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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:
1984-01-23 to 1984-10-.29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Conduction and documentation of study very acceptable. Study report available.

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:
Method: other
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): 2,4-Pentanedione
- Physical state: liquid
- Stability under test conditions: stable


Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Kingston, NY, USA
- Age at study initiation: 26-38 days old
- Fasting period before study: not reported
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported
- Acclimation period: approx. 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Groups of 5 male and 5 female Hilltop-Wistar albino rats [HLA(WI)BR] were exposed for four hours to dynamically generated vapour of 2,4- pentanedione. Concentrations tested were 628, 919, 1231 and 1508 ppm (corres ponding to 2619; 3823; 5133 and 6288 mg/m³, respectively). Chamber concentrations concurrently analysed throughout each 4-hour exposure by GC.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gas chromatography
Duration of exposure:
4 h
Concentrations:
628, 919, 1231 and 1508 ppm (corresponding to 2619; 3823; 5133 and 6288 mg/m³).
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
Postexposure period 14 d; body weight determined at 0, 7 an d 14 d postexposure. A static exposure was also performed for determination of LT50. Groups of 5 male and 5 female rats were exposed to 7732 and 6388 ppm (correspond-ing to 32242 and 26638 mg/m³) for 74 and 37 minutes (males) and 8374 and 7449 ppm (corresponding to 34920 and 31062 mg/m³ for 78 and 39 minutes (females).
Statistics:
not reported

Results and discussion

Preliminary study:
not reported
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1 224 ppm
Based on:
test mat.
95% CL:
1 063 - 1 409
Exp. duration:
4 h
Mortality:
in exposure gruops of 1231 ppm upwards
Clinical signs:
other: periocular, perinasal and perioral wetness and encrustation, forced respiration, dis-tended abdomen, tremors, ataxia, decreased motor activity, a negative tail and toe pinch reflex and a slow righting reflex; periocular wetness and decreased motor activit
Body weight:
No effects on body weight gains were observed by 14 days postexposure
Gross pathology:
red lungs, dark livers, gas-filled stomachs (no effects on sacrificed survivors)
Other findings:
not reported

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance with an LC50 of 5.1 mg/l/4h is harmful by inhalation under the conditions used .
Executive summary:

Groups of 5 male and 5 female Hilltop-Wistar albino rats [HLA(WI)BR] were exposed for four hours to dynamically generated vapour of 2,4- pentanedione. Concentrations tested were 628, 919, 1231 and 1508 ppm (corres ponding to 2619; 3823; 5133 and 6288 mg/m³, respectively). Chamber concentrations concurrently analysed throughout each 4-hour exposure by GC. Postexposure period 14 d; body weight determined at 0, 7 an d 14 d postexposure. A static exposure was also performed for determination of LT50. Groups of 5 male and 5 female rats were exposed to 7732 and 6388 ppm (corresponding to 32242 and 26638 mg/m³) for 74 and 37 minutes (males) and 8374 and 7449 ppm (corresponding to 34920 and 31062 mg/m³ for 78 and 39 minutes (females).

Dynamic exposure: The results of these tests indicate that the 4 hour dynamic LC50 (95 % confidence limits) for 2,4-pentanedione (combined male and female) is 1224 (1063 to 1409) ppm (corresponding to 5.104 (4.432 - 5.876) mg/m³). LC50 determined for combined male and female rat. Deaths were observed with both male and female rats exposed to concentrations of 1508 and 1231 ppm (mortality 8/10 and 6/10, respectively). Deaths occurred mostly during exposure or within 24 hours respectively). Deaths occurred mostly during exposure or within 24 hours post-exposure (1 exception on day 3 in male rats in the 1508 ppm group). No mortalities were observed with rats exposed to dynamic concentrations of 919 or 628 ppm. Clinical signs observed in rats of the 1508 and 1231 ppm exposure groups included periocular, perinasal and perioral wetness and encrustation, forced respiration, distended abdomen, tremors, ataxia, decreased motor activity, a negative tail and toe pinch reflex and a slow righting reflex. The respiratory difficulties decreased motor activity and ataxia persisted in survivors through post-exposure day 2. No clinical signs were observed in survivors of the 1508 and 1231 ppm exposure groups on day 6 and 5, respectively. The only clinical signs in the 919 ppm group were periocular wetness and decreased motor activity in both sexes of rats during exposure. These rats appeared normal again on post-exposure day one. In the 628 ppm exposure group, no signs of toxicity were observable during or post-exposure. Body weights were observed for all exposure groups at 14 days post-exposure; necropsy of rats that died: red lungs, dark livers, gas-filled stomachs (no effects on sacrificed survivors). Static exposure: LT50 for male rats 52 min (average concentration 7060 ppm) and 55 min for female rats (average concentration 7912 ppm). All rats exposed to static saturated vapour died during exposure in approximately 76 minutes. No mortalities occurred for either sex at the exposure time of approximately 38 minutes. Clinical signs observed for all static exposure groups included periocular and perinasal wetness, forced respiration and hypoactivity during exposure. A negative toe and tail pinch reflex, and negative surface righting were observed in rats following the 38 minutes exposure. These animals appeared normal by post-exposure day one. No effects on body weight gains were observed by 14 days postexposure. No gross lesions were found in survivors at necropsy. Discoloured lungs andlivers were observed in rats dying during static exposure. The test substance with an LC50 of 5.1 mg/l/4h is harmful by inhalation under the conditions used .