Benzaldehyde

MAK value not yet established, see Section IIb

of the List of MAK and BAT Values
Peak limitation –
Absorption through the skin –
Sensitization –
Carcinogenicity –
Prenatal toxicity –
Germ cell mutagenicity –
BAT value –
Synonyms artificial almond oil
benzoic aldehyde
phenyl methanal
Chemical name (CAS) benzaldehyde
CAS number 100-52-7
Structural formula
CHO

Molecular formula C7H6O

Molecular weight 106.13
Melting point –56°C
Boiling point 179°C
3
Density at 20°C 1.05 g/cm
Vapour pressure at 20°C 70 Pa
logPow* 1.48
3 3 3 3
1 ml/m (ppm) 4.403 mg/m 1 mg/m 0.227 ml/m (ppm)

*
n-Octanol/water distribution coefficient
14 Benzaldehyde Volume 17

Benzaldehyde is used as a perfume and flavouring agent in foodstuffs and cosmetics. In

addition it serves as a starting material for the synthesis of numerous organic intermedi-
ates, e.g. in the production of pharmaceuticals.

1 Toxic Effects and Mode of Action

Benzaldehyde is absorbed well via the gastrointestinal tract, skin and lungs. In rats ex-
posed to the substance by inhalation, benzaldehyde is rapidly distributed, especially in
the blood and kidneys, and excreted very rapidly almost exclusively with the urine with a
half-time of about 10 minutes. After oxidation of benzaldehyde to benzoic acid, the main
urinary metabolites are glucuronic acid conjugates or hippuric acid; after reduction of
benzaldehyde to benzyl alcohol, the excretion product is benzyl mercapturic acid.
The main effects during occupational exposure to benzaldehyde are irritation of the
skin, eyes and mucous membranes of the respiratory passages. Despite the relatively
widespread use of the substance there is no evidence of a pronounced sensitization
potential in man.
The acute toxicity of benzaldehyde is low. At the lowest concentration of 500 ml/m3
in short-term inhalation studies with rats, minimal to slight goblet-cell metaplasia in the
area of the nasal septum, clinical symptoms of intoxication and delays in body weight
gain were observed. In studies with medium-term ingestion of high doses, the target
organs of toxic effects are the forestomach, kidneys and brain; the NOEL (no observed
effect level) was found to be 200 mg/kg body weight and day for male rats and
400 mg/kg body weight and day for female rats. In mice, the NOEL for kidney changes
was 300 mg/kg body weight for male animals and 600 mg/kg body weight for females.
Intraperitoneal administration to rats of doses of 5 mg/kg body weight and day for 4 to
12 weeks led to damage in the proximal and distal areas of the respiratory passages.
Benzaldehyde causes moderate irritation on the skin and slight irritation in the eye. Sen-
sitizing effects on the skin can be induced in guinea pigs only after induction with intra-
dermal injection; the findings in animals, therefore, do not indicate that the substance is a
contact allergen. In vitro studies with benzaldehyde yielded evidence of, at most, weak
genotoxic activity; in the Drosophila test benzaldehyde is inactive. A carcinogenic
potential of benzaldehyde cannot be deduced from the results of long-term carcino-
genicity studies with mice and rats given the substance by oral administration.

2 Mechanism of Action

Benzaldehyde binds chemically to cellular macromolecules, in particular to free amino

groups of proteins (e.g. in cell membranes), forming Schiff’s bases (Miyakawa et al.
Volume 17 Benzaldehyde 15

1979, Sakaguchi et al. 1979, Zaugg et al. 1977). This often leads to the inhibition of
enzymatic reactions, for example as a result of the inhibition of cytochrome P450-
dependent monooxygenases (Harper and Patel 1978, Pyykkö and Vapaatalo 1980). The
inhibition of enzyme reactions and the membrane damage certainly also play a decisive
role in the cytotoxicity of benzaldehyde and the inhibiting effects it has been seen to have
on the growth of some tumour cells (see Section 5.8).
Benzaldehyde, like other aldehydes, probably induces lipid peroxidation as the perfu-
sion of isolated rat liver with a benzaldehyde concentration of 10.6 µg/ml led to
increased production of ethane (Müller and Sies 1983).

3 Toxicokinetics and Metabolism

With human abdominal skin samples the permeation rates determined for liquid and gas-
eous benzaldehyde were: undiluted liquid 1970 ± 720 µg/cm2/h, saturated aqueous solu-
tion 450 ± 70 µg/cm2/h, vapour phase above undiluted benzaldehyde 410 ± 70 µg/cm2/h
and vapour phase above saturated aqueous solution 300 ± 60 µg/cm2/h (Barry et al.
1985). Therefore benzaldehyde penetrates the skin more rapidly than do other substances
tested in parallel, e.g. benzyl alcohol.
After inhalation exposure (nose only) to 11C-benzaldehyde (about 7.4 Ci/mmol) for 2
minutes, 24 female Sprague-Dawley rats absorbed between 0.26 and 5.79 mg benzalde-
hyde. Of this only 1.2 % could still be found in the respiratory tract 1.5 minutes after the
end of exposure, a result indicative of rapid absorption. Benzaldehyde was found mainly
in the blood and in the highest concentrations in the kidneys; the maximum values were
determined 5 minutes after the end of exposure (Kutzman et al. 1980).
In the subcutaneous adipose tissue of 25 workers employed in the production of poly-
styrene, benzaldehyde concentrations of 5.68 to 53.25 mg/g adipose tissue were deter-
mined; in 2 control persons the benzaldehyde concentration was 7.1 mg/g adipose tissue
(Wolff et al. 1977). It is unclear whether the workers investigated were exposed to ben-
zaldehyde or the benzaldehyde detected was formed as a metabolite of other aromatic
hydrocarbons. In volunteers who ingested benzaldehyde doses of 5 mg/kg body weight
(as benzaldehyde/β-cyclodextrin tablets), a maximum benzaldehyde concentration in the
blood of 1.3–1.5 mg/ml was determined after 2 to 8 hours. Even without the administra-
tion of benzaldehyde, the substance was detected in the blood (no further details)
(Takeuchi et al. 1983). Benzaldehyde was one of the substances identified in the urine of
a female volunteer not occupationally exposed to benzaldehyde (no quantitative data)
(Zlatkis and Liebich 1971). Benzaldehyde was detected in both maternal blood (from
women without specific benzaldehyde exposure) and the cord blood of new-born babies.
Therefore benzaldehyde is able to cross the placental barrier (Dowty and Laseter 1976).
In vitro studies have revealed enzymes which metabolize benzaldehyde to benzoic
acid and enzymes which convert it to benzyl alcohol. In rat hepatocytes, NAD-dependent
aldehyde-dehydrogenases located in the cytosol and mitochondria oxidize benzaldehyde
16 Benzaldehyde Volume 17

to benzoic acid. The microsomes are involved only to a small extent in the oxidation of
benzaldehyde (Antonenkov et al. 1987, Hellström-Lindahl and Weiner 1985, Smith and
Packer 1972). Pretreatment of male Wistar rats with 20-methylcholanthrene, β-naphtho-
flavone or benz[a]pyrene led to reversible induction of NADP-dependent benzaldehyde-
dehydrogenase in the cytosol, whereas pretreatment with 2-acetylaminofluorene had no
effect (Ritter and Eriksson 1991). High NADP-dependent benzaldehyde-dehydrogenase
activity was observed in rats in liver nodules induced by diethylnitrosamine, and in
untreated animals in the mucous membranes of the tongue, oesophagus, forestomach and
glandular stomach, lower activity in the jejunum and no activity in the duodenum, colon
or pancreas (Chieco et al. 1987). In the livers of pigs, flavin-dependent aldehyde-
dehydrogenase (Mahler 1955) was detected, and in the livers of cattle (Racker 1955) and
rabbits (Raison et al. 1966) similar NAD-dependent enzyme activity which also accepts
benzaldehyde as a substrate. The aldehyde-dehydrogenase activity in the human liver is
independent of the presence of co-factors such as NAD, NADP or FAD (Johns 1967).
Benzaldehyde is also metabolized by a benzaldehyde-dehydrogenase in microsomes from
human nasal mucosa where the enzyme activity was up to ten times higher than that in
microsomes from human liver (Gervasi et al. 1991).
The microsomes of the rat liver can reduce benzaldehyde to benzyl alcohol. In the
oesophagus mucosa no corresponding enzyme activity was observed (Archer and Labuc
1982). For the polymorphic human alcohol dehydrogenases β1-ADH and β2-ADH no
significant differences in activity were found in the reduction of benzaldehyde to benzyl
alcohol (Kassam et al. 1989).
The metabolism of benzaldehyde to benzoic and hippuric acids which was postulated
in early metabolism studies with rats, rabbits and dogs (Cohn 1893, Friedmann and Türk
1913, Stekol 1939, Wöhler and Frerichs 1848) has been confirmed in recent studies. In
the 24-hour urine of rats, on average about 29 % of an intraperitoneal benzaldehyde dose
(about 218 mg/kg body weight) was recovered as hippuric acid (Teuchy et al. 1971).
After inhalation exposure of rats for 2 minutes (see above) more than 90 % of the radio-
active material recovered in the urine was in the form of hippuric acid (Kutzman et al.
1980). In the urine of groups of 3 male rabbits given single oral benzaldehyde doses of
350 and 750 mg/kg body weight, hippuric acid (about 68 %), benzoyl glucuronic acid
(about 10 %), benzyl glucuronide (about 3 %), free benzaldehyde (about 1.5 %) and
traces (< 0.01 %) of benzyl mercapturic acid were found, but not benzyl alcohol or ben-
zyl sulfate esters (Laham et al. 1988). Within 24 hours after ingestion of single doses of
500 to 1500 mg benzaldehyde (about 250–750 mg/kg body weight), rabbits eliminated
about 90 % of the dose almost exclusively as benzoic acid and hippuric acid (Bray et al.
1951).
After short-term oral exposure of Sprague-Dawley rats to benzaldehyde doses of up to
1000 mg/kg body weight and day, the amount of benzylmercapturic acid excreted in the
urine correlated with the dose and duration of exposure. This metabolite is probably
formed via the reduction of benzaldehyde to benzyl alcohol and the subsequent esterifi-
cation with sulfate by sulfotransferases, followed by the exchange of the sulfate group for
glutathione by glutathione-S-transferases (Laham and Potvin 1987). After a single intra-
peritoneal benzaldehyde dose of about 210 mg/kg body weight, however, the formation
Volume 17 Benzaldehyde 17

of benzylmercapturic acid could not be detected, unlike with benzaldehydes substituted

in ortho position (Seutter-Berlage et al. 1982).
After inhalation exposure of rats for 2 minutes (see above), the substance was elimi-
nated almost exclusively with the urine where it was detected as soon as 1.5 minutes after
the end of exposure. On the other hand, significant amounts of 11C activity were not
found in either the exhaled air or the small intestine. The half-life in blood and in most
organs was found to be 8.1 minutes, in less well-vascularized organs and tissues (e.g.
skin, adipose tissue) elimination began only after 5 and 12 minutes, respectively
(Kutzman et al. 1980).

4 Effects in Man

4.1 Single exposures

The odour threshold for benzaldehyde is given as 0.00018 to 0.042 ml/m3 (0.0008–
0.01849 mg/m3) (Ruth 1986). While transferring benzaldehyde from barrels to a reac-
tion vessel, workers were exposed to benzaldehyde vapour in concentrations of 0.4 to
0.7 ml/m3 (1.8–3.0 mg/m3) over a period of 85 to 210 minutes. A strong odour was per-
ceived. During a similar work process, workers were exposed to 2.1 ml/m3 (9.2 mg/m3)
for 15 minutes. The odour was described as strong and penetrating. Irritation of the eyes
or upper respiratory passages did not occur (AIHA 1993). The lowest benzaldehyde
concentration that still led to irritation of the eyes and upper respiratory passages of
volunteers exposed for 1 minute was found to be 4.6 ml/m3 (20 mg/m3) (Peresedov
1974). These observations cannot be used for the evaluation of a MAK value as the data
are inadequate, for example with regard to the number of persons exposed.
In a young girl, ingestion of about 50 to 60 ml benzaldehyde led to death. Autopsy did
not reveal any characteristic organ changes. In the stomach large amounts of a yellowish-
white mush with a strong bitter almond smell were found and the stomach mucosa were
pale and dry, and in places reddened. In the region above the small intestine hyperaemia
was detected, and in the pleura and pericardium ecchymosis (Dadlez 1928).

4.2 Repeated exposures

At workplaces in Russian chemical companies an average benzaldehyde vapour concen-

tration of 5 mg/m3 was determined. Respiratory diseases were more common here than at
other workplaces. Adverse effects of benzaldehyde on the health of the workers were,
however, not observed (Peresedov 1974). Because of the inadequacy of the documenta-
tion, these data cannot be used in the evaluation of the substance.
18 Benzaldehyde Volume 17

Benzaldehyde was tested in 102 cancer patients as a chemotherapeutic agent. Because

of its poor solubility in water, the benzaldehyde was administered orally or rectally in the
form of a β-cyclodextrin enclosure compound with a benzaldehyde content of 8.3 % in
doses of 10 mg/kg body weight and day divided into 4 portions. Even after administra-
tion for a period of more than one year, the treatment did not lead to toxic effects or
changes in haematological or biochemical parameters (Kochi et al. 1980).

4.3 Local effects on skin and mucous membranes

Skin contact with benzaldehyde led to marked itching, burning and hyperaemia; after the
skin had been cleansed, the symptoms were reversible (Peresedov 1974). On the other
hand, occlusive application of 4 % benzaldehyde in petrolatum to the skin of various
volunteers for 48 hours did not lead to skin irritation (Opdyke 1976).

4.4 Allergenic effects

Despite the relatively widespread use of the substance, only few cases of contact allergy
to benzaldehyde have been described in the literature. This may be because direct skin
contact with the substance is rare.
In a retrospective study of the cases of occupational dermatitis observed in a large
chemical concern between 1924 and 1951, 3 cases were listed as possibly caused by
benzaldehyde (Berg and Weichardt 1954). There are, however, e.g. no anamnestic data
for the exposure, the severity of the disease or the results of patch tests that might have
been carried out, so that an allergic genesis of the skin diseases has not been demon-
strated.
In patch tests with 100 patients, 10 reacted to 5 % benzaldehyde in petrolatum. Six of
12 patients tested with both benzaldehyde and 10 % bitter almond oil (in olive oil)
reacted to both substances, 5 to neither of the substances and one to the oil, but not, how-
ever, to benzaldehyde (Hjorth 1961). In another single case-report of a reaction to soap
containing bitter almond oil, details of the tests carried out are not provided (Bonnevie
1939, Hansen 1936).
Also the immediate urticarial reactions described in three patients with chronic urti-
caria (Forsbeck and Skog 1977, Ludera-Zimoch 1981, Seite-Bellezza et al. 1994) are not
indicative of a pronounced sensitizing potential of benzaldehyde. The symptoms ob-
served after 20 to 30 minutes in occlusive patch tests could also be the result of cross-
reactions with cinnamic aldehyde contained in balsam of Peru, which is frequently
responsible for urticaria.
According to an earlier study, reactions to benzaldehyde in patch tests occurred in
particular in patients who reacted to vanillic aldehyde or benzoic acid (Hjorth 1961).
Definitive statements about immunological cross-reactions with benzaldehyde and vanil-
lic acid cannot be made, however, on the basis of the little data available.
A patient who reacted strongly to 1 % benzyl alcohol reacted only weakly to 5 %
benzaldehyde (both in petrolatum) (Mitchell and Beck 1988).
Volume 17 Benzaldehyde 19

In 2 maximization tests each with 25 volunteers and 4 % benzaldehyde in petrolatum,

sensitizing effects on the skin were not detected (Opdyke 1976).
There are no data available for airway sensitization caused by the substance.

5 Animal Experiments and in vitro Studies

5.1 Acute toxicity

5.1.1 Inhalation

In the time hazard test (dynamic evaporation) groups of 5 male and 5 female Wistar rats
were exposed in whole body exposure chambers for 3 and 7 hours to a benzaldehyde
atmosphere produced at 20°C (no data on concentration) and observed for 14 days. One
male from the 7-hour group died after 2 days. Up to 9 days after exposure the animals
were apathetic and their fur was unkempt. During the first two follow-up days, laboured
breathing and a stiff gait were observed, and irritation of the mucous membranes of the
eyes and nose. The body weight gains of the surviving animals of the 7-hour group were
delayed in the first week of the recovery period. In the rat that died during the experi-
ment, reddish-grey discoloration was found in the lungs, the size of the spleen was
decreased, and the intestinal contents were dark brown. In some of the animals killed at
the end of the follow-up period the lungs were slightly inflated (Bayer 1981).
In an inadequately documented publication, irritation of the eyes and the mucous
membranes of the upper respiratory passages and slight drowsiness were reported in ani-
mals exposed briefly by inhalation to benzaldehyde vapour at about 500 mg/m3 (about
115 ml/m3); there were no deaths. The lowest concentration at which acute symptoms of
intoxication occurred was 82 mg/m3 (about 19 ml/m3). In rabbits a decrease in the respi-
ration rate was observed from a concentration of 10 mg/m3 (about 2.3 ml/m3) (Peresedov
1974).
The sensory irritation potential of benzaldehyde vapour was investigated with groups
of 3 to 4 male B6C3F1 and Swiss-Webster mice by determining the depression of the
respiration rate during exposure of the head and nose for 10 minutes followed by a
5-minute recovery period. In the first minutes of exposure the respiration rate decreased
to a minimum, followed by a slight increase and a renewed decrease towards the end of
exposure. A decrease in the respiration rate by 50 % was observed in the B6C3F1 mouse
at a concentration of 394 ml/m3 (1735 mg/m3), in the Swiss-Webster mouse at 333 ml/m3
(1466 mg/m3) (Steinhagen and Barrow 1984). Under identical experimental conditions,
the respiration rate in 4 male F344 rats at 1423 ml/m3 (6266 mg/m3) was, however,
decreased by only 30 %. This concentration was approaching the range of maximum
vapour saturation of about 1600 ml/m3 (Babiuk et al. 1985).
20 Benzaldehyde Volume 17

5.1.2 Ingestion

The acute oral toxicity of benzaldehyde (see Table 1) is low, with LD50 values from 1000
to 2850 mg/kg body weight. The unusually low LD50 values for the male Swiss mouse
(oral 27.8 mg/kg body weight; intraperitoneal 9.5 mg/kg body weight) (Caprino et al.
1976) could be the result of impurities in the test substance or a greater sensitivity of the
Swiss mouse than of other strains of mouse and other species. The symptoms of intoxi-
cation observed in the rat were narcosis, coma, sedation, depression, tremor, unkempt
fur, weight loss and decreased general well-being, as well as paralysis of the hind legs in
the female rats. Autopsy did not reveal any unusual gross pathological findings (Bayer
1978, 1982a, 1982b). In guinea pigs diuresis, tremor, irritation of the gastrointestinal
tract and haemorrhage were described (Jenner et al. 1964). In the dog, oral benzaldehyde
doses of 2100 mg/kg body weight (mixed with a little water) led to a slight decrease in
the respiration rate (Macht 1922).

Table 1. Acute toxicity of benzaldehyde

Species, strain Sex LD50 Comments References

[mg/kg body weight]

oral
rat, n.s. 2279 Bayer 1978
rat, n.s. 1502 Bayer 1982a
rat, n.s.  1292 Bayer 1982b
rat, n.s. ,  1300 Jenner et al. 1964,
Taylor et al 1964
rat, n.s. n.s. 2400 Peresedov 1974
rat, n.s. n.s. 2850 Sporn 1967
mouse, Swiss 27.29 10 % in sesame oil Caprino et al. 1976
mouse, n.s. n.s. 2020 Peresedov 1974
guinea pig, n.s. ,  1000 Jenner et al. 1964
intraperitoneal
mouse, Swiss 9.49 10 % in sesame oil Caprino et al. 1976
mouse, n.s. ,  1020 24-hour LD50, Caujolle et al.
benzaldehyde in olive oil 1956
mouse, CD-1 1150 death within 4 hours McCloskey et al.
1986
mouse, n.s. n.s. 3265 Sporn 1967
dermal
rabbit, n.s. n.s. > 1250 occlusive exposure for Opdyke 1976
24 hours

n.s. not specified

Volume 17 Benzaldehyde 21

5.1.3 Dermal and parenteral absorption

The dermal LD50 value for the rabbit was found to be over 1250 mg/kg body weight (no
further details) (Opdyke 1976).
The intraperitoneal LD50 values were similar to the oral LD50 values (see Section
5.1.2 and Table 1). Doses which were ultimately lethal led in male CD-1 mice within 15
to 30 minutes to dyspnoea, and to tremor, sedation, laboured breathing and weight loss.
In this period the maximum plasma benzaldehyde concentration of about 40 µg/ml was
reached; within 60 minutes it then decreased to about 5 µg/ml (McCloskey et al. 1986).
The lethal subcutaneous dose was given as 5250 mg/kg body weight for the rat; after
intraperitoneal injection this dose did not cause death in all animals, but was tolerated
with marked symptoms of intoxication. Benzaldehyde doses up to 21000 mg/kg body
weight could be administered to rabbits as intravenous injections of a 0.2 % aqueous
solution without serious toxic effects. In the dog, subcutaneous or intravenous injection
of benzaldehyde doses of 1050 mg/kg body weight led to a slight decrease in the respira-
tion rate. In dogs, intravenous benzaldehyde doses of more than 21000 mg/kg body
weight (0.2 % solution) caused only slight toxic effects such as decreased blood pressure,
decreased respiration rate, inhibition of intestinal contractions and dilation of the blood
vessels of the gastrointestinal tract. Injections of benzaldehyde in extremely high doses
into experimental animals caused in particular toxic effects on the medulla, reduction in
the respiration rate, even to the point of respiratory failure, but only slight impairment of
the activity of the heart (Macht 1922).

5.2 Subacute, subchronic and chronic toxicity

5.2.1 Inhalation

In a short-term inhalation study, groups of 14 Sprague-Dawley rats per sex and group
were exposed in whole animal exposure chambers on 14 consecutive days, for 6 hours a
day, to benzaldehyde vapour in concentrations of 0, 500, 750 and 1000 ml/m3 (about
2200, 3300 and 4400 mg/m3). During the experiment 11 animals from the 1000 ml/m3
group died (10 females, 1 male) and 3 female animals from the 750 ml/m3 group. In all
animals exposed to benzaldehyde, tremor, piloerection, diuresis, decreased respiration
rates, hypothermia, reduced motor activity and concentration-dependent symptoms of eye
and nose irritation occurred in the first week of the experiment. Body weight gains were
significantly reduced in all male animals. In the animals of the 1000 ml/m3 group there
were severe effects on the central nervous system, characterised by abnormal posture and
frequent seizures. In all dose groups the aspartate-aminotransferase activity in the serum
was increased. Only in the female animals were the cholinesterase activity and the albu-
min and total protein levels decreased, and the monocyte count and liver weights in-
creased. In the male animals of the 1000 ml/m3 group the haemoglobin levels, the packed
cell volume, the MCH (mean absolute haemoglobin coefficient) and MCHC (mean
haemoglobin concentration of the individual erythrocytes) were decreased, and in the
22 Benzaldehyde Volume 17

female animals the erythrocyte count. The leukocyte count was increased in the male ani-
mals of this group. Histopathological examination revealed in the 500 and 1000 ml/m3
groups slight (male animals) to minimal (female animals) goblet cell metaplasia, mainly
in the region of the nasal septa. Inflammatory or degenerative changes in the nasal mu-
cosa and changes in other organs and tissues were not detected. Because effects occurred
even at the lowest benzaldehyde concentration of 500 ml/m3, this study did not yield a
NOEL (Laham et al. 1991).
In albino rats exposed over a period of 4 months for 5 hours a day to benzaldehyde
concentrations of 26 mg/m3 (about 6.0 ml/m3) under dynamic conditions, 3 months after
the beginning of the experiment changes were detected in haematological parameters
(hypoglobulinaemia, erythrocytosis, leukocytosis, initial lymphocytosis followed by lym-
phopenia) and delays in body weight gain. At the end of the experiment all the param-
eters were within the normal range. Exposure to benzaldehyde concentrations of 6 mg/m3
(about 1.4 ml/m3) under otherwise identical conditions was tolerated by albino rats with-
out symptoms (no further details) (Peresedov 1974). Because of the only very incomplete
description of the experiment and results, this study can be validated only in part and is
not suitable for evaluating a MAK value.

5.2.2 Ingestion

3 male and 3 female rats were given gavage doses of benzaldehyde of 433 mg/kg body
weight and day (about 1/3 LD50) on 4 consecutive days, and were killed on day 5. One of
the 6 animals died during the experiment. Gross pathological liver damage was not seen
(Taylor et al. 1964). In 3 male Sprague-Dawley rats given 1 % benzaldehyde with the
diet (about 667 mg/kg body weight and day) over a period of 14 days, no structural
changes were detected in the liver cells (Klecak et al. 1977).
Groups of 5 male and 5 female F344 rats were given a total of 12 gavage doses of
benzaldehyde of 100, 200, 400, 800 and 1600 mg/kg body weight (dissolved in corn oil)
on 5 days/week, and were killed after a 2-day follow-up period. From 800 mg/kg body
weight, increased excitability, tremor and lethargy were observed in all animals. All
animals from the 1600 mg/kg group died after the second dose. In the 800 mg/kg group 2
male and 2 female animals died and body weight gains were reduced by 50 %. At the end
of the experiment the body weights of the females were lower than those of the control
animals by 11 %, and those of the males by 14 %. Autopsy did not reveal substance-
related gross pathological organ changes. This study yielded a NOEL of 400 mg/kg body
weight and day for the rat (Kluwe et al. 1983, NTP 1990).
Groups of 5 male and 5 female B6C3F1 mice were given a total of 12 gavage doses of
benzaldehyde of 200, 400, 800, 1600 and 3200 mg/kg body weight (dissolved in corn
oil) on 5 days/week. All the animals of the 1600 mg/kg and 3200 mg/kg groups died
within the first 2 to 3 days of the experiment, and in the 800 mg/kg group 1 male animal
died. Up to the end of the 2-day recovery period, clinical symptoms of intoxication and
substance-related gross pathological organ changes were not observed and the body
weight gains in all surviving animals were normal. Thus in this 2-week study for mice as
Volume 17 Benzaldehyde 23

for rats (see above) a NOEL of 400 mg/kg body weight and day was found (Kluwe et al.
1983, NTP 1990).
In albino rats given oral doses of benzaldehyde of 10 mg per animal (about 50 mg/kg
body weight) every second day over a period of 8 or 12 weeks, body weight gains and
organ weights (liver, adrenal gland), levels of nitrogen and lipid, and enzyme activities
(succinate dehydrogenase, aldolase, aspartate aminotransferase) in the liver and levels of
ascorbic acid in the adrenal gland were unaffected (Opdyke et al. 1976).
Groups of 10 male and 10 female F344 rats were given gavage doses of benzaldehyde
of 50, 100, 200, 400 and 800 mg/kg body weight (dissolved in corn oil) on 5 days/week
for a period of 13 weeks. The symptoms of intoxication observed in the animals of the
800 mg/kg group were increased activity, trembling or periodic inactivity. 6 males and 3
females of this group and 1 female animal of the 400 mg/kg group and the control group
died in the second half of the experiment. In the male animals of the 800 mg/kg group,
body weight gains and the absolute and relative weights (relative to the brain weight) of
the thymus and testes were reduced. The female animals of this group were found to have
slightly increased liver, kidney, thymus and heart weights. At the end of the experiment
the body weights of the male animals of the 800 mg/kg group were reduced by 26 %
relative to those of the vehicle controls. In the histopathological examination, damage to
the kidneys (weak to moderate degeneration and regeneration of the epithelium in the
region of the proximal tubule convolution) and the brain (minimal to marked focal to
multifocal degeneration and necrosis of the granular cells and Purkinje’s cells in the
cerebellum, and necrosis in the hippocampus) were found only in the animals of the
800 mg/kg group. In most of the animals of the 800 mg/kg group and 2 males of the
400 mg/kg group, slight hyperplasia and hyperkeratosis of the forestomach epithelium,
accompanied by increased mitotic activity in the basement membrane, were detected. For
the other dose groups gross pathological and microscopic examinations were not carried
out. This study therefore yielded a NOEL for female rats of 400 mg/kg body weight and
day and for male rats, as a result of the slight damage to the forestomach, of 200 mg/kg
body weight and day (Kluwe et al. 1983, NTP 1990).
A study with the same design was also carried out with male and female B6C3F1 mice
given benzaldehyde doses of 75, 150, 300, 600 or 1200 mg/kg body weight and day. No
clinical symptoms of intoxication were observed. All male animals and one female from
the 1200 mg/kg group died during the first 4 weeks of the experiment. The body weight
gains were reduced in the female animals after doses of 1200 mg/kg and in the male
animals after doses as low as 600 mg/kg. At the end of the experiment the body weights
of the male animals of the 600 mg/kg group were reduced by 9 % relative to those of the
controls. The organ weights did not differ from the control values. In the gross patho-
logical and microscopic examinations, weak to moderate degeneration of the renal
tubules was detected in all male animals of the 1200 mg/kg group and one male of the
600 mg/kg group. This study therefore yielded a NOEL for male mice of 300 mg/kg
body weight and day and for female mice of 600 mg/kg body weight and day (Kluwe et
al. 1983, NTP 1990).
Groups of 5 male and 5 female Osborne-Mendel rats were given benzaldehyde in the
diet in concentrations of 1000 and 10000 mg/kg (corresponding to doses of about 70 and
700 mg/kg body weight and day) for a period of 16 and 27 to 28 weeks. The control
24 Benzaldehyde Volume 17

groups comprised 10 male and 10 female animals. There were no effects on body weight
gains, organ weights or haematological parameters, or unusual findings in the gross path-
ological and microscopic examinations (Hagan et al. 1967). Likewise, administration of
1 % benzaldehyde with the diet (about 700 mg/kg body weight and day) for 15 to 19
weeks did not lead to liver damage in the rat (no further details) (Taylor et al. 1964).
In a carcinogenicity study (see Section 5.7 and Table 3), groups of 50 male and 50
female F344 rats and B6C3F1 mice were given gavage doses of benzaldehyde (dissolved
in corn oil) on 5 days/week for a period of 103 to 104 weeks. The doses given to the
female mice were 300 and 600 mg/kg body weight and day, and to all other groups 200
and 400 mg/kg body weight and day. In all the treated rats and mice, the body weights
were comparable with those of the controls; survival was significantly reduced only in
the male rats of the 400 mg/kg group after day 373 of the experiment. There were no
clinical symptoms of intoxication (Kluwe et al. 1983, NTP 1990).
In 14 dogs and 11 cats suffering from diverse malignant tumours, daily oral doses of
benzaldehyde of 10 mg/kg body weight (divided into 4 daily portions) had only minimal
therapeutic effects. Toxic side-effects did not occur even with long-term treatment for up
to 74 weeks (MacEwen 1986).

5.2.3 Intraperitoneal and subcutaneous injection

Groups of 20 female SIV-50 rats were given a daily intraperitoneal injection of 1 mg

benzaldehyde (about 5 mg/kg body weight and day) for a maximum period of 12 weeks.
4 animals were killed after 4 and 8 weeks and the remaining animals after 12 weeks and
extensive histomorphological examination of the respiratory tract was carried out. After
as little as 4 weeks, beginning hyperplasia of the peribronchial lymphatic system was
found in the treated animals and after 12 weeks pronounced hyperplasia. In addition,
after 12 weeks, atrophy of the mucosal epithelium in the proximal area of the respiratory
tract and goblet cell hyperplasia in the distal area were observed; perivasculitis was seen
as evidence of damage to vessel walls. Thus the mucosal irritation caused by benzalde-
hyde after intraperitoneal administration led in the lungs to degenerative changes and a
proliferative stimulus. These effects of benzaldehyde may play an important role in the
expression of the carcinogenic effects of DNA adducts of the carcinogen N-nitroso-
N-methylbenzylamine (NMBA), as benzaldehyde and alkylating species are formed in
equimolar amounts in the metabolism of NMBA. The simultaneous administration of
benzaldehyde, NMBA (10 mg/l drinking water) and disulfiram (DSF; 200 mg/kg diet)
led to a marked increase in the severity of the histomorphological changes induced by
benzaldehyde alone and to earlier onset of the changes. This effect is probably caused by
the DSF-induced inhibition of aldehyde dehydrogenase, which leads to higher benzalde-
hyde concentrations in the target tissue. When benzaldehyde and NMBA were adminis-
tered simultaneously, the effects were much less severe than with benzaldehyde alone.
Merely weak hyperplasia of the goblet cells and of the peribronchial lymphatic system
were detected after 8 weeks. This is possibly the result of the fact that benzaldehyde-
detoxifying enzymes are induced by the administration of NMBA, and benzaldehyde is
thus metabolized more rapidly (Schweinsberg et al. 1986).
Volume 17 Benzaldehyde 25

In rabbits, repeated subcutaneous injection of benzaldehyde doses of 1400 mg per

animal (twice daily on 7 consecutive days; total dose 19600 mg/animal or about 9800 mg
per kg body weight) led to debilitation, paralysis, tremor, diarrhoea, nephritis and to
deaths after 2 to 4 days (Cohn 1893).

5.3 Local effects on skin and mucous membranes

Application of undiluted benzaldehyde to the intact or scarified rabbit skin (occlusive;

Opdyke 1976) and to the inside of the rabbit ear (semi-occlusive; Bayer 1979) for 24
hours had moderately irritative effects. Benzaldehyde was not found to have irritative
effects on the skin of 10 guinea pigs in the patch test (no further details) (Du Pont 1947).
In non-occlusive patch tests, however, benzaldehyde concentrations of 10 % and 3 %
applied once and 21 times, respectively, produced minimal skin irritation in guinea pigs
(Klecak et al. 1977).
In the rabbit eye benzaldehyde (100 µl/animal) was slightly irritative (Bayer 1979).
The instillation of 0.2 % benzaldehyde into the conjunctival sac of rabbits and dogs led
to transient narcosis of the cornea and irritation of the conjunctiva (Macht 1922). After
instillation of benzaldehyde into the rabbit eye, blepharospasm, lacrimation and hyper-
aemia of the conjunctiva were observed (Peresedov 1974).

5.4 Allergenic effects

Positive, but incompletely documented results were obtained in a study with benzalde-
hyde in the Draize test, maximization test and FCA test with male and female guinea pigs
(Himalayan white-spotted). In the Draize test the animals were treated once intradermally
with 0.05 ml and on nine subsequent days with 0.1 ml of a 0.1 % preparation of benz-
aldehyde (in total 0.95 mg/animal) in isotonic saline. Provocation was carried out on
days 35 and 49 by intradermal injection of 0.05 ml of the 0.1 % preparation.
The test protocol of the maximization test corresponded more or less with the stan-
dard conditions: intradermal induction with 5 % benzaldehyde (in total 20 mg, vehicle
not specified), epicutaneous induction by means of 48-hour occlusive treatment with a
moderately irritative preparation of 25 % benzaldehyde (250 mg) in petrolatum, provo-
cation on day 21 with a non-irritative concentration in petrolatum (24 hours, occlusive,
no further details).
In the FCA test, induction was carried out by 5 injections in the necks of the animals
on days 0, 2, 4, 7 and 9 of 0.05 ml (in total about 250 mg) of the undiluted substance
spiked with the same amount of FCA, and provocation on days 21 and 35 with a non-
irritative concentration in petrolatum (24 hours, occlusive, no further details). Control
animals were treated intradermally with FCA only (Klecak et al. 1977).
The result of a non-occlusive patch test was, however, negative. Induction was carried
out by 21 non-occlusive applications of 1 % to 100 % benzaldehyde (vehicle not speci-
fied) to groups of 6 to 8 animals, and provocation after the 21st application and after a
26 Benzaldehyde Volume 17

further 14 days with a concentration (3 %) which caused minimal irritation at this time
and a non-irritative concentration (Klecak et al. 1977).

5.5 Reproductive and developmental toxicity

5.5.1 Fertility

10 female rats were given oral doses of 2 mg benzaldehyde per animal (about 5 mg/kg
body weight and day) every second day for a period of 223 days, and were mated with
untreated males on days 75 and 108 after the beginning of treatment. The control group
consisted of 10 untreated females. The number of offspring, the weight of the pups after
1 and 3 weeks and survival of the pups was in the range of the control values. The num-
ber of pregnant females in the test group was decreased relative to that in the control
group (Sporn et al. 1967). The study design (small number of treated animals, only one
dose group) does not meet present-day standards and cannot, therefore, be regarded as
evidence of impairment of female fertility.
In a medium-term study with male F344 rats (for more details see Section 5.2.2)
decreased testis weights were observed, but the effective dose of 800 mg/kg body weight
(dissolved in corn oil, administered by gavage) was highly toxic and led to the death of 6
of 10 animals, so that this finding cannot be regarded as evidence of an impairment in
fertility. In the 400 mg/kg group, in which there were no deaths or signs of intoxication,
this effect did not occur (Kluwe et al. 1983, NTP 1990).
There are no developmental toxicity studies available.

5.6 Genotoxicity

5.6.1 In vitro

The genotoxicity of benzaldehyde has been investigated in many in vitro test systems
(see Table 2). In Salmonella typhimurium, in mutagenicity studies with the strains TA98,
TA100, TA102, TA104, TA1535, TA1537 and TA2637, and in a DNA repair test with
and without metabolic activation, no genotoxic activity could be detected. In a muta-
genicity test with Escherichia coli WP2 uvrA and the mutagen 4-nitroquinoline-1-oxide,
benzaldehyde from concentrations of 2120 µg/plate was found to have an antimutagenic
effect (Watanabe et al. 1988). In Bacillus subtilis, DNA-damaging effects were observed
at high concentrations only after metabolic activation. An increase in the incidence of
mutants in the mouse lymphoma test occurred only in the high, cytotoxic concentration
range and the finding is therefore questionable. Evidence of a weak clastogenic potential
in the chromosomal aberration test and in the sister chromatid exchange test was also
found only with high concentrations. Therefore there is merely evidence of weak
genotoxic activity of benzaldehyde.
Volume 17 Benzaldehyde 27

Table 2. Studies of the genotoxicity of benzaldehyde

Test system S9 Result Concentration References

mix

Salmonella mutagenicity test –/+ – 3 µmol/plate Florin et al.

S. typhimurium TA98, TA100, 1980
TA1535, TA1537
S. typhimurium TA98, TA100, –/+ – 10–1000 µg/plate Haworth et al.
TA1535, TA1537 1983
S. typhimurium TA98, TA100 –/+ – 0.05–500 µg/plate Kasamaki et
al. 1982
S. typhimurium TA100, TA102, –/+ – 33–3333 µg/plate NTP 1990
TA104
S. typhimurium TA98, TA100, –/+ – 50–2000 µg/plate Nohmi et al.
TA2637 1985
S. typhimurium TA100 – – 0.1–1000 µg/plate Rapson et al.
1980
S. typhimurium TA98, TA100 –/+ – not specified Sasaki and
Endo 1978
S. typhimurium TA100 –/+ – 0.0001–2 µmol/plate Vamvakas et
al. 1989
DNA repair, umu test –/+ – 493 µg/ml Ono et al.
S. typhimurium TA1535/pSK 1991
DNA damage, rec assay – – about 1000 µg/ml Matsui et al.
Bacillus subtilis + + 1989
– – 21 µg/plate Oda et al.
1978
gene mutation, – ? after 400 and 480 µg/ml incidence McGregor et
mouse lymphoma test of mutants significantly increased; al. 1991,
from 640 µg/ml highly cytotoxic NTP 1990
chromosomal aberration –/+ – up to 1600 µg/ml Galloway et
CHO cells al. 1987,
NTP 1990
CHL cells – + effects from 1000 µg/ml Sofuni et al.
+ ? weak effects from 1000 µg/ml 1985
CH-B241 cells – ? significantly increased after 50 nM Ishidate et al.
(5.3 ng/ml); evaluation question- 1988,
able as only one very low Kasamaki et
concentration tested al. 1982
SCE – – up to 1000 µM = 106 µg/ml Sasaki et al.
CHO cells (cytotoxic range) 1989
– (+) significant from 50 µg/ml Galloway et
+ (+) significant from 1600 µg/ml al. 1987,
weak concentration-dependent NTP 1990
effects
human lymphocytes – + significantly increased from Jansson et al.
600 µM (63.6 µg/ml), not 1988
concentration-dependent

? result unclear (+) weak positive

28 Benzaldehyde Volume 17

5.6.2 In vivo

In the sex-linked recessive lethal test with Drosophila melanogaster, benzaldehyde

administered in a concentration of 1500 ppm with the diet and injection of 2500 ppm was
inactive (NTP 1990, Woodruff et al. 1985).

5.7 Carcinogenicity

Prolonged in vitro treatment of C3H/HE mouse embryo cells with benzaldehyde con-
centrations of 106 mg/ml decreased the incidence of spontaneous cell transformation
(Nambata et al. 1980).
The carcinogenicity study with F344 rats and B6C3F1 mice (NTP 1990) is described
in detail in Table 3.
Some of the rats in the 400 mg/kg group died prematurely (from week 20). The sur-
vival of the male animals was significantly decreased from day 373 of the experiment (53
weeks) up to the end of the experiment, while survival of the female animals at the end of
the experiment was comparable to that of the control animals. The increase in the inci-
dence of some tumours in the male rats was not regarded as substance-related for the
following reasons. The incidence of malignant mesotheliomas was not dose-dependent.
The incidences of mesotheliomas and pancreas adenomas were increased relative to the
experimental control values, but not relative to the historical control incidences (Table
3). The overall incidence of monocyte leukaemia was independent of the dose and only
slightly increased; the incidences of the relevant stage 2 and stage 3 changes were in the
control range. In the female rats, only increased incidences of forestomach papillomas
(c.f. findings in mice) were recorded, which are not relevant for man. The findings in the
rat were not regarded by the NTP as evidence of carcinogenic effects.
In the mice there was no evidence of toxicity in any dose group; the animals would
have tolerated even higher doses. The only pathological change which was not also found
in the control group was an increase in the incidence of hyperplasia and squamous cell
papillomas of the forestomach. These findings were regarded by the NTP as some evi-
dence of carcinogenicity, but are probably the result of the irritative effects of benzalde-
hyde and are not of relevance for man because of the species-specific location.
Overall, therefore, there was no evidence in either mice or rats of a carcinogenic
potential of benzaldehyde, which is in accordance with the, at most, low genotoxic activ-
ity of benzaldehyde in vitro.

5.8 Other effects

Benzaldehyde caused a decrease in muscle tonus and muscle contraction, and, in a 1 mM

to 2 mM concentration range, complete muscle paralysis in isolated guinea pig and rabbit
uterus and rabbit intestine (Alves et al. 1940).
 Volume 17
Table 3. Carcinogenicity studies with benzaldehyde

Author: NTP 1990

Species: F344 rat
Administration: gavage
Dose: 0, 200 and 400 mg/kg body weight and day
Duration: 2 years, 5 days/week
Toxicity: body weight gains comparable with those of the controls;
survival: from week 20 decreased in and ; after week 104: decreased in (29/50, 21/50, controls: 37/50), in  comparable with
that in the controls: 33/50, 29/50, controls: 33/50
Comments: conclusion of the NTP: tumour findings regarded as not substance-related; ‘no evidence of carcinogenic effects’

Sex 
Dose 0 200 400 0 200 400

pancreas adenoma (diameter > 3 mm) 3/49 (6 %)3 2/49 (4 %) 7/48 (15 %)1,2
pancreas hyperplasia (diameter < 3 mm) 6/49 (12 %) 6/49 (12 %) 12/48 (25 %)
4 1
malignant mesothelioma of the tunica vaginalis or 0/50 (0 %) 5/50 (10 %) 2/50 (4 %)
the peritoneum
monocyte leukaemia 10/50 (20 %) 17/50 (34 %)1 16/50 (32 %)1
of these, stage 2 or stage 3 changes 6/50 (12 %) 7/50 (14 %) 9/50 (18 %)
squamous cell papilloma of the forestomach 0/50 (0 %)5 0/50 (0 %) 2/50 (4 %)

Benzaldehyde
forestomach hyperplasia 5/50 (10 %) 2/50 (4 %) 3/50 (6 %)
1
significant increase
2
dose–response relationship
historical controls:
3
laboratory: 9 ± 9 %, NTP: 5 ± 7 %
4
laboratory: 3 ± 3 %, NTP: 4 ± 3 %
5
laboratory: 0.7 %, NTP: 0.4 %

29
 30
Table 3. continued

Author: NTP 1990

Species: B6C3F1 mouse

Benzaldehyde
Administration: gavage
Dose: : 0, 200 and 400 mg/kg body weight and day; : 0, 300 and 600 mg/kg body weight and day
Duration: 2 years, 5 days/week
Toxicity: no evidence of toxicity: body weight gains and survival comparable with in the controls
Comments: MTD not reached
evaluation of the NTP: forestomach papillomas in not significantly increased, but more frequent than in the historical controls;
in  at both doses significantly increased and a significant dose–response relationship; “some evidence of carcinogenicity”

Sex 
Dose 0 200 400 0 300 600

squamous cell papilloma of the forestomach 1/50 (2 %)3 2/50 (4 %) 5/50 (10 %) 0/50 (0 %)4 5/50 (10 %)1 6/50 (12 %)1,2
forestomach hyperplasia 7/50 (14 %) 8/50 (16 %) 16/50 (32 %)1,2 12/50 (24 %) 23/50 (46 %)1 39/50 (78 %)1,2
1
significant increase
2
dose–response relationship
historical controls:
3
laboratory: 2 ± 4 %, NTP: 2 ± 3 %
4
laboratory: 2 ± 3 %, NTP: 2 ± 3 %

Volume 17
Volume 17 Benzaldehyde 31

Benzaldehyde from concentrations of 320 µg/ml was found to be cytotoxic for HeLa
cells, and from 600 µg/ml for V79 cells and EJ-1 cells (human bladder carcinoma)
(Nishimura et al. 1981). In HeLa cells benzaldehyde caused a concentration-dependent
reversible inhibition of cell growth together with a lengthening of the S-phase and G2-
phase of the cell cycle (Nambata et al. 1981a). In a test with 9 different human tumour
cell lines, in the concentration range from 16 to 106 µg/ml, benzaldehyde caused greater
or lesser growth inhibition; monolayer cell cultures reacted more sensitively by a factor
of about 4 than did multicellular spheroids (Tanaka and Sasaki 1989). Treatment of
normal (3Y1 rat embryo fibroblasts and WI38 human fibroblasts) and transformed cells
(HeLa cells, W3Y rat embryo fibroblasts and VA13 human fibroblasts) with benzalde-
hyde under hyperthermal conditions (43°C) led to increased cytotoxic effects in the trans-
formed cell lines (Ishida et al. 1983). Cytotoxic effects of benzaldehyde were also seen
in the reduction of the rate of cell division of ascites sarcoma BP8 cells and in the
inhibition of oxidative metabolism in isolated brown fat cells of the hamster and in
inhibited ciliary activity in cultures of chicken embryo trachea. On the other hand, in a
test system for membrane damage in the human cell line MRC-5 (diploid embryonal lung
fibroblasts), no cytotoxic effects were observed (Curvall et al. 1984, Pettersson et al.
1982). The rate of cell division of human NHIK-3025 cervix carcinoma cells was
markedly decreased with concentrations from 680 µg/ml, while adverse effects on the
cell cycle were detectable at concentrations as low as 85 µg/ml. Cells treated during
mitosis reacted much more sensitively (Pettersen et al. 1983a). With concentrations as
low as 50 µg/ml, inhibition of protein biosynthesis could be detected (Pettersen et al.
1983b). Incubation of transformed rat liver epithelial cells with benzaldehyde concen-
trations of 212 µg/ml led to reversible inhibition of cell growth, probably as a result of a
regained contact inhibition of the cells (Nambata et al. 1981b). The selective reversible
inhibition of the cell growth of SV-40 transformed rat embryo fibroblasts, but not of nor-
mal rat embryo fibroblasts, by benzaldehyde concentrations of 25 to 50 µg/ml correlated
with changes which occurred only in the transformed cells, such as the inhibition of the
uptake of 2-deoxy-d-glucose, thymidine and other nucleosides into the cells, probably as
a result of binding to membrane proteins (see Section 2), and a decreased level of intra-
cellular ATP (Miyakawa et al. 1979, Watanuki and Sakaguchi 1980).
Intraperitoneal injection of benzaldehyde doses of 50 to 100 mg/kg body weight on
the first day or on several days after inoculation with P388 leukaemia cells led in
DBA/2J mice of both sexes to an increase in survival by 70 % to 100 %. No or only
minimal therapeutic effects were observed with L1210 and L5178Y leukaemia cells,
Ehrlich adenocarcinoma or Yoshida sarcoma (Balázova and Koza 1988). In BDF1 mice
with an implanted adenocarcinoma (AC 755), 10 intraperitoneal benzaldehyde injections
of 100 mg/kg body weight and day led to an average decrease in tumour weight of 40 %;
in Swiss-Webster mice, intraperitoneal injection of 10 mg/kg body weight and day for 9
days led to a 44 % reduction in the weight of solid Ehrlich carcinomas (Takeuchi et al.
1978). On the other hand, in a preclinical study of the possible use of benzaldehyde as a
chemotherapeutic agent, in vitro with a series of human tumour cell lines and in vivo
after implantation of tumours into nude mice, in most cases no growth-inhibiting and thus
no therapeutic effect on the tumour cells was observed (Taetle and Howell 1983).
32 Benzaldehyde Volume 17

6 Manifesto (MAK value/classification)

During occupational exposure to benzaldehyde, the critical effects are irritation of the
skin, eyes and mucous membranes of the respiratory passages. The data available for
man from short-term inhalation exposure of volunteers or observations at the workplace
do not provide a scientific basis for the establishment of a MAK value. Inhalation studies
with rats yielded a LOEL (lowest observed effect level) of 500 ml/m3 for goblet cell
hyperplasia of the nasal septum; there was, however, clear evidence of toxic effects, such
as clinical symptoms and delayed body weight gain. A MAK value cannot, therefore, be
deduced from the results of animal studies. Benzaldehyde is therefore listed in Section
IIb of the List of MAK and BAT Values.
The benign changes in the forestomach observed in long-term carcinogenicity studies
after oral administration of the substance to mice and rats are attributed to the irritative
effects and are not of relevance for man because of the species-specific location. Thus,
the results of the carcinogenicity study and the, at most, weak genotoxic activity provide
no evidence of a carcinogenic potential of benzaldehyde.
In the literature, and mainly in earlier publications, only few cases of eczematous or
urticarial reactions to benzaldehyde are described; the relevance and immunological
genesis of these reactions are mostly unclear. In view of the relatively widespread use of
the substance, the few case descriptions are not indicative of a pronounced sensitization
potential of benzaldehyde. This conclusion is supported by the results of animal studies.
After only epicutaneous induction there was no evidence of sensitizing effects. Positive
results have been obtained only after intradermal induction. There are no data available
for allergenic effects on the respiratory passages. Benzaldehyde is therefore not desig-
nated as sensitizing.

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