.0 % ptBP (3 x 3 cm) weeks and no skin irritation 1970
5.0 % ptBP 10 %: marked depigmentation and
10 % ptBP, moderate irritation
DMSO
guinea pig 0.1 ml: shaved dorsal skin painting daily for 3 1 % and 5 %: no depigmentation Gellin et al.
12  , black) 1.0 % ptBP (3 x 3 cm) weeks and no skin irritation 1970
5.0 % ptBP 10 %: marked depigmentation and
10 % ptBP, moderate irritation
propylene glycol
guinea pig ? skin of the flanks moistened 4–6 days transient pigment loss first local at Zavadskii and
40, black) undiluted compresses the application site; 1–2 months Khovanova
(occlusion later: depigmentation far from the 1975
bandage) application site: irreversible, new
hair growth on depigmented skin:
white

ptBP: p-tert-butyl phenol, DMSO: dimethylsulfoxide, NLS: sodium lauryl sulfate,

* synthetic phenol is not defined more clearly by the Russian authors

Volume 11
Volume 11 p-tert-Butyl phenol 21

In the other study with 15 male F344 rats given 1.5 % p-tert-butyl phenol in the diet
for 51 weeks (≈ 750 mg/kg body weight), reductions in body weights (15.7 %; p < 0.001)
and the relative liver weights (8.9 %; p < 0.001) and an increase in the relative kidney
weights (13.5 %; p < 0.001) were found. In the histological examination 14 of 15 rats
were found to have hyperplasia of the forestomach epithelium and one animal a papil-
loma. No tumours were found in the glandular stomach, oesophagus, liver, kidneys or
intestinal tract. If a dose of N-methyl-N'-nitro-N-nitrosoguanidine of 150 mg/kg body
weight were administered one week before the diet containing p-tert-butyl phenol, there
was a significant increase (from 5 % to 15 %) in the incidence of forestomach carcinomas
relative to that in the control group which received only N-methyl-N'-nitro-N-nitroso-
guanidine.

4 Manifesto (MAK value, classification)

Only few of the publications on exposure to p-tert-butyl phenol at the workplace include,
in addition to the clinical observations, data from simultaneous ambient air analyses or
analyses in biological materials. To date there is no investigation available that allows
deduction of a well-founded no effect level for p-tert-butyl phenol.
Rodermund and Wieland once suggested, after discussion with Ikeda and Hara, a
“technical guidance value” of 1 ppm ≅ 6.5 mg/m3 for p-tert-butyl phenol in analogy to
the value for hydroquinone. Later, however, investigations by Wieland et al. (Wieland
1979) showed that only after the p-tert-butyl phenol concentration had been reduced to a
level just below 1 mg/m3 did new cases of disease no longer occur; the suggested MAK
value was therefore not tenable.
Ikeda et al. (1978) also came to this conclusion and suggested a p-tert-butyl phenol
concentration of 2 µg/ml urine for biological monitoring to exclude leukodermogenic
effects (2 µg p-tert-butyl phenol per ml urine was also the detection limit). Because of
the danger of skin penetration they advised the monitoring of exposed persons by urin-
alysis. They did not correlate the concentrations found in the urine with those in the air.
Their biological monitoring included three groups of persons exposed to p-tert-butyl
phenol: 1. workers who operated the machines, 2. engineers, 3. workers in the packing
station, who very probably absorbed p-tert-butyl phenol not only via inhalation but also
as the result of skin contact. In the third group, before improvements were carried out at
the workplace, there were some persons with slight skin depigmentation. After the
improvements, i.e. after semi-automation of weighing and packing of the p-tert-butyl
phenol and the installation of an exhaust system, lower urinary concentrations were
found. Above all, the workers employed in the packing station now had more or less the
same urinary values as the workers at the machines before improvements were carried
out. There had been no cases of vitiligo previously in this group. New cases of
depigmentation were not observed after the workplace improvements. The duration of
the follow-up period—which is particularly important for risk evaluation—was, however,
not specified.
22 p-tert-Butyl phenol Volume 11

Table 6. p-tert-Butyl phenol levels in the urine (in µg/ml urine) before and after workplace
improvements (Ikeda et al. 1978)

Workplace Urine samples Workers at Engineers (7) Product packers

conditions machines (11) (9 and 7)

original during the shift 1.2 (0.5–3.0) 0.5 (0.2–1.2) 6.3 (1.8–21.7)
(exposure)
during the exposure- 0.6 (nd–6.0) tr (nd–0.4) 3.5 (1.0–12.1)
free period
improved during the shift 1.3 (0.4–3.6) tr (nd–1.0) 2.2 (0.7–6.7)
(exposure)
during the exposure- 0.8 (nd–2.3) tr (nd–0.6) 1.8 (0.6–5.6)
free period

tr: traces (below the detection limit of 0.2 µg/ml), nd: not detectable

After calculation of levels in the air from the urinary concentrations, a process which,
however, is based on much hypothesis, Ikeda comes to the conclusion that the value of
5 mg/m3 is about one power of ten too high. Later dust measurements (Ebner et al. 1979)
do not support the value of ≤ 1 mg/m3 proposed by Wieland as at values up to a maxi-
mum of 0.96 mg/m3 p-tert-butyl phenol, 10 persons with vitiligo were found among 34
exposed workers from the boiling room of a synthetic resin plant.
On the basis of this very incomplete and all in all unsatisfactory information, a provi-
sional MAK value of 0.5 mg/m3 has been suggested. It is insufficiently documented and
should be used with caution. Further systematic workplace investigations with careful
monitoring of the p-tert-butyl phenol concentration in the ambient air are urgently
necessary. The available documentation on the effects and pharmacokinetics of p-tert-
butyl phenol demonstrate that greater importance should be given to biological monitor-
ing during health surveillance.
Because very large amounts of p-tert-butyl phenol can be absorbed through the skin,
designation with an “H” is necessary. Avoidance of skin contact is of utmost importance
for occupational safety.
There are several investigations of the allergenic effects of p-tert-butyl phenol in man;
the results are inconsistent. Most of the findings indicate that after exposure to p-tert-
butyl phenol formaldehyde resin the sensitizing effects were not caused by the p-tert-
butyl phenol, but by not yet clearly identified transformation products. As contact aller-
gies to p-tert-butyl phenol have been detected only rarely, p-tert-butyl phenol has not
been designated with an “S” for substances with a sensitizing potential.
As there are no studies available on the question of a possible embryotoxic effect,
p-tert-butyl phenol has been listed in Pregnancy risk group IIc.
Volume 11 p-tert-Butyl phenol 23

5 References

Adams RM (1975) “Spontaneous flare” to p-tert-butylphenol formaldehyde resin. Contact Derm

1: 321
Agatha G, Schubert H (1979) Investigations for allergen identification in contact allergy due to p-
tert-butylphenolformaldehyde resin. (German). Derm Mschr 165: 337–345
Babanov GP, Chumakov NN(1966) The etiology and pathogenesis of occupational vitiligo
(Russian). Vestn Derm Vener 11: 44–48
Bedi TR, Pandhi RK, Bhutani LK (1974) Castellania 2: 39
Beetz D (1971) Allergenicity of shoe glues with p-tert-butylphenol base (German). Derm Mschr
157: 42–48
Bleehen SS, Pathak MA, Hori Y, Fitzpatrick TB (1968) Depigmentation of skin with
4-isopropylcatechol, mercaptoamines and other compounds. J invest Derm 50: 103–117
Bor S, Feiwel M, Chanarin I (1969) Vitiligo and its aetiological relationship to organ-specific
autoimmune disease. Brit J Derm 81: 83–88
Brehm G (1966/67) Contact eczema from synthetic resin glues in the shoe industry (German).
Arch klin exp Derm 227: 353–356
Bruze M, Fregert S, Zimerson E (1985) Contact allergy to phenol-formaldehyde resins. Contact
Dermatitis 12: 81–86
Calnan CD, Cooke MA (1974) J Soc occup Med 24: 59
Calnan CD, Harman RRM (1959) Trans St John’s Hosp derm Soc (Lond) 44: 116
Chumakov NN, Babanov GP, Smirnov AG (1962) Vestn Derm Vener 36: 3
Cunliffe WJ, Hall R, Newell DJ, Stevenson CJ (1968) Vitiligo, thyroid disease and autoimmunity.
Brit J Derm 80: 135–139
Denine (1973) cited in: Zavavskii and Khovanova 1975
DeVries HR (1964) Dermatologica (Basel) 128: 68
Ebner H, Helletzgruber M, Höfer R, Kolbe H, Weissel M, Winker N (1979) Vitiligo from p-tert-
butylphenol; a contribution to the problem of the internal manifestations of this occupational
disease (German). Dermatosen i. Beruf u. Umwelt 27: 99–104
Engel (1966) cited in: Adams 1975
Foussereau J (1976a) unpublished, cited in: Foussereau 1976b
Foussereau J, Benezra C (1970) Les eczemas allergiques professionels, Masson, Paris, p 398, cited
in: Foussereau 1976b
Foussereau J, Cavelier C, Selig D (1976b) Occupational eczema from para-tertiary-butylphenol
formaldehyde resins: a review of the sensitizing resins. Contact Derm 2: 254–258
Gellin GA, Possick PA, Perone VB (1970) Depigmentation from 4-tertiary butyl catechol—an
experimental study. J invest Derm 55: 190–197
Goldmann PJ, Thiess AM (1976) Occupational vitiligo caused by para-tertiary-butylphenol, a trias
of vitiligo, hepatosis and struma. Hautarzt 27: 155–159
Gründer K, Lenzen P, Mayser P (1993) Das Allergenspektrum bei Kontaktekzemen im mittel- und
oberhessischen Einzugsgebiet der Univ.-Hautklinik Gießen. Aktuel Dermatol 19: 269–280
Grunnet I, Howitz J, Reymann F, Schwartz M (1970) Vitiligo and pernicious anemia. Arch Derm
101: 82–85
Hamperl H (1974) Lehrbuch der allgemeinen Pathologie und pathologischen Anantomie, 30th ed,
Springer Verlag, Berlin, Heidelberg, New York, p 55
Hara I (1967) unpublished, cited in Malten et al. 1971
Hara I, Nakajima T (1969) 16th Int Congress Occup Hlth, cited in: Malten et al. 1971
Hara I, Uda K (1966) Jap J industr Hlth 8: 211, cited in: Malten 1973
Hirose M, Fukushima S, Kurata Y, Tsuda H, Tatematsu M, Ito N (1988) Modification of N-methyl-
N'-nitro-N-nitrosoguanidine-induced forestomach and glandular stomach carcinogenesis by
phenolic antioxidants in rats. Cancer Res 48: 5310–5315
24 p-tert-Butyl phenol Volume 11

Hirose M, Inoue T, Asamoto M, Tagawa Y, Ito N (1986) Comparison of the effects of 13 phenolic
compounds in induction of proliferative lesions of the forestomach and increase in the label-
ling indices of glandular stomach and urinary bladder epithelium of Syrian golden hamsters.
Carcinogenesis 7: 1285–1289
Horio T, Tanaka K, Komura J (1977) Depigmentation due to para tertiary butyl catechol. Int Arch
occup environm Hlth 39: 127–133
Ikeda M, Hirayama T, Watanabe T, Hara I (1978) GLC analysis of alkylphenols, alkylcatechols and
phenylphenols in the urine of workers as a measure to prevent occupational leucoderma. Int
Arch occup environm Hlth 41: 125–138
Industrial Hygiene Foundation of America (1976) Chemical and Toxicological Series, Bull 6: 1
cited in: Registry of Toxic Effects of Chemical Substances, NIOSH, Cincinnati, Ohio, USA,
1979, p 900
Itoh K, Nishitani K, Hara I (1968) Bull pharm Res Inst 76: 5
James O, Mayes RW, Stevenson CJ (1977) Occupational vitiligo induced by p-tert-butylphenol, a
systemic disease? Lancet II: 1217–1219
Jimbow K, Obata H, Pathak MA, Fitzpatrick TB (1974) Mechanism of depigmentation by hydro-
quinone. J invest Derm 62: 436–449
Kahn G (1970) Depigmentation caused by phenolic detergent germicides. Arch Derm 102: 177–
187
Kaniwa MA, Isama K, Nakamura A, Kantoh H, Itoh M, Miyoshi K, Saito S, Shono M (1994)
Identification of causative chemicals of allergic contact dermatitis using a combination of
patch testing in patients and chemical analysis. Contact Dermatitis 30: 26–34
Klonne DR, Myers RC, Nachreiner DJ, Homan ER (1988) Acute toxicity and primary irritation of
para-tertiary butylphenol. Drug Chem Toxicol 11: 43–54
Lerner AB (1971) On the etiology of vitiligo and gray hair. Amer J Med 51: 141–147
Loechel J (1971) Derm Mschr 157: 49
Malten KE (1958) Occupational eczema due to p-tert-butylphenol in a shoe adhesive.
Dermatologica (Basel) 117: 103
Malten KE (1967) Contact sensitizations caused by p.tert.butylphenol and certain phenol-
formaldehyde-containing glues. Dermatologica (Basel) 135: 54–59
Malten KE (1973) Occupational dermatoses in the processing of plastics. Trans St. John’s Hosp
derm Soc (Lond) 59: 78–113
Malten KE (1975) Paratertiary butylphenol depigmentation in a “consumer”. Contact Derm 1:
181–182
Malten KE, Seuter E, Hara I, Nakajima T (1971) Occupational vitiligo due to paratertiary
butylphenol and homologues. Trans St John’s Hosp derm Soc (Lond) 57: 115–134
Malten KE, Seutter E (1985) Allergenic degradation products of para-tertiary-butylphenol
formaldehyde plastic. Contact Dermatitis 12: 222–224
Malten KE, van Aerssen RGL (1962) Berufsdermatosen 10: 264
McGuire J, Hendee J (1971) Biochemical basis for depigmentation of skin by phenolic germicides.
J invest Derm 57: 256–261
Mobacken H, Hersle K (1976) Contact Derm 2: 59
Moran M, Martin-Pascual A (1978) Contact dermatitis to para-tertiary-butylphenol formaldehyde.
Contact Derm 4: 372–373
Ochi Y, DeGroot LJ (1969) Vitiligo in Graves’ disease. Ann intern Med 71: 935–940
Odom RB, Stein KM (1973) Proceedings: Depigmentation caused by a phenolic detergent-
germicide. Arch Derm 108: 848
Oettel H (1936) Naunyn-Schmiedeberg’s Arch exp Path Pharmak 183: 317
Okumura Y, Shirai T (1962) Jap J Dermatol 72: 618
Rodermund O-E (1976) Letter: Occupational vitiligo caused by paratertiary butylphenol. Arch
Derm 112: 554–555
Rodermund O-E, Jörgens H, Müller R, Marsteller H-J (1975a) Systemic changes in occupational
vitiligo (German). Hautarzt 26: 312–316
Volume 11 p-tert-Butyl phenol 25

Rodermund O-E, Wieland H (1974) Vitiligo-like depigmentation by paratertiary butylphenol. First

observations in the German Federal Republic (German). Z Hautkr 49: 459–465
Rodermund O-E, Wieland H (1975a) Vitiligo, hepato-splenomegaly, and goitre after working with
paratertiary butylphenol (German). Dtsch med Wschr 100(43): 2216
Rodermund O-E, Wieland H (1975b) Vitiliginous depigmentation, liver and splenic lesions and
struma due to occupational contact with paratertiary butylphenol—a new systemic occupa-
tional disease (German). Berufsdermatosen 23: 193–195
Rodermund O-E, Winkler C, Wuttke H (1975b) Problem of the involvement of the thyroid gland
in vitiligo. Findings in the ptBP (paratertiary butylphenol)-induced, vitiligo-like pigmentation
disorder (German) Z Hautkr 50: 365–370
Smyth HF, Carpenter CP, Weil CS, Pozzani UC, Striegel JA, Nycum JS (1969) Range-finding
toxicity data VII. Amer industr Hyg Ass J 30: 470–476
Suurmond D, Verspijck Mijnssen GAW (1967) Allergic dermatitis due to shoes and a leather
prothese. Dermatologica (Basel) 134: 371–377
Toxicology Data Sheet (1980) Tunstall Research Report TLGR. 79. 164, Jan 1980, Shell
Wieland H (1979) personal communication
Williams RT (1959) Detoxication Mechanisms, Chapman & Hall Ltd., London, England, p 302
Wozniak K-D, Hamm G (1977) Allergic contact eczema and vitiliginous depigmentations caused
by paratertiary butylphenol (German). Berufsdermatosen 25: 215–219
Zavadskii VN, Khovanova EM (1975) Experimental study of the morphogenetic properties of
several phenols inducing a phenocopy of vitiligo (Russian). Genetika 11 (2): 132–139
completed 28.06.1995