Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From September 09 to 30, 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study performed similarly to OECD Guideline 403 without any deviations
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Arsenic Acid as Desiccant L-10
- Source: Pennwalt Corporation, USA
- Physical state: Green liquid
- Analytical purity: 75%
- Lot/batch No.: 8619
- Date of receipt: July 15 and September 17, 1987 (2 shipments)
- Storage condition of test material: Room temperature

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Portage, USA
- Age at study initiation: 44 days
- Weight at study initiation: Males: 25.6-30.7 g; females: 21.8-27.8 g
- Housing: Housed individually in hanging, stainless steel, wire mesh cages
- Diet (e.g. ad libitum): Purina Certified Laboratory Chow #5002, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-70 °F
- Humidity (%): 36-69%
- Photoperiod (hours dark / hours light): 12 hours dark / 12 hours light

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexiglass and stainless steel exposure chamber
- Exposure chamber volume: 250 L
- System of generating particulates/aerosols: Two FMI RP-G20 fluid metering pumps, each equipped with a 1/4" piston, were used to pump the undiluted arsenic acid from the original container to two 1/4J Spraying Systems atomizers, each equipped with air cap #67147 and fluid cap #2050.
- Source and rate of air: Compressed air was directed through two separate Dwyer Flowmeters to the separate atomizers, at a rate of 21.5 Liters per minute (Lpm) for atomizer A and 23.1 Lpm for atomizer B, which brought about the atomization of the liquid test material.
- Method of particle size determination: Determined twice during the exposure by sampling a measured volume of test atmosphere through an Andersen Model 2000 Cascade Impactor stages containing pre-weighed glass-fiber filter designed to retain impacted particles of sequentially diminishing size.
- Temperature, humidity in air chamber: Chamber temperature was recorded half-hourly during the exposure; humidity was not recorded due to chances of generation of toxic fumes on reaction of test material with hygrometer.

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric method: Aerosol in the breathing zone was drawn through glass fibre filters (Gelman type A/E 25 or 27 mm) and the employed filters weighed before and after sampling. The difference in the two weights, divided by the product of volume of atmosphere sampled and fraction solids, gave the actual chamber concentration.
- Samples taken from breathing zone: Yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
- Target concentration: 0.5, 1 and 5 mg/L air
- Analytical (time-weighed-average) concentration: 0.57 ± 0.291, 1.01 ± 0.105 and 2.41 ± 0.086 mg/L air
- Nominal concentration: 24.9, 49.1 and 206.7 mg/L air
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed hourly during exposure and twice daily thereafter for viability; clinical signs were observed prior to exposure, at 0.5 and 1 hour after dosing and daily thereafter until termination; weighed pre-test, on Days 8 and 15 and at death or sacrifice
- Necropsy of survivors performed: Yes; surviving animals were killed on Day 14 by exsanguination under sodium pentobarbital anesthesia and examined grossly
Statistics:
LC50 was estimated using Logit analysis (Bliss CJ, 1952) and Behrens-Reed-Muench Method (Thakur AK and Fezio WL, 1981).

Results and discussion

Preliminary study:
Not applicable
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
0.794 mg/L air (analytical)
Based on:
test mat.
95% CL:
>= 0.548 - <= 1.149
Exp. duration:
4 h
Remarks on result:
other: equivalent to 37.4 (23.2-60.3) mg/L air (nominal)
Sex:
female
Dose descriptor:
LC50
Effect level:
1.153 mg/L air (analytical)
Based on:
test mat.
95% CL:
>= 0.41 - <= 1.897
Exp. duration:
4 h
Remarks on result:
other: equivalent to 41.4 (19.9-86.4) mg/L air (nominal)
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1.04 mg/L air (analytical)
Based on:
test mat.
95% CL:
>= 0.512 - <= 1.567
Exp. duration:
4 h
Remarks on result:
other: equivalent to 39.2 (27.4-55.9) mg/L air (nominal)
Mortality:
- At 0.57 mg/L (analytical): No deaths
- At 1.01 mg/L (analytical): 5/5 males and 4/5 females died within 2 days
- At 2.41 mg/L (analytical): 4/5 males and 4/5 females died within 2 days
Clinical signs:
Clinical signs noted during exposure were languid behavior, dyspnea, polypnea, salivation, eye(s) squinted, prostration, tremors, lacrimation and rough haircot. Surviving animals at 1.01 and 2.41 mg/L (analytical) exhibited respiratory distress, increased secretory responses and signs of poor condition. Animals at 0.57 mg/L (analytical) were generally unremarkable throughout the two-week post- exposure period except for four mice which had squinted eye(s) on Test Day 2.
Body weight:
Slight diminution or decrease in the anticipated gain of body weight was observed.
Gross pathology:
At necropsy, macroscopic examination revealed darkened nasal turbinates and lung, failure of the lung to collapse, mottled lung, dark area of the stomach, fluid in the uterus, and distended uterus. The respiratory findings were considered treatment related.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the inhalation LC50 for arsenic acid (aerosol) is 1 mg/L in mice therefore it is classified as ‘R23 Toxic by inhalation’ according to the Annex VI of the Directive 67/548/EEC and ‘Category 3’ in the CLP Regulation (EC) No. 1272/2008.
Executive summary:

In an acute inhalation toxicity study performed similarly to OECD guideline 403 and in compliance with GLP, groups (5/sex) of CD-1 mice were exposed (whole-body) to aerosol atmosphere of arsenic acid at concentrations of 0.57, 1.01 or 2.41 mg/L (analytical TWA) corresponding to 24.9, 49.1 or 206.7 mg/L (nominal) for 4 hours. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all macroscopically necropsied after death or sacrifice.

 

Mortalities were 0, 90 and 80% at 0.57, 1.01 and 2.41 mg/L (analytical), respectively. Clinical signs noted during the study included respiratory distress, increased secretory responses, signs of poor condition and diminution of body weight gain. At necropsy, macroscopic examination revealed lesions in the respiratory system.

The acute inhalation LC50 for males and females were determined to be 0.794 (0.548-1.149) and 1.153 (0.410-1.897) mg/L (analytical), respectively. The acute inhalation combined LC50 was 1.040 (0.512-1.567) mg/L (analytical).

 

Under the test conditions, the inhalation LC50 for arsenic acid (aerosol) is 1 mg/L in mice therefore it is classified as ‘R23 Toxic by inhalation’ according to the Annex VI of the Directive 67/548/EEC and ‘Category 3’ in the CLP Regulation (EC) No. 1272/2008.

This study is acceptable and satisfies the guideline requirement for an acute inhalation study (OECD 403).