3-chloro-p-toluidine

Endpoint summary

Description of key information

For skin and eye irritation valid in-vivo studies in rabbits according to OECD TG 404 and OECD TG 405 are available.

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

other: New Zealand

Type of coverage:

other: patch 2.5*2.5 cm pulp

Preparation of test site:

abraded

Vehicle:

other: polyethylene glycol

Controls:

not specified

Duration of treatment / exposure:

4 hours

Observation period:

The animals were observed after 30 minutes, 60 minutes, 24, 48 and 72 hours after patch removal. Due to the fact that after 72 hours still findings in the skin could be observed, additional observations after 7, 14, and 22 days were performed.

Number of animals:

3

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Time after patch removal	30 -60 min			24 hours			48 hours			72 hours			7 days			14 days			22 days
Animal No.	1	2	3	1	2	3	1	2	3	1	2	3	1	2	3	1	2	3	1	2	3
Formation of erythema and eschar	2	2	1	2	1	2	2	2	2	2	3	2	1*	2	1*	0	0	0	0	0	0
Formation of edema	2	2	1	1	0	2	1	2	1	1	1	1	0	1	0	0	0	0	0	0	0
Surface of skin
-dry, rough										x	x	x	x	x	x		x
- fine-flaked														x			x
-coarse-flaked													x		x	x		x
- hardened															x
- parchmenty														x
Skin discolouration
-small surface: light brown					x			x		x	x	x
-large surface: light brown				x			x						x		x

*- thickened, reddish-bluish, circular location (diameter 1 -1.5 cm).

Interpretation of results:

GHS criteria not met

Executive summary:

In a skin irritation study according to OECD TG 404, 3 hours before starting the experiment, 3 rabbits were depilated in the dorsal area of the torso. Only animals having an intakt skin were used. The test substance (made into a paste with polyethylene glycol) was applied to the skin using a patch. The patch was removed after 4 hours and the skin was washed with lukewarm water.

30 to 60 minutes up to 7 days after patch removal the treated skin of the animals showed marginal observable up to moderate erythema and marginal observable up to slight edema. Swelling was observed and the skin was colored on a small up to large surface, dry, rough, sclerotic and parchmenty. 14 days p.a. no erythema or edema were observed anymore. The skin surface was dry-rough. in 2 rabbits a swelling of skin with and a reddish- bluish colour was abserved. After 22 days all signs were reversible.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

other: One eye of each rabbit served as control

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

1, 24, 48, 72 hours, 7 days after application of test substance the eyes were examined

Number of animals or in vitro replicates:

3

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

reddening of conjunctiva

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 2.4

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Remarks:

swelling of conjunctivae

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1.2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Other effects:

One hour after application of test substance clearly defined swelling of the conjunctiva was observed. Some bloodvessels showed a defined hyperemia. The iris was reddened in two animals. On the cornea diffuse opacity regions were seen. These findings came along with white-brownish defluxion.
24 up to 72 Hours after application of test substance slight to clear swelling of conjunctiva was observed. The conjunctiva showed a considerable hyperemia up to diffuse strong reddening. The iris of all animals was reddened. On the cornea diffuse opacoty regions were seen. In two animals bleeding in the conjunctiva were observed. These findings came along with a white defluxion.
7 days after application of the test substance the appearance of irritation was reversible.

Results:

Time post application	1 hour			24 hours			48 hours			72 hours			7 days
Animal Number	1	2	3	1	2	3	1	2	3	1	2	3	1	2	3
Swelling of conjunctiva	2	2	2	2	2	1	1	1	1	1	1	1	0	0	0
Reddening of conjunctiva	1	1	1	2	1	2	3	3	3	3	2	3	0	0	0
Iris	0	1	1	1	1	1	1	1	1	1	1	1	0	0	0
Corneal turbidity	1	1	1	1	1	1	1	1	1	1	1	1	0	0	0
Fluorescein-Test				2	3	2				3	1	4	0	0	0
Eye defluxion
-white-brownish	x	x	x
-white				x	x	x	x		x	x		x
Bloody Conjunctiva		x	x	x	x	x	x	x	x	x	x	x
Reddened Iris		x	x	x	x	x	x	x	x	x	x	x

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Executive summary:

In an eye irritation study according to OECD TG 405 the test substance was tested in the eyes of 3 New Zealand White rabbits.

24 hours before application of test substance, the eyes of the test rabbits were examined to detect posible damages on the cornea. Only animals showing no findings were used. 100 mg test substance was applied in a single dose into the conjunctival sac of the left eye of the test animals, the other eye served as control. 1, 24, 48, 72 hours and 7 days after application of test substance the eyes were examined.

One hour after application of test substance clearly defined swelling of the conjunctiva was observed. Some bloodvessels showed a defined hyperemia. The iris was reddened in two animals. On the cornea diffuse opacity regions were seen. These findings came along with white-brownish defluxion.

24 up to 72 Hours after application of test substance slight to clear swelling of conjunctiva was observed. The conjunctiva showed a considerable hyperemia up to diffuse strong reddening. The iris of all animals was reddened. On the cornea diffuse opacoty regions were seen. In two animals bleeding in the conjunctiva were observed. These findings came along with a white defluxion.

7 days after application of the test substance the appearance of irritation was reversible.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Eye Irrit. 2 ( H319: Causes serious eye irritation.) is justified.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

According to Directive 67/548 EWG 3-chloro-p-toluidine was classified as R38 (irritating to skin). According to CLP a classification for skin irritation is not required.

Justification for classification or non-classification

In a OECD Guideline study (404) with rabbits, the dermal application of 0.5 g of the test substance to three animals for 4 hours, a mean erythema score of 2 and an edema score of 1.1 was found.

The findings were reversible within 14 days. According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

In an eye irritation study according to OECD TG 405 the test substance was tested in the eyes of 3 New Zealand White rabbits.100 mg test substance was applied in a single dose into the conjunctival sac of the left eye of the test animals, the other eye served as control. 1, 24, 48, 72 hours and 7 days after application of test substance the eyes were examined.

A mean cornea opacity score of 1, a mean conjunctiva score of ca. 2.4, a mean iris score of ca.1 and a mean chemosis score of ca. 1.2 were found. The findings were reversible within 7 days.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Eye Irrit. 2 ( H319: Causes serious eye irritation) is justified.