Bis(2-dimethylaminoethyl)(methyl)amine

Endpoint summary

Description of key information

Acute toxicity oral: study equivalent/similar to OECD Guideline 401, doses: 3200, 1600, 800 and 200 µL/kg bw, rat m/f, 8 days observation, LD50 = 1330 mg /kg bw.
Acute toxicity dermal: study equivalent or similar to OECD Guideline 402, doses: 200, 1000 mg/kg bw, Vienna White rabbit m/f, occlusive coverage, LD50>200 mg/kg bw < 1000 mg/kg bw. 
Acute toxicity ihalalation:  study comparable to OECD Guideline 403, doses: 69, 164, 230 or 366 ppm, whole body exposure, rat m/f, LC50 = 2055.5 mg/m3 (2.056 mg/L).
Acute toxicity other: intraperitoneal injection, mice m/f, 7 days observation, LD50 = 315 mg/kg.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions - limited description of test animals - observation duration of 8 days only

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(limited documentation, observation duration of only 8 days)

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Gassner
- Mean weight at study initiation: 192.5 g (males); 181.5 g (females)

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30%, 16%, 8% and 2% (v/v)

MAXIMUM DOSE VOLUME APPLIED: ca. 10.6 mL/kg bw

Doses:

3200, 1600, 800 and 200 µL/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 8 days
- Frequency of observations: daily
- Frequency of weighing: doumentation on day 0
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 330 mg/kg bw

Based on:

test mat.

95% CL:

> 663 - < 2 653

Remarks on result:

other: Corresponds to ca. 1600 µL/kg bw; Conversion based on a density of 0.829 mg/cm³.

Mortality:

- 3200 µL/kg bw: 10/10 animals died within 24 h after application.
- 1600 µL/kg bw: 4/10 animals died within 8 days after application (1 male within 8 days, 1 female within 24 h and 2 more females within the following 24 h after application)
- 800 and 200 µL/kg bw: 0/10 animals died

Clinical signs:

other: - 3200 µL/kg bw: increased respiration (immediately after application); abdominal position (few minutes after application); crouched position, irregular respiration and slight apathy (few hours after application); crouched position, increased respiration

Gross pathology:

- Animals that died: general hyperaemia, heart dilatation, hydrothorax, grey-brown liver, liquid content of intestine, edema of glandular stomach, dilated ecchymosis, injected stomach vessels, diarrhoeic content of intestine.
- Sacrificed animals: no abnormalities

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 330 mg/kg bw

Quality of whole database:

2 (reliable with restrictions)

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

not specified

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals obtained from: Charles River Breeding Laboratories, Inc., Kingston, NY
Age of animals: 6 weeks
Animal housing: 2 per cage
Acclimation: 1 week prior to exposure
Assignment to exposure group: done by computer randomisation program
Water and Purina Certified Rodent Chow (Ralston Purina Co., St. Louis, MO) were available ad libitum except during exposure.

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

Vapors of PMDETA were generated using a glass J-tube method described by Miller, et al., (1980).
Chamber air flow, temperature and relative humidity were recorded at approximately half hour intervals during the 6 hour exposure period.
Sampling for analytical verification of test atmosphere concentrations was conducted near the breathing zone of the animals.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gas chromatography (Varian 1400, Palo Alto, CA) using a flame ionization detector

Duration of exposure:

6 h

Concentrations:

69, 164, 230 or 366 ppm; corresponding nominal concentrations 54, 152, 195 and 380 ppm

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Duration of observation period following exposure: 14 days
Frequency of observations: daily during exposure and observation
Frequency of weighing: days 2, 4, 8, 11 and 15.
Necropsy of survivors performed: yes
Other examinations performed: clinical signs - changes in fur, eyes, mucous membranes and respiration; behavior pattern and nervous system
activityassessed by specific observation for tremors, convulsions, salivation, lacrimation, and diarrhea, as well as lethargy and other signs of
altered central nervous system function; body weight measurements

Statistics:

Means and standard deviations of animal body weight, chamber temperature, relative humidity, and air flow were calculated for descriptive
purposes.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

290 ppm

Based on:

test mat.

Exp. duration:

6 h

Remarks on result:

other: 290 ppm = 2055.5 mg/m3

Mortality:

Rats exposed to 366 ppm PMDETA died immediately following exposure or were found dead on test day 2.
All rats exposed to 69, 164 and 230 ppm PMDETA survived the two-week post-exposure period.

Clinical signs:

other: Concentration dependent in-life observations of eye squint, corneal cloudiness, labored breathing and porphyrin staining of the external nares and eyes indicative of eye and nasal irritation. No skin irritation observed.

Body weight:

Mean body weights were decreased from pre-exposure values in all three groups during the first week post-exposure. By the end of the post- exposure period mean body weights were approximately equal to or greater than pre-exposure weights.

Gross pathology:

Residual evidence of eye irritation was the only treatment-related change identified upon gross pathologic examination.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

2 055.5 mg/m³ air

Quality of whole database:

1 (reliable without restrictions)

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (limited documentation on test substance, occlusive treatment, 2 dose levels tested only)

Qualifier:

equivalent or similar to guideline

Guideline:

other: 40 CFR, Section 163.81-2, Federal Register, August 22, 1978 and subsequently modified in accordance with the revised EPA Pesticide Assessment Guidelines of Nov 1982

Deviations:

no

GLP compliance:

yes

Remarks:

GLP compliance statement available

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Perfection Breeders, Inc., Douglassville, PA 19518 (U.S.D.A. License 123-DG)
- Acclimating period: 5 days prior to exposure
- Animals housed individually, maintained in accordance with standards set forth in the Guide for the Care and Use of Laboratory Animals (DHEW Publica- tion No. 80-23).
- Temperature: 60°F - 75°F, Relative Humidity,%: 55 +/- 25, Light: 12 hour light/dark cycle
- Mean weight at study initiation: 2 - 3 kg
- Diet: Wayne 15% Rabbit Ration ad libitum
- Water: ad libitum

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

Test site: back
Clipping of fur: 24 h before application
Area of exposure: ca. 10% of body surface
Type of wrap used: porous gauze patch wrapped with an impervious material.
Removal of the test substance: using water or an appropriate solvent, 24 h after the start of exposure

Duration of exposure:

24 hours

Doses:

200 and 1000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Rabbits (5 animals per sex/dose) were individually housed and maintained in accordance with standards set forth in the Guide for the Care and Use of Laboratory Animals (DHEW Publica- tion No. 80-23). The rabbits were acclimated to the laboratory for at least 5 days prior to dosing. healthy intact skin were used. Approximately 24 hours before testing, the fur was clipped from the backs of the test animals. Test Article was applied to approximately 10% of the body surface on each animal. The dressings were removed after 24 hours . Two dose levels were tested. The animals were observed for a 14 day period for signs of toxicity (systemic and topical) and for mortalities.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - < 1 000 mg/kg bw

Based on:

test mat.

Mortality:

exposure 200 mg/kg bw (males and females) - no mortality
exposure 1000 mg/kg bw - 4/5 males, 3/5 females

Clinical signs:

other: Males: - 200 mg/kg bw - signs of necrosis on the skin in all animals - 1000 mg/kg bw - signs of necrosis on the skin in all animals, signs of diarrhea in 1 animal Females: - 200 mg/kg bw - signs of necrosis on the skin in all animals - 1000 mg/kg bw - s

Gross pathology:

Males:
- 200 mg/kg bw - no findings
- 1000 mg/kg bw - pale kidneys and liver noted for the 1/5 animals found dead on day 3. Enlarged and pale kidneys noted for 2/5 animals found dead on day 4.
Females:
- 200 mg/kg bw - no findings
- 1000 mg/kg bw - pale kidneys and liver noted for the 1/5 animals found dead on day 3. Enlarged and pale kidneys noted for 2/5 animals found dead on day 4.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

200 mg/kg bw

Quality of whole database:

2 (reliable with restrictions)

Additional information

One study was available for oral and 2 studies each for dermal and inhalatory routes of exposure in assessing acute toxicity.

Regarding acute oral toxicity, exposed animals showed signs of increased and irregular respiration and were in crouched position. Necropsy of animals that died as the result of exposure revealed general hyperaemia, effects on heart, liver and difestive tract and hydrothorax. Study reports an LD50 value of 1330 mg/kg bw.

Key study on the dermal acute toxicity tested 2 concentrations of the PMDTA and the LD50 higher than 200, but lower than 1000 mg/kg bw was found. Design of the study did not allow more precise determination of LD50 for dermal exposure.

Regarding inhalatory acute toxicity study, LC50 of 290 ppm was calculated (95% confidence level, nonlinear interpolation between 230 ppm to 366 ppm); besides mortality, ocular, skin and/or nasal irritation was observed.

LC50 of 290 ppm was converted to mg/L and to mg/m3, using the following algorithms (OECD TG 39, 2009):

mg/L = ppm x MW / 24,450

LC50 [mg/L] = LC50 [ppm] x MW / 24,450 = 290 x 173.299 / 24,450 = 2.056 mg/L

mg/m3 = ppm x MW / 24.45 = 290 x 173.299 / 24.45 = 2055.5 mg/m3

MW is molecular weight and 24,450 is a conversion factor at 25°C.

Justification for selection of acute toxicity – oral endpoint
one study available; equivalent or similar to OECD Guideline 401 (Acute Oral Toxicity)

Justification for selection of acute toxicity – inhalation endpoint
The study comparable to OECD TG 403 was selected

Justification for selection of acute toxicity – dermal endpoint
Two studies were available for this endpoint, the study selected as the key study was equivalent or similar to OECD TG 402 (Acute Dermal Toxicity) and it tested 2 concentrations of the test substance, instead of 1 as tested in the supporting study.

Justification for classification or non-classification

According to the CLP Regulation, the substance is classified as:

Acute Tox. 4, H302 (Harmful if swallowed) based on oral LD50 of 1330 mg/kg bw.

Acute Tox. 3, H311 (Toxic in contact with skin) based on dermal LD50 greater than 200 and less than 1000 mg/kg bw.

Acute Tox. 3, H331 (Toxic if inhaled) based on inhalation LC50 of 290 ppm (2.056 mg/l) for vapours.