p-anisylamine

Endpoint summary

Description of key information

Skin Sensitization:

5 animals showed slightly greater degree of erythema than control animals. Five of ten animals induced with the test material in Freund's Adjuvant responded to challenge with a slightly greater degree of erythema than seen in animals previously injected with Freund's Adjuvant only.

Based on these observations, 4-Methoxybenzylamine was considered to be sensitizing to guinea pig skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 dermal sensitization potential of 4-Methoxybenzylamine in guinea pigs

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

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

Sex:

female

Details on test animals and environmental conditions:

Weight at study initiation: range: 356 - 461 g

Route:

intradermal and epicutaneous

Vehicle:

not specified

Concentration / amount:

Induction: 1%
Challenge: 1%

Adequacy of induction:

not specified

No.:

#1

Route:

intradermal

Vehicle:

not specified

Concentration / amount:

Induction: 1%
Challenge: 1%

Adequacy of challenge:

not specified

No. of animals per dose:

10

Details on study design:

Negative control used but name not mentioned

Challenge controls:

no data available

Positive control substance(s):

not specified

Positive control results:

no data available

Other effects / acceptance of results:

no data available

Reading:

1st reading

Group:

test chemical

Dose level:

1%

No. with + reactions:

5

Total no. in group:

10

Clinical observations:

5 animals showed slightly greater degree of erythema than control animals.

Remarks on result:

positive indication of skin sensitisation

Reading:

1st reading

Group:

negative control

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no erythema or other dermal reactions were observed

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

other: Sensitizer

Conclusions:

5 animals showed slightly greater degree of erythema than control animals. Five of ten animals induced with the test material in Freund's Adjuvant responded to challenge with a slightly greater degree of erythema than seen in animals previously injected with Freund's Adjuvant only.
Based on these observations, 4-Methoxybenzylamine was considered to be sensitizing to guinea pig skin.

Executive summary:

Guinea pig Maximization assay was performed to determine the degree of dermal sensitization caused by 4-Methoxybenzylamine. 10 female Hartley guinea pigs were used for the study.

During the induction phase,the test chemical in Freund's Adjuvant was injected into the skin of guinea pigs, then 1% of the test material was applied onto the skin.Negative control was also used (name not specified). After few days, the induced guinea pigs were challenged with 1% test chemical and observed for signs of erythema.

5 animals showed slightly greater degree of erythema than control animals. Five of ten animals induced with the test material in Freund's Adjuvant responded to challenge with a slightly greater degree of erythema than seen in animals previously injected with Freund's Adjuvant only.

Based on these observations, 4-Methoxybenzylamine was considered to be sensitizing to guinea pig skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin Sensitization:

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

Guinea pig Maximization assay was performed to determine the degree of dermal sensitization caused by 4-Methoxybenzylamine. 10 female Hartley guinea pigs were used for the study.

During the induction phase, the test chemical in Freund's Adjuvant was injected into the skin of guinea pigs, then 1% of the test material was applied onto the skin. Negative control was also used (name not specified). After few days, the induced guinea pigs were challenged with 1% test chemical and observed for signs of erythema.

5 animals showed slightly greater degree of erythema than control animals. Five of ten animals induced with the test material in Freund's Adjuvant responded to challenge with a slightly greater degree of erythema than seen in animals previously injected with Freund's Adjuvant only.

Based on these observations, 4-Methoxybenzylamine was considered to be sensitizing to guinea pig skin.

This is supported by LLNA assay performed to evaluate the dermal sensitization potential of the structurally similar read across chemical. The study was performed as per OECD 429 Guidelines. Groups of female CBA mice (7-12 weeks of age) were exposed topically on the dorsum of both ears to 25µl of the test material or to an equal volume of relevant vehicle only. Treatment was performed daily for 3 consecutive days.Five days after the initiation of exposure, all mice were injected via the tail vein with 250 µL of phosphate buffered saline (PBS) containing 20 µCi of tritiated thymidine. Mice were sacrificed 5 hours later, and the draining auricular lymph nodes were excised and pooled for each experimental group or each individual animal. The incorporation of tritiated thymidine measured by beta scintillation counting was reported in disintegrations per minute (dpm). A stimulation index (SI) was calculated for each chemical-treated group as the ratio of the dpm of the treated group (or mean dpm when individual animals were assessed) to the dpm or mean dpm of the concurrent vehicle control group.The approach to estimation of the relative skin sensitization potential was based on the mathematical estimation of the concentration of chemical necessary to obtain a threshold positive response (SI = 3); this is termed as the EC3 value.A substance was classified as a skin sensitizer if it induced a threefold or greater increase in local lymph node proliferative activity at one or more test concentrations when compared with concurrent vehicle-treated controls (SI≥3).

The relative potency index of the test chemical was calculated to be 0.05.

Based on the relative potency index, the test chemical was considered to be an extreme sensitizer.

Similar study was performed to evaluate the sensitization potential of other structurally similar read across chemical. The EC3 value of the other structurally similar read across chemical was calculated to be 0.2%.

Based on the EC3 values, the test chemical was considered to be a strong sensitizer.

Based on the available data for the target as well as read across chemicals and applying the weight of evidence approach,4-Methoxybenzylamine was considered to sensitizing to skin.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Available data for 4-Methoxybenzylamine indicate that it is likely to cause dermal sensitization to skin.

4-Methoxybenzylamine can be considered to be sensitizer to skin.