p-phenylenebis(methylamine)

Endpoint summary

Description of key information

Skin irritation/corrosion:

Two studies are available.

One study was conducted according to OECD 404, exposure for 4 hours and the test substance is corrosive to rabbit skin. This is assigned as key study.

Another study was performed with 3 mins and 1 hour, the test item is moderately irritating to rabbit skin.

Eye irritation:

Study waived as corrosive to skin.

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:

From 2000-02-22 to 2000-03-23

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:

1981

Deviations:

no

GLP compliance:

not specified

Specific details on test material used for the study:

Batch No.: Lot. 4
Purity: 99.9%

Species:

rabbit

Strain:

other: Japanese white rabbits KbL:JW (SPF)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kitayama Labes Co., Ltd
- Age at study initiation: 10-week
- Weight at study initiation: 2.2-2.5 kg
- Housing: Animals were housed in an animal room. Animals were placed in suspension-type metallic cages, one per cage, on a z-type water washing rabbit rack.
- Diet: Animals were given free access to pellet food RC-4
- Water: Animals were given free access to water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 6
- Photoperiod (hrs dark / hrs light):12-hour light/12-hour dark

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 g of test chemical moistened with 30 μL of distilled water was applied to rabbit skin.

Duration of treatment / exposure:

4 hours

Observation period:

24, 48 and 72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6 cm2
- Type of wrap: The area was covered with 2-layer gauze, to complete a closed patch.

REMOVAL OF TEST SUBSTANCE
- Washing : Treated areas were cleaned with gauze moistened with water.

OBSERVATION TIME POINTS: Treated areas were observed 30-60 minutes after removing the test chemical and 24, 48 and 72 hours after completing exposure.

SCORING SYSTEM:
- Method of calculation: Erythema and edema observed in 3 rabbits were scored 30-60 minutes and 24 and 72 hours after removing the test chemical and means of scores obtained in 3 rabbits were calculated. Sums of mean scores obtained 30-60 minutes and 24 and 72 hours after removing the test chemical were divided by 3, i.e., the number of evaluation time points (30-60 minutes and 24 and 72 hours), to obtain primary irritation indices (P.I.I.) as a parameter of the severity of irritation. Severity of primary dermal irritation was rated based on the P.I.I. value. This grading method will not be used, however, if the test chemical is evaluated as corrosive.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Reversibility:

not reversible

Remarks on result:

other: impossible to grade at 24, 46 and 72h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Reversibility:

not reversible

Remarks on result:

other: impossible to grade at 24, 46 and 72h

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Reversibility:

not reversible

Remarks on result:

other: impossible to grade at 24, 46 and 72h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not reversible

Remarks on result:

other: impossible to grade at 72h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not reversible

Remarks on result:

other: impossible to grade at 46h and 72h

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not reversible

Remarks on result:

other: impossible to grade at 46h and 72h

Irritant / corrosive response data:

Treated skin areas turned grey-white in color and necrotic, showing slight edema, in all 3 animals 30-60 minutes after 4-hour exposure, and hemorrhage was noted on the edge of treated area. Necrotic areas turned brownish-red and became dry and hard 24 hours after completion of exposure. Eschar formation was observed in these areas 6 days after completion of exposure. Eschar exfoliated in one rabbit 22 days after completion of exposure, leaving ulcerative skin in the exfoliated area with subcutaneous tissue visible in skin defect areas. Another rabbit also showed eschar exfoliation with ulcers in exfoliated areas. The third rabbit did not show eschar exfoliation. All 3 rabbits were observed for 30 days after completion of exposure, but heal with scar formation did not occur in any of them.

Dermal reactions caused by test item in rabbits

Number of rabbits (weight)

5 (2.2 Kg)

6 (2.4 Kg)

7 (2.5 Kg)

Dermal reactions

Er

Ed

Ne

Es

Sc

Er

Ed

Ne

Es

Sc

Er

Ed

Ne

Es

Sc

Time after completion of exposure

30-60 min

/

2

4

0

0

/

2

4

0

0

/

2

4

0

0

24 h

/

1

4

0

0

/

1

4

0

0

/

1

4

0

0

46 h

/

1

4

0

0

/

/

4

0

0

/

/

4

0

0

72 h

/

/

4

0

0

/

/

4

0

0

/

/

4

0

0

6 d

/

/

/

4

0

/

/

/

4

0

/

/

/

4

0

7 d

/

/

/

4

0

/

/

/

4

0

/

/

/

4

0

15 d

/

/

/

4

0

/

/

/

4

0

/

/

/

4

0

22 d

/

/

/

4

0

/

/

/

/

0*

/

/

/

4

0

28 d

/

/

/

4

0

/

/

/

/

0*

/

/

/

/

0*

30 d

/

/

/

4

0

/

/

/

/

0*

/

/

/

/

0*

*: ulcer

/: impossible to grade  

Er: erythema

Ed: edema

Ne: necrosis

Es: eschar

Sc: scar

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

The test chemical was considered to be a corrosive substance.

Executive summary:

A primary dermal irritation study of test item was conducted in accordance with OECD Test Guideline No. 404 (1981).

The test item was locally applied to the back skin (round area of about 6 cm2) of Japanese white rabbits for 4 hours, and the skin was observed with the naked eye over time after completion of exposure.

Treated skin areas of all 3 rabbits turned grey-white and became necrotic showing slight edema 30-60 minutes after exposure for 4 hours. Hemorrhage was noted on the edge of treated area. Necrotic areas turned brownish-red and became dry and hard 24 hours after completion of exposure. Crust formation was observed in these areas 6 days after completion of exposure. Crusts exfoliated in one rabbit 22 days after completion of exposure, leaving ulcerative skin with subcutaneous tissue visible in skin defect areas. Another rabbit also showed crust exfoliation with ulcers in exfoliated areas. The third rabbit did not show crust exfoliation. All 3 rabbits were observed for 30 days after completion of exposure, but heal with scar formation did not occur in any of them.

On the basis of these findings, the test item was considered to be a corrosive substance.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study need not be conducted because the available information indicates that the criteria are met for classification as corrosive to the skin or irritating to eyes

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin irritation/corrosion:

Exposure for 4 hours, corrosive showed in all 3 animals in 24 hours. Exposure for 1 hour and 3 mins did not result corrosive.

According to Regulation (EC) No 1272/2008, table 3.2.1, this substance is classified as Skin corrosive Category 1B.

Serious eye damage/eye irritation:

This substance is skin corrosive.

According to Regulation (EC) No 1272/2008, section 3.3.2.3, Skin corrosive substances shall be considered as leading to serious damage to the eyes as well (Category 1). Hence this substance is classified as Irreversible effects on the eye (Category 1).