PROPAN-1-OL (n-PROPANOL)
Explanation
This extraction solvent was evaluated for acceptable daily intake
for man by the Joint FAO/WHO Expert Committee on Food Additives in
1980 (see Annex, Ref. 54). No toxicological monograph was issued.
Since the previous evaluation, data have become available and are
summarized and discussed in the following monograph.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
Metabolism
Orally administered n-propanyl alcohol is rapidly absorbed. In
a study in rats, the rate of metabolism was 510 (8.5 mmol) kg/h with
complete elimination from the blood, five hours post-dosing (Beauge et
al., 1979). Metabolites identified include 1-propanaldehyde,
1-propionic acid, as well as acetaldehyde and acetic acid (Rietbrock &
Abshagen, 1971; Saito, 1975). Alcohol dehydrogenase (Auty & Branch,
1976) and possibly catalase (Vatsis & Schulman, 1975) are involved in
this metabolic process.
Effects on enzymes and other biochemical parameters
Varying biochemical effects of n-propyl alcohol have been
investigated including swelling of mitochondria (Thore &
Baltscheffsky, 1965), stimulation of erythrocyte peroxidation
(Giannitsis, 1977), and disruption of their membranes (Slobozhanina et
al., 1975), decreases in polypeptide chain elongation (Igarashi et
al., 1975), increases in adenylate cyclase activity (Stock & Schmidt,
1978), depletion of cerebral calcium levels (Ross, 1976), decreases in
myocardial potassium levels (Golovinskaya, 1976), and degradation of
myelin sheaths (Rumsby & Finean, 1966). n-propyl alcohol has been
found to increase triglyceride levels in the liver of rats (Gaillard &
Derache, 1966; Beauge et al., 1974, 1979). Alteration of the cell
cycle and decreases in fibroblast proliferation have been reported at
subtoxic concentrations (Blanquet & Collyn-d'Hooghe, 1979).
Cytotoxicity to cultured neuroblastoma cells and various water
organisms has also been described (Koerker et al., 1976; Canton &
Adema, 1978).
TOXICOLOGICAL STUDIES
Special studies on mutagenicity
n-propyl alcohol was found to be inactive when tested at high
concentrations in the Ames assay in Salmonella typhimurium strain
TA-100 (Stolzenberg & Hine, 1979). In another Ames assay this alcohol
was negative for mutagenic activity in strains TA-1535, TA-1537,
TA-1538, TA-98 and D4 with or without the rat liver activation system
(Litton Bionetics, 1978a). It did not increase mutations at the TK
locus in L5178Y mouse lymphoma cells with or without activation at
doses up to 12.5 µl/ml (Litton Bionetics, 1978b). It was found to
inactivate E. coli CA 274 in a concentration-dependent manner and to
increase the reverse mutation rate (Hilscher et al., 1969).
Acute toxicity
LD50
Animal Route (g/kg bw) Reference
Mouse Oral 4.5 g/kg Weese, 1928
Rat Oral 5.4 g/kg McNerney et al., 1962
Oral 6.65 ml/kg Golovinskaya, 1976
Oral 1.9 g/kg Smyth et al., 1954
i.p. MLD 4.0 ml/kg Lendle, 1928
Rabbit Dermal 6.7 g/kg McNerney et al., 1962
Dermal 5.0 ml/kg Smyth et al., 1954
Oral MLD 3.5 ml/kg Munch & Schwartze, 1925
i.v. MLD 4.0 ml/kg Lehman & Newman, 1937
Cat i.v. MLD 1.6 ml/kg Macht, 1920
The signs of n-propyl alcohol intoxication in animals exposed
to sufficient concentrations of the vapour include: irritation of the
mucous membranes, ataxia, lethargy, prostration, narcosis, and death
(Treon, 1963). Rats exposed to a minimum of 20 000 ppm (2%) of
n-propyl alcohol in air for one hour survived the exposure and a 14-
day observation period. Weight gain was reduced, however, no gross
lesions were observed upon necroscopy (McNerney et al., 1962).
Short-term studies
Rat
Groups of four-month old male Wistar rats were given a 1 M
solution of n-propyl alcohol in water as their sole drinking fluid
for four months. Lower weight gain to caloric intake ratio was
observed in the dosed versus water control animals. The animals were
killed and their livers examined histologically. No inflammation,
cirrhosis, or other effects were noted (Teshke et al., 1974). In a
similar study, albino rats were given 1 or 2 M solutions of n-propyl
alcohol as their drinking water for several months. At necroscopy no
liver effects were observed but in some animals Mallory's alcoholic
hyaline bodies were seen (Hillbom et al., 1974).
Long-term studies
Rat
Groups of Wistar rats were given n-propyl alcohol s.c.
(0.06 ml/kg) and p.o. (0.3 ml/kg) twice per week from 10 weeks of age
until death. Liver carcinomas and sarcomas, spleen sarcomas,
proventricular carcinomas, and myeloid leukaemias were observed.
Control rats were only subject to proventricular papillomas and
mammary fibroadenomas. Malignant tumours were produced in 5/18 rats
treated p.o. and in 15/31 rats treated by the s.c. route (Gibel et
al., 1974, 1975). However, because of the limited data available for
this study, it does not provide a basis for evaluating the
carcinogenic potential of n-propanol.
OBSERVATIONS IN MAN
One fatal case of poisoning by ingestion of 400 to 500 ml of
n-propyl alcohol has been reported and was reviewed by Browning
(1965). No industrial instances of poisoning or epidemiological
studies could be identified in the literature. The current TLV is
200 ppm (0.02%) (Amer. Conf. Gov. Ind. Hyd,, 1980).
Comments
n-propyl alcohol is rapidly absorbed and metabolized.
Metabolites identified include 1-propanaldehyde, 1-propionic acid, as
well as acetaldehyde and acetic acid. In a short-term study, propyl
alcohol in the water of rats caused no liver damage. Life-time
administration of n-propanol to the Wistar rat by oral or
subcutaneous routes was stated to result in a marked increase in the
incidence of malignant tumours. However, because of the very limited
data available for this study, it does not provide a basis for
evaluating the carcinogenic potential of n-propanol. n-propyl
alcohol has been shown to be inactive in Ames assay with and without
activation, and in the mouse lymphoma cell system.
EVALUATION
No ADI allocated.
FURTHER WORK OR INFORMATION
Life-time feeding studies in two rodent species at appropriate
dose levels.
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See Also:
Toxicological Abbreviations