1,3-di-o-tolylguanidine

Endpoint summary

Description of key information

A reliable study is available for skin and eye irritation in rabbits (1975): DOTG is not irritating for skin but slightly irritating for eyes in rabbit.
No data is available on respiratory tract irritation.

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:

no guideline followed

Principles of method if other than guideline:

Method: Draize Test
Primary irritation to the skin is measured by a patch-test technique on the abraded and intact skin of albino rabbits.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

no data

Type of coverage:

semiocclusive

Preparation of test site:

other: abraded and intact skin

Vehicle:

unchanged (no vehicle)

Remarks:

undiluted

Controls:

no

Amount / concentration applied:

An amount of 500 g of DOTG

Duration of treatment / exposure:

24 hour(s)

Observation period:

24, 48 and 72 hours after application

Number of animals:

12 rabbits : 6 with intact skin, and 6 with abraded skin.

Details on study design:

DOTG is brought on the intact or abraded skin under a surgical patch measuring 1 inch x 1 inch. The patches are fixed to the application site by means of adhesive tape and the entire trunk of the rabbits is wrapped with an impervious material to maintain the test patch in position.
Twenty four hours prior to applying the materials, the hair is removed from the backs of the animals with an electric clipper in such a way as to avoid abrasions.
SCORING SYSTEM: Draize grading system.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

12 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

(with intact and abraded skin)

Irritation parameter:

edema score

Basis:

mean

Remarks:

12 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

(with intact and abraded skin)

Irritant / corrosive response data:

No signs of skin irritation could be detected in any of the test animals, either at the end of the 24 hours application period or 48 hours later.

Interpretation of results:

GHS criteria not met

Remarks:

not skin irritating according to CLP

Conclusions:

According to this study, DOTG is not a skin irritant in rabbits.

Executive summary:

DOTG was examined for possible skin irritating properties in rabbits.

DOTG was applied to rabbit during 24 hours and animals were observed at 1, 24, 48, 72 hours.

Primary irritation to the skin is measured by a patch-test technique on the abraded and intact skin of albino rabbits.

No signs of skin irritation could be detected in any of the test animals, either at the end of the 24 hours application period or 48 hours later.

DOTG did not cause any signs of skin 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:

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:

no guideline followed

Principles of method if other than guideline:

Method: Draize

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Animals were caged individually and receive no hay or others extraneous material that might enter the eyes.

Vehicle:

unchanged (no vehicle)

Remarks:

undiluted

Controls:

other: yes, the second eye

Amount / concentration applied:

Amount applied: 100 mg

Duration of treatment / exposure:

not applicable

Observation period (in vivo):

24, 48, 72 hours and 7 days after instillation of the test material.

Number of animals or in vitro replicates:

6 rabbits

Details on study design:

The eyes of the animals are examined before testing and only those animals without observable eye defacts are used.
The eyes are not washed loffowing the instillation and the animals are released immediately.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

0.39

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

0.39

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

1.6

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Scores at day 7 are 1.

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

1.56

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Scores at day 7 are 1.

Irritant / corrosive response data:

Twenty four hours after DOTG had been brought into the eyes, slight corneal damage was observed in three out of six rabbits, slight iritis in four out od six rabbits and slight or moderate conjunctivitis in all test rabbits. The eye lesions recovered gradually but incompletely, so what at the seventh day reading slight conjunctivitis was still observed in three out of 6 rabbits.

Other effects:

no data

Table of results: Eye irritation test

Individual scores awarded to the ocular reactions elicited by DOTG.

 

Rabbit n°	cornea	iris	Conjunctivae (redness)	Conjunctivae (chemosis)
AFTER 24 HOURS
1	1	1	2	3
2	1	1	2	2
3	0	1	2	2
4	0	0	1	1
5	1	1	2	3
6	0	0	1	2
AFTER 48 HOURS
1	1	1	2	2
2	1	1	2	1
3	0	0	2	1
4	0	0	1	0
5	1	0	2	2
6	0	0	1	2
AFTER 72 HOURS
1	1	0	2	2
2	0	1	2	1
3	0	0	1	1
4	0	0	1	0
5	1	0	2	2
6	0	0	1	1
AFTER 7 DAYS
1	0	0	0	0
2	0	0	1	1
3	0	0	1	1
4	0	0	0	0
5	0	0	1	1
6	0	0	0	0

 

 

Table no.2 of results :

 

Rabbits no.	Duration of observation	cornea	iris	Conjunctivae / redness	Conjunctivae / chemosis
1	Mean 24-48-72 hours	1	0.67	2	2.33
2		0.67	1	2	1.33
3		0	0.33	1.67	1.33
4		0	0	1.33	0.33
5		0.33	0.33	1.67	2.33
6		0	0	1.33	1.67

 

Interpretation of results:

GHS criteria not met

Remarks:

not eye irritating according to CLP

Conclusions:

According this study, DOTG is a slightly eye irritant in rabbits.

Executive summary:

DOTG was examined for possible eye irritating properties in rabbits. DOTG was applied to rabbit (100 mg) and rabbits were observed at 1, 24, 48, 72 hours and 7 days.

DOTG caused slight corneal damage in three out of 6 rabbits, slight iritis in four out of 6 rabbits, and slight or moderate conjunctivitis in all test rabbits. In conclusion, DOTG is slightly irritant for eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation :

DOTG was examined for possible skin irritating properties in rabbits (1975). DOTG was applied to rabbits during 24 hours and animals were observed at 1, 24, 48 and 72 hours. Primary irritation to the skin is measured by a patch-test technique on the abraded and intact skin of albino rabbits. No signs of skin irritation is detected in any of the test animals, either at the end of the 24 hours application period or 48 hours later. DOTG did not cause any signs of skin irritation.

 

Eye irritation :

DOTG was examined for possible eye irritating properties in 6 rabbits (1975). DOTG was applied to rabbits (100 mg) and rabbits were observed at 1, 24, 48, 72 hours and 7 days. DOTG caused slight corneal damage in three out of 6 rabbits, slight iritis in four out of 6 rabbits, and slight or moderate conjunctivitis in all tested rabbits. In conclusion, DOTG is slightly irritant for eyes.

Justification for classification or non-classification

Based on the available data, 1,3-di-o-tolylguanidine should not be classified as irritating according to the Regulation EC N°1272/2008.