The substance or preparation shall be classified as corrosive

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					                                                                       ECBI/73/02 Add. 2




Cyanuric Chloride Consortium
ICCA HPV Initiative
Degussa AG
Syngenta Crop Protection AG
Lonza Ltd.                                                                     14 Feb 2003



Inaddition to our statement from 13 Dec 2002 we would like to give some further information
toopen issues of local corrosive effects versus systemic effects, workplace exposure
situation and corrosovity seen in humans and animal tests, disscussed at the meeting of the
CMR Working Group, 15th - 17th January 2003.

Mode of the action (corrosivity to biologigal membranes)
In considering whether a chemical is corrosive or simply irritant, it is important to recognise
that when applied at low concentrations to skin or eye, or with low inhalation exposures,
buffering/reaction capacity of the target tissue will result only in marked symptoms of
irritancy. However, once this capacity has been exceeded, usually in a very steep
doseresponse relationship, the true corrosive nature of the chemical becomes apparent.
This is seen clearly with hydrogen chloride in aqueous solution, which is reflected in the
cassification and labelling of this chemical, and applies equally to other corrosive chemicals,
including cyanuric chloride (in presence of humidity CC hydrolyses to HCl and cyanuric
acid,14,19).

Skin irritation (1,2) and dermal toxicity studies (3,4,5) with cyanuric chloride have shown, that
the classification criteria (28th ATP, 67/548/EEC) apply to cyanuric chloride, which has to be
classified as R34. Any compound that is classified as corrosive based on skin destruction will
be corrosive to all biological membranes, especially mucous membranes which lack the
substantial protection from harm afforded by the outer layers of skin. Cyanuric chloride is no
exception to this. Eye irritation studies (1,6,7) demonstrate severe damaging effects and the
respiratory tract, lined entirely by sensitive epithelial cells covered only by a mucous, is
equally sensitive to corrosive chemicals (8,9,10). Within the GHS consideration of respiratory
tract corrosion, a draft definition has been proposed: "Corrosion to respiratory tract is defined
by destruction of the respiratory tissue after limited duration of exposure analogous to skin
corrosivity; this would include destruction of mucosa."

The effects observed after inhalation of cyanuric chloride are entirely consistent with
corrosion, both under the EC criteria and the proposed GHS definition. Pertinent clinical
symptoms from acute inhalation exposure in rats ( 8,9,10) included:
    gasping (attempts to breath by mouth in an obligate nose-breathing species when the
      respiratory tract has undergone substantial damage and is blocked with debris and
      mucous), discharge from nose
    bloody and crusted nose (nasal exudate of the debris/mucous etc described above and
      indicative of haemorrhage resulting from corrosive damage to the nasal passages).
    Shortness of breath (related also to the above tissue damage).
Post mortem examination included the following:
    In animals surviving to full termination - bloated and oedematous lungs (such effects
       are seen with gross epithelial necrosis/damage and resultant substantial extravasation
       of plasma components into the lung).
    Intercurrent deaths – bloated oedematous discoloured lungs with bronchi filled with
       slime (demonstrates extensive corrosion/necrosis of respiratory tract epithelium, the
       slime probably representing both oedematous fluid and the sloughed-off epithelium).
    Hydrothorax (a secondary effect of marked pulmonary damage).
   
Bloody-slimy contents of the gastrointestinal tract and red-staining of mucosa of small
intestine representing a combination of swallowed material derived from the lung effects and
possibly the effect of swallowed cyanuric chloride which is then corrosive to the
gastrointestinal tract. The observations in the GI-tract are consistent with descriptions of
findings following oral dosing of cyanuric chloride (11,12,13).

Hyperaemia in the intestine is attributable to possibly direct corrosive/irritant effects of
swallowed cyanuric chloride but is more likely to be induced by the hydrochloric acid which
results from the hydrolysis of the swallowed cyanuric chloride. Hyperaemia is a classic
protective reflex of the gastrointestinal tract to the presence of increased quantities of acid
and as such is a direct rather than systemic response to exposure to cyanuric chloride.

The reporting of cyanosis in some animals exposed to CC is consistent with the marked lung
toxicity rather than any indication of a systemic effect . The severe damage in the lungs, both
damage/necrosis of epithelium and influx of oedematous fluid, will compromise substantially
the normal gas-exchange function of the lung, with the resultant development of cyanosis.
Therefore, this effect, together with post-mortem findings in the liver etc, is a secondary
consequence, to the severe pulmonary effects and not considered to be attributable to any
systemic toxicity.



Workplace exposure
                                                                                  3
For the production plant a typical range of air concentrations is 0.005 - 0.3 mg/m CC,
(stationary sampling) in some cases higher concentrations (not all data could be checked
regarding the relevance of worker exposure, some data only for effectiveness of exposure
reduction measures). The results of personal sampling are in the range of 0.001-0.130
mg/m3 (max. 0.69 mg/m 3, including short term exposure). In the control room (no gas
                                                     3
masks) the concentration is lower than 0.005 mg/m . Most air measures do not differentiate
between vapor and dust (adsorption to silica), but also specific dust measures are within the
range mentioned above (0.01 – 0.24 mg/m³, gravimetric). Data are available from four
production plants (Degussa, Lonza) and one user plant (Syngenta).

Inside a CC production plant, it is obligatory to wear a gas mask. The reason for this
precaution safety measure, is not only the exposure to cyanuric chloride, but also to
cyanogen chloride. There are no definite workplaces inside a CC-plant, only control and
sampling are representative jobs for short term exposures with CC. The filling station is
spatially seperated.
Based on the sublimation/desublimation property of CC, the exposure to vapour or dust
depends on the local conditions and circumstances. Inside a plant building employees will be
exposed to vapor, whereas in a filling station a dust/vapor exposure occur.
Justification of R 34
Animal tests
In the available OECD Guideline 404 studies with a 4 hour exposure no corrosive effects
were reported (15,16,17,18). The reason could be, that the (bio)availability and the
hydrolysis is diminished and the exposure time is to short to produce a low enough pH value
to produce necroses. This would be in accordance with the result in studies with longer
application times (24 hours skin irritation study (2), and also acute dermal toxicity studies
(3,4,5)) or repeated exposures (9), which report besides erythema and oedema also about
erosions, pachydermatosis and necrosis. After exposure corrosive effects can not only occur
to mucus membranes but also at skin, when humidity/sweat, duration and
amount/concentration of CC are in favorable constellation. In this particular case it seems,
that the current test protocol and the assessment of the results cannot show the potential
corrosive effect of CC.

Human
In some cases besides skin sensitation, also skin irritation and corrosion (burns) of exposed
employees (hands, arms, wrists, neck) are reported in internal medical reports. The effects
occured within a short time and the severeness was influenced by exposure duration (time
between exposure and removement) and individual sensitivity (Degussa internal information,
BUA 1993).



Conclusion
The effects observed after inhalation of cyanuric chloride are entirely consistent with
corrosion, both under the EC criteria and the proposed GHS definition. Pertinent clinical
symptoms from acute inhalation exposure in rats as well as post mortem findings in the
respiratory tract and the gastrointestinal tract demonstrate severe damaging effects to
biological membranes, especilly to mucus membranes.

The observation in the GI-tract (bloody-slimy contents, red-staining of mucosa of small
intestine) – observed only in dead animals - represents a combination of swallowed material
derived from the lung effects and possibly the effect of swallowed cyanuric chloride which is
then corrosive to the gastrointestinal tract. (consistent with findings in oral studies).These
effect could also be seen in connection with hyperaemia in the intestine, based on the
reduced haemoglobin/oxygen content of the blood and the clinical sign cyanosis
representing a marked lung toxicity rather than any indication of a systemic effect .

 At workplaces the air concentrations are between 0.005 and 0.3 mg/m3 CC. In general the
vapor exposure is predominant, only at the filling station a vapor/dust exposure occurs.

In skin irritation studies only prolonged or repeated exposures cause corrosive effects. The
standard test protocol seems to be not relevant to show the potential of the corrosivity of CC.
This is shown by experience in humans, where burns at the skin were observed.

Based on this informations a classification with R 34 is justified.
References

(1)    Blagodatin, V. M., Gig. Tr. Prof. Zabol., Vol. 12, 35-39 (1968)
(2)    The Nofer Institute of Occupational Medicine, Lodz, Poland Cyanuric chloride,
       Testing the Primary Irritancy after single and repeated application to the skin of the
       rabbit, (1993)
(3)    The Nofer Institute of Occupational Medicine, Lodz, Poland Cyanuric chloride,
       Testing the acute Toxicity after single dermal administration in rats, (1993)
(4)    Ciba-Geigy AG, Report on acute dermal LD50 in the rat of technical GS 41'711,
       unpublished, report No. 810586 (1981)
(5)    Degussa AG, Cyanurchlorid, Akute Toxizität, Toxikologische Prüfung nach einmaliger
       dermaler Applikation am Kaninchen, unpublished, report No. Degussa AG-US-IT-No.
       88-0023-DKT (1988)
(6)    Ciba-Geigy AG, Report on eye irritation in the rabbit after single application of GS
       41711, unpublished, report No. 810585 (1981)
(7)    The Nofer Institute of Occupational Medicine, Lodz, Poland, 2,4,6-trichlorotriazine -
       cyanuric chloride testing the primary irritancy after single application to the eye of the
       rabbit, (1993)
(8)    Bayer AG, Cyanurchlorid, Untersuchungen zur akuten Inhalationstoxizität an der
       Ratte nach OECD-No. 403, unpublished, report No. 21756 (1992)
(9)    Ciba-Geigy AG, Report on acute vapor inhalation Toxicity in the rat of Cyanuric
       chloride (GS-41711), unpublished, report No. 801016 (1981)
(10)   Degussa AG, 4-hour, acute inhalation Toxicity study with Cyanuric chloride vapor, in
       rats, unpublished, report No. Degussa AG-US-IT-No. 91-0107-DGT (1991)
(11)   Degussa AG Cyanurchlorid, akute Toxizität , Prüfung der akuten Toxizität nach
       einmaliger oraler applikation an der Ratte, unpublished, report No. Degussa AG-US-
       IT-No. 86-0063-DKT (1986)
(12)   Lonza AG, acute oral toxicity assay Cyanuric chloride, unpublished, Lonza report No.
       0124 (1975)
(13)   Ciba-Geigy AG, Report on acute oral LD50 in the rat of technical GS 41'711,
       unpublished, report No. 810583 (1981)
(14)   Weigert, W.; Düsing, G.; Kriebitzsch, N.; Pfleger, H.: Cyansäure und Cyanursäure; in:
       Ullmanns Encyklopädie der technischen Chemie: 4. Auflage., 9), 647-654, Verlag
       Chemie, Weinheim 1975,
(15)   Degussa AG, Bericht über die Prüfung der lokalen Reizwirkung von 2,4,6-Trichlor-
       1,3,5-triazin (Cyanurchlorid) nach einmaliger Applikation an der Haut des Kaninchens
       (Patch-Test), unpublished, report No.Degussa AG-US-IT-No. 82-0038-DKT (1982)
(16)   Rydzynski, K and Jedrychowski, R. (1994) Sensory irritating properties of cyanuric
       chloride as revealed with plethysmographic method. Int. J. Occ. Med. Environ. Health
       7 (2): 14-154
(17)   Ciba-Geigy AG, Report on acute oral LD50 in the Rat of Technical GS 41'711,
       unpublished, report No. 810583 (1981)
(18)   Lonza Ltd., Acute dermal irritation test in the rabbit, unpublished, Lonza report No.
       3172 (2000)
(19)   Degussa AG, Kinetische Untersuchungen zur Hydrolyse von Cyanurchlorid,
       unpublished, report No. Degussa AG-US-IT-No.85-0045-DKO (1985)

REVIEWS
Cyanuric chloride (2,4,6-trichloro-1,3,5-triazine). BUA Report 125, German Chemical Society
(1993)
OECD SIAR for Cyanuric chloride, SIAM 13 (2001)