Benzoic acid, 3-[[(2,3-dihydroxypropyl)amino]carbonyl]-5-nitro-

Endpoint summary

Description of key information

Skin irritation (Rat, GLP): not skin irritanting [Schering AG, Report No. X111 -draft-, 1996-09-25]

Eye irritation (Rabbit, GLP, OECD TG 405): not eye irritanting [Schering AG, Report No. X149 -draft-, 1996-09-19]

 

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:

other information

Study period:

November to December 1995

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)

Version / remarks:

1992

Principles of method if other than guideline:

combined acute dermal toxicity and local irritation study; single dermal application of test substance (application volume 0.3 ml) to male and female rats; occlusive conditions; exposure for 24 hours; values for reddening, scab formation and swelling obtained immediately after removal of the bandage and the substance and 24, 48 and 72 h after the end of administration.

GLP compliance:

yes

Species:

rat

Strain:

Wistar

Type of coverage:

occlusive

Vehicle:

other: bidist. water with 0.9 % NaCI and 0.085% Myrj 53

Controls:

no

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

3/sex

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Other effects:

The test substance was tolerated without any local skin irritation

No compound-related findings were observed in neither clinical observation nor body weight gain nor autopsy.

No local intolerance reactions at the application sites were observed. 

 

Interpretation of results:

GHS criteria not met

Conclusions:

The test item is not irritant to skin.
No local intolerance reactions at the application sites were observed in a combined acute dermal and local tolerance study in rats.

Executive summary:

The single dermal administration of NIP-Monoamid to male and female rats at the dose of 2000 mg/kg was tolerated without any mortality or compound-related clinical or macroscopic pathological signs. The test substance was tolerated without any local skin irritations.

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

Study period:

February 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987-02-24

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Controls:

other: left eye served as control

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

test substance remained in eye and was not flushed out

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

2 males and 2 females

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.42

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Other effects:

Single application of ZK 39116 led to slight to severe reddening, swelling and vascular injection as well as secretion and eye lid closure mainly on the application day. On days 2 and 3, the findings gradually subsided and only slight findings were observed until days 5 to 6.

Results of the study

		Irritant Effects (Score)
Animal		24 h	48 h	72 h	Mean scores
1 (male)	Corneal Opacity	0	0	0	0.0
	Iris (redness, swelling, reaction of pupillary reflex etc.)	0	0	0	0.0
	Conjunctivae (reddining)	2	2	1	1.67
	Conjunctivae (swelling)	2	1	0	1.0
2 (male)	Corneal Opacity	0	0	0	0.0
	Iris (redness, swelling, reaction of pupillary reflex etc.)	0	0	0	0.0
	Conjunctivae (reddining)	2	2	1	1.67
	Conjunctivae (swelling)	1	0	0	0.33
3 (female)	Corneal Opacity	0	0	0	0.0
	Iris (redness, swelling, reaction of pupillary reflex etc.)	0	0	0	0.0
	Conjunctivae (reddining)	1	1	1	1.0
	Conjunctivae (swelling)	1	0	0	0.33
4 (female)	Corneal Opacity	0	0	0	0.0
	Iris (redness, swelling, reaction of pupillary reflex etc.)	0	0	0	0.0
	Conjunctivae (reddining)	2	1	1	1.33
	Conjunctivae (swelling)	1	1	1	1.0

Interpretation of results:

GHS criteria not met

Conclusions:

A single conjunctival application of ZK 39166 provoked on the whole transient slight to moderate intolerance reactions. Since the rabbit eye reacts more sensitively than the human eye due to anatomical and physiological differences, no significant effects are to be expected after inadvertent contact between the human eye and this substance.

Executive summary:

The local tolerance of ZK 39166 was tested after a single application of solid substance measured as 0.1 ml/eye into the conjunctival' sac of the right eye in 2 male and 2 female New Zealand White rabbits. The volume of 0.1 ml corresponded to 52 - 59 mg.
The respective left eye remained untreated and served as control.
Observations were performed before application, 0.5; 1 and 2 hours thereafter and then every 24 hours until day 7 of the test.
A single application of 0.1 ml ZK 39166 into the conjunctival sac of the rabbit eye led to slight to severe reddening, swelling and vascular injection as weil as secretion and eye lid closure mainly on the application day. On days 2 and 3, the findings gradually subsided and only slight findings were observed until days 5 to 6.
According to the system of evaluation recommended for the EU, the mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameters comea and iris, 1.4 for conjunctival reddening and 0.7 for conjunctival swelling.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The single dermal administration of NIP-Monoamid to male and female rats at the dose of 2000 mg/kg was tolerated without any mortality or compound-related clinical or macroscopic pathological signs.

Although the study was with respect to skin irritation / corrosion not conducted according to current guidelines and with the most sensitive species rabbit NIP-Monoamid can be regarded as not irritating to the skin since 24 h exposure to the test substance (instead of 4 h) under occlusive conditions (instead of semi-occlusive) was tolerated by 6 rats (instead of 3 animals) without any local skin reactions.

The single administration of NIP-Monoamid into the right eye of male and female rabbits with a volume of 0.1 ml/eye (corresponding to 52 -59 mg) results in slight to severe reddening, swelling and vascular injection as well as secretion and eye lid closure mainly on the application day. On days 2 and 3, the findings gradually subsided and only slight findings were observed until days 5 to 6. Therefore, according to EU classification criteria the test substance is not eye irritanting.

Justification for classification or non-classification

Based on the study results a classification according to Directive 67/548/EEC and Regulation (EC) No. 1272/2008 (CLP) is not required.