[No public or meaningful name is available]

Toxicity to reproduction

Administrative data

Endpoint:

extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Also assessed by OECD.

Data source

Reference

Reference Type:

publication

Title:

Teratogenic potential of triphenyl phosphate in Sprague-Dawley (Spartan) rats.

Author:

Welsh JJ, Collins TFX, Whitby KE, Black TN, Arnold A

Year:

1987

Bibliographic source:

Toxicol. Ind. Health 3(3), 357-369

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]

Principles of method if other than guideline:

Method: other: see freetext

GLP compliance:

not specified

Justification for study design:

Study is used as a read-across substance in the context of a category (see category justification document). For the category members the whole database with additional fertility studies has to be considered.

Test material

Test material information

Constituent 1

Reference substance name:

Triphenyl phosphate

EC Number:

204-112-2

EC Name:

Triphenyl phosphate

Cas Number:

115-86-6

Molecular formula:

C18H15O4P

IUPAC Name:

triphenyl phosphate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Details on exposure:

exposure period 91 days

Details on mating procedure:

TPP was administered in the diet for 91 days in a subchronic study. At the completion of this study, females were mated with males from the same group. All remained on the same diet as in the subchronic study until day 20 of gestation when dams were sacrificed.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Exposure period: 91 days
Duration of test: 3 months

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0.25, 0.5, 0.75 or 1 % in feed (= 166, 341, 516, 690 mg/kg)
Basis:
no data

No. of animals per sex per dose:

Four treated groups and an untreated control each consisting of 40 rats/sex

Control animals:

yes, concurrent no treatment

Details on study design:

TPP was administered in the diet for 91 days in a subchronic study. At the completion of this study, females were mated with males from the same group. All remained on the same diet as in the subchronic study until day 20 of gestation when dams were sacrificed.

Examinations

Parental animals: Observations and examinations:

see below

Oestrous cyclicity (parental animals):

see below

Sperm parameters (parental animals):

no effects

Litter observations:

no effects observed

Postmortem examinations (parental animals):

no adverse effects noted

Postmortem examinations (offspring):

no adverse effects noted

Statistics:

no data

Reproductive indices:

see below

Offspring viability indices:

see below

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

effects observed, treatment-related

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

Details on results (P0)

No findings reported. Food consumption increased in pregnant dams (not dose depedant).

Effect levels (P0)

Dose descriptor:

NOEL

Effect level:

690 mg/kg bw/day (actual dose received)

Sex:

male/female

Basis for effect level:

other: no adverse effects were reported

Target system / organ toxicity (P0)

Critical effects observed:

no

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

no effects observed

Histopathological findings:

no effects observed

Details on results (F1)

No adversed effects were observed.

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

690 mg/kg bw/day (actual dose received)

Sex:

male/female

Basis for effect level:

other: Examination of the foetuses indicated no effect on body weight, crown-rump length, and sex distribution. There were no external variations or skeletal variations which could be related to TPP exposure.

Target system / organ toxicity (F1)

Critical effects observed:

no

Overall reproductive toxicity

Reproductive effects observed:

no

Any other information on results incl. tables

OBSERVATION: no findings reported
FOOD CONSUMPTION: increased in pregnant dams (not dose-dependent)
BODY WEIGHT: decreased during pregnancy (non-significant)
NECROPSY: no significant differences in number of corpora lutea,  implants, implantation efficiency, viable fetuses and number of early or  late deaths. 
As there was no effect on the litter size (indirectly measured by the  number of viable fetuses and implants) and both sexes were treated in the  study, these findings indicate that fertility is not adversely affected  by TPP in male and female rats.
parental NOEL = 690 mg/kg bw

Applicant's summary and conclusion

Conclusions:

Parental NOEL = 690 mg/kg bw

Executive summary:

Fertility and developmental toxicity were examined in a dietary study in Sprague-Dawley rats at doses of 0, 0.25, 0.50, 0.75, 1.0% corresponding to 0, 166, 341, 516 or 690 mg/kg bw/day. Forty males and forty females per group were treated for 3 months and mated afterwards. Animals were treated further throughout mating and gestation and killed at day 20 of gestation.

Effects on fertility- The study included treatment of males and females for three months prior to mating throughout gametogenisis and during mating and gestation. No significant differences were recorded in the number of corpora lutea, implants, implantation efficiency, viable fetuses and the number of early or late deaths between treated and control rats. No significant signs of parental toxicity were detected. As there were no effects on the litter size (indirectly measured by the number of viable fetuses and implants) and both sexes were treated in the study, these findings indicate that fertility is not adversely affected by TPP in male and female rats. The NOEL was 690 mg/kg bw/day.