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Toxicological information

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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: For the time being, the draft report is still undergoing a multi-tiered review that includes NTP staff review and external peer review. However, the data available on the NTP website are sufficiently detailed for a preliminary assessment.

Data source

Reference
Reference Type:
other: draft study report
Title:
Unnamed
Year:
2003

Materials and methods

Principles of method if other than guideline:
SPERMATID HEAD COUNT AND VAGINAL CYTOLOGY EVALUATIONS (SCVCE)
GLP compliance:
yes
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Supplier: Midwest Research Institute (MRI, Kansas City Ohio)
Batch: 88H1166
Purity: ca. 99%

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female

Administration / exposure

Route of administration:
dermal
Vehicle:
ethanol
Details on exposure:
For more details, see IUCLID about NTP study 2003 (Thirtheen-week subchronic dermal toxicity study of sodium thioglycolate (NaT) in Fischer 344 rats and B6C3F1 mice). See section 7.5.2
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
five times per week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 45, 90 and 180 mg/kg bw/d
Basis:

No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Details on study design:
Study DesignVaginal cytology slides and frozen left testes were received from BioReliance Corporation on March 28, 2003. The testes were stored in a freezer at -80°C ± 10°C. Sperm data sheets for rats and mice, which included body weights, sperm density, sperm motility, whole left epididymal, left cauda epididymal, and left testicular weights were provided.Frozen left testes and vaginal cytology slides from mice atdose levels of 0, 90, 180, and 360 mg/kg were analyzed. The tunica albuginea and associated blood vessels were removed from the parenchyma and the testicular parenchyma was allowed to thaw. The parenchyma was weighed andthen homogenized in a solution of 10% Dimethyl Sulfoxide (DMSO) in physiological saline, stained with 0.1% Trypan Blue and the number of spermatids was counted using a haemacytometer. The vaginal cytology slides were evaluated and the oestrous cycle stage (Prooestrus, Oestrus, Metoestrus or Dioestrus) was determined for each day (Cooper et al., 1993).The cycle length, number of cycles, number of cycling females, and number of females with a regular cycle were determined.
Statistics:
Most hypotheses were tested using the nonparametric multiple comparisons procedure of Dunn (1964) or Shirley (1977), as modified by Williams (1986). Shirley's test was designed to detect treatment-related differences when the response to treatment consistently increased (or decreased) with increasing dose. Although the test employs a smoothing algorithm to adjust for dose-response inversions, Dunn's test was more appropriate if the departure from monotonicity was severe. Jonckheere's test (1954) was used to ascertain whether there was sufficient evidence of a dose-related response to apply Shirley's test. If the p-value from Jonckheere's test was less than 0.01, Shirley's test was used; otherwise, Dunn's test was applied. An arcsine transformation was applied to vaginal cytology data, representing the proportion of the observation periods that an animal was in a given oestrous stage, to bring the data into closer conformance with normality assumptions. Treatment effects were investigated by applying a multivariate analysis of variance (Wilk's criterion) to test for the simultaneous equality of measurements across dose levels (Morrison, 1976). The pairwise comparisons for data expressed as a proportion were performed using the Chi-square test (Conover, 1971).All findings described in this report as "increased" or "decreased" were statistically significant as compared to the control group.

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
>= 180 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: No effect on the reproduction parameters

Observed effects

No effects were observed.

Any other information on results incl. tables

The male terminal body weight decreased by 7% and 5% at the dose levels of 90 mg/kg and 180 mg/kg respectively (Table R-1). The absolute and relative weights of male reproductive organs were all comparable across groups (Table R-1). The percent motility, the number of sperm per mg cauda, the total number of sperm per cauda, the number of spermatids per mg testis, and the total number of spermatids per testis were all comparable across all groups (Table R-2).

The female terminal body weight was comparable across all groups (Table R-3). The evaluation of vaginal smears revealed no significant differences among the females in the cycle length, number of cycles, number of cycling females, or number of females with regular cycles (Table R-4). The relative amount of time spent in oestrous stages was heterogeneous among treatment groups, but the pair-wise comparisons between each dosed group and the control group were not significant.

Applicant's summary and conclusion

Conclusions:
Sodium thioglycolate would not be a reproductive toxicant in male and female rats following 13 weeks of administration via dermal application at concentrations up to 180 mg/kg.
Executive summary:

The purpose of this study was to determine if exposure to sodium thioglycolate (NaT) affects the reproductive system by evaluating sperm parameters and vaginal cytology data. The potential toxic effects of this compound on male and female rat reproductive system was tested by evaluation sperm parameters and vaginal cytology data.

Four groups of Sprague Dawley rats (10 males and 10 females) were treated with sodium mercaptoacetate at 0, 45, 90, 180 mg/kg bw/d. Sodium mercaptoacetate was applied on skin during 13 weeks, 5 days a week.

For males, data sheets which included body weights, sperm density, sperm motility, whole left epididymal, left cauda epididymal, and left testicular weights were provided. Spermatids in the parenchyma were counted. For females, the vaginal cytology slides were evaluated and the oestrous cycle stage (Prooestrus, Oestrus, Metoestrus or Dioestrus) was determined for each day. The cycle length, number of cycles, number of cycling females, and number of females with a regular cycle were determined.

No effects with statistically significance were observed at any doses, neither males nor females.

Based on these results, sodium thioglycolate would not be a reproductive toxicant in male and female rats following 13 weeks of administration via dermal application at concentrations up to 180 mg/kg.