6-nonyl-1,3,5-triazine-2,4-diamine

Endpoint summary

Description of key information

Caprinoguanamine was not irritating to skin and eye.

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

The exposure time was 24 hours (occlusive); observation at 24 and 72 hours after the start of application.

Qualifier:

according to guideline

Guideline:

other: US FHSA Federal regulation: 16 CFR 1500.41

Deviations:

no

GLP compliance:

no

Remarks:

study performed before implementation of GLP

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: adult

Type of coverage:

occlusive

Preparation of test site:

other: clipped; intact and abraded

Vehicle:

not specified

Controls:

no

Amount / concentration applied:

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

Duration of treatment / exposure:

24 h

Observation period:

72 h

Number of animals:

6 (intact skin) + 6 (abraded skin)

Details on study design:

TEST SITE
- Area of exposure: 1 inch x 1 inch
- Type of wrap if used: surgical patch fixed by adhesive tape and wrapped with an impervious material

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 hours

SCORING SYSTEM:
- Draize (J. Pharmacol. 82 (1944) 377-390)
- CIVO-grading system (1973)

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no irritant/corrosive effects in any animal with intact skin
One animal with abraded skin showed very slight erythema (grade 1) at the 24 hour time point. After 72 hours no skin reactions were observed in any of the rabbits.

Interpretation of results:

GHS criteria not met

Conclusions:

Caprinoguanamine was not irritating to skin. There were no skin effects observed in any animal with intact skin at 24 and 72 hours.

Executive summary:

In a primary dermal irritation study according to US FHSA Federal regulation: 16 CFR 1500.41 and similar to OECD Guideline 404, adopted 24 April 2002, 6 adult New Zealand white rabbits with intact skin were dermally exposed 24 hours to 0.5 g of Caprinoguanamine on 6.45 cm² skin surface. Animals were then observed for 72 hours. In addition, 6 rabbits with abraded skin were exposed under the same conditions.

Irritation was scored by the method of Draize (J. Pharmacol. 82 (1944) 377-390) and the CIVO-grading system (1973).

There were no skin effects observed in any animal with intact skin at 24 hours. One animal with abraded skin showed very slight erythema (grade 1) at the 24 hour time point. After 72 hours no skin reactions were observed in any of the rabbits. The result of the study is regarded as relevant and reliable although there are protocol deviations from the OECD 404 guideline (longer exposure time, shorter observation time).

In this study, Caprinoguanamine is classified as not irritating to rabbit skin according the criteria of CLP, EU GHS (Regulation (EC) No 1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not 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:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

02 October 2012

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: FDA (Fed. Reg. 28 (119), 5582, 1963

Qualifier:

according to guideline

Guideline:

other: Draize and Kelley (Drug Cosmet. Industr. 71 (1952) 36)

GLP compliance:

no

Remarks:

study performed before implementation of GLP

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: adult
- Housing: caged individually and recieved no hay or other extranous material that might enter eyes

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

7 days

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- the eyes were not washed following instillation

SCORING SYSTEM: FDA scoring scale

TOOL USED TO ASSESS SCORE: binocular magnifying glass, confirmation of corneal damage by flourescein staining if necessary

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #4, #5, #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

animal: #1, #2, #4, #5, #6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal: #2, #5

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: #3, #6

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 d

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

24 hours after Caprinoguanamine had been brought into the eyes very slight corneal opacity and slight iritis in one rabbit and slight conjunctivitis in all six rabbits were observed. In the course of the seven day observation period all lesions recovered completely, so that at the seventh day reading all eyes were normal again.

Individual scores awarded to the ocular lesions elicited by Caprinoguanamine:

Score time point	Cornea (max score 4)	Iris (max. score 2)	Conjunctivae (max. score 3)	Chemosis (max. score 4)
24 hours	0/0/1/0/0/0	0/0/1/0/0/0	1/1/1/1/1/1	0/0/1/0/1/0
48 hours	0/0/0/0/0/0	0/0/0/0/0/0	0/1/1/0/1/1	0/0/0/0/0/1
72 hours	0/0/0/0/0/0	0/0/0/0/0/0	0/0/1/0/0/1	0/0/1/0/0/0
7 days	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0

Interpretation of results:

GHS criteria not met

Conclusions:

24 hours after Caprinoguanamine had been brought into the eyes very slight corneal opacity and slight iritis in one rabbit and slight conjunctivitis in all six rabbits were observed. In the course of the seven day observation period all lesions recovered completely, so that at the seventh day reading all eyes were normal again.

Executive summary:

In a primary eye irritation study similar to OECD guideline 405, 2nd October 2012, 100 mg of Caprinoguanamine was instilled into the conjunctival sac of 6 adult New Zealand white rabbits. Animals then were observed for 7 days. Irritation was scored by the FDA scoring scale. 24 hours after Caprinoguanamine had been brought into the eyes very slight corneal opacity and slight iritis in one rabbit (score 1) and slight conjunctivitis (score 1) in all six rabbits were observed. All lesions were fully reversible within the 7 day observation period.

In this study the mean grades of ocular reactions at 24, 48 and 72 h after instillation were lower than the values classified as irritant by the Directive 67/548/EEC as well as GHS Regulation EC No 1272/2008.

When administered to the eye, the test article Caprinoguanamine is classified as "non-irritant".

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin:

In a primary dermal irritation study according to US FHSA Federal regulation: 16 CFR 1500.41 and similar to OECD Guideline 404, adopted 24 April 2002, 6 adult New Zealand white rabbits with intact skin were dermally exposed 24 hours to 0.5 g of Caprinoguanamine on 6.45 cm² skin surface. Animals were then observed for 72 hours. In addition, 6 rabbits with abraded skin were exposed under the same conditions.

Irritation was scored by the method of Draize (J. Pharmacol. 82 (1944) 377-390) and the CIVO-grading system (1973).

There were no skin effects observed in any animal with intact skin at 24 hours. One animal with abraded skin showed very slight erythema (grade 1) at the 24 hour time point. After 72 hours no skin reactions were observed in any of the rabbits. The result of the study is regarded as relevant and reliable although there are protocol deviations from the OECD 404 guideline (longer exposure time, shorter observation time).

In this study, Caprinoguanamine is classified as not irritating to rabbit skin according the criteria of CLP, EU GHS (Regulation (EC) No 1272/2008).

Similar results were obtained with the closely related read-across substances Benzoguanamine and Acetoguanamine:

In a primary dermal irritation study according to OECD Guideline 404, adopted 12 May, 1981, 3 adult female New Zealand white rabbits with intact skin were dermally exposed 4 hours to 0.5 g of Benzoguanamine on 6 cm² skin surface. Animals were then observed for 72 hours.

None of the animals showed any response to treatment throughout the observation period

In this study, Benzoguanamine is classified as not irritating to rabbit skin according the criteria of CLP, EU GHS (Regulation (EC) No 1272/2008).

 

In a primary dermal irritation study according to OECD Guideline 404, adopted 12 May, 1981, 3 adult female New Zealand white rabbits with intact skin were dermally exposed 4 hours to 0.5 g of Acetoguanamine on 6.25 cm² skin surface. Animals were then observed for 4 days.

None of the animals showed any response to treatment throughout the observation period

In this study, Acetoguanamine is classified as not irritating to rabbit skin according the criteria of CLP, EU GHS (Regulation (EC) No 1272/2008).

 

Eye:

In a primary eye irritation study similar to OECD guideline 405, 2nd October 2012, 100 mg of Caprinoguanamine was instilled into the conjunctival sac of 6 adult New Zealand white rabbits. Animals then were observed for 7 days. Irritation was scored by the FDA scoring scale. 24 hours after Caprinoguanamine had been brought into the eyes very slight corneal opacity and slight iritis in one rabbit (score 1) and slight conjunctivitis (score 1) in all six rabbits were observed. All lesions were fully reversible within the 7 day observation period.

In this study the mean grades of ocular reactions at 24, 48 and 72 h after instillation were lower than the values classified as irritant by the Directive 67/548/EEC as well as GHS Regulation EC No 1272/2008.

When administered to the eye, the test article Caprinoguanamine is classified as "non-irritant".

Similar results were obtained with the closely related read-across substances Benzoguanamine and Acetoguanamine:

In a primary eye irritation study according to EU method B.5, 94 mg of Benzoguanamine was instilled into the conjunctival sac of 3 adult New Zealand White rabbits. Animals then were observed for 72 hours.

No adverse effects on the cornea and the iris were observed in any of the rabbits during the entire observation period. Approx. 60 minutes after exposure slight chemosis in two animals were observed which resolved within 24 hours.

In this study the mean grades of ocular reactions at 24, 48 and 72 h after instillation were lower than the values classified as irritant by the Directive 67/548/EEC as well as GHS Regulation EC No 1272/2008.

When administered to the eye, the test article Benzoguanamine is classified as "non-irritant”.

 

In a primary eye irritation study according to OECD guideline 405, 85 mg of Acetoguanamine was instilled into the conjunctival sac of 3 adult New Zealand White rabbits. Animals then were observed for 7 days. Irritation was scored and it was determined that Acetoguanamine elicites only transient, corneal opacification and temporary well-defined conjuctival reactions.

In this study the mean grades of ocular reactions at 24, 48 and 72 h after instillation were lower than the values classified as irritant by the Directive 67/548/EEC as well as GHS Regulation EC No 1272/2008.

When administered to the eye, the test article Acetoguanamine is classified as "non-irritant”.

Justification for classification or non-classification

Based on data from a study similar to OECD Guideline 404, Caprinoguanamine is classified as not irritating to rabbit skin according the criteria of CLP, EU GHS (Regulation (EC) No 1272/2008).

Mean scores of ocular reactions at 24, 48 and 72 h observed in a primary eye irritation study similar to OECD guideline 405 with Caprinoguanamine indicate that the substance does not need to be classified for eye irritation as well, based on CLP criteria, EU GHS (Regulation (EC) No 1272/2008).