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Additional toxicological data

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Administrative data

Endpoint:
additional toxicological information
Type of information:
other: Review
Adequacy of study:
key study
Study period:
2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Toxicological evaluation concluded in OECD/ICCA program during SIAM 18, April 2004, published by UNEP.

Data source

Reference
Reference Type:
review article or handbook
Title:
SIDS Initial Assessment Report for SIAM 18 for Adipic acid
Author:
OECD/SIDS
Year:
2004
Bibliographic source:
published by UNEP
Report date:
2004

Materials and methods

Type of study / information:
Toxicologic evaluation of all available data on adipic acid
Principles of method if other than guideline:
Toxicological evaluation concluded in OECD/ICCA program during SIAM 18, April 2004, published by UNEP.

Test material

Constituent 1
Chemical structure
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:
See above

Results and discussion

Any other information on results incl. tables

Initial Assessment for Human Health:

In limited studies in animals and humans it was shown that adipic acid is absorbed after oral administration, partially metabolized to various metabolites and CO2 which are excreted via urine and breath, resp. None of the studies was conducted according to GLP.

Adipic acid is of very low acute toxicity. The oral LD50 in rats in a study similar to OECD TG 401 is approximately 5560 mg/kg bw. Clinical signs at lethal doses included acute dilatation of the heart and acute congestive hyperaemia, ulceration of glandular stomach (bleeding-corrosive gastritis), intestinal atony, pale liver and reddening of intestinal mucosa. The LD50 for mice was reported to be 1900 mg/kg bw. In an inhalation test similar to OECD TG 403 in rats neither mortality nor symptoms were observed during and after 4 hour exposure to 7700 mg/m3 of adipic acid. Reduced appetite and activity were the only effects reported following occlusive dermal administration of 7940 mg/kg bw of adipic acid to 2 rabbits for 24 hours.

In rabbits, 50 % adipic acid suspensions were slightly irritating to the intact skin and moderately irritating to scarified skin. The neat material was a severe eye irritant in rabbits, with symptoms being reversible within 16 days. Respiratory irritation in animals is not sufficiently examined. Workers exposed over an extensive period (av. 9.2 years) complained of respiratory irritation at adipic acid concentrations of 0.47 - 0.79 mg/m3. Due to the acidic character of the substance, a local irritation potential is plausible.

Despite the wide dispersive use of adipic acid, only very few cases of skin or respiratory tract sensitisation reactions are reported in humans. A sensitisation study in animals according to validated guidelines is not available. Overall, sensitisation is not expected for adipic acid.

There is no repeated inhalation toxicity study with histopathological examination of the nose available. Systemic effects after repeated inhalation have not been investigated in fully valid studies. There are no studies on repeated dermal application available. In a limited 2-year oral study adipic acid was of low repeated dose toxicity, however it was not tested according to modern standards. The NOAEL was 1 % for male rats (approx. 750 mg/kg bw/day) and higher doses (3 and 5 %) caused body weight retardation with no indication of specific target organ toxicity. The NOAEL for female rats was 1 % (approx. 750 mg/kg bw/day), the highest dose tested in females. In one volunteer no overt toxic symptoms were seen after oral administration of 7 g adipic acid per day for 10 days.

A variety of mutagenicity tests in vitro and in vivo have failed to demonstrate that adipic acid possesses genotoxic potential. A number of good quality Ames tests in Salmonella typhimurium similar to OECD TG 471 and an examination of chromosome damage in human lung cells in culture produced negative results. In gavage studies in male rats it did not induce chromosome damage in the bone marrow or dominant lethal mutations in a dose-response or time-trend pattern.

Adipic acid was not carcinogenic in a limited two-years feeding study where male rats were fed with up to 5 % (3750 mg/kg bw/day) adipic acid and female rats with 1 % (750 mg/kg bw/day).

No specific studies on fertility have been conducted. In a two-year feeding study in rats histopathological examination of testes, ovaries and uterus revealed no evidence of an adverse effect on the reproductive organs up to the highest doses tested (males approx. 3750 mg/kg bw/day, females approx. 750 mg/kg bw/day). Based on the available data there is no reason to expect specific reproductive toxicity of adipic acid.

Adipic acid was not embryo- or fetotoxic and not teratogenic up to the highest tested doses of 288, 263 and 250 mg/kg bw/day via oral administration to rats, mice and rabbits, respectively. In none of these studies signs of maternal toxicity have been observed and the highest dose was well below the limit dose of 1000 mg/kg bw which would be a precondition for a fully valid negative study. In view of the low systemic toxicity of the compound, however, this endpoint seems to be adequately covered despite the limitations of the studies.

Applicant's summary and conclusion

Executive summary:

SIDS INITIAL ASSESSMENT PROFILE: "The chemical is currently of low priority for further work."

The rational for this recommendation concerning human health was: "The chemical possesses properties (eye and respiratory tract irritation) indicating a hazard for human health. Although these hazards do not warrant further work, they should nevertheless be noted by chemical safety professionals and users, especially at the workplace."

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