3,3'-[butane-1,4-diylbis(oxy)]bispropanamine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3,3'-[butane-1,4-diylbis(oxy)]bispropanamine

EC Number:

230-745-9

EC Name:

3,3'-[butane-1,4-diylbis(oxy)]bispropanamine

Cas Number:

7300-34-7

Molecular formula:

C10H24N2O2

IUPAC Name:

3-[4-(3-aminopropoxy)butoxy]propan-1-amine

Specific details on test material used for the study:

- Purity: 99.7 %

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Boehringer Ingelheim Pharma KG
- Age at study initiation: young adult animals
- Weight at study initiation: 200-300 g +/- 20% of the mean weight
- Housing: single housing
- Diet (e.g. ad libitum): Kliba-Labordiaet ad libitumn
- Water (e.g. ad libitum): Tap water ad libitumn per day.
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%

- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

The test item solution 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); following 24 h incubation with the test item, the dressing was removed and the application site rinsed with warm water

Duration of exposure:

24 h

Doses:

female: 400, 1000 and 2000 mg/kg
male: 400 and 1000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

animals were observed for 14 days

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no mortality occurred

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 1 000 mg/kg bw

Remarks on result:

other: no mortality occurred

Mortality:

No mortalities occured at any dose level

Clinical signs:

other: No systemic signs of toxicity were noted in all animals.

Gross pathology:

Local effects observed in the 400, 1000 and 2000 mg/kg dose group comprised very slight to severe erythema, very slight or slight edema, scaling, crust formation, bleeding and eczematous skin changes. Additionally, necrosis was observed in the 2000 mg/kg dose group. Due to severe local effects in the female animals of the 2000 mg/kg dose group no further investigation at this dose level was performed in male animals.

Other findings:

Necropsy findings of 4 female animals of the 2000 mg/kg dose group and 1 female animal of the 1000 mg/kg dose group sacrificed at the end of the study comprised several focal skin lesions in the region of the application site, crust formation at the surface and slight focal erythema. No abnormalities were observed in all other animals sacrificed at the end of the study.
The necrotic skin changes in female animals of the 2000 mg/kg dose group assessed by histo-pathological examination indicating full thickness necrosis.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the conditions of this study the acute dermal median lethal dose (LD50) of the test substance was found to be greater than 2000 mg/kg bw for female rats and greater than 1000 mg/kg bw for male rats. Due to the severe local effects (necrosis) observed at the dose level of 2000 mg/kg bw in the female rats no higher dose levels were assessed in male rats. However, due to lacking systemic effects the acute dermal median lethal dose (LD50) of the test substance is very likely to be greater than 2000 mg/kg bw also in the male animals.

Executive summary:

The study was performed to determine the acute dermal median lethal dose (LD50) of the test substance, applied as a solution in doubly distilled water, in Wistar rats.

The study procedure was based on the EEC, OECD and EPA/OPPTS guidelines.

The test material was applied as a solution in doubly distilled water to the clipped epidermis (dorsal and dorsolateral parts of the trunk) and was covered by a semiocclusive dressing for 24 hours. Dose levels of 400 and 1000 mg/kg bw were applied to groups of 5 male and female rats each. 2000 mgkg bw were given to 5 female rats.

No systemic signs of toxicity were noted in all animals.

The expected body weight gain was generally observed in the course of the study, with the exception of 2 female animals of the 2000 mg/kg bw dose group, which showed stagnation of body weight in the first week of observation.

Local effects observed in the 400, 1000 and 2000 mg/kg bw dose group comprised very slight to severe erythema, vry slight edema, scaling, crust formation, bleeding and eczematoid skin change. In the 2000 mg/kg bw dose group additionally necrosis was observed. Due to severe local effects in the female animals of th 2000 mg/kg bw dose group no further investigation at this dose level was performed in male animals.

No mortality occurred.

Necropsy findings of 4 female animals of the 2000 mg/kg bw dose group and 1 female animal of the 1000 mg/kg bw dose group sacrificed at the end of the study comprised several focal skin lesions in the region of the application site, crust formation at the surface and slight focal erythema. No abnormalities were observed in all other animals sacrificed at the end of the study.

The necrotic skin changes in female animals of the 2000 mg/kg bw dose group assessed by histopathological examination indicating full thickness necrosis.

Under the conditions of this study the acue dermal median lethal dose (LD50) of the test substance was found to be greater than 2000 mg/kg bw for female rats and greater than 1000 mg/kg bw for male rats. Due to the severe local effects (necrosis) observed at the dose level of 2000 mg/kg bw in the female rats no higher dose levels were assessed in male rats. However, due to lacking systemic effects the acute dermal median lethal dose (LD50) of the test substance is very likely to be greater than 2000 mg/kg bw also in the male animals.