2,4,6-trichloro-1,3,5-triazine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Route of original study:

By inhalation

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Route of original study:

By inhalation

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.06 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1

Dose descriptor:

other: TWA (8h) of 0.06 mg/m³, please refer to the discussion

AF for dose response relationship:

1

Justification:

Starting point is a TWA value derived from human data.

AF for differences in duration of exposure:

1

Justification:

Starting point is based on chronic exposure.

AF for interspecies differences (allometric scaling):

1

Justification:

Starting point is based on human data.

AF for other interspecies differences:

1

Justification:

Starting point is based on human data.

AF for intraspecies differences:

1

Justification:

Starting point is based on an epidemiological study on a representiative worker group.

AF for the quality of the whole database:

1

Justification:

The study fulfill the criteria defined in ECHA (2012). Guidance on information requirements and chemical safety assessment, chapter R.8 for the use of human data (please refer to chapter 13 of IUCLID, Evaluation Epidemiological Study with Cyanuric Chloride accordingto ECHA guidance).

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factor is required.

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

6.94 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

72

Modified dose descriptor starting point:

NOAEL

Value:

500 mg/kg bw/day

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

2.4

Justification:

The default allometric scaling factor for differences between rabbits and humans is used.

AF for other interspecies differences:

1

Justification:

There is no evidence for species differences in the general mode of action or kinetics

AF for intraspecies differences:

5

Justification:

The default value for the relatively homogenous group "Workers" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole database is considered to be sufficient and uncritical

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factor is required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

Systemic effects- long term exposure

Inhalation

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 long-term DNEL.

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.

Dermal

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 derivation.

Systemic effects- acute, short term exposure

Inhalation

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 tract.

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).

Dermal

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

Inhalation

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 DNEL derivation.

Dermal

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 exposure

Inhalation

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.

Dermal

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.

 

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified