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Administrative data

Description of key information

Skin sensitisation: Category 1A (May cause allergic reaction) for the guinea pig, (OECD TG 406); study 94-0201-FGT

Respiratory sensitisation: ambiguous results, study 92-0178-FGT; No reliable study for derivation of classification and labelling available.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988-04-27 to 1988-06-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: - guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1981
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The described guinea pig sensitisation test (Buehler test) according to OECD 406 was conducted in 1988 before the guidance for the LLNA (OECD429, first adopted in 2002) was available, and before the method was fully established and validated. And since the result of the Buehler test is considered to be scientifically valid, the test was not repeated also taking into account exposure and animal welfare considerations.
Species:
guinea pig
Strain:
other: Albino Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: in-house breeding facility
- Age at study initiation: 9 - 10 weeks
- Weight at study initiation: 270 - 410 g
- Housing: 1 per cage (stainless steel cages with grating floor)
- Diet: ad libitum
- Water: ad libitum, twice weekly ascorbic acid was added)
- Acclimation period: 1 day


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5 +- 1
- Humidity (%): 55 +- 10
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
other: polyethylene glycol 400 (PEG 400), Windsor Laboratories Limited
Concentration / amount:
- 0.01 % (maximum non-irritating concentration after intradermal injection, as determined during a preliminary study). The same concentration was used also for challenge exposure.
Route:
epicutaneous, occlusive
Vehicle:
other: polyethylene glycol 400 (PEG 400), Windsor Laboratories Limited
Concentration / amount:
- 0.01 % (maximum non-irritating concentration after intradermal injection, as determined during a preliminary study). The same concentration was used also for challenge exposure.
No. of animals per dose:
- 12 animals in the treatment group
- 8 animals in the control group
Details on study design:
RANGE FINDING TESTS: no data

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Site: scapular region
- Test groups: 12 animals
- Immunostimulation: Freunds Complete Adjuvant (FCA)
- Control group: 8 animals, treated only with vehicle
- Day 1: first induction, intradermal application
- clipping of an area of 4 cm x 6 cm of the scapular region
- three pairs of intradermal injections (0.1 mL) in the neck of the animals:
mixture of adjuvant and PEG 400 (1:1) (treatment group and control group)
test compound 0.01 % in PEG 400 (treatment group) OR PEG 400 alone (control group)
test compound 0.01 % in a mixture of FCA:PEG 400 (1:1) (treatment group) OR FCA:PEG 400 (1:1) alone (control group)

- Day 7:
- clipping of an area of 4 cm x 6 cm of the scapular region

- Day 8: second induction, epicutaneous application
- test compound 0.01 % in PEG 400 (treatment group) OR PEG 400 alone (control group)
- exposure to the clipped skin area of the injection sites and coverage with an occlusive patch, secured by elastic bandage (Paso, Poland)
- exposure duration: 48 hours

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Site: flank
- Test groups: 12 animals
- Control group: 8 animals, challenged identically as the test group
- Day 21:
- clipping of an area of 5 cm x 5 cm at both flank regions
- Day 22: challenge, epicutaneous application
- application of 0.01 % of the test compound in PEG 400 with an occlusive patch (Polovis, Poland) to the left flank and PEG 400 alone with an occlusive patch to the right flank
- exposure duration: 24 h
- Day 24 and 25: evaluation
- 24 h and 48 h after removal of the dressing the reactions were graded according to the Draize scoring
- Grading according to Draize scoring:
Erythema and Eschar Formation Value
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation
injuries in depth 4

Oedema formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 mm) 3
Severe oedema (raised more than 1 mm and extending beyond
the area of exposure 4

Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.01 %
No. with + reactions:
0
Total no. in group:
8
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.01 %. No with. + reactions: 0.0. Total no. in groups: 8.0. Clinical observations: none.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.01 %
No. with + reactions:
0
Total no. in group:
8
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.01 %. No with. + reactions: 0.0. Total no. in groups: 8.0. Clinical observations: none.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.01 %
No. with + reactions:
12
Total no. in group:
12
Clinical observations:
slight to severe erythema, slight oedema in two animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.01 %. No with. + reactions: 12.0. Total no. in groups: 12.0. Clinical observations: slight to severe erythema, slight oedema in two animals.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.01 %
No. with + reactions:
12
Total no. in group:
12
Clinical observations:
slight to severe erythma
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.01 %. No with. + reactions: 12.0. Total no. in groups: 12.0. Clinical observations: slight to severe erythma.
Group:
positive control
Remarks on result:
not measured/tested
Interpretation of results:
other: Skin sensitizer Category 1A
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the conditions of this skin sensitization study all animals showed positive reactions at 24h and 48 h (slight to severe erythema at both time points, slight oedema in two animals at the first time point). No deaths occurred during the study period. Based on the results it can be concluded that the test substance is a skin sensitizer.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

In a guinea pig maximisation test (94-0201-DKT), identified as key study, animals (Hartley albino guinea pigs) were treated with cyanuric chloride in polyethylene glycol according to guideline (1 x intradermal induction - 0.01%, 1 x epidermal induction - 0.01%, 1 x epidermal challenge - 0.01%) and observed for clinical signs, weight development and overt signs of toxicity. Skin reactions were observed and scored according to the Draize score system 24 and 48 h after the start of the epicutaneous challenge. All animals showed positive reactions at both time points (slight to severe erythema at both time points, slight oedema in two animals at the first time point). No deaths occurred during the study period. Based on the stated results the following classification is regarded appropriate: Category 1A: Skin sensitizer (H 317: Warning, may cause allergic skin reaction) according to CLP as implementation of UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).

In a second guinea pig maximisation test (81-0028-DKT) animals (Pribright white guinea pigs) were treated with cyanuric chloride in polyethylene glycol according to guideline (1 x intradermal induction - 0.1%, 1 x epidermal induction - 0.5%, 1 x epidermal challenge - 0.05%) and observed for clinical signs, weight development and overt signs of toxicity. Skin reactions were observed and scored according to the Draize score system 48 h after the start of the epicutaneous challenge. 19 out of 20 animals showed positive reactions (Draize scores of 1 – 2). No deaths occurred during the study period. Based on the stated results the following classification is regarded appropriate: Category 1A: Skin sensitizer (H 317: Warning, may cause allergic skin reaction) according to CLP as implementation of UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).

One further skin sensitization study (79-0014-FKT) indicated sensitising properties of Cyanuric chloride however, due to the insufficient documentation of the study a clear classification is not possible.

 

Short description of key information:
- skin sensitisation: Category 1A (May cause allergic reaction) for the guinea pig, (OECD TG 406); study 94-0201-FGT

Justification for selection of skin sensitisation endpoint:
Most reliable study.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

In a respiratory sensitization study groups of 8 female guinea pigs were induced three times (day 0: cranial, day 2: throracal, day 4: caudal) with 200 µL of a 0.3% Solution of Cyanuric Chloride in acetone. The control group animals (8 female animals) achieved 200 µL acetone. On challenge animals were exposed (nose only) for 30 minutes. As only four animals could be exposed simultaneously the 8 animals per group were divided in two subgroups a and b each. In a first challenge group 1 (induced with vehicle) and 2 (induced with Cyanuric Chloride) on day 22 (group a) on day 24 (group b), and a second challenge with acetylcholine (3 times 15 min with 0.1% w/v, 0.3% w/v and 1.0% w/v respectively) directly after the Cyanuric chloride exposure and a third challenge with acetylcholine (3 times 15 min with 0.1% w/v 0.3% w/v and 1.0% w/v respectively) on day 23 (group a) and on day 25 (group b). Animals were sacrificed after the last challenge, sections and the lungs weighted and pathologically analyzed. Cyanuric chloride induced animals have a slightly reduced body weight. No significant difference in the absolute and relative lung weights between test item induced and control animals was observed. Lung pathology examination demonstrated that both groups showed signs of macroscopic differences from the historical data, very likely due to pneumonia in both groups. However, influence on respiration were also seen in control animals. No toxicological significant differences in the respiratory sensibility between the two groups were found. Possible differences probably were masked by the infections in the respiratory track of both groups. Due to the ambiguous results a clear classification is not possible.

In a second study published by Rydzynskie et al. 1993 the sensitizing potential of Cyanic Chloride through subacute inhalation exposure was determined in rats by a popliteal lymph node assay (PLNA). A sensitizing potential of Cyanuric chloride was identified. However, the information of the study was derived from a short abstract. Due to the insufficient documentation no classification is possible and the study was marked as disregarded.

Lalko et al. 2013 reported that Cyanuric chloride causes high levels of cysteine depletion under direct conditions in an in chemico peroxidase peptide reactivity assay (PPRA). The PPRA follows an analogous principle of peptide test substance reaction but with significant differences to the DRPA (OECD442C). Thus, the cysteine depletion under direct conditions assed in the PPRA is not sufficient to justify classification as respiratory/skin sensitiser.


Short description of key information:
- respiratory sensitisation: ambiguous results, study 92-0178-FGT

Justification for selection of respiratory sensitisation endpoint:
No reliable study for derivation of classification and labelling available.

Justification for classification or non-classification

Based on the results for the in vivo skin sensitization study, the substance should be classified as Cat. 1A, H317 (Warning, May cause an allergic skin reaction) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.

 

Based on the available data no classification for respiratory sensitisation can be deduced. According to Annex VI of Regulation (EC) No 1272/2008 Cyanuric chloride is not classified as a respiratory sensitizer.