Amines, tri-C8-10-alkyl

Endpoint summary

Description of key information

Skin:
- Skin irritation, Rabbit, 4h, OECD 404, RA from CAS 1116-76-3: severe reaction, erythema score 3.8 (average per animal: 3.7, 4.0, 3.7) and oedema score 2.6 (3.0, 2.7, 2.0), fully reversible within 15d in 2 of 3 cases (BASF SE, 1988, 18H0264/882108)
Eye: 
- Eye irritation, Rabbit, OECD 405, RA from CAS 1116-76-3: slight to mild signs (cornea, iris and chemosis score are 0, redness of conjunctiva 1.7 (1, 2, 2). Fully reversible within 8 days. (BASF SE, 1988, 11H0264/882109)

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: OECD guideline study, with acceptable restrictions (no data on test substance purity)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(adopted 1981)

Deviations:

yes

Remarks:

(test design not in accordance with sequential testing strategy as laid down in the Supplement of the recent version of the OECD TG 404 (2002))

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler, D-6050 Offenbach, Germany
- Age at study initiation: no data
- Weight at study initiation: male rabbits (mean): 2.63 kg; female rabbit 2.87 kg
- Housing: single
- Diet (ad libitum): Kliba 341, 4 mm, Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland (about 130 g per animal per day)
- Water (ad libitum): tap water (about 250 mL per animal per day)
- Acclimation period: at least 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:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated dorsal skin sites of the same animals

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

15 days

Number of animals:

3 animals (2 males, one female)

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm, upper third of the back or flanks
- Type of wrap: test patches were secured in position with a porous dressing (4 layers of absorbent gauze and porous bandage)

REMOVAL OF TEST SUBSTANCE
- Washing: yes, with lutrol and lutrol/water (1:1)
- Time after start of exposure: 4 hrs

SCORING SYSTEM: Draize scoring system

READINGS:
Readings of skin reactions were performed 30 - 60 min after removal of the test patches and then 24 h, 48 h, 72 h, 8 d, and 15 d after the beginning of application.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.7

Max. score:

4

Reversibility:

not fully reversible within: 15 days

Remarks on result:

other: Erythema and scaling beyond the area of application at study termination

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 15 days

Remarks on result:

other: Scaling beyond area of application at study termination

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.7

Max. score:

4

Reversibility:

fully reversible within: 15 days

Remarks on result:

other: Scaling at study termination

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 15 days

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

fully reversible within: 15 days

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 15 days

Remarks on result:

positive indication of irritation

Results:

Readings	Animal No.	Erythema	Edema	Additional findings
4 h	1	2	0	-
	2	2	1	-
	3	2	1	-
24 h	1	3	4	findings (ery., ed.) extending beyond the area of application
	2	4	3	findings (ery., ed.) extending beyond the area of application
	3	3	3	findings (ery., ed.) extending beyond the area of application
48 h	1	4	3	findings (ery., ed.) extending beyond the area of application
	2	4	3	findings (ery., ed.) extending beyond the area of application
	3	4	2	findings (ery., ed.) extending beyond the area of application
72 h	1	4	2	findings (ery., ed.) extending beyond the area of application
	2	4	2	findings (ery., ed.) extending beyond the area of application
	3	4	1	findings (ery., ed.) extending beyond the area of application
8 d	1	2	2	findings (ery., ed.) extending beyond the area of application, superficial scabbing extending beyond the area of exposure, hemorrhage
	2	2	1	findings (ery., ed.) extending beyond the area of application, superficial scabbing extending beyond the area of exposure
	3	2	1	findings (ery., ed.) extending beyond the area of application, superficial scabbing extending beyond the area of exposure
15 d	1	1	0	findings (ery., scaling) extending beyond the area of application
	2	0	0	findings (scaling) extending beyond the area of application
	3	0	0	scaling
mean (24 - 48 - 72 h readings)	1	3.7	3.0	n.a.
	2	4.0	2.7	n.a.
	3	3.7	2.0	n.a.

n.a.: not applicable

ery.: erythema

ed.: edema

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

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:

other: OECD guideline study, with acceptable restrictions (no data on test substance purity)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(adopted 1981)

Deviations:

yes

Remarks:

(test design not in accordance with sequential testing strategy, no systemic or ocular anesthetic used as laid down in the Supplement of the recent version of the OECD TG 405 (2012))

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Savo, Med. Versuchstierzuchten GmbH, D-7964 Kissleg, Germany
- Age at study initiation: no data
- Weight at study initiation: mean: 2.91 kg
- Housing: single
- Diet (ad libitum): Kliba 341, 4 mm; Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland (about 130 g per animal per day)
- Water (ad libitum): tap water (about 250 mL per animal per day)
- Acclimation period: at least 8 days

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

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated eyes of the same animals

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Single application to the conjunctival sac of the right eye lid; the substance was not washed out

Observation period (in vivo):

8 d
(The study was discontinued after 8 days, since all eye reactions had subsided.)

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: no data

READINGS:
Readings of eye reactions were performed 1 h, 24 h, 48 h, 72 h, and 8 days after application.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(of 3 animals)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

(of 3 animals)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 8 days

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 8 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 8 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(of 3 animals)

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results:

 

Time	Rabbit no.	Cornea		Iris	Conjunctivae			Additional findings
		Opacity	Area		Redness	Chemosis	Discharge
1 h	1	0	0	0	2	0	1	-
	2	0	0	0	2	0	1	-
	3	0	0	0	2	0	1	-
24 h	1	0	0	0	1	0	0	-
	2	0	0	0	2	0	0	-
	3	0	0	0	2	0	0	-
48 h	1	0	0	0	1	0	0	-
	2	0	0	0	2	0	0	-
	3	0	0	0	2	0	0	-
72 h	1	0	0	0	1	0	0	-
	2	0	0	0	2	0	0	-
	3	0	0	0	2	0	1	-
8 d	1	0	0	0	0	0	0	Loss of hair at margins of eyelids
	2	0	0	0	0	0	0	Loss of hair at margins of eyelids
	3	0	0	0	0	0	0	Loss of hair at margins of eyelids
mean (24-48-72 h)	1	0	0	0	1.0	0	-	-
	2	0	0	0	2.0	0	-	-
	3	0	0	0	2.0	0	-	-

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The test substance shows slight to mild eye reactions leading to cat 2 classification according to CLP.

Executive summary:

Tri-N-Octylamin was tested for acute irritation effects on eyes according to OECD 405 by single dose application (0.1ml) to the conjunctival sac of 3 male Vienna White rabbits (BASF SE, 1988, 11H0264/882109) to of three rabbits (Kleinrussen, Chbb:HM) with a single dose of 0.1 g per conjunctival sac and a duration of exposure of 24 hours. The mean cornea score and iris score was 0 (mean of all animals and timepoints). The mean chemosis score was recorded as 0, whereas slight to mild conjunctiva reactions (redness) were observed with gradings 1, 2, 2 (animal#1, animal#2, animal#3, average of 24/48 and 72 h reading) According to the test conditions the test substance has to be classified as irritating to eye cat 2 GHS.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No valid study are data available assessing the skin or eye irritation in vivo of Amines, tri-C8-10-alkyl. Nevertheless there are information from a “semi” read across substance Amines, tri C8 alkyl (CAS 1116-76-3) containing only C8 C-chains. As the substance registered here contains also C8 chains but partly C10 chains the structures are assumed to very similar and partly the same. Therefore the suitability of a read across to the pure C8 chain alkyl amine is assumed and comparable toxicological behaviour is expected. As both structures are that similar no further separate analogue document is created.

 

Skin:

In vivo OECD guideline conform studies:

A study of the skin irritant effect was performed with Tri-N-Octylamin  according to OECD No 404 (1992); EEC 92/69 - Annex V/B5 (1992) (BASF SE, 1988, 18H0264/882108).

Therefore 3 Vienna white rabbits (2male, 1female) where exposed for 4h to 0.5ml undiluted test material (Tri-N-Octylamine). After 4h the semi occlusive coverage was removed and the application site washed with Lutrol/Water. Readings were taken 30-60min after removal and 24h, 48h, 72h and as well as 8d and 15d after removal. The untreated area of each animal serves as control.

The 24/48/72 hours average scores of all animals was 3.8 (average per animal: 3.7, 4.0, 3.7) for erythema and 2.6 (3.0, 2.7, 2.0) for oedema.

In animal#1 the reaction was redness was not fully reversible within 15 days, whereas all other animals did not show any reaction (erythema or edema) on day 15.

In result the substance was severely irritating to skin.

 

Key study assignment skin irritation:

As there is only information from a study conducted with a read across substance, but this substance is a strong homologue and therefore assumed to be comparable in toxicological behaviour, this study is used assessing the skin irritation of Amines, tri-C8-10-alkyl and integrated as key study. 

 

Assessment skin irritation:

All available information is taken into account to assess the skin irritating potential of Amines, tri-C8-10-alkyl. As there is no study with the registered substance available a close structural homologue substance (Tri-N-Octylamin) is used as read across. It can be assumed that Tri-N-Octylamin  and Amines, tri-C8-10-alkyl are comparable in toxicological behaviour. Therefore the results from a skin irritation test with Tri-N-Octylamin are used to assess the skin irritation potential of Amines, tri-C8-10-alkyl. Based on the grading received from the animal study, Amines, tri-C8-10-alkyl is assumed to be severe irritating to skin. The recorded grading were very high but in all cases, except one, reversible within 15 days. Therefore the substance has to be classified as skin irritating cat 2 according GHS.

 

Eye irritation:

OECD guideline conform studies:

Tri-N-Octylamin was tested for acute irritation effects on eyes according to OECD 405 by single dose application (0.1ml) to the conjunctival sac of 3 male Vienna White rabbits (BASF SE, 1988, 11H0264/882109) to of three rabbits (Kleinrussen, Chbb:HM) with a single dose of 0.1 g per conjunctival sac and a duration of exposure of 24 hours. The mean cornea score and iris score was 0 (mean of all animals and timepoints). The mean chemosis score was recorded as 0, whereas slight to mild conjunctiva reactions (redness) were observed with gradings 1, 2, 2 (animal#1, animal#2, animal#3, average of 24/48 and 72 h reading). The effects observed were fully reversible within 8 days. According to the test conditions the test substance has to be classified as irritating to eye cat 2 GHS.

 

Key study assignment eye irritation:

As there is only information from a study conducted with a read across substance, but this substance is a strong homologue and therefore assumed to be comparable in toxicological behaviour, this study is used assessing the eye irritation of Amines, tri-C8-10-alkyl and integrated as key study. 

 

Assessment eye irritation:

All available information is taken into account to assess the skin irritating potential of Amines, tri-C8-10-alkyl. As there is no study with the registered substance available a close structural homologue substance (Tri-N-Octylamin) is used as read across. It can be assumed that Tri-N-Octylamin  and Amines, tri-C8-10-alkyl are comparable in toxicological behaviour. Therefore the results from a eye irritation test with Tri-N-Octylamin are used to assess the eye irritation potential of Amines, tri-C8-10-alkyl. As cornea, iris and chemosis score are 0 and only slight to mild redness of conjunctivae (scores between 1 and 2) the substance has to classified as irritating to skin cat. 2 GHS.

Effects on skin irritation/corrosion: highly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Skin:

Based on the available information from skin irritation study were gradings between 2.3 and 4 are observed, the substance has to be classified according to EU, UN-GHS (EC 1272/2008 ) as skin irritating Cat. 2 or DSD (67/548/EEC) R38

Labelling for skin irritation:

GHS: skin irritating Cat. 2

DSD: skin irritating R38

 

Eye:

Based on the available information from eye irritation study the test substance has to be classified according to Regulation No (EC) 1272/2008 (CLP) as eye irritant cat 2A or according to Directive 67/548/EEC (DSD) criteria as R36.

Labelling for eye irritation:

GHS: eye irritating Cat 2A

DSD: eye irritating R36