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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study has been performed according to OECD and/or EC guidelines, but not according to GLP principles. The study documentation however was acceptable and sufficient to verify that the LC50 is an accurate endpoint. The LC50 from this study is consistent with that from several studies from public literature.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
no
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): C-121 (code for 1,3-dioxolane)
- Physical state: liquid
- Analytical purity: 99.9% (statement)
- Lot/batch No.: not reported

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Wilmington, Massachusetts 01887, USA
- Age at study initiation: young adults (exact age not reported)
- Weight at study initiation: males 218-267 g, females 213-244 g.
- Fasting period before study: no information on feeding and watering regime
- Housing: Group-housed (5/cage) during study.
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%):no data
- Air changes (per hr): 45 times
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: February 06, 1980 To: May 13, 1980

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Air was bubbled through two tandem 1000 mL three-necked roundbottom flasks (kept at 25°C, wrapped in aluminium foil) containing 500 mL and 200-750 mL of test substance . The vapour laden air stream was passed through a 500-1000 mL three-necked roundbottom flask where it was diluted with additional air to achieve the desired concentration. The resulting test atmosphere was then delivered into a 26.5 l exposure chamber. Air flow was maintained at 20 L/min.
Analytical verification of test atmosphere concentrations:
no
Remarks:
The achieved concentrations were verified by weighing the two tandem flasks, test material, mixing flask, glass fittings and rubber stoppers before and after exposure. The difference represented the amount of test material delivered during exposure.
Duration of exposure:
4 h
Remarks on duration:
Exception: highest dose group (all animasl died within 145 min).
Concentrations:
37.9, 60.6, 67.9, 88.4 and 201.9 mg/L
No. of animals per sex per dose:
5 males and 5 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations on toxicological signs at 15-minute intervals during the first hour of exposure, hourly for the remainder of exposure, upon removal from the exposure chamber, hourly for the first four hours post-exposure, and daily thereafter for 14 days, weighing on day 0 and on days, 1, 2, 4, 7 and 14.
- Necropsy of survivors performed: performed on animals dying spontaneously and on all survivors on day 14.
- Other examinations performed: none
Statistics:
The LC50 was estimated using the method by Litchfield and Wilcoxon (1949).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
68.4 mg/L air
95% CL:
61 - 76.6
Exp. duration:
4 h
Mortality:
For detailed results see Table under “Remarks on results including tables and figures”. There were no differences between sexes. At 0, 37.9, 60.6, 67.9, 88.4 and 201.9 mg/L, respectively, mortality was 0%, 0, 10%, 50%, 90% and 100%. All mortalities occurred within 48 hours.
Clinical signs:
other: Treatment related signs of intoxication were excessive lacrimation, shallow breathing, rapid breathing, prostration with loss of support, ataxia, decreased activity, eyes partially or completely closed, swollen eyes or eyelids, no response to auditory sti
Body weight:
For detailed results see Table under “Remarks on results including tables and figures”. Body weight data were not analyzed for statistically significant differences. Surviving animals appeared to regain pre-exposure body weights by day 7 and showed normal weight gain during the second week, with the exception of 2 female rats in the 37.9 mg/L group and 2 female rats in the 60.6 mg/L group.
Gross pathology:
Treatment related observations were lung discolouration (foci, mottling), liver discolouration, spleen discolouration, bladders distended with fluid, gastro-intestinal tracts distended with gas. The incidence and severity of these findings appeared concentration-related.

Any other information on results incl. tables

The results on survival and body weights are summarized in the table below

Table 1.                               Detailed results for oral acute toxicity test

Concentration(mg/L)

Mortality (M)

Mortality (F)

Mean BW (g) on day 0

(M / F)

Mean BW on day 7 (M / F)

Mean BW (g) on day 14 (M / F)

0

0

0

282 / 227

314 / 236

345 / 244

37.9

0

0

285 / 255

290 / 255

318 / 262

60.6

0

1

259 / 220

268 / 222

303 / 226

67.9

4

1

248 / 223

- / 228

- / 241

88.4

4

5

274 / 241

- / -

- / -

201.9

5

5

224 / 234

- / -

- / -

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Acute inhalation LC50 (vapour, 4-hour exposure) was 68.4 mg/L.
Executive summary:

An acute inhalation toxicity study on 1,3-dioxolane(whole body exposure to vapour)was performed in young adult Sprague-Dawley CD® rat according to OECD 403 at concentrations of 37.9, 60.6, 67.9, 88.4 and 201.9 mg/L (5 males and 5 females per dose). The nominal exposure concentration was determined by dividing the amount of test material delivered (determined by weighing before and after exposure) by the total air flow though the chamber during exposure. During the 14-day observation period observations on toxicological signs were made at 15-minute intervals during the first hour of exposure, hourly for the remainder of exposure, upon removal from the exposure chamber, hourly for the first four hours post-exposure, and daily thereafter for 14 days. Rats were weighed on day 0 and on days, 1, 2, 4, 7 and 14. Necropsy of survivors was performed on animals dying spontaneously and on all survivors on day 14. At 0, 37.9, 60.6, 67.9, 88.4 and 201.9 mg/L, respectively, mortality was 0%, 0, 10%, 50%, 90% and 100%. There were no differences between sexes. All mortalities occurred within 48 hours. The acute inhalation LC50 (vapour, 4-hour exposure) was 68.4 mg/L. Treatment related signs of intoxication and gross abnormalities were observed in all treated groups.The incidence, severity and onset of these findings appeared concentration-related. Surviving animals appeared to regain pre-exposure body weights by day 7 and showed normal weight gain during the second week, with the exception of 2 female rats in the 37.9 mg/L group and 2 female rats in the 60.6 mg/L group.