N-(cyclohexylthio)phthalimide

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: USEPA TSCA Guidelines for Teratogenicity Study, Federal Register Vol. 44, No. 145, July 26, 1979

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

- Name of test material (as cited in study report): Santogard PVI - Rubber pre-vulcanization inhibitor
- Molecular formula (if other than submission substance): C14H15NO2S
- Molecular weight (if other than submission substance): 261.34 g/mol
- Substance type: organic substunce
- Physical state: solid
- Composition of test material, percentage of components: 100%
- Lot/batch No.: NC 03-036
- Storage condition of test material: Room temperature (60-85°F) in a sealed container.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation: Females - 5 - 6 months old (sesually mature, virgin)
- Weight at study initiation: Females - 2.98 to 4.20 kg
- Fasting period before study:
- Housing: Individually (except during mating) in stainless steel, suspended cages with wire mesh floors and a sub-cage, stainless floor pan.
- Diet (e.g. ad libitum): Feed was withheld on day of arrival. The following day each rabbit received one leaf of cabbage. Thereafter, Purina Certified
Rabbit Chow No. 5326 HF (high-fiber) was fed ad libitum.
- Water (e.g. ad libitum): ad libitum (tap water presented by automated watering system - Elizabethtown Water Company).
- Acclimation period: Animals were acclimated for 1 month (19 September through 19 October 1983) prior to mating. Animals were examined by the staff veterinarian at the completion of the acclimation period.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 60° to 70°F (recorded twice daily - morning and afternoon).
- Humidity (%): Relative humidity 40 - 60% (recorded once daily in the morning).

- Photoperiod (hrs dark / hrs light): Light/dark cycle - 12 hour light/12 hour dark via automatic timer.

Administration / exposure

Route of administration:

other: Gastric intubation (Route was indicated by the sponsor).

Vehicle:

corn oil

Remarks:

Corn Oil (Mazola)

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Rate of preparation of diet (frequency): Once daily, as a single dose.
- Mixing appropriate amounts with (Type of food): The appropriate amount of the test article was weighed out for each dose level into labelled beakers and appropriate volume of corn oil added. The mixture was then sonicated (ca. 30 minutes). The mixture were than transferred to glass jars with plastic, screw light lids for storage. Fresh dosing solutions/suspension were prepared weekly and stored refrigerated when not being used for dosing.
- Storage temperature of food: samples was stored frozen.

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

Natural mating was used.
Each female selected for mating was placed into the male’s cage. When coitus is observed, the female has been removed and returned to her original cage. After several hours (at least two hours), the female was placed into the cage of a second, different male. When coitus is observed with the second male, the female is considered mated and was remained with that male overnight. The day on which coitus has been observed with both males will be designated as Day 0 of gestation.

Duration of treatment / exposure:

Appropriate amounts of test article has been dissolved or suspended
in corn oil and administered at a volume of 2 mi/kg of body weight/day.
The mated female rabbits has been dosed daily, as a single dose, from Day 7 through Day 19 of gestation, a 13—day treatment period. Dosages has been adjusted during the treatment period according to most recent body weights. Animals has been dosed at approximately the same time each day.

Frequency of treatment:

Once daily, as a single dose.

Duration of test:

Days 7 through 19 of generation.

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
10 mg/kg/day
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
30 mg/kg/day
Basis:
nominal conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
100 mg/kg/day
Basis:
nominal conc.

No. of animals per sex per dose:

No. of animal
72 females
Group I - vehicle (Corn Oil) 10 ml - control sample
Group II - 10 mg/kg/day
Group III - 30 mg/kg/day
Grup IV - 100 mg/kg/day

Control animals:

yes

Examinations

Maternal examinations:

Experimental Schedules
The daily dosing of the both sexes began 14 days before mating. The dosing was continued in the both sexes during the mating period (max. 14 days - 2 complete oestrus cycles). The males were dosing after the mating period at least until the minimum total dosing period of 28 days. They were sacrificed by the overdose of the anaesthetic (dietylether). The daily dosing of the females were continued throughout the pregnancy and up to 4th day after the birth. The females showing no-evidence of copulation were dosing 28 days after the last day of mating period. They were sacrificed overdose of the anaesthetic, too. The females with the offspring were sacrificed on day 4 post-partum.
Mating procedure
Normally, 1:1 (1 male to 1 female) matings were used in this study. The female was placed with the same male until the pregnancy occurs or 14 days have elapsed. Every morning during the mating period the females were examined for the presence of sperms or vaginal plugs. The day 0 of the pregnancy was defined as the day a vaginal plug or sperm are found. The pregnant female was keeping individually up to 4th day post-partum.
Clinical Observations
General clinical observations were made once a day 1 hour after the test article application. The healt condition of the animals, reactiion of animals to the applied substance, their condition were monitored every day and recorded. The number of pregnant females was recorded. The number of live and death pups, weight of litters and sex of pups were observed, too.
Body Weight and Food Consumption
Individual weghting of the adult animals was performed once week. The body weight of the animals was recorded in the Application notebooks.

Statistics:

Data were analyzed between control and treated groups and statistically significant differences between the control and treated group data are presented in mean or summary tables.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Details on maternal toxic effects:
No mortality occurred in the control or treated groups.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

30 mg/kg bw/day (nominal)

Based on:

other: weight loss

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day (nominal)

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified