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

Endpoint summary

Description of key information

similar to OECD 401, LD50 oral, rat = 3160 mg/kg (1984, no GLP, reliability 2)
similar to OECD 402, LD50 dermal, rat > 2150 mg/kg bw (1984, no GLP, reliability 2)

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:

October 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

non-GLP

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

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

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: 182 g; mean females: 171 g
- Fasting period before study: 16 hours
- Housing: 5 animals per cage (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

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

(aqua dest.)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 14.7%, 21.5%, 31.6%
- Justification for choice of vehicle: aqueous preparation corresponds to physiological medium

DOSE VOLUME APPLIED: 10 ml/kg

Doses:

1470, 2150, 3160 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 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, 7 and 12
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 3 160 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 2 850 mg/kg bw

Based on:

test mat.

Remarks on result:

other: value from interpolation

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 3 160 mg/kg bw

Based on:

test mat.

Mortality:

The highest applied dosage caused mortality (80%, 40% mortality for male and female rats, respectively) See table1 ("Any other information on results incl. tabeles")

Clinical signs:

other: Clinical signs included dyspnoea, rattling breath, apathy, agitation, abnormal position, staggering, tremble, tremor, spastic gait, piloerection, poor general state

Gross pathology:

Animals that died: general congestive hyperemia; stomach: bloody gastritis in glandular stomach; intestine: atonic, reddened diarrheal content.
Sacrificed animals: No abnormalities.

Tab. 1: Mortality:

Dose (mg/kg)		3160	2150	1470
Males
Dead animals/total animals after	1 h	0/5	0/5	0/5
	1 d	4/5	0/5	0/5
	2 d	4/5	0/5	0/5
	7 d	4/5	0/5	0/5
	14 d	4/5	0/5	0/5
Females
Dead animals/total animals after	1 h	0/5	0/5	0/5
	1 d	2/5	0/5	0/5
	2 d	2/5	0/5	0/5
	7 d	2/5	0/5	0/5
	14 d	2/5	0/5	0/5

 

Tab. 2: Mean body weights (g):

	Dose (mg/kg)	Weight day
		0	2	7	12
Males	3160	179	186	213	253
	2150	180	204	238	263
	1470	188	219	251	278
Females	3160	171	169	189	201
	2150	167	186	199	211
	1470	176	196	212	225

 

 

Tab. 3: Symptoms (cageside observations):

Dose (mg/kg)	3160	2150	1470
Males
Dyspnoea	1H-2D
Apathy	1H-4H
Agitation	1D-2D
Staggering	1H-2D
Piloerection	1H-6D
Poor general state	1H-2D
Females
Dyspnoea	1H-2D
Rattling breath	4H-2D
Apathy	1H-2D
Abnormal position	4H
Staggering	1H-2D
Tremble	4H
Tremor	4H
Spastic gait	2D
Piloerection	4H-6D
Poor general state	1H-2D

H: Hour; D: Day

 

 

Interpretation of results:

GHS criteria not met

Conclusions:

The aute oral toxicity study revealed a LD50 of 2850 mg/kg bw for male rats and a LD50 of 3160 mg/kg bw for female rats as well as males/females.

Executive summary:

In an acute toxicity study similar to OECD guideline 401 (non-GLP, reliability 2) 5 rats/sex were exposed to 1470, 2150, 3160 mg/kg bw of the test substance per gavage. No mortality was observed the low- and mid-dose group. The dosage of 3160 mg/kg bw caused 60% mortality in the rats (80% mortality for males, 40% mortality for females). Therefore, the LD50 for male and female rats was 3160 mg/kg bw (LD50males = 2850 mg/kg bw, LD50females = 3160 mg/kg bw). Clinical observations revealed dyspnoea, rattling breath, apathy, agitation, abnormal position, staggering, tremble, tremor, spastic gait, piloerection, poor general state. Animals wich died after oral exposure had general congestive hyperemia as well as pathological findings in the stomach and intestine (bloody gastritis in glandular stomach, atonic, reddened diarrheal content). All other sacrifieced anilmals did not show abnormalities and gained bodyweight during the study.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 160 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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:

November 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

non-GLP

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

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

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

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)

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

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

 

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 150 mg/kg bw

Additional information

Acute oral toxicity:

The acute oral toxicity of the test substance was assessed similar to OECD401 (BASF, 1984). Five rats per dose (1470, 2150, 3160 mg/kg) were given the test item at aqueous solution (14.7%, 21.5%, 31.6%) once per oral gavage. Animals were observed for 14 days and mortality as well clinical signs were monitored. None of the animals died following application of the two lowest doses (i.e. 1470 and 2150 mg/kg). At the highest dose (3160 mg/kg) 4/5 males and 2/5 female died. Clinical signs included dyspnoea, rattling breath, apathy, agitation, abnormal position, staggering, tremble, tremor, spastic, gait, piloerection and poor general state. In decedent animals gross pathology findings included general congestive hyperemia, bloody gastritis in glandular stomach; atonical intestine and reddened diarrheal content. Surviving animals showed no abnormalities at sacrifice.

Based on these results, the oral LD50 was calculated as ca. 3160 mg/kg for females and as ca. 2850 mg/kg for males. The combined oral LD50 was 3160 mg/kg (males and females). The study is regarded as acceptable (key study).

Additionally, Smyth et al. (1969) reported an oral LD50 value of 4333 mg/kg bw for male rats. The study is classified as acceptable (supporting studies).

 

Acute inhalation toxicity:

In an acute inhalation toxicity study with whole body exposure (Smyth et al., 1969), six albino rats were exposed to a vapour atmosphere of the test substance for a series of time periods ranging from 15 minutes up to 8 hours and observed for 14 days. A 4 hours exposure to a flowing stream of vapor-ladened air with the test substance resulted in no mortality, whereas after 8 h exposure mortality occurred. This study is not valid and therefore disregarded because the vapor concentration is unknown and co-exposure via inhalation, oral and dermal route occurred.

 

Acute dermal toxicity:

In a single dose study (BASF, 1984) the acute dermal toxicity of the test substance was assessed according to OECD402. The test substance was administered to about 50 cm² (corresponds to at least 10 % of the body surface area) of the previously clipped skin (dorsal and dorsolateral parts of the trunk) of five Wistar rats and semi-occlusive covered. 24 h later, the dressing was removed and the application site rinsed with warm water to remove residual amounts of the test substance. Animals were observed for 14 days. One male animal died two days after application of the test substance. Clinical signs included dyspnoea, apathy, aggressiveness, staggering and poor general state. The Animal that died had severe edema in the lungs. No abnormalities were observed in organs of all other animals sacrificed at the end of the study. Moderate local skin effects were observed in one male, another male developed superficial erosions with crust formation, whereas the other animals showed profound necrosis. Taken together, the test item does not depict any risk of dermal toxicity and the LD50 is > 2150 mg/kg in males and females. The study is regarded as acceptable (key study).

Justification for selection of acute toxicity – oral endpoint
Most reliable study (key study).

Justification for selection of acute toxicity – dermal endpoint
Most reliable study (key study).

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. The substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No. 1272/2008.