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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP but overall good documentation. Study did not include a high dose that caused maternal toxicity, low number of animals per group, no statistical evaluation. Data on purity of adipic acid are lacking. No justification for dose selection was given

Data source

Reference
Reference Type:
publication
Title:
Teratologic Evaluation of Compound FDA 71-50. Adipic Acid in Rabbits.
Author:
Food and Drug Administration
Year:
1974
Bibliographic source:
PB-267 202
Report date:
1974

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
On day 0, each doe was given an injection of 0.4 ml of human chorionic gonadotropin. Three hours later, each doe was inseminated artificially with 0.3 ml of diluted semen from a proven donor buck. Beginning on day 6 and continuing daily through day 18 the females (10-14 animal per dose) were dosed with the indicated dosages by oral intubation. Body weights were recorded on days 0, 6, 12, 18 and 29 of gestation, with particular attention to food consumption and body weight. On day 14 all animals were subjected to cesarean section, and the number of corpora lutea, implantation sites, resorption sites and live and dead fetuses were recorded. The urogenetal tract of each animal was examined in detail for normality. All fetuses underwent a detailed gross examination for the presence of external congenital abnormalities. The live fetuses of each litter were then placed in an incubator for 24 hours for the evaluation of neonatal survival. All surviving pups were sacrificed, and all pups examined for visceral abnormalities and examined for skeletal defects. 6-Aminonicotinamide (2.5 mg/kg), d
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
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:
Purity not specified

Test animals

Species:
rabbit
Strain:
other: Dutch belted

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Details on exposure:
/
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
/
Details on mating procedure:
On day 0, each doe was given an injection of 0.4 ml of human chorionic gonadotropin. Three hours later, each doe was inseminated artificially
Duration of treatment / exposure:
13d
Frequency of treatment:
6.-18. gestation day, daily
Duration of test:
all animals were subjected to cesarean section on GD 29
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2.5 mg/kg bw/day
Basis:
no data
Remarks:
Doses / Concentrations:
12 mg/kg bw/day
Basis:
no data
Remarks:
Doses / Concentrations:
54 mg/kg bw/day
Basis:
no data
Remarks:
Doses / Concentrations:
250 mg/kg bw/day
Basis:
no data
No. of animals per sex per dose:
10-14 females per dose
Control animals:
yes

Examinations

Maternal examinations:
/
Ovaries and uterine content:
/
Fetal examinations:
/
Statistics:
/
Indices:
/
Historical control data:
/

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no data

Details on maternal toxic effects:
/

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Effect level:
>= 250 mg/kg bw/day
Based on:
no data
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no data

Details on embryotoxic / teratogenic effects:
/

Effect levels (fetuses)

Remarks on result:
not measured/tested

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Executive summary:

No adverse effects were seen in similar experiments after administration of adipic acid to groups of 10 to 14 pregnant rabbits (gd 6-18, up to 250 mg/kg bw/day; Food and Drug Res Labs, Inc. 1974). This study is limited to some extent by the fact that no signs of maternal toxicity have been observed and the highest doses tested , a dose below the limit dose of 1000 mg/kg bw.

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