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MindMap Gallery Toxicology-Special Toxicity of Foreign Aid Chemicals

Toxicology-Special Toxicity of Foreign Aid Chemicals

This is a mind map about the special toxicity of foreign aid chemicals, including reproductive toxicity and evaluation methods, mutagenic effects of foreign aid chemicals and evaluation methods, etc.

Edited at 2023-11-27 18:01:54

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Toxicology-Special Toxicity of Foreign Aid Chemicals

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Outline

Toxicology
- 185
- 3
Ondřej Brulík
Toxicology 1 Introduction
- 423
- 1
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Toxicology 4 Toxicology Experiment Basics
- 53
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Toxicology 3 Factors and mechanisms influencing the toxic effects of exogenous chemicals
- 20
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Toxicology 2 Biological transport and biotransformation of exogenous chemicals in the body
- 37
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Medical Toxicology Chapter 8 Mutagenic Effects of Exogenous Chemicals
- 38
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Medical Toxicology Chapter 10 Developmental Toxicity and Teratogenesis
- 58
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Mind map of basic concepts of toxicology
- 70
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Fundamentals of Toxicology Chapter 4
- 34
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Fundamentals of Toxicology Chapter 5
- 24
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Special toxicity of foreign aid chemicals

Section 1 Reproductive toxicity and evaluation methods

The concept of reproductive and developmental toxicity

Reproductive development is the normal physiological process of human and mammal reproduction, which includes the occurrence of germ cells, the release of gametes, egg cell fertilization, cleavage, implantation, embryogenesis, embryonic development, organ formation, embryonic development, childbirth and lactation, and postnatal Development to sexual maturity and other processes

The effects of exogenous chemicals on reproductive processes are called reproductive toxicity

The damaging effects of exogenous chemicals on developmental processes, i.e. developmental toxicity

Reproductive toxicity testing and evaluation

Method principles

Selection of experimental animals

Usually young, sexually mature adult nulliparous female mammals are selected.

Consider the animal's species, background information, practicality and relevance to humans.

The same animal species and strains used in other toxicology experiments should usually be used to enhance the comparability of experimental results.

Rats are the rodents of choice

In embryo-fetal developmental toxicity studies, a second mammalian species, the rabbit, is generally used.

The principle of poisoning

In general, the route of food poisoning should be consistent with the route of daily ingestion. Usually one dose per day. In order to observe the dose-effect relationship, at least three dose groups should be set up, and the dose groups can be increased if necessary. In most cases, 1g/(kg·d) is the maximum exposure limit. Low dose because of NOAEL for reproductive toxicity. Depending on the specific situation, 1 to 2 doses can be designed between high doses and low doses to observe possible dose-response relationships.

Plan formulation

Experimental observations should last for a complete life cycle, that is, the time period from the conception of one generation to the conception of the next generation. Divided into the following stages A. From before mating to conception B. From conception to implantation C. From implantation to hard jaw closure D. From hard jaw closure to pregnancy termination E. From birth to weaning F. From weaning to sexual maturity Commonly used experimental protocols: Fertility and early embryonic development Embryo-fetal development Perinatal development (including maternal functions)

Three-stage test plan

Commonly known as the three-stage one-generation breeding experiment

General reproductive toxicity testing

General reproductive toxicity experiments are also called fertility and early embryonic development toxicity experiments.

The purpose is to evaluate the effects of foreign chemicals on fertility and early embryonic development in experimental animals. The experiment includes the above-mentioned stages a and b of the life cycle. Male and female animals are exposed to the poison from before mating to mating period until embryo implantation to evaluate the toxicity or interference effect of the test substance on animal reproduction.

1. Animal selection, administration and handling methods:

Rats are generally used for experiments, usually no less than 20 rats.

Generally, female animals are sacrificed on the 13th to 15th day of gestation, and male animals are sacrificed after successful mating.

Generally divided into 2 to 3 dose groups and a control group

The high-dose group can cause mild poisoning in the mother, but no severe poisoning symptoms or more than 10% death.

The low-dose group can only eat lean foods, which may cause physiological preresponses to the human body, and pharmacological treatment effects may have some impact on the activity of certain enzymes in tissues.

The intermediate dose is proportional to the high dose and the low dose. Only very mild poisoning or no symptoms can occur.

2. Observation indicators:

Physical signs and mortality, at least once daily

Weight and weight changes, at least twice a week

Food intake, at least once a week, except during mating periods

Vaginal smears should be performed at least daily during mating to check for any effects on mating or the time before mating

Teratogenicity test

Also known as embryo-fetal developmental toxicity test

1. Animal selection, administration and handling methods:

Two animals are usually used: one is a rodent, usually a rat; the other is a non-rodent animal, usually a rabbit.

Usually there are no less than 20 rats per group and no less than 12 rabbits per group.

Sacrifice and examine female animals approximately before parturition, normally around 20 to 21 days of gestation for rats and 28 to 29 days for rabbits

Regardless of the method used, at least 50% of rat fetuses should be examined for viscera

100% of rabbit fetuses require soft tissue and bone examination

When evaluating fetal visceral and skeletal abnormalities, if there is no significant difference between the high-dose group and the control group, there is generally no need to examine the animals in the mid- and low-dose groups.

2. Observation indicators:

Physical signs and mortality, at least once daily

Weight and weight changes, at least twice a week

Food intake, at least once a week, except during mating periods

perinatal toxicity testing

The purpose is to evaluate the relationship between exogenous chemicals and late pregnancy to weaning, based on the potential adverse effects on pregnant rats/lactating rats and fetuses/newborns.

1. Animal selection, administration and handling methods:

Rats are generally used, with the number not less than 20 per group.

The exposure period for female animals should be from stage c to stage e, usually from the 15th day of pregnancy to weaning in rats.

This trial did not fully cover exposure from the weaning period to puberty, nor did it examine the possibility of shortening the childbearing period.

Female animals give birth and raise them from incubation to weaning. One male and one female offspring are selected for each litter, raised until adulthood, and then mated to test their reproductive capabilities.

2. Observation indicators:

Physical signs and mortality, at least once daily

Weight and weight changes, at least twice a week

Food intake, at least once a week, except during mating periods

Developmental Toxicity Testing and Evaluation

Traditional routine teratogenesis experiments

animal selection

Choice of rat, mouse or rabbit

dose grouping

The dose in the highest dose group generally does not exceed 1/5~1/3 of the LD50 and should cause mild maternal poisoning.

The lowest dose group can be 1/100~1/30 of LD50, and no symptoms of poisoning should be observed

The intermediate dose group can tolerate mild maternal poisoning, and no teratogenic effects have been observed.

animal mating treatment

Mate sexually mature animals in the same cage in a ratio of 1:1 or 2:1

Fetal examination

Result assessment

In vivo screening test for teratogens

In vitro test methods

Whole embryo culture method

organ culture method

cell culture method

Section 2 Mutagenic effects of foreign aid chemicals and evaluation methods

concept

Differences between individuals and generations of organisms are often called variations

Variations based on chromosomes and genes that are heritable are called mutations

The occurrence and process of mutation is mutagenicity

Mutations can be divided into spontaneous mutations and induced mutations

The frequency of spontaneous mutations in various species is low, while induced mutations are more common. Induced mutations refer to mutations caused by physical, chemical, biological and other environmental factors.

Exogenous chemicals can damage genetic material and induce mutations. These substances are called mutagens or mutagens, also known as genetic toxicants

type

Generally, it is divided into chromosomal aberrations and gene mutations based on whether the damage to genetic material can be directly observed under a microscope.

When the chromosome damage is greater than or equal to 0.2, it can be observed under an optical microscope and becomes a chromosomal aberration; if it is less than this lower limit, it cannot be directly observed under the microscope and must be judged based on the physiological, biochemical, structural and other expression changes of the offspring. The occurrence of mutations is called a genetic mutation, also known as a point mutation

1. Gene mutation: base substitution, frameshift mutation, large fragment damage

2. Chromosome aberrations: Chromosome structural abnormalities: (cracks and breaks, acentric fragments and deletions, circular chromosomes, inversions, insertions and duplications, translocations) Abnormal chromosome number: (non-disjunction, chromosome loss, chromosome bridges, intranuclear replication)

consequences of mutations

Consequences of somatic mutations: Mainly carcinogenic, may also be associated with atherosclerosis. In addition, defects in DNA repair ability are also related to premature aging syndrome.

Consequences of germ cell mutations: their consequences can be divided into lethal and non-lethal

Lethal effects may be overt lethal or covert lethal

Dominant lethality and early embryonic death before or after implantation after the combination of mutant gametes and normal gametes

Recessive death is a death effect that can only occur in homozygotes or hemizygotes.

If genital cell mutations become non-lethal, dominant or recessive genetic disorders may occur, including congenital malformations