Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Experimental data with study designed according to standard methods

Data source

Reference
Reference Type:
grey literature
Title:
Unnamed
Year:
1981
Report Date:
1981

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:
- Name of test material (as cited in study report): Nadic methyl anhydride
- Physical state: Liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
No data
TEST ANIMALS
- Source: Blue Spruce Farms Inc.
- Fasting period before study: None
- Housing: During acclimatisation group caged, 5 same sex/cage. During study Individually caged in wire mesh cages
- Diet (e.g. ad libitum): ad libitum except during 4 hour exposure period
- Water (e.g. ad libitum): ad libitum except during 4 hour exposure period
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS - No data

IN-LIFE DATES: From: 1981-2-12 To: 1981-2-26

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: ethanol
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Stainless steel and glass cylindrical chamber
- Exposure chamber volume: 361 L
- Method of holding animals in test chamber: Whole body exposure with animals in wire mesh cages within exposure chamber
- Source and rate of air: Room air drawn into chamber by Vortex transvector jet at flow rate of 70 L/minute
- Method of conditioning air: Not applicable
- System of generating particulates/aerosols: Fluid metering pump feeding an atomiser
- Method of particle size determination: Cascade impactor
- Treatment of exhaust air: Vented to extraction hood
- Temperature, humidity, pressure in air chamber: 21-22 deg C; 41-57% RH; no data on pressure

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric analysis - 5L of chamber air drawn through glass fibre filter. Weight of trapped material used to calculate chamber concentration. Samples taken twice/hour and time weighted average concentration calculated for the 4 hour exposure period
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): Ethanol
- Concentration of test material in vehicle (if applicable): 90% w/w
- Justification of choice of vehicle: No data

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Particles <10 micron - 93%
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 3.2 / 2.1 micron
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Nominal - 4.9 mg/L
Achieved - 0.75 mg/L
No. of animals per sex per dose:
5 males / 5 female
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations at intervals on day of exposure and daily thereafter. Body weight recorded Prior to exposure (Day 1) and on Days 3, 4, 5, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: Whole head with nasal passages, trachea, bronchi, lungs, liver and kidneys preserved in buffed formalin
Statistics:
No data

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
< 4.9 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
< 0.75 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
3/5 males and 5/5 females
Clinical signs:
Laboured breathing, nasal discharge and wet coat noted in all animals during exposure.
Urinary incontinence, bloody urine, bloody discharge around ano-genital region and film covered appearance of eyes seen in individual animals following exposure.
Body weight:
Weight loss occurred in all animals following exposure. Only 1 of the 2 surviving animals re-gained its original body weight.
Gross pathology:
No unusual findings

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Acute toxicity has been determined in the rat following 4 hours inhalation exposure. A single group of rats were exposed to a nominal concentration of 4.9 mg/L (achieved concentration was 0.75 mg/L) and 80% mortality occurred. The median lethal concentration (LC50) is therefore less than the concentration investigated.
Executive summary:

Acute toxicity has been determined in the rat following 4 hours inhalation exposure. A single group of rats were exposed to a nominal concentration of 4.9 mg/L (achieved concentration was 0.75 mg/L) and 80% mortality occurred. The median lethal concentration (LC50) is therefore less than the concentration investigated.