Registration Dossier

Administrative data

Endpoint:
two-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992
Reference Type:
publication
Title:
Two generation study of dietary tributyl phosphate in CD rats
Author:
Gerhart JM, Tyl RW, Myers CB, Marr MC, Brine DR, Seely JC
Year:
1993
Bibliographic source:
Toxicologist 13, 76 (1993)

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OTS 798.4700 (Reproduction and Fertility Effects)
Principles of method if other than guideline:
Male and female weanling rats (F0 generation) were administered tributyl phosphate in the feed at 0, 200, 700 and 3000 ppm, 30 animals/sex/dose, for 10 weeks. Animals were then randomly mated within treatment groups for a 3 week mating period to produce the F1 generation, with exposure continued. F0 males were necropsied after the mating period, with histologic evaluation of reproductive and target tissues for high dose and control males. F1 litters were culled to 8 pups on postnatal day (pnd) 4 and weaned on pnd 21. At weaning, 10 weanlings/sex/dose were necropsied and 30/sex/dose were selected as F1 parents of the F2 generation. Selected F1 weanlings, 30 sex/sex/dose, were administerd tributyl phosphate in the diet prebreed exposure period and then mated for a 3 week mating period as described above. At weaning of F2 litters, 10 weanlings/sex7dose were necropsied.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purity 99.7 %

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: diet
Details on mating procedure:
F1: 30 animals per sex per dose (F0 generation) were treated for 10 weeks followed by a 3 weeks mating period
F2: Selected F1 weanlings, 30/sex/dose were administered tributyl phosphate in the diet for a 11-week prebreed
exposure period and and then mated for a 3 week mating period
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
F0 generation: 10 weeks
F1 generation: 11 weeks
Frequency of treatment:
daily (feeding study)
Doses / concentrations
Remarks:
Doses / Concentrations:
200, 700 and 3000 mg/kg diet (approx 15, 53 and 225 mg/kg bw/day)
Basis:

No. of animals per sex per dose:
30/sex/dose
Control animals:
yes

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

open allclose all
Dose descriptor:
NOAEL
Effect level:
>= 3 000 ppm (nominal)
Sex:
male/female
Basis for effect level:
other: The NOAEL for reproductive toxicity was at least 3000 ppm (= 225 mg/kg bw)
Remarks on result:
other: Generation not specified (migrated information)
Dose descriptor:
NOAEL
Effect level:
ca. 200 ppm (nominal)
Sex:
male/female
Basis for effect level:
other: NOAEL for postnatal toxicity (reduced pup body weights) was at or below 200 ppm (15 mg/kg bw)
Remarks on result:
other: Generation not specified (migrated information)

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

with 700 and 3000 ppm reductions of body weights, weight
gain and food consumption during F0 and F1 prebreed dosing
periods, no signs of toxicity, no treatment related
mortality; with 200 ppm only transient effects on body
weight and food consumption. No NOAEL for adult toxicity. 
No evidence of reproductive organ histopathology at any
dose, no effect on pre- and postnatal mortality. NOAEL for
reproductive toxicity (reduced pup body weights) was at or

below 200 ppm.

Applicant's summary and conclusion

Executive summary:

Male and female weanling rats (F0 generation) were administered tributyl phosphate in the feed at 0, 200, 700 and 3000 ppm, 30 animals/sex/dose, for 10 weeks. Animals were then randomly mated within treatment groups for a 3 week mating period to produce the F1 generation, with exposure continued. F0 males were necropsied after the mating period, with histologic evaluation of reproductive and target tissues for high dose and control males. F1 litters were culled to 8 pups on postnatal day (pnd) 4 and weaned on pnd 21. At weaning, 10 weanlings/sex/dose were necropsied and 30/sex/dose were selected as F1 parents of the F2 generation. Selected F1 weanlings, 30 sex/sex/dose, were administerd tributyl phosphate in the diet prebreed exposure period and then mated for a 3 week mating period as described above. At weaning of F2 litters, 10 weanlings/sex7dose were necropsied.

The NOAEL for reproductive toxicity was at least 3000 ppm (= 225 mg/kg bw) and the NOAEL for postnatal toxicity (reduced pup body weights) was at or below 200 ppm (=15 mg/kg bw).