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Germicides in soap
742
LETTERS TO THE EDITOR
In the severely affected cases the axons had either disappeared completely or were represented by smudges of eosinophilic material in the vesicles (Fig. 1). The degenerating neurones were often rounded, showing margination of granules and nucleus and, in some cases, complete lysis (Fig. 2). There was a definite correlation between the dose rate of the drug and the severity of the lesions. Sections from lambs dosed at' 100 mg/kg showed slight dilatation of the myelin sheaths. Those from lambs dosed at 150 mg/kg showed axonal swelling and ballooning of the sheaths whilst the sections from the group dosed at the highest rate showed axonal and neuronal degeneration as well as severe ballooning of myelin sheaths. The toxic effects of the compound following acute oral administration have also been studied in different laboratory animals. Rats developed weakness and tremor within 20 hr after 400 mg/kg or more, and died from haemorrhage and gastric ulceration between 24 and 96 hr after dosing. The oral LDs0 was between 400 and I000 mg/kg. None of the survivors of 400 mg/kg showed any changes in behaviour or gait during the 4 wk that followed treatment. Rabbits, cats and dogs (one male and one female of each species) were given either 50 or 200 mg/kg. The compound was administered by oral intubation to rabbits in a single dose, and in gelatine capsules to cats and dogs, in a divided dose, morning and afternoon. At various times afterwards the eyes were examined ophthalmoscopically until the animals were killed 4 wk after dosing. Rabbits showed no overt reactions to treatment; however, in cats and dogs emesis occurred within 24 hr and dogs lost appetite for several days. Stiffness of the hind legs was suspected in one cat 8 days after dosing but at all other times gait appeared normal. During the period of observation none of the animals showed signs of ocular changes and at autopsy no abnormalities were noted. Hens, 18 months of age, were unaffected by 400 mg/kg given by oral intubation, and when killed after observation for 3 wk no gross abnormalities were seen postmortem. These studies have shown that acute administration ofp-bromophenyl isothiocyanate in doses that cause paraplegia in lambs failed to produce neurological disturbances involving either locomotor activity or vision in rats, rabbits, cats, dogs or hens. The reported lack of toxicity of the compound to older lambs may be due to the fact that the rumen in animals of this age is better developed and therefore the compound is diluted and partially broken down prior to absorption. The reason for the species difference in sensitivity is unknown. B. LESSELand R. G. TOWLERTON, Research Department, Boots Pure Drug Co. Ltd., Nottingham, Eng land GERMICIDES IN SOAP Sir,--The editorial comments in Food and Cosmetics Toxicology (1967, 5, 588) pertain to photosensitization and sensitization arising from the use of bacteriostats in soap. The work of Vinson & Borselli (:7. Soc. cosmet. Chem. 1966, 17, 123) which you report in Foodand Cosmetics Toxicology (1967, 5, 588) does, I think give the proper answer to the question, particularly when coupled with the reports of Peck & Vinson (d. Soc. cosmet. Chem. 1967, 18, 361) and of Leonard (Archs Derm. 1967, 95, 520.)
LwI-I;t~RS TO THE EDITOR
743
The way I see it is that there are a very few people, certainly not more than one in 100,000 and even less than that, who may become cross-photosensitized. Considering the hundreds o f millions of bars that are sold in the United States with tribromsalan or hexachlorophene, the incidence of photodermatitis is indeed rare. The guinea-pig test.described by Vinson and Borselli, the work of Peck and Vinson and of Leonard, surely establish the safety and efficacy of the antimicrobial agents tribromsalan and hexachlorophene. N. M. MOLNAa,
Fine Organics, Inc., 205 Main Street, Lodi, New Jersey 07644, USA
LETTERS TO THE EDITOR
FIG. 1. Photomicrograph of transverse sectmn of spinal cord of a lamb given an oral dose of 200 mg/kg of p-bromophenyl isothlocyanate showing ddatatlon of myehn sheaths and lysls of the axons Haematoxyhn and eosm × 400.
FIG. 2. Photomicrograph of similar section displayed in Fig. 1 showing degeneration of neurones. Haematoxylin and eosin × 400.
LETTERS TO THE EDITOR
In the severely affected cases the axons had either disappeared completely or were represented by smudges of eosinophilic material in the vesicles (Fig. 1). The degenerating neurones were often rounded, showing margination of granules and nucleus and, in some cases, complete lysis (Fig. 2). There was a definite correlation between the dose rate of the drug and the severity of the lesions. Sections from lambs dosed at' 100 mg/kg showed slight dilatation of the myelin sheaths. Those from lambs dosed at 150 mg/kg showed axonal swelling and ballooning of the sheaths whilst the sections from the group dosed at the highest rate showed axonal and neuronal degeneration as well as severe ballooning of myelin sheaths. The toxic effects of the compound following acute oral administration have also been studied in different laboratory animals. Rats developed weakness and tremor within 20 hr after 400 mg/kg or more, and died from haemorrhage and gastric ulceration between 24 and 96 hr after dosing. The oral LDs0 was between 400 and I000 mg/kg. None of the survivors of 400 mg/kg showed any changes in behaviour or gait during the 4 wk that followed treatment. Rabbits, cats and dogs (one male and one female of each species) were given either 50 or 200 mg/kg. The compound was administered by oral intubation to rabbits in a single dose, and in gelatine capsules to cats and dogs, in a divided dose, morning and afternoon. At various times afterwards the eyes were examined ophthalmoscopically until the animals were killed 4 wk after dosing. Rabbits showed no overt reactions to treatment; however, in cats and dogs emesis occurred within 24 hr and dogs lost appetite for several days. Stiffness of the hind legs was suspected in one cat 8 days after dosing but at all other times gait appeared normal. During the period of observation none of the animals showed signs of ocular changes and at autopsy no abnormalities were noted. Hens, 18 months of age, were unaffected by 400 mg/kg given by oral intubation, and when killed after observation for 3 wk no gross abnormalities were seen postmortem. These studies have shown that acute administration ofp-bromophenyl isothiocyanate in doses that cause paraplegia in lambs failed to produce neurological disturbances involving either locomotor activity or vision in rats, rabbits, cats, dogs or hens. The reported lack of toxicity of the compound to older lambs may be due to the fact that the rumen in animals of this age is better developed and therefore the compound is diluted and partially broken down prior to absorption. The reason for the species difference in sensitivity is unknown. B. LESSELand R. G. TOWLERTON, Research Department, Boots Pure Drug Co. Ltd., Nottingham, Eng land GERMICIDES IN SOAP Sir,--The editorial comments in Food and Cosmetics Toxicology (1967, 5, 588) pertain to photosensitization and sensitization arising from the use of bacteriostats in soap. The work of Vinson & Borselli (:7. Soc. cosmet. Chem. 1966, 17, 123) which you report in Foodand Cosmetics Toxicology (1967, 5, 588) does, I think give the proper answer to the question, particularly when coupled with the reports of Peck & Vinson (d. Soc. cosmet. Chem. 1967, 18, 361) and of Leonard (Archs Derm. 1967, 95, 520.)
LwI-I;t~RS TO THE EDITOR
743
The way I see it is that there are a very few people, certainly not more than one in 100,000 and even less than that, who may become cross-photosensitized. Considering the hundreds o f millions of bars that are sold in the United States with tribromsalan or hexachlorophene, the incidence of photodermatitis is indeed rare. The guinea-pig test.described by Vinson and Borselli, the work of Peck and Vinson and of Leonard, surely establish the safety and efficacy of the antimicrobial agents tribromsalan and hexachlorophene. N. M. MOLNAa,
Fine Organics, Inc., 205 Main Street, Lodi, New Jersey 07644, USA
LETTERS TO THE EDITOR
FIG. 1. Photomicrograph of transverse sectmn of spinal cord of a lamb given an oral dose of 200 mg/kg of p-bromophenyl isothlocyanate showing ddatatlon of myehn sheaths and lysls of the axons Haematoxyhn and eosm × 400.
FIG. 2. Photomicrograph of similar section displayed in Fig. 1 showing degeneration of neurones. Haematoxylin and eosin × 400.