4-methoxyphenylacetic acid

Endpoint summary

Description of key information

Guinea pig maximisation test was used to test the sensitizing capability of 4 methoxyphenyl acetic acid ( 104-01-8) in Hartley male guinea pigs. The shaved skin of twenty Hartley male guinea pigs was treated with the test matarial. (a solid) by intrademal injection (as a 5% solution in propylene glycol as vehicle with and without Freund's adjuvant) and then by topical application (5% in propylene glycol) eight days later. Two weeks after the final induction administration, animals were challenged with the test material as a 75% preparation in petrolatum using a 24-hour dermal exposure. Ten non-induced animak were also challenged and served as control. The site of exposure was examined for erythema and edema 24 and 48 hours following removal of the test material. 'The dose levels for challenge (75% in petrolatum) was based on a topical range-finding study to select the highest non-irritating dose which was also the highest practical dose for this material. At the 24hour examination, 1/20 animals demonstrated a slight response to the challenge dose no animal demonstrated a response at the 48 hour examination. Negative controls showed minimal response with 1/10 animals showing minimal irritation at 24 hours only. Positive control (DNCB) demonstrated a 100% response. 4-Methoxyphenylacetic Acid (MPAA) was found to be a non sensitizing to guinea pig under test condition. Therefore 4-Methoxyphenylacetic Acid (MPAA, CAS no-104 -1 -8) was considered to be a non sensitizing.

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 NTIS study report.

Qualifier:

no guideline available

Principles of method if other than guideline:

Guinea pig maximisation test was used to test the sensitizing capability of 4 methoxyphenyl acetic acid in Hartley male guinea pigs.

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Sufficient for classification .

Specific details on test material used for the study:

- Name of test material (as cited in study report):4-METHOXYPHENYL.ACETIC ACID
- Molecular formula: C9H10O3
- Molecular weight : 166.175 g/mol
- Substance type: Organic
- Physical state: Solid

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

No data available

Route:

intradermal and epicutaneous

Vehicle:

other: intradermal injection - propylene glycol as a vehicle wilh and without Freund's adjuvant Epicutaneous route- propylene glycol

Concentration / amount:

intradcmal injection - 5%
Epicutaneous route- 5%

Day(s)/duration:

Epicutaneous application was performed eight days later of Intradermal induction .

Route:

other: Epicutaneous

Vehicle:

petrolatum

Concentration / amount:

75%

Day(s)/duration:

24 hour

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

20

Details on study design:

RANGE FINDING TESTS: The dose levels for challenge (75% in petrolatum) was based on a topical range -finding study to select the highest non-irritating dose which was also the highest practical dose for this material.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 8 days
- Test groups:1 test group
- Control group:Yes
- Site: Not specified
- Frequency of applications: 2
- Duration:8 days
- Concentrations:
intradcmal injection - 5%
Epicutaneous route- 5%

B. CHALLENGE EXPOSURE
- Day(s) of challenge: 2 week
- Concentrations: 75% preparation in petrolatum
- Exposure period:24 hr
- Evaluation (hr after challenge): 24 and 48 hrs

Challenge controls:

Yes

Positive control substance(s):

yes

Remarks:

DNCB (Dinitrochlorobenzene)

Positive control results:

100% response was observed .

Reading:

other: challenge

Hours after challenge:

24

Group:

negative control

Dose level:

5%

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

Erythema and edema were observed

Remarks on result:

other: No sensitization was observed.

Reading:

other: challenge

Hours after challenge:

48

Group:

positive control

Dose level:

5%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

Erythema and edema were examined

Remarks on result:

other: Sensitization was observed.

Reading:

other:

Hours after challenge:

24

Group:

test chemical

Dose level:

75%

No. with + reactions:

1

Total no. in group:

20

Clinical observations:

Slight sensitization was observed

Remarks on result:

other: Slight sensitization was observed in one animal

Reading:

other: challenge

Hours after challenge:

48

Group:

test chemical

Dose level:

75%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No sensitization was observed.

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

other: Not sensitising

Conclusions:

At the 24hour examination, 1/20 animals demonstrated a slight response to the challenge dose no animal demonstrated a response at the 48 hour examination. Negative controls showed minimal response with 1/10 animals showing minimal irritation at 24 hours only. Positive control (DNCB) demonstrated a 100% response.4-Methoxyphenylacetic Acid (MPAA) was considered to be a non sensitizing to guinea pig under test condition.

Executive summary:

Guinea pig maximisation test was used to test the sensitizing capability of 4 methoxyphenyl acetic acid in Hartley male guinea pigs. The shaved skin of twenty Hartley male guinea pigs was treated with the test matarial. (a solid) by intrademal injection (as a 5% solution in propylene glycol as vehicle with and without Freund's adjuvant) and then by topical application (5% in propylene glycol) eight days later. Two weeks after the final induction administration, animals were challanged with the test material as a 75% preparation in petrolatum using a 24-hour dermal exposure. Ten non-induced animak were also challanged and Served as control. The site of exposure was examined for erythema and edema 24 and 48 hours following removal of the test material. 'The dose levels for challenge (75% in petrolatum) was based on a topical range-finding study to select the highest non-irritating dose which was also the highest practical dose for this material. At the 24hour examination, 1/20 animals demonstrated a slight response to the challenge dose no animal demonstrated a response at the 48 hour examination. Negative controls showed minimal response with 1/10 animals showing minimal irritation at 24 hours only. Positive control (DNCB) demonstrated a 100% response. 4-Methoxyphenylacetic Acid (MPAA) was found to be a non sensitizing to guinea pig under test condition. Therefore 4-Methoxyphenylacetic Acid (MPAA, CAS no-104 -1 -8) was considered to be a non sensitizing .

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitisation

Various studies for target (4-Methoxyphenylacetic acid, CAS No-104-01-8) and its read across were summarized as follows:

Guinea pig maximisation test was used to test the sensitizing capability of 4 methoxyphenyl acetic acid ( 104-01-8) in Hartley male guinea pigs (NTIS study report, 1991).The shaved skin of twenty Hartley male guinea pigs was treated with the test matarial. (a solid) by intrademal injection (as a 5% solution in propylene glycol as vehicle with and without Freund's adjuvant) and then by topical application (5% in propylene glycol) eight days later. Two weeks after the final induction administration, animals were challenged with the test material as a 75% preparation in petrolatum using a 24-hour dermal exposure. Ten non-induced animak were also challenged and served as control. The site of exposure was examined for erythema and edema 24 and 48 hours following removal of the test material. 'The dose levels for challenge (75% in petrolatum) was based on a topical range-finding study to select the highest non-irritating dose which was also the highest practical dose for this material. At the 24hour examination, 1/20 animals demonstrated a slight response to the challenge dose no animal demonstrated a response at the 48 hour examination. Negative controls showed minimal response with 1/10 animals showing minimal irritation at 24 hours only. Positive control (DNCB) demonstrated a 100% response. 4-Methoxyphenylacetic Acid (MPAA) was found to be a non sensitizing to guinea pig under test condition. Therefore 4-Methoxyphenylacetic Acid (MPAA, CAS no-104 -1 -8) was considered to be a non sensitizing.

The skin sensitizing potential for 4-Methoxyphenylacetic acid is estimated using OECD QSAR toolbox version 3.4. The test substance 4-Methoxy phenylacetic acid (MPAA, CAS no-104 -1 -8) is estimated to be not sensitizing in mouse.

Based on the QSAR prediction done using the Danish (Q) SAR Database, the skin sensitization was estimated to be not sensitizing on guinea pig and human for 4-Methoxyphenylacetic acid. Thus it can be concluded that the substance 4-Methoxyphenylacetic acid (104-1-8) has non skin sensitization effects and based on the CLP criteria for classification it can be classified as non sensitizer to skin sensitization effects.

In other study by (Sustainability Support Service (Europe) AB with acess rights from Givaudan UK Ltd., 1978) with similar substance (CAS No: 105-13-5) was assayed in guinea pig. A skin sensitization reaction was observed for 4-methoxybenzyl alcohol (105 -13 -5) in guinea pig at the concentration 60, 30, 10 and 3%. On day 0, 0.1ml of the test material, undiluted and, if possible or necessary of its progressively diluted solutions or emulsions or suspensions is applied to an area measuring 8cm2 on the clipped flank skin of 6-8 guinea pigs per concentration group, using 1-6 such groups for each test material .After 21 days of induction period ,challenge dose was applied. These tests are performed by applying with a pipette 0.025ml of each concentration to skin areas measuring 2 cm2, the reactions being read after 24,48 and /or 72 hours. As though weak sensitization was observed at the 60 and 30% concentration in half of the animals .No sensitization was observed at the concentration of 10 and 3%. Therefore 4-methoxybenzyl alcohol (105 -13 -5)was considered to be not sensiting in guinea pig at the concentration of 10 and 3%.

 In another study by (Klecak G, Geleick H, Frey JR, 1977) with similar substance (100-51-6) was observed in male and female  Himalayan white-spotted guinea pigs. Skin sensitization test was observed guinea pigs by Draize test. A dose of 0.05 ml of a 0.1% solution of the compound tested in isotonic saline was injected intradermally on day 0 and further doses of 0.1 ml each were injected on 9 alternate days (total dose = 0.95 rag). The treated animals and untreated controls were challenged intradermally with 0.05 ml of a 0.1 per cent solution on days 35 and 49. No sensitization was observed after challenge treatment. Therefore Benzyl alcohol (100 -51 -6) was considered to be not sensitizing in guinea pigs by Draize test.

On the basis of available information for the target as well as read across substance and applying weight of evidence approach, the test substance can be considered as not sensitising to the skin.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

According to CLP Regulation EC No. 1272/2008 and based on the above studies, it is concluded that the substance 4-methoxyphenylacetic acid (CAS No. 104-01-8) is not classified as skin sensitizer.