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

Genetic toxicity: in vivo

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

Study period:

1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Rationale: GLP Guideline study

Data source

Reference

Reference Type:

other: Unpublished data

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)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Phosphorous acid, diphenyl isodecyl ester

Molecular formula:

C22H31O3P

IUPAC Name:

Phosphorous acid, diphenyl isodecyl ester

Constituent 2

Reference substance name:

Triphenyl phosphite

EC Number:

202-908-4

EC Name:

Triphenyl phosphite

Cas Number:

101-02-0

Molecular formula:

C18H15O3P

IUPAC Name:

triphenyl phosphite

Constituent 3

Reference substance name:

Diisodecyl phenyl phosphite

EC Number:

247-098-3

EC Name:

Diisodecyl phenyl phosphite

Cas Number:

25550-98-5

Molecular formula:

C26H47O3P

IUPAC Name:

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

Constituent 4

Reference substance name:

Grouped, low level constituents (1) - see description

Molecular formula:

C21H29O3P and C23H33O3P

IUPAC Name:

Grouped, low level constituents (1) - see description

Constituent 5

Reference substance name:

Grouped, low level constituents (2) - see description

Molecular formula:

N/A

IUPAC Name:

Grouped, low level constituents (2) - see description

Constituent 6

Reference substance name:

Triisodecyl phosphite

EC Number:

246-998-3

EC Name:

Triisodecyl phosphite

Cas Number:

25448-25-3

Molecular formula:

C30H63O3P

IUPAC Name:

Phosphorus acid, triisodecyl ester

Constituent 7

Reference substance name:

Grouped, low level constituents (3) - see description

Molecular formula:

N/A

IUPAC Name:

Grouped, low level constituents (3) - see description

Test material form:

liquid

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
- Fasting period before study: The animals were fasted overnight prior to dosing.
- Housing: group-housed in plastic caging maintained in a controlled environment
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22oC
- Air changes (per hr): 30 air changes/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

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

Duration of treatment / exposure:

24 hours

Frequency of treatment:

Two oral gavage doses administered over 24 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 2250, 4500, and 9000 mg/kg (total dose)
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

The concurrent positive control group was given an intraperitoneal injection of mitomycin C at a concentration of 0.4 mg/mL.

Examinations

Tissues and cell types examined:

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

Positive controls validity:

valid

Additional information on results:

After administration of DPDP at 9000 mg/kg, signs of toxicity (hypopnea and lethargy) were observed 30 minutes after dosing in both sexes. The symptoms decreased over the next few hours and were not observed 3 hours after administration. A single female died within 7 hours after this highest dose. Macroscopic examination at post mortem did not reveal abnormalities in any animal. No toxic reactions were observed in the corn oil negative control group or the 2250 and 4500 mg/kg group. After administration of mitomycin C, no toxic reactions or mortality were observed.

Any other information on results incl. tables

DPDP Mouse Micronucleus Results

 

Test Group	Micronucleated Cells per 1000 PCEs/animal mean (range)	PCE/NCE Ratiomean (range)
Negative Control	0.4 (0–2)	2.69 (1.19–5.29)
Mitomycin C	32.2 (9-96)	9.09 (14.73)
2250 g/kg DPDP	0.4 (0–1)	*
4500 g/kg DPDP	1.1 (0-3)	*
9000 g/kg DPDP	0.8 (0–2)	2.32 (1.36–3.27)
Historical Control	0.79 (0.1-1.8)	0 - 5

 

*Criteria for evaluating results: 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.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Based on the conditions of this study, it was concluded that the test article, DPDP, was considered to be negative in both sexes for mutagenic potential and bone marrow toxicity when administered orally.

Executive summary:

Based on the conditions of this study, it was concluded that the test article, DPDP, was considered to be negative in both sexes for mutagenic potential and bone marrow toxicity when administered orally.