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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:
4 - 21 June 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

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:
Product name: Amgard V6
Appearance: light brown liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, UK
- Weight at study initiation: 107 - 130g
- Housing: 1 or 2 rats per cage
- Diet: ad libitum (Rat and Mouse No.1 Diet SQC Expanded), except during exposure period
- Water: ad libitum, except during exposure period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 24
- Humidity (%): 38 - 60
- 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:
- Exposure chamber volume: 41.5 L
- Method of holding animals in test chamber: restraint tube, nose only exposure
- Method of conditioning air: concentration in exposure chamber controlled by adjusting feed rate of test substance and air flow rate
- System of generating particulates/aerosols: Sage syring pump, Schlick atomiser
- Method of particle size determination: Marple Cascade Impactor (inline sampler + series of impaction stages)
- Temperature, humidity in air chamber: 18 - 20 degrees, 18 - 62 % relative humidity

TEST ATMOSPHERE
- Brief description of analytical method used: nominal and gravimetric chamber concentration estimated (using sorbent silica gel sampling tubes)
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
- Range finding study: 5.06 mg/L nominal, 2.32 mg/L gravimetric
- Main study: 4.50 mg/L nominal, 1.65 mg/L gravimetric
- These chamber concentrations were the highest achievable concentrations (due to the viscous nature of the test substance chamber concentrations closer to 5 mg/L could not be achieved)
No. of animals per sex per dose:
- Range finding study: 2 male and 2 female rats
- Main study: 5 male and 5 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 3 days (range finding study) / 14 days (main study)
- Frequency of observations: continuously during exposure and first 1-2h after dosing, afterwards at least once daily
- Frequency of weighing: immediately before dosing and on day 1, 3 after dosing (range finding study) / days 2, 3, 4, 7, 10, 14 after dosing (main study)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, lung weights, gross pathology

Results and discussion

Preliminary study:
- No mortalities
- Red staining around snout and eyes immediately after exposure
- No abnormalities during subsequent observation period
- No effect on body weight gain
- No gross pathological abnormalities
Effect levels
Dose descriptor:
LC50
Effect level:
> 1.65 mg/L air
Exp. duration:
4 h
Mortality:
No mortalities
Clinical signs:
- Red staining around snout and eyes immediately after exposure
- No abnormalities during subsequent observation period
Body weight:
No effect on body weight gain
Gross pathology:
No gross pathological abnormalities. Lung to body weight ratios were in the normal range.

Any other information on results incl. tables

Highest achievable test chamber concentration: nominal: 4.5 mg/L, measured in animal breathing zone: 1.65 mg/L

Percentage of particles < 3.5 micro m: 70.2 weight percent, mass median aerodynamic diameter: 2.5 micro m.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal concentration (LC50) of the test substance by inhalation in rats is greater than 1.65 mg/L.
Executive summary:

In an acute inhalation toxicity study conducted according to OECD Guideline No.403, male and female Sprague-Dawley rats were exposed by inhalation route to 2,2-bis(chloromethyl)trimethylene bis(bis(2-chloroethyl)phosphate) for 4 hours nose only at concentrations of 1.65 mg/L (limit test). This was the highest attainable concentration, due to the viscous nature of the test material.

Animals were observed for up to 14 days. No mortalities were observed during the course of the study.

LC50 males > 1.65 mg/L

LC50 females > 1.65 mg/L