Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 22 March, 1996
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
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): 1,6-Hexanediol dimethacrylate
- Substance type: organic
- Physical state at room temperature: liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Species: rats (HsdBrl:WH,Full-Barrier, SPF)
- Source: Harlan Winkelmann GmbH, D-33178 Borchen, Germany
- Age at study initiation: no data
- Weight at study initiation: female 151-157 g and male 165-172 g
- Fasting period before study: Prior to administration of the test item animals were fasted by withholding food over-night Following the period of
fasting the animals were weighed and the test substance was administered. Then the food was withhold for a further 3-4 hours.
- Housing: animals were individually kept in Macrolon cages on Altromin saw fiber bedding
- Diet: ad libitum, Altromin 1324 maintenance diet for rats and mice, totally-pathogen-free-TPF
- Water: ad libitum, tap water (drinking water, municipal residue control, microbial. controlled periodically)
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 10 °C
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
cotton seed oil
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: The vehicle was chosen due to its non-toxic characteristics.
- Lot/batch no. (if required): Lot 65 H 0629
- Purity: no data, commercial grade assumed (Sigma Chemicals)

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
The starting dose was 2000 mg/kg body weight. Since no presence of compound-related mortality of the animals was observed no further testing was required.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were weighed prior to first application and once a week there­after.
- Necropsy of survivors performed: yes
- Other examinations performed: A careful clinical examination was made once a day.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central
nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor,
convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality and clinical signs observed
Mortality:
No compound related mortalities observed up to the oral application of 2000 mg/kg/bw.
Clinical signs:
No clinical signs of toxicity were observed throughout the observation period, except a reduced activity until 1 hour after dosing with all animals This reduction in activity is caused by the manipulation and oral gavage, respectively. 3 hours after dosing no specific clinical signs were found.
Body weight:
No weight loss was recorded. The weight gain was within the expected range.
Gross pathology:
Necropsy revealed an acute injection of blood vessels in all animals in the abdominal region. This finding is due to euthanasia with an overdose of pentobarbital injected intraperitoneally.
No other macroscopic necropsy findings were observed.

Any other information on results incl. tables

Body weight gain

 

 

Animal No. Sex

 

Day O

 

Day 7

 

Day 14

 

1 male

 

172

 

224

 

260

 

2  male

 

165

 

213

 

258

 

3  male

 

172

 

227

 

263

 

1 female

 

151

 

166

 

177

 

2  female

 

157

 

168

 

192

3  female

 

156

 

172

192

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
According to the test result according to OECD guideline 423 (acute toxic class method): LD50(14days) > 2000 mg/kg bw the test substance 1,6-Hexanedioldimethacrylate has to be classified as nontoxic in respect of its acute oral toxicity (EU). According to OECD GHS the substance is to be classified.
Executive summary:

In an acute oral toxicity study according to OECD guideline 423 (acute toxic class method), a group of male and female Wistar rats were given a single oral (gavage) dose of 1,6 -Hexanedioldimethacrylate at a dose of 2000 mg/kgbw and observed for 14 days.

A careful clinical examination was made once a day. At the end of the observation period the animals were sacrificed and necropsy was carried out to record gross pathological changes.

A maximum dosage of 2000 mg/kg BW according to the acute toxic class method regime, caused no compound related mortality within 14 days post application. No clinical signs of toxicity were observed throughout the observation period.

 

Therefore the oral LD50 (combined) was determined to be > 2000 mg/kg bw.

OECD GHS Category 5 ranges from 2000 - 5000 mg/kg bw and represents the lowest hazard category for classifying the acute oral toxicity of a chemical substance. ("Criteria for hazard Category 5 are intended to enable the identification of the test substances which are of relatively low acute toxicity hazard but which, under certain circumstances may present a danger to vulnerable populations". (OECD guideline 425 annex 4)).

    

Based on the results of this study ( LD50 acute toxic class test in male and female rats) 1,6 -Hexanedioldimethacrylate is not classified according to EU-GHS and according to OECD GHS criteria Category 5.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.