Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
up-and-down procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Oxirane, [(4-nonylphenoxy)methyl]-, reaction product with ethylene glycol
EC Number:
807-586-4
Cas Number:
634602-80-5
Molecular formula:
UVCB - so Molecular formula i snot applicable
IUPAC Name:
Oxirane, [(4-nonylphenoxy)methyl]-, reaction product with ethylene glycol
Test material form:
liquid: viscous
Remarks:
Reddish-Brown
Details on test material:
Lot #: LL6I0011

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Age: 10 - 12 weeks
Nulliparous and non-pregnant
Acclimatisation - 6-12 days
Housed in dividually in polypropylene solid bottom cages
Food: Adlibitum: Teklad Certified Global High fiber rat pellet feed manufactured by Envigo, USA
Water provided ad libitum via a water bottle: UV sterilized water filtered through Reverse Osmosis water filtration system
Enrichment was provided (Wooden block)
Rooms were cleaned daily.
All animals identified using a tattoo on the tail
Cages labeled with study id, test item code, sex, dose study code, cage number and animal number.

Environmental Conditions
Animal Room : BMR 28, Department of Toxicology
Environmental
Conditions
Temperature : 20 to 23 °C
Humidity : 57 to 66% relative humidity
Air Changes : 17 air changes/hour
Photoperiod : The photoperiod was 12 hours artificial light and 12 hours darkness, light hours being 06:00 h – 18:00 h which was maintained through an automatic timer.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test item was a liquid product and was tested undiluted, as received and the dose volume was adjusted according to the dose level, density of test item and body weight to permit constant dose administration. All rats were dosed by gavage (day 1) using a metal cannula attached to a BD 1 mL disposable syringe which was graduated up to 1 mL. Rats were fasted overnight prior to dosing and until three hours post-dosing.
Doses:
This study was conducted as a limit study with the dose level of 2000 mg/kg body weight. The first rat was given a single dose of 2000 mg/kg body weight. No mortality was observed at this dose level up to 48 h post dosing. Therefore, rat N° 2, 3, 4 and 6 were treated with the same dose level of 2000 mg/kg body weight, one at a time, separated by minimum 48 h intervals.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Rats were observed for toxicity and mortality at 0.5, 1, 2, 3, 4, and 6 hours post dosing, and then twice daily for the remainder of the 14 day observation period. Clinical signs were recorded daily, and body weights were taken prior to dosing on day 1 and then on days 8 and 15.

At study termination, all rats were humanely euthanised by carbon dioxide asphyxiation. All rats on the study were subject to a gross pathological examination consisting of an external examination and opening of abdominal and thoracic cavities. The stomach of each rat was opened, the contents
rinsed/removed, and the mucosal surface was examined for signs of irritation, erosions, ulcers or any other findings. Gross macroscopic changes, if any, were recorded.
Statistics:
The LD50 was calculated using the Dixon’s maximum likelihood method using software (AOT 425 StatPgm)

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
there were no deaths during the study
Clinical signs:
No clinical signs reported
Body weight:
BW increase was normal
Gross pathology:
External
External examination of the terminally sacrificed rats did not reveal any abnormality.
Internal
Visceral examination of terminally sacrificed rats did not reveal any lesions. In absence of any pathological lesion in terminally sacrificed animals, it is concluded that the test item did not produce any treatment related effect at the dose level used in the present study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test material produced no mortalities at the limit dose of 2000 mg/kg bw. Therefore the LD50 is determined to be >2000 mg/kg bw and it is not classificable for acute toxicity.
Executive summary:

An acute oral toxicity study (Up-and-Down Procedure) was conducted using five female Wistar rats given a single oral dose of the test material (Undiluted, as received). A limit Test was conducted with 2000 mg/kg body weight. The first rat survived; hence the four additional female Wistar rats each received a single dose of 2000 mg/kg body weight according to the Up-and-Down Procedure.

No sign of toxicity was observed in the rats treated with the test material at 2000 mg/kg body weight.

All rats were active and healthy during the study. All rats gained body weight by the end of the study period. External and visceral examination of terminally sacrificed rats did not reveal any lesions of pathological significance. In absence of any pathological lesion in terminally sacrificed animals, it is concluded that the test item did not produce any treatment related effect at the dose level used in the present study. The acute oral estimated LD50 was found to be greater than 2000 mg/kg body weight in female Wistar rats.