1-ethylpiperazine

Endpoint summary

Description of key information

- skin: corrosive (rabbit; 1988; Bomhard, 1997) 
- eye: severe damage to eyes (rabbit; Bomhard, 1997)
- respiratory: irritation to respiratory tract cannot be excluded.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

xposure period was not 4 hours, but the test substance is corrosive

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

(animals were used for a 3 minutes and 1 hour exposure; exposure period was not 4 hours, but the test substance is corrosive)

GLP compliance:

not specified

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler, Offenbach/Main, Germany (female rabbit) and Savo, med. Versuchstierzuchten, Kissling/Germany (males)
- Weight at study initiation: 2.77 kg (female), 2.3 kg (males)
- Housing: singly
- Diet: Kliba 341, about 130 g/animal/day
- Water: tap water, about 250 mL/animal/day
- Acclimation period: 8 days

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

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin sites of the same animal

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

3 minutes (right flank) and 1 hour (left flank)

Observation period:

72 hours

Number of animals:

1 female and 2 male animals

Details on study design:

TEST SITE
Clipping of the fur: at least 15 hours before the beginning of the study.
- Area of exposure: 2.5 x 2.5 cm, upper third of the back or flanks

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lutrol and lutrol/water (1:1)
- Time after start of exposure: at the end of the exposure period

SCORING SYSTEM:
based on J .H . Draize: Appraisal of the safety of chmemicals in foods, drugs and cosmetics. In dermal toxicity pp. 46 - 59, 1959 Austin, TEX.

Irritation parameter:

other: necrosis

Basis:

mean

Time point:

other: 3 minutes exposure

Remarks on result:

other: superficial/medium thickness scabbing was observed but no necrosis

Irritation parameter:

other: necrosis

Basis:

mean

Time point:

other: 1 hour exposure

Reversibility:

not reversible

Remarks on result:

other: necrosis was observed immediately after exposure and during the whole observation period; full thickness necrosis was confirmed 72 hours after exposure at gross pathology

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24-48-72 hours post treatment

Score:

3

Max. score:

4

Reversibility:

no data

Remarks on result:

other: 3 minutes exposure; Erythema extending beyond the area of exposure

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24-48-72 hours post treatment

Score:

1

Max. score:

4

Reversibility:

no data

Remarks on result:

other: 3 minutes exposure; Edema extending beyond the area of exposure

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24-48-72 hours post treatment

Score:

3.7

Max. score:

4

Reversibility:

no data

Remarks on result:

other: 1 hour exposure

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24-48-72 hours post treatment

Score:

1.7

Max. score:

4

Reversibility:

no data

Remarks on result:

other: 1 hour exposure; Edema extending beyond the area of exposure

Irritant / corrosive response data:

3 minutes exposure:
Edema and erythema extending beyond the area of exposure and hemorrhage was observed in the male animals up to 24 hours after exposure. Superficial scabbing/medium thickness scabbing was additionally observed 72 hours post exposure in the male test animals.
1 hour exposure:
Edema extending beyond the area of exposure was observed in all test animals at any time post exposure. Necrosis was observed one hour after exposure up to 48 hours, resulting in full thickness necrosis after 72 hours in the male animals and superficial scabbing in the female animal. Findings were confirmed by gross pathology examination.

Table 1: Erythema and Edema scores of animals treated for 3 minutes with the unchanged test substance

Observation time	Animal	Erythema	Edema	Add. information
3 minutes	1	2	0
	2	2	2	Edema and erythema extending beyond the area of exposure
	3	4	0	hemorrhage
24 hours	1	2	0
	2	3	1	Edema and erythema extending beyond the area of exposure
	3	4	2	hemorrhage
48 hours	1	3	0
	2	4	1
	3	3	2
72 hours	1	2	0
	2	3	1	Superficial scabbing
	3	3	2	Medium thickness scabbing
Mean	1	2.3	0
	2	3.3	1
	3	3.3	2
Mean		3	1

Table 2: Erythema and Edema scores of animals treated for 1 hour with the unchanged test substance

Observation time	Animal	Erythema	Edema	Add. information
1 hour	1	3	1	Edema extending beyond the area of exposure
	2	4	3	Necrosis; Edema extending beyond the area of exposure
	3	4	3	Necrosis; Edema extending beyond the area of exposure
24 hours	1	3	2	Edema extending beyond the area of exposure
	2	4	2	Necrosis; Edema extending beyond the area of exposure
	3	4	2	Necrosis; Edema extending beyond the area of exposure
48 hours	1	3	1	Edema extending beyond the area of exposure
	2	4	2	Necrosis; Edema extending beyond the area of exposure
	3	4	2	Necrosis; Edema extending beyond the area of exposure
72 hours	1	3	1	Superficial scabbing; Edema extending beyond the area of exposure
	2	4	2	Full thickness necrosis; Edema extending beyond the area of exposure
	3	4	1	Full thickness necrosis; Edema extending beyond the area of exposure
Mean	1	3	1.3
	2	4	2
	3	4	1.7
Mean		3.7	1.7

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

no data on test substance purity

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 3.1 - 3.4 kg
No further information.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 µL

Duration of treatment / exposure:

24 h

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsed with physiologic saline
- Time after start of exposure: 24 h

SCORING SYSTEM: according to Draize; the irritation indices were calculated in accordance with Guideline 83/467/EC No. 8

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

3

Max. score:

4

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

1

Max. score:

2

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

3

Max. score:

3

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

3

Max. score:

4

Reversibility:

not specified

Irritant / corrosive response data:

After 7 d the nictitating membrane and the palpebral conjunctiva showed necrotic changes. Therefore, the test substance was found to cause severe damage to the eyes.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation

In a study (1988, reliability score 2) conducted according to OECD 404, the potential of the test substance to cause acute dermal irritation or corrosion was assessed by single topical application of 0.5 mL unchanged test substance for 4 hours to the intact skin of 1 male Vienna White rabbit using a test patch of 2.5 x 2.5 cm, covered with a semiocclusive dressing. The cutaneous reactions were assessed 24, 48 and 72 hours after removal of the patch. Mean 24-48-72-hour scores were 4 (max. 4) and 2 (max. 4) for erythema and edema, respectively. Necrosis was firstly observed 4 hours after application. Erythema extending beyond the area of exposure and necrosis was observed after termination of exposure. The effects were not reversible. At pathology, full thickness necrosis was confirmed.

In a second study (1988, reliability score 2) the potential of the test substance to cause corrosion was assessed by single topical application of 0.5 mL unchanged test substance for 3 minutes and 1 hour, respectively, to the shaved skin of 1 male and 2 female Vienna White rabbits using a test patch of 2.5 x 2.5 cm, covered with a semiocclusive dressing. The cutaneous reactions were assessed 24, 48 and 72 hours after removal of the patch. Mean 24-48-72-hour scores were 3 and 3.7 (3 min and 1 h exposure) and 1 and 1.7 (3 min and 1 h exposure) for erythema and edema, respectively. Erythema (3 min exposure) and edema (3 min and 1 h exposure) extended beyond the area of exposure. After 3 min exposure superficial/medium thickness scabbing was observed but no necrosis. After 1 h exposure necrosis was observed immediately after exposure and during the whole observation period; full thickness necrosis was confirmed 72 hours after exposure at gross pathology.

Additionally, there is a publication from Bomhard E. et al. (1997, reliability score 4) which is not assignable, because only short method and result descriptions were available, but supports the results of the described studies.

 

Eye Irritation

There is one study concerning eye irritation available which confirmed the corrosive potential of the test substance (Bomhard E. et al., 1997, reliability score 2). A dose of 100μL was administered into one eye of three young adult female New Zealand White rabbits for an exposure period of 24 hours. Then the treated eyes were rinsed with physiologic saline. The eyes were examined and the grade of ocular reaction was recorded at 1, 24, 48 and 72 hours and again on day 7 according to Draize. Mean irritation scores at the 24, 48 and 72 hour readings were 3.0 for corneal opacity. 1.0 for iritis, 3.0 for conjunctival redness and swelling. At 7 d the nictitating membrane and the palpebral conjunctiva showed necrotic changes. Therefore the test substance was found to cause severe damage to eyes.

 

Respiratory irritation

In an inhalation hazard test (1989, reliability score 2) irritating effects to the eyes and the respiratory tract (accelerated/intermittent respiration, eyelid closure, wiping of snouts, salivation, nasal discharge, reddish nasal/eye discharge) were observed during exposure of rats to a test atmosphere saturated with vapours of the test substance for 7 hours. Additionally, based on the available data on skin corrosivity and severe damage to eyes irritation to the respiratory tract cannot be excluded.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, the test substance has to be classified as irritating to respiratory tract (STOT SE 3), causing risk of serious damage to eyes (Eye Dam. 1) and corrosivity to the skin (Skin Corr. 1B).