Decahydronaphthalene

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Induction and exacerbation of hyaline droplet formation in the proximal tubular cells of the kidneys from male rats receiving a variety of pharmacological agents

Author:

Read NG, Astbury PJ, Morgan RJI, Parsons DN and Port CJ

Year:

1988

Bibliographic source:

Toxicology 52, 81-101

Materials and methods

Principles of method if other than guideline:

daily oral dosing up to 28 days

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Decahydronaphthalene

EC Number:

202-046-9

EC Name:

Decahydronaphthalene

Cas Number:

91-17-8

Molecular formula:

C10H18

IUPAC Name:

decahydronaphthalene

Details on test material:

decahydronaphthalene, purity not reported

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

no data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 10, 100, 1000 mg/kg bw/d
Basis:
actual ingested

No. of animals per sex per dose:

30 male
5 female

Control animals:

yes, concurrent vehicle

Details on study design:

5 males each were sacrificed on days 1, 3, 7, 14, 28 and 14 days post -treatment
5 females were sacrificed on day 28

Positive control:

no data

Examinations

Observations and examinations performed and frequency:

no data

Sacrifice and pathology:

no data

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

kidney toxicity in male rats at dose levels >10 mg/kg bw/d

Histopathological findings: neoplastic:

not specified

Details on results:

Increased incidences of hyaline droplets in the renal proximal tubule cells of male rats, increased cell turnover, and focal renal tubule damage were seen in the 100 and 1,000 mg/kg groups.

Effect levels

1

Key result

Dose descriptor:

NOAEL

Effect level:

> 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: no adverse effects were seen up to the highest dose level

2

Key result

Dose descriptor:

NOAEL

Effect level:

> 10 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: Kidney toxicity, hyaline droplets

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Male specific kidney toxicity was observed upon oral administration of decahydronaphthalene at dose levels of 100 and 1000 mg/kg bw/d administered by gavage. Hystology of kidneys identified possible mechanism for this sex and species specific toxicity.

Executive summary:

Kidneys from male and female Wistar rats dosed with Decalin, were examined by light and electron microscopy. Paraffin histology showed hyaline droplet accumulation in the renal proximal tubular cells of the male rats. Resin histology at both the light and electron microscope level, along with cytochemical procedures for acid phosphatase and the protein 'alpha 2U globulin', helped further in the characterisation of these cytoplasmic inclusions. These techniques confirmed that the accumulation of hyaline droplets seen by paraffin histology represented an increase in the size and number of secondary lysosomes which have been shown to be involved in protein uptake and metabolism. Time course studies showed that increased numbers of small dense lysosomes appear first, which then increase in size, presumably by fusion. Crystalloid bodies form in these large lysosomes eventually giving rise to rectilinear bodies. The accumulation of these protein laden secondary lysosomes took place primarily in the cells of the S1 and S2 segments of the proximal tubules. In extreme cases of lysosomal accumulation however, loading of the S3 segments was noted. In tubules where cellular inclusion loading was heavy, there was evidence of increased cell turnover. The kidneys of female rats appeared normal.