Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018/04/17 - 2018/05/03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Hydroxyacetone
EC Number:
204-124-8
EC Name:
Hydroxyacetone
Cas Number:
116-09-6
Molecular formula:
C3H6O2
IUPAC Name:
1-hydroxypropan-2-one
Test material form:
liquid
Specific details on test material used for the study:
The test item with a suitable chemical purity, analytical certificate, safety data sheet and information of the product were supplied by the Sponsor. All precautions required in the handling of the test item were outlined by the Sponsor. Identification of test item was made in the Toxi-Coop Zrt. on the basis of the information included in the analytical certificate, safety data sheet and analytical standard data sheet which was supplied by the Sponsor. These documenst are part of the raw data.

Test animals

Species:
rat
Strain:
Wistar
Remarks:
HsdHan
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: TOXI COOP ZRT. Cserkesz u. 90. 1103 Budapest, Hungary
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 weeks (first and second step)
- Weight at study initiation: 165 - 168 g (first step), 176 - 178 g (second step)
- Fasting period before study: 1 d
- Housing: Group caging (3 animals/cage) in Type III polypropylene/polycarbonate cage.
- Diet (e.g. ad libitum): ssniff® SM R/M-Z+H complete diet for rats and mice produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany, ad libitum
- Water (e.g. ad libitum): tap water from municipal supply, as for human consumption from bottle, ad libitum
- Acclimation period: 12 days in first step and 13 days in second step

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): above 10 air exchanges/hour by central air-condition system
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: approx. 2018/02/13 To: 2018/05/02 (first group), 2018/05/03 (second group)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mg/kg bw
- Lot/batch no. (if required): 1803-5501

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose of 2000 mg/kg bw was selected based on data for similar substances.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 (2 groups of 3 animals)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h after the treatment and twice each day for 14 days thereafter. Weighing was performed on day 0 (just before the treatment), on day 7 and on day 15
- Necropsy of survivors performed: yes
- Other examinations performed: Individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Statistics:
not applicable

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
not observed
Clinical signs:
other: no treatment related symptoms were observed
Gross pathology:
Moderate hydrometra was found in animal No.: 521 of group 1 and slight hydrometra was found in animal No.: 536 of group 2. Hydrometra is physiological finding and connected to the cycle of the animal.
No pathological changes were found indicate a toxic effect of the test item during the macroscopic examination of animals.
Other findings:
no other findings

Applicant's summary and conclusion

Interpretation of results:
other: EU GHS criteria not met
Conclusions:
No death occurred after the single 2000 mg/kg bw oral dose of Hydroxyacetone. There were no toxic clinical signs and any test item related effect found on body weights and body weight gains during the study. Autopsy revealed no treatment related pathological changes.
Executive summary:

To investigate the acute oral toxicity of Hydroxyacetone, the acute toxic class method according to OECD Guideline No. 423 was carried out involving a stepwise procedure. Based on data for similar substances 2000 mg/kg bw was used as the starting dose and administered to three female Wistar rats. No animal died in the first step at the 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, as the stopping criteria of Annex 2d of OECD Guideline No. 423 were met. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out 15th day after the treatment.

No lethality was noted at a single oral dose of 2000 mg/kg bw in female Wistar rats.

In the first step, no clinical symptoms were observed on the day of the treatment and during the 14-day observation period, the general state and behaviour of experimental animals were normal.

In second step, no clinical symptoms were observed on the day of the treatment and during the 14-day observation period, the general state and behaviour of experimental animals were normal.

The body weight development was undisturbed in all animals.

All organs of the animals treated with 2000 mg/kg bw proved to be free of treatment related gross pathological changes. Therefore, a LD50 exceeding 2000 mg/kg bw was determined for the test item.