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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:
5 October 1983 - 27 October 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Clear report, early GLP, similar to OECD Guideline 403
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:
1984
Report Date:
1984

Materials and methods

Test guideline
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
Remarks:
early GLP
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Santicizer 148
- Physical state: liquid
- Analytical purity: confidential
- Lot/batch No.: confidential
- Stability under test conditions: no data
- Storage condition of test material: Temperature monitored room (15.6 – 29.4 °C)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories Wilmington, Delaware 01887, USA
- Age at study initiation: Males: 9 weeks; Females: 10 weeks
- Weight at study initiation: Males- Mean: 274 g (range 246 to 303 g); Females - Mean: 229 g (range: 222 to 238 g)
- Fasting period before study: no data
- Housing: Animals were group housed in elevated stainless steel wire mesh cages during the acclimation period and individually housed during all subsequent non-exposure periods.
- Diet: ad libitum, standard laboratory diet (Purina-Rodent Laboratory Chow)
- Water: ad libitum, by automated watering system (Elizabethtown Water Company)
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.6 - 24.4
- Humidity (%): 25-76
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: no data

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 Exposure chamber
- Exposure chamber volume: 100 liter
- Method of holding animals in test chamber: no data
- Source and rate of air: flow rate: 10 l/min.
- Method of conditioning air:
- System of generating particulates/aerosols: A large three-neck round bottom flask fitted with a Laskin Aerosol Generator.
- Method of particle size determination: Particle size distribution samples were obtained using a Casella cascade impactor at approx. 1 hour intervals throughout the exposure. The distribution was calculated based on the amount of test substance collected on the impactor stages (glass slides).
- Treatment of exhaust air:
- Temperature, humidity, pressure in air chamber: A thermometer and Airguide relative humidity indicator were used to record temperature and humidity in the chamber. Recordings were made at approx. hourly intervals throughout the exposure. The average chamber temperature and humidity were 25°C and 35%, resp.

TEST ATMOSPHERE
- Brief description of analytical method used:Gravimetry
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Analysis of particle size distribution data revealed a mass median aerodynamic diameter of 2.5 microns with a geometric standard deviation of 2.4
Analytical verification of test atmosphere concentrations:
yes
Remarks:
The amount and distribution of the test substance was determined gravimetrically. Particle size distribution samples were obtained using a Casella cascade impactor
Duration of exposure:
ca. 4 h
Concentrations:
Nominal exposure concentration: 13 mg/l
Mean analytical concentration (gravimetry): 6.3 mg/l
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed prior to exposure, at approximately 15 minute intervals during the first hour of exposure, hourly for the remainder of the exposure, upon removal from the chamber, and hourly for two hours post-exposure. Detailed observations were recorded at each interval. Body Weight: Day I (immediately prior to exposure) and on Days 2, 3, 5, 8 and 15 (post-exposure period).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy
Statistics:
Not relevant

Results and discussion

Preliminary study:
Not relevant
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC0
Effect level:
ca. 6.3 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
other: No deaths. Signs exhibited during exposure: increases in secretory responses and reduced activity. Signs during the post-exposure period: incidences of secretory responses, rough coat and yellow ano-genital fur A transient decrease in body weight.
Sex:
male/female
Dose descriptor:
LC0
Effect level:
ca. 13 mg/L air (nominal)
Exp. duration:
4 h
Remarks on result:
other: No deaths. Signs exhibited during exposure: increases in secretory responses and reduced activity. Signs during the post-exposure period: incidences of secretory responses, rough coat and yellow ano-genital fur A transient decrease in body weight.
Mortality:
No mortality was observed.
Clinical signs:
other: Exposure observations revealed some to most animals exhibited lacrimation, salivation, chromodacryorrhea and reduced activity during the entire exposure. Upon removal from the chamber, the animals exhibited increased incidences of secretory responses (lac
Body weight:
Slight decreases in body weights for both sexes of animals were exhibited following exposure (Test Day 2). Most of the females had regained their pretest body weights by Test Day 3; however, all males did not regain their pretest body weights until Test Day 8. The body weights were considered unremarkable for the remainder of the post-exposure period.
Gross pathology:
Gross postmortem findings occurred sporadically and were not considered related to the test material.
Other findings:
Not relevant

Any other information on results incl. tables

Not relevant

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
A single four-hour exposure to 6.3 mg/l Santicizer 148 as a respirable aerosol mixture produced no mortality in a group of 10 rats. Signs exhibited during exposure included increases in secretory responses and reduced activity. Signs during the post-exposure period: incidences of secretory responses, rough coat and yellow ano-genital fur. A transient decrease in body weight was observed. As no deaths occurred the tested concentration can be considered as LC0. Based on these results, the test substance does not need to be classified for acute inhalation toxicity according to the criteria outlined in Annex I of 1272/2008/EC and Annex VI of 67/548/EEC.
Executive summary:

This acute inhalation toxicity study in rats was conducted according to a method resembling OECD guideline 403. A single 4-hour exposure to 6.3 mg/l Santicizer 148 as a respirable aerosol mixture produced no mortality in a group of 5 male and 5 female Sprague-Dawley rats. Rats were observed for 14 days after exposure. Signs exhibited during exposure included increases in secretory responses and reduced activity. Incidences of secretory responses, rough coat and yellow ano-genital fur persisted during the two-week post-exposure period. A transient decrease in body weight was noted an Test Day 2. Subsequently, female body weights were unremarkable, while all males did not regain their pretest body weights until Test Day 8. Gross postmortem findings occurred sporadically and were not considered related to the test material. As no deaths occurred the tested concentration can be considered as LC0. Based on these results, the test substance does not need to be classified for acute inhalation toxicity according to the criteria outlined in Annex I of 1272/2008/EC and Annex VI of 67/548/EEC.