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Toxicity to reproduction: other studies

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toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no Guideline followed; dosing and calculation of internal doses not described; GLP not followed;

Data source

Reference Type:

Materials and methods

Principles of method if other than guideline:
no guideline followed
GLP compliance:
not specified
Type of method:
in vivo

Test material

Constituent 1
Chemical structure
Reference substance name:
Triphenyl phosphate
EC Number:
EC Name:
Triphenyl phosphate
Cas Number:
Molecular formula:
triphenyl phosphate
Specific details on test material used for the study:
TPP, purity > 99%, purchased from Sigma-Aldrich

Test animals

Details on test animals or test system and environmental conditions:
- Source: China National Laboratory Animal Resource Center (Shanghai, China)
- Age at study initiation: (P) x wks; (F1) x wks
- Weight at study initiation: (P) Males: x-x g; Females: x-x g; (F1) Males: x-x g; Females: x-x g
- Fasting period before study:
- Housing:
- Use of restrainers for preventing ingestion (if dermal): yes/no
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):


Results and discussion

Any other information on results incl. tables

In a publication of Chen et al. (2015) seven male mice/group were orally treated with 100 and 300 mg/kg/bw/day triphenyl phosphate in food for 35 days in a non-GLP and non-Guideline conform study. No stability, homogeneity and accuracy data are given for the test item in the food. The study design is not transparent since the application of test item and the calculation of effective doses is not comprehensible. Parameters investigated are restricted to body weight development, liver (weight, biochemical parameters and gene expression) and testes (weight and testosterone concentration). Additionally, the right testis of 2 males per group is investigated by histopathology for the number of seminiferous tubules.

The mean final body weight at termination is reported to be significantly lower in the 300 mg group than in the control group. The values can, however, only be estimated from figures and are about 32 or 35 g in the control group (different values shown) and about 28 g (i.e. 87.5% or 80% of control value, respectively) in the 300 mg group. Liver weight is not affected by triphenyl phosphate treatment. Different enzyme activities in the liver and their related gene expression were reported to be affected by triphenyl phosphate exposure pointing to oxidative stress. However, the significance of such measurements is not clear.

For the males (n=7) treated with 300 mg/kg bw a significant decrease in absolute testes weight (minus 18.9%) versus control is reported. No information is given for testes weights relative to body weight. Since body weight reduction is up to 20% at this dose a distinct influence on testes weight by general toxicity can be expected.  

It is described that 300 but not 100 mg/kg bw/day of triphenyl phosphate resulted in slight histopathological changes in the testes (slight Sertoli cell disorganization, reduced number of seminiferous tubules) and in a decrease of testicular testosterone levels. However, only 2 animals per dose were included in the histopathological investigations and the testosterone levels may be a result of reduced testes/body weight and do not as such point to an adverse effect on reproduction.

In summary, effects described as adverse are small and of unclear biological relevance. Together with technical insufficiencies and poor documentation this investigation is not of relevance for the assessment of potential effects of triphenyl phosphate on the reproductive toxicity of mice.

Applicant's summary and conclusion