Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
GLP compliance:
yes (incl. certificate)
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Cyanuric acid
- Physical state: White powder
- Analytical purity: 99%
- Composition of test material, percentage of components: Cyanuric acid : 98.55%, Ameline:0.03, Amelide: 0.22 and Iron 20.0 PPM
- Purity test date: 20/05/2009
- Lot/batch No.: Lot # 3209E3
- Stability under test conditions: Exp: May 2011 per provided information
- Storage condition of test material: Room temperature
- Other: Date and Quantity recieved: 5 Oct 09; 3010.9 (GW)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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

Administration / exposure

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

Results and discussion

Effect levels
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:
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.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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