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Skin sensitisation

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Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
other: CBA/J
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague-Dawley; Indianapolis, IN
- Age at study initiation: ~ 2 months
- Weight at study initiation: 21.6-26.8 g
- Housing: Housed individually in stainless steel cages, suspended with wire bottom
- Diet: PMI Feeds Inc. Formulab #5008; available ad libitum
- Water: Municipal water supply analyzed by TCEQ Water Utilities Division; available ad libitum
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C):19-21
- Humidity (%): 45-97
- Air changes (per hr): 10-12
- Photoperiod (hrs dark / hrs light): 12/12


Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
100% undiluted; 50% and 25% w/v in 80% acetone; 20% olive oil
No. of animals per dose:
5
Details on study design:

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: OECD 429
- Criteria used to consider a positive response: Stimulation index of ≥ 3.


TREATMENT PREPARATION AND ADMINISTRATION:
On days 1 ,2 and 3 each test animal received an open application of 25µL of an appropriate dilution (25% or 50%) of the test substance, or 100% test substance moistened with acetone:olive oil to the dorsum of both ears. On day 6 of the study all test and control animals were injected in the tail vein with 250µL of 0.01M phosphate-buffered saline (PBS), pH 7.4, containing 20 µCi of (methyl 11, 21 – 3H] Thymidine. Five hours after the injection, the animals were sacrificed, the draining auricular lymph nodes were excised and pairs from each animal were processed.
A single cell suspension was prepared by gentle mechanical disintegration through 200 mesh stainless steel gause. The cells were washed twice with an excess of PBS and precipitated with 5% trichloroacetic acid at 4C for 18 hours.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
None applied
Positive control results:
The positive control elicited a stimulation index of 9.5.
Parameter:
SI
Remarks on result:
other: Cyanuric acid produced a stimulation index of ≤ 3 in two of three groups of test animals. However, based on the severity of the response the positive results were considered indicators of borderline or mild skin sensitization potential.
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Vehicle control: 668 Test group I (25%): 1390 Test group II (50%): 2244 Test group III (100%): 2500 Positive control: 6346

Table 1:Ratio derived for each test group based on group mean DPM

Animal group

Test substance concentration

Average count per mouse

Num. of mice in group

Test/vehicle control ratio

Vehicle control

NA

668

5

NA

Test group I

25%

1390

5

2.1

Test group II

50%

2244

5

3.4

Test group III

100%

2500

5

3.7

Positive control

NA

6346

5

9.5*

NA – not applicable

* - Positive control used to confirm animal sensitization potential and validate procedures 

The test substance produced a stimulation index (SI) of ≤3 in the 25% dose group and ≥3 in the 50% and 100% dose groups, which is considered a positive sensitization response. However, based on the low magnitude of the SI compared to that of the positive control, which is a moderate sensitizer, cyanuric acid is considered to have weak or mild sensitization potential in this LLNA test. There were no signs of excessive irritation at any test site

Interpretation of results:
other: mild sensitiser
Conclusions:
Cyanuric acid produced a stimulation index of ≥ 3 in two groups of animals. However based on the severity of the response the positive results were considered indicators of borderline or mild skin sensitisation.
Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In an OECD guideline study (Kuhn 2008) the sensitisation potential of cyanuric acid was investigated in female mice in a local lymph node assay.

The results of the LLNA study indicated that CYA elicited a positive response for potential skin sensitization, based on test/vehicle control ratio or stimulation index (SI) of 3 or greater in two of the three concentrations tested (50% and 100%). These positive results were considered indicators of borderline or mild skin sensitization potential. The test group at 25% CYA was below the SI of 3 threshold for a positive response. The severity of response was low, just above the SI threshold of 3 for only two of the three concentrations tested, which were considered borderline positive. In addition, the response at 25% CYA was below this threshold and not considered a positive response.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The results of the LLNA study (Kuhn JO 2008) indicated that CYA elicited a positive response for potential skin sensitization, based on test/vehicle control ratio or stimulation index (SI) of 3 or greater in two of the three concentrations tested (50% and 100%). These positive results were considered indicators of borderline or mild skin sensitization potential. The test group at 25% CYA was below the SI of 3 threshold for a positive response. The severity of response was low, just above the SI threshold of 3 for only two of the three concentrations tested, which were considered borderline positive. In addition, the response at 25% CYA was below this threshold and not considered a positive response. On this basis CYA should not be classified as a skin sensitiser.