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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29APR2015 - 02JUN2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
(2001)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
(Official Journal of the European Union No. L142, May 2008, including the most recent amendments)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
(2002)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147 (November 2000, including the most recent partial revisions)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetraethylammonium hydroxide
EC Number:
201-073-3
EC Name:
Tetraethylammonium hydroxide
Cas Number:
77-98-5
Molecular formula:
C8H20N.HO
IUPAC Name:
N,N,N-triethylethanaminium hydroxide
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): TEAH 35% in water
- Substance type: Organic
- Physical state: Clear colourless liquid
- Purity/composition correction factor required: Yes, correction factor is 2.87 (correction of water content, adjust to 100% TEAH)
- Storage condition of test material: In refrigerator (2-8°C) in the dark
- pH: >13
- Specific Gravity / Density: 1.02

Test animals

Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
female
Details on test animals or test system and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young females (approx. 8-10 weeks old)
- Weight at study initiation: 144-184g
- Fasting period before study: yes
- 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), except o/n prior to dosing and until 3-4 hours after administration of the test substance
- Water: Free access to tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 29APR2015 to: 02JUN2015

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: test substance provided as 35% solution in water
Details on oral exposure:
GAVAGE METHOD: plastic feeding tubes.

Frequency: Single dosage, on day 1.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (5.627 mL/kg) bw and 300 mg/kg (0.844 mL/kg) bw.

DOSAGE PREPARATION: The test substance was dosed undiluted as delivered by the sponsor. The test substance was kept at room temperature for a maximum of 4 hours prior to dosing. A factor of 2.87 was used to correct for the purity/composition of the test substance to adjust to 100% TEAH (adjustment was made for specific gravity of the test substance). The test item was stirred on a magnetic stirrer during dosing.
Doses:
300 and 2000 mg/kg body weight

No. of animals per sex per dose:
300 mg/kg bw: 6 (2 groups of three females in a stepwise manner)
2000 mg/kg bw: 3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.
- Necropsy of survivors performed: The animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
The oral LD50 value of the test substance was ranked within the following ranges: 0-5, 5-50, 50-300 or 300-2000 mg/kg bw or as exceeding 2000 mg/kg bw. The LD50 cut-off value was established based on OECD guideline 423. No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 0.844 - < 5.627 mL/kg bw
Based on:
test mat.
Remarks:
(TEAH 35% in water)
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
other: TEAH
Mortality:
At 300 mg/kg bw, one animal was found dead between 2 and 4 hours after application.
At 2000 mg/kg bw, all three animals died within 2 hours after application.
Clinical signs:
At 300 mg/kg bw, all animals showed hunched posture and piloerection, accompanied by lethargy (3 rats). In addition, two rats showed uncoordinated movements and tremors of the head. These effects were resolved on day 2, except for hunched posture in two rats which resolved after day 3. Two rats were noted to have lean appearance from day 7 on. One of these two rats had ptosis (grade 2) on days 13 and 15. One additional rat had piloerection and hunched posture from day 8 (with chromodacryorrhoea at the snout on day 13).
At 2000 mg/kg bw, hunched posture was noted for all animals.
Body weight:
Body weight loss (on day 8) or reduced body weight gain was noted for most surviving animals treated at 300 mg/kg bw.
Gross pathology:
At 300 mg/kg bw, dark, red discolouration of the stomach was noted for the animal found dead. Reduced thymus was noted for another animal. Macroscopic post mortem examination of the other animals did not reveal any abnormalities.
At 2000 mg/kg bw, dark, red discolouration of the stomach was noted for all animals at macroscopic examination.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In an acute oral toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 of >0.844 mL/kg bw and < 5.627 mL/kg bw 35% diluted TEAH was found. This corresponds to an LD50 > 300 mg/ kg bw and <2000 mg/kg bw for undiluted TEAH.
Executive summary:

An acute oral toxicity study with rats was performed according to OECD/EC test guidelines and GLP principles. Female rats were dosed with 0.844 mL/kg bw and 5.627 mL/kg bw of 35% TEAH (resp. 300 mg/kg bw or 2000 mg/kg bw pure TEAH).

At 300 mg/kg bw, one animal was found dead between 2 and 4 hours after application. At 2000 mg/kg bw, all three animals died within 2 hours after application. At 300 mg/kg bw, lethargy, tremor, hunched posture, uncoordinated movements, piloerection, pale appearance, lean appearance, ptosis and/or chromodacryorrhoea (snout) were noted for the animals throughout the observation period. At 2000 mg/kg bw, hunched posture was noted for all animals on day 1. Body weight loss or reduced body weight gain was noted for most surviving animals treated at 300 mg/kg bw. Necropsy revealed dark, red discolouration of the stomach of all animals found dead. No substance-related findings were seen in surviving animals. Based on these results, an LD50 > 300 mg/ kg bw and < 2000 mg/ kg bw was determined for undiluted TEAH (which corresponds to an LD50 of >0.844 mL/kg bw and <5.627 mL/kg bw 35% diluted TEAH). Both TEAH and 35% TEAH are classified for acute toxicity category 4 according to regulation (EC) No 1272/2008.