spirodiclofen (ISO);3-(2,4-dichlorophenyl)-2-oxo-1-oxaspiro[4.5]dec-3-en-4-yl 2,2-dimethylbutyrate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 June 1997 - 23 June 1997 (in-life)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The MMAD at the highest concentration was larger than specified by the test guideline, resulting in a slightly low proportion of particles of respirable size. However, this is stated to be a consequence of attempts to reach the limit concentration.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EEC 92/69/EEC

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

Principles of method if other than guideline:

The MMAD at the highest concentration was larger than specified by the test guideline, resulting in a relatively low proportion of particles of respirable size. However, this is stated to be a consequence of attempts to reach the limit concentration.

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(3,5-Dichlorophenyl)-2-oxo-1-oxaspiro[4.5]dec-3-en-4-yl 2,2-dimethylbutanoate

Cas Number:

148477-71-8

Molecular formula:

C21H24Cl2O4

IUPAC Name:

3-(3,5-Dichlorophenyl)-2-oxo-1-oxaspiro[4.5]dec-3-en-4-yl 2,2-dimethylbutanoate

Test material form:

aerosol dispenser: not specified

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan-Winkelmann
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 2-3 months
- Fasting period before study: no
- Housing: single
- Diet: ad libitum except during exposure
- Water: ad libitum except during exposure
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): ~50
- Air changes (per hr): ~10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 4 June 1997 To: 23 June 1997

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Remark on MMAD/GSD:

The MMAD at the highest concentration was larger than specified by the test guideline, resulting in a relatively low proprtion of particles of respirable size. However, this is stated to be a consenquence of attempts to reach the limit concentration.

Details on inhalation exposure:

Test material was undiluted, single administration, 4 hours, inhalation dynamic spraying, directed flow nose only. 520-5030 mg/m³ air, aerosol generation conditions: 28 L air /minute.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The test-substance concentration was determined by gravimetric analysis. The particle-size distribution was analyzed using a critical orifice cascade impactor.

Duration of exposure:

4 h

Remarks on duration:

Standard exposure period according to the test guideline

Concentrations:

520, 5030 mg/m³ air (measured)

No. of animals per sex per dose:

5/sex

Control animals:

yes

Remarks:

Controls were exposed to conditioned air using similar exposure conditions

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Body weights were measured before exposure, on days 3 and 7, and weekly thereafter. Individual weights are also recorded at death, if applicable. The appearance and behavior of each rat were examined carefully several times on the day of exposure and at least once daily thereafter. Weekend assessments were made once a day (morning).

- Necropsy of survivors performed: yes

- Other examinations performed: Rectal temperatures were measured directly after cessation of exposure

Statistics:

Data of rectal temperature measurements were statistically evaluated using ANOVA

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.03 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

There was no mortality

Clinical signs:

other: There were no signs of toxicity

Body weight:

There were no bodyweight effects

Gross pathology:

No treatment-related findings.

Other findings:

Statistical comparison between groups did indicate an effect on body temperature, however, the extent of change is considered to be of no clinical or pathodiagnostic relevance.

Any other information on results incl. tables

Group/Sex	Gravimetric Concentration (mg/L)	Toxicological Result#	Onset and Duration of Signs	Rectal Temperature	Onset of Mortality (%)
1 / m	0	0 / 0 / 5	--	38.0	--
2 / m	0.520	0 / 0 / 5	--	37.9	--
3 / m	5.030	0 / 0 / 5	--	37.8	--
1 / f	0	0 / 0 / 5	--	38.5	--
2 / f	0.520	0 / 0 / 5	--	38.1**	--
3 / f	5.030	0 / 0 / 5	--	38.0*	--

m = males, f = females, -- not applicable; * p ≤ 0.05, ** p ≤ 0.01
# 1st figure = number of dead animals
2nd figure = number of animals with signs
3rd figure = number of animals in the group

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Spirodiclofen does not require classification for acute inhalation toxicity according to the CLP criteria, on the basis of this study.

Conclusions:

Spirodiclofen showed no acute toxicity to rats following inhalation administration under the conditions of this study. The acute (4-hour, nose-only) LC50 was found to be >5.03 mg/L,

Executive summary:

The acute inhalation toxicity of spirodiclofen was investigated in a study performed to OECD 403.  Groups of Wistar rats (5/sex) were exposed for four hours (nose only) to analytical concentrations of 0.520 and 5.030 mg/L and observed for 14 days.  There were no mortalities or clinical signs; body weights were unaffected by exposure.  The MMAD at the highest concentration was larger than specified by the test guideline, resulting in a relatively low proportion of particles of respirable size. However, this is stated to be a consenquence of attempts to reach the limit concentration.  The acute (4-hour, nose-only) LC50 of spirodiclofen was found to be >5.03 mg/L,  under the conditions of this study.  Spirodiclofen does not require classification for acute inhalation toxicity acceding to the CLP criteria, on the basis of this study.