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Toxicity to reproduction: other studies

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Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Unknown
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published study of non-standard design

Data source

Reference
Reference Type:
publication
Title:
Testicular effects of acrylonitrile in mice.
Author:
Tandon, R., Saxena, D.K., Chandra, S.V., Seth, P.K., Srivastava, S.P.
Year:
1988
Bibliographic source:
Toxicology Letters 42(1): 55-63

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Investigations of sperm count, selected enzyme measurements and testicular histopathology in mice following 60 days acrylonitrile exposure by gavage
GLP compliance:
no
Type of method:
in vivo

Test material

Constituent 1
Chemical structure
Reference substance name:
Acrylonitrile
EC Number:
203-466-5
EC Name:
Acrylonitrile
Cas Number:
107-13-1
Molecular formula:
C3H3N
IUPAC Name:
acrylonitrile
Specific details on test material used for the study:
No details

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
physiological saline
Details on exposure:
Male mice were dosed by gavage administration at 1 or 10 mg/kg bw/d for 60 days.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Not reported
Duration of treatment / exposure:
60 days
Frequency of treatment:
Daily
Duration of test:
60 days
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Remarks:
Vehicle control
Dose / conc.:
1 mg/kg bw/day
Dose / conc.:
10 mg/kg bw/day
No. of animals per sex per dose:
10 (males)
Control animals:
yes, concurrent vehicle
Details on study design:
No further information available

Results and discussion

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
1 mg/kg bw/day
Based on:
test mat.
Sex:
male
Basis for effect level:
histopathology: non-neoplastic

Observed effects

There were no overt signs of toxicity or changes in body weight. At 10 mg/kg bw/d the authors reported decreased sorbitol DH and acid phosphatase, increased LDH and B-glucuronidase (according to the study authors, these findings suggest degeneration of germinal epithelium). Decreased epidydimal sperm count was reported. Histopathological evaluations showed seminiferous tubule degeneration.
Leydig cells were not affected.

Any other information on results incl. tables

Testicular damage was observed in mice gavaged with 10 mg/kg bw/d acrylonitrile, consisting of tubular atrophy and degeneration in approximately 40% of seminiferous tubules, with cytolysis and nuclear pyknosis of spermatids, formation of multinucleate giant cells and interstitial oedema. These changes were accompanied by a decrease in testicular sorbitol dehydrogenase (22% decrease, p<0.05) and acid phosphatase (16% decrease p < 0.05) and an increase in lactate dehydrogenase (12% increase, p < 0.05) and B-glucuronidase (36.7% increase, p < 0.05). Glucose-6-phosphatase was unaffected. These changes were seen in the absence of overt signs of toxicity or any effect on body weight or testicular weight. No effects were seeen in mice gavaged with 1 mg/kg bw/d acrylonitrile.

Applicant's summary and conclusion

Conclusions:
Gavage administration of acrylonitrile at 10 mg/kg bw/d caused testicular effects in the absence of overt toxicity; no effects were seen at a dose level of 1 mg/kg bw/d.
Executive summary:

Daily oral administration of acrylonitrile (10 mg/kg bw/d) to mice for a period of 60 days caused a significant decrease in the activity of testicular sorbitol dehydrogenase and acid phosphatase, and an increase in that of lactate dehydrogenase and beta-glucuronidase. Histopathological studies revealed degeneration of the seminiferous tubules. A decrease in the sperm counts of the epididymal spermatozoa was also observed in the animals of the acrylonitrile-exposed group. The authors suggest that acrylonitrile may affect male reproductive function by causing testicular injury. No effects were seen at a dose level of 1 mg/kg bw/d.