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Toxicological information

Toxicity to reproduction

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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

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.