Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Adopted according to OECD SIDS (publicly available peer reviewed source). Original document not available.

Data source

Referenceopen allclose all

Reference Type:
secondary source
Title:
SIDS Initial Assessment Report For SIAM 16 (Triethyl Phosphite), 2003 Paris.
Author:
OECD
Year:
2003
Bibliographic source:
UNEP Publications
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Version / remarks:
(adopted 1983)
Deviations:
no
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Reference substance name:
Triethylphosphite
IUPAC Name:
Triethylphosphite
Details on test material:
Purity: 98.8%

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
Paraffinum perliquidum
Details on exposure:
Dose volume: 5 mL/kg bw (10 mL/kg bw in the positive control)
Duration of treatment / exposure:
Not applicable.
Frequency of treatment:
Single treatment.
Post exposure period:
16, 24, and 48 h after treatment.
Doses / concentrations
Remarks:
Doses / Concentrations:
1500 mg/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide, 20 mg/kg bw, dissolved in deionised water.
Route of application: intraperitoneally. Animals were sacrificed 24 hours after the administration.

Examinations

Tissues and cell types examined:
Normochromatic and polychromatic erythrocytes in blood smears prepared from femur bone marrow.
Details of tissue and slide preparation:
PREPARATION OF SPECIMENS: at least one intact femur was prepared from each sacrificed animal, and smears were prepared according to the method as described by Schmid (Mut. Res. 31, 9-15, 1975).
Evaluation criteria:
EVALUATION: Coded slides were evaluated using light microscopy. Generally, 1000 polychromatic erythrocytes were counted per animal. The incidence of cells with micronuclei was determined, as well as the ratio of polychromatic to normochromatic erythrocytes (number of normochromatic erythrocytes per 1000 polychromatic ones). In addition, also the number of micronucleated normochromatic erythrocytes was determined.

ASSESSMENT CRITERIA: A result was considered positive if, at any of the intervals, there was a relevant and significant increase in the number of polychromatic erythrocytes showing micronuclei in comparison to the negative control. A test was considered negative if there was no relevant or significant increase in the rate of micronucleated polychromatic erythrocytes at any time. A test was also considered negative if there was no significant increase in that rate which according to the laboratory`s experience was within the range of negative controls.

ACCEPTANCE CRITERIA: A test was considered acceptable if the figures of negative and positive controls were within the expected range, in accordance with the laboratory`s experience and/or the available literature data.
Statistics:
Standard deviation, Wilcoxon`s non-parametric rank sum test at a 5% significance level, or one-sided chi-square-test, if the micronulei rate for polychromatic erythrocytes was increased in the negative controls.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
Clinical signs as well as a shift in PCE/NCE ratio.
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
PRE-TEST:
In a pre-test groups of five females and five males were intraperitoneally administered with 1000 mg/kg bw, 1500 mg/kg bw, 1750 mg/kg bw and 2500 mg/kg bw triethyl phosphite dissolved in corn oil. The following symptoms were recorded up to 48 hours, starting at exposure levels of 1000 mg/kg bw: apathy, semianaesthetised state, roughened fur, staggering gait, sternal and lateral recumbency, spasm, twitching, shivering, difficulty in breathing and flat breathing. In addition, 2 of 5 animals died in the 1750 mg/kg bw group, and 4 out of 5 animals in the 2500 mg/kg bw group. As the test substance was shown to be not stable in corn oil at a concentration of 10 mg/mL, an additional study was performed with paraffinum perliquidum as vehicle. In this study no animal died after a single intraperitoneal dose of 1500 mg/kg bw. The following symptoms were recorded for up to 48 hours: apathy, roughened fur, staggering gait, sternal and lateral recumbency, spasm, shivering and difficulty in breathing.

TOXICITY:
All treated animals showed the following symptoms of toxicity after administration of 1500 mg/kg bw triethyl phosphite until sacrifice: apathy, semi-anaesthetised state, roughened fur, pallor, staggering gait, sternal position, spasm, twitching, shivering and difficulty in breathing. No symptoms were recorded for the control group. All animals survived until the end of the test.
There was an altered ratio between normochromatic and polychromatic erythrocytes with relevant variations noted for the 16 hours group.

CLASTOGENICITY:
No effect. There were also no relevant variations in results between males and females. The ratio of polychromatic to normochromatic erythrocytes was altered by the treatment with triethyl phosphite in the 16-hours group as shown in the following:
Negative control: 1000:711;
Triethyl phosphite: 1000:1450 (16 hours group);
Triethyl phosphite: 1000:940 (24 hours group);
Triethyl phosphite: 1000:1004 (48 hours group);
Positive control: 1000:680

There was no increase in the incidence of micronucleated polychromatic erythrocytes in the triethyl phosphite treated groups, whereas the positive control showed a significant increase:
Negative control: 2.0 +/- 1.3 / 1000;
Triethyl phosphite: 2.3 +/- 1.6 / 1000 (16 hours group);
Triethyl phosphite: 2.2 +/- 1.9 / 1000 (24 hours group);
Triethyl phosphite; 2.5 +/- 1.9 / 1000 (48 hours group);
Positive control: 15.9 +/- 5.9 / 1000

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative