Registration Dossier

Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
other information

Data source

Reference
Reference Type:
publication
Title:
U.S. EPA HIGH PRODUCTION VOLUME CHEMICAL CHALLENGE PROGRAM - ISODECYLJPHENYL PHOSPHITE CATEGORY
Year:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
Doverphos 10, Batch 237T03101
purity 99.7%

Test animals

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

Administration / exposure

Route of administration:
oral: gavage
Details on mating procedure:
Premating exposure period for males and females: 2 weeks
Duration of treatment / exposure:
16 weeks
Premating exposure period for males and females: 2 weeks
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
5 mg/kg bw/day (actual dose received)
Dose / conc.:
15 mg/kg bw/day (actual dose received)
Dose / conc.:
40 mg/kg bw/day (actual dose received)

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

open allclose all
Dose descriptor:
NOAEL
Effect level:
15 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: reduced body weights, ataxia, and foot splay
Dose descriptor:
NOAEL
Remarks:
fertility
Effect level:
40 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects on fertility

Results: F1 generation

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
15 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: profound toxicity, including increased mortality and reduced pup body weights/litter

Any other information on results incl. tables

TPPi administered by gavage once daily at 0, 5, 15 and 40 mg/kg/day to parental F0 CD (SD) rats, 10/sex/group, through prebreed, mating and gestation and lactation and direct dosing to the F1 offspring (10/sex/group) from weaning to scheduled sacrifice, resulted in adult F0 parental toxicity at 40 mg/kg/day, increasing over time (reduced body weights, ataxia, and foot splay). Reproductive toxicity was not present in F0 males or females. There was profound F1 offspring toxicity observed postnatally during lactation at 40 mg/kg/day (so the group was terminated on pnd 21) , including increased mortality, especially for pnd 0-4 and reduced pup body weights/litter starting on pnd 7-21. Acquisition of puberty in F1 males and females was unaffected. Twenty eight-day males (same as F0) and females and 28 day recovery males and females exhibited the same progressive systemic toxicity at 40 mg/kg/day as in the F0 parental animals, although the effects were less severe, most likely due to the shorter dosing duration.

Applicant's summary and conclusion

Conclusions:
The F0 male and female systemic no observable adverse effect (NOAEL) was 15 mg/kg/day. The NOAELs for F0 reproductive toxicity were at or above 40 mg/kg/day for males and females. The NOAELs for F1 offspring toxicity during lactation were 15 mg/kg/day for males and females. The F1 male and female systemic NOAEL was also 15 mg/kg/day.