LETTERS TO THE EDITOR

SHORT-TERM TOXICITY STUDY OF AMMONIUM

SULPHAMATE IN RATS

Sir,-There has been a rapid increase in recent years in the number and type or herbicides used in agriculture. Ammonium sulphamate. introduced as a herbicide in lY45 by E.I. du Pont de Nemours & Co.. Inc.. under the trade name “Ammate”. has been round to be very ehective in the manufacture of weed-killing formulations (Bel’kov & Shutov. Les. K/to:. 1960. 13(1 I. 7) and of fire-retardant compositions for extinguishing forest fires (Krasavina. ihill 1965. 18(6). 52). Its strong phytotoxic activity makes it useful as a non-selective herbicide for the control of woody plants (Leonard & Harvey. Bull. Ca/$ agric. Esp. .%,I IY65. no. 812. p. 26) and of poison ivy in fruit orchards (Ahrens & Stoddard. Circ. Corni. rrgric. Esp. St77 1062. no. 221. p. I).

Little information is available regarding the toxicity of ammonium sulphamatc. The LD,,, of ammonium sulphamate administered orally is 3.1 and 4.4g/kg body weight in mice and rats. rcspect- ively (Vinokurova & Mal’kova. Gic/. Trar/ll pro/: Z&o/. 1963. 7(5). 56). Concentrations 01‘0.2550.5Og litre in air caused damage to the respiratory system: application of a Xl”,, solution to the skin caused only local changes (Vinokurova & Mal’kova. lot. cir.).

Manufacture of ammonium sulphamate on a commercial scale has been started recently in India. The product. supplied by Dharamsi Morarji Chemical Co. Ltd.. Bombay. is a white crystalline hygroscopic and odourless solid of YY.O”,, purity. containing 0.5”,, moisture and 100.0 ppm (maximum) iron. Its melting point is 130 C and it is extremely soluble in water and moderately soluble in glycerol. glycol and formamide.

We have studied the short-term toxicity or this compound in albino weanling rats or either sex (body weight 30-50g) and albino adult rats (body weight l70-2OOg) of the ITRC strain. Six groups of ten rats were housed individually in wire cages. The experimental rats were given 500mg ammonium sulphamate/kg in distilled water (100 mg/ml) by gavage on 6days’wk over a period of YOdays extending from May to July. The control animals. kept under similar conditions. were given equivalent volumes of distilled water. This dose of ammonium sulphamate was approximately l/Y of the oral LD,, (4,4g/kg) for rats (Vinokurova & Mal’kova. lot. Cir.). Throughout the esperimen- tal period. the animals were maintained on a standard diet (67”,, pellets from Hindustan Lever. India, Ltd.. and 33”,, green vegetables). Food and water consumption were measured fortnightly. The weight of the animals was recorded twice weekly during the first 2 months and weekly in month 3. The dose of ammonium sulphamate was adjusted to the body weight whenever the animals were weighed.

The appearance and behaviour of the rats were recorded daily and deaths. if any. were noted. Haematological studies were carried out at monthly intervals and included the measurement of haemoglobin and packed cell volume. total red cell counts and total and differential white cell counts. Two animals from each group were killed at the end of 30. 60 and YO days of treatment and were autopsied. The stomach. intestine. liver. kidney, heart and testis or ovary were fixed in IO% formol-saline solution. Paraffin-embedded sections were cut at 6 ltrn and stained with haematoxy- lin and eosin for histological examination.

Throughout the period of observation. the general condition and health of all the rats appeared good. One rat from the group of treated adults and two from the treated group of male weanlings died during the experimental period. These deaths were apparently unrelated to treatment. as three animals among the control adults also died. No cause of death could be assigned at autopsy.

The male and female weanling rats grew well and there were no significant differences between the mean body weights of control or treated animals during or at the end of the observation period. However. although the adults showed no differences in weight gain between the treated and control groups over the first 60-day period, the treated group started to lag behind in weight gain at the end of this period. By the end of the 90 days. the body weights of the treated adults were significantly less than those of the controls.

In general the food intake of all animals, treated or controls, weanlings or adults, gradually reduced as the experiment progressed. Comparison between treated and control groups indicated that while there was no noticeable difference in the case of adults, rood intake by the treated weanlings (both males and females) was significantly lower than that in the controls. On the other hand, water intake generally increased in all the animals. The treated weanlings. males as well as females, drank significantly more water than did the controls, but no such difference was noted among the adult rats.

Haematological examination conducted at 30, 60 and 90 days revealed no changes other than a non-significant increase in the neutrophils in the treated adults and in the male-weanling group.

81

82 Letters to the Editor

In the histological examination. organs in all the six groups of animals appeared normal. However, the liver of one adult rat treated with ammonium sulphamate showed slight fatty degenerative changes in the cytoplasm.

Short-term administration of ammonium sulphamate to rats produced no toxic effect of conse- quence at the level of 500 mg/kg body weight. The general health, survival and organ pathology of the test animals remained unaffected by this treatment.

The chemical structure of ammonium sulpbamate is such that it is readily dissociated in the body into its biodegradable ammonium and sulphate radicals. which then enter the general metabolic pool of the organism. The significance of the observation that adult rats fed ammonium sulphamate showed a lower weight gain than the controls is not understood. It is noteworthy that there was no difference in the food and water intake of these two groups. Further study either with higher doses or over longer periods could throw some light on this observation. On the other hand, an increase in water intake along with a decrease in food intake without any change in growth rate among the weanlings is also intriguing. In view of the chemical structure of ammonium sulphamate, one might expect a change in the acid-base balance of the organism and this might, in turn, influence the food and water intake of the growing animals.

The authors are grateful to Dr. S. H. Zaidi. Director, Industrial Toxicology Research Centre, Lucknow. India. for his keen interest in this work. They wish also to thank Mr. H. K. Sharma and Mr. G. S. D. Gupta for technical assistance.

B. N. GUPTA, R. N. KHANNA, K. K. DATTA and J. D. KOHLI, Iuhstrid Tosicology Research Centre. PD. Box No. 80. Luck~low. India

DIETARY TRADITIONS AND TOXIC FOODS

Sir.-According to the Jewish tradition. food sources and food preparation have to comply with strict laws and prescriptions dating from the times of the Bible, when the Jews lived in the Middle East. Religious Jews still observe traditions of kosher food regardless of where they live at present.

Recent scientific evidence indicates that some of these dietary traditions may be sound and may have served to prevent health hazards. This is particularly so as regards consumption of meat from ‘unclean’ animals, such as pigs (a meat also forbidden by the Muslim religion). The omnivorous pig is often fed the left-overs of human foods, and such feeds are likely to become mouldy, especially during rainy seasons or in the humid heat prevailing in some parts of the Middle East.

It has now been recognized that under appropriate conditions some of the common moulds can produce toxic and/or carcinogenic secondary metabolites, such as the trichothecenes, ochratoxins, sterigmatocystins and aflatoxins, which may present health hazards not only to those who ingest them directly but also to those who are exposed to them ‘by proxy’ when consuming meat and other products derived from animals that have ingested toxic fungal metabolites in their feeds (Schoental, Int. J. enriron. Stud. 1975. 7, 1). Instances have been reported of high concentrations of aflatoxins (100@5OOO~g/kg) in some samples of bacon and lard in a cake factory (Hanssen, Nattrr~\lisserlschclfrerl 1969, 56, 90: Hanssen & Jung, Pure nppl. Chem. 1973, 35, 239), and significant amounts of aflatoxins have also been found in the carcasses of pigs, which on gross inspection appeared not unhealthy and which passed inspection after slaughter (Krogh et al. ibid 1973, 35, 275).

Other effective carcinogens are the nitrosamines. These can be formed under appropriate condi- tions from food constitutents and the nitrite used in the curing of foods. Fried bacon can contain relatively high concentrations of nitrosopyrrolidine (Bills er al. J. agric. Fd C/Tern. 1973, 21, 876). I have already pointed out that the preparation of kosher meat, which includes salting and soaking the meat in water, is likely to diminish the risk of nitrosamine formation by removing the water- soluble products of protein autolysis and amines (Schoental, Fd Comet. Toxicol. 1974, 12, 167).

It makes one wonder how people so many centuries ago could have acquired the insight into problems that only now receive scientific explanation.

R. SCHOENTAL, Department of Pathology, Royal Veterinary College, University of London, London N WI OTU, England