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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04 Dec - 23 Dec 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF), Testing Guidelines for Toxicology Studies, 59 NohSan No. 4200, January 28 1985
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
446-630-3
EC Name:
-
Cas Number:
181587-01-9
Molecular formula:
C13H9Cl2F3N4OS
IUPAC Name:
5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(ethanesulfinyl)-1H-pyrazole-3-carbonitrile
Details on test material:
- Name of test material (as cited in study report): RPA 107382
- Analytical purity: 93%
- Lot/batch No.: CDR 9706

Test animals

Species:
rat
Strain:
other: Sprague-Dawley Crl : CD® BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Ltd, Margate, United Kingdom
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 292-313 g (males) and 226-244 g (females)
- Housing: rats were housed in groups of five by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes (Datesand Ltd., Cheshire, UK).
- Diet: Rat and Mouse Expanded Diet No. 1 (Special Diets Services Limited, Witham, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical exposure chamber
- Exposure chamber volume: 30 L
- Method of holding animals in test chamber: each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber 'O' ring.
- Source and rate of air: filtered air at 20 L/min
- System of generating particulates: a dust atmosphere was produced from the test material using a 'Wright's Dust Feed' mechanism located at the top of the exposure chamber and driven by a variable speed motor. The dust feed was connected to a metered compressed air supply.
- Method of particle size determination: the particle size was determined four times during the exposure period using a Marple Cascade Impactor (Schaefer Instruments Ltd, UK). The collection substrates and backup glass fibre filter of the Marple Cascade Impactor were weighed before and after sampling and the weight of test material, collected at each stage, calculated by difference.
- Temperature, humidity, pressure in air chamber: 20-21 °C, 48-54%, negative pressure (value not reported)

TEST ATMOSPHERE
- Brief description of analytical method used: the chamber concentration was estimated at regular intervals during the exposure period. The gravimetric method used, employed glass fibre filters (Gelman type A/E 25 mm) placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals’ breathing zone. Exposure chamber air was drawn through the filter at a measured rate using a vacuum pump for a suitable time period. Each filter was weighed before and after sampling in order to calculate the weight of collected test material. The difference in the two weights divided by the volume of atmosphere sampled was the chamber concentration.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- Particle size distribution: see Table 1 under “Any other information on materials and methods incl. tables"
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 3.6 µm / 0.28 µm

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: a single female rat was exposed to an atmosphere of the test material at a concentration of 2.8 mg/L for 2 h. Since no severe effects were observed after exposure, it was considered acceptable to perform the study at the limit test concentration of 5 mg/L.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric
Duration of exposure:
4 h
Concentrations:
Exposure chamber atmosphere concentration:
5 mg/L (nominal concentration)
5.21 ± 0.86 mg/L (analytical concentration)

Nominal chamber concentration: 60.1 mg/L
No. of animals per sex per dose:
5
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to treatment on the day of exposure and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: the respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.
Statistics:
Mean values and standard deviations of the achieved atmosphere concentration were calculated.

Results and discussion

Preliminary study:
A single female rat was exposed to an atmosphere of the test material at a concentration of 2.8 mg/L for 2 h. Since no severe effects were observed after exposure, it was considered acceptable to perform the study at the limit test concentration of 5 mg/L.
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.21 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred during the study period.
Clinical signs:
other: Abnormalities noted during the study included wet fur, hunched posture, piloerection, lethargy, ptosis, red/brown staining around the eyes and snout and on the head and isolated incidents of decreased respiratory rate, ataxia, occasional body tremors and
Body weight:
Normal body weight gain was noted during the study apart from one female, which showed a body weight loss of 8 g during Week 1.
Gross pathology:
Necropsy revealed no substance-related findings. Individual findings are given in Table 3 under "Any other information on results incl. tables".

Any other information on results incl. tables

Table 3. Table for acute inhalation toxicity.

Target concentration
[mg/L air]

Number of animals with clinical signs*

Mortality (%)

Time of death

Duration of clinical signs

Gross pathology

Males

5.21

0/5/5

0

---

1 h - Day 1

4/5: dark foci on lungs

Females

5.21

0/5/5

0

---

2 h - 1 h post exposure

no abnormalities

LC50 > 5.21 mg/L air

* first number = number of dead animals

second number = number of animals with clinical signs

third number = number of animals used

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified