Cyclohexane, oxidized, aq. ext.

Endpoint summary

Description of key information

COP acid and its primary component, adipic acid, are slightly irritating to the skin but does not warrant classification as a skin irritant according to current EU or GHS criteria. COP Acid and adipic acid are highly irritating to the eyes warranting classification in Category 1 according to EU and GHS criteria. Respiratory irritation in animals is not sufficiently examined. Due to the acidic character of the substance, a local irritation potential is plausible.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Cyclohexane, oxidized, aquous extract (COP Acid) has been adequately tested for its potential to cause irritation and determined to be only slightly irritating to skin (BASF, 1987), but not warranting classification as a skin irritant, and severely irritating to eyes (BASF, 1987). No adequate studies on the potential for COP Acid to cause respiratory irritation are available.

Skin Irritation (Key Study):

In a non-GLP OECD 404 guideline study (BASF, 1987), 3 male rabbits were exposed under semi-occlusive conditions for 4 hours with a 72 hour observation period. No signs of erythema or edema were observed.

Eye Irritation (Key Study):

In a non-GLP OECD 405 guideline study (BASF, 1987), 3 rabbits (male and female) were exposed and the unwashed eyes were observed for 8 days. Corneal effects scoring > 3 over the 24 -72 hour period were observed in 1 animal and were not fully reversible in this or the other animals that had slightly lower corneal scores in the 8 day observation period.

Supporting Studies - Adipic Acid (Read Across):

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

Skin irritation:

"500 mg of a 50 % aqueous suspension of adipic acid (99.8 %) was tested on intact and scarified skin of six rabbits, respectively. The compound was applied to an area of 5 x 5 cm, covered and held in contact for 24 hours. Responses were scored immediately after dosing (24 hours), 3 and 8 days. Reversible reddening was observed at the intact skin (scored 2-3 on a scale up to a maximum of 4) which disappeared after three days. Mild to severe reddening and edema was observed at the scarified skin (scores 24 h: 2, 3 days: 0 - 2). These effects were reversible after 1 week (all scores 0) and scale formation was observed (BASF 1978d)."

Eye irritation:

"Severe irritation was observed in a recent study according to OECD TG 405, conducted in compliance with GLP after the application of 100 mg adipic acid. Corneal opacity and irritation of the iris was observed in all animals up to grade 3 and grade 2, respectively. The observed effects were reversible within 16 days (LPT 2004)."

Respiratory irritation:

"Evidence of respiratory tract irritation was reported neither in an acute inhalation study where 20 rats were exposed to up to 7700 mg/m3 of adipic acid dust (MMAD 3.5 µm) for 4 hours (BASF 1981) nor in an subacute study with limited documentation where four rats were exposed to 126 mg/m3 of adipic acid dust for 6 hours per day for 15 days. The reliability of the sub-acute study is limited because only four animals were investigated, the MMAD was not determined and histopathology was performed only on nine organs, including the lung (Gage 1970). Both of these studies are however not suited to fully assess the local irritation potential of adipic acid, as the nose was not examined histopathologically. Additionally, cytotoxicity to rat nasal explants has been shown in vitro for adipic acid at 3.5 g/l (Trela and Bogdanffy 1991)."

Studies in Humans:

"7 of 12 workers exposed (for an average of 9.2 years) to various glycols, glycerine, other compounds, and adipic acid dust particles (8 h average concentration 0.47-0.79 mg/m3 [0.08-0.13 ppm]) complained of mucosal irritation (eye, nose, throat). There was no local exhaust ventilation and the workers did not wear respiratory protection. They reported that clouds of adipic acid and other materials were routinely generated during charging of reaction vessels. The investigators suggested that, since the glycol level was kept below 1 ppm, adipic acid was more likely to be the cause of these complaints (Cummings and Roseman 1985). This report is difficult to evaluate, because of the mixed exposure of the workers to a series of different compounds, including adipic acid. Due to the acidic character of adipic acid, a local irritation potential is plausible."

Updated relevant information:

None

Justification for selection of skin irritation / corrosion endpoint:

Key study supported by read-across.

Justification for selection of eye irritation endpoint:

Key study supported by read-across.

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Skin Irritation:

Cyclohexane, oxidized, aquous extract (COP Acid) is not classifiable as a skin irritatnt according to EU criteria in 67/548/EEC (DSD) or Regulation (EC) 1272/2008 (CLP) based on the results observed in the key study (BASF, 1987) and various supporting studies (Haskell, 1974; BASF, 1978; Solutia, 1975; and BASF, 1978) for the primary ingredient (Adipic Acid).

Eye Irritation:

COP Acid meets the criteria for classification as R41 ("Risk of Serious Damage to Eyes") and Category 1 ("Irreversible Effects on the Eye") according to EU criteria in 67/548/EEC (DSD) and Regulation (EC) 1272/2008 (CLP), respectively, based on the results observed in the key study (BASF, 1987) and various supporting studies (Bayer, 2004 and BASF, 1978) for the primary ingredient (Adipic Acid).