Reaction products of triphenyl phosphite and isodecanol (1:2)

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Principles of method if other than guideline:

The protocol used is comparable to OECD Test Guideline 474.

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of triphenyl phosphite and isodecanol (1:2)

EC Number:

701-374-4

Cas Number:

25550-98-5

Molecular formula:

C26H47O3P

IUPAC Name:

Reaction products of triphenyl phosphite and isodecanol (1:2)

Details on test material:

- Name of test material (as cited in study report): Diisodecyl phenyl phosphite - Commercial, purity: Not stated (Phosphorus content = 7.09%)- Lot/batch No.: PDDP-002-03240A - Supplier: Borg Warner Company, Parkersburg, WV

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 18 and 21 grams
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Fasting period before study: fasted overnight prior to dosing.
- Housing: group-housed in plastic caging
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature:: 22oC
- Air changes: 30 air changes/hour
- Photoperiod: 12-hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: corn oil

Details on exposure:

The test article was administered (diluted in corn oil) via oral gavage to groups of mice (5/sex), at a volume of 0.1 mL per 10 grams of body weight.

Duration of treatment / exposure:

.

Post exposure period:

6 hours

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

2 500 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

5 000 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

10 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

Mitomycin C, The concurrent positive control group was administed by intraperitoneal injection at a concentration of 0.4 mg/mL.

Examinations

Tissues and cell types examined:

Bone marrow; erythrocytes

Details of tissue and slide preparation:

A direct bone marrow smear from each femur was placed onto a slide and prepared for microscopic analysis to determine the incidence of micronucleated cells per 1000 polychromatic erythrocytes per animal and the ratio of normochromatic to polychromatic erythrocytes (PCE/NCE ratio).

Evaluation criteria:

A material was considered to show evidence of mutagenic activity if it produced a statistically significant increase (p>0.05 using Wilcoxin’s ‘sum or ranks test’) in micronucleated cells compared to the concurrent negative control group values. If the erythrocyte ratios at the top dose were not significantly different from the concurrent negative control values, then the ratios of the two lower doses were not scored.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

See summary in "Additional information on results"

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

There was no statistically significantly difference between any of the test article treatments and the negative control. After administration of PDDP at all doses, signs of toxicity (hypopnea and lethargy) were observed 30 minutes after dosing. The symptoms decreased over the next few hours and were not observed 5 hours after each dose. At the top dose of 10000 mg/kg, there were 4 (2 males and 2 females) deaths. The animals were found dead between 2 and 5 hours after the second dose. Macroscopic examination at post mortem did not reveal abnormalities in any animal. After administration of mitomycin C, no toxic reactions or mortality were observed.

Any other information on results incl. tables

After administration of PDDP at all dosages, the group mean number of micronucleated cells per 1000 polychromatic erythrocytes per animal was comparable to the concurrent control value and within the laboratory standard range for negative controls obtained in 18 previous experiments. The PCE/NCE ratio for the test article 10,000 mg/kg was comparable to that of the negative corn oil control group.

The mean number of micronucleated cells per 1000 polychromatic erythrocytes per animal for the concurrent positive control group (mitomycin C) was significantly higher than the negative control group (27.7 versus 0.1, respectively). Also, the PCE/NCE for mitomycin C was significantly higher than the negative control group (7.52, range 3.24-16.37). Based on the conditions of this study, the test article, PDDP, was considered to be negative for mutagenic potential and bone marrow toxicity when administered orally.

Applicant's summary and conclusion

Conclusions:

Negative, no indication of genetic toxicity.

Executive summary:

After administration of PDDP at all dosages, the group mean number of micronucleated cells per 1000 polychromatic erythrocytes per animal was comparable to the concurrent control value and within the laboratory standard range for negative controls obtained in 18 previous experiments. The PCE/NCE ratio for the test article 10,000 mg/kg was comparable to that of the negative corn oil control group.

The mean number of micronucleated cells per 1000 polychromatic erythrocytes per animal for the concurrent positive control group (mitomycin C) was significantly higher than the negative control group (27.7 versus 0.1, respectively). Also, the PCE/NCE for mitomycin C was significantly higher than the negative control group (7.52, range 3.24-16.37). Based on the conditions of this study, the test article, PDDP, was considered to be negative for mutagenic potential and bone marrow toxicity when administered orally.