A.7.1.4 Adverse effects on or via lactation are also included in
reproductive toxicity, but for classification purposes, such effects
are treated separately (See A.7.2.1).

A.7.2 Classification Criteria for Substances

    A.7.2.1 For the purpose of classification for reproductive
toxicity, substances shall be classified in one of two categories in
accordance with Figure A.7.1(a). Effects on sexual function and
fertility, and on development, shall be considered. In addition,
effects on or via lactation shall be classified in a separate hazard
category in accordance with Figure A.7.1(b).

      Figure A.7.1(a)--Hazard Categories for Reproductive Toxicants
------------------------------------------------------------------------

-------------------------------------------------------------------------
CATEGORY 1: Known or presumed human reproductive toxicant.
    Substance shall be classified in Category 1 for reproductive
     toxicity when they are known to have produced an adverse effect on
     sexual function and fertility or on development in humans or when
     there is evidence from animal studies, possibly supplemented with
     other information, to provide a strong presumption that the
     substance has the capacity to interfere with reproduction in
     humans. The classification of a substance is further distinguished
     on the basis of whether the evidence for classification is
     primarily from human data (Category 1A) or from animal data
     (Category 1B).
Category 1A: Known human reproductive toxicant.
    The classification of a substance in this category is largely based
     on evidence from humans.
Category 1B: Presumed human reproductive toxicant.
    The classification of a substance in this category is largely based
     on evidence from experimental animals. Data from animal studies
     shall provide sufficient evidence of an adverse effect on sexual
     function and fertility or on development in the absence of other
     toxic effects, or if occurring together with other toxic effects
     the adverse effect on reproduction is considered not to be a
     secondary non-specific consequence of other toxic effects. However,
     when there is mechanistic information that raises doubt about the
     relevance of the effect for humans, classification in Category 2
     may be more appropriate.
CATEGORY 2: Suspected human reproductive toxicant.
    Substances shall be classified in Category 2 for reproductive
     toxicity when there is some evidence from humans or experimental
     animals, possibly supplemented with other information, of an
     adverse effect on sexual function and fertility, or on development,
     in the absence of other toxic effects, or if occurring together
     with other toxic effects the adverse effect on reproduction is
     considered not to be a secondary non-specific consequence of the
     other toxic effects, and where the evidence is not sufficiently
     convincing to place the substance in Category 1. For instance,
     deficiencies in the study may make the quality of evidence less
     convincing, and in view of this, Category 2 would be the more
     appropriate classification.
------------------------------------------------------------------------

    Figure A.7.1(b)--Hazard Category for Effects on or Via Lactation
------------------------------------------------------------------------

-------------------------------------------------------------------------
EFFECTS ON OR VIA LACTATION
Effects on or via lactation shall be classified in a separate single
 category. Chemicals that are absorbed by women and have been shown to
 interfere with lactation or that may be present (including metabolites)
 in breast milk in amounts sufficient to cause concern for the health of
 a breastfed child, shall be classified to indicate this property
 hazardous to breastfed babies. This classification shall be assigned on
 the basis of:
    (a) absorption, metabolism, distribution and excretion studies that
     indicate the likelihood the substance would be present in
     potentially toxic levels in breast milk; and/or

    (b) results of one or two generation studies in animals which
     provide clear evidence of adverse effect in the offspring due to
     transfer in the milk or adverse effect on the quality of the milk;
     and/or
    (c) human evidence indicating a hazard to babies during the
     lactation period.
------------------------------------------------------------------------

A.7.2.2 Basis of Classification

    A.<IP_ADDRESS> Classification is made on the basis of the criteria,
outlined above, an assessment of the total weight of evidence, and
the use of expert judgment. Classification as a reproductive
toxicant is intended to be used for substances which have an
intrinsic, specific property to produce an adverse effect on
reproduction and substances should not be so classified if such an
effect is produced solely as a non-specific secondary consequence of
other toxic effects.
    A.<IP_ADDRESS> In the evaluation of toxic effects on the developing
offspring, it is important to consider the possible influence of
maternal toxicity.
    A.<IP_ADDRESS> For human evidence to provide the primary basis for a
Category 1A classification there must be reliable evidence of an
adverse effect on reproduction in humans. Evidence used for
classification shall be from well conducted epidemiological studies,
if available, which include the use of appropriate controls,
balanced assessment, and due consideration of bias or confounding
factors. Less rigorous data from studies in humans may be sufficient
for a Category 1A classification if supplemented with adequate data
from studies in experimental animals, but classification in Category
1B may also be considered.

A.7.2.3 Weight of Evidence

    A.<IP_ADDRESS> Classification as a reproductive toxicant is made on
the basis of an assessment of the total weight of evidence using
expert judgment. This means that all available information that
bears on the determination of reproductive toxicity is considered
together. Included is information such as epidemiological studies
and case reports in humans and specific reproduction studies along
with sub-chronic, chronic and special study results in animals that
provide relevant information regarding toxicity to reproductive and
related endocrine organs. Evaluation of substances chemically
related to the material under study may also be included,
particularly when information on the material is scarce. The weight
given to the available evidence will be influenced by factors such
as the quality of the studies, consistency of results, nature and
severity of effects, level of statistical significance for
intergroup differences, number of endpoints affected, relevance of
route of administration to humans and freedom from bias. Both
positive and negative results are considered together in a weight of
evidence determination. However, a single, positive study performed
according to good scientific principles and with statistically or
biologically significant positive results may justify classification
(See also A.<IP_ADDRESS>).
    A.<IP_ADDRESS> Toxicokinetic studies in animals and humans, site of
action and mechanism or mode of action study results may provide
relevant information, which could reduce or increase concerns about
the hazard to human health. If it is conclusively demonstrated that
the clearly identified mechanism or mode of action has no relevance
for humans or when the toxicokinetic differences are so marked that
it is certain that the hazardous property will not be expressed in
humans then a chemical which produces an adverse effect on
reproduction in experimental animals should not be classified.
    A.<IP_ADDRESS> In some reproductive toxicity studies in experimental
animals the only effects recorded may be considered of low or
minimal toxicological significance and classification may not
necessarily be the outcome. These effects include, for example,
small changes in semen parameters or in the incidence of spontaneous
defects in the fetus, small changes in the proportions of common
fetal variants such as are observed in skeletal examinations, or in
fetal weights, or small differences in postnatal developmental
assessments.
    A.<IP_ADDRESS> Data from animal studies shall provide sufficient
evidence of specific reproductive toxicity in the absence of other
systemic toxic effects. However, if developmental toxicity occurs
together with other toxic effects in the dam (mother), the potential
influence of the generalized adverse effects should be assessed to
the extent possible. The preferred approach is to consider adverse
effects in the embryo/fetus first, and then evaluate maternal
toxicity, along with any other factors which are likely to have
influenced these effects, as part of the weight of evidence. In
general, developmental effects that are observed at maternally toxic
doses should not be automatically discounted. Discounting
developmental effects that are observed at maternally toxic doses
can only be done on a case-by-case basis when a causal relationship
is established or refuted.
    A.<IP_ADDRESS> If appropriate information is available it is
important to try to determine whether developmental toxicity is due
to a specific maternally mediated mechanism or to a non-specific
secondary mechanism, like maternal stress and the disruption of
homeostasis. Generally, the presence of maternal toxicity should not
be used to negate findings of embryo/fetal effects, unless it can be
clearly demonstrated that the effects are secondary non-specific
effects. This is especially the case when the effects in the
offspring are significant, e.g., irreversible effects such as
structural malformations. In some situations it is reasonable to
assume that reproductive toxicity is due to a secondary consequence
of maternal toxicity and discount the effects, for example if the
chemical is so toxic that dams fail to thrive and there is severe
inanition; they are incapable of nursing pups; or they are prostrate
or dying.

A.7.2.4 Maternal Toxicity

    A.<IP_ADDRESS> Development of the offspring throughout gestation and
during the early postnatal stages can be influenced by toxic effects
in the mother either through non-specific mechanisms related to
stress and the disruption of maternal homeostasis, or by specific
maternally-mediated mechanisms. So, in the interpretation of the
developmental outcome to decide classification for developmental
effects it is important to consider the possible influence of
maternal toxicity. This is a complex issue because of uncertainties
surrounding the relationship between maternal toxicity and
developmental outcome. Expert judgment and a weight of evidence
approach, using all available studies, shall be used to determine
the degree of influence to be attributed to maternal toxicity when
interpreting the criteria for classification for developmental
effects. The adverse effects in the embryo/fetus shall be first
considered, and then maternal toxicity, along with any other factors
which are likely to have influenced these effects, as weight of
evidence, to help reach a conclusion about classification.
    A.<IP_ADDRESS> Based on pragmatic observation, it is believed that
maternal toxicity may, depending on severity, influence development
via non-specific secondary mechanisms, producing effects such as
depressed fetal weight, retarded ossification, and possibly
resorptions and certain malformations in some strains of certain
species. However, the limited numbers of studies which have
investigated the relationship between developmental effects and
general maternal toxicity have failed to demonstrate a consistent,
reproducible relationship across species. Developmental effects
which occur even in the presence of maternal toxicity are considered
to be evidence of developmental toxicity, unless it can be
unequivocally demonstrated on a case by case basis that the
developmental effects are secondary to maternal toxicity. Moreover,
classification shall be considered where there is a significant
toxic effect in the offspring, e.g., irreversible effects such as
structural malformations, embryo/fetal lethality, or significant
post-natal functional deficiencies.
    A.<IP_ADDRESS> Classification shall not automatically be discounted
for chemicals that produce developmental toxicity only in
association with maternal toxicity, even if a specific maternally-
mediated mechanism has been demonstrated. In such a case,
classification in Category 2 may be considered more appropriate than
Category 1. However, when a chemical is so toxic that maternal death
or severe inanition results, or the dams (mothers) are prostrate and
incapable of nursing the pups, it is reasonable to assume that
developmental toxicity is produced solely as a secondary consequence
of maternal toxicity and discount the developmental effects.

Classification is not necessarily the outcome in the case of minor
developmental changes, e.g., a small reduction in fetal/pup body
weight or retardation of ossification when seen in association with
maternal toxicity.
    A.<IP_ADDRESS> Some of the endpoints used to assess maternal toxicity
are provided below. Data on these endpoints, if available, shall be
evaluated in light of their statistical or biological significance
and dose-response relationship.
    (a) Maternal mortality: An increased incidence of mortality
among the treated dams over the controls shall be considered
evidence of maternal toxicity if the increase occurs in a dose-
related manner and can be attributed to the systemic toxicity of the
test material. Maternal mortality greater than 10% is considered
excessive and the data for that dose level shall not normally be
considered to need further evaluation.
    (b) Mating index (Number of animals with seminal plugs or sperm/
Number of mated x 100)
    (c) Fertility index (Number of animals with implants/Number of
matings x 100)
    (d) Gestation length (If allowed to deliver)
    (e) Body weight and body weight change: Consideration of the
maternal body weight change and/or adjusted (corrected) maternal
body weight shall be included in the evaluation of maternal toxicity
whenever such data are available. The calculation of an adjusted
(corrected) mean maternal body weight change, which is the
difference between the initial and terminal body weight minus the
gravid uterine weight (or alternatively, the sum of the weights of
the fetuses), may indicate whether the effect is maternal or
intrauterine. In rabbits, the body weight gain may not be a useful
indicator of maternal toxicity because of normal fluctuations in
body weight during pregnancy.
    (f) Food and water consumption (if relevant): The observation of
a significant decrease in the average food or water consumption in
treated dams (mothers) compared to the control group may be useful
in evaluating maternal toxicity, particularly when the test material
is administered in the diet or drinking water. Changes in food or
water consumption must be evaluated in conjunction with maternal
body weights when determining if the effects noted are reflective of
maternal toxicity or more simply, unpalatability of the test
material in feed or water.
    (g) Clinical evaluations (including clinical signs, markers, and
hematology and clinical chemistry studies): The observation of
increased incidence of significant clinical signs of toxicity in
treated dams (mothers) relative to the control group is useful in
evaluating maternal toxicity. If this is to be used as the basis for
the assessment of maternal toxicity, the types, incidence, degree
and duration of clinical signs shall be reported in the study.
Clinical signs of maternal intoxication include, but are not limited
to: coma, prostration, hyperactivity, loss of righting reflex,
ataxia, or labored breathing.
    (h) Post-mortem data: Increased incidence and/or severity of
post-mortem findings may be indicative of maternal toxicity. This
can include gross or microscopic pathological findings or organ
weight data, including absolute organ weight, organ-to-body weight
ratio, or organ-to-brain weight ratio. When supported by findings of
adverse histopathological effects in the affected organ(s), the
observation of a significant change in the average weight of
suspected target organ(s) of treated dams (mothers), compared to
those in the control group, may be considered evidence of maternal
toxicity.

A.7.2.5 Animal and Experimental Data

    A.<IP_ADDRESS> A number of scientifically validated test methods are
available, including methods for developmental toxicity testing
(e.g., OECD Test Guideline 414, ICH Guideline S5A, 1993), methods
for peri- and post-natal toxicity testing (e.g., ICH S5B, 1995), and
methods for one or two-generation toxicity testing (e.g., OECD Test
Guidelines 415, 416)
    A.<IP_ADDRESS> Results obtained from screening tests (e.g., OECD
Guidelines 421--Reproduction/Developmental Toxicity Screening Test,
and 422--Combined Repeated Dose Toxicity Study with Reproduction/
Development Toxicity Screening Test) can also be used to justify
classification, although the quality of this evidence is less
reliable than that obtained through full studies.
    A.<IP_ADDRESS> Adverse effects or changes, seen in short- or long-
term repeated dose toxicity studies, which are judged likely to
impair reproductive function and which occur in the absence of
significant generalized toxicity, may be used as a basis for
classification, e.g., histopathological changes in the gonads.
    A.<IP_ADDRESS> Evidence from in vitro assays, or non-mammalian tests,
and from analogous substances using structure-activity relationship
(SAR), can contribute to the procedure for classification. In all
cases of this nature, expert judgment must be used to assess the
adequacy of the data. Inadequate data shall not be used as a primary
support for classification.
    A.<IP_ADDRESS> It is preferable that animal studies are conducted
using appropriate routes of administration which relate to the
potential route of human exposure. However, in practice,
reproductive toxicity studies are commonly conducted using the oral
route, and such studies will normally be suitable for evaluating the
hazardous properties of the substance with respect to reproductive
toxicity. However, if it can be conclusively demonstrated that the
clearly identified mechanism or mode of action has no relevance for
humans or when the toxicokinetic differences are so marked that it
is certain that the hazardous property will not be expressed in
humans then a substance which produces an adverse effect on
reproduction in experimental animals should not be classified.
    A.<IP_ADDRESS> Studies involving routes of administration such as
intravenous or intraperitoneal injection, which may result in
exposure of the reproductive organs to unrealistically high levels
of the test substance, or elicit local damage to the reproductive
organs, e.g., by irritation, must be interpreted with extreme
caution and on their own are not normally the basis for
classification.
    A.<IP_ADDRESS> There is general agreement about the concept of a
limit dose, above which the production of an adverse effect may be
considered to be outside the criteria which lead to classification.
Some test guidelines specify a limit dose, other test guidelines
qualify the limit dose with a statement that higher doses may be
necessary if anticipated human exposure is sufficiently high that an
adequate margin of exposure would not be achieved. Also, due to
species differences in toxicokinetics, establishing a specific limit
dose may not be adequate for situations where humans are more
sensitive than the animal model.
    A.<IP_ADDRESS> In principle, adverse effects on reproduction seen
only at very high dose levels in animal studies (for example doses
that induce prostration, severe inappetence, excessive mortality) do
not normally lead to classification, unless other information is
available, for example, toxicokinetics information indicating that
humans may be more susceptible than animals, to suggest that
classification is appropriate.
    A.<IP_ADDRESS> However, specification of the actual ``limit dose''
will depend upon the test method that has been employed to provide
the test results.

A.7.3 Classification Criteria for Mixtures 9
---------------------------------------------------------------------------

    \9\ It should be noted that the classification criteria for
health hazards usually include a tiered scheme in which test data
available on the complete mixture are considered as the first tier
in the evaluation, followed by the applicable bridging principles,
and lastly, cut-off values/concentration limits or additivity.
However, this approach is not used for Reproductive Toxicity. These
criteria for Reproductive Toxicity consider the cut-off values/
concentration limits as the primary tier and allow the
classification to be modified only on a case-by-case evaluation
based on available test data for the mixture as a whole.
---------------------------------------------------------------------------

A.7.3.1 Classification of Mixtures When Data Are Available for All
Ingredients or Only for Some Ingredients of the Mixture

    A.<IP_ADDRESS> The mixture shall be classified as a reproductive
toxicant when at least one ingredient has been classified as a
Category 1 or Category 2 reproductive toxicant and is present at or
above the appropriate cut-off value/concentration limit specified in
Table A.7.1 for Category 1 and 2, respectively.
    A.<IP_ADDRESS> The mixture shall be classified for effects on or via
lactation when at least one ingredient has been classified for
effects on or via lactation and is present at or above the
appropriate cut-off value/concentration limit specified in Table
A.7.1 for the additional category for effects on or via lactation.

     Table A.7.1--Cut-Off Values/Concentration Limits of Ingredients of a Mixture Classified as Reproductive
             Toxicants or for Effects on or via Lactation That Trigger Classification of the Mixture
----------------------------------------------------------------------------------------------------------------
                                     Cut-off values/concentration limits triggering classification of a mixture
                                                                         as:
                                   -----------------------------------------------------------------------------
    Ingredients classified as:                                                           Additional category for
                                     Category 1 reproductive   Category 2 reproductive      effects on or via
                                            toxicant                  toxicant                  lactation
----------------------------------------------------------------------------------------------------------------
Category 1 reproductive toxicant..                    >=0.1%  ........................  ........................
Category 2 reproductive toxicant..  ........................                    >=0.1%  ........................
Additional category for effects on  ........................  ........................                    >=0.1%
 or via lactation.................
----------------------------------------------------------------------------------------------------------------

A.7.3.2 Classification of Mixtures When Data Are Available for the
Complete Mixture

    Available test data for the mixture as a whole may be used for
classification on a case-by-case basis. In such cases, the test
results for the mixture as a whole must be shown to be conclusive
taking into account dose and other factors such as duration,
observations and analysis (e.g., statistical analysis, test
sensitivity) of reproduction test systems.

A.7.3.3 Classification of Mixtures When Data Are Not Available for the
Complete Mixture: Bridging Principles

    A.<IP_ADDRESS> Where the mixture itself has not been tested to
determine its reproductive toxicity, but there are sufficient data
on both the individual ingredients and similar tested mixtures to
adequately characterize the hazards of the mixture, these data shall
be used in accordance with the following bridging principles as
found in paragraph A.0.5 of this Appendix: Dilution, Batching, and
Substantially similar mixtures.

A.8 SPECIFIC TARGET ORGAN TOXICITY SINGLE EXPOSURE

A.8.1 Definitions and General Considerations

    A.8.1.1 Specific target organ toxicity--single exposure, (STOT-
SE) means specific, non-lethal target organ toxicity arising from a
single exposure to a chemical. All significant health effects that
can impair function, both reversible and irreversible, immediate
and/or delayed and not specifically addressed in A.1 to A.7 and A.10
of this Appendix are included. Specific target organ toxicity
following repeated exposure is classified in accordance with
SPECIFIC TARGET ORGAN TOXICITY--REPEATED EXPOSURE (A.9 of this
Appendix) and is therefore not included here.
    A.8.1.2 Classification identifies the chemical as being a
specific target organ toxicant and, as such, it presents a potential
for adverse health effects in people who are exposed to it.
    A.8.1.3 The adverse health effects produced by a single exposure
include consistent and identifiable toxic effects in humans; or, in
experimental animals, toxicologically significant changes which have
affected the function or morphology of a tissue/organ, or have
produced serious changes to the biochemistry or hematology of the
organism, and these changes are relevant for human health. Human
data is the primary source of evidence for this hazard class.
    A.8.1.4 Assessment shall take into consideration not only
significant changes in a single organ or biological system but also
generalized changes of a less severe nature involving several
organs.
    A.8.1.5 Specific target organ toxicity can occur by any route
that is relevant for humans, i.e., principally oral, dermal or
inhalation.
    A.8.1.6 The classification criteria for specific organ systemic
toxicity single exposure are organized as criteria for substances
Categories 1 and 2 (See A.8.2.1), criteria for substances Category 3
(See A.8.2.2) and criteria for mixtures (See A.8.3). See also Figure
A.8.1.

A.8.2 Classification Criteria for Substances

A.8.2.1 Substances of Category 1 and Category 2

    A.<IP_ADDRESS> Substances shall be classified for immediate or
delayed effects separately, by the use of expert judgment on the
basis of the weight of all evidence available, including the use of
recommended guidance values (See A.<IP_ADDRESS>). Substances shall then
be classified in Category 1 or 2, depending upon the nature and
severity of the effect(s) observed, in accordance with Figure A.8.1.

   Figure A.8.1--Hazard Categories for Specific Target Organ Toxicity
                        Following Single Exposure
------------------------------------------------------------------------

-------------------------------------------------------------------------
CATEGORY 1: Substances that have produced significant toxicity in
 humans, or that, on the basis of evidence from studies in experimental
 animals can be presumed to have the potential to produce significant
 toxicity in humans following single exposure
Substances are classified in Category 1 for STOT-SE on the basis of:
(a) reliable and good quality evidence from human cases or
 epidemiological studies; or
(b) observations from appropriate studies in experimental animals in
 which significant and/or severe toxic effects of relevance to human
 health were produced at generally low exposure concentrations. Guidance
 dose/concentration values are provided below (See A.<IP_ADDRESS>) to be used
 as part of weight-of-evidence evaluation.
CATEGORY 2: Substances that, on the basis of evidence from studies in
 experimental animals, can be presumed to have the potential to be
 harmful to human health following single exposure
Substances are classified in Category 2 for STOT-SE on the basis of
 observations from appropriate studies in experimental animals in which
 significant toxic effects, of relevance to human health, were produced
 at generally moderate exposure concentrations. Guidance dose/
 concentration values are provided below (See A.<IP_ADDRESS>) in order to
 help in classification.
In exceptional cases, human evidence can also be used to place a
 substance in Category 2 (See A.<IP_ADDRESS>).
CATEGORY 3: Transient target organ effects
There are target organ effects for which a substance does not meet the
 criteria to be classified in Categories 1 or 2 indicated above. These
 are effects which adversely alter human function for a short duration
 after exposure and from which humans may recover in a reasonable period
 without leaving significant alteration of structure or function. This
 category only includes narcotic effects and respiratory tract
 irritation. Substances are classified specifically for these effects as
 discussed in A.8.2.2.
Note: The primary target organ/system shall be identified where
 possible, and where this is not possible, the substance shall be
 identified as a general toxicant. The data shall be evaluated and,
 where possible, shall not include secondary effects (e.g., a
 hepatotoxicant can produce secondary effects in the nervous or gastro-
 intestinal systems).
------------------------------------------------------------------------

    A.<IP_ADDRESS> The relevant route(s) of exposure by which the
classified substance produces damage shall be identified.
    A.<IP_ADDRESS> Classification is determined by expert judgment, on
the basis of the weight of all evidence available including the
guidance presented below.

    A.<IP_ADDRESS> Weight of evidence of all available data, including
human incidents, epidemiology, and studies conducted in experimental
animals is used to substantiate specific target organ toxic effects
that merit classification.
    A.<IP_ADDRESS> The information required to evaluate specific target
organ toxicity comes either from single exposure in humans (e.g.,
exposure at home, in the workplace or environmentally), or from
studies conducted in experimental animals. The standard animal
studies in rats or mice that provide this information are acute
toxicity studies which can include clinical observations and
detailed macroscopic and microscopic examination to enable the toxic
effects on target tissues/organs to be identified. Results of acute
toxicity studies conducted in other species may also provide
relevant information.
    A.<IP_ADDRESS> In exceptional cases, based on expert judgment, it may
be appropriate to place certain substances with human evidence of
target organ toxicity in Category 2: (a) when the weight of human
evidence is not sufficiently convincing to warrant Category 1
classification, and/or (b) based on the nature and severity of
effects. Dose/concentration levels in humans shall not be considered
in the classification and any available evidence from animal studies
shall be consistent with the Category 2 classification. In other
words, if there are also animal data available on the substance that
warrant Category 1 classification, the chemical shall be classified
as Category 1.
    A.<IP_ADDRESS> Effects considered to support classification for
Category 1 and 2
    A.<IP_ADDRESS>.1 Classification is supported by evidence associating
single exposure to the substance with a consistent and identifiable
toxic effect.
    A.<IP_ADDRESS>.2 Evidence from human experience/incidents is usually
restricted to reports of adverse health consequences, often with
uncertainty about exposure conditions, and may not provide the
scientific detail that can be obtained from well-conducted studies
in experimental animals.
    A.<IP_ADDRESS>.3 Evidence from appropriate studies in experimental
animals can furnish much more detail, in the form of clinical
observations, and macroscopic and microscopic pathological
examination and this can often reveal hazards that may not be life-
threatening but could indicate functional impairment. Consequently
all available evidence, and evidence relevance to human health, must
be taken into consideration in the classification process. Relevant
toxic effects in humans and/or animals include, but are not limited
to:
    (a) Morbidity resulting from single exposure;
    (b) Significant functional changes, more than transient in
nature, in the respiratory system, central or peripheral nervous
systems, other organs or other organ systems, including signs of
central nervous system depression and effects on special senses
(e.g., sight, hearing and sense of smell);
    (c) Any consistent and significant adverse change in clinical
biochemistry, hematology, or urinalysis parameters;
    (d) Significant organ damage that may be noted at necropsy and/
or subsequently seen or confirmed at microscopic examination;
    (e) Multi-focal or diffuse necrosis, fibrosis or granuloma
formation in vital organs with regenerative capacity;
    (f) Morphological changes that are potentially reversible but
provide clear evidence of marked organ dysfunction; and,
    (g) Evidence of appreciable cell death (including cell
degeneration and reduced cell number) in vital organs incapable of
regeneration.
    A.<IP_ADDRESS> Effects considered not to support classification for
Category 1 and 2
    Effects may be seen in humans and/or animals that do not justify
classification. Such effects include, but are not limited to:
    (a) Clinical observations or small changes in bodyweight gain,
food consumption or water intake that may have some toxicological
importance but that do not, by themselves, indicate ``significant''
toxicity;
    (b) Small changes in clinical biochemistry, hematology or
urinalysis parameters and/or transient effects, when such changes or
effects are of doubtful or of minimal toxicological importance;
    (c) Changes in organ weights with no evidence of organ
dysfunction;
    (d) Adaptive responses that are not considered toxicologically
relevant; and,
    (e) Substance-induced species-specific mechanisms of toxicity,
i.e., demonstrated with reasonable certainty to be not relevant for
human health, shall not justify classification.
    A.<IP_ADDRESS> Guidance values to assist with classification based on
the results obtained from studies conducted in experimental animals
for Category 1 and 2
    A.<IP_ADDRESS>.1 In order to help reach a decision about whether a
substance shall be classified or not, and to what degree it shall be
classified (Category 1 vs. Category 2), dose/concentration
``guidance values'' are provided for consideration of the dose/
concentration which has been shown to produce significant health
effects. The principal argument for proposing such guidance values
is that all chemicals are potentially toxic and there has to be a
reasonable dose/concentration above which a degree of toxic effect
is acknowledged.
    A.<IP_ADDRESS>.2 Thus, in animal studies, when significant toxic
effects are observed that indicate classification, consideration of
the dose/concentration at which these effects were seen, in relation
to the suggested guidance values, provides useful information to
help assess the need to classify (since the toxic effects are a
consequence of the hazardous property(ies) and also the dose/
concentration).
    A.<IP_ADDRESS>.3 The guidance value (C) ranges for single-dose
exposure which has produced a significant non-lethal toxic effect
are those applicable to acute toxicity testing, as indicated in
Table A.8.1.

                          Table A.8.1--Guidance Value Ranges for Single-Dose Exposures
----------------------------------------------------------------------------------------------------------------
                                                                      Guidance value ranges for:
        Route of exposure                Units       -----------------------------------------------------------
                                                          Category 1          Category 2          Category 3
----------------------------------------------------------------------------------------------------------------
Oral (rat)......................  mg/kg body weight.  C <=300...........  2000 >=C >300.....  Guidance values do
                                                                                not apply.
Dermal (rat or rabbit)..........  mg/kg body weight.  C <=1,000.........  2000 >=C >1,000...
Inhalation (rat) gas............  ppmV/4h...........  C <=2,500.........  20,000 >=C >2,500.
Inhalation (rat) vapor..........  mg/1/4h...........  C <=10............  20 >=C >10........
Inhalation (rat) dust/mist/fume.  mg/l/4h...........  C <=1.0...........  5.0 >=C >1.0......
----------------------------------------------------------------------------------------------------------------

    A.<IP_ADDRESS>.4 The guidance values and ranges mentioned in Table
A.8.1 are intended only for guidance purposes, i.e., to be used as
part of the weight of evidence approach, and to assist with
decisions about classification. They are not intended as strict
demarcation values. Guidance values are not provided for Category 3
since this classification is primarily based on human data; animal
data may be included in the weight of evidence evaluation.
    A.<IP_ADDRESS>.5 Thus, it is feasible that a specific profile of
toxicity occurs at a dose/concentration below the guidance value,
e.g., <2000 mg/kg body weight by the oral route, however the nature
of the effect may result in the decision not to classify.
Conversely, a specific profile of toxicity may be seen in animal
studies occurring at above a guidance value, e.g., >=2000 mg/kg body
weight by the oral route, and in addition there is supplementary
information from other sources, e.g., other single dose studies, or
human case experience, which supports a conclusion that, in view of
the weight of evidence, classification is the prudent action to
take.
    A.<IP_ADDRESS> Other considerations
    A.<IP_ADDRESS>.1 When a substance is characterized only by use of
animal data the classification process includes reference to dose/
concentration guidance values as one of

the elements that contribute to the weight of evidence approach.
    A.<IP_ADDRESS>.2 When well-substantiated human data are available
showing a specific target organ toxic effect that can be reliably
attributed to single exposure to a substance, the substance shall be
classified. Positive human data, regardless of probable dose,
predominates over animal data. Thus, if a substance is unclassified
because specific target organ toxicity observed was considered not
relevant or significant to humans, if subsequent human incident data
become available showing a specific target organ toxic effect, the
substance shall be classified.
    A.<IP_ADDRESS>.3 A substance that has not been tested for specific
target organ toxicity shall, where appropriate, be classified on the
basis of data from a scientifically validated structure activity
relationship and expert judgment-based extrapolation from a
structural analogue that has previously been classified together
with substantial support from consideration of other important
factors such as formation of common significant metabolites.

A.8.2.2 Substances of Category 3

    A.<IP_ADDRESS> Criteria for respiratory tract irritation
    The criteria for classifying substances as Category 3 for
respiratory tract irritation are:
    (a) Respiratory irritant effects (characterized by localized
redness, edema, pruritis and/or pain) that impair function with
symptoms such as cough, pain, choking, and breathing difficulties
are included. It is recognized that this evaluation is based
primarily on human data;
    (b) Subjective human observations supported by objective
measurements of clear respiratory tract irritation (RTI) (e.g.,
electrophysiological responses, biomarkers of inflammation in nasal
or bronchoalveolar lavage fluids);
    (c) The symptoms observed in humans shall also be typical of
those that would be produced in the exposed population rather than
being an isolated idiosyncratic reaction or response triggered only
in individuals with hypersensitive airways. Ambiguous reports simply
of ``irritation'' should be excluded as this term is commonly used
to describe a wide range of sensations including those such as
smell, unpleasant taste, a tickling sensation, and dryness, which
are outside the scope of classification for respiratory tract
irritation;
    (d) There are currently no scientifically validated animal tests
that deal specifically with RTI; however, useful information may be
obtained from the single and repeated inhalation toxicity tests. For
example, animal studies may provide useful information in terms of
clinical signs of toxicity (dyspnoea, rhinitis etc) and
histopathology (e.g., hyperemia, edema, minimal inflammation,
thickened mucous layer) which are reversible and may be reflective
of the characteristic clinical symptoms described above. Such animal
studies can be used as part of weight of evidence evaluation; and,
    (e) This special classification will occur only when more severe
organ effects including the respiratory system are not observed as
those effects would require a higher classification.
    A.<IP_ADDRESS> Criteria for narcotic effects
    The criteria for classifying substances in Category 3 for
narcotic effects are:
    (a) Central nervous system depression including narcotic effects
in humans such as drowsiness, narcosis, reduced alertness, loss of
reflexes, lack of coordination, and vertigo are included. These
effects can also be manifested as severe headache or nausea, and can
lead to reduced judgment, dizziness, irritability, fatigue, impaired
memory function, deficits in perception and coordination, reaction
time, or sleepiness; and,
    (b) Narcotic effects observed in animal studies may include
lethargy, lack of coordination righting reflex, narcosis, and
ataxia. If these effects are not transient in nature, then they
shall be considered for classification as Category 1 or 2.

A.8.3 Classification Criteria for Mixtures

    A.8.3.1 Mixtures are classified using the same criteria as for
substances, or alternatively as described below. As with substances,
mixtures may be classified for specific target organ toxicity
following single exposure, repeated exposure, or both.

A.8.3.2 Classification of Mixtures When Data Are Available for the
Complete Mixture

    When reliable and good quality evidence from human experience or
appropriate studies in experimental animals, as described in the
criteria for substances, is available for the mixture, then the
mixture shall be classified by weight of evidence evaluation of this
data. Care shall be exercised in evaluating data on mixtures, that
the dose, duration, observation or analysis, do not render the
results inconclusive.

A.8.3.3 Classification of Mixtures When Data Are Not Available for the
Complete Mixture: Bridging Principles

    A.<IP_ADDRESS> Where the mixture itself has not been tested to
determine its specific target organ toxicity, but there are
sufficient data on both the individual ingredients and similar
tested mixtures to adequately characterize the hazards of the
mixture, these data shall be used in accordance with the following
bridging principles as found in paragraph A.0.5 of this Appendix:
Dilution, Batching, Concentration of mixtures, Interpolation within
one toxicity category, Substantially similar mixtures, or Aerosols.

A.8.3.4 Classification of Mixtures When Data Are Available for All
Ingredients or Only for Some Ingredients of the Mixture

    A.<IP_ADDRESS> Where there is no reliable evidence or test data for
the specific mixture itself, and the bridging principles cannot be
used to enable classification, then classification of the mixture is
based on the classification of the ingredient substances. In this
case, the mixture shall be classified as a specific target organ
toxicant (specific organ specified), following single exposure,
repeated exposure, or both when at least one ingredient has been
classified as a Category 1 or Category 2 specific target organ
toxicant and is present at or above the appropriate cut-off value/
concentration limit specified in Table A.8.2 for Categories 1 and 2,
respectively.

  Table A.8.2--Cut-Off Values/Concentration Limits of Ingredients of a
    Mixture Classified as a Specific Target Organ Toxicant That Would
        Trigger Classification of the Mixture as Category 1 or 2
------------------------------------------------------------------------
                                           Cut-off values/concentration
                                                 limits triggering
                                            classification of a mixture
        Ingredient classified as:                       as:
                                         -------------------------------
                                            Category 1      Category 2
------------------------------------------------------------------------
Category 1 Target organ toxicant........          >=1.0%  ..............
Category 2 Target organ toxicant........  ..............          >=1.0%
------------------------------------------------------------------------

    A.<IP_ADDRESS> These cut-off values and consequent classifications
shall be applied equally and appropriately to both single- and
repeated-dose target organ toxicants.
    A.<IP_ADDRESS> Mixtures shall be classified for either or both single
and repeated dose toxicity independently.
    A.<IP_ADDRESS> Care shall be exercised when toxicants affecting more
than one organ system are combined that the potentiation or
synergistic interactions are considered, because certain substances
can cause target organ toxicity at <1% concentration when other
ingredients in the mixture are known to potentiate its toxic effect.
    A.<IP_ADDRESS> Care shall be exercised when extrapolating the
toxicity of a mixture that contains Category 3 ingredient(s). A cut-
off value/concentration limit of 20%, considered as an additive of
all Category 3 ingredients for each hazard endpoint, is appropriate;
however, this cut-off value/concentration limit may be higher or
lower depending on the Category 3 ingredient(s) involved and the
fact that some effects such as respiratory tract irritation may not
occur below a certain concentration while other effects such as
narcotic effects may occur below this 20% value. Expert judgment
shall be exercised. Respiratory tract irritation and narcotic

effects are to be evaluated separately in accordance with the
criteria given in A.8.2.2. When conducting classifications for these
hazards, the contribution of each ingredient should be considered
additive, unless there is evidence that the effects are not
additive.

A.9 SPECIFIC TARGET ORGAN TOXICITY REPEATED OR PROLONGED EXPOSURE

A.9.1 Definitions and general considerations

    A.9.1.1 Specific target organ toxicity--repeated exposure (STOT-
RE) means specific target organ toxicity arising from repeated
exposure to a substance or mixture. All significant health effects
that can impair function, both reversible and irreversible,
immediate and/or delayed and not specifically addressed in A.1 to
A.7 and A.10 of this Appendix are included. Specific target organ
toxicity following a single-event exposure is classified in
accordance with SPECIFIC TARGET ORGAN TOXICITY--SINGLE EXPOSURE (A.8
of this Appendix) and is therefore not included here.
    A.9.1.2 Classification identifies the substance or mixture as
being a specific target organ toxicant and, as such, it may present
a potential for adverse health effects in people who are exposed to
it.
    A.9.1.3 These adverse health effects produced by repeated
exposure include consistent and identifiable toxic effects in
humans, or, in experimental animals, toxicologically significant
changes which have affected the function or morphology of a tissue/
organ, or have produced serious changes to the biochemistry or
hematology of the organism and these changes are relevant for human
health. Human data will be the primary source of evidence for this
hazard class.
    A.9.1.4 Assessment shall take into consideration not only
significant changes in a single organ or biological system but also
generalized changes of a less severe nature involving several
organs.
    A.9.1.5 Specific target organ toxicity can occur by any route
that is relevant for humans, e.g., principally oral, dermal or
inhalation.

A.9.2 Classification Criteria for Substances

    A.9.2.1 Substances shall be classified as STOT-RE by expert
judgment on the basis of the weight of all evidence available,
including the use of recommended guidance values which take into
account the duration of exposure and the dose/concentration which
produced the effect(s), (See A.9.2.9). Substances shall be placed in
one of two categories, depending upon the nature and severity of the
effect(s) observed, in accordance with Figure A.9.1.

   Figure A.9.1--Hazard Categories for Specific Target Organ Toxicity
                       Following Repeated Exposure
------------------------------------------------------------------------

-------------------------------------------------------------------------
CATEGORY 1: Substances that have produced significant toxicity in
 humans, or that, on the basis of evidence from studies in experimental
 animals can be presumed to have the potential to produce significant
 toxicity in humans following repeated or prolonged exposure
    Substances are classified in Category 1 for specific target organ
     toxicity (repeated exposure) on the basis of:
    (a) reliable and good quality evidence from human cases or
     epidemiological studies; or,
    (b) observations from appropriate studies in experimental animals in
     which significant and/or severe toxic effects, of relevance to
     human health, were produced at generally low exposure
     concentrations. Guidance dose/concentration values are provided
     below (See A.9.2.9) to be used as part of weight-of-evidence
     evaluation.
CATEGORY 2: Substances that, on the basis of evidence from studies in
 experimental animals can be presumed to have the potential to be
 harmful to human health following repeated or prolonged exposure
    Substances are classified in Category 2 for specific target organ
     toxicity (repeated exposure) on the basis of observations from
     appropriate studies in experimental animals in which significant
     toxic effects, of relevance to human health, were produced at
     generally moderate exposure concentrations. Guidance dose/
     concentration values are provided below (See A.9.2.9) in order to
     help in classification.
    In exceptional cases human evidence can also be used to place a
     substance in Category 2 (See A.9.2.6).
Note: The primary target organ/system shall be identified where
 possible, or the substance shall be identified as a general toxicant.
 The data shall be carefully evaluated and, where possible, shall not
 include secondary effects (e.g., a hepatotoxicant can produce secondary
 effects in the nervous or gastro-intestinal systems).
------------------------------------------------------------------------

    A.9.2.2 The relevant route of exposure by which the classified
substance produces damage shall be identified.
    A.9.2.3 Classification is determined by expert judgment, on the
basis of the weight of all evidence available including the guidance
presented below.
    A.9.2.4 Weight of evidence of all data, including human
incidents, epidemiology, and studies conducted in experimental
animals, is used to substantiate specific target organ toxic effects
that merit classification.
    A.9.2.5 The information required to evaluate specific target
organ toxicity comes either from repeated exposure in humans, e.g.,
exposure at home, in the workplace or environmentally, or from
studies conducted in experimental animals. The standard animal
studies in rats or mice that provide this information are 28 day, 90
day or lifetime studies (up to 2 years) that include hematological,
clinico-chemical and detailed macroscopic and microscopic
examination to enable the toxic effects on target tissues/organs to
be identified. Data from repeat dose studies performed in other
species may also be used. Other long-term exposure studies, e.g.,
for carcinogenicity, neurotoxicity or reproductive toxicity, may
also provide evidence of specific target organ toxicity that could
be used in the assessment of classification.
    A.9.2.6 In exceptional cases, based on expert judgment, it may
be appropriate to place certain substances with human evidence of
specific target organ toxicity in Category 2: (a) when the weight of
human evidence is not sufficiently convincing to warrant Category 1
classification, and/or (b) based on the nature and severity of
effects. Dose/concentration levels in humans shall not be considered
in the classification and any available evidence from animal studies
shall be consistent with the Category 2 classification. In other
words, if there are also animal data available on the substance that
warrant Category 1 classification, the substance shall be classified
as Category 1.

A.9.2.7 Effects Considered To Support Classification

    A.<IP_ADDRESS> Classification is supported by reliable evidence
associating repeated exposure to the substance with a consistent and
identifiable toxic effect.
    A.<IP_ADDRESS> Evidence from human experience/incidents is usually
restricted to reports of adverse health consequences, often with
uncertainty about exposure conditions, and may not provide the
scientific detail that can be obtained from well-conducted studies
in experimental animals.
    A.<IP_ADDRESS> Evidence from appropriate studies in experimental
animals can furnish much more detail, in the form of clinical
observations, hematology, clinical chemistry, macroscopic and
microscopic pathological examination and this can often reveal
hazards that may not be life-threatening but could indicate
functional impairment. Consequently all available evidence, and
relevance to human health, must be taken into consideration in the
classification process. Relevant toxic effects in humans and/or
animals include, but are not limited to:
    (a) Morbidity or death resulting from repeated or long-term
exposure. Morbidity or death may result from repeated exposure, even
to relatively low doses/concentrations, due to bioaccumulation of
the substance or its metabolites, or due to the overwhelming of the
de-toxification process by repeated exposure;
    (b) Significant functional changes in the central or peripheral
nervous systems or other organ systems, including signs of central
nervous system depression and effects on special senses (e.g.,
sight, hearing and sense of smell);
    (c) Any consistent and significant adverse change in clinical
biochemistry, hematology, or urinalysis parameters;
    (d) Significant organ damage that may be noted at necropsy and/
or subsequently seen or confirmed at microscopic examination;

    (e) Multi-focal or diffuse necrosis, fibrosis or granuloma
formation in vital organs with regenerative capacity;
    (f) Morphological changes that are potentially reversible but
provide clear evidence of marked organ dysfunction (e.g., severe
fatty change in the liver); and,
    (g) Evidence of appreciable cell death (including cell
degeneration and reduced cell number) in vital organs incapable of
regeneration.

A.9.2.8 Effects Considered Not To Support Classification

    Effects may be seen in humans and/or animals that do not justify
classification. Such effects include, but are not limited to:
    (a) Clinical observations or small changes in bodyweight gain,
food consumption or water intake that may have some toxicological
importance but that do not, by themselves, indicate ``significant''
toxicity;
    (b) Small changes in clinical biochemistry, hematology or
urinalysis parameters and/or transient effects, when such changes or
effects are of doubtful or of minimal toxicological importance;
    (c) Changes in organ weights with no evidence of organ
dysfunction;
    (d) Adaptive responses that are not considered toxicologically
relevant;
    (e) Substance-induced species-specific mechanisms of toxicity,
i.e., demonstrated with reasonable certainty to be not relevant for
human health, shall not justify classification.

A.9.2.9 Guidance Values To Assist With Classification Based on the
Results Obtained From Studies Conducted in Experimental Animals

    A.<IP_ADDRESS> In studies conducted in experimental animals, reliance
on observation of effects alone, without reference to the duration
of experimental exposure and dose/concentration, omits a fundamental
concept of toxicology, i.e., all substances are potentially toxic,
and what determines the toxicity is a function of the dose/
concentration and the duration of exposure. In most studies
conducted in experimental animals the test guidelines use an upper
limit dose value.
    A.<IP_ADDRESS> In order to help reach a decision about whether a
substance shall be classified or not, and to what degree it shall be
classified (Category 1 vs. Category 2), dose/concentration
``guidance values'' are provided in Table A.9.1 for consideration of
the dose/concentration which has been shown to produce significant
health effects. The principal argument for proposing such guidance
values is that all chemicals are potentially toxic and there has to
be a reasonable dose/concentration above which a degree of toxic
effect is acknowledged. Also, repeated-dose studies conducted in
experimental animals are designed to produce toxicity at the highest
dose used in order to optimize the test objective and so most
studies will reveal some toxic effect at least at this highest dose.
What is therefore to be decided is not only what effects have been
produced, but also at what dose/concentration they were produced and
how relevant is that for humans.
    A.<IP_ADDRESS> Thus, in animal studies, when significant toxic
effects are observed that indicate classification, consideration of
the duration of experimental exposure and the dose/concentration at
which these effects were seen, in relation to the suggested guidance
values, provides useful information to help assess the need to
classify (since the toxic effects are a consequence of the hazardous
property(ies) and also the duration of exposure and the dose/
concentration).
    A.<IP_ADDRESS> The decision to classify at all can be influenced by
reference to the dose/concentration guidance values at or below
which a significant toxic effect has been observed.
    A.<IP_ADDRESS> The guidance values refer to effects seen in a
standard 90-day toxicity study conducted in rats. They can be used
as a basis to extrapolate equivalent guidance values for toxicity
studies of greater or lesser duration, using dose/exposure time
extrapolation similar to Haber's rule for inhalation, which states
essentially that the effective dose is directly proportional to the
exposure concentration and the duration of exposure. The assessment
should be done on a case-by-case basis; for example, for a 28-day
study the guidance values below would be increased by a factor of
three.
    A.<IP_ADDRESS> Thus for Category 1 classification, significant toxic
effects observed in a 90-day repeated-dose study conducted in
experimental animals and seen to occur at or below the (suggested)
guidance values (C) as indicated in Table A.9.1 would justify
classification:

   Table A.9.1--Guidance Values To Assist in Category 1 Classification
                     [Applicable to a 90-day study]
------------------------------------------------------------------------
                                                       Guidance values
      Route of exposure               Units         (dose/concentration)
------------------------------------------------------------------------
Oral (rat)..................  mg/kg body weight/    C <=10.
                               day.
Dermal (rat or rabbit)......  mg/kg body weight/    C <=20.
                               day.
Inhalation (rat) gas........  ppmV/6h/day.........  C <=50.
Inhalation (rat) vapor......  mg/liter/6h/day.....  C <=0.2.
Inhalation (rat) dust/mist/   mg/liter/6h/day.....  C <=0.02.
 fume.
------------------------------------------------------------------------

    A.<IP_ADDRESS> For Category 2 classification, significant toxic
effects observed in a 90-day repeated-dose study conducted in
experimental animals and seen to occur within the (suggested)
guidance value ranges as indicated in Table A.9.2 would justify
classification:

   Table A.9.2--Guidance Values To Assist in Category 2 Classification
                     [Applicable to a 90-day study]
------------------------------------------------------------------------
                                                       Guidance values
      Route of exposure               Units         (dose/concentration)
------------------------------------------------------------------------
Oral (rat)..................  mg/kg body weight/    10 =100 mg/kg body weight/day by the oral route, and in addition there
is supplementary information from other sources, e.g., other long-
term administration studies, or human case experience, which
supports a conclusion that, in view of the weight of evidence,
classification is prudent.

A.9.2.10 Other Considerations

    A.<IP_ADDRESS> When a substance is characterized only by use of
animal data the classification process includes reference to dose/
concentration guidance values as one of the elements that contribute
to the weight of evidence approach.
    A.<IP_ADDRESS> When well-substantiated human data are available
showing a specific target organ toxic effect that can be reliably
attributed to repeated or prolonged exposure to a substance, the
substance shall be classified. Positive human data, regardless of
probable dose, predominates over animal data. Thus, if a substance
is unclassified because no specific target organ toxicity was seen
at or below the dose/concentration guidance value for animal
testing, if subsequent human incident data become available showing
a specific target organ toxic effect, the substance shall be
classified.
    A.<IP_ADDRESS> A substance that has not been tested for specific
target organ toxicity may in certain instances, where appropriate,
be classified on the basis of data from a scientifically validated
structure activity relationship and expert judgment-based
extrapolation from a structural analogue that has previously been
classified together with substantial support from consideration of
other important factors such as formation of common significant
metabolites.

A.9.3 Classification Criteria for Mixtures

    A.9.3.1 Mixtures are classified using the same criteria as for
substances, or alternatively as described below. As with substances,
mixtures may be classified for specific target organ toxicity
following single exposure, repeated exposure, or both.

A.9.3.2 Classification of Mixtures When Data Are Available for the
Complete Mixture

    When reliable and good quality evidence from human experience or
appropriate studies in experimental animals, as described in the
criteria for substances, is available for the mixture, then the
mixture shall be classified by weight of evidence evaluation of
these data. Care shall be exercised in evaluating data on mixtures,
that the dose, duration, observation or analysis, do not render the
results inconclusive.

A.9.3.3 Classification of Mixtures When Data Are Not Available for the
Complete Mixture: Bridging Principles

    A.<IP_ADDRESS> Where the mixture itself has not been tested to
determine its specific target organ toxicity, but there are
sufficient data on both the individual ingredients and similar
tested mixtures to adequately characterize the hazards of the
mixture, these data shall be used in accordance with the following
bridging principles as found in paragraph A.0.5 of this Appendix:
Dilution; Batching; Concentration of mixtures; Interpolation within
one toxicity category; Substantially similar mixtures; and Aerosols.

A.9.3.4 Classification of Mixtures When Data Are Available for All
Ingredients or Only for Some Ingredients of the Mixture

    A.<IP_ADDRESS> Where there is no reliable evidence or test data for
the specific mixture itself, and the bridging principles cannot be
used to enable classification, then classification of the mixture is
based on the classification of the ingredient substances. In this
case, the mixture shall be classified as a specific target organ
toxicant (specific organ specified), following single exposure,
repeated exposure, or both when at least one ingredient has been
classified as a Category 1 or Category 2 specific target organ
toxicant and is present at or above the appropriate cut-off value/
concentration limit specified in Table A.9.3 for Category 1 and 2
respectively.

   Table A.9.3--Cut-Off Value/Concentration Limits of Ingredients of a
    Mixture Classified as a Specific Target Organ Toxicant That Would
        Trigger Classification of the Mixture as Category 1 or 2
------------------------------------------------------------------------
                                           Cut-off values/concentration
                                                 limits triggering
                                           classification of a  mixture
        Ingredient classified as:                       as:
                                         -------------------------------
                                            Category 1      Category 2
------------------------------------------------------------------------
Category 1 Target organ toxicant........          >=1.0%  ..............
Category 2 Target organ toxicant........  ..............          >=1.0%
------------------------------------------------------------------------

    A.<IP_ADDRESS> These cut-off values and consequent classifications
shall be applied equally and appropriately to both single- and
repeated-dose target organ toxicants.
    A.<IP_ADDRESS> Mixtures shall be classified for either or both
single- and repeated-dose toxicity independently.
    A.<IP_ADDRESS> Care shall be exercised when toxicants affecting more
than one organ system are combined that the potentiation or
synergistic interactions are considered, because certain substances
can cause specific target organ toxicity at <1% concentration when
other ingredients in the mixture are known to potentiate its toxic
effect.

A.10 ASPIRATION HAZARD

A.10.1 Definitions and General and Specific Considerations

    A.10.1.1 Aspiration means the entry of a liquid or solid
chemical directly through the oral or nasal cavity, or indirectly
from vomiting, into the trachea and lower respiratory system.
    A.10.1.2 Aspiration toxicity includes severe acute effects such
as chemical pneumonia, varying degrees of pulmonary injury or death
following aspiration.
    A.10.1.3 Aspiration is initiated at the moment of inspiration,
in the time required to take one breath, as the causative material
lodges at the crossroad of the upper respiratory and digestive
tracts in the laryngopharyngeal region.
    A.10.1.4 Aspiration of a substance or mixture can occur as it is
vomited following ingestion. This may have consequences for
labeling, particularly where, due to acute toxicity, a
recommendation may be considered to induce vomiting after ingestion.
However, if the substance/mixture also presents an aspiration
toxicity hazard, the recommendation to induce vomiting may need to
be modified.

A.10.1.5 Specific Considerations

    A.<IP_ADDRESS> The classification criteria refer to kinematic
viscosity. The following provides the conversion between dynamic and
kinematic viscosity:
[GRAPHIC] [TIFF OMITTED] TR26MR12.130

    A.<IP_ADDRESS> Although the definition of aspiration in A.10.1.1
includes the entry of solids into the respiratory system,
classification according to (b) in table A.10.1 for Category 1 is
intended to apply to liquid substances and mixtures only.
    A.<IP_ADDRESS> Classification of aerosol/mist products.
    Aerosol and mist products are usually dispensed in containers
such as self-pressurized containers, trigger and pump sprayers.
Classification for these products shall be considered if their use
may form a pool of product in the mouth, which then may be
aspirated. If the mist or aerosol from a pressurized container is
fine, a pool may not be formed. On the other hand, if a pressurized
container dispenses product in a stream, a pool may be formed that
may then be aspirated. Usually, the mist produced by trigger and
pump sprayers is coarse and therefore, a pool may be formed that
then may be aspirated. When the pump mechanism may be removed and
contents are available to be swallowed then the classification of
the products should be considered.

A.10.2 Classification Criteria for Substances

             Table A.10.1--Criteria for Aspiration Toxicity
------------------------------------------------------------------------
                Category                             Criteria
------------------------------------------------------------------------
Category 1: Chemicals known to cause     A substance shall be classified
 human aspiration toxicity hazards or     in Category 1:
 to be regarded as if they cause human   (a) If reliable and good
 aspiration toxicity hazard.              quality human evidence
                                          indicates that it causes
                                          aspiration toxicity (See
                                          note); or
                                         (b) If it is a hydrocarbon and
                                          has a kinematic viscosity
                                          <=20.5 mm\2\/s, measured at 40
                                          [deg]C.
------------------------------------------------------------------------
Note: Examples of substances included in Category 1 are certain
  hydrocarbons, turpentine and pine oil.

A.10.3 Classification Criteria for Mixtures

A.10.3.1 Classification When Data Are Available for the Complete
Mixture

    A mixture shall be classified in Category 1 based on reliable
and good quality human evidence.

A.10.3.2 Classification of Mixtures When Data Are Not Available for the
Complete Mixture: Bridging Principles

    A.<IP_ADDRESS> Where the mixture itself has not been tested to
determine its aspiration toxicity, but there are sufficient data on
both the individual ingredients and similar tested mixtures to
adequately characterize the hazard of the mixture, these data shall
be used in accordance with the following bridging principles as
found in paragraph A.0.5 of this Appendix: Dilution; Batching;
Concentration of mixtures; Interpolation within one toxicity
category; and Substantially similar mixtures. For application of the
dilution bridging principle, the concentration of aspiration
toxicants shall not be less than 10%.

A.10.3.3 Classification of Mixtures When Data Are Available for All
Ingredients or Only for Some Ingredients of the Mixture

    A.<IP_ADDRESS> A mixture which contains >=10% of an ingredient or
ingredients classified in Category 1, and has a kinematic viscosity
<=20.5 mm\2\/s, measured at 40 [deg]C, shall be classified in
Category 1.
    A.<IP_ADDRESS> In the case of a mixture which separates into two or
more distinct layers, one of which contains >=10% of an ingredient
or ingredients classified in Category 1 and has a kinematic
viscosity <=20.5 mm\2\/s, measured at 40 [deg]C, then the entire
mixture shall be classified in Category 1.

APPENDIX B TO Sec.  1910.1200--PHYSICAL CRITERIA (MANDATORY)

B.1 EXPLOSIVES

B.1.1 Definitions and General Considerations

    B.1.1.1 An explosive chemical is a solid or liquid chemical
which is in itself capable by chemical reaction of producing gas at
such a temperature and pressure and at such a speed as to cause
damage to the surroundings. Pyrotechnic chemicals are included even
when they do not evolve gases.
    A pyrotechnic chemical is a chemical designed to produce an
effect by heat, light, sound, gas or smoke or a combination of these
as the result of non-detonative self-sustaining exothermic chemical
reactions.
    An explosive item is an item containing one or more explosive
chemicals.
    A pyrotechnic item is an item containing one or more pyrotechnic
chemicals.
    An unstable explosive is an explosive which is thermally
unstable and/or too sensitive for normal handling, transport, or
use.
    An intentional explosive is a chemical or item which is
manufactured with a view to produce a practical explosive or
pyrotechnic effect.
    B.1.1.2 The class of explosives comprises:
    (a) Explosive chemicals;
    (b) Explosive items, except devices containing explosive
chemicals in such quantity or of such a character that their
inadvertent or accidental ignition or initiation shall not cause any
effect external to the device either by projection, fire, smoke,
heat or loud noise; and
    (c) Chemicals and items not included under (a) and (b) above
which are manufactured with the view to producing a practical
explosive or pyrotechnic effect.

B.1.2 Classification Criteria

    Chemicals and items of this class shall be classified as
unstable explosives or shall be assigned to one of the following six
divisions depending on the type of hazard they present:
    (a) Division 1.1--Chemicals and items which have a mass
explosion hazard (a mass explosion is one which affects almost the
entire quantity present virtually instantaneously);
    (b) Division 1.2--Chemicals and items which have a projection
hazard but not a mass explosion hazard;
    (c) Division 1.3--Chemicals and items which have a fire hazard
and either a minor blast hazard or a minor projection hazard or
both, but not a mass explosion hazard:
    (i) Combustion of which gives rise to considerable radiant heat;
or
    (ii) Which burn one after another, producing minor blast or
projection effects or both;
    (d) Division 1.4--Chemicals and items which present no
significant hazard: chemicals and items which present only a small
hazard in the event of ignition or initiation. The effects are
largely confined to the package and no projection of fragments of
appreciable size or range is to be expected. An external fire shall
not cause virtually instantaneous explosion of almost the entire
contents of the package;
    (e) Division 1.5--Very insensitive chemicals which have a mass
explosion hazard: chemicals which have a mass explosion hazard but
are so insensitive that there is very little probability of
initiation or of transition from burning to detonation under normal
conditions;
    (f) Division 1.6--Extremely insensitive items which do not have
a mass explosion hazard: items which contain only extremely
insensitive detonating chemicals and which demonstrate a negligible
probability of accidental initiation or propagation.

B.1.3 Additional Classification Considerations

    B.1.3.1 Explosives shall be classified as unstable explosives or
shall be assigned to one of the six divisions identified in B.1.2 in
accordance with the three step procedure in Part I of the UN ST/SG/
AC.10 (incorporated by reference; See Sec.  1910.6). The first step
is to ascertain whether the substance or mixture has explosive
effects (Test Series 1). The second step is the acceptance procedure
(Test Series 2 to 4) and the third step is the assignment to a
hazard division (Test Series 5 to 7). The assessment whether a
candidate for ``ammonium nitrate emulsion or suspension or gel,
intermediate for blasting explosives (ANE)'' is insensitive enough
for inclusion as an oxidizing liquid (See B.13) or an oxidizing
solid (See B.14) is determined by Test Series 8 tests.
    Note: Classification of solid chemicals shall be based on tests
performed on the chemical as presented. If, for example, for the
purposes of supply or transport, the same

chemical is to be presented in a physical form different from that
which was tested and which is considered likely to materially alter
its performance in a classification test, classification must be
based on testing of the chemical in the new form.
    B.1.3.2 Explosive properties are associated with the presence of
certain chemical groups in a molecule which can react to produce
very rapid increases in temperature or pressure. The screening
procedure in B.1.3.1 is aimed at identifying the presence of such
reactive groups and the potential for rapid energy release. If the
screening procedure identifies the chemical as a potential
explosive, the acceptance procedure (See section 10.3 of the UN ST/
SG/AC.10 (incorporated by reference; See Sec.  1910.6)) is necessary
for classification.
    Note: Neither a Series 1 type (a) propagation of detonation test
nor a Series 2 type (a) test of sensitivity to detonative shock is
necessary if the exothermic decomposition energy of organic
materials is less than 800 J/g.
    B.1.3.3 If a mixture contains any known explosives, the
acceptance procedure is necessary for classification.
    B.1.3.4 A chemical is not classified as explosive if:
    (a) There are no chemical groups associated with explosive
properties present in the molecule. Examples of groups which may
indicate explosive properties are given in Table A6.1 in Appendix 6
of the UN ST/SG/AC.10 (incorporated by reference; See Sec.  1910.6);
or
    (b) The substance contains chemical groups associated with
explosive properties which include oxygen and the calculated oxygen
balance is less than -200.
    The oxygen balance is calculated for the chemical reaction:

CxHyOz + [x + (y/4) - (z/2)]
O2 [rarr] x. CO2 + (y/2) H2O

using the formula:

oxygen balance = -1600 [2x +(y/2) -z]/molecular weight;
    or
    (c) The organic substance or a homogenous mixture of organic
substances contains chemical groups associated with explosive
properties but the exothermic decomposition energy is less than 500
J/g and the onset of exothermic decomposition is below 500 [deg]C
(932 [deg]F). The exothermic decomposition energy may be determined
using a suitable calorimetric technique; or
    (d) For mixtures of inorganic oxidizing substances with organic
material(s), the concentration of the inorganic oxidizing substance
is:
    (i) Less than 15%, by mass, if the oxidizing substance is
assigned to Category 1 or 2;
    (ii) Less than 30%, by mass, if the oxidizing substance is
assigned to Category 3.

B.2 FLAMMABLE GASES

B.2.1 Definition

    Flammable gas means a gas having a flammable range with air at
20 [deg]C (68 [deg]F) and a standard pressure of 101.3 kPa (14.7
psi).

B.2.2 Classification Criteria

    A flammable gas shall be classified in one of the two categories
for this class in accordance with Table B.2.1:

                                    Table B.2.1--Criteria for Flammable Gases
----------------------------------------------------------------------------------------------------------------
                  Category                                                 Criteria
----------------------------------------------------------------------------------------------------------------
1...........................................  Gases, which at 20 [deg]C (68 [deg]F) and a standard pressure of
                                               101.3 kPa (14.7 psi):
                                               (a) are ignitable when in a mixture of 13% or less by volume in
                                               air; or
                                               (b) have a flammable range with air of at least 12 percentage
                                               points regardless of the lower flammable limit.
2...........................................  Gases, other than those of Category 1, which, at 20 [deg]C (68
                                               [deg]F) and a standard pressure of 101.3 kPa (14.7 psi), have a
                                               flammable range while mixed in air.
----------------------------------------------------------------------------------------------------------------

    Note: Aerosols should not be classified as flammable gases. See
B.3.

B.2.3 Additional Classification Considerations

    Flammability shall be determined by tests or by calculation in
accordance with ISO 10156 (incorporated by reference; See Sec.
1910.6). Where insufficient data are available to use this method,
equivalent validated methods may be used.

B.3 FLAMMABLE AEROSOLS

B.3.1 Definition

    Aerosol means any non-refillable receptacle containing a gas
compressed, liquefied or dissolved under pressure, and fitted with a
release device allowing the contents to be ejected as particles in
suspension in a gas, or as a foam, paste, powder, liquid or gas.

B.3.2 Classification Criteria

    B.3.2.1 Aerosols shall be considered for classification as
flammable if they contain any component which is classified as
flammable in accordance with this Appendix, i.e.:

Flammable liquids (See B.6);
Flammable gases (See B.2);
Flammable solids (See B.7).

    Note 1: Flammable components do not include pyrophoric, self-
heating or water-reactive chemicals.
    Note 2: Flammable aerosols do not fall additionally within the
scope of flammable gases, flammable liquids, or flammable solids.
    B.3.2.2 A flammable aerosol shall be classified in one of the
two categories for this class in accordance with Table B.3.1.

                                  Table B.3.1--Criteria for Flammable Aerosols
----------------------------------------------------------------------------------------------------------------
                  Category                                                 Criteria
----------------------------------------------------------------------------------------------------------------
1...........................................  Contains >=85% flammable components and the chemical heat of
                                               combustion is >=30 kJ/g; or
                                              (a) For spray aerosols, in the ignition distance test, ignition
                                               occurs at a distance >=75 cm (29.5 in), or
                                              (b) For foam aerosols, in the aerosol foam flammability test.
                                              (i) The flame height is >=20 cm (7.87 in) and the flame duration
                                               >=2 s; or
                                              (ii) The flame height is >=4 cm (1.57 in) and the flame duration
                                               >=7 s.
2...........................................  Contains >1% flammable components, or the heat of combustion is
                                               >=20 kJ/g; and
                                              (a) for spray aerosols, in the ignition distance test, ignition
                                               occurs at a distance >=15 cm (5.9 in), or in the enclosed space
                                               ignition test, the
                                              (i) Time equivalent is <=300 s/m\3\; or
                                              (ii) Deflagration density is <=300 g/m\3\.
                                              (b) For foam aerosols, in the aerosol foam flammability test, the
                                               flame height is >=4 cm and the flame duration is >=2 s and it
                                               does not meet the criteria for Category 1.
----------------------------------------------------------------------------------------------------------------

    Note: Aerosols not submitted to the flammability classification
procedures in this Appendix shall be classified as extremely
flammable (Category 1).

B.3.3 Additional Classification Considerations

    B.3.3.1 To classify a flammable aerosol, data on its flammable
components, on its chemical heat of combustion and, if applicable,
the results of the aerosol foam flammability test (for foam
aerosols) and of the ignition distance test and enclosed space test
(for spray aerosols) are necessary.
    B.3.3.2 The chemical heat of combustion ([Delta]Hc), in
kilojoules per gram (kJ/g), is the product of the theoretical heat
of combustion ([Delta]Hcomb), and a combustion efficiency, usually
less than 1.0 (a typical combustion efficiency is 0.95 or 95%).
    For a composite aerosol formulation, the chemical heat of
combustion is the summation of the weighted heats of combustion for
the individual components, as follows:
[GRAPHIC] [TIFF OMITTED] TR26MR12.067

Where:

[Delta]Hc = chemical heat of combustion (kJ/g);
wi% = mass fraction of component i in the product;
[Delta]Hc(i) = specific heat of combustion (kJ/g) of component i in
the product;

    The chemical heats of combustion shall be found in literature,
calculated or determined by tests (See ASTM D240-02, ISO 13943,
Sections 86.1 to 86.3, and NFPA 30B (incorporated by reference; See
Sec.  1910.6)).
    B.3.3.3 The Ignition Distance Test, Enclosed Space Ignition Test
and Aerosol Foam Flammability Test shall be performed in accordance
with sub-sections 31.4, 31.5 and 31.6 of the of the UN ST/SG/AC.10
(incorporated by reference; See Sec.  1910.6).

B.4 OXIDIZING GASES

B.4.1 Definition

    Oxidizing gas means any gas which may, generally by providing
oxygen, cause or contribute to the combustion of other material more
than air does.
    Note: ``Gases which cause or contribute to the combustion of
other material more than air does'' means pure gases or gas mixtures
with an oxidizing power greater than 23.5% (as determined by a
method specified in ISO 10156 or 10156-2 (incorporated by reference,
See Sec.  1910.6) or an equivalent testing method.)

B.4.2 Classification Criteria

    An oxidizing gas shall be classified in a single category for
this class in accordance with Table B.4.1:

                                    Table B.4.1--Criteria for Oxidizing Gases
----------------------------------------------------------------------------------------------------------------
                  Category                                                 Criteria
----------------------------------------------------------------------------------------------------------------
1...........................................  Any gas which may, generally by providing oxygen, cause or
                                               contribute to the combustion of other material more than air
                                               does.
----------------------------------------------------------------------------------------------------------------

B.4.3 Additional Classification Considerations

    Classification shall be in accordance with tests or calculation
methods as described in ISO 10156 (incorporated by reference; See
Sec.  1910.6) and ISO 10156-2 (incorporated by reference; See Sec.
1910.6).

B.5 GASES UNDER PRESSURE

B.5.1 Definition

    Gases under pressure are gases which are contained in a
receptacle at a pressure of 200 kPa (29 psi) (gauge) or more, or
which are liquefied or liquefied and refrigerated.
    They comprise compressed gases, liquefied gases, dissolved gases
and refrigerated liquefied gases.

B.5.2 Classification Criteria

    Gases under pressure shall be classified in one of four groups
in accordance with Table B.5.1:

                                 Table B.5.1--Criteria for Gases Under Pressure
----------------------------------------------------------------------------------------------------------------
                    Group                                                  Criteria
----------------------------------------------------------------------------------------------------------------
Compressed gas..............................  A gas which when under pressure is entirely gaseous at -50 [deg]C
                                               (-8 [deg]F), including all gases with a critical temperature\1\
                                               <=-50 [deg]C (-58 [deg]F).
Liquefied gas...............................  A gas which when under pressure is partially liquid at
                                               temperatures above -50 [deg]C (-58 [deg]F). A distinction is made
                                               between:
                                                 (a) High pressure liquefied gas: A gas with a critical
                                                  temperature \1\ between -50 [deg]C (-58 [deg]F) and +65 [deg]C
                                                  (149 [deg]F); and
                                                 (b) Low pressure liquefied gas: A gas with a critical
                                                  temperature \1\ above +65 [deg]C (149 [deg]F).
Refrigerated liquefied gas..................  A gas which is made partially liquid because of its low
                                               temperature.
Dissolved gas...............................  A gas which when under pressure is dissolved in a liquid phase
                                               solvent.
----------------------------------------------------------------------------------------------------------------
\1\ The critical temperature is the temperature above which a pure gas cannot be liquefied, regardless of the
  degree of compression.

B.6 FLAMMABLE LIQUIDS

B.6.1 Definition

    Flammable liquid means a liquid having a flash point of not more
than 93 [deg]C (199.4 [deg]F).
    Flash point means the minimum temperature at which a liquid
gives off vapor in sufficient concentration to form an ignitable
mixture with air near the surface of the liquid, as determined by a
method identified in Section B.6.3.

B.6.2 Classification Criteria

    A flammable liquid shall be classified in one of four categories
in accordance with Table B.6.1:

                                                       Table B.6.1--Criteria for Flammable Liquids
--------------------------------------------------------------------------------------------------------------------------------------------------------
                  Category                                                                     Criteria
--------------------------------------------------------------------------------------------------------------------------------------------------------
1...........................................  Flash point <23 [deg]C (73.4 [deg]F) and initial boiling point <=35 [deg]C (95 [deg]F).

2...........................................  Flash point <23 [deg]C (73.4 [deg]F) and initial boiling point >35 [deg]C (95 [deg]F).
3...........................................  Flash point >=23 [deg]C (73.4 [deg]F) and <=60 [deg]C (140 [deg]F).
4...........................................  Flash point >60 [deg]C (140 [deg]F) and <=93 [deg]C (199.4 [deg]F).
--------------------------------------------------------------------------------------------------------------------------------------------------------

B.6.3 Additional Classification Considerations

    The flash point shall be determined in accordance with ASTM D56-
05, ASTM D3278, ASTM D3828, ASTM D93-08 (incorporated by reference;
See Sec.  1910.6), or any other method specified in GHS Revision 3,
Chapter 2.6.
    The initial boiling point shall be determined in accordance with
ASTM D86-07a or ASTM D1078 (incorporated by reference; See Sec.
1910.6).

B.7 FLAMMABLE SOLIDS

B.7.1 Definitions

    Flammable solid means a solid which is a readily combustible
solid, or which may cause or contribute to fire through friction.
    Readily combustible solids are powdered, granular, or pasty
chemicals which are dangerous if they can be easily ignited by brief
contact with an ignition source, such as a burning match, and if the
flame spreads rapidly.

B.7.2 Classification Criteria

    B.7.2.1 Powdered, granular or pasty chemicals shall be
classified as flammable solids when the time of burning of one or
more of the test runs, performed in accordance with the test method
described in the UN ST/SG/AC.10 (incorporated by reference; See
Sec.  1910.6), Part III, sub-section 33.2.1, is less than 45 s or
the rate of burning is more than 2.2 mm/s (0.0866 in/s).
    B.7.2.2 Powders of metals or metal alloys shall be classified as
flammable solids when they can be ignited and the reaction spreads
over the whole length of the sample in 10 min or less.
    B.7.2.3 Solids which may cause fire through friction shall be
classified in this class by analogy with existing entries (e.g.,
matches) until definitive criteria are established.
    B.7.2.4 A flammable solid shall be classified in one of the two
categories for this class using Method N.1 as described in Part III,
sub-section 33.2.1 of the UN ST/SG/AC.10 (incorporated by reference;
See Sec.  1910.6), in accordance with Table B.7.1:

               Table B.7.1--Criteria for Flammable Solids
------------------------------------------------------------------------
                Category                             Criteria
------------------------------------------------------------------------
1......................................  Burning rate test:
                                            Chemicals other than metal
                                             powders:
                                              (a) Wetted zone does not
                                               stop fire; and
                                              (b) Burning time <45 s or
                                               burning rate >2.2 mm/s.
                                            Metal powders: Burning time
                                             <=5 min.
2......................................  Burning rate test:
                                            Chemicals other than metal
                                             powders:
                                              (a) Wetted zone stops the
                                               fire for at least 4 min;
                                               and
                                              (b) Burning time <45 s or
                                               burning rate >2.2 mm/s.
                                            Metal powders: Burning time
                                             >5 min and <=10 min.
------------------------------------------------------------------------

    Note: Classification of solid chemicals shall be based on tests
performed on the chemical as presented. If, for example, for the
purposes of supply or transport, the same chemical is to be
presented in a physical form different from that which was tested
and which is considered likely to materially alter its performance
in a classification test, classification must be based on testing of
the chemical in the new form.

B.8 SELF-REACTIVE CHEMICALS

B.8.1 Definitions

    Self-reactive chemicals are thermally unstable liquid or solid
chemicals liable to undergo a strongly exothermic decomposition even
without participation of oxygen (air). This definition excludes
chemicals classified under this section as explosives, organic
peroxides, oxidizing liquids or oxidizing solids.
    A self-reactive chemical is regarded as possessing explosive
properties when in laboratory testing the formulation is liable to
detonate, to deflagrate rapidly or to show a violent effect when
heated under confinement.

B.8.2 Classification Criteria

    B.8.2.1 A self-reactive chemical shall be considered for
classification in this class unless:
    (a) It is classified as an explosive according to B.1 of this
appendix;
    (b) It is classified as an oxidizing liquid or an oxidizing
solid according to B.13 or B.14 of this appendix, except that a
mixture of oxidizing substances which contains 5% or more of
combustible organic substances shall be classified as a self-
reactive chemical according to the procedure defined in B.8.2.2;
    (c) It is classified as an organic peroxide according to B.15 of
this appendix;
    (d) Its heat of decomposition is less than 300 J/g; or
    (e) Its self-accelerating decomposition temperature (SADT) is
greater than 75 [deg]C (167 [deg]F) for a 50 kg (110 lb) package.
    B.8.2.2 Mixtures of oxidizing substances, meeting the criteria
for classification as oxidizing liquids or oxidizing solids, which
contain 5% or more of combustible organic substances and which do
not meet the criteria mentioned in B.8.2.1 (a), (c), (d) or (e),
shall be subjected to the self-reactive chemicals classification
procedure in B.8.2.3. Such a mixture showing the properties of a
self-reactive chemical type B to F shall be classified as a self-
reactive chemical.
    B.8.2.3 Self-reactive chemicals shall be classified in one of
the seven categories of ``types A to G'' for this class, according
to the following principles:
    (a) Any self-reactive chemical which can detonate or deflagrate
rapidly, as packaged, will be defined as self-reactive chemical TYPE
A;
    (b) Any self-reactive chemical possessing explosive properties
and which, as packaged, neither detonates nor deflagrates rapidly,
but is liable to undergo a thermal explosion in that package will be
defined as self-reactive chemical TYPE B;
    (c) Any self-reactive chemical possessing explosive properties
when the chemical as packaged cannot detonate or deflagrate rapidly
or undergo a thermal explosion will be defined as self-reactive
chemical TYPE C;
    (d) Any self-reactive chemical which in laboratory testing meets
the criteria in (d)(i), (ii), or (iii) will be defined as self-
reactive chemical TYPE D:
    (i) Detonates partially, does not deflagrate rapidly and shows
no violent effect when heated under confinement; or

    (ii) Does not detonate at all, deflagrates slowly and shows no
violent effect when heated under confinement; or
    (iii) Does not detonate or deflagrate at all and shows a medium
effect when heated under confinement;
    (e) Any self-reactive chemical which, in laboratory testing,
neither detonates nor deflagrates at all and shows low or no effect
when heated under confinement will be defined as self-reactive
chemical TYPE E;
    (f) Any self-reactive chemical which, in laboratory testing,
neither detonates in the cavitated state nor deflagrates at all and
shows only a low or no effect when heated under confinement as well
as low or no explosive power will be defined as self-reactive
chemical TYPE F;
    (g) Any self-reactive chemical which, in laboratory testing,
neither detonates in the cavitated state nor deflagrates at all and
shows no effect when heated under confinement nor any explosive
power, provided that it is thermally stable (self-accelerating
decomposition temperature is 60 [deg]C (140 [deg]F) to 75 [deg]C
(167 [deg]F) for a 50 kg (110 lb) package), and, for liquid
mixtures, a diluent having a boiling point greater than or equal to
150 [deg]C (302 [deg]F) is used for desensitization will be defined
as self-reactive chemical TYPE G. If the mixture is not thermally
stable or a diluent having a boiling point less than 150 [deg]C (302
[deg]F) is used for desensitization, the mixture shall be defined as
self-reactive chemical TYPE F.

B.8.3 Additional Classification Considerations

    B.8.3.1 For purposes of classification, the properties of self-
reactive chemicals shall be determined in accordance with test
series A to H as described in Part II of the UN ST/SG/AC.10
(incorporated by reference; See Sec.  1910.6).
    B.8.3.2 Self-accelerating decomposition temperature (SADT) shall
be determined in accordance with the UN ST/SG/AC.10, Part II,
section 28 (incorporated by reference; See Sec.  1910.6).
    B.8.3.3 The classification procedures for self-reactive
substances and mixtures need not be applied if:
    (a) There are no chemical groups present in the molecule
associated with explosive or self-reactive properties; examples of
such groups are given in Tables A6.1 and A6.2 in the Appendix 6 of
the UN ST/SG/AC.10 (incorporated by reference; See Sec.  1910.6); or
    (b) For a single organic substance or a homogeneous mixture of
organic substances, the estimated SADT is greater than 75 [deg]C
(167 [deg]F) or the exothermic decomposition energy is less than 300
J/g. The onset temperature and decomposition energy may be estimated
using a suitable calorimetric technique (See <IP_ADDRESS> in Part II of
the UN ST/SG/AC.10 (incorporated by reference; See Sec.  1910.6)).

B.9 PYROPHORIC LIQUIDS

B.9.1 Definition

    Pyrophoric liquid means a liquid which, even in small
quantities, is liable to ignite within five minutes after coming
into contact with air.

B.9.2 Classification Criteria

    A pyrophoric liquid shall be classified in a single category for
this class using test N.3 in Part III, sub-section <IP_ADDRESS> of the
UN ST/SG/AC.10 (incorporated by reference; See Sec.  1910.6), in
accordance with Table B.9.1:

                                  Table B.9.1--Criteria for Pyrophoric Liquids
----------------------------------------------------------------------------------------------------------------
                  Category                                                 Criteria
----------------------------------------------------------------------------------------------------------------
1...........................................  The liquid ignites within 5 min when added to an inert carrier and
                                               exposed to air, or it ignites or chars a filter paper on contact
                                               with air within 5 min.
----------------------------------------------------------------------------------------------------------------

B.9.3 Additional Classification Considerations

    The classification procedure for pyrophoric liquids need not be
applied when experience in production or handling shows that the
chemical does not ignite spontaneously on coming into contact with
air at normal temperatures (i.e., the substance is known to be
stable at room temperature for prolonged periods of time (days)).

B.10 PYROPHORIC SOLIDS

B.10.1 Definition

    Pyrophoric solid means a solid which, even in small quantities,
is liable to ignite within five minutes after coming into contact
with air.

B.10.2 Classification Criteria

    A pyrophoric solid shall be classified in a single category for
this class using test N.2 in Part III, sub-section <IP_ADDRESS> of the
UN ST/SG/AC.10 (incorporated by reference; See Sec.  1910.6), in
accordance with Table B.10.1:

                                                      Table B.10.1--Criteria for Pyrophoric Solids
--------------------------------------------------------------------------------------------------------------------------------------------------------
                   Category                                                                     Criteria
--------------------------------------------------------------------------------------------------------------------------------------------------------
1.............................................  The solid ignites within 5 min of coming into contact with air.
--------------------------------------------------------------------------------------------------------------------------------------------------------

    Note: Classification of solid chemicals shall be based on tests
performed on the chemical as presented. If, for example, for the
purposes of supply or transport, the same chemical is to be
presented in a physical form different from that which was tested
and which is considered likely to materially alter its performance
in a classification test, classification must be based on testing of
the chemical in the new form.

B.10.3 Additional Classification Considerations

    The classification procedure for pyrophoric solids need not be
applied when experience in production or handling shows that the
chemical does not ignite spontaneously on coming into contact with
air at normal temperatures (i.e., the chemical is known to be stable
at room temperature for prolonged periods of time (days)).

B.11 SELF-HEATING CHEMICALS

B.11.1 Definition

    A self-heating chemical is a solid or liquid chemical, other
than a pyrophoric liquid or solid, which, by reaction with air and
without energy supply, is liable to self-heat; this chemical differs
from a pyrophoric liquid or solid in that it will ignite only when
in large amounts (kilograms) and after long periods of time (hours
or days).
    Note: Self-heating of a substance or mixture is a process where
the gradual reaction of that substance or mixture with oxygen (in
air) generates heat. If the rate of heat production exceeds the rate
of heat loss, then the temperature of the substance or mixture will
rise which, after an induction time, may lead to self-ignition and
combustion.

B.11.2 Classification Criteria

    B.11.2.1 A self-heating chemical shall be classified in one of
the two categories for this class if, in tests performed in
accordance with test method N.4 in Part III, sub-section <IP_ADDRESS> of
the UN ST/SG/AC.10 (incorporated by reference; See Sec.  1910.6),
the result meets the criteria shown in Table B.11.1.

                                Table B.11.1--Criteria for Self-Heating Chemicals
----------------------------------------------------------------------------------------------------------------
                  Category                                                 Criteria
----------------------------------------------------------------------------------------------------------------
1...........................................  A positive result is obtained in a test using a 25 mm sample cube
                                               at 140 [deg]C (284 [deg]F).
2...........................................  A negative result is obtained in a test using a 25 mm cube sample
                                               at 140 [deg]C (284 [deg]F), a positive result is obtained in a
                                               test using a 100 mm sample cube at 140 [deg]C (284 [deg]F), and:
                                                 (a) The unit volume of the chemical is more than 3 m\3\; or
                                                 (b) A positive result is obtained in a test using a 100 mm cube
                                                  sample at 120 [deg]C (248 [deg]F) and the unit volume of the
                                                  chemical is more than 450 liters; or
                                                 (c) A positive result is obtained in a test using a 100 mm cube
                                                  sample at 100 [deg]C (212 [deg]F).
----------------------------------------------------------------------------------------------------------------

    B.11.2.2 Chemicals with a temperature of spontaneous combustion
higher than 50 [deg]C (122 [deg]F) for a volume of 27 m\3\ shall not
be classified as self-heating chemicals.
    B.11.2.3 Chemicals with a spontaneous ignition temperature
higher than 50 [deg]C (122 [deg]F) for a volume of 450 liters shall
not be classified in Category 1 of this class.

B.11.3 Additional Classification Considerations

    B.11.3.1 The classification procedure for self-heating chemicals
need not be applied if the results of a screening test can be
adequately correlated with the classification test and an
appropriate safety margin is applied.
    B.11.3.2 Examples of screening tests are:
    (a) The Grewer Oven test (VDI guideline 2263, part 1, 1990, Test
methods for the Determination of the Safety Characteristics of
Dusts) with an onset temperature 80[deg]K above the reference
temperature for a volume of 1 l;
    (b) The Bulk Powder Screening Test (Gibson, N. Harper, D. J.
Rogers, R. Evaluation of the fire and explosion risks in drying
powders, Plant Operations Progress, 4 (3), 181-189, 1985) with an
onset temperature 60[deg]K above the reference temperature for a
volume of 1 l.

B.12 CHEMICALS WHICH, IN CONTACT WITH WATER, EMIT FLAMMABLE GASES

B.12.1 Definition

    Chemicals which, in contact with water, emit flammable gases are
solid or liquid chemicals which, by interaction with water, are
liable to become spontaneously flammable or to give off flammable
gases in dangerous quantities.

B.12.2 Classification Criteria

    B.12.2.1 A chemical which, in contact with water, emits
flammable gases shall be classified in one of the three categories
for this class, using test N.5 in Part III, sub-section <IP_ADDRESS> of
the UN ST/SG/AC.10 (incorporated by reference; See Sec.  1910.6), in
accordance with Table B.12.1:

             Table B.12.1--Criteria for Chemicals Which, in Contact With Water, Emit Flammable Gases
----------------------------------------------------------------------------------------------------------------
                  Category                                                 Criteria
----------------------------------------------------------------------------------------------------------------
1...........................................  Any chemical which reacts vigorously with water at ambient
                                               temperatures and demonstrates generally a tendency for the gas
                                               produced to ignite spontaneously, or which reacts readily with
                                               water at ambient temperatures such that the rate of evolution of
                                               flammable gas is equal to or greater than 10 liters per kilogram
                                               of chemical over any one minute.
2...........................................  Any chemical which reacts readily with water at ambient
                                               temperatures such that the maximum rate of evolution of flammable
                                               gas is equal to or greater than 20 liters per kilogram of
                                               chemical per hour, and which does not meet the criteria for
                                               Category 1.
3...........................................  Any chemical which reacts slowly with water at ambient
                                               temperatures such that the maximum rate of evolution of flammable
                                               gas is equal to or greater than 1 liter per kilogram of chemical
                                               per hour, and which does not meet the criteria for Categories 1
                                               and 2.
----------------------------------------------------------------------------------------------------------------

    Note: Classification of solid chemicals shall be based on tests
performed on the chemical as presented. If, for example, for the
purposes of supply or transport, the same chemical is to be
presented in a physical form different from that which was tested
and which is considered likely to materially alter its performance
in a classification test, classification must be based on testing of
the chemical in the new form.
    B.12.2.2 A chemical is classified as a chemical which, in
contact with water emits flammable gases if spontaneous ignition
takes place in any step of the test procedure.

B.12.3 Additional Classification Considerations

    The classification procedure for this class need not be applied
if:
    (a) The chemical structure of the chemical does not contain
metals or metalloids;
    (b) Experience in production or handling shows that the chemical
does not react with water, (e.g., the chemical is manufactured with
water or washed with water); or
    (c) The chemical is known to be soluble in water to form a
stable mixture.

B.13 OXIDIZING LIQUIDS

B.13.1 Definition

    Oxidizing liquid means a liquid which, while in itself not
necessarily combustible, may, generally by yielding oxygen, cause,
or contribute to, the combustion of other material.

B.13.2 Classification Criteria

    An oxidizing liquid shall be classified in one of the three
categories for this class using test O.2 in Part III, sub-section
34.4.2 of the UN ST/SG/AC.10 (incorporated by reference; See Sec.
1910.6), in accordance with Table B.13.1:

                                  Table B.13.1--Criteria for Oxidizing Liquids
----------------------------------------------------------------------------------------------------------------
                  Category                                                 Criteria
----------------------------------------------------------------------------------------------------------------
1...........................................  Any chemical which, in the 1:1 mixture, by mass, of chemical and
                                               cellulose tested, spontaneously ignites; or the mean pressure
                                               rise time of a 1:1 mixture, by mass, of chemical and cellulose is
                                               less than that of a 1:1 mixture, by mass, of 50% perchloric acid
                                               and cellulose;

2...........................................  Any chemical which, in the 1:1 mixture, by mass, of chemical and
                                               cellulose tested, exhibits a mean pressure rise time less than or
                                               equal to the mean pressure rise time of a 1:1 mixture, by mass,
                                               of 40% aqueous sodium chlorate solution and cellulose; and the
                                               criteria for Category 1 are not met;
3...........................................  Any chemical which, in the 1:1 mixture, by mass, of chemical and
                                               cellulose tested, exhibits a mean pressure rise time less than or
                                               equal to the mean pressure rise time of a 1:1 mixture, by mass,
                                               of 65% aqueous nitric acid and cellulose; and the criteria for
                                               Categories 1 and 2 are not met.
----------------------------------------------------------------------------------------------------------------

B.13.3 Additional Classification Considerations

    B.13.3.1 For organic chemicals, the classification procedure for
this class shall not be applied if:
    (a) The chemical does not contain oxygen, fluorine or chlorine;
or
    (b) The chemical contains oxygen, fluorine or chlorine and these
elements are chemically bonded only to carbon or hydrogen.
    B.13.3.2 For inorganic chemicals, the classification procedure
for this class shall not be applied if the chemical does not contain
oxygen or halogen atoms.
    B.13.3.3 In the event of divergence between test results and
known experience in the handling and use of chemicals which shows
them to be oxidizing, judgments based on known experience shall take
precedence over test results.
    B.13.3.4 In cases where chemicals generate a pressure rise (too
high or too low), caused by chemical reactions not characterizing
the oxidizing properties of the chemical, the test described in Part
III, sub-section 34.4.2 of the UN ST/SG/AC.10 (incorporated by
reference; See Sec.  1910.6) shall be repeated with an inert
substance (e.g., diatomite (kieselguhr)) in place of the cellulose
in order to clarify the nature of the reaction.

B.14 OXIDIZING SOLIDS

B.14.1 Definition

    Oxidizing solid means a solid which, while in itself is not
necessarily combustible, may, generally by yielding oxygen, cause,
or contribute to, the combustion of other material.

B.14.2 Classification Criteria

    An oxidizing solid shall be classified in one of the three
categories for this class using test O.1 in Part III, sub-section
34.4.1 of the UN ST/SG/AC.10 (incorporated by reference; See Sec.
1910.6), in accordance with Table B.14.1:

                                   Table B.14.1--Criteria for Oxidizing Solids
----------------------------------------------------------------------------------------------------------------
                  Category                                                 Criteria
----------------------------------------------------------------------------------------------------------------
1...........................................  Any chemical which, in the 4:1 or 1:1 sample-to-cellulose ratio
                                               (by mass) tested, exhibits a mean burning time less than the mean
                                               burning time of a 3:2 mixture, by mass, of potassium bromate and
                                               cellulose.
2...........................................  Any chemical which, in the 4:1 or 1:1 sample-to-cellulose ratio
                                               (by mass) tested, exhibits a mean burning time equal to or less
                                               than the mean burning time of a 2:3 mixture (by mass) of
                                               potassium bromate and cellulose and the criteria for Category 1
                                               are not met.
3...........................................  Any chemical which, in the 4:1 or 1:1 sample-to-cellulose ratio
                                               (by mass) tested, exhibits a mean burning time equal to or less
                                               than the mean burning time of a 3:7 mixture (by mass) of
                                               potassium bromate and cellulose and the criteria for Categories 1
                                               and 2 are not met.
----------------------------------------------------------------------------------------------------------------

    Note 1: Some oxidizing solids may present explosion hazards
under certain conditions (e.g., when stored in large quantities).
For example, some types of ammonium nitrate may give rise to an
explosion hazard under extreme conditions and the ``Resistance to
detonation test'' (IMO: Code of Safe Practice for Solid Bulk
Cargoes, 2005, Annex 3, Test 5) may be used to assess this hazard.
When information indicates that an oxidizing solid may present an
explosion hazard, it shall be indicated on the Safety Data Sheet.
    Note 2: Classification of solid chemicals shall be based on
tests performed on the chemical as presented. If, for example, for
the purposes of supply or transport, the same chemical is to be
presented in a physical form different from that which was tested
and which is considered likely to materially alter its performance
in a classification test, classification must be based on testing of
the chemical in the new form.

B.14.3 Additional Classification Considerations

    B.14.3.1 For organic chemicals, the classification procedure for
this class shall not be applied if:
    (a) The chemical does not contain oxygen, fluorine or chlorine;
or
    (b) The chemical contains oxygen, fluorine or chlorine and these
elements are chemically bonded only to carbon or hydrogen.
    B.14.3.2 For inorganic chemicals, the classification procedure
for this class shall not be applied if the chemical does not contain
oxygen or halogen atoms.
    B.14.3.3 In the event of divergence between test results and
known experience in the handling and use of chemicals which shows
them to be oxidizing, judgements based on known experience shall
take precedence over test results.

B.15 ORGANIC PEROXIDES

B.15.1 Definition

    B.15.1.1 Organic peroxide means a liquid or solid organic
chemical which contains the bivalent -0-0- structure and as such is
considered a derivative of hydrogen peroxide, where one or both of
the hydrogen atoms have been replaced by organic radicals. The term
organic peroxide includes organic peroxide mixtures containing at
least one organic peroxide. Organic peroxides are thermally unstable
chemicals, which may undergo exothermic self-accelerating
decomposition. In addition, they may have one or more of the
following properties:
    (a) Be liable to explosive decomposition;
    (b) Burn rapidly;
    (c) Be sensitive to impact or friction;
    (d) React dangerously with other substances.
    B.15.1.2 An organic peroxide is regarded as possessing explosive
properties when in laboratory testing the formulation is liable to
detonate, to deflagrate rapidly or to show a violent effect when
heated under confinement.

B.15.2 Classification Criteria

    B.15.2.1 Any organic peroxide shall be considered for
classification in this class, unless it contains:
    (a) Not more than 1.0% available oxygen from the organic
peroxides when containing not more than 1.0% hydrogen peroxide; or
    (b) Not more than 0.5% available oxygen from the organic
peroxides when containing more than 1.0% but not more than 7.0%
hydrogen peroxide.
    Note: The available oxygen content (%) of an organic peroxide
mixture is given by the formula:
[GRAPHIC] [TIFF OMITTED] TR26MR12.068

Where:

ni = number of peroxygen groups per molecule of organic peroxide i;
ci = concentration (mass %) of organic peroxide i;
mi = molecular mass of organic peroxide i.

    B.15.2.2 Organic peroxides shall be classified in one of the
seven categories of ``Types A to G'' for this class, according to
the following principles:
    (a) Any organic peroxide which, as packaged, can detonate or
deflagrate rapidly shall be defined as organic peroxide TYPE A;
    (b) Any organic peroxide possessing explosive properties and
which, as packaged, neither detonates nor deflagrates rapidly, but
is liable to undergo a thermal explosion in that package shall be
defined as organic peroxide TYPE B;
    (c) Any organic peroxide possessing explosive properties when
the chemical as packaged cannot detonate or deflagrate rapidly or
undergo a thermal explosion shall be defined as organic peroxide
TYPE C;
    (d) Any organic peroxide which in laboratory testing meets the
criteria in (d)(i), (ii), or (iii) shall be defined as organic
peroxide TYPE D:
    (i) Detonates partially, does not deflagrate rapidly and shows
no violent effect when heated under confinement; or
    (ii) Does not detonate at all, deflagrates slowly and shows no
violent effect when heated under confinement; or
    (iii) Does not detonate or deflagrate at all and shows a medium
effect when heated under confinement;
    (e) Any organic peroxide which, in laboratory testing, neither
detonates nor deflagrates at all and shows low or no effect when
heated under confinement shall be defined as organic peroxide TYPE
E;
    (f) Any organic peroxide which, in laboratory testing, neither
detonates in the cavitated state nor deflagrates at all and shows
only a low or no effect when heated under confinement as well as low
or no explosive power shall be defined as organic peroxide TYPE F;
    (g) Any organic peroxide which, in laboratory testing, neither
detonates in the cavitated state nor deflagrates at all and shows no
effect when heated under confinement nor any explosive power,
provided that it is thermally stable (self-accelerating
decomposition temperature is 60 [deg]C (140 [deg]F) or higher for a
50 kg (110 lb) package), and, for liquid mixtures, a diluent having
a boiling point of not less than 150 [deg]C (302 [deg]F) is used for
desensitization, shall be defined as organic peroxide TYPE G. If the
organic peroxide is not thermally stable or a diluent having a
boiling point less than 150 [deg]C (302 [deg]F) is used for
desensitization, it shall be defined as organic peroxide TYPE F.

B.15.3 Additional Classification Considerations

    B.15.3.1 For purposes of classification, the properties of
organic peroxides shall be determined in accordance with test series
A to H as described in Part II of the UN ST/SG/AC.10 (incorporated
by reference; See Sec.  1910.6).
    B.15.3.2 Self-accelerating decomposition temperature (SADT)
shall be determined in accordance with the UN ST/SG/AC.10
(incorporated by reference; See Sec.  1910.6), Part II, section 28.
    B.15.3.3 Mixtures of organic peroxides may be classified as the
same type of organic peroxide as that of the most dangerous
ingredient. However, as two stable ingredients can form a thermally
less stable mixture, the SADT of the mixture shall be determined.

B.16 CORROSIVE TO METALS

B.16.1 Definition

    A chemical which is corrosive to metals means a chemical which
by chemical action will materially damage, or even destroy, metals.

B.16.2 Classification Criteria

    A chemical which is corrosive to metals shall be classified in a
single category for this class, using the test in Part III, sub-
section 37.4 of the UN ST/SG/AC.10 (incorporated by reference; See
Sec.  1910.6), in accordance with Table B.16.1:

                             Table B.16.1--Criteria for Chemicals Corrosive to Metal
----------------------------------------------------------------------------------------------------------------
                  Category                                                 Criteria
----------------------------------------------------------------------------------------------------------------
1...........................................  Corrosion rate on either steel or aluminium surfaces exceeding
                                               6.25 mm per year at a test temperature of 55 [deg]C (131 [deg]F)
                                               when tested on both materials.
----------------------------------------------------------------------------------------------------------------