N,N'-propane-1,3-diylbis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionamide]

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Additional documentation, provided within the IUCLID Assessment Reports (Section 13), supports the read-across approach.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

genetic toxicity in vivo, other

Remarks:

Dominant Lethal assay

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Additional documentation, provided within the IUCLID Assessment Reports (Section 13), supports the read-across approach.

Reason / purpose for cross-reference:

read-across source

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Remarks on result:

other: No evidence of dominant lethal effect was observed in the progeny of male mice treated with test substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The test was conducted to evaluate the cytotoxic or mutagenic effects on male germinal cells produced by test substance.

GLP compliance:

not specified

Type of assay:

rodent dominant lethal assay

Test material

Test material information

Constituent 1

Reference substance name:

N,N'-propane-1,3-diylbis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionamide]

EC Number:

274-157-0

EC Name:

N,N'-propane-1,3-diylbis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionamide]

Cas Number:

69851-61-2

Molecular formula:

C37H58N2O4

IUPAC Name:

N,N'-propane-1,3-diylbis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanamide]

Details on test material:

- Purity: Not reported

Test animals

Species:

mouse

Strain:

other: Tif: MAG f (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animals were obtained from closed breeding colony
- Age at study initiation: Female: 2 months; Males: 2 1/2 to 6 months
- Diet: Standard diet (NAFAG No .890)
- Water: Tap water ad litium

ENVIRONMENTAL CONDITIONS
- Temperature : 21 ± 1°C
- Humidity: 60 ± 5%
- Photoperiod (hrs dark / hrs light): 14 hours dark and 10 hours light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle used: CMC (carboxymethyl cellulose)
- Amount of vehicle: 0.2 mL/10 g of body weight

Duration of treatment / exposure:

Single exposure

Post exposure period:

Each group consisted of 20 males, each of which was placed in a cage with 2 untreated females immediately after treatment. At the end of 1 week, the females were removed and replaced by another group of 2 females. The procedure was continued for six consecutive weeks. The females were daily examined for successful mating indicated by the occurrence of a vaginal plug. The day that the vaginal plug was observed was designated as "day 0" of gestation. The whole time of six "mating periods" comprises all the stages of the maturation of the germ cell from the A-spermatogonia to the mature spermatozoon.
- Males were observed first week after administration of test substance for general condition and symptomatology.
- Autopsy of females was done and progeny were examined.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

1 000 other: mg/kg

Doses / concentrations 2

Dose / conc.:

3 000 other: mg/kg

No. of animals per sex per dose:

20 males/group

Control animals:

yes, concurrent vehicle

Examinations

Statistics:

- Student's t test or Mann-Whitney u-test is used to compare the total no of implanatations indicating possible pre-implantation losses
- X²-test or fischer's exact test is used to compare total number of mated and pregnant dams or embryonic deaths.
- Experimental data, particularly on the number of implantations and early embryonic deaths were compared with spontaneous data of a cummulative of treated controls observed over a longer period of time (autopsy on day 18 of pregnancy).

Results and discussion

Test results

Key result

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Remarks on result:

other: No evidence of dominant lethal effect was observed in the progeny of male mice treated with test substance.

Additional information on results:

The females mated to males which had been treated with the test substance did not differ significantly from the females mated to control, neither in mating ratio nor in the number of implantations and embryonic deaths (resorptions).

Applicant's summary and conclusion

Conclusions:

No evidence of dominant lethal effects were observed in progeny of male mice tretaed with test substance.

Executive summary:

The test was conducted to evaluate the cytotoxic or mutagenic effects on male germinal cells produced by test substance The test substance was administered orally by intubation in single doses to male albino mice which were then mated to untreated females from the same strain over a period of six weeks. At the end of each week the females were replaced by new ones. Doses of 1000 and 3000 mg/kg were given. The test was done to evaluate any cytotoxic or mutagenic effects on the male germinal cells as expressed by the loss of pre-implantation zygotes as well as by the rate of deaths of post-implantation stages of embryonic development.

The results showed that the females mated to males which had been treated with the test substance did not differ significantly from the females mated to control, neither in mating ratio nor in the number of implantations and embryonic deaths (resorptions). No evidence of dominant lethal effect was observed in the progeny of male mice treated with test substance.