Registration Dossier

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

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Sex:
male/female

Results and discussion

Effect levels

open allclose all
Key result
Dose descriptor:
NOAEL
Effect level:
1 720 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
clinical signs
mortality
body weight and weight gain
gross pathology
histopathology: non-neoplastic
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.