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Acute Toxicity: inhalation

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acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guideline
according to
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
traditional method
Limit test:

Test material

Test material form:
solid: crystalline
Details on test material:
the racemate is characterized by CAS-number 7696-12-0

Test animals

Details on test animals and environmental conditions:
Age at exposure: 10 -11 weeks
Body weight at treatment
Males: 225 - 258 g
Females: 81 - 201 g
Identification: Rat accession number, cage card and turmeric colour body marking. During the acclimatization period the rats were temporarily identified by crystal violet colour body marking.
Acclimatization: After veterinary examination, the animals were acclimatized for seven days before treatment. Females were nulliparous and non-pregnant.
Animals were housed under standard laboratory conditions:
·Air conditioned with adequate fresh air supply (12 - 15 air changes/hour),
·Temperature 20 - 24 °C,
·Relative humidity 30 - 70%,
·Photoperiod: 12 hour light and 12 hour dark cycle.
The animals were housed individually in standard polypropylene rat cages (size: approximately L 410 x B 282 x H 150 mm), with stainless steel top grills having facilities for providing pelletted food and drinking water in glass bottle; steam sterilized clean paddy husk was used as bedding material which was changed twice a week.
Diet ad libitum

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
other: Cyclohexanone
Mass median aerodynamic diameter (MMAD):
>= 0.67 - <= 0.68 µm
Geometric standard deviation (GSD):
Remark on MMAD/GSD:
The mean aerosol particle size obtained was 0.67 ±0.26 and 0.68 ±0.26 micrometers for the G1 and G2 groups, respectively.
Details on inhalation exposure:
Exposure chambers are rectangular and made of stainless steel / glass, pyramidal at top and bottom. The rats were housed in special rat restrainers made of cylindrical glass and brass metal (Diameter: 5.7 cm, Length: 16.0 cm) having holes at the anterior end and closed at the posterior end. This enabled the rats to inhale the test item aerosol (head and nose exposure) with minimum deposition on the skin. The restrainers with the rats were kept inside the exposure chambers. The volume of each exposure chamber was 0.5 m³.

The chamber temperature and humidity were recorded at hourly intervals four times during the exposure period using a dry and wet thermometer placed inside each chamber near the glass surface. The chamber temperature of 21 - 22 °C was maintained.
Chamber pressure: The chamber pressure was maintained at -5 mm H2O.
Atomizer pressure: The atomizer pressure of 1.2 kg/cm² was maintained.
Injection rate: The test item solution was injected at the rate of 0.8 ml/min.
Airflow rate: The airflow rate was monitored continuously and the airflow of 28 l/min was maintained.
Analytical verification of test atmosphere concentrations:
HPLC analysis
Duration of exposure:
4 h
Group 1 (vehicle only): 100% Cyclohexanone was used.
Group 2 (test item, 50% w/v in Cyclohexanone): 100 g of the finely ground test item was dissolved and made up to 200 ml with Cyclohexanone to achieve the concentration of 50% w/v.
No. of animals per sex per dose:
10 animals (5 males + 5 females) exposed to test item, tetramethrin concentration 5.63 ±0.86 mg/l air
Control animals:
10 animals exposed to vehicle control
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
The toxic signs could not be ascertained during the exposure period due to dense aerosol accumulation inside the chamber in the G2 group and due to the special housing method (restrainers) in the G1 group. The observations for toxic signs and pre-terminal deaths were performed immediately after exposure, while releasing the rats from the restrainers. Thereafter, the observations for toxic signs and pre-terminal deaths were made once daily during days 2 to 15.
The body weights of individual animals were recorded on test day 1 (pre-exposure) and days 8 and 15.
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:
A pre-study was conducted using 2 male and 2 female rats/group, where the rats were exposed to the aerosol generated under the conditions given below:
Atomizer used: Glass atomizer
Atomizer pressure: 1.2 kg/cm²
Injection rate: 0.8 ml/min (0.4 ml x 2)
Airflow rate: 28 I/ min
Sampling duration: 10 min
Sampling rate: 10 l/min

The animals were exposed in inhalation equipment with dynamic airflow. A slight negative pressure was maintained inside the chamber to prevent leakage of the test item into the surrounding area.
Based on the pre-study results, the following doses are selected for
the main study.
G1: 0 — Vehicle control (Cyclohexanone)
G2 : 50 % w/v in Cyclohexanone.
Effect levels
Key result
Dose descriptor:
Effect level:
>= 5.63 mg/L air (analytical)
Based on:
test mat.
95% CL:
>= 4.77 - <= 6.49
Exp. duration:
4 h
There were no pre-terminal deaths in either of the groups
Clinical signs:
Body weight:
All the rats gained body weight during the observation period
Gross pathology:
No abnormality was detected at necropsy

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
The acute inhalation (4 hours) LC50 value of tetramethrin aerosol is greater than 5.63 mg/I air.
Executive summary:

An acute inhalation toxicity study with tetramethrin in Wistar rats was conducted to assess the toxicological profile of tetramethrin.

The inhalation toxicity of tetramethrin was determined in Wistar rats by exposure to the test item as an aerosol in cyclohexanone generated by a glass atomizer with an injection rate of 0.8 ml/min, and with 1.2 kg/cm² pressure. Similarly, rats in the vehicle control group were exposed to an aerosol of cyclohexanone. The analytically determined average concentration of tetramethrin was 0 and 5.63 (maximum attainable concentration) mg per litre of chamber air in the G1 and G2 groups, respectively. The rats, housed in special rat restrainers, were continuously exposed to the aerosol (head and nose exposure) for four hours in a 0.5 m³ glass/stainless steel inhalation exposure chamber (dynamic state). The aerosol sampled from the inhalation chamber for particle size analysis showed a mean aerosol particle size of 0.67 ±0.26 and 0.68 ±0.26 micrometers for the G1 and G2 groups, respectively. Slight lacrimation and nasal discharge was observed in all the rats in the G2 group on day 1. There were no pre-terminal deaths and no abnormality detected at necropsy in either of the groups.

The acute inhalation (4 hours) LC50 value of tetramethrin is more than 5.63 mg aerosol/l (maximum attainable concentration).