p-anisylamine

Endpoint summary

Description of key information

Skin irritation:

4-Methoxybenzylamine caused erythema, edema, necrosis, and subsequent eschar formation at the site of application. The eschars persisted throughout the 14-day observation period.

Since the effects were persistent throughout the observation period, 4-Methoxybenzylamine was considered to be corrosive to skin.

Eye Irritation:

4-Methoxybenzylamine caused strong edema, erythema, necrosis of the adnexal structures, corneal opacity, and discharge within one hour in both washed and unwashed eyes. The irises could not be evaluated due to the presence of extensive corneal opacity. The animals were euthanatized for humane reasons at the one-hour observation point.

Since the animals were killed before the end of observation period due to severity of the effects, 4-Methoxybenzylamine can be considered to be corrosive to rabbit eyes.

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:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

data is from NTRL reports

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

To determine the dermal irritation potential of 4-Methoxybenzylamine in guinea pigs

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 4-Methoxybenzylamine
- IUPAC name: p-anisylamine
- Molecular formula: C8H11NO
- Molecular weight: 137.181 g/mole
- Smiles :O(c1ccc(cc1)CN)C
- Inchl: 1S/C8H11NO/c1-10-8-4-2-7(6-9)3-5-8/h2-5H,6,9H2,1H3
- Substance type: Organic
- Physical state: Liquid (Colorless to pale yellow)

Species:

guinea pig

Strain:

Hartley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: range: 358 - 416 g

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

5

Details on study design:

Test substance was applied for 24 hour to the skin of guinea pigs under occlusive conditions. The effects on skin were observed for 14 days.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

14 d

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

The test article was a strong skin irritant. It caused erythema, edema, necrosis, and subsequent eschar formation at the site of application. The eschars persisted throughout the 14-day observation period.

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

4-Methoxybenzylamine caused erythema, edema, necrosis, and subsequent eschar formation at the site of application. The eschars persisted throughout the 14-day observation period.
Since the effects were persistent throughout the observation period, 4-Methoxybenzylamine was considered to be corrosive to skin.

Executive summary:

The dermal irritation potential of 4-Methoxybenzylamine was assessed in guinea pigs.

4-Methoxybenzylamine was applied for 24 hour to the skin of 5 Hartley guinea pigs under occlusive conditions. The effects on skin were observed for 14 days.

4-Methoxybenzylamine caused erythema, edema, necrosis, and subsequent eschar formation at the site of application. The eschars persisted throughout the 14-day observation period.

Since the effects were persistent throughout the observation period, 4-Methoxybenzylamine was considered to be corrosive to skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

data is from NTRL reports

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

To assess the ocular irritation potential of 4-Methoxybenzylamine in rabbits

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 4-Methoxybenzylamine
- IUPAC name: p-anisylamine
- Molecular formula: C8H11NO
- Molecular weight: 137.181 g/mole
- Smiles :O(c1ccc(cc1)CN)C
- Inchl: 1S/C8H11NO/c1-10-8-4-2-7(6-9)3-5-8/h2-5H,6,9H2,1H3
- Substance type: Organic
- Physical state: Liquid (Colorless to pale yellow)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

single treatment

Observation period (in vivo):

14 days

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): 3 animals eyes were washed with distilled water and for 3 animals eyes were not washed out
- Time after start of exposure: no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

14 d

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

It caused strong edema, erythema, necrosis of the adnexal structures, corneal opacity, and discharge within one hour in both washed and unwashed eyes. The irides could not be evaluated due to the presence of extensive corneal opacity. The animals were euthanatized for humane reasons at the one-hour observation point.

Interpretation of results:

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

Conclusions:

4-Methoxybenzylamine caused strong edema, erythema, necrosis of the adnexal structures, corneal opacity, and discharge within one hour in both washed and unwashed eyes. The irises could not be evaluated due to the presence of extensive corneal opacity. The animals were euthanatized for humane reasons at the one-hour observation point.
Since the animals were killed before the end of observation period due to severity of the effects, 4-Methoxybenzylamine can be considered to be corrosive to rabbit eyes.

Executive summary:

The ocular irritation potential of 4-Methoxybenzylamine was assessed in rabbits. 0.1 ml of undiluted test chemical was instilled in to the eyes of 6 New Zealand White rabbits. 3 animals eyes were washed with distilled water and for 3 animals eyes were not washed out(duration not specified). The rabbits were observed for signs of irritation till 14 days.

4-Methoxybenzylamine caused strong edema, erythema, necrosis of the adnexal structures, corneal opacity, and discharge within one hour in both washed and unwashed eyes. The irises could not be evaluated due to the presence of extensive corneal opacity. The animals were euthanatized for humane reasons at the one-hour observation point.

Since the animals were killed before the end of observation period due to severity of the effects, 4-Methoxybenzylamine can be considered to be corrosive to rabbit eyes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

Various studies have been investigated for assessing the dermal irritation potential of 4-Methoxybenzylamine to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs, rabbits for target chemical and its structurally similar read across chemicals.

The dermal irritation potential of 4-Methoxybenzylamine was assessed in guinea pigs.

4-Methoxybenzylamine was applied for 24 hour to the skin of 5 Hartley guinea pigs under occlusive conditions. The effects on skin were observed for 14 days.

4-Methoxybenzylamine caused erythema, edema, necrosis, and subsequent eschar formation at the site of application. The eschars persisted throughout the 14-day observation period.

Since the effects were persistent throughout the observation period, 4-Methoxybenzylamine was considered to be corrosive to skin.

A study was conducted as per Consumer Product Safety Commission of the USA (Code of Federal Regulations, Title 16, Sec. 1500.41). to determine the degree of dermal irritation caused by the structurally similar read across chemical. 2.5% (w/v) Suspension of the test chemical in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3was applied to the intact and abraded skin of 3 New Zealand White albino rabbits. The rabbits were observed for signs of irritation till 72 hours and the reactions were scored based on the definition of skin irritation given in the  (Code of Federal Regulations, Title 16, Sec.1500.41).

The Primary Irritation Index was 0.3.

The test chemical was considered to be mildly irritating to rabbit skin.

The above studies are further supported by the experimental study performed to assess the irritation potential of other structurally similar read across chemical. A total of 6 albino rabbits, undifferentiated as to sex and ranging in weight from 2890 to 4050 grams were used for this study. The animals were divided into 2 groups of 3 animals each. The dorsal skin of each rabbit was prepared for treatment by close clipping of the hair with an electric clipper. In addition, the skin of the rabbits in 1-of-the-2 groups was abraded by producing shallow incisions 3 -4 cm. apart with a 5calpel blade. The remaining group remained intact. Undiluted 0.5 ml of the test chemical was applied toon the back of each rabbit.The material was applied to the back and the area; then covered withrubber damming and surgical gauze and overwrapped with elastic bandages to prevent evaporation.The rabbits were confined in holders designed to immobilize the animal for a total of 24 hours to permit percutaneous absorption and prevent oral ingestion of the compound. The rabbits were then placed in individual metal cages suspended above the droppings with food and water available, ad libitum. At the end of the 24-hour period of confinement in the holder, the bandages were removed and the back of each rabbit vas washed with lukewarm water and the area of compound application examined for evidence of irritation.

The rabbits were scored for erythema and edema according to scale of Draize.

The test chemical when applied to the intact and abraded skin of the albino rabbits caused death in all 6 animals tested within 18 hour following application. Three animals succumbed within 2 hours, 2 rabbits within 4 hours, and the remaining animal within 18 hours following derma1 application. Signs noted prior to death tnc1uded dyspnea, tremors, salivation, nasal discharge, rales and slight convulsions. Due to the mortality observed with the test chemical, a primary irritation score was not obtainable.

Based on these observations, the test chemical was considered to be corrosive to rabbit skin.

Based on the available data for the target as well as read across chemicals and applying the weight of evidence approach, 4-Methoxybenzylamine was corrosive to skin. Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Category 1”.

Eye Irritation:

Various studies have been investigated for assessing the ocular irritation potential of 4-Methoxybenzylamine to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical and its structurally similar read across chemicals.

The ocular irritation potential of 4-Methoxybenzylamine was assessed in rabbits. 0.1 ml of undiluted test chemical was instilled in to the eyes of 6 New Zealand White rabbits. 3 animals eyes were washed with distilled water and for 3 animals eyes were not washed out(duration not specified). The rabbits were observed for signs of irritation till 14 days.

4-Methoxybenzylamine caused strong edema, erythema, necrosis of the adnexal structures, corneal opacity, and discharge within one hour in both washed and unwashed eyes. The irises could not be evaluated due to the presence of extensive corneal opacity. The animals were euthanatized for humane reasons at the one-hour observation point.

Since the animals were killed before the end of observation period due to severity of the effects, 4-Methoxybenzylamine can be considered to be corrosive to rabbit eyes.

This is supported by the ocular irritation study performed on rabbits to determine the degree of irritation caused by the structurally similar read across chemical. The test chemical was applied to rabbit eyes and after 24 hours of dosing effects was observed.

The test chemical after 24 hours of exposure was irritating to the rabbit eye without irreversible effects.

These results are further supported by another study for the structurally similar read across chemical. The study was performed according to the Draize method. The test was conducted on New Zealand White rabbits.

Test was first performed on one rabbit with 0.1gm of test substance, the treated eye showed moderate irritation, Thereafter 8 additional animals were tested and subjected to rinsing with normal saline after 30 seconds of administration .Ocular lesions were scored approx 1 hr, 1 day upto 21 days. Even 21 days after treatment, un-rinsed eyes in 5/6 treated animals displayed corneaI opacity, iritis and conjunctival irritation. The maximum mean irritation score was 71.2 (of 110 possible maximum) which occurred on day 3, the rinsed eyes showed milder effects; however, serious adverse effects persisted to day 21.

The test chemical was considered to be a very severe irritant to the eye of New Zealand White rabbits under the conditions of these studies causing effects which were not reversed within 21 days of treatment. Immediate washing of the eyes resulted in reduced irritation and more rapid recovery.

Based on the available data for the target as well as read across chemicals and applying the weight of evidence approach, 4-Methoxybenzylamine was corrosive to eyes. Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Category 1”.

Justification for classification or non-classification

Available data for 4-Methoxybenzylamine indicate that it is corrosive to eyes and skin.

Hence, 4-Methoxybenzylamine can be classified under the category “Category 1” for skin and eye irritation as per CLP regulation.