Adipic acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Limited documentation, no positive control group, no historical data, study design does not accord to modern guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1974

Report date:

1974

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A test for primary irritation was conducted on the shaved intact shoulder skin of male albino guinea pigs. To test for sensitization potential, a series of four sacral intradermal injections was given, one each week over a 3-week period. Following a 2-week rest period, the test animals were challenged for sensitization dermally on the shaved intact shoulder skin. A group of previously unexposed guinea pigs received similar applications at challenge to provide a comparison of the challenge reactions on skin of similar age.

GLP compliance:

not specified

Type of study:

other: skin sensitization study on Guinea pigs

Justification for non-LLNA method:

The Guinea pig test was performed in 1974.

Test material

Test material information

Constituent 1

Reference substance name:

Adipic acid

EC Number:

204-673-3

EC Name:

Adipic acid

Cas Number:

124-04-9

Molecular formula:

C6H10O4

IUPAC Name:

adipic acid

Details on test material:

- Purity: 99.99%

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: albino

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Age at study initiation: Not reported
- Weight at study initiation: 502-766 g
- Housing: Not reported
- Diet (e.g. ad libitum): Not reported
- Water (e.g. ad libitum): Not reported
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

propylene glycol

Induction 2

Concentration / amount:

Primary Irritation: One drop (~0.05 mL) of 50% and 25% suspension (wt./wt.) of test material in propylene glycol
Induction: 0.1 mL of a 1.0% solution (wt./vol) of test material in water
Challenge: One drop (~0.05 mL) of 50% and 25% suspension (wt./wt.) of test material in propylene glycol

Challenge

Challenge 1

Route:

epicutaneous, open

Vehicle:

propylene glycol

Challenge 2

Concentration / amount:

Primary Irritation: One drop (~0.05 mL) of 50% and 25% suspension (wt./wt.) of test material in propylene glycol
Induction: 0.1 mL of a 1.0% solution (wt./vol) of test material in water
Challenge: One drop (~0.05 mL) of 50% and 25% suspension (wt./wt.) of test material in propylene glycol

No. of animals per dose:

10

Details on study design:

RANGE FINDING TESTS: The test for primary irritation was conducted by applying and lightly rubbing one drop of test material on the shaved intact shoulder skin.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 4 intradermal injections
- Exposure period: 3 weeks
- Site: Not reported
- Frequency of applications: once per week
- Concentrations: 0.1 mL of a 10% solution (wt./vol.) of test material in water

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Site: Shoulder
- Concentrations: 1 drop (~0.05ml) of 50% and 25% suspensions of test material in propylene glycol
- Evaluation (hr after challenge): 24 and 48 hours

Challenge controls:

A group of 10 previously unexposed guinea pigs received similar applications at the time of challange to provide a direct comparison of the challange reaction on skin of similar age.

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Results 3

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Results 5

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

25% for challenge only

No. with + reactions:

2

Total no. in group:

10

Results 6

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

25% for challenge only

No. with + reactions:

2

Total no. in group:

10

Results 7

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

50% for challenge only

No. with + reactions:

1

Total no. in group:

10

Results 8

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

50% for challenge only

No. with + reactions:

2

Total no. in group:

10

Results 9

Group:

positive control

Remarks on result:

not measured/tested

Remarks:

not measured/tested

Any other information on results incl. tables

Table 1: Results
	Test Area		Control Area for Challenge Test
Concentration in Propylene glycol	50%	25%	50%	25%
Primary Irritation Test
24 hours	10 neg.	10 neg.
48 hours	10 neg.	10 neg.
Challenge Test
24 hours	10 neg.	10 neg.	1+, 9 neg.	2+, 8 neg.
48 hours	10 neg.	10 neg.	2+, 8 neg.	2+, 8 neg.
Reaction Code: +, ++, +++ = mild, moderate, strong erythema; ++++ = erythema plus edema; +++++ = necrosis

Adipic acid produced very mild to no skin irritation when tested on the shaved intact skin of male albino guinea pigs at a concentration up to 50% in propylene glycol. It did not cause skin sensitization at concentrations of 25 and 50%.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Adipic acid produced very mild to no skin irritation when tested on the shaved intact skin of male albino guinea pigs at a concentration up to 50% in propylene glycol. It did not cause skin sensitization.

Executive summary:

Groups of 10 guinea pigs were given series of four sacral intradermal injections, one each week over a three-week period, which consisted of 0.1 ml of a 1.0 % solution of adipic acid (99.99 %) in water. Following a two-week rest period, the test animals were challenged for sensitisation by applying, and lightly rubbing in, approximately 0.05 ml of a 50 % and 25 % suspension of the test material in propylene glycol on the shaved intact shoulder skin. A group of 10 previously unexposed animals received similar applications at the time of challenge to provide direct comparison of the challenge reactions on the skin of similar age. The compound produced very mild to no skin irritation to previously unexposed guinea pigs and did not cause sensitisation (Haskell 1974). The study design does not accord to modern guidelines.