reaction products of acetic anhydride and adipic acid

Endpoint summary

Description of key information

As the substance is classified as corrosive to skin, no acute toxicity studies need to be conducted. The hazard assessment is based on the available data on the most hazardous constituents of the substance, acetic anhydride and the hydrolysis products, acetic acid and adipic acid.
Oral:
The oral LD50 (rat) is 1780 mg/kg bw for acetic anhydride
The oral LD50 (rat) is 3310 mg/kg bw for acetic acid
The oral LD50 (mouse) is 1900 mg/kg bw for adipic acid
Inhalation:
The inhalation LC50 (rat) is 1680 mg/m3 for acetic anhydride
The inhalation LC50 (rat) is 2248 mg/m3 for acetic acid
The inhalation LC50 (rat) is > 7700 mg/m3 for adipic acid
Dermal:
No data available

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 780 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

1 680 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The weight of evidence approach is used to assess the acute toxicity of the target substance. No studies are conducted for the target substance since it is classified for corrosive to skin. The substance is composed of acetic anhydride (typical conc. ca. 7 wt. %), adipic acid, di-anhydride with bis (acetic acid) (typical conc. ca. 57 wt. %) and acetic acid (typical conc. ca. 33 wt. %). The main and the most hazardous component of this substance is acetic anhydride which has well-known corrosive and irritating effects on the eyes, skin and respiratory tract.Since acetic anhydride readily hydrolyzes to acetic acid in water (half-life about 4 minutes), systemic toxicity is unlikely. As adipic acid anhydride is hydrolytically unstable information on adipic acid is used in the assessment as well.

Oral exposure

There are few studies via oral route available from acetic anhydride, acetic acid and adipic acid. The acute oral toxicity value (LD50; rat) for acetic anhydride is 1 780 mg/kg bw (OECD; SIDS, 1997). The oral LD50 for acetic acid is 3 310 and 4 960 mg/kg bw in rats and mice, respectively (Woodard, G et al., 1941; HSDB, 2016). Furthermore, for adipic acid oral toxicity values are 1 900 mg/kg and 11000 mg/kg in mice and rats (Bingham, E. et al., 2001).

Inhalation

Acetic anhydride: Inhalation LC₅₀was approximately 400 ppm (1 680 mg/m³; rats, 6 hrs, vapor) (OECD; SIDS, 1997). In this two-week inhalation study, rats were exposed for 6 hrs/day, 5 days per week (or less) to 25, 100 or 400 ppm acetic anhydride vapor. Mortality (40%) was observed in the 400 ppm (1680 mg/m³) group after the first 6-hr. exposure period. In the study by Smyth et al., 1951 rats were exposed to 1000 ppm and 2000ppm concentration of acetic anhydride for 4 hours. Mortality of 0% and 100% was observed at 1000 ppm (4240 mg/m3) and 2000 ppm (8480 mg/m3), respectively.

 

Acetic acid: The LC50 for mice was found to be 5 620 ppm (2 248 mg/m³) for 1-hour exposures. Symptoms were mainly irritation of the upper respiratory tract and of the conjunctiva. Most of the surviving animals recovered quickly and showed no abnormal condition after 30–35 hours (HSDB, 2016)

 

Adipic acid: In a study similar to OECD TG 403, neither mortality, toxic symptoms nor macroscopic pathological changes were observed in 20 rats exposed for 4 hours (nose only) to the maximal attainable concentration of 7700 mg/m3 of adipic acid (99.8 %) dust (OECD; SIDS, 2004).

Justification for selection of acute toxicity – oral endpoint
No study was selected since hazard assessment is based on WoE from the studies conducted for acetic anhydride, acetic acid and adipic acid.

Justification for selection of acute toxicity – inhalation endpoint
No study was selected since hazard assessment is based on WoE from the studies conducted for acetic anhydride, acetic acid and adipic acid.

Justification for classification or non-classification

The target substance will be classified for Acute tox. 4 H302 (oral) and Acute tox. 4 H332 (inhalation)according to CLP Regulation 1272/2008.This is line with the harmonized classification of the most hazardous component (acetic anhydride) of the target substance.