Dipotassium adipate

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1957

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No GLP, short description of the results, low number of animals, few organs examined, unclear number of animals examined histopathologically, only one dose for females, purity not specified

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1957

Report date:

1957

Materials and methods

Test guideline

Qualifier:

no guideline followed

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. The brain, thyroid, lung, heart, liver, spleen, kidneys and adrenals, stomach of approximately half of each group of males were weighed. The kidneys, spleen, liver and heart of each female were weighed. Microscopic examination of thyroid, lung, heart, liver, spleen, kidneys, adrenals, stomach, pancreas, bone marrow, large and small intestine and testis or ovaries and uterus on a representative number of animals was performed.

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:

hexanedioic acid

Test material form:

not specified

Details on test material:

Test substance purity not specified

Test animals

Species:

rat

Strain:

other: Catworth Farm

Sex:

male/female

Details on test animals or test system and environmental conditions:

/

Administration / exposure

Route of administration:

oral: feed

Type of inhalation exposure (if applicable):

not specified

Vehicle:

other: diet

Details on exposure:

/

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

/

Duration of treatment / exposure:

2 years

Frequency of treatment:

diet ad libitum

Post exposure period:

no

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
75 mg/kg bw/day
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
750 mg/kg bw/day
Basis:
nominal in diet

Doses / concentrations 3

Remarks:

Doses / Concentrations:
2250 mg/kg bw/day
Basis:
nominal in diet

Doses / concentrations 4

Remarks:

Doses / Concentrations:
3750 mg/kg bw/day
Basis:
nominal in diet

No. of animals per sex per dose:

19-20 per sex and per dose

Control animals:

yes

Details on study design:

/

Positive control:

/

Examinations

Observations and examinations performed and frequency:

/

Sacrifice and pathology:

/

Other examinations:

/

Statistics:

/

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Relevance of carcinogenic effects / potential:

/

Effect levels

Dose descriptor:

NOAEL

Effect level:

> 3 750 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no caricnogenic effect up to the highest dose tested

Remarks on result:

other: Effect type: carcinogenicity (migrated information)

Any other information on results incl. tables

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. At the end of the study the body weight of males was reduced by 10% and more in the two highest exposure groups. There was slight, but consistent, reduction in food consumption at 5%. There was no evidence of gross pathology associated with the feeding of adipic acid (see chapter Repeated Dose Toxicity). Results males (control, 0.1, 1, 3, 5% adipic acid; 20 male animals/group): Autopsy data for the male animals that died during the course of the two-year feeding program and for the sacrificed rats were analyzed for incidence of tumors and/or lung pathology. Only tumors presenting gross evidence of being a new growth were scored. Male group: 0/0.1/1/3/5% Deaths: total deaths 12/7/5/4/5 lung pathology 7/3/1/3/- tumors 3/2/2/-/4 other causes 3/3/2/1/1 Sacrificed: lung pathology 4/7/7/3/4 tumors 1/2/2/-/- Results females (10 control animals and 19 animals dosed with 1% adipic acid): The results of microscopic examination appeared to be within normal limits. One experimental and two control animals died during the final six months. Upon autopsy, one control rat and one experimental rat were found to have tumors.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: the incidence of tumors observed in the adipic acid treated groups was as frequent as in the control groups.

Applicant's summary and conclusion

Conclusions:

/

Executive summary:

Adipic acid was not carcinogenic in a two-years feeding study where groups of twenty male rats were dosed with food containing 0, 0.1, 1, 3 and 5 % adipic acid (approx. 0, 75, 750, 2250, 3750 mg/kg bw/day), and female rats were dosed with 0 (n = 10) and 1 % (n = 19) adipic acid (approx. 0, 750 mg/kg bw/day), respectively. Animals that died during the study and survivors were analyzed for incidences of tumor growth and lung pathology. The incidences of tumors observed in the adipic acid treated groups were as frequent as in the control groups (Horn et al. 1957). The study does not comply with the current guidelines for carcinogenicity studies because the number of animals used was low, microscopic examination of only 15 tissues was done only on a representative number of animals for each group, only one concentration was tested for females, the MTD for females was not reached, and the purity of adipic acid is not indicated.