Glutaric acid

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

other: expert assessment

Adequacy of study:

weight of evidence

Study period:

14 December 2016

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: An assessment was performed based on literature data on the substance and literature data on an analogous substance.

Data source

Reference

Reference Type:

other: expert assessment

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

An assessment was performed based on literature data on the substance and literature data on an analogous substance.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glutaric acid

EC Number:

203-817-2

EC Name:

Glutaric acid

Cas Number:

110-94-1

Molecular formula:

C5H8O4

IUPAC Name:

pentanedioic acid

Test animals

Sex:

male/female

Results and discussion

Effect levels

1

Key result

Dose descriptor:

NOAEL

Effect level:

1 720 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

body weight and weight gain

clinical signs

gross pathology

histopathology: non-neoplastic

mortality

2

Key result

Dose descriptor:

NOAEL

Effect level:

980 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

body weight and weight gain

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

The overall conclusion for this Registration Assessment Report, is a proposed NOAEL of 1,720 mg/kg bw/day of glutaric acid in the diet for male rats and 980 mg/kg bw/day of glutaric acid in the diet for female rats. These values are deemed to be conservative because they are derived from the results of longer-term exposure to glutaric acid while the purpose of this assessment is to assess the toxicity of glutaric acid following a short-term exposure. These values are also lower than those derived from the testing performed on the analogous substance adipic acid. No specific target organ toxicity was identified.

Executive summary:

The toxicity of glutaric acid following short-term repeated exposure was assessed using a read-across from the analogous substance adipic acid supported by available experimental data on glutaric acid.

Horn et al. (1957) derived a NOAEL of 3% for adipic acid in the diet for male rats following a chronic exposure, and above 0.1% of adipic acid in the diet for female rats as it was the highest concentration evaluated. These values are equivalent respectively to 2,070 mg/kg bw/day and 80 mg/kg bw/day. No specific target organ toxicity was identified, as the only adverse effects observed were a reduced body weight and a lower body weight gain in the groups receiving the highest concentrations of adipic acid in the diet when compared to the control groups, related to a reduced food consumption. These results were supported by Moody et al. (1978) who did not observe any significant effects when focusing on the liver of male rats exposed to 2% of adipic acid in the diet for three weeks – considered as equivalent to 2,000 mg/kg bw/day – and by the historical uses of adipic acid in foodstuff, feed and industrial processes.

The experimental data on adipic acid are supported by the consistent results obtained from two subchronic studies on glutaric acid performed by Solutia Inc. (1977a, 1977b) and used as a weight of evidence for the purpose of this assessment. Results from these studies were used to derive a NOAEL above 2% in the diet for the male rats and 1% for the females following subchronic exposure to glutaric acid, equivalent to 1,720 mg/kg bw/day for the males and 980 mg/kg bw for the female rats. No specific target organ toxicity has been identified as the only significant effect observed was a reduction of the body weight of the female rats. These results are supported by the fact that glutaric acid is naturally produced in the human body during the metabolisation of several amino acids.

The overall conclusion for this Registration Assessment Report, is a proposed NOAEL of 1,720 mg/kg bw/day of glutaric acid in the diet for male rats and 980 mg/kg bw/day of glutaric acid in the diet for female rats. These values are deemed to be conservative because they are derived from the results of longer-term exposure to glutaric acid while the purpose of this assessment is to assess the toxicity of glutaric acid following a short-term exposure. These values are also lower than those derived from the testing performed on the analogous substance adipic acid. No specific target organ toxicity was identified.