FAO Meeting Report No. PL/1965/10/1
WHO/Food Add./27.65
EVALUATION OF THE TOXICITY OF PESTICIDE RESIDUES IN FOOD
The content of this document is the result of the deliberations of the
Joint Meeting of the FAO Committee on Pesticides in Agriculture and
the WHO Expert Committee on Pesticide Residues, which met in Rome,
15-22 March 19651
Food and Agriculture Organization of the United Nations
World Health Organization
1965
1 Report of the second joint meeting of the FAO Committee on
Pesticides in Agriculture and the WHO Expert Committee on Pesticide
Residues, FAO Meeting Report No. PL/1965/10; WHO/Food Add./26.65
PROPHAM
Chemical name
Isopropyl N-phenylcarbamate; N-phenyl-isopropylcarbamate;
isopropyl-carbanilate.
Synonym
IPC
Empirical formula
C10H13O2N
Structural formula
BIOLOGICAL DATA
Acute toxicity
Animal Route LD50 mg/kg References
body-weight
Mouse Oral approx. 3000 van Esch et al., 1958
Mouse Intraperitoneal approx. 1000 van Esch et al., 1958
Rat Oral 9000 van Esch et al., 1958
Rat Intraperitoneal 600 van Esch et al., 1958
Short-term studies
Mouse. Groups of 30 mice, 15 females and 15 males were given
the following oral doses of propham: one group, a single dose of 750
mg/kg body-weight, a second group, once a week an oral dose of 750
mg/kg body-weight, and a third group, 1000 ppm in the diet for 6
months. Propham was used as initiator and croton oil was painted on
the skin as a promoter. Although in some of the original groups skin
papillomas developed following applications of croton oil in mice fed
propham, this result could not be confirmed in a number of subsequent
experiments carried on in the same institution. No lung tumours were
found in these experiments. Positive controls given ethylurethane in
the place of propham developed both skin papillomas and lung adenomas
(van Esch et al., 1958; van Esch, 1965).
Rat. Ten rats were fed for one month a diet containing 10 000
ppm of propham. No differences in weight gain in comparison with the
control rats were found (Brown & Gross, 1949).
Groups of 4 rats were fed 400, 800 and 1600 ppm for 3 months;
the growth rate and reproduction was normal. No gross abnormalities
were seen in the lung, liver, intestine or kidneys (Schuurmans
Stekhoven et al., 1955).
Pig. Groups of 4 pigs were fed 3300 ppm of propham for 19
weeks. No differences in weight gain from the controls were found. At
autopsy no gross abnormalities were seen. Liver, kidney and spleen
were histologically normal. No changes in the blood picture were
observed (van Esch & van Genderen, 1956-57).
Long-term studies
Mouse. Groups of 30 mice were given 10 000 and 20 000 ppm of
propham in their diet for approximately 18 months. The mortality rate
was very high, especially in the beginning. Further groups each of 50
mice were given 1000 and 5000 ppm. The mice became emaciated, lost
appetite and many of them died unless they were taken off the
experimental diet every 2 weeks and placed on normal diet for an equal
period. Loss of hair was noticed. At autopsy no benign or malignant
tumours were found in the lungs or other organs.
Sixty mice were given injections every 2 weeks of a suspension
of propham in lanolin into the right femoral muscle; the doses were
equivalent to 40 mg/100 g body-weight. The injections were continued
for 6 months. The duration of the experiment was 10 months. At the
site of injection encapsulated injection material was present without
reaction of the surrounding tissue. There was no evidence of any
neoplastic reaction (Hueper, 1952).
The experiment was repeated in 60 mice, but the injections were
given in the right pleural cavity. The duration of the experiment was
18 months. No evidence of tumour formation was present (Hueper, 1952).
Rat. Fifteen adult rats were given 20 000 ppm propham in their
diet for 18 months. The rats were given alternately the propham diet
for 1-2 months and a normal diet for 1-2 weeks; at autopsy no tumours
were found. No histopathological changes were seen (Hueper, 1952).
Fifteen rats were given monthly injections of a suspension of
propham in lanolin into the right femoral muscle in doses equivalent
to 40 mg/100 g body-weight. The injections were continued for 6
months. The duration of the experiment was 18 months. At the site of
injection, encapsulated injected material was present with
inflammatory foam cell reaction around it but no other reaction. The
experiments were repeated with 15 rats but the injections were given
in the right pleural cavity. The duration of the experiment was 18
months. In these experiments no tumours of any kind were present
(Hueper, 1952).
Three groups each of 9 rats were given orally approximately
1000 and 1500 ppm propham and 1000 ppm ethylurethane in dry feed.
Twelve more animals were added as controls. The first group was fed
for 18 months, the other 2 groups for 15 months. After 15 and 18
months no lung tumours were seen (Engelhorn, 1954).
Comments on experimental work reported
The suspicion that propham could be a co-carcinogen for mice
could not be confirmed. In other species experiments purposely
designed did not indicate any tumorigenic effect.
EVALUATION
Not enough toxicological data on animals are available at
present to set a no-effect level.
Further work required
Biochemical studies. Further long-term feeding studies in the
rat and other species.
Further work considered desirable
Biochemistry of propham and further work on carcinogenicity.
REFERENCES
Brown, J. H. & Gross, P. (1949) Report of Ind. Hyg. Foundation to
Pittsburgh Plate Glass Co.
van Esch, G. J. (1965) Personal communication concerning data from the
National Institute of Public Health, Utrecht, The Netherlands
van Esch, G. J. & van Genderen, H. (1956-57) Preliminary reports of
the National Institute of Public Health
van Esch, G. J., van Genderen, H. & Vink, H. H. (1958) Brit. J.
Cancer, 12, 355
Engelhorn, R. (1954) Naunyn-Schmiedeberg's Arch. exp. Path.
Pharmak., 223, 177
Hueper, W. C. (1952) Industr. Med. Surg., 21, 71
Schuurmans Stekhoven, J. H., Roskott, L. & Veenhof, M. J. (1955) T.
Diergeneesk., 80, 400
See Also:
Toxicological Abbreviations
Propham (Pesticide residues in food: 1992 evaluations Part II Toxicology)
Propham (IARC Summary & Evaluation, Volume 12, 1976)