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: inhalation

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

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

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: 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 or test system 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 / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/L air (analytical)

Doses / concentrations 2

Dose / conc.:

0.64 mg/L air (analytical)

Doses / concentrations 3

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:

body weight and weight gain

clinical biochemistry

clinical signs

haematology

histopathology: neoplastic

histopathology: non-neoplastic

mortality

organ weights and organ / body weight ratios

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.