Methyl 1-methyl-4-[(methylphenylhydrazono)methyl]pyridinium sulphate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Initiated 11Sep2001; Reported 19Oct2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

not specified

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl 1-methyl-4-[(methylphenylhydrazono)methyl]pyridinium sulphate

EC Number:

269-503-2

EC Name:

Methyl 1-methyl-4-[(methylphenylhydrazono)methyl]pyridinium sulphate

Cas Number:

68259-00-7

Molecular formula:

C14H16N3.CH3O4S

IUPAC Name:

methyl 1-methyl-4-[(methylphenylhydrazono)methyl]pyridinium sulphate

Test material form:

solid: particulate/powder

Details on test material:

See study reports for batch and purity information

Specific details on test material used for the study:

The test article, MIP 2982, Lot Number 028400A8AA (Vibracolor Yellow) (identified at receipt as MIP Yellow 2982, Batch Number 028400A8AA, Expiration Date: September 2006), was received fix)m the Sponsor on September 10,2001. The test article was received and stored under ambient conditions. Upon receipt, the test article was described as yellowish-orange powder with chunks.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Test Animals
Naive, young-adult, albino Hra:(NZW)SPF rabbits were received on September 06, 2001 from Covance Research Products, Inc., a USDA-approved supplier located in Denver, Pennsylvania.

Housing
The animals were housed individually in stainless steel, screen-bottomed cages, measuring 60.7 cm X 60.3 cm x 40.7 cm (DxWxH).

Diet
The animals were presented with a measured amount of PMI* Feeds Certified Rabbit High Fiber Diet #5325 daily. Each lot of feed was analyzed by the manufacturer for concentrations of specified heavy metals, aflatoxin, chlorinated hydrocarbons, organophosphates, and specified nutrients.

Water
Water was available ad libitum throughout the acclimation and study periods. Samples of the water were analyzed by a certified laboratory approximately every 6 months for specified microorganisms and environmental contaminants.

Nutrient and Contaminant Analyses
Specified nutrient and contaminant analyses are on file at Covance - Vienna. There were no contaminants, known or reasonably anticipated, in the diet or water at levels that might interfere with the validity of this study.

Environment
Controls in the animal room were set to maintain temperatures and relative humidity of 16-22°C (61-72°F) and 50±20%, respectively, a 12-hour light/12-hour dark cycle (lights on approximately 0600 to 1800 hours), and 10 or greater air changes per hour.

Acclimation
Before being considered for study use, the animals were acclimated to laboratory conditions. After at least 5 days of acclimation, a staff veterinarian deemed them to be healthy and free from disease and physical abnormalities, and then released the animals for use in the study.

Environmental Enrichment
The animals were given plastic balls as a form of environmental enrichment.

Selection of Animals
Only healthy animals, free from skin defects or alterations in coloration or texture, were used in this study. Three rabbits (two males and one female), approximately 14 weeks old and weighing from 2328 to 2694 g, were randomly selected from the animals available for this study. Each animal was assigned a unique animal number and affixed with an ear tag marked with the corresponding animal number; the corresponding number was also affixed to the cage housing the animal.

Justification of Species Selection
Historically, the New Zealand White albino rabbit has been the animal of choice for evaluating the effects of chemicals on the skin. This species is designated by federal regulations and has a large historical database for dermal irritation assays.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

0.5 mL distilled water

Amount / concentration applied:

Approximately 0.5 g of test material in a paste with 0.5mL distilled water

Duration of treatment / exposure:

4-hour exposure period

Observation period:

Dermal irritation was evaluated at approximately 0.5 to 1, 24,48, and 72 hours after patch removal.

Number of animals:

Two males and one female

Details on study design:

Dose Administration
On the day of dosing, the test material was finely ground with a mortar and pestle and pasted with approximately 0.5 mL distilled water (Crystal Springs, Lot No. BTLD:03/20/01 LANP Exp:03/20/03) prior to application. A total of 0.5 g of the test article was applied to one intact test area (approximately 6.25 cm^) of each animal. To provide a semi-occlusive dressing, each area of exposure was covered with a gauze patch secured with paper tape, loosely overwrapped with Saran Wrap , and secured with Elastoplast tape. The animals were uncollared during the 4-hour exposure period. The dressing for each animal remained intact during the 4-hour exposure period. The adjacent, untreated skin sites of each animal served as the control.

Removal of Test Article
After a 4-hour exposure period, the dressings were removed. The residual test article was removed by spraying the treated area with tap water and soap and gently wiping with soft paper towels.

Body Weights
The animals were weighed prior to test article application.

Health and Mortality
The animals were observed twice daily (at least 4 hours apart) for general health and mortality for the duration of the study.

Reading of Dermal Irritation
Approximately 0.5 to 1,24,48, and 72 hours after patch removal, the exposure site was examined for the degree of erythema (redness) and edema (swelling). The adjacent, untreated clipped area on each animal's back was used for control. The test sites were scored according to the primary dermal irritation scoring scale (see report for details).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no irritation observed

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Other effects:

Animals did not exhibit gross evidence of treatment-related toxicity during the course of the study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

No findings of erythema or edema were noted in any animal at any observation period. The Primary Dermal Irritation Index (PDII) was calculated to be 0.0. No evidence of corrosion was observed. The test article is considered to be non-irritating to the skin of the rabbit under the conditions of this study.

Executive summary:

The acute dermal irritation of the test article on rabbits under semi-occluded conditions was evaluated in general compliance with the conditions specified in the US EPA Health Effects Testing Guidelines OPPTS 870.2500 Acute Dermal Irritation (dated August 1998) and the OECD Guidelines for Testing of Chemicals, Section 4, Health Effect, No 404.

 

On the day of dosing, approximately 0.5 g of the test article was applied to one intact test area (approximately 6.25 cm2) on each back of three New Zealand White rabbits (two males and one female) for a 4-hour exposure period. Dermal irritation was evaluated at approximately 0.5 to 1, 24,48, and 72 hours after patch removal.

 

Animals did not exhibit gross evidence of treatment-related toxicity during the course of the study.

 

No findings of erythema or edema were noted in any animal at any observation period. The Primary Dermal Irritation Index (PDII) was calculated to be 0.0. No evidence of corrosion was observed. The test article is considered to be non-irritating to the skin of the rabbit under the conditions of this study.