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

Endpoint summary

Description of key information

- Oral:LD50: 333.6 mg/kg bw (293.4 — 373.8 95% CL)  for the rat (OECD TG 401); study 93-0170-FGT
- Dermal: LD50: > 2000 mg/kg bw  for the rabbit (limit test, OECD TG 402); study 88-0023-DKT
- Inhalation:LC50: 170 (137 — 213; 95 % CL) mg/m³ for the male and female rat (OECD TG 403); study 92-0177-FKT

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions (e.g. non GLP study, report finalized 5 years after study conduction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

as at 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

as at 1984,

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: in house breeding colony
- Age at study initiation: 6-10 (males) and 8-10 weeks (females)
- Weight at study initiation: 215-400 g (males) and 190 - 250 g (females)
- Fasting period before study: 16 h
- Housing: stainless steel cages with grating floor, 1 animal per cage
- Diet: standard diet ad libitum
- Water: ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 22.5
- Humidity (%): 50 -65
- Photoperiod (hrs dark / hrs light): 6 a.m - 6 p.m. artificial lighting, 6 p.m.- 6 a.m. natural light dark cycle

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10 % (w/v)
- Amount of vehicle: 2.4, 3.0, 3.25, 3.75, 4.70 ml/kg bw


MAXIMUM DOSE VOLUME APPLIED: 470 mg/kg bw

Doses:

- 240, 300, 325, 375, 470 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: first 4 h after administration, then daily; Weighing: day 0 and day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy, histopathology of stomach and liver

Statistics:

- probit analysis

Sex:

male

Dose descriptor:

LD50

Effect level:

315 mg/kg bw

95% CL:

303 - 357

Sex:

female

Dose descriptor:

LD50

Effect level:

356 mg/kg bw

95% CL:

317 - 426

Remarks on result:

other: error in calculation (report)

Sex:

female

Dose descriptor:

LD50

Effect level:

327 mg/kg bw

Remarks on result:

other: as recalculated by reviewer of the SIDS dossier on CAS 108-77-0

Sex:

male/female

Dose descriptor:

LD50

Effect level:

333.6 mg/kg bw

95% CL:

293.4 - 373.8

Remarks on result:

other: recalculated by the reviewer using the probit analysis using AnalystSoft, BioStat, statistische Analyse. Version 2008. (http://www.analystsoft.com/de/products/biostat/)

Mortality:

Mortality was observed between 24h post application and day 2
males: 240 mg/kg bw 0/5
300 mg/kg bw 0/5
325 mg/kg bw 4/5
375 mg/kg bw 5/5
470 mg/kg bw 5/5
females: 240 mg/kg bw 0/5
300 mg/kg bw 0/5
325 mg/kg bw 3/5
375 mg/kg bw 2/5
470 mg/kg bw 5/5

Clinical signs:

other: - hypokinesia, somnolency, decreased muscle tone, loss of righting reflex, loss of pain reflex, loss of corneal reflex, piloerection, accelerated respiration and decreased body temperature

Gross pathology:

- Macroscopic findings noted at necropsy included: stomach lesions such as reddening, inflation,
reddened gastric mucous membrane, thickened fundus, fusion with peritoneum/liver/spleen and reddening
of the intestinal mucosa

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

Under the conditions of this acute oral toxicity study a combined LD50 for both sexes of 333.6 mg/Kg bw (293.4 — 373.8 95% CL) was deduced in rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

333.6 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991-08-19 to 1991-09-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted: 1981-02-02

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Versuchstierzucht Winkelmann, Borchen, Kreis Paderborn, Germany
- Age at study initiation: 2 to 3 months
- Weight at study initiation: 170 - 210 g
- Housing: 5 animals per cage (Makrolon type III)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C +- 2
- Humidity (%): ca. 50 %
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: inhalation chamber (TSE Labortechnik, Bad Homburg)
- Exposure chamber volume: 20 L
- Method of conditioning air: VIA-Drucklufttrockner
- System of generating particulates/aerosols: Wright-Dust-Feeder + self constructed metal cyclone as particle precipitator (used at higher doses)
- Method of particle size determination: Berner- or Andersen-cascade impactor
- Treatment of exhaust air: aerosol filter (absorbent cotton) and + combustor
- Temperature, humidity, pressure in air chamber: 24 °C, 25 %


TEST ATMOSPHERE
- Brief description of analytical method used: GC
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: see "any other information on materials and methods including tables"
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): see "any other information on materials and methods including tables"
- stability of test atmosphere: total carbon analyzer (Ratfisch RS 55)

Analytical verification of test atmosphere concentrations:

yes

Remarks:

see (I)

Duration of exposure:

4 h

Concentrations:

- 37.6, 150.6, 177.3, 289.3, 449.1 mg/m³, (respective contribution to the concentrations by particles: 0.0, 2.3, 18.8, 44.7, 165.5 mg/m³)

No. of animals per sex per dose:

- 5

Control animals:

other: animals of the study were compared to periodically tested animals (once per 3 month, clean air)

Details on study design:

- Duration of observation period following administration: 28 days
- Frequency of observations: several times on day 0, daily thereafter; frequency of weighing: day 1, day 3, day 7, day 14 and day 28
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, gross necropsy

Statistics:

Maximum-Likelihood where applicable

Sex:

male/female

Dose descriptor:

LC50

Effect level:

170 mg/m³ air

Based on:

test mat.

95% CL:

137 - 213

Exp. duration:

4 h

Sex:

male

Dose descriptor:

LC50

Effect level:

150 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: this value was approximated, as the slope of dose response curve was very steep

Sex:

female

Dose descriptor:

LC50

Effect level:

201 mg/m³ air

Based on:

test mat.

95% CL:

157.7 - 257.9

Exp. duration:

4 h

Mortality:

- see table on mortality, body weight decrease, clinical signs and necroscopy
- mortality occurred between day 1 and day 14 post application

Clinical signs:

other: - clinical signs reported for days 0,1,2,3,7,14,21,28 - see table on mortality, body weight decrease, clinical signs and necroscopy

Body weight:

- see table on mortality, body weight decrease, clinical signs and necroscopy

Gross pathology:

- see table on mortality, body weight decrease, clinical signs and necroscopy

Other findings:

- reflexes: see table on mortality, body weight decrease, clinical signs and necroscopy

Interpretation of results:

Category 2 based on GHS criteria

Remarks:

Migrated information

Conclusions:

Under the conditions of this acute inhalation toxicity study a combined LC50 for both sexes of 170 mg/m³ air (137 — 213, 95% CL) and a LD50 for males of 150 mg/m³ air were deduced for rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

170 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-07-12 to 1988-07-26

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: - Guideline study with acceptable restrictions (e.g. size of application area not reported)

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

as at 1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

as at 1984

Deviations:

no

GLP compliance:

no

Remarks:

study performed prior to implementation of GLP

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

other: Russian White (albino)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Asta Pharma AG, D-4800 Bielefeld 14
- Age at study initiation: 18 - 24 weeks (males) 22 - 24 weeks (females)
- Weight at study initiation: 2.19 - 2.31 kg (males), 2.49 - 2.65 kg (females)
- Fasting period before study: food withheld at day of application start
- Housing: 1 per cage (stainless steel cages model ASTA, ASTA Pharma AG, D-4800 Bielefeld 14)
- Diet: not reported
- Water: ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 22
- Humidity (%): 45 - 65
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

paraffin oil

Details on dermal exposure:

TEST SITE
- Area of exposure: between shoulder and os sacrum
- % coverage: not reported
- Type of wrap if used: not reported

REMOVAL OF TEST SUBSTANCE
- Washing: with water
- Time after start of exposure: 24 h

TEST MATERIAL
- Constant volume or concentration used: yes
- For solids, paste formed: yes, 1g of test substance moistured in 0.567 ml paraffin oil (vehicle)

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 4-8 h post application, daily thereafter; Frequency of weighing: day 1, day 7 and day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology of skin of the application site, other: gross necroscopy

Statistics:

- not applicable as no deaths occurred during the test procedure

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

- no deaths occurred during the test period

Clinical signs:

other: - No systemic toxicity. At the application site: red/brown staining, swelling and hardening - Staining and swelling reversed between day 8 and day 13

Gross pathology:

- no lesions in internal organs were found
- Pathology findings in the skin at the application site included: acanthosis, hyperkeratosis, subepidermal mixed inflammatory cell infiltration, erosion, superficial exudate, subepidermal haemorrhages, ulceration, epidermal proliferation, secondary built hairfollicle cysts, epidermal necrosis and slight pustule forming

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

Under the conditions of this acute dermal toxicity study a combined LD50 for both sexes of > 2000 mg/Kg was deduced in rabbits.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

- oral toxicity:

In an acute oral toxicity key study (93 -0170 -DKT) wistar rats (5 per sex per dose) of both sexes were treated with Cyanuric chloride in polyethylene glycol in a single dose of 240, 300, 325, 375 and 470 mg/kg bw/d via gavage. Animals were observed for clinical signs, weight development and overt signs of toxicity for 14 days.

During the first week post dosing animals showed the following clinical signs: hypokinesia, somnolency, decreased muscle tone, loss of righting reflex, loss of pain reflex, loss of corneal reflex, piloerection, accelerated respiration and decreased body temperature. Macroscopic findings noted at necropsy included: stomach lesions such as reddening, inflation, reddened gastric mucous membrane, thickened fundus, fusion with peritoneum/liver/spleen and reddening of the intestinal mucosa. Body weights were comparable in the two lowest dose groups (240 and 300 mg/kg bw). A combined LD50 for both sexes of 333.6 mg/kg bw (293.4 — 373.8 95% CL) was deduced under the test conditions. Based on the determined LD 50 value the substance has to be classified as Category IV (harmful if swallowed) 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 10 supporting acute oral toxicity studies in different species (rats, mice, dogs and rabbits) the LD50 value was in the range of 1143 – 340 mg/kg bw/d.

In two acute oral toxicity studies in rats the LD50 value of 208 mg/kg bw and 200 mg/kg bw was reported. However, at necropsy indications for aspiration of the substance could be found for both studies and therefore the derived LD50 are questionable as the toxicity to the lungs might very well be the cause of death. Due to that the studies are marked as disregarded.

In one acute oral toxicity study an LD50 between 930 mg/kg bw/d was deduced in rats. However, due to insufficient documentation the study was marked as disregarded.

- inhalation toxicity:

In an acute inhalation toxicity key study (92-0177-FGT) rats were treated once with cyanuric chloride via inhalation for 4h and observed for clinical signs, weight development and overt signs of toxicity for 28 d post administration. The animals were exposed to both vapour and dust of the test substance. Concentrations mentioned are the sum of both fractions (concentrations: 37.6, 150.6, 177.3, 289.3, 449.1 mg/m³). A combined LC50 for both sexes of 170 mg/m³ air (137 — 213, 95% CL) and a LD50 for males of 150 mg/m³ air were deduced under the test conditions. During the first week post dosing animals showed the following clinical signs: laboured respiration, ruffled fur, rhinorrhea, reduced motility in the low dose group, in addition at 150.6 mg/m³: dyspnea, atony, bloody rhinarium, periorbital blood incrustation, cyanosis and cachexia and at the three highest concentrations in addition: stiff gait and prostration. Body weights were reduced dose dependently in the survivors during the first 2 weeks post administration. The dose-response correlation in fatalities for females was not continuous, in general males appear to be more sensitive. Based on the determined LC50 value the substance was classified as Category II (toxic if inhaled, vapour, mist) according to UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).

 

In four supporting acute inhalation toxicity studies in rats the LC50 was in the range of < 152 mg/m³ air to 60 mg/m³ air indicating a classification of Category II (toxic if inhaled, vapour, mist).

- dermal toxicity:

In the acute dermal toxicity key study (88-0023-DKT) three rabbits were treated (concentration: 2000 mg/kg bw) once with Cyanuric chloride in paraffin oil via occlusive dermal exposure for 24h and observed for clinical signs, weight development and overt signs of toxicity for 14 d post administration. No deaths occurred during the study period. During the first week post dosing animals showed the following clinical signs: red/brown staining, swelling and hardening at the application site, staining and swelling reversed between day 8 and day 13. At gross necroscopy no lesions in internal organs were found. Pathology findings in the skin at the application site included: acanthosis, hyperkeratosis, subepidermal mixed inflammatory cell infiltration, erosion, superficial exudate, subepidermal haemorrhages, ulceration, epidermal proliferation, secondary builded hairfollicle cysts, epidermal necrosis and slight pustule forming. As the test substance is corrosive and as no deaths occurred in either sex (3 animals each) at the limit dose, no further animals were tested. Body weights were slightly reduced during the whole observation period. No systemic toxicity was demonstrated. A combined LD50 for both sexes of > 2000 mg/kg was deduced under the test conditions. Based on the determined LD50 value no classification is necessary according to UN GHS and under CLP in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).

Two acute dermal toxicity studies showed a LD50 of > 5000 mg/kg bw (5 male rats) and > 1000 mg/kg bw (5 male, 5 female animals), respectively. In one study Cyanuric chloride must not be subjected to C&L. In the second study no clear classification was possible because the highest concentration tested was 1000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Most reliable study.

Justification for selection of acute toxicity – inhalation endpoint
Most reliable study.

Justification for selection of acute toxicity – dermal endpoint
Most reliable study.

Justification for classification or non-classification

Based on the results of the acute oral toxicity study, the substance should be classified as Cat. 4 H302 (Warning, Harmful if swallowed) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.

 

Based on the results of the acute inhalation toxicity study, the substance should be classified as Cat. 2 H330 (Danger, Fatal if inhaled (mist)) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.

Based on the results of the acute dermal toxicity study, the substance is not subject to C&L according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008 and according to UN GHS.