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

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Non-GLP and some deviations from OECD guidelines.

Data source

Reference

Reference Type:

publication

Title:

Cyanuric chloride (2,4,6-trichloro-1,3,5-triazine): 90-days repeated exposure inhalation toxicity study in rats

Author:

Jedrychowski R.

Year:

1994

Bibliographic source:

The Nofer intitute of occupational medicine, Lodz, Poland

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

Deviations:

yes

Remarks:

The list of examined organs is not fully in accordance with OECD 413; Air changes were below OECD recommendations (10-12/h rec.)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EEC 84/449/EEC.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

203-614-9

EC Name:

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

Cas Number:

108-77-0

Molecular formula:

C3Cl3N3

IUPAC Name:

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

Details on test material:

purity >95%.

Test animals

Species:

rat

Strain:

other: DAK Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

6-8 weeks old
weighing 145-190 g (males) and 120-160 g (females)

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Details on inhalation exposure:

Air changes 7.2/hour.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Analyses of test substance: 0.012, 0.051 and 0.241 mg/m3 for nominal concentrations of 0.01, 0.05 and 0.25 mg/m3 resp.

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

5 days per week, 6 hours per day

Doses / concentrations

Remarks:

Doses / Concentrations:
0.01, 0.05 and 0.25 mg/m3
Basis:

No. of animals per sex per dose:

10/sex/treatment

Control animals:

other: air-exposed controls

Examinations

Observations and examinations performed and frequency:

General:
Mortality daily; Clinical signs daily before and after exposure; Body weight at study initiation and weekly thereafter; Food consumption.
Clinical pathology:
Blood chemistry at end of treatment period: aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), sorbitol dehydrogenase (SDH), γ-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), ornithine carbamoyltransferase (OCT), total billirubin, total protein, albumin, blood urea nitrogen (BUN), glucose, natrium, potassium, chloride, inorganic phosphate and calcium; Hematology at end of treatment period: red blood cell count (RBC), white blood cell count (WBC), hemoglobin, hematocrit value, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), platelet count, percentage of reticulocytes and differential leukocyte count.
Necropsy:
Macroscopy: external appearance, body orifices, body cavities and their contents; Organ weights: brain, lungs, heart, liver, kidneys, adrenals, thymus, ovaries/testes and spleen; Histopathology: nose, trachea, lungs, heart, liver, kidneys, adrenal gland, spleen, stomach, duodenum, pancreas, small and large intestine, testes and epididymides/uterus and ovaries, brain, cerebellum, (para)thyroid, salivary gland, thymus, oesophagus, mediastinal lymph nodes, urinary bladder, prostate gland, seminal vesicles, mammary glands, lacrimal glands, eye with optic nerve, skin, femur muscles, spinal cord and spinal medulla.
Analysis of test substance:
Analysis of test substance concentrations at least every two hours by gas chromatography.

Statistics:

Bartlett’s test for homogeneity of variance, ANOVA, Dunnett’s test, Kruskal-Wallis test, Dunn’s summed rank test, Jonkheere’s test for trend and ANCOVA.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

Phosphate, Glucose

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Testes, Adrenals, Heart

Details on results:

Macroscopy: Consisting an of increased amount of yellowish exudate in the nose of males (6/10), and congested lungs. In control and other treatment groups incidence of exudate was 0-1/10 males and 2/10 females

Microscopy:
Nose : Presence of PMN in the lumen
Trachea (tracheitis): Incidence 5/10. Also findings in females. Increased incidence at all treatment groups and controls (1-3/10)
Bronchi: Higher incidence of increased cellularity of BALT in high dose males compared to control and other groups.
Lungs: Congestion and/or foamy macrophages in alveoli and/or interstitial lymphocytic infiltrations; effects in females appeared less frequently.
Small intestine: Proliferation of lymphatic tissue
Liver: Fast red (+) droplets in hepatocytes
Testes/epidymides/prostate/seminal vesicles: No treatment related effects
Uterus/ovaries: No treatment related effects

Effect levels

1

Dose descriptor:

NOAEC

Remarks:

for systemic toxicity

Effect level:

0.25 mg/m³ air

2

Dose descriptor:

NOAEC

Remarks:

for local effects

Effect level:

0.05 mg/m³ air

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Analyses of test substance: 0.012, 0.051 and 0.241 mg/m3 for nominal concentrations of 0.01, 0.05 and 0.25 mg/m3 resp.

Applicant's summary and conclusion

Conclusions:

NOAEC = 0.25 mg/m3 for systemic toxicity.
NOAEC = 0.05 mg/m3 for local effects.

Executive summary:

A 90-days repeated exposure inhalation toxicity study for Cyanuric chloride was carried out in rats. The number of animals was 10/sex/treatment. Doses of 0.01, 0.05 and 0.25 mg/m3 were studied, as well as air-exposed controls, according to a whole-body inhalation exposure system. The exposure period was 13 weeks. Mortality, clinical signs, body weight, food compsumption, clinical pathology and necropsy were observed. The test substance concentrations was also analysed.

The results were as follows:
NOAEC = 0.25 mg/m3for systemic toxicity.

NOAEC = 0.05 mg/m3for local effects.