Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 January to 18 August 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-Study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): "3-hydroxy-2-(hydroxymethyl)-2-methylpropionaldehyde"
- Molecular formula (if other than submission substance): C5H10O3
- Physical state: Colourless, high viscous
- Composition of test material, percentage of components: ~ 82 % Dimethylpropanale, ~ 10 % Hydroxyethanesulfonic acid, Na-salt (CAS No.: 870-72-4), ~ 6 % water, ~ 2 % Potassiumformiate (CAS No.: 590-29-4)
- Lot/batch No.: CH 138067/001
- Expiration date of the lot/batch: 30 November 2010
- Stability under test conditions: Min. 1 year
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Species, strain: Rats, Crl:CD(SD).
Supplier: Charles River Deutschland GmbH, D-97633 Sulzfeld.
Number and sex: 6 females.
Age: Approx. 8 weeks at the time of the administration.
Health conditions: A health inspection was performed prior to the commencement of treatment to ensure that the animals were in a good state of health.
Hygiene: Optimal hygienic conditions.
Room number: EI1-11.
Room temperature: Ranges from 22 °C +/- 3 °C (continuous control and recording).
Relative humidity: Ranges from 30 - 70 % (continuous control and recording).
Air exchange: 12 per hour.
Light: Artificial light from 6 a.m. to 6 p.m.
Cages: Single caging in Makrolon cages type III (39 cm x 23 cm bottom area, 18 cm height). Wire mesh lids. Sanitation of cages once a week.
Bedding material: Aspen wood chips, Fa. ABEDD Dominik Mayr KEG, A-8580 Köflach, autoclaved. Random samples of the bedding material are analysed for contaminants by the supplier. Changes 1 / week.
Environmental enrichment: Nibbling wood bricks (10 cm x 2 cm x 2 cm) and nesting material, both from the same material and source as the bedding material, were offered to the animals once a week.
Feed: Ssniff R/M-H maintenance diet for rats and mice (item V1534-300) ad libitum, supplied by Ssniff Spezialdiäten GmbH, 59494 Soest, Germany. Analysis of the feed for ingredients and contaminants is performed randomly by Ssniff.
Exception: The feed was withdrawn the evening before the administration of the test substance and was offered again about three hours afterwards.
Water: Tap water from an automatic watering system, ad libitum. Random samples of the water are analysed by the "AGES", A-1226 Vienna, to check, if the water fulfils the requirements for drinking water for humans.
Identification: Labelling with felt-tipped pen on the tail and on the cage.
Acclimatisation: At least 7 days.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
deionised
Details on oral exposure:
A peroral administration was performed once in the morning by stomach intubation using a metal gavage.
Vehicle: deionised water.
Dose volume: 10 mL per kg body weight.
Justification: The test substance was sufficeiently soluble in water and water shalll be used pfeferagly, according to the guiedelines.
The solutions were prepared freshly before administration and were administered within 10 minutes after the preparation.
The selection of the starting dose was based on available data on the acute toxicity of a 50 % solution of the test substance, submitted by the sponsor (LD50 > 2000 mg/kg) and on the results of a dose range finding study for a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (internal study code ZSI32), where all animals survived a dose of 1000 mg/kg given on 7 consecutive days.
Therefore a LD50, oral > 2000 mg/kg was assumed.
The further proceeding was in accordance with the guideline/directive:
• Step 1: 2000 mg per kg body weight.
• Step 2: 2000 mg per kg body weight.



Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
3 per step (6 females per dose)
Control animals:
no
Details on study design:
Observations were performed within the periods 0 - 0.5, 0.5 - 1, 1 - 2, 2 - 4 and 4 - 6 hours after administration (p.a.) of the test substance and then at least once a day for a total of 14 days. Observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions.
Body weights were determined
• before administration.
• 7 days p.a.
• 14 days p.a.
Body weight gain was calculated for each week of the study, i.e. between
• 0 and 7 days p.a.
• 7 and 14 days p.a.
The animals were sacrificed by inhalation of 80 % CO2 + 20 % air 14 days p.a. and subjected to a necropsy including a gross pathological examination.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
All animals survived until the scheduled termination of the study.
Clinical signs:
All animals showed signs of reduced well-being from 1 h until 6 h p. a. This term encompasses unspecific alterations, like sedation, apathy, piloerection, hunched posture or closed eyes, in single or multiple occurrence.
Body weight:
All animals gained weight in both weeks p.a.
Gross pathology:
No abnormal findings were made in all animals at the necropsy 14 d p.a.

Any other information on results incl. tables

Table:    Body weights and body weight gain

             Individual data, means and standard deviations SD.

Dose

Animal

Body weight (g)

Body weight gain (g)

mg/kg (Step No.)

No.

before
administr.

7 days
p.a.

14 days
p.a.

death

0-7 days
p.a.

7-14 days
p.a.

2000

21

193

208

223

-

15

15

(1)

22

189

230

233

-

41

3

 

23

188

217

235

-

29

18

 

mean

190.0

218.3

230.3

-

28.3

12.0

 

SD

2.6

11.1

6.4

-

13.0

7.9

2000

24

187

214

232

-

27

18

(2)

25

183

210

221

-

27

11

 

26

187

214

230

-

27

16

 

mean

185.7

212.7

227.7

-

27.0

15.0

 

SD

2.3

2.3

5.9

-

0.0

3.6

Table:    Observations in life

             A grade of severity was recorded where applicable (low - mid - high).

Findings

Dose
(mg/kg), Step No.

Animal Nos.

Observation time
(p.a.)
first    last

signs of reduced well-being

2000, 1

21, 22, 23

1 h / 6 h

 

2000, 2

24, 25, 26

1 h / 6 h

Table:    Necropsy findings

             Number of animals examined: 6 females.

SYSTEM
Organ, finding

Dose
(mg/kg)

Step No.

Animal Nos.

no abnormal findings

2000

1

21, 22, 23

 

2000

2

24, 25, 26

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to Commission Directive 2001/59/EC "3-hydroxy-2-(hydroxymethyl)-2-methylpropionaldehyde" does not require classification for acute oral toxicity.
Executive summary:

The aim of the study was to investigate acute toxic effects of the test substance after a single peroral administration to rats.

Methods

Methods and investigations were performed in conformance with the OECD-Guideline 423, 17 December 2001 and theCouncil Regulation (EC) No 440/2008,Method B.1 tris.

Administration of the test substance

"3-hydroxy-2-(hydroxymethyl)-2-methylpropionaldehyde"was administered once orally via gavage as a solution in deionised water to female Crl:CD(SD) rats.

The dosing was performed sequentially to groups of 3 animals per step using a starting dose 2000 mg per kg body weight.

The dose volume was 10 mL per kg body weight for all groups.

Investigations

·      Body weights: before administration, 7 and 14 days after the administration (p.a.).

·      Clinical observations: at least once per day.

·      Necropsy: The animals were sacrificed and necropsied 14 days p.a.

Results

Dose
(mg/kg)

Step No.

No. of animals

Prominent findings

exposed

affected

deceased

in life

post mortem

2000

1

3

3

0

signs of reduced well-being

none

2000

2

3

3

0

signs of reduced well-being

none

 

Presence of signs in life

from 1 h until 6 h p.a.

Full recovery of the animals

yes

Body weights

all animals gained weight in both weeks p.a.

 

 

Findings in life and post mortem indicate

no severe toxic effects present

 

 

LD50, oralaccording to OECD

> 5000 mg/kg body weight