Disodium adipate

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Remarks:

other: chronic two-year study

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1957

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No GLP, short documentation, unclear number of animals examined histopathologically, only one dose for females, purity not specified.

Data source

Reference

Reference Type:

publication

Title:

Safety of adipic acid as compared with citric and tartaric acid.

Author:

Horn HJ, Holland EG, Hazleton LW

Year:

1957

Bibliographic source:

Agricult. Food Chem. 5, 759-762.

Materials and methods

Principles of method if other than guideline:

see repeated dose toxicity Horn et al. 1957. Rats were fed either the basal laboratory diet, or the basal diet to which adipic acid was added. Body weights, food consumption, and general appearance were recorded weekly throughout the experimental period. Whenever possible, gross autopsy was performed on those animals that died during the course of the experiment. After two years, surviving rat were weighed, killed, and examined grossly. Organs were weighed. Microscopic examination of several organs, including testis or ovaries and uterus was performed on a representative number of animals.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Adipic acid

EC Number:

204-673-3

EC Name:

Adipic acid

Cas Number:

124-04-9

Molecular formula:

C6H10O4

IUPAC Name:

adipic acid

Details on test material:

Test substance purity not specified

Test animals

Species:

rat

Strain:

other: Carworth Farm strain

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Details on mating procedure:

no mating

Duration of treatment / exposure:

Exposure period: 2 years

Frequency of treatment:

diet ad libitum

Details on study schedule:

2 year cancer study

Doses / concentrations

Remarks:

Doses / Concentrations:
male rats: 0, 0.1, 1, 3, and 5%; (ca. 75, 750, 2250, 3750 mg/kg bw/day) female rats: 0, 1%; (ca. 750 mg/kg bw/day)
Basis:

No. of animals per sex per dose:

19-20 per sex and dose

Control animals:

yes

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

RS-Freetext:
During the rapid growth of the 2-year feeding studies,
weight gains for the male rats receiving 3 or 5% adipic acid was  significantly 

less than the controls. Growth for other groups, 0, 0.1, 1%  male and 

0,1% female, was comparable to that of the respective controls.  

There was no evidence of gross pathology associated with the feeding of  

adipic acid (see Repeated Dose Toxicity).

Males (control, 0.1, 1, 3, 5% adipic acid; 20 male
animals/group):
When the surviving males were sacrificed there was no
significant gross pathology that could be related to adipic
acid. Histopathologic examination of the testes revealed no
evidence of an adverse effect on the reproductive organs up
to the highest dose. Soft edematous testes were noted at
least as frequent in the controls as in the experimental
animals.

Females (10 control animals and 19 animals dosed with 1%
adipic acid):
When the surviving females were sacrificed there was no
significant gross pathology that could be related to adipic
acid. Histopathologic examination of the ovaries and uterus
revealed no evidence of an adverse effect on the
reproductive organs. Two of the surviving control animals and one of the  

experimental animals had ovarian tumors, ovarian cysts were noted in both  

control and experimental rats.

In summary: histopathologic examination of the testes,
ovaries and uterus revealed no evidence of an adverse effect
on the reproductive organs.

Applicant's summary and conclusion

Executive summary:

Studies on fertility are not available. In the previously described two-years feeding study in rats (see chapter 3.1.5. Repeated Dose Toxicity) histopathological examination of testes, ovaries and uterus revealed no evidence of an adverse effect on the reproductive organs up to the highest tested doses (3750 mg/kg bw/day in males, 750 mg/kg bw/day in females). Soft edematous testes were observed at least as frequent in the controls as in the adipic acid dosed animals. Two of the surviving control female animals and one of the experimental females had ovarian