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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 days
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Purity of test substance not reported, whole body exposure in a test chamber.

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 412 (Subacute Inhalation Toxicity: 28-Day Study)
Deviations:
yes
Remarks:
particle size distribution not determined
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 COBS
Sex:
male/female
Details on test animals and environmental conditions:
Young adult rats, no further details reported.

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
air
Remarks on MMAD:
MMAD / GSD: About 60% of particles with particle size of 10 µm or less.
Details on inhalation exposure:
Target concentrations of 0, 0.5, and 1.0 mg/l were administered for 6 hours per day for 5 days per week for 4 weeks.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Analytical concentrations of 0, 0.640, and 1.524 mg/l were determined, total dust weight per volume of air was recorded.
Duration of treatment / exposure:
6 hours per day for 5 days per week for 4 weeks.
Frequency of treatment:
5 days per week
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/L air (analytical)
Dose / conc.:
0.64 mg/L air (analytical)
Dose / conc.:
1.524 mg/L air (analytical)
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
yes, concurrent vehicle
Details on study design:
Dechlorane Plus 25 was administered by inhalation for 6 hours per day for 5 days per week for 4 weeks to groups of 5 males and 5 females at concentrations of 0, 0.5, or 1.0 mg/l nominal concentration corresponding to 0, 0.64, and 1.524 mg/l analytical concentration.
Positive control:
none

Examinations

Observations and examinations performed and frequency:
The following parameters were recorded: mortality daily, clinical signs of toxicity daily, bodyweights weekly, haematology at study start and end, clinical chemistry at study start and end, urinalyses at study start and end, macroscopic and microscopic pathology, organ weights.
Sacrifice and pathology:
All animals were subjected to macroscopic and microscopic pathology and organ weight determination.
Other examinations:
Haematolog and clinical chemistry including urinalysis.
Statistics:
not reported

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
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:
effects observed, treatment-related
Description (incidence and severity):
Slight diuresis in both treated groups
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
increased liver and lung weights in both treated groups
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
hepatocellular hypertrophy
Histopathological findings: neoplastic:
no effects observed
Details on results:
Increased liver weights with hepatocellular hypertrophy, increased lung weights without histological correlate, slight diuresis, all changes in both dose groups without dose-dependence, no clear adverse effect observed.

Effect levels

Key result
Dose descriptor:
NOAEC
Effect level:
1.524 mg/L air
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
haematology
clinical biochemistry
organ weights and organ / body weight ratios
histopathology: non-neoplastic
histopathology: neoplastic

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEC at 1.524 mg/l dust in air with slight effects on liver and lung and slight functional effects on the kidneys, no clear adverse effect observed, all changes are compatible with functional adaption, but occurred in both dose groups.
Executive summary:

Groups of 5 male and 5 female rats were exposed to Dechlorane Plus for 6 hours per day for 5 days per week in whole body exposure chambers at nominal concentrations of nominal 0.5 and 1.0 mg/l corresponding to analytical 0.64 and 1.524 mg/l for 28 days. In both dose groups slightly increased liver weights with hepatocellular hypertrophy, slightly increased lung weights, and slight diuresis were seen without dose-dependence. No clear adverse effect occurred. The NOAEC was determined at 1.524 mg/l.