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

Acute Toxicity: dermal

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

temperature slightly outside recommended range

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

229-764-5

EC Name:

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

Cas Number:

6712-98-7

Molecular formula:

C7H17NO3

IUPAC Name:

1-[bis(2-hydroxyethyl)amino]propan-2-ol

Test material form:

other: Clear liquid

Details on test material:

- Name of test material (as cited in study report): Diethanolisopropanolamine (DEIPA)
- Substance type: Technical product
- Physical state: Liquid
- Analytical purity: 93%
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: No data
- Isomers composition: No data
- Purity test date: Not specified
- Lot/batch No.: 980035B
- Expiration date of the lot/batch: Not specified
- Stability under test conditions: Not specified
- Storage condition of test material: Not specified

Test animals

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

Administration / exposure

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.

Results and discussion

Preliminary study:

None

Effect levels

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

Applicant's summary and conclusion

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.