N-(1,1-dimethyl-3-oxobutyl)acrylamide

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Remarks:

other: Effects on reproductive organs

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Publication in a recognized journal.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1981

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Comparison of the known neurotoxicity and the effects on testis for acrylamide and possible effects for 13 related compounds.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

diacetone acrylamide

IUPAC Name:

diacetone acrylamide

Details on test material:

Supplier: Tokyo Kasei Co

Test animals

Species:

mouse

Strain:

other: ddY

Sex:

male

Details on test animals or test system and environmental conditions:

- Age at study initiation: 5-6 weeks- Weight at study initiation: 29 +- 2.2 g- Housing: 5-7 per cage- Diet: ad libitum- Water: ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

physiological saline

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

8 - 10 weeks

Frequency of treatment:

twice weekly

Doses / concentrations

Remarks:

Doses / Concentrations:Doses ranging from 1/2 to 1/5 of the LD50. The LD50 = 7.7. mmol/kg. Doses therefore ranging from 261 to 651 mg/kg bw.Basis:

No. of animals per sex per dose:

5-7 animals per dose.

Control animals:

yes, concurrent vehicle

Details on study design:

To examine the effect of metabolic activation, sodium phenobarbital (PB), which was prepared from phenobarbital before use, was given intraperitoneally at 50 mg/kg for five successive days per week, from one week before, up until the last week of treatment with the test compounds

Examinations

Postmortem examinations (offspring):

Histopathological study of the testis and examination of blood: After treatment with the test compounds for 8-10 weeks, mice were killed under ether anesthesia for histology and blood examination. The testis was weighed and fixed in 10% neutral formalin, processed, and embedded in paraffin. Ten-micron sections were stained with hematoxylin and eosin. Blood was taken from the right atrium with a heparinized syringe. Measurements of red and white blood cell counts, hemoglobin concentration, and hematocrit value, and differentiation of white blood cells, were conducted by routine methods.

Statistics:

Intergroup comparison was conducted by the Student's t-test.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

not examined

Body weight and weight changes:

no effects observed

Description (incidence and severity):

body weight

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

body weight

Organ weight findings including organ / body weight ratios:

not examined

Other effects:

not examined

Reproductive function / performance (P0)

Reproductive function: sperm measures:

not examined

Reproductive performance:

not examined

Details on results (P0)

Effect on testis: Atrophy and reduced testis weight was noted in 5 compounds, but not in diacetone acrylamide. No histopathological lesions were reported for diacetone acrylamide.Effect of PB treatment: diacetone acrylamide was not tested.Blood study: Effects of test compounds on the blood were examined after the last treatment. Only one compound, N,N'-methylene-bis-acrylamide, produced marked effects on red and white blood cell counts, hemoglobin concentration and hematocrit value.

Results: F1 generation

General toxicity (F1)

Clinical signs:

not examined

Mortality / viability:

not examined

Body weight and weight changes:

not examined

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings:

not examined

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Diacetone acrylamide did not produce lesions of the testes in this type of experiment.

Executive summary:

Neurotoxicity of acrylamide and related compounds and their effects on the testis after repeated oral doses were studied in mice. Of fourteen analogues tested, five produced neuropathy; but diacetone acrylamide did not.

No effects on testis or blood were noted for diacetone acrylamide.