1-(N,N-bis(2-hydroxyethyl)amino)propan-2-ol

Endpoint summary

Description of key information

In a GLP study conducted according to OECD Guideline 401, an acute oral LD50 of greater than 2000 mg/kg bw (limit test) was determined for DEIPA in rats (Stebbins and Brooks, 1999a).

In a poorly-reported acute inhalation study, no deaths were seen following exposure of 6 male rats to DEIPA saturated air (16.4 mg/L) for 7 hours. An acute inhalation LC50 of greater than 16.4 mg/L [about 16,400 mg/m3] can be determined (Vaughn et al. 1975).

In a GLP study, conducted according to OECD Guideline 402, an acute dermal LD50 of greater than 2000 mg/kg bw (limit test) was determined for DEIPA in New Zealand White rabbits (Stebbins and Brooks, 1999b).

Overall, NICNAS (2009) considered DEIPA to be of low acute toxicity via the oral, dermal and inhalation routes.

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:

26 Jan to 9 Feb 1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OECD guideline study 401 (1987; available at time of study, deleted in 2002) to GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Inc. (Raleigh, NC)
- Age at study initiation: 2 months
- Weight at study initiation: 111-226 g
- Fasting period before study: Fasted the night prior to treatment
- Housing: No data
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3oC
- Humidity (%): 40-70%
- Air changes (per hr): 12-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Not applicable

Doses:

2000 mg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed at least once per day, weighed pre study and on test days 1, 2, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, eye examinations

Statistics:

Mean and standard deviations calculated for body weights, outliers included.

Preliminary study:

None

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95% confidence level not applicable as no deaths occurred.

Mortality:

All rats survived to the end of the 2-week observation period.

Clinical signs:

other: On test day 1, there was faecal soiling in 3 males and 3 females, watery or soft faeces in 1 male and 2 females and diarrhoea in 1 female. All signs resolved for all animals on test days 2 or 3. No other treatment-related clinical signs observed for the

Gross pathology:

No treatment-related gross pathologic observations.

Other findings:

1 male had a cloudy eye on test day 10 and one female had urine perineal soiling on test day 15. The investigators interpreted these observations to be not treatment-related.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

From the results of this GLP study conducted according to OECD Guideline 401 (1987; available at time of study) an acute oral LD50 of DEIPA in rats was determined to be greater than 2000 mg/kg bw (limit test).

Executive summary:

In a GLP acute oral toxicity study, conducted according to OECD guideline 401 (1987; available at time of study) groups of 5 male and female Fischer 344 rats were administered a single dose of 2000 mg/kg bw of neat DEIPA by gavage. During the two-week observation period the animals were frequently evaluated for weight changes and clinical signs of toxicity. All survivors were examined for gross pathological changes.

 

No mortality occurred over the two-week observation period and very few clinical treatment-related signs were observed. Faecal soiling in 3 males and 3 females, watery or soft faeces in a male and 2 females and diarrhoea in a female were noted on test day 1, which resolved for all animals by test day 3. All rats gained body weight over the 2-week ovservation period following a transient decrease in body weight on test day 1. There were no treatment-related gross pathological observations.

 

From the results of this study, an acute oral LD50 of DEIPA in rats was determined to be greater than 2000 mg/kg bw (limit test).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Good-quality, reliable, GLP-compliant, OECD-guideline study on DEIPA (Stebbins and Brooks, 1999a), which meets the REACH tonnage-driven data requirements. Some additional, very poorly-reported data (reliability 4) also available, which indicates a oral LD50 of between 1 and 2 g/kg bw in male rats [no further details given] (Vaughn, et al. 1985). As no deaths were seen in the more recent, reliability 1, OECD guideline GLP study, involving rats of both sexes, this is considered the most appropriate study on which to base the acute oral toxicity hazard conclusion.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: No details if guideline followed or if to GLP, limited reporting on methods and results

Principles of method if other than guideline:

Acute inhalation toxicity was assessed in male rats following a 7-hr exposure to DEIPA saturated air.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
No data

TEST ATMOSPHERE
No data

VEHICLE
- Composition of vehicle (if applicable): No data
- Concentration of test material in vehicle (if applicable): 16.4 mg/L (approx 3060 ppm)
- Justification of choice of vehicle: No data
- Lot/batch no. (if required): No data
- Purity: No data

TEST ATMOSPHERE (if not tabulated)
No data

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

ca. 7 h

Concentrations:

16.4 mg/L of air or approximately 3060 ppm

No. of animals per sex per dose:

6 males

Control animals:

not specified

Details on study design:

No data

Statistics:

None reported

Preliminary study:

None reported

Sex:

male

Dose descriptor:

LC50

Effect level:

> 16.4 mg/L air

Based on:

test mat.

Exp. duration:

7 h

Remarks on result:

other: 95% confidence levels not applicable since no deaths occurred

Mortality:

No deaths occured

Clinical signs:

other: None reported

Body weight:

None reported

Gross pathology:

None reported

Other findings:

All animals exhibited eye and nasal irritation which subsided 24 hours after exposure

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an acute inhalation study, no deaths were seen following exposure of 6 males rats to DEIPA saturated air (16.4 mg/L) for 7 hours. An acute inhalaiton LC50 of greater than 16.4 mg/L can be determined.

Executive summary:

In a poorly-reported acute inhalation toxicity study, 6 male rats were exposed to DEIPA saturated air (16.4 mg/L) for 7 hours at room temperature.

No mortality occurred. However, all animals exhibited eye and nasal irritation which had subsided 24-hr after exposure. From the results of this study, an LC50 of greater than 16.4 mg/L for DEIPA in rats can be determined.

Critical details were missing on the test substance identifty (e.g. purity/impurity profile), test methods (including species, number of animals, concentration used, level of examination) and results. Therefore, the findings of this early study should be interpreted with caution.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

16 400 mg/m³ air

Quality of whole database:

In a poorly-reported acute inhalation study, no deaths were seen following exposure of 6 males rats to DEIPA saturated air (16.4 mg/L) for 7 hours. An acute inhalation LC50 of greater than 16.4 mg/L [about 16,400 mg/m3] can be determined (Vaughn et al. 1975).

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:

26 Jan to 9 Feb 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study to GLP with slight deviations which are not expected to affect the outcome.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

temperature slightly outside recommended range

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

yes

Remarks:

temperature slightly outside recommended range

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Covance Research Products, Inc (Kalamazoo, MI)
- Age at study initiation: 3 months
- Weight at study initiation: 2.3-2.6 kg
- Fasting period before study: Not specified
- Housing: Not specified
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 +/-3 [OECD guideline recommends 20 +/-3, but unlikely to affect outcome]
- Humidity (%): 40-60
- Air changes (per hr): 12-15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Approx 10 by 14 cm
- % coverage: Approx 10%
- Type of wrap if used: Gauze/cotton patch held in place by an elastic rabbit jacket

The trunk of each rabbit was clipped free of fur the day prior to DEIPA application

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Skin wiped thoroughly with a water moistened soft disposable towel and dried with a soft disposable towel
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): 100%
- Constant volume or concentration used: yes

VEHICLE
Not applicable

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:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations at least once per work day, weighed pre-study and on test days 1, 2, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, eye examinations

Statistics:

Mean and standard deviations calculated for body weights, including outliers.

Preliminary study:

None

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95% confidence intervals not applicable since no deaths occurred

Mortality:

All rabbits survived to the end of the 2-week observation period

Clinical signs:

other: No clinical signs of systemic toxicity. All rabbits had reddened and/or thickened skin at the test site on day 2 which was resolved by day 3 in all rabbits apart from one male whose skin was reddened on day 3 and 4 with flaking/scaling skin on day 4 which

Gross pathology:

No visible lessions

Other findings:

None reported

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a GLP acute dermal toxicity study, conducted according to OECD Guideline 402, a dermal LD50 of greater than 2000 mg/kg bw (limit test) was determined for DEIPA in New Zealand White rabbits.

Executive summary:

In a GLP acute dermal toxicity study, conducted according to OECD Guideline 402, groups of 5 male and 5 female New Zealand White rabbits received a single application of 2000 mg/kg bw of neat DEIPA to clipped skin of the trunk. This treated area was subsequently covered for 24 hours and the application site washed on patch removal. During the two week observation period the animals were frequently evaluated for weight changes and clinical signs of toxicity. All survivors were examined for gross pathological changes.

 

No mortality occurred over the 2-week observation period and there were no signs of systemic toxicity. All male and female rabbits had reddened and/or thickened skin at the site of application on day 2. This was resolved by day 3 in all rabbits apart from one male whose skin was reddened on day 3 and 4 with flaking/scaling skin on day 4, returning to normal by day 7. A female was also noted to have had faecal soiling of the perineum on test day 2 only. All rabbits gained or maintained body weight over the 2 week period following a transient weight loss on day 1 and/or 2. There were no treatment-related gross pathological observations.

 

From the results of this study, an acute dermal LD50 of greater than 2000 mg/kg bw (limit test) was determined in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Good-quality, reliable, GLP-compliant, OECD-guideline study on DEIPA, which meets the REACH tonnage-driven data requirements.

Additional information

Oral

In a GLP acute oral toxicity study (reliability 1), conducted according to OECD Guideline 401 (1987; available at time of study) groups of 5 male and 5 female Fischer 344 rats were administered a single dose of 2000 mg/kg bw of neat DEIPA by gavage. During the 2-wk observation period the animals were frequently evaluated for weight changes and clinical signs of toxicity. All survivors were examined for gross pathological changes. No mortality occurred over the 2-wk observation period and very few clinical treatment-related signs were observed. Faecal soiling in 3 males and 3 females, watery or soft faeces in a male and 2 females and diarrhoea in a female were noted on test day 1, which resolved for all animals by test day 3. All rats gained body weight over the 2-wk observation period following a transient decrease in body weight on test day 1. There were no treatment-related gross pathological observations. From the results of this study, an acute oral LD₅₀ of greater than 2000 mg/kg bw (limit test) was determined for DEIPA in rats (Stebbins and Brooks, 1999a). In reviewing this study, NICNAS (2009) considered DEIPA to be of low acute oral toxicity.

According to an early study, the single-dose oral LD₅₀ for male rats is between 1 and 2 g/kg of test material. “There is little likelihood that internal injury would result from ingestion of amounts of the material one might encounter incidental to industrial handling" [no further details provided] (Vaughn et al., 1975). Critical details were missing on the test substance identity (e. g. purity/impurity profile), test methods (including species, number of animals, concentration used, level of examination) and results. Therefore, the findings of this early study should be interpreted with caution.

Inhalation

In accordance with column 2 of REACh Annex VIII, acute toxicity information should be provided for at least one other route in addition to the oral route, for substances other than gases. The choice of the second route depends on the nature of the substance and the likely route of human exposure. The acute inhalation test (required for section 8.5.2) does not need to be conducted as inhalation is not the most likely route of exposure (due to its expected low volatility). A reliable acute dermal study is available for DEIPA (see Stebbins and Brooks, 1999c, described below).

In an early, poorly-reported acute inhalation toxicity study (reliability 4), 6 male rats were exposed to DEIPA saturated air (16.4 mg/L) for 7 hr at room temperature. No mortality occurred. However, all animals exhibited eye and nasal irritation which had subsided 24-hr after exposure. From the results of this study, an LC₅₀ value of greater than 16.4 mg/L can be determined (Vaughn et al., 1975). Critical details were missing on the test substance identify (e. g. purity/impurity profile), test methods (including species, number of animals, concentration used, level of examination) and results. Therefore, the findings of this early study should be interpreted with caution. In reviewing this study, NICNAS (2009) considered DEIPA to be of low acute inhalation toxicity.

Dermal

In a GLP acute dermal toxicity study (reliability 1), conducted according to OECD Guideline 402, groups of 5 male and 5 female New Zealand White rabbits received a single application of 2000 mg/kg bw of neat DEIPA to clipped skin of the trunk. This treated area was subsequently covered for 24 hr and the application site washed on patch removal. During the 2-wk observation period the animals were frequently evaluated for weight changes and clinical signs of toxicity. All survivors were examined for gross pathological changes. No mortality occurred over the 2-wk observation period and there were no signs of systemic toxicity. All rabbits had reddened and/or thickened skin at the site of application on day 2. This was resolved by day 3 in all rabbits apart from one male whose skin was reddened on day 3 and 4 with flaking/scaling skin on day 4, returning to normal by day 7. A female was also noted to have had faecal soiling of the perineum on test day 2 only. All rabbits gained or maintained body weight over the 2-wk period following a transient weight loss on day 1 and/or 2. There were no treatment-related gross pathological observations. From the results of this study, an acute dermal LD₅₀ of greater than 2000 mg/kg bw (limit test) was determined in rats (Stebbins and Brooks, 1999b). In reviewing this study, NICNAS (2009) considered DEIPA to be of low acute dermal toxicity.

In addition, no significant adverse effects on body weight or "systemic effects" [extent of examination unclear] was seen in an acute dermal irritation study following a 4-hr occluded application of 0.5 ml of DEIPA to the clipped (intact) skin of 3 New Zealand White rabbits (Stebbins and Brooks, 1999c).

References

NICNAS (2009). Australian National Industrial Chemicals Notification and Assessment Scheme. Full Public Report. DEIPA. File No: STD/1344. December 2009.http://www.nicnas.gov.au/publications/CAR/new/Std/StdFULLR/std1000FR/std1344FR.pdf 

Justification for selection of acute toxicity – oral endpoint
GLP, OECD guideline study (reliability 1).

Justification for selection of acute toxicity – inhalation endpoint
The only inhalation study available (reliability 4).

Justification for selection of acute toxicity – dermal endpoint
GLP, OECD guideline study (reliability 1).

Justification for classification or non-classification

Based on the weight-of-evidence on DEIPA (including results from the GLP and OECD-compliant acute oral and dermal toxicity studies, and a limited acute inhalation toxicity study), classification and labelling under CLP for acute toxicity (or STOT SE) is not warranted.