Concise International Chemical Assessment Document 19


    This report contains the collective views of an international group of
    experts and does not necessarily represent the decisions or the stated
    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization.

    First draft prepared by

    Mr R. Cary, Health and Safety Executive, Liverpool, United Kingdom,

    Dr S. Dobson, Institute of Terrestrial Ecology, Huntingdon, United
    Kingdom, and

    Dr I. Brooke, Health and Safety Executive, Liverpool, United Kingdom

    Published under the joint sponsorship of the United Nations
    Environment Programme, the International Labour Organisation, and the
    World Health Organization, and produced within the framework of the
    Inter-Organization Programme for the Sound Management of Chemicals.

    World Health Organization
    Geneva, 2000

         The International Programme on Chemical Safety (IPCS),
    established in 1980, is a joint venture of the United Nations
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    sound management of chemicals in relation to human health and the

    WHO Library Cataloguing-in-Publication Data


    (Concise international chemical assessment document ; 19)

    1.Phenylhydrazines - toxicology 2.No-observed-adverse-effect level
    3.Risk assessment 4.Environmental exposure I.International Programme
    on Chemical Safety II.Series

    ISBN 92 4 153019 7           (NLM classification: QV 180)
    ISSN 1020-6167

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        6.1. Environmental levels

        6.2. Human exposure



        8.1. Single exposure

        8.2. Irritation and sensitization

        8.3. Short-term exposure

        8.4. Long-term exposure

             8.4.1. Subchronic exposure

             8.4.2. Chronic exposure and carcinogenicity

        8.5. Genotoxicity and related end-points

        8.6. Reproductive and developmental toxicity

        8.7. Immunological and neurological effects



        10.1. Aquatic environment

        10.2. Terrestrial environment


        11.1. Evaluation of health effects

             11.1.1. Hazard identification and dose-response assessment

             11.1.2. Criteria for setting guidance values for phenylhydrazine

             11.1.3. Sample risk characterization

        11.2. Evaluation of environmental effects



        13.1. Human health hazards

        13.2. Advice to physicians

        13.3. Health surveillance advice










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    1  International Programme on Chemical Safety (1994)
        Assessing human health risks of chemicals: deriviation of
        guidance values for health-based exposure limits. Geneva, World
       Health Organization (Environmental Health Criteria 170).


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         This CICAD on phenylhydrazine was based on a review of human
    health concerns (primarily occupational) prepared by the United
    Kingdom's Health and Safety Executive (Brooke et al., 1997) and a
    report prepared for the German Advisory Committee on Existing
    Chemicals of Environmental Relevance (BUA, 1995). Hence, this document
    focuses on exposures via routes relevant to occupational settings but
    also contains environmental information. Data identified as of
    December 1993 and December 1994, respectively, were covered. A further
    literature search was performed up to January 1998 to identify any
    extra information published since these reviews were completed.
    Information on the nature of the peer review and availability of the
    source documents is presented in Appendix 1. Information on the peer
    review of this CICAD is presented in Appendix 2. This CICAD was
    approved as an international assessment at a meeting of the Final
    Review Board, held in Washington, DC, USA, on 8-11 December 1998.
    Participants at the Final Review Board meeting are listed in Appendix
    3. The International Chemical Safety Card (ICSC 0938) for
    phenylhydrazine, produced by the International Programme on Chemical
    Safety (IPCS, 1993), has also been reproduced in this document.

         Phenylhydrazine (CAS No. 100-63-0) exists as yellow to pale brown
    crystals or as a yellowish oily liquid. It is sparingly soluble in
    water and is miscible with other organic solvents.

         Phenylhydrazine is used worldwide mainly as a chemical
    intermediate in the pharmaceutical, agrochemical, and chemical

         The number of persons potentially exposed to phenylhydrazine or
    its hydrochloride salt is not known, but it is expected to be small.
    No personal exposure data were available, although the Estimation and
    Assessment of Substance Exposure (EASE) model predicted exposure
    (8-h time-weighted average) to be around 2.3 mg/m3 (0.5 ppm). In
    practice, the 8-h time-weighted average exposure will be less than
    this figure.

         The limited data on toxicokinetics indicate that phenylhydrazine
    is well absorbed by inhalation, oral, and dermal routes and binds
    readily to haemoglobin in red blood cells. Metabolism seems to occur
    via ring hydroxylation and conjugation, probably with glucuronic acid.
    Excretion is primarily via the urine.

         Phenylhydrazine is toxic by single exposure via the oral route
    (LD50 80-188 mg/kg body weight) and is expected to be toxic by the
    inhalation and dermal routes (data from these routes of exposure are
    less clear). Phenylhydrazine has potential for skin and eye

    irritation, and there is evidence that it has skin-sensitizing
    properties in humans. Exposure to phenylhydrazine may cause damage to
    red blood cells, potentially resulting in anaemia and consequential
    secondary involvement of other tissues, such as the spleen and liver.
    Phenylhydrazine is mutagenic  in vitro, and there is some evidence to
    indicate that it may express genotoxic activity  in vivo. The
    substance is clearly carcinogenic in mice following oral dosing,
    inducing tumours of the vascular system. The mechanism for tumour
    formation is unclear, but a genotoxic component cannot be excluded.
    Hence, it is not considered possible to reliably identify a level of
    exposure at which there will be no risk of carcinogenic or genotoxic

         There are no adequate data available regarding reproductive or
    developmental effects; hence, it is not possible to evaluate the risk
    to human health for these end-points.

         The level of risk in occupational settings is uncertain; as a
    result, there is a continuing requirement to reduce exposure levels as
    much as is reasonably practicable with the technology that is
    currently available.

         The lack of available data to serve as a basis for estimation of
    indirect exposure of individuals to phenylhydrazine from the general
    environment precludes the characterization of potential cancer risks
    for the general population.

         No atmospheric effects are expected given the release of
    phenylhydrazine predominantly to water, its extremely low
    volatilization from water to the atmosphere, and its rapid calculated
    atmospheric half-life following reaction with hydroxyl radicals.

         Phenylhydrazine is degraded photochemically and autoxidizes in
    water. It is readily biodegradable, and this is expected to be the
    major route of breakdown in the environment. There is minimal sorption
    to particulates.

         Phenylhydrazine is toxic to aquatic organisms, with the lowest
    reported no-observed-effect concentration (NOEC) in standard acute
    fish tests at 0.01 mg/litre; fish are generally more sensitive than
    either daphnids or bacteria. A NOEC of 0.49 µg/litre has been reported
    for embryo-larval stages of the zebra fish ( Brachydanio rerio).

         The risk to aquatic organisms is expected to be low, based on
    very conservative assumptions.


         Phenylhydrazine (C6H8N2; molecular weight 108; CAS No.
    100-63-0; see structural diagram below) exists as yellow to pale brown
    crystals or as a yellowish oily liquid, with a freezing point of
    19.6°C, a boiling point of 243.4°C, and a vapour pressure of 133 Pa at
    72°C. It is soluble in water (values ranging from 145 to 837 g/litre
    at 24°C have been reported) and is miscible with alcohol, ether,
    chloroform, benzene, and acetone. The conversion factor for
    phenylhydrazine is 1 ppm = 4.5 mg/m3 (at 20°C, 101 kPa). Additional
    physical/chemical properties of phenylhydrazine are presented in the
    International Chemical Safety Card reproduced in this document.



         For measurement of phenylhydrazine in water, reduction of Cu(II)
    to Cu(I) by phenylhydrazine has been used as the basis for
    spectrometric analytical methods measuring coloured complexes (Besada,
    1988; Hasan, 1988). The methods are not specific and react to other
    reducing substances. A detection limit of 10 µg/litre is given for one
    method (Hasan, 1988).

         In a method published by NIOSH (1994) for measurement of
    phenylhydrazine in workplace air, the air is sampled into a midget
    bubbler containing hydrochloric acid. Phosphomolybdic acid is added to
    the resulting solution, and the reaction with phenylhydrazine causes
    the formation of a bluish-green complex that can be measured at 730 nm
    with a spectrophotometer. This method has a detection limit of about 5
    mg/m3 (about 1 ppm), based on a 100-litre sample. Potential
    interferences are listed as other hydrazine derivatives, aldehydes,
    and ketones.

         Both the MIRAN 1B and the Bruel and Kjaer 1302 Multigas Monitor
    may be used to measure phenylhydrazine in air, with a detection limit
    of around 13.5 mg/m3 (3 ppm) (Brooke et al., 1997). Any other
    substance having similar infrared absorbances can be expected to
    interfere with the measurement.

         There are no published biological monitoring methods available
    for phenylhydrazine.


         There are a few reports of the natural occurrence of
    phenylhydrazine in plants (BUA, 1995). Phenylhydrazine is produced
    commercially by the diazotization of aniline followed by reduction of
    the azo compound.

         Production figures for 1990-1992 in Germany were about 3000-4000
    t/year; use figures for Western Europe in 1988 totalled 6650 t (BUA,
    1995). Use patterns for Western Europe in 1988 and for Germany in
    1990-1992 are shown in Table 1.

    Table 1: Phenylhydrazine use patterns in Western Europe
    and Germany.
                            Phenylhydrazine use (%)
    Industry             Western Europe,       Germany,
                         1988                  1990-1992

    Pharmaceuticals      37.6                  70.2
    Agrochemicals        42.9                  7.2
    Dyes                 15                    21.8
    Others               4.5                   0.8

         From production and processing of phenylhydrazine in Germany
    during 1990-1992, an estimated 50 kg and <13 t were emitted to the
    atmosphere and the hydrosphere, respectively, each year. Less than
    50 t of phenylhydrazinium chloride were released to water each year in
    the same period (BUA, 1995).

         There are now no manufacturers of phenylhydrazine or the
    phenylhydrazine hydrochloride salt in the United Kingdom
    (Brooke et al., 1997). Two firms are known to import phenylhydrazine
    into the United Kingdom, one from its manufacturing site in Germany
    and the other from Japan. The total market for phenylhydrazine in the
    United Kingdom is thought to be about 20 t/year, whereas the market
    for phenylhydrazine hydrochloride is not known. The market for
    phenylhydrazine has been static for several years.

         Phenylhydrazine is used worldwide mainly as a chemical
    intermediate in the pharmaceutical, agrochemical, and chemical
    industries. The United Kingdom's pattern of use appears
    representative. One company uses phenylhydrazine to produce a chemical
    intermediate for use in the photographic industry. Another
    manufacturer uses the chemical in the synthesis of organic chemicals.

    Phenylhydrazine is also used as a chemical intermediate in the
    pharmaceutical and agrochemical industries in the United Kingdom. In
    addition, there is some laboratory-scale use of this chemical.

         There are no known consumer uses of phenylhydrazine or its
    hydrochloride salt in the United Kingdom or Germany. No information is
    available regarding the potential for consumer exposure in other


         Most emissions of phenylhydrazine into the environment are into
    the hydrosphere. At acidic pH, phenylhydrazine occurs as the salt
    (BUA, 1995).

         In the atmosphere, phenylhydrazine would exist solely in the
    vapour phase (HSDB, 1998). Calculated half-lives of 3.1 h (BUA, 1995)
    and 9 h (Meylan & Howard, 1993) have been reported for phenylhydrazine
    following reaction with hydroxyl radicals in the atmosphere.

         Phenylhydrazine strongly absorbs ultraviolet light in the
    environmentally significant range, suggesting that it may photolyse in
    sunlight (HSDB, 1998); slow photodecomposition in diffuse daylight in
    the absence of oxygen is deduced in BUA (1995). In the presence of
    oxygen, phenylhydrazine is subject to autoxidation, the reaction being
    accelerated by light and heat; the substance becomes reddish brown on
    exposure to air as a result of this autoxidation (Ullmann, 1977).

         No hydrolysis is expected to occur (BUA, 1995).

         The Henry's law constant for phenylhydrazine has been calculated
    at 9.69 × 10-3 Pa.m3/mol (BUA, 1995). This is equivalent to a
    dimensionless Henry's law constant (air/water partition coefficient)
    of 3.92 × 10-6. These values indicate that phenylhydrazine is
    essentially non-volatile from water surfaces.

         Reported log octanol/water partition coefficients (log Kow)
    range from 1.25 to 1.90 (BUA, 1995); an estimated bioconcentration
    factor of 5 was based on the lower value (HSDB, 1998), indicating a
    low capacity for bioaccumulation. However, sorption based on chemical
    binding is possible, which could lead to some bioaccumulation (BUA,
    1995). The sorption coefficient ( Koc) can be calculated to range
    between 7.3 (Organisation for Economic Co-operation and Development
    [OECD] Technical Guidance Manual) and 11 (Karickhoff et al., 1979),
    indicating little sorption to particulates and a capacity for mobility
    in soil. However, the regression equations on which these estimates
    are based derive from hydrophobic compounds and may not adequately
    reflect the likely sorption of the hydrophilic phenylhydrazine.

         In a modified OECD ready biodegradability screening test (OECD
    301E), phenylhydrazine was "readily biodegradable"; elimination was
    77% after 10 days and 97% after 28 days using non-adapted inoculum.
    Elimination through abiotic processes in controls was 11% after both
    10 and 28 days (BASF, 1993). In the Zahn-Wellens test for inherent
    biodegradability (OECD 302B), 20-30% elimination occurred over 3 h
    (sorption), with 80% chemical oxygen demand achieved over 15 days
    using non-acclimatized industrial activated sludge. Using acclimatized
    activated sludge, 85% elimination was seen after 10 days (Hoechst,
    1980, 1992). A similar value of 85% elimination in 9-13 days was
    reported in the same test by Wellens (1990).


    6.1  Environmental levels

         Phenylhydrazine was not detected (detection limit 0.002 µg/ml
    with high-performance liquid chromatography) in 30 samples of surface
    water in the 1986 monitoring of the general environment by the Japan
    Environment Agency (1987). It was also not detected in 30 samples of
    sediment (detection limit 0.2 µg/kg with high-performance liquid

         Monitoring of wastewater at the Hoechst production plant in
    Germany failed to detect the compound in either inflow or outflow
    wastewater (detection limit 500 µg/litre) (BUA, 1995).

    6.2  Human exposure

         The number of persons potentially exposed to phenylhydrazine or
    its hydrochloride salt is not known, but it is expected to be small
    (Brooke et al., 1997). Industry in the United Kingdom has not been
    able to provide any personal exposure data, although it has been
    indicated that exposure to airborne phenylhydrazine between 1993 and
    1994 was controlled by process enclosure, the provision of local
    exhaust ventilation, and personal protective equipment.

         As there are no measured data available, the sections below
    describe the use of computer-modelled exposure data from the EASE
    model. This is a general-purpose predictive model for workplace
    exposure assessments, which is used when measured exposure data are
    limited or not available. In its present form, the model is in
    widespread use across the European Union for the occupational exposure
    assessment of new and existing substances.

         Following descriptions of precautions taken during use, the most
    appropriate parameters for the use of the EASE model are
    non-dispersive use with local exhaust ventilation in place. Exposure
    between 25 and 40°C with these assumptions is predicted to be within
    the range 2.3-13.5 mg/m3 (0.5-3 ppm) (8-h time-weighted average).
    Further, as only small quantities are involved, and as extensive
    containment is provided by the combination of a vessel open only at
    the bung hole and transfer being achieved by vacuum transfer, exposure
    will be at the low end of this range (i.e., 2.3 mg/m3 [0.5 ppm] 8-h
    time-weighted average). In practice, the 8-h time-weighted average
    exposure will be less than this figure, as the activities involving
    exposure to phenylhydrazine will take place for only part of the

         These predicted exposures would be even lower for work carried
    out in fume cupboards and would be extensively mitigated at the
    operator by use of respiratory protective equipment; air-fed suits
    would effectively reduce exposures of these magnitudes to zero.

         For direct handling and non-dispersive use with a contact level
    assumed to be incidental from the process descriptions, EASE predicts
    dermal exposures to range from 0 to 0.1 mg/cm2 per day. If direct
    handling is eliminated, dermal exposure is very low. Again, these
    exposures would effectively be reduced to zero by adoption of
    high-quality personal protective equipment and distancing procedures
    described in this assessment.


         Phenylhydrazine reacts readily with the carbonyl group, -C=O,
    which is common among biological molecules. It is therefore expected
    that direct binding to biological molecules would occur.

         There is only limited information available on the toxicokinetics
    of phenylhydrazine. Evidence from toxicokinetic and toxicity studies
    and from human experience indicates that phenylhydrazine is well
    absorbed by the inhalation, oral, and dermal routes in animals and

         Once absorbed, some phenylhydrazine appears to be rapidly taken
    up by red blood cells, where destructive intracellular reactions may

         Evidence from a number of studies  in vitro and  in vivo
    suggests that phenylhydrazine interacts with haemoglobin and
    cytochrome P-450 in an oxidation reaction, resulting in the generation
    of destructive free radicals, which are responsible for subsequent
    haemolysis (e.g., Itano et al., 1975; Valenzuela et al., 1977, 1981;
    Goldberg et al., 1979; Jain & Hochstein, 1979; Jonen et al., 1982;
    Hill, 1985; Marks, 1985; Di Cola et al., 1988, 1989; Maples et al.,

         There is little information available on tissue distribution.

         There is only one study available that investigates the
    metabolism and excretion of phenylhydrazine, following oral dosing in
    rabbits (McIsaac et al., 1958). This study shows that phenylhydrazine
    is extensively metabolized following oral administration, although the
    complete metabolic pathway has not been characterized. The main
    reactions identified in this study were hydroxylation of the aromatic
    ring to  p-hydroxyphenylhydrazine, followed by conjugation, probably
    with glucuronic acid, and production of phenylhydrazones, by reaction
    with natural keto acids.

         This study also indicated that the major route of excretion is
    via the urine. A significant proportion of a single dose was excreted
    relatively slowly; 50% of the dose was excreted within 4 days of
    dosing. There are insufficient data to determine whether there is any
    accumulation of phenylhydrazine in body tissues on repeated exposure.


         Many of the studies reported for phenylhydrazine have been
    conducted using phenylhydrazine hydrochloride. This salt is a weak,
    complex-forming compound, and either the salt or the free base will
    form depending on the physiological medium, regardless of the form in
    which the phenylhydrazine is administered (NIOSH, 1978). The
    toxicological properties of the salt can therefore be considered to be
    at least equivalent to those of free phenylhydrazine. Differences in
    toxicity may arise when properties such as pH or solubility contribute
    to the expression of toxicity. All dose values quoted throughout this
    document refer to free phenylhydrazine.

    8.1  Single exposure

         In relation to inhalation exposure, there is only one very poorly
    reported study, which reports LC50 values for an unstated exposure
    period of 2745 mg/m3 (610 ppm) in the rat and 2093 mg/m3 (465 ppm)
    in the mouse (Pham, 1979). However, it is expected that the marked
    toxicity seen following oral and dermal exposure would also be
    expressed following inhalation. Phenylhydrazine is toxic by oral
    administration, and oral LD50 values in the range 80-188 mg/kg body
    weight have been reported for the rat, mouse, guinea-pig, and rabbit
    (Ekshtat, 1965; Pham, 1979). Clinical signs reported were motor
    excitation and tonic/clonic spasms. In rabbits, dermal exposure to 380
    mg phenylhydrazine/kg body weight for 24 h resulted in 20-30%
    mortality, although no deaths occurred in rats at this dose
    (Derelanko et al., 1987). The toxic effects are characterized by
    destruction of red blood cells, causing a reduction in erythrocyte
    count, increased reticulocyte count, methaemoglobin formation, and the
    formation of Heinz bodies, and a cyanotic external appearance may
    develop. Enlargement and dark coloration of the spleen are also
    reported, effects that are considered to be secondary to the
    erythrocyte damage.

    8.2  Irritation and sensitization

         In the single-dose dermal toxicity study in rabbits and rats
    reported in the previous section, phenylhydrazine hydrochloride was
    applied to the skin as a solid moistened with distilled water, under
    either an occlusive or semi-occlusive dressing, for 24 h (Derelanko et
    al., 1987). Skin irritation was seen in all rabbits, with some
    necrosis at the treated site at 24 h post-application and sloughing of
    the skin reported in some animals. Skin irritation, which appeared
    within 24 h and persisted for up to 7 days post-exposure, was seen in
    a high proportion of rats. Necrosis developed in a small number of

         The quality of skin irritation data from other studies is
    limited; overall, however, the results support the conclusion reached
    by Derelanko et al. (1987) - that phenylhydrazine should be considered
    a skin irritant (Jadassohn, 1930; von Oettingen & Deichmann-Gruebler,
    1936; Roudabush et al., 1965; Schuckmann, 1969; Derelanko et al.,
    1987). Further details of these studies can be obtained in the source
    document (Brooke et al., 1997).

         The only available information on the eye irritation potential of
    phenylhydrazine in animals comes from a poorly described study in
    which application of a 50% solution of phenylhydrazine to the eyes of
    rabbits was reported to cause severe suppurative conjunctivitis (Pham,

         There are no good-quality studies available in animals that
    investigate the skin sensitization potential of phenylhydrazine. Only
    one poorly described study in guinea-pigs is available (Jadassohn,
    1930). When a 10% solution of phenylhydrazine in alcohol was painted
    on a skin site that had been pretreated 2-3 weeks previously with
    undiluted phenylhydrazine, very intense erythema and swelling,
    followed by scaling and encrustation, were consistently seen. This
    response to 10% phenylhydrazine was more severe than that described in
    animals that had not been pretreated.

         No information is available in relation to respiratory tract

    8.3  Short-term exposure

         There are only very limited, poor-quality data available in
    relation to short-term repeated-dose toxicity. The effects seen are
    similar to those seen following single exposure - in particular,
    destruction of circulating red blood cells. Toxicity to the spleen,
    liver, and kidney has also been observed in animal studies, possibly
    secondary to haemolysis.

         Kelly et al. (1969) administered phenylhydrazine hydrochloride to
    21 mice by oral gavage once weekly for 8 weeks, at an estimated dose
    of 85 mg/kg body weight per week. There were 10 saline-treated
    controls. The study report described only tumour-related findings.
    There was 30% mortality in treated mice compared with none in

         Haematological changes were reported in four dogs administered 60
    mg phenylhydrazine/kg body weight, either as a single dose or as 2, 3,
    or 10 equal doses on consecutive days (Giffin & Allen, 1928). There
    was a marked reduction in erythrocyte count that was comparable in
    magnitude in all dogs at the end of 10 days, but that occurred at a
    faster rate after a single high dose compared with repeated lower

         In another dog study, 60 mg phenylhydrazine/kg body weight was
    administered daily to three dogs for 5 days (Allen & Giffin, 1928).
    One animal was moribund at sacrifice on the fifth day and one animal
    died on the fifth day, although it is not specified that death was
    treatment related. Full necropsy was performed on only one animal, in
    which it was found that the blood was brown and did not coagulate
    readily. Several organs, including the liver and kidneys, were darkly
    coloured, and several organs contained capillaries engorged with
    blood. Blood pigment and partially destroyed erythrocytes were found
    in the spleen. Hepatic cell atrophy was noted, and there was an
    increase in the iron content of the liver. Similar liver effects were
    seen in the two other dogs.

         Bolton (1935) briefly reported the effect of repeated oral
    administration of 14 mg phenylhydrazine hydrochloride/kg body weight
    to one dog on 4 consecutive days. There was a reduction in erythrocyte
    count and haemoglobin concentration, whereas white cell count
    gradually increased. These parameters had returned towards
    pretreatment values 12 days after the last dose. Pathological findings
    were reported to be non-conclusive, but no details were given.

         Overall, the frequency, duration, and level of exposure often
    varied throughout the studies reported above, so that interpretation
    of results is very difficult. In all studies, phenylhydrazine as
    phenylhydrazine hydrochloride was administered either by stomach tube
    or by subcutaneous injection. The authors report that similar findings
    were obtained regardless of route. There were no control animals. None
    of the treated animals showed clinical signs of toxicity, and there
    was no excessive weight loss or gain reported.

         There have been a number of studies that investigate the effect
    of short-term repeated parenteral administration of phenylhydrazine
    (Bodansky, 1923; von Oettingen & Deichmann-Gruebler, 1936; Säterborg,
    1974; Ades & Cascarano, 1979; Jain & Hochstein, 1979; Goldstein et
    al., 1980; Nishida et al., 1982; Dornfest et al., 1986). These studies
    confirm the ability of phenylhydrazine to damage red blood cells but
    otherwise do not provide any other information in relation to the
    toxicity of phenylhydrazine administered by occupationally relevant
    routes of exposure.

    8.4  Long-term exposure

    8.4.1  Subchronic exposuren

         In a very poorly reported study from which limited conclusions
    can be drawn, rats, mice, guinea-pigs, and rabbits were exposed to
    phenylhydrazine vapour at 0, 0.1, 15.8, 22.5, or 225 mg/m3 (0, 0.03,
    3.5, 5, or 50 ppm) (Pham, 1979). Group sizes, duration of exposure,
    and exposure regime were not given, although it can be inferred that

    some animals were exposed for at least 6 months. Deaths were reported
    to occur in animals exposed to 225 mg phenylhydrazine/m3 (species not
    specified). Severe weight loss and unspecified haematological changes
    and changes in central nervous system function were reported to
    precede death, and there was evidence of haemolysis and dystrophic
    changes in the liver, spleen, and cerebrum. Animals exposed to 15.8
    and 22.5 mg/m3 were reported to have a reduction in erythrocyte count
    and haemoglobin concentration, an increase in reticulocytes, and
    methaemoglobinaemia; these changes were reversible at 15.8 mg/m3.
    Haemolysis and dystrophic changes in the liver and other unspecified
    organs were also reported for animals exposed to 22.5 mg/m3. No
    further information is available on pathological changes at 0.1
    mg/m3. It is not clear if there were lung effects at any of the
    exposure concentrations.

         It is not possible to draw firm conclusions from a poorly
    reported study in three dogs in which the effect of phenylhydrazine
    administration on renal and hepatic function and on erythropoiesis was
    investigated (Allen & Giffin, 1928). Three dogs were administered
    phenylhydrazine in 146 daily doses over a period of 8 months, to give
    a total dose of 950 mg/kg body weight; the dosing regimen included a
    period of about 60 days of uninterrupted administration of a single
    dose level or of two dose levels (6-12 mg/kg body weight per day).
    Again, the route of administration was unclear. Kidney function and
    hepatic function were unaffected by treatment. Erythrocyte count was
    reduced by treatment but recovered after cessation of treatment, at a
    rate that was unrelated to the duration of exposure, thus indicating
    that the administered dose had no effect on erythropoietic function.
    Pathological examination was conducted on two of these dogs at 12 or
    13 months. There was evidence of spleen toxicity, liver congestion,
    and kidney damage.

         In a very briefly reported study, phenylhydrazine was
    administered to 25 female Swiss mice by oral gavage, 5 days/week for
    40 weeks, at an estimated daily dose of 17-33 mg/kg body weight
    (Roe et al., 1967). There were 85 untreated controls. Marked anaemia
    necessitated a reduction in the dose during the sixth week of
    treatment. No other toxic effects were observed.

    8.4.2  Chronic exposure and carcinogenicity

         Phenylhydrazine hydrochloride was administered daily by stomach
    tube for 42 weeks to 30 BALB/c mice, at an estimated dose level of 25
    mg phenylhydrazine/kg body weight (Clayson et al., 1966). Thirty
    control animals were included in the study, but a control animal was
    killed whenever a treated animal died, to match survival rates. There
    was a statistically significant increase in the incidence of animals
    with lung tumours in the treated group (53%) compared with controls

    (13%). There was also a slight increase in the average number of
    tumours per mouse, and the majority of treated mice had multiple
    pulmonary tumours. Adenomas accounted for 83% of pulmonary tumours in
    the treated group, half of which were judged to be becoming malignant,
    and 17% of tumours were carcinomas.

         Phenylhydrazine hydrochloride was administered in drinking-water
    to 100 Swiss mice for their lifetime, at an estimated daily dose of 22
    mg/kg body weight (Toth & Shimizu, 1976). There were 200 control mice.
    Complete necropsy was performed on all animals. All organs were
    examined macroscopically, and histological analysis was performed on a
    wide range of tissues as well as on any organ showing gross pathology.
    Phenylhydrazine was reported to decrease survival in comparison with
    controls, and many of the treated decedents showed splenomegaly,
    although numbers were not given. There was a statistically significant
    increased incidence of blood vessel tumours (mainly angiosarcomas and
    angiomas) in the liver of treated animals (21%) compared with
    controls (0%).

    8.5  Genotoxicity and related end-points

         Phenylhydrazine and phenylhydrazine hydrochloride have been
    investigated in a number of Ames tests, in a variety of strains, and
    in the presence and absence of exogenous metabolic activation using up
    to 1000 µg phenylhydrazine or phenylhydrazine hydrochloride per plate
    (Shimizu et al., 1978; Tosk et al., 1979; De Flora, 1981; Parodi et
    al., 1981; Levin et al., 1982; Malca-Mor & Stark, 1982; Rogan et al.,
    1982; De Flora et al., 1984a,b; Wilcox et al., 1990; Muller et al.,
    1993). The quality of these studies is generally high, and the studies
    were apparently conducted according to standard methodology, although
    detailed reporting of the results is not always available.

         There is some variability in the findings, although positive
    results have been obtained in  Salmonella typhimurium strains TA97,
    TA100, TA102, TA1537, and TA1538 in the absence of exogenous metabolic
    activation. In addition, positive results were obtained in the
    presence of metabolic activation in TA98 and TA1535. Some
    investigators have reported that the mutagenic action is slightly
    decreased by the presence of exogenous metabolic activation (Parodi et
    al., 1981; Malca-Mor & Stark, 1982; De Flora et al., 1984a,b).
    However, one study reports an increase in mutagenic activity in the
    presence of metabolic activation (Rogan et al., 1982).

         Phenylhydrazine has also given positive results in a number of
    other, less well validated bacterial assays (using  S. typhimurium
    strains such as TA2638, TP138, BA9, and BA13), in the presence and
    absence of exogenous metabolic activation (De Flora et al., 1984b;
    Ulitzur et al., 1984; Ruiz-Rubio et al., 1985; Levi et al., 1986;
    Muller et al., 1993).

         Phenylhydrazine has not been tested in an  in vitro chromosomal
    aberration assay. In a brief abstract of a mammalian cell gene
    mutation assay in V79 cells, with and without metabolic activation, a
    positive result was reported for phenylhydrazine (Kuszynski et al.,
    1981). However, no firm conclusions can be drawn from this report
    because of deficiencies in the reporting.

         In an unscheduled DNA synthesis assay in rat and mouse primary
    hepatocytes, concentrations of 0.0144-144 mg phenylhydrazine
    hydrochloride/litre were assessed (Mori et al., 1988). Although
    toxicity was measured, no details were given, and quantitative data
    were not reported. A positive result was obtained in both cell types,
    although the effect was small.

         Phenylhydrazine was tested in a micronucleus assay  in vitro
    using primary mouse bone marrow cells (Suzuki, 1985). Bone marrow
    cells from the femur were exposed to 1-50 µg phenylhydrazine/ml for 30
    min, in the presence and absence of metabolic activation. A total of
    1500 polychromatic erythrocytes (PCEs) per concentration was scored
    for the presence of micronuclei. There was no measure of cytotoxicity.

         The percentage of micronucleated PCEs was statistically
    significantly increased, in the presence of S9 only, at
    phenylhydrazine concentrations of 5 µg/ml and greater in a
    concentration-related manner.

         BALB/c mice were administered a single intraperitoneal injection
    of phenylhydrazine, and the incidence of micronucleated PCEs in the
    bone marrow was measured at 24 and 48 h (Suzuki, 1985).
    Phenylhydrazine was reported to be positive in this test, but no
    details of the results or of the test were given. In view of the poor
    reporting, no firm conclusions can be drawn from this study.

         Groups of 11-12 female BALB/c mice were given a single
    intraperitoneal injection of 50 mg phenylhydrazine/kg body weight in
    saline (Steinheider et al., 1985). Blood smears of tail vein blood
    were prepared at 24-h intervals for 7 or 11 days, and reticulocytes
    and micronuclei in normochromatic erythrocytes (NCEs) and PCEs were
    counted. It is not stated how many cells were counted per mouse. There
    was no reporting of toxicity.

         Phenylhydrazine caused a statistically significant increase in
    the reticulocyte count on days 2-4 post-injection and in PCEs on day
    3. There was a statistically significant increase in the incidence of
    micronucleated PCEs at 24 h post-injection (from 1 to 4.7 per 1000)
    and in micronucleated NCEs at 48 h post-injection (from 0.7 to 2.3 per

         However, similar increases in micronucleated NCEs were also seen
    following bleeding of the animals and splenectomy. The authors suggest
    that the increase in micronuclei seen following phenylhydrazine
    treatment was due at least partly to stimulation of erythropoiesis
    because of the haemolysis induced by phenylhydrazine, thus leading to
    more errors of nuclear expulsion; hence, the results do not
    necessarily indicate a direct genotoxic action of phenylhydrazine.

         Groups of 7-12 mice were given a single intraperitoneal injection
    of either 85 or 170 mg phenylhydrazine/kg body weight and killed 1 and
    6 h, respectively, after treatment (Parodi et al., 1981). In addition,
    six mice were given a series of five daily intraperitoneal injections
    of 7.6 mg phenylhydrazine/kg body weight and sacrificed 6 h after the
    last injection. Control animals were injected with saline only. DNA
    damage was assessed by measurement of the alkaline elution rate of
    single-strand DNA from liver and lung tissue extracts.

         A statistically significant change in the elution rate of liver
    and lung DNA was seen in all groups of treated animals compared with
    controls, except in the case of lung tissue DNA from mice given a
    single dose of 85 mg phenylhydrazine/kg body weight. Phenylhydrazine
    is considered to give a positive result in this assay for DNA damage.

         The formation of DNA adducts ( N7-methylguanine and a trace of
     O6-methylguanine) in the liver was demonstrated in rats receiving
    65 mg phenylhydrazine/kg body weight by oral gavage (Mathison et al.,
    1994). Other tissues were not examined.

    8.6  Reproductive and developmental toxicity

         Each of three dogs (one dog per dose group) received 20, 30, or
    40 mg phenylhydrazine/kg body weight in saline by subcutaneous
    injection on 2 consecutive days (Witchett, 1975). Two control animals
    were not injected. At necropsy, performed on all three animals within
    a few days of dosing, a "striking" reduction in spermatogenesis was
    reported, with an absence of sperm in the epididymis. The validity of
    this result is not clear, given the apparent extreme rapidity of the

         Groups of 8-12 pregnant Wistar rats were given an intraperitoneal
    injection of 7.5 mg phenylhydrazine/kg body weight as phenylhydrazine
    hydrochloride on days 17, 18, and 19 of gestation; or 15 mg
    phenylhydrazine/kg body weight as phenylhydrazine hydrochloride on
    days 18 and 19 of gestation (Tamaki et al., 1974). Control animals
    were not treated. There was no reporting of maternal toxicity or of
    the effect of treatment on gestation or pup viability. Toxicity of the
    pups was reported only insofar as there was incidence of jaundice

    and/or anaemia among the offspring of treated animals. Twelve male
    offspring with severe jaundice and anaemia, selected from treated
    dams, and nine males from control dams were assessed at 9-22 weeks of
    age for functional and behavioural status.

         Although the authors reported that experimental animals showed
    statistically significant differences from controls in some tests,
    these findings are not considered to be reliable because of the small
    numbers of animals used and the exclusion of a control animal from the
    analysis. In addition, it is noted that only a brief part of the
    gestation period was covered by the treatment regime (days 17-19); no
    explanation is available for this choice of dosing regime.

         Yamamura et al. (1973) reported in a brief abstract that
    intraperitoneal injection of pregnant rats with 15 mg
    phenylhydrazine/kg body weight as phenylhydrazine hydrochloride on
    days 18 and 19 of gestation produced hyperbilirubinaemia (resulting
    from haemolysis) in fetuses and newborns.

    8.7  Immunological and neurological effects

         No studies are available that specifically investigate the
    immunological and neurological end-points, and there is no relevant
    information from toxicity studies in animals.


         In humans, no information is available in relation to single
    exposure via the inhalation or oral routes, although effects similar
    to those seen following dermal exposure would be expected to occur.
    Systemic toxicity developed in humans after dermal exposure to liquid
    phenylhydrazine, despite immediate attempts to reduce exposure by
    removal of contaminated clothing and washing of skin (Schuckmann,
    1969). Toxicity was manifest by damage to red blood cells, in one case
    resulting in haemolytic jaundice. No such systemic effects were
    reported in two cases of skin contamination with solid phenylhydrazine

         In relation to skin irritation, information is available from
    worker exposure data. There was no reporting of irritancy effects in
    workers exposed to liquid phenylhydrazine following accidental
    exposure, although systemic effects were seen (Schuckmann, 1969). Skin
    irritation following contact with phenylhydrazine hydrochloride powder
    was reported in two workers following accidental exposure. Local
    irritation, superficial erythema, and partly bullous-papular changes
    were noted in one case following spillage of powder on arms; multiple
    burn marks and small blisters at the site of contact were reported in
    the second case in which phenylhydrazine hydrochloride had spilled
    into the worker's gloves and shoes. The author also refers to medical
    records at the works that describe a number of cases of skin
    irritation of differing severity due to phenylhydrazine hydrochloride,
    but no details are given.

         There are no data available on the eye irritation potential of
    phenylhydrazine in humans.

         There are a number of case reports of skin hypersensitivity
    reactions to phenylhydrazine and its hydrochloride salt in humans.
    Solomons (1946) conducted a patch test in one subject with a
    phenylhydrazine crystal placed on the forearm under a dressing for an
    unstated exposure period. Marked erythema and some oedema developed on
    the exposure site after 18 h, with the formation of vesicles after 30
    h and crusting after a further 24 h.

         Similar hypersensitive skin reactions were reported following
    individual exposures to solid or aqueous solutions of phenylhydrazine
    or phenylhydrazine salts (Wright & Joyner, 1930; Frost & Hjorth, 1959;
    Pevny & Peter, 1983).

         There is also evidence that cross-sensitization can occur between
    hydrazine compounds, so that subjects already sensitized to hydrazine,
    a known skin sensitizer, are also sensitized to hydrazine derivatives,
    including phenylhydrazine (Malten, 1962; Van Ketel, 1964; Hovding,
    1967; Rothe, 1988).

         No data are available on the potential of phenylhydrazine to
    cause respiratory tract sensitization.

         Earlier this century, phenylhydrazine and phenylhydrazine
    hydrochloride were administered orally (usually around 100-200 mg/day)
    for the treatment of blood disorders (e.g., Giffin & Allen, 1933). In
    some cases, treatment was effective; in others, however, the outcome
    was fatal (e.g., Giffin & Conner, 1929). The effects seen (beneficial
    or otherwise) may have been related to the disease process and cannot
    be attributed entirely to phenylhydrazine.


    10.1  Aquatic environment

         Results of acute toxicity tests on aquatic organisms are
    summarized in Table 2. All concentrations are nominal. 

         In the early life stage test summarized in Table 2 (Xiu et al.,
    1992), newly fertilized eggs of the zebra fish were exposed to
    concentrations of phenylhydrazine through hatch and into the larval
    stage (total exposure time was 16 days). A NOEC (survival) was
    established for eggs at 5 days post-fertilization at 0.0039 mg/litre,
    with a lowest-observed-effect concentration (LOEC) at 0.0078 mg/litre.
    At the end of the test (16 days), the NOEC for larvae was 0.000 49
    mg/litre, and the LOEC was 0.000 98 mg/litre. The study was conducted
    according to a Swedish standard protocol (ss 028193).

         In a study on the goldfish ( Carassius auratus), 40% of fish
    died when exposed to phenylhydrazine at a nominal concentration of 1
    mg/litre for 48 h. Signs of toxicity included erratic swimming,
    sinking to the bottom of the test tank, and slowed and erratic
    respiration. No gross lesions were found following dissection,
    although all viscera showed focal haemorrhaging (Houston et al.,

         Effects on blood cells and the haematopoietic system, comparable
    to those found in mammals, were seen in fish injected with
    phenylhydrazine. Chinook salmon ( Oncorhynchus tshawytscha) juveniles
    were injected with 12.5 mg phenylhydrazine/kg body weight. Red cell
    count, haemoglobin, and haematocrit fell to 1-5% of their normal
    values within 10 days of treatment; a slight improvement was reported
    15 days following injection, and values had returned to normal 95 days
    after treatment (Smith et al., 1971).

    10.2  Terrestrial environment

         Phenylhydrazine at 21.6 mg/litre in a nutrient culture medium had
    no effect on the growth of various soil fungi (Zsolnai, 1975).

         A phenylhydrazine concentration of 50 mg/litre in a hydroponic
    culture solution inhibited germination of  Hordeum seeds for at least
    6 days, whereas growth was stimulated in  Lepidium. At 100 mg/litre,
    seedling growth was stimulated in  Hordeum but not in  Lepidium. At
    500 mg/litre, phenylhydrazine inhibited growth in seedlings of both
    species, although the seedlings were still apparently "healthy"
    (Bokorny, 1933).

         Exposure of soil nematodes  Caenorhabditis briggsae in culture
    to phenylhydrazine at 50 mg/litre of medium resulted in reduced growth
    of all four larval stages (the effect was most marked on the last

    larval instar) and therefore delayed development to adults. However,
    the adults formed were capable of reproduction, although the number of
    progeny was reduced. A concentration of 15 mg/litre also delayed
    development, although to a lesser degree compared with the higher
    concentration (Kampfe et al., 1986a,b). A 6-day EC50 of 12 mg/litre
    was reported for production of progeny in culture for the same
    nematode (Kreil, 1982).

         No dietary or oral toxicity studies have been performed on birds.
    However, injection studies have shown haemolytic anaemia and reduced
    white cell counts in birds. In contrast to mammals, cell division in
    erythropoietic tissue is unaffected by phenylhydrazine (Williams,
    1972; Clark et al., 1988; Datta et al., 1989, 1990).

        Table 2: Acute toxicity of phenylhydrazine to aquatic organisms.

    Organism                      End-point              Concentration       Reference


    Photobacterium phosphoreum    30-min EC50            66.9                Kaiser et al.
                                  (luminescence)                             (1987)

    Facultative anaerobes         24-h toxic             60                  Hoechst (1980)
    (mixed culture)               threshold

    Escherichia coli              minimum                109.3               Romero & Canada
                                  inhibitory                                 (1991)

    Escherichia coli,             minimum                >3000               Zemek et al.
    Micrococcus luteus,           inhibitory                                 (1978)
    Bacillus licheniformis        concentration


    water flea                    LC50                   2-5                 Hoechst (1980)
    (Daphnia magna)               (immobilization)


    zebra fish                    96-h LC50              0.16-0.25           Hoechst (1982)
    (Brachydanio rerio)           96-h NOEC              0.1

    zebra fish                    5-day NOEC (eggs)      0.0039              Xiu et al.
    (Brachydanio rerio)           16-day NOEC (larvae)   0.000 49            (1992)

    Japanese killifish            48-h LC50              15.7                Tonogai et al.
    (Oryzias latipes)                                                        (1982)

    Table 2 (cont'd)

    Organism                      End-point              Concentration       Reference
    common carp                   24-h LC100             1.0                 Menzie (1979)a
    (Cyprinus carpio)             96-h NOEC              0.1

    bluegill                      48-h LC50              0.1                 Menzie (1979)a
    (Lepomis                      96-h NOEC              0.01

    a  Menzie C (1979) Value taken from the DIMDI/ECDIN database. Test performed by the
       United States Fish and Wildlife Service, Bureau of Sports, Fisheries and Wildlife,
       Department of the Interior, Washington, DC [cited in BUA, 1995].


    11.1  Evaluation of health effects

    11.1.1  Hazard identification and dose-response assessment

         Phenylhydrazine is toxic by single exposure via the oral route
    (LD50 80-188 mg/kg body weight) and is expected to be toxic by the
    inhalation and dermal routes (data from these routes of exposure are
    less clear). Phenylhydrazine solution was severely irritating to
    rabbit eyes; hence, it is reasonable to predict that it would have
    significant eye irritation potential in humans.

         Phenylhydrazine also has skin irritation potential, and there is
    evidence from human case reports that it has skin sensitizing
    properties. Exposure to phenylhydrazine may cause damage to red blood
    cells, potentially resulting in anaemia and consequential secondary
    involvement of other tissues, such as the spleen and liver. The dose
    (exposure)-response characteristics for the induction of damage to the
    red blood cells are poorly defined, and a no-effect level has not been
    identified. Where phenylhydrazine has been used therapeutically in
    humans, via the oral route, for the treatment of blood disorders,
    daily doses of the order of 1.5-4 mg/kg body weight per day have
    caused a reduction in the numbers of red blood cells; given the health
    status of the individuals concerned, however, these data are of
    limited use. Phenylhydrazine is mutagenic in vitro, and, although not
    conclusive, there is some evidence to indicate that it may express
    genotoxic activity  in vivo. The substance is clearly carcinogenic in
    mice following oral dosing, inducing tumours of the vascular system.
    The mechanism for tumour formation is unclear, and, given the
    genotoxic profile of phenylhydrazine, a genotoxic component cannot be
    excluded. Carcinogenic potential in humans cannot be excluded given
    the profile of genotoxicity and animal carcinogenicity, particularly
    as other expressions of phenylhydrazine toxicity are common to a
    number of species, including humans.

         No conclusions can be drawn from the available information on
    fertility or development.

    11.1.2  Criteria for setting guidance values fon phenylhydrazine

         There are no adequate data available regarding reproductive or
    developmental effects; hence, it is not possible to evaluate the risk
    to human health for these end-points.

         The use pattern and physical/chemical characteristics of the
    compound suggest that exposure of the general population would be

         Using United Kingdom workplace conditions as an example (section
    6.2), exposure to phenylhydrazine vapour during most occupational
    processes would result in a body burden of up to 0.33 mg/kg body
    weight per day, assuming a 70-kg worker breathes 10 m3 of air in a
    working day and that 100% phenylhydrazine is absorbed. There are no
    data available from which to estimate the contribution to body burden
    from dermal uptake, although this is expected to be negligible. A
    threshold for the induction of red blood cell damage probably exists
    but has not been identified, although daily oral doses calculated at
    about 1.5 mg/kg body weight per day and above are associated with such
    effects. Overall, at these levels of predicted inhalation exposure,
    the risk of developing damage to the red blood cells is considered to
    be low; if the levels were exceeded (e.g., of the order of a few ppm,
    approximately 15-20 mg/m3), however, then this would be cause for
    some concern.

         On the basis that the carcinogenicity of phenylhydrazine may
    involve a genotoxic mechanism, it is not possible to reliably identify
    a threshold below which occupational exposure to phenylhydrazine would
    not result in some risk to human health.

    11.1.3  Sample risk characterization

         The scenario chosen as an example is occupational exposure in the
    United Kingdom.

         The main health concerns associated with exposure to
    phenylhydrazine are damage to the red blood cells, deleterious effects
    on genetic material, and the development of cancer.

         It is recognized that there are a number of different approaches
    to assessing the risks to human health for genotoxic and carcinogenic
    substances and in the subsequent risk management steps that may be
    taken. In addition, although not used in the United Kingdom, there are
    models for characterizing potency that may be of some benefit in
    priority-setting schemes. In the United Kingdom occupational setting,
    a Maximum Exposure Limit or MEL (which is not a health-based standard)
    has been proposed at 0.9 mg/m3 (0.2 ppm), 8-h time-weighted average.
    The numerical value for the MEL was based on a level of control that
    was deemed (by tripartite agreement) to be reasonably practicable
    under United Kingdom workplace conditions, and in the United Kingdom
    there is a continuing requirement to reduce exposure levels as far as
    reasonably practicable with the technology that is currently

         Phenylhydrazine also possesses skin and eye irritant properties
    and possibly skin sensitizing potential. The information available
    indicates that local exposure of these tissues is unlikely; if it did
    occur, however, then there would be risk of irritation to the eyes and
    the development of irritant and/or allergic dermatitis.

    11.2  Evaluation of environmental effects

         No atmospheric effects are expected given the release of
    phenylhydrazine predominantly to water, its extremely low
    volatilization from water to the atmosphere, and its rapid calculated
    atmospheric half-life following reaction with hydroxyl radicals.

         Few toxicity studies are available for terrestrial organisms, and
    little emission to land is expected; on this basis, no quantitative
    risk assessment can be attempted for the terrestrial environment.

         Phenylhydrazine is degraded photochemically and autoxidizes in
    water. It is readily biodegradable, and this is expected to be the
    major route of breakdown in the environment. There is minimal sorption
    to particulates.

         Phenylhydrazine is toxic to aquatic organisms, with the lowest
    reported NOEC in acute fish tests at 0.01 mg/litre; fish are generally
    more sensitive than either daphnids or bacteria. A NOEC for
    embryo-larval stages following 16 days of exposure from fertilization
    has been reported at 0.000 49 mg/litre for the zebra fish.

         There are no reported measurements of phenylhydrazine in
    environmental media. Monitoring studies of both inflow and outflow to
    the wastewater treatment plant of the Hoechst Hochst production plant
    in Germany showed no detectable phenylhydrazine (detection limit 500
    µg/litre) in weekly samples. Maximum emission to wastewater was
    estimated at 13 t/year, and this will be used as a worst-case example.

         Based on this emission rate, and using mainly default values from
    the OECD Technical Guidance Manual, the initial predicted
    environmental concentration of phenylhydrazine in river water
    (PEClocal (water), in g/litre) would be as follows:

    PEClocal (water) =                                

                          (1 +  Kp(susp) ×  Csusp) ×  D


    *     Ceffluent is the concentration of phenylhydrazine in the
         wastewater treatment plant effluent (g/litre), calculated as
          Ceffluent =  W × (100 -  P)/(100 ×  Q), where:

              W    =    emission rate (35.6 kg/day)

              P    =    percent removal in the wastewater treatment plant
                        (based on the "ready biodegradability" of the
                        compound, 91%)

              Q    =    volume of wastewater in m3/day (default 200
                        litre/day per capita for a population of 10 000
                        inhabitants; wastewater volume for the production
                        plant is unknown)

    *     Kp(susp) is the suspended matter/water adsorption coefficient,
         calculated as  Kp(susp) =  Koc ×  foc(susp), where:

          Koc        =    organic carbon/water partition 
                         coefficient (7.3)

          foc(susp)  =    fraction of organic carbon in suspended matter
                         (default 0.1)

    *     Csusp is the concentration of suspended matter in the river
         water (in kg/litre; default 15 mg/litre)

    *     D is the dilution factor for river flow (flow rate for the
         River Main averages 188 m3/s compared with the estimated flow
         rate of the wastewater at 0.02 m3/s; dilution factor
         approximately 10 000)

    Under these very conservative conditions, PEClocal (water)
    = 0.16 µg/litre.

         Of the reported acute toxicity test results for organisms in the
    environment, those for the majority of fish tested are substantially
    lower than those for other organisms tested. The predicted no-effect
    concentration (PNEC) will therefore be based on the fish results.

         No long-term test results are available. Applying an uncertainty
    factor of 1000 to the lowest reported standard acute LC50 value of
    0.1 mg/litre for the bluegill ( Lepomis macrochirus) would give a
    PNEC of 0.1 µg/litre. This is a factor of 100 lower than the lowest
    reported NOEC for the same species. Alternatively, applying an
    uncertainty factor of 10 to the NOEC for the early life stage test on
    the zebra fish larvae gives a PNEC of 0.049 µg/litre. The more
    conservative value will be used in estimating risk.

         The low PEC of 0.16 µg/litre would not have been detected in the
    monitoring at the site. Assuming that this value is the worst case, a
    PEC/PNEC ratio of 3.2 is generated. This indicates that the risk to
    aquatic organisms is low, based on very conservative assumptions. The
    distribution of reported toxicity test results against the worst-case
    PEC is plotted in Figure 1, illustrating the safety margin.

    FIGURE 2



         Previous evaluations by other international bodies were not
    identified. Information on international hazard classification and
    labelling is included in the International Chemical Safety Card (ICSC
    0938) reproduced in this document.


         Human health hazards, together with preventive and protective
    measures and first aid recommendations, are presented in the
    International Chemical Safety Card (ICSC 0938) reproduced in this

    13.1  Human health hazards

         Phenylhydrazine induces damage to red blood cells. Repeated or
    prolonged contact with the substance causes skin sensitization, and
    there is cause for concern for carcinogenicity.

    13.2  Advice to physicians

         Phenylhydrazine is a haemolytic agent. There is no specific
    antidote, but treatment should be supportive.

    13.3  Health surveillance advice

         Periodic medical examination of the area of the skin exposed to
    phenylhydrazine and annual blood count should be included in the
    health surveillance programme.


         Information on national regulations, guidelines, and standards
    may be obtained from UNEP Chemicals (IRPTC), Geneva.

         The reader should be aware that regulatory decisions about
    chemicals taken in a certain country can be fully understood only in
    the framework of the legislation of that country. The regulations and
    guidelines of all countries are subject to change and should always be
    verified with appropriate regulatory authorities before application.


        PHENYLHYDRAZINE                                                       ICSC: 0938
                                                                          November 1998

    CAS #          100-63-0            Hydrazinobenzene
    RTECS #        MV8925000           Monophenylhydrazine
    UN #           2572                C6H8N2/C6H5NHNH2

                                       Molecular mass: 108.1

    TYPES OF HAZARD        ACUTE HAZARDS/                  PREVENTION               FIRST AID/
                           SYMPTOMS                                                 FIRE FIGHTING

    FIRE                   Combustible. Gives off          NO open flames.          Water spray, alcohol-resistant
                           irritating or toxic                                      foam, powder, carbon dioxide.
                           fumes (or gases) in
                           a fire.

    EXPLOSION              Above 88°C explosive            Above 88°C use           In case of fire: keep drums, etc.,
                           vapour/air mixtures             a closed system,         cool by spraying with water.
                           may be formed.                  ventilation.             

    EXPOSURE                                               STRICT HYGIENE!          

    Inhalation             Cough. Laboured                 Local exhaust or         Fresh air, rest. Refer for
                           breathing. Sore                 breathing                medical attention.
                           throat. Cyanosis.               protection.

    Skin                   MAY BE ABSORBED!                Protective gloves.       Remove contaminated clothes.
                           Dry skin. Redness.              Protective clothing.     Rinse skin with plenty of water
                           Pain.                                                    or shower. Refer for medical

    Eyes                   Redness. Pain. Blurred          Face shield, or eye      First rinse with plenty of
                           vision                          protection in            water for several minutes
                                                           combination with         (remove contact lenses if easily
                                                           breathing                possible), then take to a
                                                           protection.              doctor.

    Ingestion              Abdominal pain. Diarrhoea.      Do not eat, drink or     Rest. Refer for medical
                           Nausea. Vomiting. Weakness.     smoke during work        attention.

    SPILLAGE DISPOSAL                                      PACKAGING & LABELLING

    If the substance is melted: collect leaking and        Airtight. Do not transport with food and feedstuffs.
    spilled liquid in sealable containers as far as        EU Classification:
    possible. Absorb remaining liquid in sand or inert     Symbol: T, N
    absorbent and remove to safe place. Do NOT wash        R: 23/24/25-36-50
    away into sewer. If the substance is solid: sweep      S: (1/2-)28-45-61
    spilled substance into container, carefully collect    UN Classification
    remainder, then remove to a safe place. Do NOT let     UN Hazard Class: 6.1
    this chemical enter the environment. (Extra personal   UN Pack Group: II
    protection: complete protective clothing including     
    self-contained breathing apparatus).                   

    EMERGENCY RESPONSE                                     STORAGE

    Transport Emergency Card: TEC (R)-61/G61b              Separated from strong oxidants, food and 
    NFPA Code: H3; F2; R0;                                 feedstuffs. Cool. Keep in the dark.

                                            IMPORTANT DATA

    PHYSICAL STATE; APPEARANCE:                            ROUTES OF EXPOSURE:
    COLOURLESS TO YELLOW OILY LIQUID OR CRYSTALS.          The substance can be absorbed into the
    TURNS BROWN RED ON EXPOSURE TO AIR AND LIGHT.          body by inhalation of its aerosol, through
                                                           the skin, by ingestion.

    CHEMICAL DANGERS:                                      INHALATION RISK:
    The substance decomposes on heating and on             A harmful contamination of the air can be reached
    burning producing toxic fumes including nitrogen       rather quickly on evaporation of this substance at 20°C.
    oxides. Reacts with oxidants. Reacts violently         
    with lead dioxide.                                     

    TLV: 0.1 ppm; 0.44 mg/m3 A3 (skin)(ACGIH 1998).        The substance irritates the eyes, the skin, the 
                                                           respiratory tract. The substance may cause effects on
                                                           the blood, resulting in hemolysis, kidney impairment,
                                                           liver impairment. The effects may be delayed. Medical
                                                           observation is indicated.

                                                           EFFECTS OF LONG-TERM OR REPEATED EXPOSURE:
                                                           Repeated or prolonged contact with skin may cause
                                                           dermatitis. Repeated or prolonged contact may cause 
                                                           skin sensitization. The substance may have effects 
                                                           on the blood, resulting in anaemia.

                                               PHYSICAL PROPERTIES

    Boiling point (decomposes):    243.5°C                 Octanol/water partition coefficient as log Pow: 1.25
    Melting point:                 19.5°C                  
    Relative density (water = 1):  1.09
    Solubility in water:           poor
    Vapour pressure, Pa at 71.8°C: 133
    Relative vapour density
    (air = 1):                     3.7
    Flash point:                   88°C c.c.
    Auto-ignition temperature:     174°C

                                               ENVIRONMENTAL DATA
    The substance is toxic to aquatic organisms.


    The symptoms of hemolysis do not become manifest until hours have passed.

                                               ADDITIONAL INFORMATION

    LEGAL NOTICE           Neither the CEC nor the IPCS nor any person acting on behalf of the CEC
                           or the IPCS is responsible for the use which might be made of this

                                          (c) IPCS, CEC 1999


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    studies on the developmenal disorder due to icterus gravis neonatorum:
    I. Perinatal hemolytic jaundice and its effect on postnatal
    development.  Teratology, 8:110.

    Zemek J, Bilik V, Kucar S, Linek K, Augustin J (1978) Antibacterial
    effect of some phenylhydrazones.  Folia Microbiologica (Prague),

    Zsolnai T (1975) Neure Antimycotika. I Phenylhydrazin-Derivate.
     Zentralblatt fuer Bakteriologie, Parasitenkunde,
     Infektionskrankheiten und Hygiene, Abteilung 1: Originale, Reihe A,


    Brooke I, Cain J, Cocker J, Groves J (1997)  Phenylhydrazine.
    Sudbury, Suffolk, HSE Books (Risk Assessment Document EH72/1; ISBN
    0 7176 1355 0)

         The author's draft version is initially reviewed internally by a
    group of approximately 10 Health and Safety Executive experts - mainly
    toxicologists, but also experts in other relevant disciplines, such as
    epidemiology and occupational hygiene. The toxicology section of the
    amended draft is then reviewed by toxicologists from the United
    Kingdom Department of Health. Subsequently, the entire Criteria
    Document is reviewed by a tripartite advisory committee to the United
    Kingdom Health and Safety Commission, the Working Group for the
    Assessment of Toxic Chemicals (WATCH). This committee is composed of
    experts in toxicology and occupational health and hygiene from
    industry, trade unions, and academia.

         The members of the WATCH committee at the time of the peer review
    were Mr S.R. Bailey, Independent Consultant; Professor J. Bridges,
    University of Surrey;    Dr H. Cross, Trade Unions Congress; Dr A.
    Fletcher, Trade Unions Congress; Dr I.G. Guest, Chemical Industries
    Association; Dr A. Hay, Trade Unions Congress; Dr J. Leeser, Chemical
    Industries Association; Dr L. Levy, Institute of Occupational Hygiene,
    Birmingham; Mr A. Moses, Chemical Industries Association; Dr R. Owen,
    Trade Unions Congress; Mr J. Sanderson, Independent Consultant; and Dr
    M. Sharratt, University of Surrey.

    BUA (1995)  Phenylhydrazine. Beratergremium fur Umweltrelevante
    Altstoffe (BUA). GDCh Advisory Committee on Existing Chemicals of
    Environmental Relevance. Stuttgart, S. Hirzel, Wissenschaftliche
    Verlagsgesellschaft (Report No. 120; ISBN 3-7776-0691-X)

         For the BUA review process, the company that is in charge of
    writing the report (usually the largest producer in Germany) prepares
    a draft report using literature from an extensive literature search as
    well as internal company studies. This draft is subject to a peer
    review during several readings of a working group consisting of
    representatives from government agencies, the scientific community,
    and industry.


         The draft CICAD on phenylhydrazine was sent for review to
    institutions and organizations identified by IPCS after contact with
    IPCS national Contact Points and Participating Institutions, as well
    as to identified experts. Comments were received from:

    Department of Health, London, United Kingdom 

    Federal Institute for Health Protection of Consumers & Veterinary
    Medicine, Berlin, Germany

    Institut de Recherches en Santé et Sécurité du Travail du Québec,
    Montreal, Canada

    Institute of Occupational Medicine, Chinese Academy of Preventive
    Medicine, Ministry of Health, Beijing, People's Republic of China

    National Institute of Health Sciences, Tokyo, Japan

    Senatskommission der Deutschen GSF-Forschungszentrum für Umwelt und
    Gesundheit GmbH, Institut für Toxikologie, Oberscheissheim, Germany

    United States Department of Health and Human Services (National
    Institute for Occupational Safety and Health, Cincinnati; National
    Institute of Environmental Health Sciences, Research Triangle Park;
    Agency for Toxic Substances and Disease Registry, Atlanta), USA

    United States Environmental Protection Agency (National Center for
    Environmental Assessment, Washington, DC; Region VIII), USA


    Washington, DC, USA, 8-11 December 1998


    Dr T. Berzins, National Chemicals Inspectorate (KEMI), Solna, Sweden
    ( Vice-Chairperson)

    Mr R. Cary, Toxicology Unit, Health Directorate, Health and Safety
    Executive, Bootle, Merseyside, United Kingdom ( Rapporteur)

    Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood, Abbots
    Ripton, Huntingdon, Cambridgeshire, United Kingdom

    Dr O. Faroon, Agency for Toxic Substances and Disease Registry,
    Centers for Disease Control and Prevention, Atlanta, GA, USA

    Dr G. Foureman, National Center for Environmental Assessment, US
    Environmental Protection Agency, Research Triangle Park, NC, USA

    Dr H. Gibb, National Center for Environmental Assessment, US
    Environmental Protection Agency, Washington, DC, USA ( Chairperson)

    Dr R.F. Hertel, Federal Institute for Health Protection of Consumers &
    Veterinary Medicine, Berlin, Germany

    Dr I. Mangelsdorf, Documentation and Assessment of Chemicals,
    Fraunhofer Institute for Toxicology and Aerosol Research, Hanover,

    Dr A. Nishikawa, Division of Pathology, National Institute of Health
    Sciences, Tokyo, Japan

    Dr E.V. Ohanian, Office of Water/Office of Science and Technology,
    Health and Ecological Criteria Division, US Environmental Protection
    Agency, Washington, DC, USA

    Dr J. Sekizawa, Division of Chem-Bio Informatics, National Institute
    of Health Sciences, Tokyo, Japan

    Professor P. Yao, Institute of Occupational Medicine, Chinese Academy
    of Preventive Medicine, Ministry of Health, Beijing, People's Republic
    of China


    Dr K. Austin, National Center for Environmental Assessment, US
    Environmental Protection Agency, Washington, DC, USA

    Dr I. Daly (ICCA representative), Regulatory and Technical Associates,
    Lebanon, NJ, USA

    Ms K.L. Lang (CEFIC, European Chemical Industry Council,
    representative), Shell International, London, United Kingdom

    Ms K. Roberts (ICCA representative), Chemical Self-funded Technical
    Advocacy and Research (CHEMSTAR), Chemical Manufacturers Association,
    Arlington, VA, USA

    Dr W. Snellings (ICCA representative), Union Carbide Corporation,
    Danbury, CN, USA

    Dr M. Sweeney, Document Development Branch, National Institute for
    Occupational Safety and Health, Cincinnati, OH, USA 

    Dr K. Ziegler-Skylakakis, GSF-Forschungszentrum für Umwelt und
    Gesundheit GmbH, Institut für Toxikologie, Oberschleissheim, Germany


    Dr M. Baril, Institut de Recherches en Santé et Sécurité du Travail du
    Québec (IRSST), Montreal, Quebec, Canada

    Dr H. Galal-Gorchev, Chevy Chase, MD, USA

    Ms M. Godden, Health and Safety Executive, Bootle, Merseyside, United

    Dr R.G. Liteplo, Environmental Health Directorate, Health Canada,
    Ottawa, Ontario, Canada

    Ms L. Regis, Programme for the Promotion of Chemical Safety, World
    Health Organization, Geneva, Switzerland

    Mr A. Strawson, Health and Safety Executive, London, United Kingdom

    Dr P. Toft, Programme for the Promotion of Chemical Safety, World
    Health Organization, Geneva, Switzerland


         Ce CICAD relatif à la phénylhydrazine résulte d'une étude des
    risques pour la santé humaine (principalement dans un cadre
    professionnel) rédigée par le  Health and  Safety Executive du
    Royaume-Uni (Brooke et al., 1997) et d'un rapport préparé par le
    Comité consultatif allemand sur les substances chimiques importantes
    pour l'environnement (BUA, 1995). Il est donc consacré aux divers
    types d'exposition par les voies existant sur les lieux de travail,
    mais contient également des données concernant l'environnement
    général. Les données prises en compte dans ces deux documents de base
    remontent respectivement à décembre 1993 et décembre 1994. Une étude
    bibliographique complémentaire arrêtée à janvier 1998 a été effectuée
    à la recherche de données supplémentaires qui auraient pu être
    publiées postérieurement à ces documents. On trouvera à l'appendice 1
    des indications sur le mode d'examen par des pairs ainsi que sur les
    sources documentaires utilisées. Les renseignements concernant
    l'examen du CICAD par les pairs font l'objet de l'appendice 2. Ce
    CICAD a été approuvé en tant qu'évaluation internationale lors de la
    réunion du Comité d'évaluation finale qui s'est tenue à Washington du
    8 au 11 décembre 1998. La liste des participants à cette réunion
    figure à l'appendice 3. La fiche d'information internationale sur la
    sécurité chimique (ICSC No 0938) relative à la phénylhydrazine,
    établie par le Programme international sur la sécurité chimique (IPCS,
    1993), est également reproduite dans ce document.

         La phénylhydrazine (CAS No 100-63-0) se présente sous la forme de
    cristaux de couleur jaune à brun pâle ou d'un liquide jaunâtre de
    consistance huileuse. Il est légèrement soluble dans l'eau et miscible
    aux solvants organiques.

         La phénylhydrazine est utilisée dans le monde entier comme
    intermédiaire dans l'industrie chimique, pharmaceutique et

         On ignore combien de personnes sont susceptibles d'être exposées
    à la phénylhydrazine ou à son chlorhydrate, mais elles sont
    vraisemblablement un petit nombre. On ne dispose d'aucune donnée sur
    l'exposition individuelle, mais le modèle EASE ( Estimation and
     Assessment of Substance Exposure) permet de prédire une exposition
    d'environ 2,3 mg/m3 (0,5 ppm) en moyenne pondérée par rapport au
    temps sur 8 h. En pratique, l'exposition moyenne pondérée par rapport
    au temps sur 8 h est inférieure à cette valeur.

         Les données limitées dont on dispose au sujet de la
    pharmacocinétique de la phénylhydrazine indiquent que ce composé est
    bien absorbé après inhalation, ingestion ou par voie percutanée et
    qu'il se combine facilement à l'hémoglobine des hématies. Il semble

    que sa métabolisation implique une hydroxylation du cycle suivie
    probablement de la formation d'un glucuro-conjugué. Il est
    principalement éliminé par voie urinaire.

         L'ingestion d'une seule dose peut provoquer une intoxication
    (DL50 : 80-188 mg/kg de poids corporel) et la phénylhydrazine est sans
    doute également toxique si elle est inhalée ou entre en contact avec
    la peau (les données concernant ces deux voies d'exposition sont moins
    précises). La phénylhydrazine pourrait être irritante pour la peau et
    les yeux et on est fondé à penser qu'elle produit une sensibilisation
    cutanée chez l'homme. L'exposition à ce composé peut endommager les
    hématies, d'où un risque d'anémie et d'atteinte secondaire d'autres
    tissus comme le tissu splénique et le tissu hépatique. La
    phénylhydrazine est mutagène  in vitro et selon certaines données,
    elle pourrait également avoir une activité génotoxique  in vivo. Elle
    est de toute évidence cancérogène pour la souris (administration par
    voie orale) et provoque des tumeurs vasculaires. On ne peut, à la
    lumière de toutes ces données, indiquer le niveau d'exposition en
    dessous duquel il n'y a pas de risque d'effets cancérogènes ou

         On ne possède pas de données suffisantes concernant les effets
    sur la reproduction ou le développement; il n'est donc pas possible de
    dire si l'homme court des risques de cette nature.

         Le degré de risque professionnel n'est pas connu avec certitude.
    Il s'ensuit qu'il est toujours nécessaire de réduire le niveau
    d'exposition au minimum raisonnable compte tenu de l'état actuel de la

         Comme on ne dispose pas de données qui puissent servir à estimer
    l'exposition individuelle à la phénylhydrazine présente dans
    l'environnement général, on ne peut pas préciser quel risque de cancer
    elle représente pour la population.

         On n'envisage pas d'effets atmosphériques, étant donné que le
    composé est essentiellement libéré dans l'eau et qu'une fois dans ce
    milieu, il ne s'en évapore que très faiblement. En outre, le calcul
    montre que sa demi-vie atmosphérique est très courte par suite de sa
    combinaison avec les radicaux hydroxyles.

         La phénylhydrazine subit une décomposition photochimique et
    s'oxyde dans l'eau. Elle est facilement biodégradable et c'est
    probablement ainsi qu'elle se décompose dans l'environnement. Sa
    sorption par les matières particulaires est minime.

         La phénylhydrazine est toxique pour les organismes aquatiques, la
    concentration sans effet observable (NOEC) la plus faible qui ait été
    indiquée lors d'épreuves classique de toxicité aiguë sur des poissons
    étant de 0,01 mg/litre. Les poissons sont habituellement plus
    sensibles que les daphnies ou les bactéries. On a fait état d'une NOEC
    de 0,49 µg/litre pour les stades embryo-larvaires d'un poisson, le
    danio ( Brachydanio rerio).

         Le risque pour les organismes aquatiques devrait être faible,
    même dans l'hypothèse la plus prudente.


         El presente CICAD sobre la fenilhidrazina se basa en un examen de
    problemas relativos a la salud humana (fundamentalmente ocupacionales)
    preparado por el  Health and  Safety Executive del Reino Unido
    (Brooke et al., 1997) y un informe preparado por el Comité Consultivo
    Alemán sobre las Sustancias Químicas Importantes para el Medio
    Ambiente (BUA, 1995). Por consiguiente, este informe se concentra en
    la exposición a través de las vías de interés para los entornos
    ocupacionales, pero también contiene información medioambiental.
    Incluye los datos identificados a partir de diciembre de 1993 y
    diciembre de 1994, respectivamente. Se realizó una nueva búsqueda en
    lo publicado hasta enero de 1998 para localizar toda la información
    aparecida desde la terminación de estos exámenes. La información
    relativa al carácter del examen colegiado y a la disponibilidad de los
    documentos originales figura en el apéndice 1. La información sobre el
    examen colegiado de este CICAD aparece en el apéndice 2. Este CICAD se
    aprobó como evaluación internacional en una reunión de la Junta de
    Evaluación Final celebrada en Washington, DC (Estados Unidos de
    América), del 8 a 11 de diciembre de 1998. En el apéndice 3 figura la
    lista de los participantes en esta reunión. La ficha internacional de
    seguridad química (ICSC No 0938) para la fenilhidrazina, preparada
    por el Programa Internacional de Seguridad de las Sustancias Químicas
    (IPCS, 1993), también se reproduce en el presente documento.

         La fenilhidrazina (CAS No 100-63-0) se encuentra en forma de
    cristales de un color entre amarillo y marrón claro o como líquido
    oleoso amarillento. Es moderadamente soluble en el agua y es miscible
    con otros disolventes orgánicos.

         La fenilhidrazina se usa en todo el mundo, principalmente como
    intermediario químico en las industrias farmacéutica, agroquímica y

         No se conoce el número de personas potencialmente expuestas a la
    fenilhidrazina o sus hidrocloruros, pero se supone que es bajo. No hay
    datos disponibles sobre la exposición personal, aunque el modelo EASE
    ( Estimation and Assessment of Substance Exposure) predecía (como
    promedio ponderado en función del tiempo durante ocho horas) una
    exposición de unos 2,3 mg/m3 (0,5 ppm). En la práctica, la exposición
    promedio ponderada en función del tiempo durante ocho horas es
    inferior a esa cifra.

         Los limitados datos sobre la toxicocinética indican que la
    fenilhidrazina se absorbe bien por inhalación y por vía oral y cutánea
    y se une fácilmente a la hemoglobina en las glóbulos rojos. El
    metabolismo parece que se produce por hidroxilación del anillo y
    conjugación, probablemente con el ácido glucurónico. La excreción
    tiene lugar fundamentalmente por vía urinaria.

         La fenilhidrazina es tóxica en una exposición única por vía oral
    (DL50 80-188 mg/kg de peso corporal) y es de prever que sea tóxica
    por inhalación y por vía cutánea (los datos relativos a esas vías de
    exposición son menos claros). Puede provocar irritación cutánea y
    ocular y hay pruebas de que tiene propiedades de sensibilización
    cutánea en el ser humano. La exposición a la fenilhidrazina puede
    provocar daños en los glóbulos rojos, pudiendo producir anemia y en
    consecuencia afectar de manera secundaria a otros tejidos, por ejemplo
    los del bazo o del hígado. La fenilhidrazina es mutagénica  in vitro
    y hay algunos indicios de que puede mostrar actividad genotóxica
     in vivo. Esta sustancia es claramente carcinogénica en ratones tras
    la administración oral, induciendo la formación de tumores en el
    sistema vascular. No está claro el mecanismo de formación de tumores,
    pero no se puede descartarr un componente genotóxico. Por
    consiguiente, no parece que sea posible identificar con seguridad un
    nivel de exposición para el cual no haya riesgo de efectos
    carcinogénicos o genotóxicos.

         No se dispone de datos adecuados relativos a los efectos en la
    reproducción o el desarrollo; no es posible, pues, evaluar el riesgo
    para la salud humana de esos efectos finales.

         El nivel de riesgo en el entorno ocupacional es incierto; en
    consecuencia es constante la necesidad de reducir los niveles de
    exposición todo lo que sea razonablemente posible con la tecnología
    disponible en la actualidad.

         La falta de datos disponibles que sirvan como base para la
    estimación de la exposición indirecta de las personas a la
    fenilhidrazina a partir del medio ambiente impide determinar los
    riesgos potenciales de cáncer para la población general.

         No son de prever efectos atmosféricos, debido a que la
    fenilhidrazina se libera fundamentalmente en el agua, a su escasa
    volatilización del agua a la atmósfera y a su rápida semivida en la
    atmósfera calculada tras la reacción con los radicales hidroxilo.

         La fenilhidrazina se degrada por vía fotoquímica y se autooxida
    en el agua. Es fácilmente biodegradable y se supone que es ésta la
    principal ruta de descomposición en el medio ambiente. La sorción en
    partículas es mínima.

         La fenilhidrazina es tóxica para los organismos acuáticos, siendo
    de 0,01 mg/litro la concentración sin efectos observados (NOEC) más
    baja notificada en pruebas normalizadas de toxicidad aguda en peces;
    en general, los peces son más sensibles que los dáfnidos o las
    bacterias. Se ha notificado una NOEC de 0,49 µg/litro para las fases
    embriolarvarias del pez  Brachydanio rerio.

         Se supone que el riesgo para los organismos acuáticos es bajo, a
    partir de hipótesis muy prudentes.

    See Also:
       Toxicological Abbreviations
       Phenylhydrazine (ICSC)