1,6,7,8,9,14,15,16,17,17,18,18-dodecachloropentacyclo[12.2.1.16,9.02,13.05,10]octadeca-7,15-diene

Repeated dose toxicity: dermal

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

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

Test material information

Constituent 1

Reference substance name:

1,6,7,8,9,14,15,16,17,17,18,18-dodecachloropentacyclo[12.2.1.16,9.02,13.05,10]octadeca-7,15-diene

EC Number:

236-948-9

EC Name:

1,6,7,8,9,14,15,16,17,17,18,18-dodecachloropentacyclo[12.2.1.16,9.02,13.05,10]octadeca-7,15-diene

Cas Number:

13560-89-9

Molecular formula:

C18H12Cl12

IUPAC Name:

1,2,3,4,7,8,9,10,13,13,14,14-dodecachloro-1,4,4a,5,6,6a,7,10,10a,11,12,12a-dodecahydro-1,4:7,10-dimethanodibenzo[a,e][8]annulene

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 or test system 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 / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

500 mg/kg bw/day (nominal)

Doses / concentrations 3

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:

body weight and weight gain

clinical signs

dermal irritation

gross pathology

haematology

histopathology: neoplastic

histopathology: non-neoplastic

mortality

organ weights and organ / body weight ratios

urinalysis

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.