Benzenamine, N,N-dimethyl-, oxidized, molybdatetungstatephosphates

Endpoint summary

Description of key information

skin irritation, OECD 404, WoE, not skin irritant

eye irritation, OECD 405, H318, Eye Damage 1

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

January - March 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

2004

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147

Version / remarks:

2000

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: at least 6 weeks old
- Weight at study initiation: at least 1.0 kg
- Housing: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm).
- Diet: Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approx. 100 g. per day.
- Water: tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.4 -21.7°C
- Humidity (%): 32 - 57%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

CONTROL
Adjacent areas of the untreated skin of each animal served as controls.

Duration of treatment / exposure:

4 h

Observation period:

72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2x3 cm
- Type of wrap if used: Micropore tape, secured with Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: with tab water
- Time after start of exposure: 4h

OBSERVATION TIME POINTS
1, 24, 48 and 72 hours

SCORING SYSTEM:
- Method of calculation: Draize scheme

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

There was no evidence of a corrosive or irritation effect on the skin.

Other effects:

Purple staining of the treated skin by the test substance was observed throughout the study period, which did not hamper the scoring of the skin reactions.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Interpretation of results:

GHS criteria not met

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

other: BASF-Test

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

BASF-TEST: Before OECD guideline 404 was established, skin irritation was tested using an internal method. White Vienna rabbits were used. Usually, 2 animals were treated for 1, 5, 15 min and/or 20 h using occlusive conditions. An application site of 2.5 x 2.5 cm was covered with the liquid or powdered and moistened test substance. In addition, skin tissue from the ear was tested by wrapping the ear. These results from the ear, however, would not be taken into account for evaluation as they do not represent testing of the dorsal/lateral flank of the back. After the application time, the skin was washed with water which sometimes contained a mild detergent. The animals were observed 7 to 8 days and skin changes were recorded on working days.

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler
- Age at study initiation: not specified
- Weight at study initiation: 2.94 and 3.51 kg

ENVIRONMENTAL CONDITIONS
not specified

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

water

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount applied: not specified
- Concentration: 50% aqueous preparation (solid paste)

VEHICLE
water

Duration of treatment / exposure:

20 h

Observation period:

8 days

Number of animals:

2

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Site: at the back of the test animal, not further specified
- Application: on intact skin

REMOVAL OF TEST SUBSTANCE
- Washing: yes, with water
- Time after start of exposure: 20 h

OBSERVATION TIME POINTS
24 h, 48 h, 72 h, 6 days, 8 days

SCORING SYSTEM:
- Method of calculation: Draize Test

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Remarks:

only purple substance residues were observed

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No irritation or corrosion was determined.

Other effects:

Purple-coloured staining of the skin and substance residues.

Interpretation of results:

GHS criteria not met

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler
- Age at study initiation: not specified
- Weight at study initiation: mean 2.92 kg
- Diet: Ssniff

ENVIRONMENTAL CONDITIONS
not specified

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount applied: not specified
- Concentration: 50% aqueous preparation (solid paste)

VEHICLE
water

Duration of treatment / exposure:

ca. 24 h

Observation period:

8 days

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Site: Front, middle or at the back of the test animal, not further specified
- Application: on intact and on scarified skin, scarification only on the left side

REMOVAL OF TEST SUBSTANCE
- Washing: yes, with water
- Time after start of exposure: ca. 24 h

OBSERVATION TIME POINTS
24, 48, 72h, 8 days

SCORING SYSTEM:
- Method of calculation: Draize Test

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Max. score:

4

Remarks on result:

not determinable

Remarks:

on intact skin: Purple-coloured staining was noted, exact calculation of the score was not possible

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Max. score:

4

Reversibility:

other: After 8 days, scarified: low to high scurfs or lentil-sized necrosis

Remarks on result:

not determinable

Remarks:

on scarified skin: Purple-coloured staining was noted, exact calculation of the score was not possible

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: on intact skin

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.9

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: on scarified skin

Irritant / corrosive response data:

For erythema, no score could be calculated due to purple-coloured staining of the skin.
An irritant response was only observed on scarified skin: On scarified skin, after 8 days lentil-sized necrosis could be detected in 4 animals, as well as low to high scurfs in 2 animals. Edema were only detected on scarified skin with a maxiumum value of 1. After 8 days a tendency towards reversibility was observed.

Interpretation of results:

GHS criteria not met

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:

1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

old scoring system

Principles of method if other than guideline:

The study is disregarded due to the old and non-standard scoring system.

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: approximately twelve to sixteen weeks
- Weight at study initiation: 2.54 - 2.84 kg
- Housing: individually housed in suspended metal cages
- Diet: ad libitum, (RABMA Rabbit Diet, Special Diet Services Ltd., Witham, Essex, U.K.)
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 - 24°C
- Humidity: 56 - 75%
- Air changes: approximately 15 changes per hour
- Photoperiod: 12 hours light and 12 hours darkness

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL (approximately 88 mg)

Duration of treatment / exposure:

21 days

Observation period (in vivo):

21 days (oservations at 1 hour, 24, 48 and 72 hours; additional observations were made on days four, seven, fourteen and twenty-one to assess the reversibility of the ocular effects).

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: Draize J.H. 1959, Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics"

TOOL USED TO ASSESS SCORE: ophthalmoscope

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

not reversible

Remarks:

within 21 days

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2.1

Max. score:

3

Reversibility:

not reversible

Remarks:

within 21 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritant / corrosive response data:

Areas of diffuse corneal opacity were noted in all treated eyes at the 24-hour observation with areas of diffuse to translucent corneal opacity at the 48 and 72-hour observations. Areas of translucent corneal opacity were noted in one treated eye at the 4-day observation. Opalescent corneal opacity over approximately 25% of the area with diffuse to translucent corneal opacity in the remaining area was noted in one treated eye at the 7-day observation. Areas of translucent corneal opacity were noted in one treated eye at the 7-day observation, in two treated eyes at the 14-day observation with diffuse to translucent corneal opacity at the 21-day observation. Vascularisation of the cornea was noted in two treated eyes at the 7, 14 and 21-day observations. The shape of the eyebal1 was distorted in two animals at the 14-day observation and persisted in one animal at the 21-day observation.
Iridial inflammation was noted in all treated eyes one hour after treatment and at the 24, 48 and 72-hour observations. Iridial inflammation was noted in one treated eye at the 4-day observation. Iridial inflammation was noted in two treated eyes at the 7 and 14-day observations.
Moderate conjunctival irritation was noted in all treated eyes one hour after treatment and at the 24 and 48-hour observations with moderate to severe conjunctival irritation at the 72-hour observation. Moderate conjunctival irritation was noted in one treated eye at the 4-day observation. Moderate conjunctival irritation was noted in two treated eyes at the 7 and 14-day observations with minimal to moderate conjunctival irritation at the 21-day observation. Sloughing of the conjunctival membranes was noted in one treated eye at the 4-day observation. Ectropion was noted in one treated eye at the 7-day observation and in two treated eyes at the 14 and 21-day observations.

Other effects:

- Other observations: Residual test material was noted around the treated eye of all animals throughout the study. Purple-coloured staining was noted in all treated eyes during the study. The staining did not affect evaluation of ocular effects.
Due to sloughing of the conjunctival membranes, one animal was killed for humane reasons immediately after the 4-day observation in accordance with current U.K. Home Office guidelines.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

SKIN IRRITATION/CORROSION:

WOE: Skin irritation in vivo (Sun Chemical, 2006)

The potential of an aqueous preparation of Pigment Violet 3 PTM (21% PV3 PTM, 76.6% water, 2.4% additives) to cause acute dermal irritation or corrosivity was assessed by a single topical application of an amount of 0.5 mL of the test item for 4 hours to the intact skin of three New Zealand White rabbits (stepwise procedure starting with one animal and supplementing two additional animals), using a patch of 2 cm x 3 cm, covered with semi-occlusive dressing. After removal of the patch the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch and approximately 1, 24, 48 and 72 hours after removal of the patch. There was no evidence of a corrosive or irritation effect on the skin, erythema and edema score 0.

 

WOE: Skin irritation in vivo (BASF, 1980)

The primary skin irritation potential of the read-across substance Similar Substance 01 was investigated by topical application to 2.5 cm x 2.5 cm intact or scarified skin of each of six young adult Vienna White rabbits. The duration of treatment was ca. 24 h, the test site on the front, middle or at the back. The scoring of skin reactions was performed 24, 48, 72 hours and 8 days after removal of the dressing. Local signs consisted of grade 0 edema for intact skin and grade 0 – 1 edema for scarified skin. After 8 days no improvement of effects on scarified skin was detected. For erythema no score could be calculated due to purple-colored staining of the skin. But with scarified skin, after 8 days necrosis could be detected in 4 animals, as well as low to high scurfs in 2 animals. in conlusion, signs of skin irritation were only observed on scarified rabbit skin. Based on these results, the test article is considered to be not irritating to rabbit skin.

 

WOE: Skin irritation in vivo (BASF, 1975)

The primary skin irritation potential of the read-across substance Similar Substance 02 was investigated by topical application to 2.5 cm x 2.5 cm intact skin of each of two young adult Vienna White rabbits. The duration of treatment was 20 h, the test site on the back of the test animal. The scoring of skin reactions was performed 24, 48, 72 hours and 8 days after removal of the dressing.

No local signs of irritation were observed. Purple-coloured staining of the skin and substance residues was noted. Based on these results, the test article is considered to be not irritating to rabbit skin.

 

EYE IRRITATION:

KEY: Eye irritation in vivo (Ferro, 1993)

The potential of Pigment Violet 3 PTM to cause damage to the conjunctiva, iris or cornea was assessed by a single ocular administration of 0.1 mL bulk volume (about 88 mg) of the undiluted substance to one eye each of three New Zealand White rabbits. The eye was not rinsed. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after administration and in weekly intervals until day 21. The following test item-related clinical observations were recorded during the course of the study in the three animals:Areas of diffuse corneal opacity were noted in all treated eyes at the 24-hour observation with areas of diffuse to translucent corneal opacity at the 48 and 72-hour observations. Areas of translucent corneal opacity were noted in one treated eye at the 4-day observation. Opalescent corneal opacity over approximately 25% of the area with diffuse to translucent corneal opacity in the remaining area was noted in one treated eye at the 7-day observation. Areas of translucent corneal opacity were noted in one treated eye at the 7-day observation, in two treated eyes at the 14-day observation with diffuse to translucent corneal opacity at the 21-day observation. Vascularisation of the cornea was noted in two treated eyes at the 7, 14 and 21-day observations. The shape of the eyeball was distorted in two animals at the 14-day observation and persisted in one animal at the 21-day observation.Iridial inflammation was noted in all treated eyes one hour after treatment and at the 24, 48 and 72-hour observations. Iridial inflammation was noted in one treated eye at the 4-day observation. Iridial inflammation was noted in two treated eyes at the 7 and 14-day observations.Moderate conjunctival irritation was noted in all treated eyes one hour after treatment and at the 24 and 48-hour observations with moderate to severe conjunctival irritation at the 72-hour observation. Moderate conjunctival irritation was noted in one treated eye at the 4-day observation. Moderate conjunctival irritation was noted in two treated eyes at the 7 and 14-day observations with minimal to moderate conjunctival irritation at the 21-day observation. Sloughing of the conjunctival membranes was noted in one treated eye at the 4-day observation. Ectropion was noted in one treated eye at the 7-day observation and in two treated eyes at the 14 and 21-day observations.Scores calculated for the animals after 72 hours were 20 - 30 for corneal opacity (not reversible), 5 for iris lesions (not fully reversible) and 12 - 16 for conjunctiva (not reversible). Considering the irreversibility of the described ocular reactions the test item causes serious eye damage under the test conditions chosen.  

SUPPORTING: Eye irritation in vivo (BASF, 1980)

In a Draize test in rabbits, 30 mg of the read-across substance Similar Substance 01 was applied into the conjunctival sac of one eye each of 6 Vienna White rabbits followed by a 8-day observation period. Signs of ocular irritation were scored according to the Draize scheme 1, 24, 48, 72 hours and 8 days after administration of the test substance. Corneal opacity, iritis, reddening of conjunctivae and chemosis were observed. The pathological findings on the eye and the irritation symptoms on the mucous membrane did not reverse within 8 days. In conclusion, the test item caused serious eye damage under the test conditions chosen.  

 

SUPPORTING: Eye irritation in vivo (BASF, 1975)

In a Draize test in rabbits, 50 mg of the read-across substance Similar Substance 02 was applied into the conjunctival sac of the right eye each of two Vienna White rabbits followed by a 8-day observation period. As control, talcum was applied to the left eyes of the same animals. The test material caused severe and non-reversible inflammation and scarring on the mucous membrane of the eye. In conclusion, the test material caused serious eye damage under the conditions of this study.

 

Eye irritation in vivo (Sun Chemical, 2006)

The potential of an aqueous preparation of Pigment Violet 3 PTM (21% PV3 PTM, 76.6% water, 2.4% additives) to cause damage to the conjunctiva, iris or cornea was assessed by a single ocular administration of 0.1 mL bulk volume of the undiluted test substance to one eye of three New Zealand White rabbits. The eye was not rinsed. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after administration. The following test item-related clinical observations were recorded during the course of the study in the three animals:

Irritation of the conjunctivae, which consisted of redness and discharge. The irritation had completely resolved within 24 hours. No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage. There was no evidence of ocular corrosion.

Purple staining of the fur on the head and paws, caused by the test substance, was noted during the observation period. No test substance remnants were noted. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

In conclusion, the test material was not irritating to the eye. However, as an aqueous preparation of PV3 PTM was tested, the result of this study was not taken into account for the assessment of the eye irritation potential of PV3 PTM in its pure form.

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.

An aqueous preparation of the registered substance did not show a skin irritating potential in vivo. Furthermore, two analogous substances were not irritationg to the skin in vivo. In conclusion, there is sufficient weight of evidence to conclude that the substance does not have to be classified as skin irritant or corrosive under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.

The substance caused serious eye damage in vivo. As a result, the substance is classified with Eye Dam. 1; H318 under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.