3,3'-oxybis(ethyleneoxy)bis(propylamine)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

non-GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3,3'-oxybis(ethyleneoxy)bis(propylamine)

EC Number:

224-207-2

EC Name:

3,3'-oxybis(ethyleneoxy)bis(propylamine)

Cas Number:

4246-51-9

Molecular formula:

C10H24N2O3

IUPAC Name:

3,3'-[oxybis(ethane-2,1-diyloxy)]dipropan-1-amine

Specific details on test material used for the study:

- Physical state/appearance: yellowish liquid
- Purity: min 95%
- Expiration date of the lot/batch: July 1985

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, FRG
- Weight at study initiation: mean males: 259 g; mean females: 218 g
- Housing: single housing (type DK-III, Becker & Co., Castrop-Rauxel, FRG)
- Diet: Kliba-Labordiaet (Klingentalmuehle AG, Kaiseraugst, CH) ad libitum
- Water: tap water ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: ca. 50 cm² of shaved dorsal/dorsolateral skin
- Type of wrap if used: semiocclusive

REMOVAL OF TEST SUBSTANCE
- Washing: with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 2.15 mL/kg
- Concentration: undiluted

Duration of exposure:

24 hours

Doses:

2150 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: check for mortality/moribund animals twice per day on working days and once per day on weekends/public holidays; clinical observation several times on the day application, afterwards at least once per day on working days; weighing on the day of application and on days 2, 6 and 13
- Necropsy of survivors performed: yes
- Other examinations performed: assessment of local effects (30 - 60 min after removal of semiocclusive coverage and afterwards at least once per week)

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 150 mg/kg bw

Based on:

test mat.

Mortality:

One male animal died 2 days after application of the test substance.

Clinical signs:

other: Clinical signs included dyspnoea, apathy, aggressiveness, staggering, poor general state

Gross pathology:

Animal that died: lungs: severe edema
Sacrificed animals: no abnormalities in organs observed

Other findings:

Local skin effects: 1 male animal moderate, 1 male animal superficial erosions with crust formation; other animals: profound necrosis

Any other information on results incl. tables

Tab. 1: Mortality:

Dose (mg/kg)		2150
Males
Dead animals/total animals after	1 h	0/5
	1 d	0/5
	2 d	1/5
	7 d	1/5
	14 d	1/5
Females
Dead animals/total animals after	1 h	0/5
	1 d	0/5
	2 d	0/5
	7 d	0/5
	14 d	0/5

 

Tab. 2: Mean body weights (g):

	Dose (mg/kg)	Weight day
		0	2	6	13
Males	2150	259	241	263	292
Females	2150	218	241	211	231

 

Tab.3: Symptoms (cageside observations):

Dose (mg/kg)	2150
Males
Dyspnoea	2D-5D
Apathy	2D-5D
Agressiveness	8D-9D
Staggering	2D-5D
Poor general state	2D-5D
Females
Dyspnoea	2D-6D
Apathy	2D-5D
Agressiveness	6D-9D
Staggering	2D-6D
Poor general state	2D-6D

D: Day

 

Tab. 4: Local effects

Dose (mg/kg)	2150
Males
Profound necrosis	1D-14D
Edema	1D-14D
Females
Profound necrosis	1D-14D
Edema	1D-14D

D: Day

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The aute dermal toxicity study revealed a LD50 > 2150 mg/kg bw for male and female rats.

Executive summary:

In an acute dermal toxicity study similar to OECD guideline 402 (non-GLP, reliability 2) 5 rats/sex were exposed to a single dose of 2150 mg/kg bw of the test substance in a semiocclusive manner. Therefore, 2.15 mL/kg of the undiluted test substance were applied to 50 cm² of the shaved dorsal/dorsolateral skin for 24 hours. Washing with warm water was performed after exposure. One male animal died 2 days after application of the test substance and showed severe edema of the lung. Clinical signs of the surviving animals included dyspnoea, apathy, aggressiveness, staggering, poor general state. No abnormal organs were observed in these rats. Exposure caused severe skin reactions as 1 male animal had moderate, 1 male animal superficial erosions with crust formation and all other animals profound necrosis. Due to the mortality of 1/10 animals in this study a LD50 was set to be greater than the tested limit dose of 2150 mg/kg bw.