4-[(3,5-Dichlorobenzoyl)amino]-3-hydroxybenzoic acid

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 2014 - April 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: US EPA, OPPTS 870.2500 (1998), Acute Dermal Irritation

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

4-(3,5-dichlorobenzamido)-3-hydroxybenzoic acid

EC Number:

832-365-4

Cas Number:

1184581-58-5

Molecular formula:

C14H9Cl2NO4

IUPAC Name:

4-(3,5-dichlorobenzamido)-3-hydroxybenzoic acid

Test material form:

solid: particulate/powder

Details on test material:

Batch E010014831, re-test date: 30 June 2015

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

3 Males. Animals were between 12 and 24 weeks old and body weights were at least 1.5kg. Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, at least 10 air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study. Animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm). Acclimatization period was at least 5 days before start of treatment under laboratory conditions. Pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy)
approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands) were available
during the study period

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Each animal was treated by dermal application of 0.5 grams of the test substance. The test substance was moistened with 1 mL of the vehicle and applied to the skin of one flank, using a metalline patch# of 2x3 cm. The patch was mounted on Micropore tape#, which was wrapped around the abdomen and secured with Coban elastic bandage

Duration of treatment / exposure:

Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.

Observation period:

Mortality/Viability - Twice daily.
Toxicity - At least once daily.
Body Weight - Day of treatment (prior to application) and after the final observation.
Necropsy - No necropsy was performed according to protocol.
Irritation - The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.

Number of animals:

3

Details on study design:

The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner three weeks later, after
considering the degree of skin irritation observed in the first animal.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on these results PF-06410251 does not have to be classified and has no obligatory
labelling requirement for skin irritation according to the:- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) (including all amendments),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).

Executive summary:

Primary skin irritation/corrosion study withPF-06410251 in the rabbit (4-hoursemi-occlusive application). The study was carried out based on the guidelines described in: OECD No.404, "Acute Dermal Irritation/Corrosion" (2002) EC, No 440/2008; B4: "Acute Toxicity: Dermal Irritation/Corrosion" US EPA, OPPTS 870.2500 (1998), Acute Dermal Irritation FAMIC Guidelines (2011), including the most recent revisions. Three rabbits were exposed to 0.5 grams ofPF-06410251, moistened with water by application onto clipped skin for 4 hours using asemi-occlusivedressing. Skin reactions were assessed 1, 24, 48 and 72 hours after exposure. No skin irritation was caused by 4 hours exposure to PF-06410251. Based on these results PF-06410251 does not have to be classified and has no obligatory labelling requirement for skin irritation according to the: - Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) (including all amendments), - Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).