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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 August 2010 - ........................................
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to GLP and testing guideline; adequate coherence between data, comments and conclusions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
for ethical reasons, as neither death nor clinical signs were noted among 3 rats at 300 mg/kg, no 2nd assay was done at this dose; however two assays were done at 2000 mg/kg as required by guideline
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
idem above
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Details on test material:
- Name of test material (as cited in study report): Distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products.
- Physical state: yellow liquid
- Purity: not indicated (complex composition)
- Lot/batch No.: LR_OXO_2010-07-12
- Date of analysis: 12 July 2010
- Expiration date of the lot/batch: July 2011
- Storage conditions of test material: at +4°C and under nitrogen gas.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Breeder: Janvier, Le Genest Saint-Isle, France
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: 208 +/- 4 g
- Fasting period before study: 18 hours
- Housing: polycarbonate cages with stainless steel lid
- Diet (e.g. ad libitum): free access to SSNIFF R/M-H pelleted diet
- Water (e.g. ad libitum): free access to bottles containing tap water (filtered with a 0.22 µm filter)
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 50 +/- 20%
- Air changes (per hr): 12 cycles/hour
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (7:00 - 19:00)

IN-LIFE DATES: From: 20 August 2010 To: 22 September 2010.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Justification for choice of vehicle: The test item was not soluble in purified water. A solution was obtained in corn oil at the concentration of 200 mg/mL.

DOSE VOLUME APPLIED: 10 mL/kg.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As no information on the toxic potential of the test item was available, for animal welfare reasons,
the starting dose-level of 300 mg/kg was chosen.
Doses:
300 and 2000 mg/kg.
No. of animals per sex per dose:
3 females per treatment step (300, 2000 and 2000 mg/kg).
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality: frequently during the hours following administration, then daily.
Clinical signs: at least once during the first 30 minutes, periodically during the first 24 hours for detection of possible treatment-related clinical signs and then daily.
Body weight: just before administration on day 1, then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic)

Results and discussion

Preliminary study:
not applicable
Effect levels
Sex:
female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
At the 300 and 2000 mg/kg dose-level, no deaths were noted.
Clinical signs:
At the 300 mg/kg dose-level (three females), no clinical signs were noted.
At the 2000 mg/kg dose-level, hypoactivity or sedation and piloerection (in all animals), staggering gait (in 4 animals) and dyspnea (in 3 animals) were observed on day 1 only.
Body weight:
At the 300 mg/kg dose-level, when compared to CIT historical control data the body weight gain of the animals was not affected by treatment with the test item.
At the 2000 mg/kg dose-level, a body weight loss (-3%) was noted between day 8 and day 15 in one female.
When compared to CIT historical control data, a lower body weight gain was noted between day 1 and day 8 (vs. 41 ±in control data base) in one female and between day 8 and day 15 (vs.15 ±in control data base) in another female. 
Gross pathology:
At necropsy, no apparent abnormalities were observed in any animal.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD0 of the test item, distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products, was higher than 2000 mg/kg in rats.
Executive summary:

The objective of this study was to evaluate the toxicity of the test item, distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products, following a single oral administration in ratsaccording to OECD(No. 423, 17th December 2001) andCommission Regulation (EC) (No. 440/2008, B.1tris, 30 May 2008) guidelines.

The study was conducted in compliance with the principles of Good Laboratory Practice.

 

Methods

The test item, distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products, was administered once by oral route (gavage) to groups of three fasted female Sprague-Dawley rats at dose-levels of 300 or 2000 mg/kg under a dosage-volume of 10 mL/kg. The test item was prepared in corn oil. 

The study design was as follows:

 

Dose-level

(mg/kg)

Dosage-volume

(mL/kg)

Female

300

10

3

2000

10

3

2000

10

3

 

Each animal was observed at least once a day for mortality and clinical signs for a period of up to 14 days following the single administration. Body weight was recorded on day 1 and then on days 8 and 15.

On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. No organ samples were taken.

The interpretation of results was based on the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations).

 

Results

At the 300 mg/kg dose-level (three females), no deaths and no clinical signs were noted.

When compared to CIT historical control data the body weight gain of the animals was not affected by treatment with the test item.

At necropsy, no apparent abnormalities were observed in any animal.

 

At the 2000 mg/kg dose-level (three females then confirmation on three other females), no deaths occurred.

Hypoactivity or sedation and piloerection (in all animals), staggering gait (in 4 animals) and dyspnea (in 3 animals) were observed on day 1 only. A body weight loss (-3%) was noted between day 8 and day 15 in one female.

When compared to CIT historical control data, a lower body weight gain was noted between day 1 and day 8 (vs. 41 ±in control data base) in one female and between day 8 and day 15 (vs.15 ±in control data base) in another female. 

At necropsy, no apparent abnormalities were observed in any animal.

Conclusion

The oral LD0of the test item, distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products, was higher than 2000 mg/kg in rats.

According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations), concerning the potential toxicity by oral route, the test item should not be classified.