Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 Oct 2018 - 01 Nov 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report Date:
2019

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
Dec 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
no
Qualifier:
according to
Guideline:
other: Appendix to Director General Notification, No. 12-Nousan-8147. Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF), November 2000, including the most recent revisions.
Version / remarks:
Nov 2000
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical appearance: clear colourless liquid
- Storage conditions: at room temperature
- Test item name as cited in the report: C12-14 Alcohol ethoxylated (EO<2.5), reaction products with epichlorohydrin
- Purity: UVCB
- Purity test date: 21 Sept 2018
- Batch: 1658866
- Expiry date of batch: 15 August 2019
Specific details on test material used for the study:
Specific gravity: 0.94 g/mL (determined by Charles River Den Bosch)

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 8-11 weeks old)
- Weight at study initiation: 151 to 203 g.
- Fasting period before study: Yes, animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item. Water was available.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 45 to 63%
- Air changes (per hr): approx 10
- Photoperiod (hrs dark / hrs light): 12/12
- For psychological/environmental enrichment, animals were provided with paper (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom), except when interrupted by study procedures/activities.

IN-LIFE DATES: From 18 Oct 2018 to 01 Nov 2018

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (10 mL/kg) body weight.
The dose volume (mL/kg bw) for each animal was based on the body weight measurement prior to dosing and was calculated as follows:
Dose level (g/kg) / spec.gravity or density (g/mL).

DOSAGE PREPARATION:
- The test substance was administered as received with a single dose on day 1.
- Adjustment was made for specific gravity of the test item. No correction was made for the purity/composition of the test item.
- The dosing formulations were stirred continuously during dose administration.

CLASS METHOD
- Rationale for the selection of the starting dose: The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. Based on the results, one additional group was dosed at 2000 mg/kg.
- The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.
Doses:
2000 mg/kg body weight


No. of animals per sex per dose:
6 (2 groups of three females in a stepwise manner)

Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
Mortality/Viability: twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings.
Body weights: Animals were weighed individually on day 1 (predose), 8 and 15. A fasted weight was recorded on the day of dosing.
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.
All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs were recorded if appropriate.

- Terminal procedures: All animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded.

Statistics:
No statistical analysis was performed (the method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture and piloerection were noted for the animals on days 1 and/or 2.
Body weight:
The mean body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Not classified according to Regulation (EC) No. 1272/2008
Conclusions:
In an acute oral toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined for C12-14 Alkyl ethoxylated glycidylether. The LD50 cut-off exceeded 5000 mg/kg bw. Based on these results, the substance is not classified for oral toxicity according to GHS and Regulation (EC) No. 1272/2008.
Executive summary:

Acute oral toxicity of C12-14 Alkyl ethoxylated glycidylether was evaluated by dosing two consecutive groups of three female Wistar Han rats at 2000 mg/kg body weight by oral gavage. The test item was administered as received. Adjustment was made for density of the test item (0.94 g/mL). 

Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred. Hunched posture and piloerection were noted for the animals on Days 1 and/or 2. The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals.

The LD50 of C12-14 Alkyl ethoxylated glycidylether exceeds 2000 mg/kg bw, with a LD50 cut-off exceeding 5000 mg/kg bw.