Glycollic acid

Endpoint summary

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:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-6 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

Adequate data from an in vivo guinea pig study were available.

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Inc. (Boyertown, PA.)
- Weight at study initiation: 341 and 516 grams on the day prior to the first induction application or on the day of the range-finding application.
- Housing: Animals were housed (1 animal per cage) in elevated stainless steel cages with wire mesh flooring.
- Diet (e.g. ad libitum): Purina Certified Guinea Pig Diet #5026 was provided ad libitum.
- Water (e.g. ad libitum): Supplied ad libitum.
- Acclimation period: Screen animals were acclimated for at least 6 days. All other animals were acclimated for 20 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19C-23C (66F-74F).
- Humidity (%): 45-78%.

Route:

epicutaneous, occlusive

Vehicle:

physiological saline

Concentration / amount:

for induction: 26% w/v glycolic acid in normal saline solution
for challenge: 20% w/v glycolic acid in normal saline solution
Based on results of preliminary testing, in which 10, 20, 23, 26, 30 and 40% w/v glycolic acid in normal saline solution were used.

A 0.5 mL aliquot of 26% wlv Glycolic Acid in normal saline solution was applied to a 25-mm Hill Top Chamberm (Hill Top
Research Inc., Cincinnati, OH) for induction and a 0.5 mL aliquot of 20% wlv Glycolic Acid in normal saline solution was used for challenge.

Route:

epicutaneous, occlusive

Vehicle:

physiological saline

Concentration / amount:

for induction: 26% w/v glycolic acid in normal saline solution
for challenge: 20% w/v glycolic acid in normal saline solution
Based on results of preliminary testing, in which 10, 20, 23, 26, 30 and 40% w/v glycolic acid in normal saline solution were used.

A 0.5 mL aliquot of 26% wlv Glycolic Acid in normal saline solution was applied to a 25-mm Hill Top Chamberm (Hill Top
Research Inc., Cincinnati, OH) for induction and a 0.5 mL aliquot of 20% wlv Glycolic Acid in normal saline solution was used for challenge.

No. of animals per dose:

20 in treated group, 10 in vehicle control. 12 used for preliminary investigations.

Details on study design:

Challenge: Day 29
Reactions were assessed 24 h and 48 h after each induction application and following the challenge application. Treatment sites were cleaned with normal saline after removal of Hilltop chambers after each induction and challenge exposure of 6 hours duration.

Preparation of Animals:
An area measuring approximately 2.5 x 2.5 inches on the left flank of each animal to be exposed to the test article in the induction phase was closely clipped on the day prior to test article administration (Day 1). The animals had also been clipped in this manner on the day of randomization and allocation (Day 8) but due to additional screens introducing an additional week of acclimation, the additional clipping was required. The clipping was repeated weekly during the induction phase of the study. Due to focal ulceration, focal necrosis or other signs of tissue injury at the test sites, the induction sites for thirteen animals were moved posterior prior to the third induction. An area measuring approximately 2.5 x 2.5 inches on the left flank of each animal to be exposed to the vehicle in the induction phase was similarly clipped on the day prior to vehicle control administration and repeated weekly during the induction phase of the study. An area measuring approximately 2.5 x 2.5 inches on the right flank of each animal (exposed to the test article in the induction phase) was closely clipped on the day prior to the challenge application. Similar areas were clipped on the left flank (caudal) and right flank of each animal (exposed to vehicle in the induction phase) on the day prior to challenge applications.

RANGE FINDING TESTS:
The doses in the induction study were based on a range-finding study.
Induction:
A group of 20 animals were clipped as described above. A 0.5 mL aliquot of 26% wlv Glycolic Acid in normal saline solution was applied to a 25-mm Hill Top Chamber, placed on the test site, and covered with a piece of dental dam (approximately 2 x 2 inches). After positioning the chamber and the occlusive dental dam on the prepared skin site, plastic was wrapped snugly around the trunk of the animal and overwrapped with Elastikon. Approximately 6 hours after application, the entire wrapping was removed, and the test sites were wiped with normal saline solution and then deionized water. A separate group of 10 animals (vehicle and test article irritation control) were clipped as described above. Normal saline solution was applied to the chambers and the animals wrapped as described above. Approximately 6 hours after application, the entire wrapping was removed, and the test sites were wiped with normal saline solution and then deionized water. The test sites were scored for irritation at approximately 24 and 48 hours following application. This above procedure was performed for both treated and control animals at 7-day intervals for 3 consecutive weeks.

Challenge:
Following the third application of test article to the test sites, the animals were rested for approximately 15 days. On Day 29, the animals were clipped as described above. The challenge application was performed on the right flank using a 0.5 mL aliquot of a 20% w/v solution of Glycolic Acid in normal saline solution. Similarly, animals in the vehicle and test article irritation control group were rested after the third application of the vehicle. These animals were challenged with normal saline solution on the left flank (caudal) and a 0.5 mL aliquot of a 20% w/v solution of Glycolic Acid in normal saline solution on the right flank. The applications of the test article and vehicle were as described in Section 13.3 of the attached study report. Approximately 6 hours after application of test article and/or vehicle, the entire wrapping was removed, and the test site(s) wiped with normal saline solution and then deionized water. Approximately 24 and 48
hours after the challenge application, the test sites were examined for dermal irritation or signs of elicited sensitization.

Challenge controls:

No further information.

Positive control substance(s):

yes

Remarks:

not run concurrently with the test article.Routine historical testing with hexylcinnamaldehyde

Positive control results:

Alpha-hexylcinnamaldehyde (HCA) is tested periodically but was not conducted concurrently with the present investigation. Results of a positive control study conducted in June 1998 are presented in the study report but are not reproduced in this summary. The results confirm validity of methods used in the current study.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.5 mL of 20% w/v solution of glycolic acid in normal saline solution

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no reactions indicative of skin sensitisation

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5 mL of 20% w/v solution of glycolic acid in normal saline solution. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no reactions indicative of skin sensitisation .

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5 mL of 20% w/v solution of glycolic acid in normal saline solution

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no reactions indicative of skin sensitisation

Remarks on result:

other: see Remark

Remarks:

Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5 mL of 20% w/v solution of glycolic acid in normal saline solution. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no reactions indicative of skin sensitisation .

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

normal saline solution

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no reactions indicative of skin sensitisation

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: normal saline solution. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no reactions indicative of skin sensitisation .

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

normal saline solution

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no reactions indicative of skin sensitisation

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: normal saline solution. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no reactions indicative of skin sensitisation .

Reading:

rechallenge

Hours after challenge:

24

Group:

positive control

Dose level:

1.5%

No. with + reactions:

10

Total no. in group:

20

Remarks on result:

positive indication of skin sensitisation

Vehicle and Test Article Irritation Control Group

- Induction and Challenge: Dermal irritation was not observed after the induction applications to control animals. Challenge application at the vehicle sites also failed to induce dermal irritation. No redness was observed at the test article irritation control sites 24 and 48 hours after the challenge application. . All vehicle and test article irritation control animals appeared to be normal throughout the study. All animals exhibited an overall gain in body weight during the study. There were no statistically significant differences identified between the individual body weight percentage gains of the test article group and vehicle and test article irritation control group.

 

Other findings: During the induction phase faint redness was occasionally observed at 24 or 48 hours after dosing.  Additional effects included instances of scratches at test sites (guinea pigs are adept at using hind legs to self-inflict such injuries when reactions at sites cause some discomfort).  There were also incidences of focal ulceration, focal necrosis and some instances of exfoliation observed.  The location of the test site was altered for the third induction application to avoid further insult at areas affected by necrosis or ulceration.  24 and 48 hours after the third induction application there were instances of exfoliation and scratches.

All test animals appeared to be clinically normal throughout the study.

One animal exhibited a weight loss from day 14 to 21.  All animals exhibited an overall gain in body weight during the study.  There were no statistically significant differences identified between the individual body weight percentage gains of the test article group and vehicle group and test irritation control group. 

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

It was concluded that repeated administration of glycolic acid did not produce a delayed contact sensitisation response in guinea pigs and is not considered a dermal sensitizer under the study conditions utilised. The positive control study gave a positive response confirming validity and sensitivity of the methods used in this assay.

Executive summary:

A test group of twenty Hartley guinea pigs and a control group of ten Hartley guinea pigs were prepared by clipping the hair from the dorsal region. The animals were weighed prior to dosing, at weekly intervals thereafter and following completion of the challenge phase. The guinea pigs were observed for clinical signs of reaction to treatment throughout the induction and challenge phases.

 

Challenge phase:

- 24 hours after challenge. A) Incidence index (Number of erythema scores of greater than 0.5 / number of animals evaluated) = 0/20 for test animals and 0/10 for the controls, B) Severity index (Sum of erythema scores at 24 hours post challenge / number of animals evaluated) = 0 for test animals and 0 for controls.

 

Challenge phase:

- 48 hours after challenge. A) Incidence index (Number of erythema scores of greater than 0.5 / number of animals evaluated) = 0/20 for test animals and 0/10 for the controls, B) Severity index (Sum of erythema scores at 24 and 48 hours post challenge / number of animals evaluated) = 0 for test animals and 0 for controls.

 

All test animals appeared to be normal throughout the study. One animal exhibited a weight loss from day 14 to 21. All animals exhibited an overall gain in body weight during the study. There were no statistically significant differences identified between the individual body weight percentage gains of the test article group and vehicle group and test irritation control group.

 

Glycolic acid did not produce a delayed contact sensitisation response in guinea pigs and is not considered a dermal sensitizer under the study conditions utilised. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In a standard Buehler test, guinea pigs were treated with glycolic acid by topical application on repeated occasions.

The results of the challenge application - 24 or 48 hours after dosing were:

 

Challenge phase: - 24 hours after challenge. Incidence index (Number of erythema scores of greater than 0.5 / number of animals evaluated) = 0/20 for test animals and 0/10 for the controls. Severity index (Sum of erythema scores at 24 hours post challenge / number of animals evaluated) = 0 for test animals and 0 for controls.

  

Challenge phase: - 48 hours after challenge. Incidence index (Number of erythema scores of greater than 0.5 / number of animals evaluated) = 0/20 for test animals and 0/10 for the controls

 

Severity index (Sum of erythema scores at 24 and 48 hours post challenge / number of animals evaluated) = 0 for test animals and 0 for controls. All test animals appeared to be normal throughout the study. One animal exhibited a weight loss from day 14 to 21.

  

Glycolic acid did not produce a delayed contact sensitisation response in guinea pigs and is not considered a dermal sensitizer under the study conditions.

Migrated from Short description of key information:
Repeated administration of glycolic acid did not produce a delayed contact sensitisation response in guinea pigs. The Beuhler test results did not indicate potential for glycolic acid to act as a dermal sensitiser

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The negative results in a Buehler skin sensitisation study indicate no potential for an immune response. According to Regulation (EC) 1272/2008, Glycolic acid does not require any classification for sensitisation.