1,3,5-trioxane

Toxicity to reproduction

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

Reference

Reference 1

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 2

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

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

Test material information

Constituent 1

Reference substance name:

1,3,5-trioxane

EC Number:

203-812-5

EC Name:

1,3,5-trioxane

Cas Number:

110-88-3

Molecular formula:

C3H6O3

IUPAC Name:

1,3,5-trioxane

Details on test material:

Trioxane
No further data

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system 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 generation)

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.