Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From 15 DEC 1994 to 01 AUG 1995 (Analysis Dates)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well conducted and reported GLP study, but no histologic evaluation for testicular staging and spermatogenic index was performed
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report date:
1996
Reference Type:
publication
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Principles of method if other than guideline:
Analysis of the number and concentration of testicular spermatids and epididymal spermatozoa in male rats exposed for 13-weeks by inhalation
GLP compliance:
yes
Type of method:
in vivo

Test material

Constituent 1
Chemical structure
Reference substance name:
N-butyl acetate
EC Number:
204-658-1
EC Name:
N-butyl acetate
Cas Number:
123-86-4
Molecular formula:
C6H12O2
IUPAC Name:
butyl acetate
Details on test material:
- Name of test material (as cited in study report): n-butyl acetate
- Physical state: clear liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
6 hours per day, 5 days per week
Duration of test:
13 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 500, 1500, 3000
Basis:
nominal conc.
No. of animals per sex per dose:
10 males per dose
Control animals:
yes, sham-exposed
Details on study design:
- tissues were removed at necropsy (12/14/94) at Eastman Kodak Company and shipped to RTI overnight
- right testes from 40 animals were embedded in plastic, then cut, and slides prepared and stained for histological evaluations (fixation at necropsy: Millonig's fixative = NBF formalin diluted with phosphate buffered sline at pH 7.4; embedded in glycol methacrylat, one slight per testes stained with hematoxylin and eosin and the other with hematoxylin and periodic acid Schiff's reagent)
- left testes and left epididymidies from the same animals were frozen and processed to determine sperm concentrations (counting of homogenization resistant spermatids or sperms)
Statistics:
- Bartlett's test for homogeneity of variances and normality of distribution
- anayllis of variance for overall significance
- Dunnett's test for comparisons of dosed groups to the controls

Results and discussion

Effect levels

Dose descriptor:
NOAEC
Effect level:
3 000 ppm
Sex:
male
Basis for effect level:
other: no effects on epididymial spermatozoa counts or testicular spermatid counts; the analytical exposure concentration for the 3000 ppm group was 3010 ppm (14.5 mg/L)

Observed effects

- testicular weight and testicular spermatid head counts showed no difference in the various treatment groups
- there was no statistical difference between epididymal weights and epididymal spermatozoa count between control and treatment groups; one, four, five, and four animals from the dose groups 0, 500, 1500 and 3000 ppm, respectively, had low counts (

Any other information on results incl. tables

Effects of n-Butyl Acetate on Sperm Parameters in Sprague Dawley Rats

 

 

n-Butyl Acetate (ppm)

 

0

500                              1500

3000

Testis:

 

 

 

 

Testicular Weight (g)

1.78 ± 0.04

1.73 ± 0.07

1.79 ± 0.06

1.74 ± 0.04

Testicular Spermatict:

 

 

 

 

Total Count (x 106)

105.00 ± 14.27

107.30 ± 14.24

116.10 ± 8.61

89.80 ± 10.21

Count per mg (x 103)

58.74 ± 7.46

61.93 ± 7.50

65.26 ± 5.13

51.54 ± 5.55

Epididymis:

 

 

 

 

Epididymidal Weight (mg)

823.42 ± 36.16

788.23 ± 16.86

764.73 ± 21.51

736.27 ± 25.81

Epididymidal Spermatozoa:

 

 

 

 

Total Count (x 106)

33.36 ± 5.09

23.04 ± 6.12

25.20 ± 10.33

18.48 ± 4.91

Count per mg (x 103)

41.48 ± 6.67

29.12 ± 7.61

33.15 ± 13.71

24.14 ± 6.15

Values are means ± standard error of the means; n=10. Testes weights are from fresh tissue taken at necropsy. Epididymides weights are from frozen tissue taken at the time the spermatozoan counts were done.

ANOVA detected no significant differences among dose groups.

Applicant's summary and conclusion

Conclusions:
Inhalation exposure of n-butyl acetate at levels up to 3000 ppm (14.5 mg/L) for 13 weeks had no effect on the number of maturing spermatids or spermatozoa in male Sprague Dawley rats when epxosure began on at least eight weeks of age.
Executive summary:

Male and female Sprague-Dawley rats were exposed to nominal concentrations of 0, 500, 1500 or 3000 ppm of n-butyl acetate for 6 hours per day, 5 days per week for 13 consecutive weeks. The time-weighted average analytical concentrations were within 10% of the target concentrations. At the end of the exposure period the animals were necropsied and testes and epididymis of the male animals (10 males per dose group) were collected and processed for the assessment of sperm count. n-Butyl acetate exposure had no effect on epididymidal spermatozoa counts or testicular spermatid counts. Testicular staging and determination of spermatogenic index was not performed. The NOAEC for andrological effects in this study was 3000 ppm (14.5 mg/L) (Francis and Fail, 1995; Bernard and David, 1996; David et al., 2001).

The study is reliable with restrictions (RL2).