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Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
Endpoint:
toxicity to reproduction
Data waiving:
other justification
Justification for data waiving:
other:
Reproductive effects observed:
not specified
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

From the repeated dose toxicity study (See 7.5.1 from Horn et al., 1957), it could be concluded that the substance did not exhibit a significant effect on the reproductive organs of males and females. 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. 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.

Effects on developmental toxicity

Link to relevant study records
Reference
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
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
Species:
rabbit
Strain:
other: Dutch belted
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
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
Maternal examinations:
/
Ovaries and uterine content:
/
Fetal examinations:
/
Statistics:
/
Indices:
/
Historical control data:
/
Details on maternal toxic effects:
Maternal toxic effects:no data

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

Details on embryotoxic / teratogenic effects:
/
Remarks on result:
not measured/tested
Abnormalities:
not specified
Developmental effects observed:
not specified
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.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
subacute
Species:
rabbit
Quality of whole database:
No GLP but overall good documentation. Study did not include a high dose that caused maternal toxicity, no statistical evaluation. Data on purity of adipic acid are lacking. No justification for dose selection was given.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Developmental toxicity was assessed on three species, rat, mouse and rabbit. The lowest NOAEL level was observed in the rat and was 250 mg/kg bw/day.

Justification for selection of Effect on developmental toxicity: via oral route:

The lowest NOAEL was selected.

Justification for classification or non-classification

Additional information

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