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Biomedical subjects

A M Goldberg

Publications and source records attributed to A M Goldberg.

At least 19 recordsLinked to original sources

Status of in vitro ocular irritation testing.

This paper reviews advances in the validation of alternative methods for eye irritation testing since the 1987 publication, A Critical Evaluation of Alternatives to Acute Ocular Irritation Testing (1). We have highlighted details of methods that appear promising and identified the minimum needs and endpoints necessary to develop a battery or batteries of in vitro tests to evaluate eye irritancy. We have recommended a series of workshops to provide identified batteries for specific classes of chemicals or for specific uses of eye irritancy testing. We have also identified the need for consensus meetings and peer-reviewed publication to ensure that the most predictive batteries become parts of validation studies. Finally, we note that academic scientists, industry, government and the animal protection community must work together in order to replace in vivo eye irritancy testing with appropriately validated in vitro methods.

Allantois

An approach to the development of in vitro toxicological methods.

Over the last few years there has been increased societal pressure on the one hand and self-generated scientific pressure on the other to develop new and better in vitro techniques for the evaluation of the safety of commercial products. In vitro methodology addresses four major areas within toxicology. It provides the basic science of the discipline with new information. In acute toxicity testing, it can provide alternatives to current approaches, e.g. the Draize irritation tests. In the area of chronic toxicity testing, it will allow us to define the mechanisms associated with organ specific insults. In the area of risk assessment, the combined knowledge obtained by superior methods will allow us to assess risk more accurately. The results of studies on alternatives to the Draize irritation tests being carried out at or supported by The Johns Hopkins Center for Alternatives to Animal Testing will be reviewed.

Animal Testing Alternatives

Chronic lead intoxication: effects on developing optic nerve.

The effects of chronic lead intoxication were studied by examining the optic nerve of mice given lead-containing mother's milk from day 1 to day 21 of life. Biochemical assays for myelin basic protein, 2',3'-cyclic nucleotide phosphodieterase, and cerebroside sulfotransferase showed that the total amount of myelin produced by the lead-exposed animals was decreased. Lead exposure did not alter the number of oligodendroglia or the relationship between axons and myelin sheaths. The hypomyelination was paralleled by a reduction in size of optic axons in the lead-exposed animals. The data suggest that chronic exposure to lead in developing mice results in a primary effect on neurons and that hypomyelination is secondary to reduction in axon size.

2',3'-Cyclic-Nucleotide Phosphodiesterases

The effect of disuse on cholinergic enzymes.

1. The effects of disuse on the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) have been investigated in the sciatic nerve and leg muscles of the rat. 2. Disuse was produced by blockade of nerve conduction by repeated subperineurial injection of tetrodotoxin (TTX), and the effects were compared to those of denervation. 3. After 8 days of disuse there was no change in neural ChAT activity in the sciatic nerves, anterior roots or intramuscular terminals. By contrast, surgical section of the sciatic nerve resulted in a marked decrease of ChAT in the nerve terminals. 4. Similarly, after 8 days of disuse there was no change in neural AChE activity in the sciatic nerves or anterior roots. 5. AChE activity in the disused muscles decreased by more than 50%, which was comparable to the effect of surgical denervation. 6. These results indicate that disuse produced by TTX blockade of nerve conduction does not affect the cholinergic enzymes ChAT and AChE in nerves, but does lead to a significant decrease in muscle AChE.

Acetylcholinesterase

Alterations in consummatory behavior of mice produced by dietary exposure to inorganic lead.

Mice suckled by mothers given tap water and by mothers given a 5 mg/ml lead acetate solution during lactation were given a choice between tap water and a lead acetate solution after lactation. All offspring demonstrated an immediate aversion to the lead acetate solution. The offspring from the mothers receiving lead acetate during lactation demonstrated a greater aversion to the lead acetate solution than did the offspring from mothers receiving tap water. In addition, the lead acetate offspring drank more total fluid (tap water plus lead acetate solution) after weaning than the control offspring. The results indicate both learned and unlearned changes in motivation for fluid following ingestion of lead via the mother's milk in infancy.

Animals