Diethyl bis(2-hydroxyethyl)aminomethylphosphonate

Endpoint summary

Description of key information

Acute toxicity via Oral route: Combined Rat LD50 > 5000 mg/kg bw (OECD 401, K, Rel.2).

Acute toxicity via Dermal route: Combined Rabbit LD50 > 2000 mg/kg bw (OECD 402, K, Rel.2).

Acute toxicity via Inhalation route: Combined Rat LC50 > 520 mg/m3 (eq. OECD 403, K, Rel.2)

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

Study period:

15 Jul - 16 Dec 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Version / remarks:

1978

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Receipt date: 25 Jun 1981
- Color: amber
- Form: viscous liquid

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Portage, USA
- Weight at study initiation: 152-185 g (females), 176-212 g (males)
- Fasting period before study: 16-18 hours prior to treatment

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Amount of vehicle: 10 mL/kg bw

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10 males and females per dose group and per control

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: minimally twice a day; only once a day on holidays and weekends
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: other: Females: piloerection and red facial stains in all animals; one rat with alopecia Males: mild depression and red facial stains

Gross pathology:

Females: reddened intestines
Males: no adverse effects

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test material is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

Executive summary:

In an acute toxicity study conducted according to the OECD TG 401, Sprague-Dawley rats (5/sex) were administed with the test material diluted in corn oil at a single oral (gavage) dose of 5000 mg/kg bw.

 

No mortality occurred during the study period.

Piloerection and red facial stains were observed in in all females. One female also had alopecia. Mild depression and red facial stains were noted in males.

 

Combined Oral LD50 > 5000 mg/kg bw.

 

Under the test conditions, the test material is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 5 000 mg/kg bw

Quality of whole database:

The Key study is of adequate reliability (Klimisch score = 2).

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

old study report with limited documentation

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981

GLP compliance:

no

Test type:

traditional method

Limit test:

no

Specific details on test material used for the study:

- Color: yellow-brown
- Form: liquid
- Relative density: 1.164 (at 20°C)

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeder Winkelmann, Borchen, Germany
- Weight at study initiation: 160-180 g
- Housing: 5 animals of same sex per cage in makrolon cages (type III)
- Diet: "Altromin-R-Standardkost" ad libitum
- Water: tap water ad libitum

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- System of generating aerosols: The test substance was mixed with a solution of alcohol-Lutrol (1:1) containing oil red and sprayed in the inhalation chambers.

TEST ATMOSPHERE
- Brief description of analytical method used: Spray mist from the inhalation chamber was absorbed with cotton wool and oil red was extracted with Xylol. The concentration of the test substance in the air was indirectly measured by the extinction of the red coloured solution at 525 nm (the amount of oil red/L air equals the amount of test substance).
- Samples taken from breathing zone: yes

Duration of exposure:

>= 1 - <= 4 h

Remarks on duration:

Exposure for 1 or 4 h

Concentrations:

524 mg/m^3 for 1 h exposure
243 and 520 mg/m^3 for 4 h exposure

No. of animals per sex per dose:

10 males and 10 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: no

Statistics:

LC50 was calculated via probit analysis

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 524 mg/m³ air

Based on:

test mat.

Exp. duration:

1 h

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 520 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No clinical signs were observed during the study period.

Body weight:

Body weight was not examined during the study period.

Gross pathology:

Gross pathology was not performed.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test material is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

Executive summary:

In an acute inhalation toxicity study conducted similarly to the OECD TG 403, groups of Wistar rats (10/sex) were exposed by inhalation route to the test material mixed with a solution of alcohol-Lutrol (1:1) for 1 or 4 hours to whole body at concentrations of 524 mg/m3 (1-hour exposure), 243 or 520 mg/m3 (4-hour exposure). Animals were then observed for 7 days.

 

No mortality occurred during the study period. No clinical signs were observed.

 

Combined Inhalation LC50 > 524 mg/m3 (1-hour exposure).

Combined Inhalation LC50 > 520 mg/m3 (4-hour exposure).

 

Under the test conditions, the test material is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 520 mg/m³ air

Physical form:

inhalation: aerosol

Quality of whole database:

The Key study is of adequate reliability (Klimisch score = 2).

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:

15 Jul - 16 Dec 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Version / remarks:

1978

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Receipt date: 25 Jun 1981
- Color: amber
- Form: viscous liquid

Species:

rabbit

Strain:

other: Stauffland albino rabbits

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Phillips Rabbitry, Soquel, USA
- Weight at study initiation: 1.550-1.866 kg

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: abdominal skin
- Treatment of skin: abration of skin on half of the test animals
- Type of wrap: protective binder (during treatment with test material), gauze binder (during 14-day follow-up period)

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males and females per dose and 2 males and females per control

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: minimally twice a day; only once a day on holidays and weekends
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: other: Mild depression in all rabbits; one rabbit with diarrhea.

Gross pathology:

Necropsy and histopathological examination revealed no substance-related findings.

Other findings:

- Local dermal effects: mild erythema and edema

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test material is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

Executive summary:

In an acute dermal toxicity study performed according to the OECD TG 402, groups of Stauffland albino rabbits (5/sex) were dermally exposed to the undiluted test material for 24 hours to abraded and unabraded abdominal skin at doses of 2000 mg/kg bw. Animals then were observed for 14 days.

 

No mortality occurred during the study period. The only adverse clinical sign in all rabbits was mild depression. One rabbit had diarrhea.

Necropsy and histopathological examination revealed no substance-related findings.

Local dermal effects included mild erythema and edema.

 

Combined Dermal LD50  > 2000 mg/kg bw

Under the test conditions, the test material is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

The Key study is of adequate reliability (Klimisch score = 2).

Additional information

Acute toxicity: via Oral route

A key study is identified. This study was conducted according to the OECD TG 401. Piloerection and red facial stains were observed in in all females. One female also had alopecia. Mild depression and red facial stains were noted in males.

Combined Rat Oral LD50  > 5000 mg/kg bw

 

Acute toxicity: via Dermal route

A key study is identified. This study was conducted according to the OECD TG 402. No mortality occurred during the study period. The only adverse clinical sign in all rabbits was mild depression. One rabbit had diarrhea. Necropsy and histopathological examination revealed no substance-related findings. Local dermal effects included mild erythema and edema.

Combined Rabbit Dermal LD50  > 2000 mg/kg bw

 

Acute toxicity: via Inhalation route

A key study is identified. This study was conducted similarly to the OECD TG 403. Groups of Wistar rats (10/sex) were exposed by inhalation route to the test material mixed with a solution of alcohol-Lutrol (1:1) for 1 or 4 hours to whole body at concentrations of 524 mg/m3 (1-hour exposure), 243 or 520 mg/m3 (4-hour exposure). Animals were then observed for 7 days.

No mortality occurred during the study period. No clinical signs were observed.

Combined Inhalation LC50 > 524 mg/m3 (1-hour exposure).

Combined Inhalation LC50 > 520 mg/m3 (4-hour exposure).

 

 

Justification for classification or non-classification

Harmonised classification:

The substance has no harmonised classification according to the Regulation (EC) No. 1272/2008 (CLP). 

 

Self classification:

Acute toxicity via Oral route:

Based on the available information, the substance is not classified according to the CLP and the GHS as the LD50 is greater than 5000 mg/kg bw.

 

Acute toxicity via Dermal route: 

Based on the available information, the substance is:

- not classified according to the CLP as the LD50 is greater than 2000 mg/kg bw 

- not classified according to the GHS as the LD50 is greater than 2000 mg/kg bw and reliable evidence do not indicate the LD50 to be in the range of Category 5 values.

 

Acute toxicity via Inhalation:

Based on the limited available information, the substance is not classified according to the CLP and to the GHS.

 

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required. 

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute oral toxicity study. 

 

Specific target organ toxicity: single exposure (Dermal):

The classification criteria according to the CLP and the GHS as specific target organ toxicant (STOT) – single exposure, dermal are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (dermal) for a Category 1 classification (C ≤ 1000 mg/kg bw) and at the guidance value (dermal) for a Category 2 classification (2000 mg/kg bw ≥ C > 1000 mg/kg bw). No classification is required. 

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute dermal toxicity study. 

 

Specific target organ toxicity: single exposure (Inhalation):

Based on the limited available information, the substance is not classified according to the CLP and to the GHS.

 

Aspiration hazard:

The substance is not a hydrocarbon and no effects were observed on lungs in oral studies, therefore the criteria for aspiration toxicity according to the CLP and to the GHS are not met.