Registration Dossier

Toxicological information

Carcinogenicity

Currently viewing:

Administrative data

Description of key information

Carcinogenicity study, oral exposure, Due to insufficient documentation the study is not adequate for classification,  SIDS Initial Assessment Report For SIAM 13, cyanuric chloride may induce tumours at the injection site associated with the development of necrosis due to its highly irritating/caustic properties. 

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records
Reference
Endpoint:
carcinogenicity
Remarks:
other: group1: subcutaneous injection for 3.5 months and subsequent for 20.5 months oral in the diet, group2: 24 months oral in the diet
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (e.g. limited information on study design, no information on control animals)
Qualifier:
no guideline followed
Principles of method if other than guideline:
- 2 treatment groups, 50 animals/treatment
- group 1: 25 males/25 females, once weekly subcutaneous injection of 10 mg in 0.5 mL sunflower oil for 3.5 months and subsequently, 6 times/week 10 mg in 0.5 mL sunflower oil in the diet for 20.5 months
- group 2: 27 males/23 females, 6 times/week 10 mg in 0.5 mL sunflower oil in the diet for 24 months.
GLP compliance:
no
Remarks:
study performed prior to implementation of GLP
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 100 - 110 g



Route of administration:
other: group1: subcutaneous injection for 3.5 months and subsequent for 20.5 months oral in the diet, group2: 24 months oral in the diet
Vehicle:
other: sunflower oil
Details on exposure:
group 1:

Subcutaneous injection of 10 mg in 0.5 mL sunflower oil once weekly for 3.5 months. Due to necrosis at the injection side the application method was changed thereby animals applied 10 mg in 0.5 mL sunflower oil six times a week via diet for further 20.5 months.

group 2:

Animals applied the test substance via diet (10 mg in 0.5 mL sunflower oil) six times a week for 24 months.

- DIET PREPARATION
- Rate of preparation of diet (frequency): daily
- Mixing appropriate amounts with (Type of food): 10 mg in 0.5 mL sunflower oil added to the diet, method not further detailed
- Storage temperature of food: - not reported


VEHICLE
- Justification for use and choice of vehicle (if other than water): - not reported
- Concentration in vehicle: 10 mg in 0.5 mL
- Lot/batch no. (if required): - not reported
- Purity: - not reported
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
see principle of method
Frequency of treatment:
see principle of method
Post exposure period:
none
Remarks:
Doses / Concentrations:
10 mg in 0.5 mL sunflower oil
Basis:
other: see principles of method
No. of animals per sex per dose:
- group 1: 25 males/25 females
- group 2: 27 males/23 females
Positive control:
- not reported
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: No data

FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data



OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: No data

CLINICAL CHEMISTRY: No data

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, but methods not detailed
HISTOPATHOLOGY: Yes, but methods not detailed
Conclusions:
Under the conditions of the present carcinogenicity study Cyanuric chloride leads to the development of sarcomas after subcutaneous injection and application via diet. However, due to insufficient documentation and lacking control group animals the study is not adequate for evaluation.
Endpoint conclusion
Study duration:
chronic
Species:
rat
Quality of whole database:
Due to the insufficient documentation the study is not adequate for classification.

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral: In a carcinogenicity study (Pliss_1966) rats were exposed to Cyanuric chloride (10 mg in 0.5 mL sunflower oil/ once a week) by subcutaneous injection for 3.5 months followed by dietary exposure for 20.5 months (10 mg in 0.5 mL sunflower oil/ six times a week). In a second group rats applied the test substance (10 mg in 0.5 mL sunflower oil/six times a week) for 24 month by diet. Animals injected subcutaneous developed subcutaneous sarcomas near the application site. Animals exposed with Cyanuric chloride via diet developed fibroadenomas of the mammary gland, ileocaecal lymphosarcomas, a carinoma of the prostate and leiomyosarcoma in the uterus. However, no control group animals were involved in the study and the information on animal housing and treatment was very poor. Following the judgement of the reviewers of the SIDS Initial Assessment Report For SIAM 13, cyanuric chloride may induce tumours at the injection site associated with the development of necrosis due to its highly irritating/caustic properties. The other tumours found in both tests were considered incidental findings without relationship to the treatment with cyanuric chloride. Nevertheless due to the insufficient documentation the study is not adequate for classification.


Justification for selection of carcinogenicity via oral route endpoint:
A Carcinogenicity study after oral exposure represents the relevant exposure route.

Justification for classification or non-classification

Based on the available data Cyanuric chloride is not subject for C&L regarding repeated dose or specific target organ toxicity according to Directive 67/548/EEC and Regulation (EC) No 1272/2008.