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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:
Initiated on February 6, 1980 and completed on May 13, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
Adopted in 1981. The study was performed before the adoption of the first OECD Guideline 403.
Deviations:
yes
Remarks:
Only minor deviations were observed. No information were provided on acclimation period, nulliparous and non-pregnancy status of females and on temperature and humidity in the animal room.
GLP compliance:
no
Test type:
traditional method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1,3-dioxolane
EC Number:
211-463-5
EC Name:
1,3-dioxolane
Cas Number:
646-06-0
Molecular formula:
C3H6O2
IUPAC Name:
1,3-dioxolane
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories Wilmington Massachussetts
- Age at study initiation: no data
- Weight at study initiation: males: 204 to 295 grams; females: 211 to 273 grams
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data
- Method of randomisation in assigning animals to test and control groups: no data

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Two tandem 1000 mL three-neck round bottom flasks, containing 500 mL and 200 mL of C-121, respectively, were submerged in individual waterbaths heated to 25°C by a B. Brawn Thermomix 1420. Each flask was wrapped in aluminium foil to shield the compound from direct light. Dry air at various flow rates (depending on desired concentration) was bubbled through the tandem bubblers to create a vapor. The vapor laden airstream was passed through a 500 mL three-neck round bottom flask where it was diluted with additional dry air to insure complete mixing and to achieve desired concentration.
- Exposure chamber volume: 26.5 liters
- Source and rate of air (airflow): 20 liters per minutes for four hours
- Temperature in air chamber: 22-27.8°C - monitored hourly during each exposure
Analytical verification of test atmosphere concentrations:
no
Remarks:
The nominal exposure concentration was determined by dividing the amount of test material delivered by the total air flow through the chamber during the exposure.
Duration of exposure:
4 h
Concentrations:
37.9, 60.6, 67.9, 88.4, 201.9 mg/L
No. of animals per sex per dose:
5
Control animals:
yes
Remarks:
A group of 5 males and 5 females was exposed to dry air, at a flow rate of 20 liters per minute for four hours. Body weight for these animals ranged from 266-298 grams (males) and 210 to 247 grams (females).
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for basic health prior to exposure and for abnormalities at 15-minute intervals during the first hour of exposure, hourly for the remainder of the exposure period, upon removal from the exposure chamber, hourly for the first four hours post-exposure, and daily thereafter for 14 days.
Individual body weights were recorded on Days 0 (prior to exposure), and on Days 1, 2, 4, 7, and 14 (terminus).
- Necropsy of survivors performed: yes, at day 14. Necrospy was also performed as soon as possible after death on all animals dying spontaneously.
Statistics:
Calculation of the median lethal concentration and 95% confidence limits performed according to the method of Litchfiels and Wilcoxon.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
68.4 mg/L air (nominal)
Based on:
test mat.
95% CL:
61 - 76.6
Exp. duration:
4 h
Mortality:
Mortality during the exposure followed a dose-related pattern and in all cases mortality occured within 48 hours following the exposure. In Group I (201.9 mg/L) ten out of ten animals died, and in Group III (88.4 mg/L) nine of ten animals died. Five out of ten animals died in Group IV (67.9 mg/L) and one of ten animals died in Group V (60.6 mg/L). In both groups II (37.9 mg/L) and VI (control), no animals died spontaneously.
Clinical signs:
other: Excessive lacrimation, shallow breathing, rapid breathing, prostration with loss of support, ataxia, decreased activity, eyes partially or completely closed, swollen eyes or eyelids, and no response to auditory stimuli during the exposure.
Remarks:
The severity and time of onset of these signs appeared concentration-related.
Body weight:
Individual body weights for surviving animals appeared to be reduced from Day 1 through Day 4 but most appeared to return to pre-exposure levels by Day 7. Body weights appear normal during the second week with the exception of two females in Group II and Group V. The rats exhibited slower than normal weight gains.
Gross pathology:
Necropsy of Group I (201.9 mg/L) animals revealed lung discoloration in all animals and liver discoloration in six of ten animals. Also observed at this time were bladders distended with fluid in six of ten rats, and gastrointestinal tracts distended with gas in eight of ten animals.

The male rat surviving to the exposure to 88.4 mg/L (Group III) exhibited lacrimation, labored breathing, moist rales, and corneal opacities on Day 1. Corneal opacities were exhibited throughout the 14-day post-exposure observation period. On Day 9 through 14 additional eye irritation was observed in this animal.

Necrospy observations for animals in Group IV and V dying spontaneously were similiar to observations for those animals dying spontaneously in Group III. All animals in each exposure group surviving through Day 14 showed minor lung discoloration (foci or mottling) or no observed abnormalities.

Any other information on results incl. tables

Due to sudden onset of mortality in Group I (prior to scheduled exposure termination), this group was not included in the calculation of the median lethal concentration (LC50)


 


Table 1 : Mortality data (number of dead animals)






























































































































































Group



Nominal exposure concentration (mg/L)



Sex



Exposure



48-Hour post-exposure



14-Day post-exposure



I



201.9



Male



5



5



5



 



 



Female



5



5



5



 



 



Total



10



10



10



II



37.9



Male



0



0



0



 



 



Female



0



0



0



 



 



Total



0



0



0



III



88.4



Male



3



4



4



 



 



Female



4



5



5



 



 



Total



7



9



9



IV



67.9



Male



1



4



4



 



 



Female



1



1



1



 



 



Total



2



5



5



V



60.6



Male



0



0



0



 



 



Female



1



1



1



 



 



Total



1



1



1



VI



Control



Male



0



0



0



 



 



Female



0



0



0



 



 



Total



0



0



0



 


Table 2 : Body weights (g)
























































































































































































































































































































































































Groups


/Sex



 



Day 0



Day 1



Day 2



Day 4



Day 7



Day 14



I M



Mean



224



 



 



 



 



 



 



SD



18



 



 



 



 



 



 



N



5



 



 



 



 



 



I F



Mean



234



 



 



 



 



 



 



SD



11



 



 



 



 



 



 



N



5



 



 



 



 



 



II M



Mean



285



264



263



276



290



318



 



SD



8



10



16



11



12



12



 



N



5



5



5



5



5



5



II F



Mean



255



240



244



244



255



262



 



SD



10



6



8



10



12



8



 



N



5



5



5



5



5



5



III M



Mean



274



 



 



 



 



 



 



SD



13



 



 



 



 



 



 



N



5



 



 



 



 



 



III F



Mean



241



 



 



 



 



 



 



SD



9



 



 



 



 



 



 



N



5



 



 



 



 



 



IV M



Mean



248



231



 



 



 



 



 



SD



18



11



 



 



 



 



 



N



5



2



 



 



 



 



IV F



Mean



223



200



208



216



228



241



 



SD



10



7



6



7



13



14



 



N



5



4



4



4



4



4



V M



Mean



259



232



243



254



268



303



 



SD



22



20



23



24



26



27



 



N



5



5



5



5



5



5



V F



Mean



220



203



209



214



222



226



 



SD



6



8



8



10



7



5



 



N



5



4



4



4



4



4



VI M



Mean



282



281



285



297



314



345



 



SD



11



11



14



15



18



21



 



N



5



5



5



5



5



5



VI F



Mean



227



225



228



231



236



244



 



SD



14



14



13



18



20



21



 



N



5



5



5



5



5



5



 

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
A series of four-hour inhalation exposures to vapors of C-121 was performed on Sprague-Dawley rats. The nominal exposure concentrations for Groups I, II, III, IV and V were 201.9, 37.9, 88.4, 67.9 and 60.6 milligrams per liter (mg/L), respectively.
Respiratory and neuromuscular abnormalities were the immediate responses to the test material during the exposure and during the four-hour post-exposure observation period. The severity and incidences of these findings follow a concentration-related pattern. During the14-day post-exposure observation period all survivors appeared to recover by Day 4.
Suriviving animals appeared to regain pre-exposure body weights by Day 7 and showed normal weight gain patterns during the second week, with the exception of two female rats in Group II, and two female rats in Group V.
Necropsy findings revealed high incidences of lung and liver discoloration as well as bladders distended with fluid and gastrointestinal tracts distended with gas in animals dying spontaneously. The frequency of these findings appears to be concentration related.
Mortality during the studies followed a concentration related pattern and all spontaneous deaths occurred within 48 hours following exposure.
Based on nominal concentrations and mortality results, the median lethal concentration for a four-hour exposure to C-121 was determined to be 68.4 mg/L, with 95% confidence limits of 61.0 and 76.6 mg/L.

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