Registration Dossier

Toxicological information

Toxicity to reproduction

Currently viewing:

Administrative data

Endpoint:
fertility, other
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Original publication in Czech; only few data could be extracted from an English abstract and from tables; However, peer reviewed data used as supporting data for HPV submission (US EPA); Scientifically acceptable.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Mutagenic and gonadotoxic properties of trioxane and dioxolane
Author:
Baranski B et al.
Year:
1984
Bibliographic source:
Med Pr 35: 245-255
Reference Type:
secondary source
Title:
1,3,5-TRIOXANE, CAS Number 110-88-3, USEPA HPV Challenge Program Submission
Author:
Trioxane Manufacturers Consortium Members, BASF Performance Copolymers, LLC (Formerly Ultraform Company) and Ticona
Year:
2000
Bibliographic source:
USEPA HPV Submission

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: Test conduct was similar to OECD Guideline 478; the study was a combination between Dominant lethal assay and Fertility study.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Trioxane
No further data

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
Designation: albino Wistar rats
Source: no data
Age at test initiation: 3.5 to 4 months old
Body weight at test initiation: 300 to 320

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure (if applicable):
not specified
Vehicle:
other: air
Details on exposure:
- Males only were treated with the test substance by inhalation over a period of 12 months;
- The concentration of test material was measured by chromatography;
- Mating was conducted during one week at the end of the treatment period;
- Mating ratio was 2 untreated females: 1 treated male;
- The treated males were observed and examined for mortality and clinical symptoms of toxicity, and body weights were recorded;
- At test ending, the males were sacrificed for the purpose of necropsy; particular attention was given to the reproductive organs;
- Dams were sacrificed 13-14 days after the middle of mating intervals;
- The number of pregnant dams, live fetuses, dead implants, total implants, pre-implantation losses and corpora lutea were considered as parameters for the assessment of a dominant lethal effect, which was the main aim of present study.
Details on mating procedure:
- Mating was conducted during one week at the end of the treatment period;
- Mating ratio was 2 untreated females: 1 treated male;
- The treated males were observed and examined for mortality and clinical symptoms of toxicity, and body weights were recorded;
- At test ending, the males were sacrificed for the purpose of necropsy; particular attention was given to the reproductive organs;
- The number of pregnant dams, live fetuses, dead implants, total implants, pre implantation losses and corpora lutea were considered.
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
12 months
Frequency of treatment:
5 hours/day
Five days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 2500 mg/m3 (i.e. 0.25 mg/l)
Basis:

No. of animals per sex per dose:
14 animals were used
Control animals:
yes, concurrent vehicle

Examinations

Statistics:
Kruskal-Wallis Test followed by non-parametric tests for groups with and without normal distribution

Results and discussion

Results: P0 (first parental animals)

Details on results (P0)

- Histopathology of the testes revealed no differences between control and treated animals with regard to Leydig cells; seminiferous tubule pathology was not reported;
- All considered reproductive parameters (number of pregnant dams, live fetuses, dead implants, total implants, pre implantation losses and corpora lutea) were inconspicuous, i.e., without treatment-related changes;
- No mortalities were observed;
- No data on clinical symptoms of toxicity and body weight were reported;
- No data on organ weights were reported.

Effect levels (P0)

Dose descriptor:
NOAEC
Remarks:
Fertility
Effect level:
0.25 mg/L air
Sex:
male
Basis for effect level:
other: Assuming a 270 ml/min volume, a mean body weight of 350 g and 100% absorption, the test concentration of 0.25 mg/l corresponded to a dosage of 580 mg/kg bw/day.
Remarks on result:
other: Generation not specified (migrated information)

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

The prolonged exposure of male rats to 0.25 mg/l air of  Trioxane did not affect the fertility of males.
No histopathological changes in the testes were reported.

Applicant's summary and conclusion