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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
one-generation reproductive toxicity
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:
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

Test material

Reference
Name:
Unnamed
Type:
Constituent

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 animals)

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
Gross pathological findings:
no effects observed
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.