1,2-Propanediamine, N1-(2-aminoethyl)-3-(4-ethoxyphenyl)-, hydrochloride (1:2), (2S)-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from January to February 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

A combined study on acute dermal toxicity and on local tolerance was used to assess skin irritation/corrosion. The study design and reporting deviates from the current OECD TG 404, however, the study is considered sufficient for assessment of this endpoint.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

17 July 1992

Deviations:

yes

Remarks:

- exposure time 24 hrs instead of 4 hrs, 6 animals instead of 3, few details in test description and reporting

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

(S)-1-(4-Ethoxybenzyl)-3-azapentane-1,5-diaminedihydrochloride

EC Number:

606-947-1

Cas Number:

221640-21-7

Molecular formula:

C13 H23 N3 O . 2 Cl H

IUPAC Name:

(S)-1-(4-Ethoxybenzyl)-3-azapentane-1,5-diaminedihydrochloride

Test material form:

solid

Test animals

Species:

rat

Strain:

other: Han:WIST (SPF)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Schering AG, Germany
- Mean weight at study initiation: 104-106 g (males) or 98-105 g (females)
- Housing: 1 animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23
- rel. Humidity (%): 50 - 58
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

other: 900 mg NaCl ad 100 mL bidist. water

Controls:

other: the untreated skin served as control

Amount / concentration applied:

208-212 mg/male animal or 196-210 mg/female animal

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

3 males and 3 females

Details on study design:

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) On day 1 at application and after 24 h, 48 h and 72 h.

SCORING SYSTEM: According to Draize et al.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #1M; #3M, #4F, #5F, #6F

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 2

Irritation parameter:

erythema score

Basis:

animal: #2M

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 11 days

Results 3

Irritation parameter:

edema score

Basis:

animal: #1- #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Any other information on results incl. tables

2 out of 4 animals showed local irritations as folIows: animal no. 4F showed a very slight reddening (immediately after removal of the bandage and the substance), patchy on day 2, and animal no. 2M showed reddening, patehy (day 2 and 3), hardening of the skin, patehy (day 4) and skin neerosis (initial stage), spotty (day 5 to 10). All animals were without local findings trom day 11 onwards.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

A combined study on acute dermal toxicity and on local tolerance was conducted . The study design and reporting deviates from the current OECD TG 404, however, the study was considered sufficient for assessment of skin irritation/corrosion.A single dermal administration of the test substance for 24 hours to male and female rats at a dose of 2000 mg/kg was tolerated without any local irritations in 4/6 animals. Following grading at 24, 48 and 72 hours after patch removal 1/6 animals shows a mean value of 2 for erythema/eschar. All animals were without local findings trom day 11 onwards.

Executive summary:

In a primary dermal irritation study similar to OECD TG 404, young adult Wistar rats, female and male (3/sex) were dermally exposed to 208-212 mg/male animal or 196-210 mg/female animal of Triamine Dihydrochloride in physiological saline for 24 hours. Animals then were observed for 14 days. Irritation was scored by the method according to Draize et al..

Only in one male animal local irritations were observed at 24, 48, and 72 h. These irritations were reversible within 11 days. In this study, the test item is not a dermal irritant.