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Administrative data

Description of key information

Oral toxicity: 
In an acute oral toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 > 300 mg/ kg bw and <2000 mg/kg bw was determined for TEAH. This corresponds to an LD50 of >0.844 mL/kg bw and < 5.627mL/kg bw for TEAH 35% in water.
Dermal toxicity:
One reliable study (without restrictions) with TEAH 35% in water is available, which shows that the dermal LD50 > 2000 mg/kg bw. This is equivalent to an LD50 of >700 mg/kg bw for TEAH.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
300 mg/kg bw
Quality of whole database:
The study has been performed according to OECD and/or EC guidelines and according to GLP principles (Klimisch 1).

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 September, 2010 - 14 October, 2010
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.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Boyertown, PA
- Age at study initiation: no data
- Weight at study initiation: males: 268 - 286 g; females: 188 - 240 g
- Housing: Individually housed in suspended wire cages
- Diet: Free access to PMI Rat Chow diet
- Water: Free access to water.
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
The day prior to application of the test article, the dorsal area of the trunk of each animal was clipped free of hair. The prepared site was approximately 10% of the body surface and remained intact.

A single dose of the test substance was applied to the prepared site, over a porous gauze dressing measuring 4 x 6 cm. The torso was wrapped with ppastic in a semi-occlusive manner and was secured with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
Residual test sbstance was removed by gently washing with distilled water.
Duration of exposure:
24 hours.
Doses:
2000 mg/kg bw


No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Dose volume: no data

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: twice a day
Body weights: pretest, weekly and at termination
Clinical signs: 1, 2 and 4 hours and once daily for 14 days
- Necropsy of survivors performed: All animals were examined for gross pathology.
Statistics:
None.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
dissolved
Remarks:
35% aqueous solution
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 700 mg/kg bw
Based on:
other: pure test substance
Mortality:
2 males and 1 female died.
Clinical signs:
The male and female rats were normal up to 4 hours after dosing. Shortly after the 4 hour observation, among 2 males convulsing and vocalizing were observed. The 2 males were found dead on day 1. All remaining males were normal at all other observation periods. One female was found dead on day 1. One female was noted with few feces, wetness of the anogenital area and chromorhinorrhea on days 1 through 3. All remaining females were normal at all other observation periods.
Body weight:
All surviving animals gained weight.
Gross pathology:
Necropsy observations were normal except for the skin, which appeared to have pale and dark areas (necrotic). The dose sites appeared to have been depilated for 3 out of 10 animals. Two males were noted with redness and/or brown staining of the nose/mouth area. One female was noted with red staining of the nose/mouth area.
Other findings:
Skin observations of the surviving animals at 24 hours were necrotic with pale areas. Edema was absent to very slight. On days 7 and 14, skin was necrotic with flaking of the skin on 2 animals by day 14. There was no edema noted.
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
In an acute dermal toxicity study with rats, performed according to OECD 402 guideline and GLP principles, an LD50 >2000 mg/kg bw was determined for TEAH (35% aqueous solution). This is equivalent to an LD50 of >700 mg/kg bw for the pure substance.
Executive summary:

An acute dermal toxicity test with 35% tetraethylammonium hydroxide was performed according to OECD 402 test guideline and GLP principles. Male and female rats were exposed to 2000 mg/kg bw. Two males and one female died.

Clinicals signs included convulsing, vocalizing, few feces, wetness of the anogenital area and chromorhinorrhea. Skin observations of the surviving animals at 24 hours revealed necrotic tissue with pale areas. Edema was absent to very slight. The LD50 was found to be >2000 mg/kg bw, this is equivalent to an LD50 of >700 mg/kg bw for the pure substance.

Therefore, TEAH (pure substance) is classified as category 3 for dermal toxicity according to Regulation No. 1272/2008 and should be labelled with H311: Toxic in contact with skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
700 mg/kg bw
Quality of whole database:
Two studies are available performed with TEAH. The key study (Klimisch 1) and a disregarded study (Klimisch 3).

Additional information

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 TEAH 35% in water (resp. 300 mg/kg bw or 2000 mg/kg bw 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 TEAH, which corresponds to an LD50 of >0.844 mL/kg bw and <5.627 mL/kg bw for TEAH 35% in water.

Dermal toxicity was addressed by an acute dermal toxicity test with TEAH 35% in water, performed according to OECD 402 test guideline and GLP principles. Male and female rats were exposed to 2000 mg/kg bw. Two males and one female died. Clinicals signs included convulsing, vocalizing, few feces, wetness of the anogenital area and chromorhinorrhea. Skin observations of the surviving animals at 24 hours revealed necrotic tissue with pale areas. Edema was absent to very slight. The LD50 was found to be >2000 mg/kg bw, this is equivalent to an LD50 of >700 mg/kg bw for TEAH.


Justification for selection of acute toxicity – oral endpoint
One reliable study available

Justification for selection of acute toxicity – dermal endpoint
The study has been performed according to OECD and/or EC guidelines and according to GLP principles (Klimisch 1).

Justification for classification or non-classification

Based on the oral LD50 of >300 mg/ kg bw, TEAH is classified in category 4 for acute oral toxicity according to CLP Regulation (EC) No. 1272/2008. The oral LD50 of TEAH 35% in water was found to be >0.844 mL/kg bw (corresponding to >861 mg/kg bw) and is classified cat. 4 as well.

Based on the dermal LD50 of > 700 mg/kg bw, TEAH is classified in category 3 for acute dermal toxicity according to CLP Regulation (EC) No. 1272/2008. As TEAH 35% in water was found to have a dermal LD50 of > 2000 mg/kg bw, a 35% aqueous solution of TEAH is not classified.

At 300 mg/kg bw, effects were seen that indicate effects of TEAH on central nervous system (uncoordinated movements, tremors of the head (2/6 rats) and ptosis (1/6 rats). Severe clinical effects were observed with substance analogues TMAH and TMAC indicating an effect on the central nervous system after oral exposure. Although effects of TEAH were less severe, based on the data from analogues it cannot be excluded that CNS is affected at 300 mg/kg bw. Based on these considerations, TEAH is classified STOT Single Exp. 1 according to CLP Regulation (EC) No. 1272/2008. As the generic concentration limit triggering classification 1 of a mixture is ≥ 10%, a 35% aqueous solution of TEAH is also classified STOT Single Exp. 1.

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