The Use of Indirect Indicator Systems to Detect Mutagenic Activity in Human Subjects and Experimental Animals

There is ample evidence that high doses of phenothiazines and other neuroleptics depress the pituitary-gonadal axis in experimental animals (De Wied, 1967), but the effects of these drugs on sex hormones in human subjects are still controversial (Shader and Di Mascio, 1970). Literature concerning growth hormone (GH) is even more controversial, since phenothiazines have been found to inhibit GH release in rodents (Muller et al., 1967) but to increase it in the rhesus monkey (Meyer and Knobil, 1967). In human subjects phenothiazines have been reported to depress both basal levels of GH and the response to hypoglycaemia (Sherman et al., 1971), while others have found that this response is enhanced (Schimmelbusch, Mueller and Scheps, 1971). Studies of prolactin levels are more consistent, showing raised prolactin both in experimental animals and in human subjects following administration of phenothiazines (Apostolakis et al., 1972; Hwang et al., 1971; Kleinberg et al., 1971; Sulman, 1970).

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7 Final Report on the Safety Assessment of Dibutyl Phthalate, Dimethyl Phthalate, and Diethyl Phthalate

Journal of the American College of Toxicology ◽

10.3109/10915818509078674 ◽

1985 ◽

Vol 4 (3) ◽

pp. 267-303 ◽

Cited By ~ 29

Keyword(s):

Safety Assessment ◽

Dibutyl Phthalate ◽

Mutagenic Activity ◽

Diethyl Phthalate ◽

Testicular Atrophy ◽

Final Report ◽

Dimethyl Phthalate ◽

Experimental Animals ◽

Animal Feeding ◽

Skin Irritants

Dibutyl Phthalate (DBP), Dimethyl Phthalate (DMP), and Diethyl Phthalate (DEP) are dialkyl phthalates used primarily in cosmetics at concentrations of less than 10 percent as plasticizers, solvents, and perfume fixatives. These phthalates are rapidly absorbed, metabolized, and excreted. Acute animal feeding studies indicate that these ingredients are nontoxic. The results of most subchronic and chronic tests indicate that these ingredients are relatively nontoxic to rats. The oral administration of DBP produced testicular atrophy in various test rodents. The available data are not adequate to prove that these ingredients are teratogenic agents to experimental animals. This was not observed after the administration of DMP and DEP. Undiluted DBP, DMP, and DEP produced only minimal irritation to eyes of rabbits. The mutagenic activity of DBP, DMP, and DEP toward Salmonella typhimurium mutants is essentially negative, but some assays reported positive findings. Carcinogenesis was not observed in DBP feeding studies. Limited clinical data on DBP, DMP, and DEP indicate that these ingredients are not human skin irritants, sensitizers, or phototoxic agents. On the basis of the available data, it is concluded that these compounds are safe for topical application in the present practices of use and concentration in cosmetics.

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A Test of Sensory Pre-Conditioning in Pigeons

Quarterly Journal of Experimental Psychology ◽

10.1080/17470215208416603 ◽

1952 ◽

Vol 4 (2) ◽

pp. 49-56 ◽

Cited By ~ 4

Author(s):

R. L. Reid

Keyword(s):

Test Stimulus ◽

Light Stimulus ◽

Human Subjects ◽

Control Group ◽

Similar Degree ◽

Control Procedure ◽

Learning Mechanisms ◽

Experimental Animals ◽

Functional Relationships ◽

Control Procedures

Sixteen pigeons were used in an experiment designed to show the sensory preconditioning effect as originally reported by Brogden. An experimental group received 200 simultaneous presentations of a buzzer paired with a light stimulus. They were then trained to respond to one of these stimuli alone and tested for response to the other. A control group received the same treatment except in the initial stage when 200 presentations of the test stimulus only were given. The results provided no evidence that the pairing of stimuli affected behaviour during the critical test. Both groups responded to the test stimulus to a similar degree in this experiment, whereas in Brogden's original study with dogs experimental animals responded significantly more frequently than did their controls. The discrepancy in results can be attributed to the use of different control procedures in the two experiments. Brogden's controls were not exposed to presentations of the test stimulus before training. Differences in familiarity with this stimulus may have produced the differences between the behaviour of his control and experimental animals. This interpretation is supported by the result of a preliminary experiment with pigeons in which Brogden's control procedure was used and his original results confirmed. With human subjects there is some evidence that pairing procedures may result in enhanced generalization, alterations in sensory thresholds or hallucinations. However, these effects are little understood and difficult to predict. Although no functional relationships like those found in ordinary conditioning have yet been shown to apply, the terms “sensory conditioning” and “sensory pre-conditioning” have been widely used and the data have been quoted in support of theories of learning that require the setting up of direct sensory-sensory relationships. Until there is unequivocal evidence of pairing effects with animals or fuller knowledge of the occurrence of such effects with human subjects, it is considered unadvisable to link them even by name with basic learning mechanisms such as conditioning.

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Effects of anticonvulsant agents on halothane-induced liver injury in human subjects and experimental animals

Hepatology ◽

10.1002/hep.1840060523 ◽

1986 ◽

Vol 6 (5) ◽

pp. 952-956 ◽

Cited By ~ 16

Author(s):

Fumio Nomura ◽

Hitoshi Hatano ◽

Kunihiko Ohnishi ◽

Bunshiro Akikusa ◽

Kunio Okuda

Keyword(s):

Liver Injury ◽

Human Subjects ◽

Experimental Animals ◽

Anticonvulsant Agents

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Possible Mechanisms of Vasectomy-exacerbated Atherosclerosis

Australian Journal of Biological Sciences ◽

10.1071/bi9820469 ◽

1982 ◽

Vol 35 (5) ◽

pp. 469 ◽

Cited By ~ 5

Author(s):

Nancy J Alexander

Keyword(s):

Blood Pressure ◽

Immune Complexes ◽

Animal Studies ◽

Reproductive Tract ◽

Human Subjects ◽

Human Beings ◽

Renal Glomerulus ◽

Experimental Animals ◽

Complex Deposition ◽

Over Time

Our laboratory as well as those of others have demonstrated that in experimental animals vasectomy results in immune-complex deposition not only in the reproductive tract but also in the renal glomerulus. We have shown that in two species of monkeys vasectomy results in a significant increase in atherosclerosis and have postulated that this may be due to circulating immune complexes. We have shown a mild change in arteriolar vessels in a small study of vasectomized men and have found a mild but insignificant increase in systolic blood pressure in vasectomized men over time compared to an age-matched group. One cannot ignore the fact that persistent autoimmune responses to spermatozoal antigens are generated in both vasectomized men and animals. The paucity of direct information about whether vasectomy exacerbates atherosclerosis in human subjects has made reliance on animal studies unavoidable. But to date there is no evidence that vasectomy causes a similar effect in human beings.

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