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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
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 and physical chemical properties of test substance not reported, the dose level was not analytically verified.

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 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
Deviations:
yes
Remarks:
Only two dose levels were investigated, the suspension of the test substance was applied openly without any covering
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid - liquid: suspension
Details on test material:
Dechlorane 25, 50% suspension in 3% aqueous methylcellulose

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
No further details reported

Administration / exposure

Type of coverage:
open
Vehicle:
other: 3% aqueous methylcellulose
Details on exposure:
After open application as 50% suspension in 3% aqueous methylcellulose, the substance remained in place for 24 hours until the next application. The animals received a plastic collar to avoid oral intake.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
28 days for up to 24 hours per day
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
500 mg/kg bw/day (nominal)
Dose / conc.:
2 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
5 males and 5 females
Control animals:
yes, concurrent no treatment
Details on study design:
Dechlorane 25 was applied epicutaneously to groups of 5 males and 5 females openly epicutaneously at dose levels of 500 or 2,000 mg/kg bw once daily for 5 days per week for 28 days. The application site was not covered, but the animals received collars to prevent oral intake. Negative controls remained untreated. The skin was scarified in two rabbits per sex per group before substance application.
Positive control:
none

Examinations

Observations and examinations performed and frequency:
The following parameters were recorded: mortality, clinical signs of toxicity, bodyweights, haematology, clinical chemistry, urinalysis, gross and microscoic pathology including organ weights.
Sacrifice and pathology:
All rabbits were subjected to necropsy and histological examination of a total of 38 organs and tissues including skin of the application site. Organ weights were recorded from brain, liver, kidneys, spleen, heart, gonads, thyroid gland, and adrenal glands.
Other examinations:
mortality, clinical signs of toxicity including skin reactions, haematology, clinical chemistry, urinalysis
Statistics:
not reported

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Description (incidence and severity):
minimal barely perceptible erythema in both dose groups in both sexes
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Water consumption and compound intake (if drinking water study):
not specified
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:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
No systemic effects of treatment observed in any animal in any group, only minimal local erythema at the application site without histological correlate after 18 and 20 applications. No local irritation was seen after one or up to 17 applications.

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
> 2 000 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
dermal irritation
body weight and weight gain
haematology
urinalysis
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic
histopathology: neoplastic

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Not systemically toxic at dose levels up to 2,000 mg/kg bw applied dermally for up to 24 hours per day for 5 days per week for 28 days. Minimal local irritation after 18 - 20 applications.
Executive summary:

Dechlorane 25 was not systemically toxic at dose levels up to 2,000 mg/kg bw. The NOAEL for systemic effects was above 2,000 mg/kg bw. Minimal local irritation was only observed after repeated application for more than 18 days. No irritation was seen after one day of dermal application.