Lexikon

the integrated effect of more toxic substances, mixtures of chemical substances, xenobiotica or drogs, which can be quantified as the sum of the effects of the components, contrary to not additive effects, such as antagonism or sinergism.

change in morphology, physiology, growth, development or lifespan of an organism which results in impairment of its functional capacity or impairment of its capacity to compensate for additional stress or increased susceptibility to the harmful effects of other environmental influences. (Source: REACH Glossary)

a change in body function or cell structure that might lead to disease or health problems.

carcinogenic effect has a substance or a mixture of substances which induces cancer or increases its incidence and/or malignancy or shorten the time to tumour occurrence. Causing cancer may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Carcinogenic chemicals have conventionally been divided into two categories according to the presumed mode of action. Non-genotoxic modes of action include epigenetic changes, i.e., effects that do not involve alterations in DNA but that may influence gene expression, altered cell-cell communication, or other factors involved in the carcinogenic process.

Cancer is a disorder of the cells, characterized by the lack of programmed cell death. Carcinogens induces the uncontrolled, malignant division pf cells, ultimately leading to the formation of tumors. Usually DNA damage leads to programmed cell death, but if the programmed cell death pathway is damaged, then the cell cannot prevent itself from becoming a cancer cell. The objective of investigating the carcinogenicity of chemicals is to identify potential human carcinogens, their modes of action, and their potency. Once a chemical has been identified as a carcinogen, there is a need to elucidate the underlying mode of action, i.e. whether the chemical is directly genotoxic or not. For genotoxic carcinogens it is assumed that, unless exception, there is no discernible threshold and that any level of exposure carries a risk. For non-genotoxic carcinogens, no-effect-thresholds are assumed to exist and to be discernable. Human studies are generally not available for making a distinction between the above mentioned modes of action; and a conclusion on this, in fact, depends on the outcome of mutagenicity testing and other mechanistic studies. In addition to this, animal studies may also inform on the underlying mode of carcinogenic action.

The cancer hazard and mode of action may also be highly dependent on exposure conditions such as the route of exposure. Therefore, all relevant effect data and information on human exposure conditions are evaluated.

a disease or an injury that happens as a result of exposures that might have occurred in the past.

for non-threshold effects, the underlying assumption is that a no-effect-level cannot be established and a DMEL therefore expresses an exposure level corresponding to a low, possibly theoretical, risk, which should be seen as a tolerable risk. (Source: REACH Glossary)

noise consequences on human health consist in loss of hearing and psychological effects.

mutagenic substances or agents are, those, which induce mutation in living cells. Mutagenicity refers to the induction of permanent transmissible changes in the amount or structure of the genetic material of cells or organisms. These changes may involve a single gene or gene segment, a block of genes or chromosomes.

Alterations to the genetic material of cells may occur spontaneously or be induced as a result of exposure to ionising or ultraviolet radiation, or genotoxic substances. In principle, human exposure to substances that are mutagens may result in increased frequencies of mutations above baseline. Heritable damage to the offspring, and possibly to subsequent generations, of parents exposed to substances that are mutagens may follow if mutations are induced in parental germ cells (reproduction cells). Mutations in somatic cells (cells others than reproduction cells) may be lethal or may be transferred to daughter cells with deleterious consequences for the affected organism. There is considerable evidence of a positive correlation between the mutagenicity of substances in vivo and their carcinogenicity in long-term studies with animals. The aims of testing for mutagenicity are to assess the potential of substances to induce effects which may cause heritable damage in humans or lead to cancer.

Mutagens are usually chemical compounds or ionizing radiation. Mutagens can be divided into different categories according to their effect on DNA replication:

• Some mutagens act as base analogs and get inserted into the DNA strand during replication in place of the substrates.
• Some react with DNA and cause structural changes that lead to miscopying of the template strand when the DNA is replicated.
• Some work indirectly by causing the cells to synthesize chemicals that have the direct mutagenic effect.

highest dose with No Observable Adverse Effect. It is the highest tested dose or exposure level at which there are no statistically significant increases in the frequency or severity of adverse effects between exposed population and an appropriate control group. Some effects may be produced at this level, but they are not considered adverse ort precursors of adverse effects (Source: REACH).

concentration of the substance below which adverse effects in the environmental sphere of concern are not expected to occur. PNEC is relevant for an ecosystem, e.g. aquatic or terrestrial. PNEC is generally calculated from the ecotoxicity test results of testorganisms of three different trophic levels by factorial extrapolation, using safety factors or by statistical extrapolation.

Applying factorial extrapolation the following assessment factors are applied according to uniform protocols:

f=1000: at least one short-term EC50 from each of three trophic levels,
f = 100: long-term NOEC from one trophic level besides 2 acute,
f = 50: long-term NOEC from species representing two trophic levels besides one acute,
f = 10: long-term NOEC from at least three trophic levels,
f = 1: PNEC can be directly measured in microcosms, mesocosms or ecosystem-field-testing.

Another method to determine a PNEC value is the use of statistical extrapolation methods using the variation in species sensitivity. If a large data set with NOECs from long-term experiments for different taxonomic groups is available, these values can be used to draw a distribution. This distribution that describes the variability of hazard of a substance to organisms is called a Species Sensitivity Distribution (SSD). This distribution can be presented as a frequency distribution (cumulative normal distribution curves or other similar distribution curves) of NOEC values for species. From this curve we can read Xm, the mean toxicity expressed as the mean NOEC value of a substance. The Sm represents the toxicity range or variation in sensitivity of a substance.

The main assumption on the use of SSDs in risk assessment is that the distribution based on a selection of species (tested in laboratory experiments) are representative for all species (in the field).

Statistical extrapolation methods may be used to derive a PNEC from a SSD by taking a prescribed percentile of this distribution. For pragmatic reasons it has been decided that the concentration corresponding with the point in the SSD profile below which 5% of the species occur, should be derived as an intermediate value in the determination of a PNEC. This 5% point in the SSD is also identified as a hazardous concentration (HC) at which a certain percentage (in this case 5%) of all species is assumed to be affected.

a biologic response to multiple substances where one substance worsens the effect of another substance. The combined effect of the substances acting together is greater than the sum of the effects of the substances acting by themselves.

See also additive effect and antagonistic effect.

target organ effects indicate which bodily organs are most likely to be affected by exposure to a chemical substance.The classes of target organ effects are summarized in the table below.

The following is a target organ categorization of effects which may occur, including examples of signs and symptoms and chemicals which have been found to cause such effects. These examples are presented to illustrate the range and diversity of effects and hazards found in the workplace, and the broad scope employers must consider in this area, but are not intended to be all-inclusive.

In the table we give the type of chemical substance and its organ-specific effect, the signs and symptoms, and some chemical substances as examples.

When working with chemical substances that have target organ effects it is critical to prevent exposure. This is especially true if you have a pre-existing condition, disease or injury to that particular organ.

While this environmnetal lexikon refers specifically to organs that can be damaged by a substance, the medical community also refers to organs targeted by diseases or other conditions. For example, the medical literature discusses target organ damage to the brain, heart and kidneys in the context of hypertension (high blood pressure). These target organ effects can manifest themselves even before hypertension is diagnosed or progresses from the pre-hypertensive state. Other diseases/conditions target other organs, of course.

Source: http://www.ilpi.com/msds/osha/1910_1200_APP_A.html#targetorgan