Manganese, 3-hydroxy-4-[(1-sulfo-2-naphthalenyl)azo]-2-naphthalenecarboxylic acid complex

Endpoint summary

Description of key information

An acute skin irritation/corrosion study (1975) according to a national standard method, non-GLP, and an acute eye irritation/corrosion study (1975) similar to OECD TG 404, non-GLP were conducted to determine the skin and eye irritating potential of the test substance. Based on the results of these studies, the test substance is not considered 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

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: The method given in the "Hazardous Substance Regulations" unter the U.S. Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 11 - 16 weeks
- mean weight at study initiation: males 2.57 kg and females 2.60 kg
- Housing: animals were caged singly in an experimental room
- Diet: a commercial irradiated diet (Styles-Oxoid) was fed ad libitum
- Water: sterile filtered water was available at all time

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 50-70
- Photoperiod: Animals were exposed to artificial light for 10 hours daily from 08.00 - 18.00 hours

Type of coverage:

occlusive

Preparation of test site:

other: abraded and shaved

Vehicle:

other: polyethylene glucol

Controls:

other: untreated skin of the same animals

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 10 g of the test item was mixed with 20 mL of 50% solution polyethylene glycol and water to make a solution of 20 mL

Duration of treatment / exposure:

24 hours

Observation period:

6 days

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Application side: back
- % coverage: at least 10% of the total body surface
- Type of wrap if used: aluminium foil secured with "sleek" adhersive tape. The test sides were than enclosed by a 6 wide Coban self adhesive bandage the edges of which were fixed to the skin by stripes.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24h - 72h

Score:

0

Max. score:

4

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24h - 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24h - 72h

Score:

0

Max. score:

4

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24h - 72h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24h - 72h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #4

Time point:

other: 24h - 72h

Score:

0

Max. score:

4

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: 24h - 72h

Score:

0

Max. score:

4

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #6

Time point:

other: 24h - 72h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: intact skin

Irritant / corrosive response data:

The test substance ist not irritating to intact skin within 72 hours.

Table 1: Erythema formation

Erythema Formation
	Intact		Abraded		Total
No	24h	72h	24h	72h
11	0	0	1	0
13	0	0	1	0
15	0	0	1	0
12	0	0	1	0
14	0	0	1	0
16	0	0	1	0
Mean	0.00	0.00	1.00	0.00	1.00

 

Table 2: Oedema formation

Oedema Formation
	Intact		Abraded		Total
No	24h	72h	24h	72h
11	0	0	2	0
13	1	0	2	0
15	1	0	2	1
12	0	0	2	0
14	0	0	2	0
16	2	0	3	1
Mean	0.67	0.00	2.17	0.33	3.17

 

Interpretation of results:

GHS criteria not met

Conclusions:

Because of the findings regarding the intact skin, the test substance is not considered irritating to the skin.

Executive summary:

Groups of six New Zealand White rabbits (4 females, 2 males) were dermally exposed to the test item. Twenty-four hours prior to the dermal application, the backs of the rabbits were shaved over an area consisting of at least 10% of the total body surface. Two test sites lateral to the mid line of the back were used. Immediately before the application of the test compound, the right hand site was abraded, the left hand site remained intact. 10 g of the test item was mixed with 20 mL of a 50% solution of polyethylene glycol and water to make a solution of 20 mL. 1.5 mL was applied to each test site on a 2.5 cm gauze pad. The test sites were covered with an occlusive dressing for 24 hours. No erythema effect was observed on the intact skin sites after application of the test compound. On the abraded sites 6/6 animals showed a slight erythema effect, which was fully reversible within 72 hours. Slight to moderate edema was seen on 3/6 intact sites and 6/6 abraded sites, 24 hours after application of the compound. Verly slight edema was still present on 2/6 abraded sites at 72 hours, but had returned to normal by day 6. The observed edema effect to the intact skin was also fully reversible within 72 hours. The observed mean edema and erythema score for the intact skin were 0.33 and 0, repectively. 

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:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

no GLP study, no information about cornea and iris scores.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

no information about cornea and iris scores.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 11-16 weeks
- Mean body weight at study initiation: males 2.57 and females 2.60 kg
- Housing: the rabbits were caged singly in an experimental room
- Diet: A commercial diet (Styles-Oxid) was fed ad lib.
- Water: sterile filtered water was available at all times
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 50-70
- Photoperiod: Animals were exposed to artificial light for 10 hours daily from 08.00 - 18.00 hours

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 100 mg

Duration of treatment / exposure:

single treatment

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

6

Details on study design:

- the test substance was instilled into the conjunctival sac of the left eye. The eyelids were then closed for one second.
- the non-treated left eye served as control

REMOVAL OF TEST SUBSTANCE
- Washing: after 30 seconds the compounds was, as far as possible, flushed out of the eyes of three of the six rabbits with warm water for 1 minute

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.11

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: washed eyes

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: washed eyes

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.55

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: not washed eyes

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: not washed eyes

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: washed eyes

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

other: washed eyes

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

other: washed eyes

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: washed eyes

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: washed eyes

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: washed eyes

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: not washed eyes

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 28 hours

Remarks on result:

other: not washed eyes

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

other: not washed eyes

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: not washed eyes

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: not washed eyes

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: not washed eyes

Interpretation of results:

GHS criteria not met

Conclusions:

Only based on the given results for the conjunctiva, the test compound is not considered irritating to the eye.

Executive summary:

In an acute eye irritation/corrosion study with New Zealand White rabbits, 100 mg of the test compound were instilled into the conjunctival sac of the left eye of six rabbits (3/sex). The eyelids were then closed for one second. After 30 seconds the test item was washed out of the eyes of three of the rabbits. The eyes of the remaining three animals were not washed out. The rabbits were examined 1, 24, 48 and 72 hours after application of the test compound. A very slight to mild conjuctival reaction was seen in 3/3 unwashed and 2/3 washed eyes one hour after application of the compound. By 24 hours 3/3 unwashed and 1/3 washed eyes were showing a very slight reaction. These rapidly returned to normal by 48 hours (2/3 unwashed, 1/3 washed eyes) and 72 hours (1/2 in washed eyes). The observed mean conjunctivae scores for the washed and unwashed eyes were 0.11 and 0.55, respectively. After 1 hour of application 2/3 washed and unwashed eyes showed slight chemosis. This effects were fully reversible within 48 hours and a mean chemosis score (24,48,72h) of 0 was determined for both, washed and unwashed eyes.The effects of the test substance on the iris and the cornea were not investigated in this study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion

In an acute skin irritation/corrosion study, groups of six New Zealand White rabbits (4 females, 2 males) were dermally exposed to the test item in accordance to the method given in the "Hazardous Substance Regulations" unter the U.S. Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965). Twenty-four hours prior to the dermal application, the backs of the rabbits were shaved over an area consisting of at least 10% of the total body surface. Two test sites lateral to the mid line of the back were used. Immediately before the application of the test compound, the right hand site was abraded, the left hand site remained intact. 10 g of the test item was mixed with 20 mL of a 50% solution of polyethylene glycol and water to make a solution of 20 mL. 1.5 mL was applied to each test site on a 2.5 cm gauze pad. The test sites were covered with an occlusive dressing for 24 hours. No erythema effect was observed on the intact skin sites after application of the test compound. On the abraded sites 6/6 animals showed a slight erythema effect, which was fully reversible within 72 hours. Slight to moderate edema was seen on 3/6 intact sites and 6/6 abraded sites, 24 hours after application of the compound. Verly slight edema was still present on 2/6 abraded sites at 72 hours, but had returned to normal by day 6. The observed edema effect to the intact skin was also fully reversible within 72 hours. The observed mean edema and erythema score for the intact skin were 0.33 and 0, repectively. Because of the findings regarding the intact skin, the test substance is not considered irritating to the skin.

 

Eye irritation

In an acute eye irritation/corrosion study with New Zealand White rabbits was performed according to the procedure set out in the "Hazardous Substance Regulations" under the U.S.A. Federal Hazardous Substance Labelling Act Sect. 191.12 (February 1965). 100 mg of the test compound were instilled into the conjunctival sac of the left eye of six rabbits (3/sex). The eyelids were then closed for one second. After 30 seconds the test item was washed out of the eyes of three of the rabbits. The eyes of the remaining three animals were not washed out. The rabbits were examined 1, 24, 48 and 72 hours after application of the test compound. A very slight to mild conjuctival reaction was seen in 3/3 unwashed and 2/3 washed eyes one hour after application of the compound. By 24 hours 3/3 unwashed and 1/3 washed eyes were showing a very slight reaction. These rapidly returned to normal by 48 hours (2/3 unwashed, 1/3 washed eyes) and 72 hours (1/2 in washed eyes). The observed mean conjunctivae scores for the washed and unwashed eyes were 0.11 and 0.55, respectively. After 1 hour of application 2/3 washed and unwashed eyes showed slight chemosis. This effects were fully reversible within 48 hours and a mean chemosis score (24,48,72h) of 0 was determined for both, washed and unwashed eyes.The effects of the test substance on the iris and the cornea were not investigated in this study. Only based on the given results for the conjunctiva, the test compound is not considered irritating to the eye.

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 1272/2008. In both studies, the scores for the test item treated tissues were below the thresholds for classification as an irritant. As a result, the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EC) No. 2020/217.