N,N'-diphenylguanidine monohydrochloride

Endpoint summary

Description of key information

Based on experimental data with a read-across substance the test item is considered severely irritating to the eye and non-irritating to the skin.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

The test item (target substances, CAS 24245-27-0) is the salt of 1,3-diphenylguanidine and mono-hydrochloride. As read-across source substance the uncharged free base of 1,3-diphenylguanidine (CAS 102-06-7) is applied. This is considered appropriate since the target substance is expected to readily dissociate in contact with water such as surface water in the environment or the intestinal fluids or mucosal membranes of an organism. 1,3-diphenylguanidine is considered a weak base. Therefore, it is expected to be present as uncharged molecule at neutral and high pH solutions. However, acidic conditions will lead to protonation of the molecule and the charged ion is expected to be the main present form. Since transformation of the target to the source substance and vice versa is anticipated, kinetics and toxicological behaviour are well transferable from the source to the target substance. This applies for human health endpoints as well as for the aquatic environment.
Moreover, chloride ions are ubiquitously present in every-day nutrition and are part of numerous physiological processes. Therefore, this constituent does not require further assessment in regards to its toxicological behaviour. It is expected to be well regulated by endogenous physiological mechanisms of the organism.
Based on the considerations above, a read-across is considered appropriate and further tests, especially vertebrate studies, are not needed to adequately address this endpoint. Information Requirements are fulfilled according to REACH Annex XI Section 1.5.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

The test item (target substances, CAS 24245-27-0) is the salt of 1,3-diphenylguanidine and mono-hydrochloride. As read-across source substance the uncharged free base of 1,3-diphenylguanidine (CAS 102-06-7) is applied. This is considered appropriate since the target substance is expected to readily dissociate in contact with water such as surface water in the environment or the intestinal fluids or mucosal membranes of an organism. 1,3-diphenylguanidine is considered a weak base. Therefore, it is expected to be present as uncharged molecule at neutral and high pH solutions. However, acidic conditions will lead to protonation of the molecule and the charged ion is expected to be the main present form. Since transformation of the target to the source substance and vice versa is anticipated, kinetics and toxicological behaviour are well transferable from the source to the target substance. This applies for human health endpoints as well as for the aquatic environment.
Moreover, chloride ions are ubiquitously present in every-day nutrition and are part of numerous physiological processes. Therefore, this constituent does not require further assessment in regards to its toxicological behaviour. It is expected to be well regulated by endogenous physiological mechanisms of the organism.
Based on the considerations above, a read-across is considered appropriate and further tests, especially vertebrate studies, are not needed to adequately address this endpoint. Information Requirements are fulfilled according to REACH Annex XI Section 1.5.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Remarks:

(severity)

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 6 weeks

Irritation parameter:

cornea opacity score

Remarks:

(severity)

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 6 weeks

Irritation parameter:

cornea opacity score

Remarks:

(severity)

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 6 weeks

Irritation parameter:

cornea opacity score

Remarks:

(area)

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 6 weeks

Irritation parameter:

cornea opacity score

Remarks:

(area)

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 6 weeks

Irritation parameter:

cornea opacity score

Remarks:

(area)

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 6 weeks

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 4 weeks

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 4 weeks

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 4 weeks

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 3 weeks

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 3 weeks

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 3 weeks

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 1 - <= 3

Max. score:

4

Reversibility:

fully reversible within: 3 weeks

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

>= 1 - <= 3

Max. score:

4

Reversibility:

fully reversible within: 3 weeks

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

>= 1 - <= 3

Max. score:

4

Reversibility:

fully reversible within: 3 weeks

Irritation parameter:

conjunctivae score

Remarks:

(discharge)

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

3

Reversibility:

fully reversible within: 3 weeks

Irritation parameter:

conjunctivae score

Remarks:

(discharge)

Basis:

animal #2

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

3

Reversibility:

fully reversible within: 3 weeks

Irritation parameter:

conjunctivae score

Remarks:

(discharge)

Basis:

animal #3

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

3

Reversibility:

fully reversible within: 3 weeks

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Read-across approach:

There are no experimental data available regarding skin or eye irritating properties of the test item. However, data are available with a structural analogues substance which are suitable and adequate to fulfill these endpoints. For Read-across justification please refer to the respective IUCLID Section.

Skin irritation in vivo

In a skin irritation study 0.5 g of the read-across substance (CAS 102 -06 -7) was administered for 4 hours on 2 areas (scratched and intact areas) of the closed skin on the back of 3 rabbits. No skin reaction, including erythema or edema, was observed on either of the scratched or intact during the observation period (72 h). Based on these results, the read-across substance was considered to be non-irritating to rabbit skin.

Eye irritation in vivo

In an in vivo eye irritation study, the read-across substance (CAS 102 -06 -7) was administered to 6 rabbits. Three rabbits received the substance on an eye and skin. The other 3 rabbits received the substance on an eye and their eyes were washed after the administration.

In the eye irritation test, a dose of 0.1 g of 1,3-diphenylguanidine was administered to one eye of each rabbit. After the administration, strong cornea opacity, conjunctival chemosis, obvious iris congestion, conjunctival redness, a low level of eye discharge and neovascular in cornea were observed. The local reaction on the conjunctivae and the iris congestion disappeared in 3 weeks and 4 weeks, respectively, but local reactions in cornea were still recognized 6 weeks after the administration. Based on these results, the read-across substance was considered to be eye damaging to the eyes in rabbits. When the test was repeated with a group of 3 rabbits and eyes were washed 30 seconds after administration, obvious iris congestion, conjunctival chemosis, and a low level of conjunctival redness were observed after the administration. All of these local reactions disappeared within 72 hours after the administration, and therefore, there was a washing effect.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data with a read-across substance the test item is classified and labelled as eye damaging Cat. 1 (H318: "Causes severe eye damage") according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.

The test item does not require classification as being skin irritating according to CLP.