Butyric anhydride

Endpoint summary

Description of key information

The oral LD50 of butyric acid was determined to be 1632 mg/kg bw in rats (BASF, 1978).
Hydrolysis study data, provided in section 5.1.2 will be used to demonstrate that butyric anhydride in an aqueous environment will undergo almost immediate hydrolysis to butyric acid. Thus, study data from butyric acid will be used to satisfy all data points in section 7, as water will be present in all of the studies.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

1 632 mg/kg bw

Additional information

Acute toxicity: oral

 

For assessment of the acute oral toxicity of butyric acid three valid studies are available. Two of them (Smyth, 1951 and 1954) originate from the same laboratory and were performed basically using the same method but with male and female rats at different times respectively. The LC50 for male rats is much lower than for females. The third study used rat of both sexes. No differences were notice. In this study the lowest LD50 was determined. This study is taken as key study.

 

BASF 1978 (key study)

 

In an acute oral toxicity study, groups of 5 male and 5 female Sprague-Dawley rats were given a single oral dose of butyric acid (purity ≥ 99%) in water at doses of 960, 1400, 2060, 3030, 4450, and 6520 mg/kg bw. Test animals were then observed for 14 days.

 

There were no obvious differences between sexes. Clinical signs were dyspnea, apathy, atonia, abdominal position, stagger, reduced general condition, spastic gait, exsiccosis. Dead animals showed acute dilatation and acute congestion hyperemia of the heart. In the stomach, fibrinous hemorrhagic caustic gastritis was noticed. Intestine content was hemorrhagic and loose. In the organs of sacrificed animals, no abnormalities were detected.

 

The acute oral LD50 was determined to be 1630 mg/kg bw in male and female rats (BASF, 1978)

 

Smyth 1951

 

The acute oral toxicity of butyric acid was determined in groups of 5 male Sherman rats receiving each a single oral dose of the test substance by gavage. The doses were spaced by a factor of 2 (geometrical series, at least four graduate doses, individual doses not specified). The observation period was 14 days. The LD50 and a range of ± 1.96 SD was calculated according to the method of Thomson (1947). Overall, the study was conducted similar to the recently retracted OECD test guideline 401.

 

The acute oral LD50 was 2940 mg/kg bw in male rats (Smyth, 1951).

 

Smyth 1954

 

The acute oral toxicity of butyric acid was determined in groups of 5 female Carworth-Wistar rats receiving each a single oral dose of the test substance by gavage. The doses were spaced by a factor of 2 (geometrical series, at least four graduate doses, individual doses not specified). The observation period was 14 days. The LD50 and a range of ± 1.96 SD was calculated according to the method of Thomson (1947). Overall, the study was conducted similar to the recently retracted OECD test guideline 401.

 

The acute oral LD50 was 8790 mg/kg bw in female rats (Smyth, 1954).

 

Justification for classification or non-classification

Acute oral toxicity

 

The LD50 of the key study (lowest reported LD50) was 1632 mg/kg bw in rats. According to Regulation (EC) No 1272/2008 classification as acute toxic Category 4 is required.