Adipic acid

Endpoint summary

Description of key information

Adipic acid caused no skin sensitization in a Guinea pig test (Haskell, 1974).

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:

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.

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.

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

Route:

intradermal

Vehicle:

propylene glycol

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

Route:

epicutaneous, open

Vehicle:

propylene glycol

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

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

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

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

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

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

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

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

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

Group:

positive control

Remarks on result:

not measured/tested

Remarks:

not measured/tested

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%.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Hazards identified by OECD/ICCA high production volume chemicals program in 2004:

Animal data:

"There is only one sensitisation study available and it produced no evidence of a sensitising action but its reliability can not be fully assigned. 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 because the number of animals per group was low, no data were presented to justify the induction concentration used, no adjuvant was used, and no positive control or historical data were presented."

Human data:

"Despite the wide use of adipic acid, only very few cases of skin or respiratory tract reactions are reported: A positive patch test reaction to adipic acid (probably 1 % in alcoholic solution) was reported in a 51-year-old machine repairman with a 3- to 4-year history of work-related dermatitis of the hands and other exposed sites when working with powders in the synthesis of polyesters (Guin 2001). Delayed cutaneous hypersensitivity to adipic acid was reported in a patch test (100 %) with a laboratory worker in a factory producing polyester resins. No further details are available in this case (Malten and Zielhuis 1964)."

Updated relevant information:

Potential skin sensitizing effects of a mixture of dicarboxylic acids containing 23.8% adipic acid, 50.9% glutaric acid and 18.6% succinic acid were investigated in a Guinea pig maximization test according to OECD TG 406. Ten guinea pigs received 0.1% test compound in 0.9% NaCl in the presence of Freud's complete adjuvant during the intradermal induction and 10% test compound during the following dermal induction after application of 10% sodium lauryl sulfate to induce local irritation. The challenge was performed with 5% test compound for 24 hours and skin reaction was evaluated 24 and 48 hours after removal of the dressing.

After the challenge application, no cutaneous reactions were observed in the animals of the control group. In the treatment group, a discrete erythema was observed in 1/10 animals at the 24-hour reading and in another animal at the 48-hour reading. Dryness of the skin was also observed in 1/10 animals at the 48-hours reading only. The authors concluded that the test item is not sensitizing to skin.

Overall, it can be concluded that adipic acid alone or in a mixture with glutaric and succinic acid is not sensitizing to skin.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Hazards identified by OECD/ICCA high production volume chemicals program in 2004:

"Despite the wide dispersive use of adipic acid, only very few cases of skin or respiratory tract sensitisation reactions are reported in humans.

Overall, sensitisation is not expected for adipic acid."

Justification for classification or non-classification

Adipic acid was shown to be not sensitizing to skin in Guinea pigs. In humans, despite the wide use of adipic acid, there is no indication of a skin sensitizing potential. Thus, no classification is required according to the EU Regulation no. 1272/2008 (GHS).