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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable and well documented GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Principles of method if other than guideline:
Thirty male and thirty female CD rats were fed 0, 40, 200, or 1000 ppm (males: 0, 2.9, 14, or 74 mg/kg/day; females: 0, 3.5, 17, or 85 mg/kg/day) PPG-844 in their diet for at least 91 consecutive days. Body weights and feed consumptions were collected weekly and abnormal appearance and behaviour were recorded throughout the study. clinical laboratory studies were conducted after 45 and 91 days on test. Major organs were weighed at terminal necropsy. Histopathological examination was conducted on all tissues from control and high lecel animals and on selected tissues in the low and mid level groups.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
PPG-844 = lactofen; purity: 72.4 %

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
corn oil
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
91 days (13 weeks)
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 40, 200, or 1000 ppm ( (males: 0, 2.9, 14, or 74 mg/kg/day; females 0, 3.5, 17, or 85 mg/kg/day)
Basis:
nominal in diet
No. of animals per sex per dose:
30 male and 30 female rats/dose
Control animals:
yes, plain diet

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOEL
Effect level:
14 mg/kg diet
Based on:
test mat.
Sex:
male
Dose descriptor:
NOEL
Effect level:
17 mg/kg diet
Based on:
test mat.
Sex:
female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Cumulative body weight gain was ca. 15% lower in the high level males, and absolute body weight was ca. 11% lower after 13 weeks on test. There were no differences apparent in high level females.

At 45 days on test, high level males had significant lower RBC, hemoglobin, and hematocrit values and females had lower hemoglobin values. however , after 90 days on test there were no significant differences in hematology parameters..

Clinical chemistry values indicated hepatic and renal dysfunction or damage in high level males and females. At 45 fays significant increase in BUN, choloesterol, AST, ALT, alkaline phosphatase and total bilirubin were noted for males and in cholosterol and total bilirubin for females.

At necropsy, liver weights and liver weight ratios were increased in high level males and females, and kidney weights were increased slightly. approximately 80% of the males and 15% of the females had dark livers and dark kidneys while none were found in the control groups.

Histopathologic examination revealed an accumulation of pigment in hepatocytes and Kupffer cells in high level males and females and acidophilic degeneration of hepatocytes and bile duct hyperplasia in high level males.

There were no treatment related effects noted for any of the parameters measured in groups receiving 40 or 200 ppm (males: 2.9 or 14 mg/kg/day; females: 3.5 or17 mg/kg/day) PPG-844.

Applicant's summary and conclusion

Executive summary:

Thirty male and thirty female CD rats were fed 0, 40, 200, or 1000 ppm (males: 0, 2.9, 14, or 74 mg/kg/day; females: 0, 3.5, 17, or 85 mg/kg/day) PPG-844 in their diet for at least 91 consecutive days. Body weights and feed consumptions were collected weekly and abnormal appearance and behaviour were recorded throughout the study. clinical laboratory studies were conducted after 45 and 91 days on test. Major organs were weighed at terminal necropsy. Histopathological examination was conducted on all tissues from control and high lecel animals and on selected tissues in the low and mid level groups.

Cumulative body weight gain was ca. 15% lower in the high level males, and absolute body weight was ca. 11% lower after 13 weeks on test. There were no differences apparent in high level females.

At 45 days on test, high level males had significant lower RBC, hemoglobin, and hematocrit values and females had lower hemoglobin values. however , after 90 days on test there were no significant differences in hematology parameters..

Clinical chemistry values indicated hepatic and renal dysfunction or damage in high level males and females. At 45 fays significant increase in BUN, choloesterol, AST, ALT, alkaline phosphatase and total bilirubin were noted for males and in cholosterol and total bilirubin for females.

At necropsy, liver weights and liver weight ratios were increased in high level males and females, and kidney weights were increased slightly. approximately 80% of the males and 15% of the females had dark livers and dark kidneys while none were found in the control groups.

Histopathologic examination revealed an accumulation of pigment in hepatocytes and Kupffer cells in high level males and females and acidophilic degeneration of hepatocytes and bile duct hyperplasia in high level males.

There were no treatment related effects noted for any of the parameters measured in groups receiving 40 or 200 ppm (males: 2.9 or 14 mg/kg/day; females: 3.5 or17 mg/kg/day) PPG-844.

Therefore the NOEL for male rats is 14 mg/kg bw and for female rats 17 mg/kg bw.