Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-11-15 until 2012-12-19
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
other: Commission Regulation (EC) No 440/2008
Qualifier:
according to
Guideline:
other: Japan MAFF 8147
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Aminopropyl Vinyl Ether
- Test substance No: 12/0567-1
- Homogeneity: The test substance was homogenous by visual inspection.
- Analytical purity: > 99.6 corrected area%
- Batch No.: C520/070/2012/2
- Physical state/colour: Liqiud/colourless, clear
- Storage conditions: room temperature; avoid temperatures >25°C
- Storage stabilityl: The stability under storage conditions over the study period was guarenteed by the sponsor, and the sponsor
holds this responsibility.
- Other: Density[g/mL] 0.892

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany.
- Age at study initiation: young adult animals (female animals approx. 10 weeks)
- Weight at study initiation: 181 - 190 g
- Housing: The animals were single housed in fully air-conditioned rooms.
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diet Services, 67122 Altrip, Germany
- Water (e.g. ad libitum): tap water ad libtum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30-70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
300 mg/kg bw: 6 females
2000 mg/kg bw: 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration, weekly thereafter and on the last day of observation. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Mortality:
All animals of the 300 mg/kg bw dose group survived.
All animals of the 2000 mg/kg bw dose group died within hour 0 after administration.
Clinical signs:
Clinical observation in the 2000 mg/kg bw test group revealed poor general state, pronounced dyspnoea, piloerection and salivation in all three animals. Additionally, one animal showed clonic convulsions and respiration noises.
In the first 300 mg/kg test group impaired general state and piloerection were noted in all animals from hour 0 until study day 2 after administration In one animal dyspnoea was noted from hour 0 until hour 5. In the other two animals dyspnoea was noted at hour 0 and enhanced to pronounced
dyspnoea from hour 1 up to hour 2 or 3, respectively. Thereafter dyspnoea was noted until hour 5 after administration. In addition, exophthalmos
was noted from hour 1 until hour 3 in two animals. From hour 0 until hour 5 salivation was noted in all animals of this test group while lacrimation
was noted at hour 3 and/or hour 4 in two animals.
In the second 300 mg/kg bw test group impaired general state and piloerection were noted in all animals from hour 0 until hour 5 and persistent in one animal until study day 6. In another animal these findings were also noted on study day 1 and 3. In all animals of this test group pronounced dyspnoea was noted from hour 0 until hour 2. Thereafter dyspnoea was noted from hour 3 until hour 5. Salivation was noted from hour 0 until hour 3 in all animals.
Body weight:
The body weight of three animals in both 300 mg/kg dose groups decreased during the first post-observation week, but increased normally
during the second post-observation week. The body weight of the three other animals increased normally during the observation period.
Gross pathology:
The following macroscopic pathologic findings were observed in all animals that died in the 2000 mg/kg bw test group: Severe swelling of the
stomach mucosa, dark red discoloration of the stomach content, extensive bleeding in the glandular stomach and forestomach, dark red
discoloration of the small intestine and its content, spotted discoloration of the liver and congestion in the kidneys.
There were no macroscopic pathological findings in the animals sacrificed at the end of observation period (300 mg/kg bw: 6 females).

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the conditions of this study the median lethal dose of Aminopropyl Vinyl Ether after oral administration was found to be greater than 300 mg/kgbw and less than 2000 mg/kg bw in rats.
Based on the results of this study, the test substance has to be classified Acute Tox Cat 4 (Directive 1272/2008 of CLP) and R22 (67/548/EWG).