Registration Dossier

Administrative data

Description of key information

- Skin irritation / corrosion: similar to OECD TG 404, rabbit, TS purity >97% (BASF AG, 1977); corrosive
- Eye irritation: similar to OECD TG 405, rabbit, TS purity >97% (BASF AG, 1977); corrosive

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:
other: Acceptable study comparable to guideline (non GLP; occlusive conditions; 1 min, 5 min, 15 min or 20 hours treatment duration; applied volume of TS preparation: 1 mL, up to 8 days observation period)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Acceptable study comparable to guideline (non GLP; occlusive conditions; 1 min, 5 min, 15 min or 20 hours treatment duration; applied volume of TS preparation: 1 mL, up to 8 days observation period)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Weight at study initiation: 2.85 kg (mean)
- Diet: Ssniff
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 mL
Duration of treatment / exposure:
1, 5, 15 minutes, 20 hours
Observation period:
8 days
reading time points: 24 h and 8 days
Number of animals:
2 per treatment
Details on study design:
TEST SITE: area of test sites: 2.5 x 2.5 cm² on the animal back.

SCORING SYSTEM: Draize

2 animals were treated for 1, 5, 15 minutes and 2 other animals for 20 hours with undiluted test substance using occlusive conditions. An application site of 2.5 x 2.5 cm was covered with test substance on a patch. In addition, skin from the ear was tested by wrapping the ear. These results from the ear, however, would not be taken into account for evaluation as they do not represent testing of the dorsal/lateral flank of the back. After the application time, the skin was washed with water which sometimes contained a mild detergent. The animals which had been treated for 20 hours were not washed after removal of the substance patch. The animals were observed 8 days and skin changes were recorded on working days.
Irritation parameter:
other: necrosis
Basis:
animal #1
Remarks:
1 minute exposure
Time point:
other: 24 h
Reversibility:
fully reversible
Remarks on result:
other: smooth necrosis
Irritation parameter:
other: necrosis
Basis:
animal #2
Remarks:
1 minute exposure
Time point:
other: 72 h
Reversibility:
no data
Remarks on result:
other: laminar necrosis was observed on day 3
Irritation parameter:
other: necrosis
Basis:
animal #1
Remarks:
5 minute exposure
Time point:
other: 24, 48, 72 h
Reversibility:
not reversible
Remarks on result:
other: leathery necrosis
Irritation parameter:
other: necrosis
Basis:
animal #2
Remarks:
5 minute exposure
Time point:
other: 24, 48, 72 h
Reversibility:
not reversible
Remarks on result:
other: laminar necrosis
Irritation parameter:
other: necrosis
Basis:
animal #1
Remarks:
15 minute exposure
Time point:
other: 24, 48, 72 h
Reversibility:
not reversible
Remarks on result:
other: parchmentary necrosis
Irritation parameter:
other: necrosis
Basis:
animal #2
Remarks:
15 minute exposure
Time point:
other: 48, 72 h
Reversibility:
not reversible
Remarks on result:
other: parchmentary necrosis
Irritation parameter:
other: necrosis
Basis:
mean
Remarks:
20 hour exposure
Time point:
other: 24, 48, 72 h
Reversibility:
not reversible
Remarks on result:
other: parchmentary necrosis on day 1 after exposure which developed to leathery necrosis on day 2 and 3
Irritant / corrosive response data:
Laminar necrosis was found directly after 15 minute exposure in one animal which was still seen until animal died.

Undiluted N-4-Amin gave indication of slight edema and slight necrosis as a result of an exposure period of 1 minute. After application of the test substance for 5, 15 min and 20 hours, respectively, erythema and necrosis were observed.

Necropsy findings of the animals that died comprised enteritis and peritonitis with agglutinations. All findings were not reversible within 6 days.

Animal

Readings

Exposure period: 15 minutes

Erythema

Edema

Additional findings

01

24 h

2

2

 

48 h

2

2

parchment-like necrosis

72 h

2

2

parchment-like necrosis

Mean score

2

2

 

02

24 h

2

2

 

48 h

2

2

parchment-like necrosis

72 h

2

2

parchment-like necrosis

Mean score

2

2

 

 

 

Animal

Readings

Exposure period: 20 hours

Erythema

Edema

Additional findings

01

24 h

2

3

parchment-like necrosis

48 h

2

2

hard, relocatable necrosis

72 h

2

3

hard, relocatable necrosis

Mean score

2

2.7

 

02

24 h

2

2

parchment-like necrosis

48 h

2

2

leather-like necrosis

72 h

2

2

leather-like necrosis

Mean score

2

2

 

Interpretation of results:
corrosive
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In a BASF AG (1977) study performed similar to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion), but under occlusive conditions, 1 mL unchanged test substance (TS purity >97%) was applied to the shaved skin sites of 2 female Vienna White rabbits for up to 20 hours (1 min, 5 min, 15 min and 20 hours). The untreated contra-lateral flank of the same animals was used as control. The skin reaction was observed from 1 hour up to 8 days observation period, and evaluated according to the OECD scoring system. Necrosis was generally observed for all exposure duration sites, but full thickness necrosis was present in one animal, already 48 hours after the 5 minute treatment period. The necrotic reaction was generally milder in the second animal. The treatment was lethal for the two animals within 6 days. Based on the necrotic reaction, the substance has to be judged as corrosive to skin.

 

 

Eye irritation

Only one eye irritation study is available, performed similar to the OECD Guideline 405 (Acute Eye Irritation / Corrosion; BASF AG, 1977). 0.05 mL unchanged test substance (TS purity >97%) was applied to the conjunctival sac of each one eye of 2 male Vienna White rabbits (no wash out) while the remaining untreated one served as negative control. The ocular reactions were then evaluated 1, 24, 48 and 72 hours after instillation, as well as at the end of the observation period (limited to 8 days) according to the Draize scoring system. The animals were also checked daily for systemic symptoms and mortality. Severe corrosion of the conjunctiva and cornea occurred in the course of the observation period and was not reversible within the 8 days.

 

Respiratory irritation

No data available


Justification for selection of skin irritation / corrosion endpoint:
Only one study available

Justification for selection of eye irritation endpoint:
Only one study available

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Based on the available skin and eye irritation studies, the substance has to be classified as corrosive according to Annex VI of the EU directive 67/548/EEC (R34) and to the EU Regulation (EC) No 1272/2008 (Cat 1B).