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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study generated according to internationally accepted testing guidelines and according to GLP. However, animal groups one and two contained 2 animals/sex as opposed to 5 animals/sex recommended by the OECD guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
TDCP in liquid aerosol form.
- Name of test material (as cited in study report): Amgard TDCP
- Physical state: colourless liquid
- Storage condition of test material: Stored in the dark at ambient temperature
- Analytical purity: not stated

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited.
- Age at study initiation: Not recorded
- Weight at study initiation: 118 - 138g
- Fasting period before study: no fasting prior to exposure
- Housing: 1-2 males or females per cage in suspended polypropylene cages with stainless steel mesh tops and bottoms, over trays of absorbent paper. All cages were supplied with polypropylene water bottles (capacity 500ml) with rubber washers and melamine caps.
- Diet: ad libitu except suring the 4h exposure period (Rat and mouse (modified) No. 1 diet SQC expanded.
- Water: ad libitumexcept suring the 4h exposure period


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 (+/- 2)
- Humidity (%): ca 55
- Air changes (per hr): not recorded
- Photoperiod (hrs dark / hrs light): 12h/12h

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: Sage syringe pump to continuously meter Amgard through a glass concentric jet atomiser located at the top of the exposure chamber.
- Exposure chamber volume: 41.5L
- Method of holding animals in test chamber: Animals were loaded into a tapered, polycarbonate restraint tube which fitted onto the exposure chamber and sealed by means of a rubber 'o' ring.
- Source and rate of air: Filtered, oil-free compressed air for production of the test atmospheres were supplied by hyrdovane compressors.
- System of generating particulates/aerosols: A single pass of freshly generated material was passed through the system, particles dispersed throughout the chamber and exited through the base to a filtered vaccum line.
- Method of particle size determination: Particle size distribution was determined twice throughout the exposure period using an inline sampler and a series of impaction stages which fractionated the aerosol into the size range 0.25 - 10 micrometers.
- Temperature, humidity, pressure in air chamber: Temperature and humidity were recorded at 30min intervals throughout the exposure period: temperature was 18-19 degrees centigrade and relative humidity varied between 38 and 81 %.


TEST ATMOSPHERE
- Brief description of analytical method used: Nominal chamber concentration was determined by calculation (weight of material used / total air flow through chamber). Gravimetric chamber concentration was analysed using sorbent (silica) gel sampling tubes which were positioned and temporarily sealed in the port of the exposure chamber at the animals' breathing zone.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Estimation on the particle size distribution revealed that the percentage of particles < 3.5 µm for Group 3 was 29.5% by weight.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD for Group 3 was determined to be 4.0 µm
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
11.72, 17.54 and 23.99mg/L (nominal concentrations) or 2.07, 1.16 and 5.22mg/L air (measured gravimetric).
No. of animals per sex per dose:
Group 1: dose 2.07mg/L; 2 males and 2 females
Group 2: dose 1.16mg/L; 2 males and 2 females
Group 3: dose 5.22mg/L; 5 males and 5 females
Group 4: untreated and humanely killed without necropsy upon completion of the study; 5 males and 5 females.
Group 5: untreated and humanely killed without necropsy upon completion of the study; 5 males and 5 females.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 3 days for groups 1 and 2 and 14 days for group 3.
- Frequency of observations: continuous observation for clinical signs throughout the exposure period, for the first 1-2h post dosing and thereafter at least once daily during the study period.
- Frequency of weighing: All rats were weighed immediately before dosing and on days 2 and 3 post exposure for groups 1 and 2 and on days 2,3,4,7,10 and 14 post exposure for group 3.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.22 mg/L air
Exp. duration:
4 h
Mortality:
Animals were observed for 3 or 14 days, no mortalities were observed.
Clinical signs:
other: No clinical signs of toxicity during the exposure period. All animals appeared slightly unkempt and had red staining around the snout and eyes immediately after dosing. No abnormalities were observed during the subsequent 3 day or 14 day observation perio
Body weight:
Body weight profiles were considered to be satisfactory.
Gross pathology:
No abnormalities detected.Lung:body weight ratios observed were considered to be within normal limits.
Other findings:
The measured gravimetric concentration is the aerosol concentration to which the animals were exposed. The difference between this and the nominal concentration mainly arises because the calculated nominal concentration includes all of the larger particles at the centre of the aerosol stream which are rarely present in the animals’ breathing zone or atmospheric samples measured from this breathing zone. Thus, the difference noted can be explained by the difference between total and measured aerosol mass and is a reflection of the efficiency of generation of the test aerosol. Estimation of particle size distribution revealed that 29.5% of particles were < 3.5 um for 5.22 mg/l with a MMAD of 4.0 um.

Applicant's summary and conclusion

Interpretation of results:
other: low acute toxicity.
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The LC50 value was not demonstrated other than an indication that the value was in excess of a measured gravimetric concentration of 5.22 mg/l of Amgard TDCP.