N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1985-06-12 - 1985-06-28

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Internal laboratory standard protocol

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Principles of method if other than guideline:

No guideline methods were documented in the study report, although the study was conducted according to the following protocol. The test substance was maintained in contact with shaven trunk skin of male and female New Zealand White rabbits, for a either 4 or 24 hours, using an occlusive dressing. Groups containing 5 animals were used, and rabbits were observed for 14 days after application of test substance to the skin. Studies were conducted using undiluted test substance with contact periods of 4 and 24 hr, and a 20% aqueous solution (v/v) maintained in contact for 24 hr. LD50's were calculated by the moving average method and are based on a 14-day observation period. Animal weights were recorded at 0 days (before dose), 7 days and 14 days (just prior to sacrifice). At death or sacrifice, each animal is subjected to gross pathologic evaluation.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)

EC Number:

221-220-5

EC Name:

N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)

Cas Number:

3033-62-3

Molecular formula:

C8H20N2O

IUPAC Name:

{2-[2-(dimethylamino)ethoxy]ethyl}dimethylamine

Test material form:

liquid

Specific details on test material used for the study:

- Name of test material (as cited in study report): N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)
- Molecular formula (if other than submission substance): (CH3)2NCH2CH2OCH2CH2N(CH3)2
- Molecular weight (if other than submission substance): 160.26
- Substance type: Pure active substance
- Physical state: Yellow, transparent, slightly viscous liquid
- Analytical purity: N/A
- Impurities (identity and concentrations): N/A
- Composition of test material, percentage of components: N/A
- Purity test date: N/A
- Expiration date of the lot/batch: N/A
- Storage condition of test material: N/A
- Other: N/A
- Lot/batch No.: Identification: S-867907; Charge No.: 502670-0000-2286; BRRC Sample No. 48-97

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2.0 and 3.0 kg
- Fasting period before study: Yes, during exposure
- Housing: no data
- Diet (e.g. ad libitum): Commercial diet, ad libitum
- Water (e.g. ad libitum): Municipal water, ad libitum
- Acclimation period: 24 hours

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

IN-LIFE DATES: From: 1985-06-12 To: 1985-06-26

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: 4 and 24 hour test were unchanged test substance; 24 hour test with 20% dilution with distilled water.

Details on dermal exposure:

TEST SITE
- Area of exposure: Trunk (clipped and intact)
- % coverage: no data
- Type of wrap if used: Impervious sheeting

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, after the contact period, excess fluid was removed to diminish ingestion.
- Time after start of exposure: no data

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): no data
- Concentration (if solution): pure substance and 20% solution
- Constant volume or concentration used: No, doses were varied by adjusting the volume or weight of the test substance.
- For solids, paste formed: not applicable

VEHICLE
- Amount(s) applied (volume or weight with unit): no data
- Concentration (if solution): no data
- Lot/batch no. (if required): no data
- Purity: no data

Duration of exposure:

4 or 24 hour exposure periods.

Doses:

- 4-hour contact period: 1.00, 0.50, 0.25 mL/kg (Males) and 1.00, 0.71, 0.50 mL/kg (Females).
- 24-hours contact period: 0.80, 0.40, 0.20 mL/kg (Males) and 0.80, 0.40, 0.20, 0.10 mL/kg (Females)
- 24-hours contact period with 20% dilution: 4.00, 2.00, 1.00 mL/kg (Males) and 8.00, 4.00, 2.00 mL/kg (Females)

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animal weights were recorded at 0 days (before dose), 7 days and 14 days (just prior to sacrifice).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, and gross pathology

Statistics:

LD50's are calculated by the moving average method and are based on a 14-day observation period.

Results and discussion

Preliminary study:

N/A

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

0.406 mL/kg bw

Based on:

test mat.

95% CL:

0.295 - 0.559

Remarks on result:

other: 4-hr Contact with Undiluted Sample; Rabbit

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

0.633 mL/kg bw

Based on:

test mat.

95% CL:

0.542 - 0.739

Remarks on result:

other: 4-hr Contact with Undiluted Sample; Rabbit

Effect levels 3

Sex:

male

Dose descriptor:

LD50

Effect level:

0.373 mL/kg bw

Based on:

test mat.

95% CL:

0.252 - 0.552

Remarks on result:

other: 24-hr Contact with Undiluted Sample; Rabbit

Effect levels 4

Sex:

female

Dose descriptor:

LD50

Effect level:

0.367 mL/kg bw

Based on:

test mat.

95% CL:

0.202 - 0.668

Remarks on result:

other: 24-hr Contact with Undiluted Sample; Rabbit

Effect levels 5

Sex:

male

Dose descriptor:

LD50

Effect level:

2.14 mL/kg bw

Based on:

test mat.

95% CL:

1.45 - 3.17

Remarks on result:

other: 24-hr Contact with 20% Aqueous Dilution; Rabbit

Effect levels 6

Sex:

female

Dose descriptor:

LD50

Effect level:

2.83 mL/kg bw

Based on:

test mat.

95% CL:

1.68 - 4.77

Remarks on result:

other: 24-hr Contact with 20% Aqueous Dilution; Rabbit

Mortality:

- 4-hour contact period: Deaths occurred at one to 4 days.
- 24-hours contact period: One animal died at 3 hours, but most animals died at one or 2 days. Survivors recovered at 2 days.
- 24-hours contact period with 20% dilution: Deaths occurred at one to 4 days. Survivors appeared normal after 2 days.

Clinical signs:

other: - 4-hour contact period: Skin reaction included erythema, edema, necrosis, scabs and a few instances of ulceration. One or 2 animals exhibited sluggishness, salivation and prostration. - 24-hours contact period: Irritation of the skin was severe and cons

Gross pathology:

- 4-hour contact period: Findings at necropsy included mottled and red lungs, subcutaneous edema (in 2) and one dark red thymus.
- 24-hours contact period: At necropsy, lungs were mottled and red, a few stomachs had multiple black surface foci and a few animals had subcutaneous edema. There were also instances of enlarged kidneys and one spleen with adhesions.
- 24-hours contact period with 20% dilution: Gross pathologic findings included mottled and red lungs, a few enlarged kidneys and subcutaneous edema.

Other findings:

No data

Any other information on results incl. tables

Body Weight Change Results:

4 hour contact period	Male	Female
1.00 mL/kg	7 days: N/A 14 days: N/A
0.50 mL/kg	7 days: -308 g 14 days: -238 g
0.25 mL/kg	7 days: -304 to -43 g (mean= -198 g) 14 days: -65 to -170 g (mean= 62)
1.00 mL/kg		7 days: N/A 14 days: N/A
0.71 mL/kg		8 days: -241 g 14 days: -334 g
0.50 mL/kg		7 days: -381 to -282 (mean= -329 g) 14 days: -319 to -17 g (mean= -188 g)
24 hour contact period	Male	Female
0.80 mL/kg	7 days: N/A 14 days: N/A
0.40 mL/kg	7 days: -488 and -280 g (mean= -384 g) 14 days: -195 and -188 g (mean= -192 g)
0.20 mL/kg	7 days: -207 to -121 g (mean= -167 g) 14 days: 51 to 118 (mean= 82 g)
0.80 mL/kg		7 days: N/A 14 days: N/A
0.40 mL/kg		7 days: -403 to -142 g (mean= -307 g) 14 days: -358 to -71 g (mean= -243 g)
0.20 mL/kg		7 days: -405 to -110 g (mean= -222 g) 14 days: -180 to 271 g (mean= 37 g)
0.10 mL/kg		7 days: -121 to 28 g (mean= 48 g) 14 days: 50 to 323 g (mean= 188 g)
24 hour contact period with 20% dilution	Male	Female
4.00 mL/kg	7 days: N/A 14 days: N/A
2.00 mL/kg	7 days: -370 to -270 g (mean= -329 g) 14 days: -285 to -63 (mean= -195 g)
1.00 mL/kg	8 days: -251 to 108 g (mean= -65 g) 14 days: 15 to 382 g (mean= 192 g)
8.00 mL/kg		7 days: N/A 14 days: N/A
4.00 mL/kg		7 days: -416 and -302 g (mean= -359 g) 14 days: -590 and -373 g (mean= -482 g)
2.00 mL/kg		7 days: -322 to -184 g (mean= -234 g) 14 days: -385 to 146 g (mean= -85 g)
1.0 mL/kg		7 days: -172 to 50 g (mean= -76) 14 days: 25 to 347 g (mean= 157 g)

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Percutaneous LD50 = 0.406 mL/kg (Males) and 0.633 mL/kg (Females) for the 4-hr contact with undiluted sample group; Percutaneous LD50 = 0.373 mL/kg (Males) and 0.367 mL/kg (Females) for the 24-hr contact with undiluted sample group; Percutaneous LD50 = 2.14 mL/kg (of dilution, Males) and 2.83 mL/kg (of dilution, Females) for the 24-hr contact with 20% aqueous dilution group.
The test substance was moderately to highly toxic following dermal application for 4 hours or 24 hours. A 20% (v/v) dilution in water was moderately toxic following a 24-hour dermal application. Severe, persistent dermal irritation was evident in each test.
The dermal LD50 value was converted using the density of the test substance : 0.848 g/mL. For males 0.373 mL/kg = 316 mg/kg; for females 0.367 mL/kg = 311 mg/kg