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EC number: 203-614-9
CAS number: 108-77-0
Systemic effects- long term exposure
In a subchronic inhalation toxicity study
(94 -0211 -DKT) rats were exposed to Cyanuric chloride vapour
concentrations of 0.01, 0.05 and 0.25 mg/m³ for 90 d (5 d/wk 6h/d). A
true systemic NOAEC could not be established since no adverse systemic
effects were noted in the study. The highest test concentration of 0.25
mg/m³ is 80000 fold lower than the limit concentration of 20000 mg/m³
given in OECD test guideline 413 (2009) for vapour. Thus, the systemic
NOAEC could be much higher than 0.25 mg/m³. In order to prevent an
exaggerate conservatism of the risk assessment the study should not be
used to establish a starting point for the derivation of a systemic
In human studies (Blagidation et al., 1971
and 1965; Mertschenk et al., 1998; Kaskevich et al., 1984) local effects
due to irritating/caustic nature of Cyanuric chloride occurred whereas
no systemic effects related to test item treatment were seen.
In an epidemiological study on workers
(Morfeld etal 2011) with a mean exposure time of 11.3 years no systemic
effects were reported. This study comprises the worldwide most extensive
data base regarding the effects of long term Cyanuric chloride exposure
on human health.
In conclusion, no adequate animal data are
available for the derivation of a long-term inhalation DNEL for systemic
effects. However, the available data regarding long term inhalation
toxicity indicated that the toxicity of Cyanuric chloride is triggered
by local and not by systemic effects. Thus, the derivation of a DNEL for
long term systemic effects is not required.
In a repeated dose dermal toxicity study
(83-0093) rabbits were treated during 21 days with Cyanuric chloride in
mineral oil via occlusive dermal application (5 days/weekly 6h/day; 50,
150, 500 mg/kg bw). Generally, effects were only seen at the portal of
entry due to the irritation and caustic effects of Cyanuric chloride.
One animal died due to multifocal ulcerative dermatitis and associated
debilitating effects. The following clinical signs were noted: nasal
discharge in the high dose groups and significant dermal irritation in
the three dose groups. A dose- and duration-related progression of
dermal irritation was noted in all dose groups (sequence: blanching,
fissuring, desquamation, eschar (if present) and exfoliation). Treatment
related body weight losses were noted for mid dose males and high dose
males and females. The body weight effects were assigned to reduced food
intake due to the stress caused by repeated treatment with the corrosive
substance and thus, secondary to test item treatment. Since no systemic
toxicity occurred which was primarily caused by Cyanuric chloride the
derivation of a systemic NOAEL was regarded as scientifically
questionable. However, since the highest dose tested (500 mg/kg bw ) is
nearby the recommended limit dose according to OECD 410, 1981 (i.e.1000
mg/kg bw) this dose can be used as conservative starting point for DNEL
Systemic effects- acute, short term
In an acute inhalation toxicity study
(92-0177-FGT) with nose/head exposure, the LC50 value was 170 mg/m³.
Mortality and clinical signs were caused by the corrosive potential of
the test substance and the resulting local effects of the respiratory
One case of intoxication with Cyanuric
chloride that occurred accidentally in a plant producing herbicides is
reported (Catenacci et al., 1987). Irritation to the skin, eyes and
pharynx followed later by a serious obstructive pulmonary syndrome with
impairment of alveolar-caplillary exchanges was mentioned. The worker
fully recovered from the skin, eye and lung disorders in three weeks.
The effects reported demonstrate that the toxicity of Cyanuric chloride
is triggered by local not by systemic effects. This conclusion is
further supported by the epidemiological study of Morfeld et al. (2011)
on workers where a threshold for local effects was established in the
absence of systemic effects.
In conclusion, based on the available animal
and human data no adverse systemic effects after short term inhalation
exposure of Cyanuric chloride were observed even at concentrations
causing local effects (irritation).
In an acute dermal toxicity study
(88-0023-DKT) in rabbits a combined LD50 for both sexes of > 2000 mg/kg
was deduced under the test conditions. According to ECHA Guidance on IR
& CSA (2010) a DNEL for acute toxicity should be derived if an acute
toxicity hazard (leading to C&L) has been identified. Since the LD50
value for acute dermal toxicity is > 2000 mg/kg Cyanuric chloride is not
subjected to C&L and thus no DNEL for acute toxicity is needed.
Local effects - long term exposure
The epidemiological study of Morfeld et al.
(2011) on 394 male employees represents the most reliable study for DNEL
derivation since the study comprises the worldwide most extensive data
base regarding the effect of long term Cyanuric chloride exposure on
human health. In this study the lung function parameters FEV1, VC or FVC
and FEV1%FVC were used to assess local effects on the respiratory tract
after long-term inhalation exposure. In relation to external pulmonary
reference values the results indicated no abnormalities of lung function
parameters. When considering models with maximum estimates of pulmonary
function loss, a long-term threshold value for cumulative exposure could
be identified. Using a representative model that described the estimated
average loss, the result was a threshold band which offers a best value
estimate of 0.3 mg/m³-years. Taking into consideration mean exposure
period of 11.2 years, a tolerable additional loss of lung function of
10% of the age typical loss and a factor of two for the conversion of
long term values into an occupational exposure limit a TWA (time
weighted average, 8h) of 0.06 mg/m³ was calculated. The TWA is
identified as the most relevant dose descriptor and starting point for
In two guinea pig maximisation tests
(94-0201-DKT, 81-0028-DKT) Cyanuric chloride was identified as skin
sensitizer category 1A. In study 94-0201-DKT the non-irritating
concentration of 0.01 % (used for induction and challenge treatment)
caused sensitisation in all animals. This result shows that
sensitisation is the more sensitive end point in comparison to
irritation. Thus, hazard assessment is triggered by the sensitizing
effects of Cyanuric chloride. However, since only qualitative data are
available a quantitative assessment of skin sensitisation and a DNEL
derivation is not feasible.
Local effects - acute, short term
The substance caused respiratory irritation
in an acute inhalation toxicity test and is classified with H335,
corresponding to the medium hazard category. A quantitative assessment
for respiratory irritation is not possible since only qualitative data
are available and therefore, no DNEL for acute short term inhalation
could be derived. However, the long-term inhalation DNEL (local effects)
is sufficient to ensure that no local effects after acute/short term
inhalation exposure occur.
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