Bis(2-hydroxyethyl)ammonium acetate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

1999-07-29 to 1999-08-19

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is the result of a structural analogue substance used as read-across substance. Study is conducted according to Guidelines in a GLP certified laboratory.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

RA1

IUPAC Name:

RA1

Test material form:

other: liquid

Details on test material:

- Physical state: Pale yellow liquid
- Stability under test conditions: Stable under storage conditions
- Storage condition of test material: At room temperature (17-23°C)away from direct sunlight.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd.,
Biotechnology & Animal Breeding Division,
CH-4414 Füllinsdorf,
Switzerland.
- Age at study initiation: Males: 9 weeks
Females: 12 weeks
- Housing: During Acclimatization: In groups of five in Makrolon type-4 cages with standard softwood bedding.
During treatment and observation: Individually in Makrolon type-3 cages with standard softwood bedding.
- Diet (e.g. ad libitum): Pelleted standarad Kliba 3433, batch no. 37/99, rat maintenance diet.
- Water (e.g. ad libitum): Community tap water from Itingen.
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C
- Humidity (%): 40-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light.


IN-LIFE DATES: From: August 5th 1999 To: August 19th 1999.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Backs of the animals.
- % coverage: 10%
- Type of wrap if used: Semi-occlusive dressing.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Lukewarm tap water amd dried with disposable paper towels.
- Time after start of exposure: Twenty-four hours after the application.


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0 ml.
- Constant volume or concentration used: yes

Duration of exposure:

24 hours of exposure with an observation period of 14 days.

Doses:

2000 mg/kg body weight.

No. of animals per sex per dose:

5 males
5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/viability four times during test day 1 and once daily during days 2 - 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs: Examined for changes in appearance and behaviour four times during day 1 and once daily during days 2 - 15.
- Body weight: On test day 1 (pre-administration), 8 and 15.

Necropsies were performed by experienced prosectors. At the end of the observation period all animals were sacrificed by intreperitoneal injection of NARCOREN at a dose of at least 2.0 ml/kg bw (equivalent to at least 320 mg sodium pentobarbitone/kg body weight). The animals were examined macroscopically and all abnormalities recorded. Thereafter, they were discarded.

Statistics:

No statistical analysis was used as no deaths occurred.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No systemic or local signs of toxicity were observed during the study period.

Gross pathology:

No macroscopic findings were observed at necropsy.

Any other information on results incl. tables

Table 1: Clinical/Local Signs

Sex	Animal No.	Signs	Test Day
			1				2	3	4	5	6	7	8	9	10	11	12	13	14	15
			1h	2h	3h	4h
Female 2000 mg/kg	1	No clinical signs
	2	No clinical signs
	3	No clinical signs
Male 2000 mg/kg	1	No clinical signs
	2	No clinical signs
	3	No clinical signs

Table 2: Body Weights

Body Weights
Sex	Animal No.	Day of Treatment	Day 8	Day 15
Male 2000 mg/kg	1 2 3 4 5	254.6 247.3 262.9 242.8 223.5	296.3 284.3 301.9 268.5 249.2	334.8 322.1 345.7 285.8 270.2
Female 2000 mg/kg	6 7 8 9 10	200.3 202.3 210.3 209.8 205.0	200.4 202.3 208.1 215.5 212.8	205.9 216.1 213.6 226.0 221.5

Table 3: Macroscopic Findings

Sex	Animal No.	Type of death	Findings
Female 2000 mg/kg	1	Scheduled necropsy	No macroscopic findings
	2	Scheduled necropsy	No macroscopic findings
	3	Scheduled necropsy	No macroscopic findings
	4	Scheduled necropsy	No macroscopic findings
	5	Scheduled necropsy	No macroscopic findings
Male 2000 mg/kg	1	Scheduled necropsy	No macroscopic findings
	2	Scheduled necropsy	No macroscopic findings
	3	Scheduled necropsy	No macroscopic findings
	4	Scheduled necropsy	No macroscopic findings
	5	Scheduled necropsy	No macroscopic findings

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose of RA1 after single dermal administration to rats of both sexes, observed over a period of 14 days, could not be estimated as no death occurred. The 24-hr LD50 is greater than 2000 mg/kg bw.

Executive summary:

RA1 was evaluated for its potential to induce acute toxicity following dermal administration at a dose of 2000 mg/kg bw in male and female Wistar rats.

Animals were treated with RA1 at 2000 mg/kg bw by dermal application for 24 hr. The test article was administered undiluted at a volume of 2 ml/kg. The animals were examined for clinical signs and mortality/viability for 14 days after application of the test substance.

No deaths occurred during the study and no clinical signs were observed. In addition, the body weight of the animals was unaffected by treatment and no macroscopic findings were observed at necropsy.

Based on these results, the 24-hr median lethal dose of RA1 after single dermal administration to rats of both sexes is greater than 2000 mg/kg bw.