Cyanuric acid

Endpoint summary

Description of key information

Acute oral, dermal and inhalation studies have been performed with cyanuric acid. Experimental data showed no evidence of acute toxicity to cyanuric acid.

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:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, MA. USA.
- Weight at study initiation: Males: 249 – 276 g; females: 181 – 202 g

Route of administration:

oral: gavage

Vehicle:

other: tap water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 397 mg/mL
- Amount of vehicle (if gavage): males ~0.7 ml; females ~0.5 ml

DOSAGE PREPARATION: The test material was ground into a powder and suspended in tap water at a concentration of 397 mg/ml.

Doses:

5000 mg/kg bw by gavage

No. of animals per sex per dose:

10 (5 male and 5 female)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations 3 times within the first 8 hours and twice daily thereafter. Body weights recorded on day 0, 7 and 14.
- Necropsy of survivors performed: yes(day 15)

Statistics:

None applied

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortalities occured

Clinical signs:

other: Clinical abnormalities were observed in 2 animals, one of each sex, including lack of faecal material in both animals and sedation, ataxia and piloerection, porphyrin around the nose . With the exception of body weight loss these effects subsided by the 4

Gross pathology:

No effects noted

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Cyanuric acid is not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

GLP compliance:

yes (incl. QA statement)

Remarks:

USEPA FIFRA 40 CFR 160, USEPA TSCA 40 CFR 792, OECD principle of GLP, Annex 2, C(98) 17 and Japan Ministry of Agriculture Forestry & Fisheries, Notification No.11 Nousan 6283.

Test type:

fixed concentration procedure

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Texas Animal Specialties, Humble, TX
- Age at study initiation: ~ 2 months old
- Weight at study initiation: Male: 250-254g: Female: 177-189g
- Fasting period before study: Not reported
- Housing: Suspended, wire bottom, stainless steel cage. One animal per cage
- Diet : PMI Lab Diet Formula # 5008, was available ad libitum except during the exposure period
- Water: Municipal water supply analysed by TCEQ Water Ultilities Division; from automatic water system, was available ad libitum except during the exposure period
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23°c
- Humidity (%): 32-88%
- Air changes (per hr): 10-12
- Photoperiod (hrs dark / hrs light): 12-hour light/ dark cycle

IN-LIFE DATES: From:8 Sep 09 To: 18 Nov 09

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:Nose-only stainless steel, dynamic flow inhalation chamber. The body of the chamber has 25 ports in 5 rows. Polycarbonates tubes were inserted into 10 designated individual ports. The test substance was introduced through the opening in the top of the chamber. The bottom section has a corresponding air outlet and a drain valve for cleaning the chamber.
- Exposure chamber volume: 500 L
- Method of holding animals in test chamber: The individual polycarbonate tubes were tapered at one end to fit the shape of the animal's head and the back portion was sealed with a rubber cap. The tubes containing the animals fit tightly into the ports, and were sealed with O-rings.
- Source and rate of air: Air flow into the chamber was maintained through the use of a calibrated orifice plate at a rate of 22.4 air changes per hour.
- Method of conditioning air:Air flow was recorded at 30 minutes intervals during the exposure period, and was sufficient to ensure an oxygen content of at least 19% of the exposure atmosphere.
- System of generating particulates/aerosols: The aerosol was generated by a Venturi Aspirator which aspirated the test substance from a coupled motorised revolving disc delivery system, then sprayed the resulting aerosol directly into the exposure chamber.
- Temperature, humidity, pressure in air chamber: Temperature and humidity were recorded at 30 minutes intervals during the exposure period from an Extech Instruments humidity/temperature pen inserted in an unused port of the exposure chamber.


TEST ATMOSPHERE
- Brief description of analytical method used: The concentration of the test substance in the exposure atmosphere (taken fromt he breathing zone of the animals) was determined gravimetrically twice per hour and nominally at the end of the exposure. The gravimetric concentration was determined by passing a known volume of exposure air through a pre-weighed filter and dividing the amount of test substance deposited on the filter by the volume of air that passed through the filter. The nominal concentration was determined by divding the loss in weight of the test substance after the exposure by the total volume of air that passed through the chamber.
- Samples taken from breathing zone: yes

VEHICLE
Not applicable

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Particle size, taken from the breathing zone of the animals, was determined twice during the exposure, using a cascade impactor, at a rate of 7.9 L/minute for a duration of 18 seconds. The MMAS and particle size distributions were calculated from these data by a computer program utilising probit analysis (See table 4 & 5).


CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Not reported

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Determined gravimetricaaly twice per hour and nominally at the end of the exposure

Duration of exposure:

4 h

Concentrations:

5.25 mg/L

No. of animals per sex per dose:

5 males & 5 females (nulliparous & non-pregnant)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for mortality and signs of pharmacologic and/or toxicologic effects were made frequently on the day of exposure and at least once daily therafter for 14 days (Day 0 is day of exposure). Individual body weights were recorded just prior to the inhalation exposure and on Days 7 and 14.
- Necropsy of survivors performed: Yes

Statistics:

In order to calculate a mean exposure, the mean value theorem of calculus was used to properly weight the concentration, since the concentrations could not be measured continuously. This method weights concentrations based on the time span of each concentration. A concentration can be calculated for each minutes, which better represents the exposure concentration recieved by each animals

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.25 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There was no mortality during the study.

Clinical signs:

other: Clinical signs are presented in Table 8. Prominent in-life observations included activity decrease and piloerection. Animals were asymptomatic by Day 5.

Body weight:

Individual body weights are presented in Table 7. Body weight gain was unaffected by the administration of the test substance.

Gross pathology:

Not applicable

Other findings:

- Other observations: Necropsy findings : Individual necropsy finding are presented in table 7. The gross necropsy conducted on each animal at termination of the study revealed no observable abnormalities.

Table 7– Body weights, Time of Death, and Gross Necropsy

 

Animal Number	Body weights (g)			Time of Death*	Gross Necropsy Findings
	Day 0	Day 7	Final
31-M	252	281	309	Day 14	NOA
32-M	250	279	319	Day 14	NOA
33-M	252	285	320	Day 14	NOA
34-M	254	285	318	Day 14	NOA
35-M	250	274	294	Day 14	NOA
36-F	180	190	201	Day 14	NOA
37-F	179	188	201	Day 14	NOA
38-F	184	200	215	Day 14	NOA
39-F	177	191	211	Day 14	NOA
40-F	189	209	234	Day 14	NOA

* - Day of dosing considered Day 0; Day 14 is terminal sacrifice. M-Male; F-Female; NOA – No observable Abnormalities.

 

Table 8:Pharmacologic and/or Toxicologic Signs

 

	Time After Exposure Begins
	Hours					Days
Reaction and Severity	0.5	1.0	2.5	4.5	6.0	1	2	3	4	5	6	7	8	9	10	11	12	13	14
Males
Piloerection (s)	0	0	0	5	5	5	5	0	0	0	0	0	0	0	0	0	0	0	0
Activity decrease (v-s)	0	0	0	5	5	5	5	5	5	0	0	0	0	0	0	0	0	0	0
Females
Piloerection (s)	0	0	0	5	5	5	5	0	0	0	0	0	0	0	0	0	0	0	0
Activity decrease (v-s)	0	0	0	5	5	5	5	5	5	0	0	0	0	0	0	0	0	0	0

v- Very slight, s- slight; m-moderate; e- extreme. Note: Digits indicate number of animals exhibiting reaction.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

There were no mortalities during the study. Clinical signs included activity decrease and piloerection, which were no longer evident by Day 5. Body weights were unaffected by exposure. The gross necropsy revealed no observable abnormalities. As indicated by the data, the acute inhalation LC50 for Cyanuric Acid is greater than 5.25 mg/L

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 250 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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Isaac’s Farm, Litchfield, Illinois, USA
- Age at study initiation: Young adults
- Weight at study initiation: 2.51 – 2.79 kg
- Diet (e.g. ad libitum): provided ad libitum
- Water (e.g. ad libitum): provided ad libitum

Type of coverage:

occlusive

Vehicle:

physiological saline

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal surface
- % coverage: 10%
- Type of wrap if used: Latex rubber


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test material wiped from animal
- Time after start of exposure: ~ 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg

Duration of exposure:

~ 24 hours

Doses:

5000 mg/kg

No. of animals per sex per dose:

10

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations made 3 times during the first 8 hours of the study and twice daily thereafter. Body weights recorded on day 0, 7 and 14.
- Necropsy of survivors performed: yes (day 15)

Statistics:

None applied

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortalities occurred.

Clinical signs:

other: No clinical abnormalities were observed.

Gross pathology:

Pale kidneys in one male, pale, mottled kidneys in one female, tapeworm cysts in one female. None of the effects were attributed to toxicity of the test material.

Males: No clinical abnormalities were observed. No necropsy findings were attributed to toxicity of the test material. One animal had pale kidneys.

Females: No clinical abnormalities were observed. No necropsy findings were attributed to toxicity of the test material. One animal had pale mottled kidneys and another had tapeworm cysts in the mesentery.

Interpretation of results:

not classified

Remarks:

Migrated information

Conclusions:

LD50 (dermal, rabbit) > 5000 mg/kg

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Additional information

Acute toxicity: Oral route

In an acute oral study (Branch 1981) 5 male and 5 female rats were administered 5000 mg/kg bw CYA and observed for 14 days. No mortalities were observed in either sex. The LD50 was determined to be > 5000 mg/kg bw.

Acute toxicity: Inhalation route

In an acute inhalation limit test (Younger 2009) 5 male and 5 female rats were exposed nose only to 5.25 mg/L cyanuric acid and observed for 14 days. No mortalities were observed in the study and the LC50 was > 5.25 mg/L.

Acute toxicity: Dermal toxicity

In an acute dermal toxicity study (Branch 1981) 5000 mg/kg CYA was applied to the shaved and abraded dorsal surface of 5 male and 5 female New Zealand White rabbits. After 24 h the occlusive dressing was removed and observations were made up to 14 days following exposure.

No deaths were observed in either sex therefore the LD50 was considered to be > 5000 mg/kg

Justification for classification or non-classification

The LD50 values exceeded the limit of classification in the oral, dermal and inhalation studies and therefore CYA need not be classified.