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Toxicological information

Toxicity to reproduction

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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable and well documented

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
Principles of method if other than guideline:
PPG-844 was administered continuously in the diet to CD rats (f0 generation, 60 males and 120 females; 15 males and 30 females/group) at dose levels of 0, 50, 500 or 2000 ppm for 14 weeks prior to mating and throughout mating, gestation and lactation periods. All F0 animals were sacrificed after weaning of the F1 generation. One hundred and eighty weanlings (15 males and 30 females/group) were selected to produce the F2 generation and received the test substance at the same dose levels noted above for ca. 18 weeks prior to mating and throughout the mating, gestation and lactation periods. All F2 animals were sacrificed at weaning. The F1 parents remained on test and were sacrificed ca. 5 weeks after the last F2 litter was weaned.
The main weekly test substance intake values for the treated animals during growth periods were as follows: F0 animals (male/female) - 3.3/4.0 (low-), 33.4/40.6 (mid-) and 132.2/154.9 (hig-dose) mg/kg bw; and f1 animals - 3.5/4.2, 34.1/42.0 and 147.4/177.3 mg/kg bw, respectively.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test substance:PPG-844 technical
Active ingeredient: assume 100.0%
Description: viscous, brown fluid

Test animals

Species:
rat
Strain:
other: Charles River CD
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
corn oil
Details on mating procedure:
F0 generation: One male was co-housed with the same 2 females from the same treatment group nightly until evidence of mating was observed or until 15 days had elapsed. Once mated, females werwe removed from the mating unit and housed individually for the raminder of gestation.
F1 generation: One male was co-housed with the same 2 females from the same treatment group nightly until evidence of mating was observed or until 15 days had elapsed. Once mated, females werwe removed from the mating unit.to achive a greater number of matings, the initial procedure was extended.
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
F0 males - 169 days
Fo females - 170 days
F1 males - 243 to 246 days
F1 females - 243 to 246 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
The main weekly test substance intake values for the treated animals during growth periods were as follows: F0 animals (male/female)-3.3/4.0, 33.4/40.6 and 132.2/154.9 mg/kg bw; and F1 animals-3.5/4.2, 34.1/42.0 and 147.4/177.3 mg/kg bw, respectively.
Basis:
nominal in diet
No. of animals per sex per dose:
15 males and 30 females/dose
Control animals:
yes, plain diet

Results and discussion

Results: P0 (first parental animals)

Effect levels (P0)

Dose descriptor:
NOEL
Effect level:
50 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: F0 animals - 50 ppm = 3.3/4.0 mg/kg bw

Results: F1 generation

Effect levels (F1)

Dose descriptor:
NOEL
Generation:
F1
Effect level:
50 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: F1 animals - 50 ppm = 3.5/4.2 mg/kg bw

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

Treatment of rats with PPG-844 Technical through two generations at a daily dietary level of 50 ppm produced no adverse effects on reproductive performance or fertility. Likewise, no adverse effects of treatment were evident in low-dose adult animals through either generation or in pups delivered and weaned to these same animals.

At the mid-dose level (500 ppm), treatment related effects were evident in body weight data (F0 and F1 males - adult generations), male mating indices (reduced for F1 males) and organ weight data (Fl females - increased relative liver weight data). Pups weaned to mid-dose females during the F1 litter interval had reduced weights; however, no such effect was evident in the F2 offspring and no adverse effects of treatment were evident in pup survival incidences or organ weight data during either litter interval. Postmortern and microscopic evaluations of mid-dose adult and offspring generations revealed no adverse effect of treatment. At the highdose level (2000 ppm) , adverse effects of treatment were evident in increased mortality (Fl adults), reduced body weights (F0 and F1 adults), and organ weight data (increased brain to body weight ratios, lower kidney weights and increased liver, spleen wei ght data). Pups delivered and weaned to high-dose females experienced lower survival rates; lower growth rates (reduced pup weight data) during both litter intervals; and organ weight effects (brain, heart, kidneys , testes and spleen). Postmortern and microscopic evaluation of

F1 adult animals revealed compound-related toxic effects in the liver (both sexes) and testes (Fl males that died during study). Postmortern and micrrocopic evaluation of the F1 and F2 offspring weaned to high-dose females revealed no compound-related effects.

Applicant's summary and conclusion

Executive summary:

PPG-844 was administered continuously in the diet to CD rats (f0 generation, 60 males and 120 females; 15 males and 30 females/group) at dose levels of 0, 50, 500 or 2000 ppm for 14 weeks prior to mating and throughout mating, gestation and lactation periods. All F0 animals were sacrificed after weaning of the F1 generation. One hundred and eighty weanlings (15 males and 30 females/group) were selected to produce the F2 generation and received the test substance at the same dose levels noted above for ca. 18 weeks prior to mating and throughout the mating, gestation and lactation periods. All F2 animals were sacrificed at weaning. The F1 parents remained on test and were sacrificed ca. 5 weeks after the last F2 litter was weaned.

The main weekly test substance intake values for the treated animals during growth periods were as follows: F0 animals (male/female) - 3.3/4.0 (low-), 33.4/40.6 (mid-) and 132.2/154.9 (hig-dose) mg/kg bw; and f1 animals - 3.5/4.2, 34.1/42.0 and 147.4/177.3 mg/kg bw, respectively.

No adverse effects on reproductive peformance or fertility were seen in the low-dose group (50 ppm). Therefore a NOEL of 50 ppm (= ca. 3.3/4.0 mg/kg bw) was determined.