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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study, but restricted for use for purposes of classification and labeling given the air concentration tested relative to the active ingredient.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
, restricted for use for purposes of classification and labeling given the air concentration tested relative to the active ingredient.
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
425-950-7
EC Name:
-
Cas Number:
187393-00-6
Molecular formula:
C38-H49-N3-O5
IUPAC Name:
5-[(2-ethylhexyl)oxy]-2-(4-{4-[(2-ethylhexyl)oxy]-2-hydroxyphenyl}-6-(4-methoxyphenyl)-1,3,5-triazin-2-yl)phenol
Details on test material:
- Name of test material (as cited in study report): FAT 70'884
- Composition of test material, percentage of components: 10% bemotrizinol in phenethyl benzoate

Test animals

Species:
rat
Strain:
other: HanRCC: WIST (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd; Wölferstrasse 4; 4414 Füllinsdorf; Switzerland
- Age at study initiation: 9 weeks (males); 10 weeks (females)
- Weight at study initiation: 253.4 g - 262.3 g (males); 210.4 g - 220.7 g (females)
- Fasting period before study: no
- Housing: Makrolon Type-IV wire cages with softwood bedding
- Diet (e.g. ad libitum): ad libitum except during 4-hr exposure period
- Water (e.g. ad libitum): ad libitum except during 4-hr exposure period
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20
- Humidity (%): 33 to 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 04-Apr-2007 (day of exposure) To: 18-Apr-2007 (day of necropsy)

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Remarks:
compressed, filtered
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass nebuliser (Lomir Biomedical, Inc.)
- Exposure chamber volume: not applicable
- Method of holding animals in test chamber: restraint tubes
- Source and rate of air: compressed, filtered; 18 liters per minute (equated to aerosol flow rate of 1 L/min/animal port)
- Method of particle size determination: Mercer 7-stage cascade impactor (Model 02-130, In-Tox Products, Inc.)
- Temperature, humidity, pressure in air chamber: >22 °C

TEST ATMOSPHERE
- Brief description of analytical method used: collection of aerosol on Millipore HVLP, polyvinylidinediflouride, 0.45 µm pore size filters in 47 mm stainless sampling cassettes. Analysis by gravimetric and HPLC.

- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.05 µm / 2.66 to 2.10 µm / 2.62
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
6.492 mg/L (SD +- 0.237 mg/L, n=4) based on the analytical measured concentrations of FAT 70'884 consisting of 10% bemotrizinol in phenethyl benzoate. This equates to approximately 0.649 mg/L of bemotrizinol.
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 and weighing: Daily observation, with weighing on days 4, 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology (macroscopic)
Statistics:
None, given lack of findings.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC0
Effect level:
> 0.649 mg/L air (analytical)
Based on:
act. ingr.
Remarks:
Bemotrizinol
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
other: LOAEC
Effect level:
0.649 mg/L air (analytical)
Based on:
act. ingr.
Exp. duration:
4 h
Mortality:
None
Clinical signs:
other: Because there was no vehicle control group and because there are no inhalation studies on the vehicle used, the clinical signs presented here cannot be attributed to the active ingredient. All animals: salivation (slight to moderate in degree), tachypnea
Body weight:
There were no adverse effects on body weight gain of male animals and three of five female animals (male nos. 1 to 5, and female nos. 6, 8 and 9) during the 15-day observation period. Marginal body weight loss or retardation in body weight gain were occasionally seen in the other two female animals, i.e. female no. 7 (+0.4% weight gain from test day 1 to 4 and –0.4% weight loss from test day 8 to 15) and female no. 10 (+0.8% weight gain from test day 4 to 8). In view of the concomitant clinical signs noted in all animals, a relationship of these minor effects on female body weight to the treatment with the test item could not be entirely discounted, although slight physical stress, e.g. during restraint in the exposure tubes, may have contributed to these effects.
Gross pathology:
No macroscopic findings.

Any other information on results incl. tables

Body Weights (grams)

Group

Animal
No.

Sex

Test Day 1
(Treatment)

Test Day 4

Test Day 8

Test Day 15

1

(6.492 mg/L)

1

M

255.2

264.9

276.0

306.7

2

M

262.3

268.8

290.5

325.0

3

M

253.4

259.6

266.8

290.0

4

M

257.7

266.8

280.9

311.9

Mean

257.4

265.6

278.9

308.3

+S.D.

3.4

3.7

8.6

12.6

N

5

5

5

5

 *Group 1 (10% active ingredient): 0.649 mg/L (active ingredient)

Group

Animal
No.

Sex

Test Day 1
(Treatment)

Test Day 4

Test Day 8

Test Day 15

1

(6.492 mg/L)

6

F

220.7

231.5

235.7

242.4

7

F

213.2

214.1

216.9

216.0

8

F

210.4

214.2

218.7

225.6

9

F

217.9

224.0

226.6

239.6

Mean

216.2

221.1

224.3

231.4

+S.D.

4.3

7.3

7.4

10.7

N

5

5

5

5

*Group 1 (10% active ingredient): 0.649 mg/L (active ingredient)

Applicant's summary and conclusion

Conclusions:
The LC50 of FAT 70’884 [undiluted formulation comprising approximately 10% FAT 70’884 in X-Tend (phenethyl benzoate)] obtained in this study was estimated to be >6.492 mg/L air (chemically determined mean aerosol concentration), which equates to >0.649 mg/L for the active ingredient. There was no indication of relevant sex-related differences in toxicity of the test item.