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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
Study period:
90 days
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Only purity and physical chemical properties of test substance not given.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report Date:
1975

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Deviations:
yes
Remarks:
no ophthalmoscopy was performed
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Dechlorane Plus 25, no further details reported
Particle Size Distribution
TI, for weeks 1 through 4
Total number counted: 330, 433, 507, 386 µm
smallest particles observed: 2.5, 2.5, 2.0, 2.5 µm
largest particles observed: 110, 131, 112, 106 µm
TII, for weeks 1 through 4
Total number counted: 362, 411, 433, 421 µm
smallest particles observed: 2.0, 2.5, 2.5, 2.5 µm
largest particles observed: 130, 154, 142, 159 µm

Test animals

Species:
rat
Strain:
other: Charles River
Sex:
male/female
Details on test animals and environmental conditions:
Rats were included in the test at an age of 28 days. No information on environmental conditions reported.

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Dechlorane Plus 25 was blended into the diet in a high-speed blending apparaus. Fresh diets were prepared each week. The diet was offered ad libitum.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
90 days
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 ppm
Remarks:
Basis: nominal in diet
Dose / conc.:
10 000 ppm
Remarks:
Basis: nominal in diet
Dose / conc.:
30 000 ppm
Remarks:
Basis: nominal in diet
Dose / conc.:
100 000 ppm
Remarks:
Basis: nominal in diet
No. of animals per sex per dose:
15 males and 15 females per dose
Control animals:
yes, concurrent vehicle
Details on study design:
Groups of 15 male and 15 female rats were given diet containing Dechlorane Plus 25 at 0, 10,000, 30,000, or 100,000 ppm daily for 90 days.
Positive control:
none

Examinations

Observations and examinations performed and frequency:
mortality and clinical signs of toxicity daily, food consumption weekly, bodyweights weekly, haematology and clinical chemistry including urinalysis on days 45 and 84, macroscopic pathology including organ weight determination and microscopic pathology at the end of treatment.
Sacrifice and pathology:
All rats were subjected to necropsy and organ weight determination (weights of brain, gonads, heart, kidneys, liver, and spleen), in control animals and animals of the high dose group, microscopic pathology examination was performed. A total of 37 organs and tissues were examined histologically.
Statistics:
Analysis of variance, Tukey's or Scheffe's Multiple Comparison tests, Kruskel-Wallis Statistics and Multiple Comparisons.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
2 deaths accidental at blood collection in the high dose group
Mortality:
no mortality observed
Description (incidence):
2 deaths accidental at blood collection in the high dose group
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
slightly increased liver weight at the high dose
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
At the high dose level, slightly increased liver weight was seen without histological correlate. No other test substance related effects occurred.

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
>= 100 000 ppm
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: Besides slightly increased liver weights at the highest dose level without histological correlate, no test substance related effects at all were seen.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Dechlorane Plus 25 was essentially nontoxic upon administration in the diet at concentrations up to 10000 ppm.
Executive summary:

Dechlorans Plus 25 was administered to groups of 15 male and 15 female rats in the diet at concentrations of 0, 10,000, 30,000, or 100,000 ppm daily for 90 days. The following parameters were recorded: mortality, clinical signs of toxicity, bodyweights, food consumption, haematology, clinical chemistry and urinalysis, macroscopic and microscopic pathology including organ weights. Besides slightly increased liver weight without histological correlate, thus indicating a functional adaption of the liver to an increased metabolic load, no substance related effects were seen. Dechlorane Plus was essentially nontoxic. The NOAEL was determined at 100,000 ppm in diet corresponding to about 5,870 mg/kg bw for males and to about 7,670 mg/kg bw for females.