Decahydronaphthalene

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May - August 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study

Objective of study:

toxicokinetics

Principles of method if other than guideline:

NTP method detailed in the report

GLP compliance:

yes

Radiolabelling:

no

Species:

other: rat and mice

Strain:

other: F344/N rats and B6C3F1 mice.

Sex:

male/female

Route of administration:

inhalation: vapour

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

single 6-hour whole body inhalation exposure

Remarks:

Doses / Concentrations:
25, 100, or 400 ppm

Control animals:

no

Positive control reference chemical:

no positive control

Details on dosing and sampling:

Heparinized blood was collected from the retroorbital plexus (rats) or supraorbital sinus (mice) under 70% carbon
dioxide (in room air) anesthesia after exposure. Each animal was bled twice, once in each eye (except rats, which
were sampled three times at less than 5 minutes after exposure, 60 minutes, and approximately 1440 minutes after
exposure). Rats from all exposure groups were bled at 5 minutes or less and at 10, 20, 30, 60, 120, 240, 480, and
1440 minutes postexposure. Mice from the 25 ppm group were bled at 5 minutes or less and at 10, 20, 40, 60, 120,
240, and 360 minutes postexposure. Mice from the 100 and 400 ppm groups were bled at less than 5 minutes and
at 10, 20, 40, 60, 180, 360, and 480 minutes postexposure. Samples were stored at –70° C until analyses.

Test no.:

#1

Toxicokinetic parameters:

half-life 1st: 23.0-26.6 min

Test no.:

#1

Toxicokinetic parameters:

half-life 2nd: 418-511 min

Test no.:

#1

Toxicokinetic parameters:

AUC: 2.18-5.26 µg min/g ppm

Decalin exhibited biexponential blood elimination kinetics in rats and mice after a single 6-hour whole body inhalation exposure. A rapid initial phase (") representing elimination from blood and rapidly perfused tissues such as liver, lung, and kidney was followed by a slower phase ($) representing elimination from slowly perfused tissues such as muscle and fat. The biexponential curves, weighted using [mean decalin blood concentrations]–2, that were used to model the data and to estimate toxicokinetic parameters for rats are presented in Figures M1 and M2; parameter estimates, A0, ", B0, and $, were obtained from these models. The biexponential curves, weighted using [mean decalin blood concentration]–1, that were used to model the data and to estimate toxicokinetic parameters for mice are presented in Figures M2 and M3; parameter estimates, A0, ", B0, and $, were obtained from these models . The parameter estimates, A0, ", B0, and $ were used to calculate t½", t½$, C0, and AUC4.

Conclusions:

Decahydronaphthalene is rapidly eliminated by rats or mice following a single inhalation exposure. No sex differences were noted.
Therefore, no significant bioaccumulation potential is expected based on the study results.

Executive summary:

The single exposure inhalation study was designed to estimate toxicokinetic parameters relevant to the elimination

of decalin from the blood of F344/N rats and B6C3F1 mice. Male and female F344/N rats and B6C3F1 mice

received a single 6-hour whole body inhalation exposure to 25, 100, or 400 ppm decahydronaphthalene. Postexposure blood

samples were analyzed for decalin, and the results were used to estimate toxicokinetic parameters.

The half-lives for the initial elimination phase were not significantly different between sexes for rats and mice.

Differences in the terminal phase half-lives as a function of exposure concentration were also not significant

between sexes for rats or mice. At each decalin exposure concentration, no significant differences in the initial or

terminal half-lives as a function of sex for either species was observed. Half-lives for the initial elimination phase

were approximately 1.1 to 6.0 times shorter in mice than those in rats. Half-lives for the terminal elimination

phase in mice were approximately 3.4 to 5.4 times shorter than those in rats.

There are several conclusions that can be drawn from the PBPK model. First, it is not possible to detect any

differences in the metabolism of decalin between male and female mice in these data. There are significant

differences between male and female rats driven by the difference in kidney decalin concentrations. Second, the

model predicts a higher rate of metabolism for mice, but this metabolism pathway saturates at a lower

concentration than that in rats. Third, the model indicates that the highest dose (400 ppm) selected for the study

was at a concentration where metabolism was saturated. Finally, it is not possible to determine if the metabolism

and permeability parameters for male and female rats are the same; the only difference between the sexes were

parameters associated with the binding to alpha-2u-globulin.

Reference 2

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 1984 - July 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: published peer reviewed report

Objective of study:

metabolism

Principles of method if other than guideline:

Groups of male and female Fischer 344 rats with 7-9 animals/group were dosed intragastrically with 0.5 mL cis, trans decahydronaphthalene or water (controls) on an every-other-day regimen for 14 days. Urine was collected during the first two day following initial dosing and analysed for metabolites. At the end of the dosing period animals were sacrificed and one kidney analsed for metabolites. Metabolites were identified by GC/MS and comparison to authentic standards.

GLP compliance:

not specified

Radiolabelling:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

no data

Route of administration:

oral: gavage

Details on exposure:

Rats were dosed orally with cis- or trans-decahydronaphthalene (each  isomer: 2500 mg/kg bw, males; 3000 mg/kg bw, females) every second day  
for 14 days.

Duration and frequency of treatment / exposure:

every second day  for 14 days

Remarks:

Doses / Concentrations:
 2500 mg/kg bw, males; 
3000 mg/kg bw, females

No. of animals per sex per dose / concentration:

7-9

Control animals:

yes

Type:

metabolism

Results:

Metabolism of cis-decahydronaphthalene in rats yielded  cis,trans-1-decalol and cis,cis-2-decalol in the urine of both sexes,  with the  male also producing cis,cis-1-decalol.

Type:

metabolism

Results:

Metabolites were excreted as glucuronic and sulfat conjugates

Metabolites identified:

yes

Details on metabolites:

Metabolism of cis-decahydronaphthalene in rats yielded  cis,trans-1-decalol and cis,cis-2-decalol in the urine of both sexes,  with the 
male also producing cis,cis-1-decalol. The urinary metabolites  of trans-decahydronaphthalene included trans,cis-2-decalol in both sexes  
and trans,trans-1-decalol in males.  In male rat kidney extracts decahydronaphthalene metabolites found were  the respective 2-decalones. The female  rats exhibited no detectable  decahydronaphthalene metabolites in the kidney extracts.  Females showed no recognizable renal lesions, whereas 7/7 (cis) and 5/6  (trans) males had renal lesions (severe hyaline droplet 
accumulation in  the cells of the proximal convoluted tubules and multifocal casts of  necrotic cells and debris in the tubules near the 
corticomedullary  junction). The one male rat dosed with trans-decahydronaphthalene that  did not exhibit trans-2-decalone in the 
kidney extract had a  histologically normal kidney.

Conclusions:

Metabolism of cis-decalin yielded cis,trans-1-decalol and cis,cis-2-decalol in the urine of both sexes, with the male also producing cis,cis-1-decalol. The urinary metabolites of trans-decalin included trans,cis-2-decalol in both male and female rats and trans,trans-1-decalol in males.
Therefore, no bioaccumulation potential based on study results is expected.

Executive summary:

The cis- and trans-decalin stereoisomers have found many uses as solvents and fuel components. The metabolism of the decalin isomers in male and female Fischer-344 rats and the effects of the decalins on renal damage were evaluated. Only male rats had kidney damage. Metabolism of cis-decalin yielded cis,trans-1-decalol and cis,cis-2-decalol in the urine of both sexes, with the male also producing cis,cis-1-decalol. The urinary metabolites of trans-decalin included trans,cis-2-decalol in both male and female rats and trans,trans-1-decalol in males. Extracts of kidney homogenates from male rats, but not from females, dosed with cis- and trans-decalin yielded cis-2-decalone and trans-2-decalone, respectively. A single male rat treated with trans-decalin produced no 2-decalone in the kidney extract and also showed no renal damage.

Reference 3

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: published peer reviewed, no guidelien mentioned but study was conducted and reported up to current standards

Objective of study:

metabolism

Principles of method if other than guideline:

single dose, gavage application,

GLP compliance:

no

Radiolabelling:

no

Species:

rabbit

Strain:

not specified

Sex:

female

Route of administration:

oral: gavage

Vehicle:

other: no vehicle but followed by 20 mL water

Duration and frequency of treatment / exposure:

single treatment

Remarks:

Doses / Concentrations:
cis decahydronaphthalene: 3.53 mmol/kg bw
trans decahydronaphthalene: 3.9 mmol/kg bw

No. of animals per sex per dose / concentration:

3

Control animals:

no

Positive control reference chemical:

no positive controls

Details on dosing and sampling:

Cis- and trans-decahydronaphthalene (2 ml each) were administered by  stomach tube to adult rabbits and the metabolism had been investigated.  
About 60 % of the dose given was excreted as ether-linked glucuronides.  The aglycones isolated after feeding with cis-decahydronaphthalene were  
cis,cis-2-decalol (mainly) and cis,trans-2-decalol, whereas a  trans-decahydronaphthalene feed yielded racemic trans,cis-2-decalol  (mainly) and 
trans,trans-2-decalol. These results suggest that biological  oxidation of decahydronaphthalene doses not occur via a free-radical  mechanism.

Metabolites identified:

yes

Details on metabolites:

racemic secondary alcohols and excreted as ether glucuronides in amounts equal to about 60% of the dose administered.
The principal glucuronides were isolated as triacetyl methyl esters and as sodium salts.
cis-Decalin gave rise mainly to (+/-)-cis-cis-2-decalol, together with a little cis-trans-2-decalol, and trans-decalin mainly to (+/-)-trans-cis-2-decalol and a small amount of trans-trans-2-decalol.

Conclusions:

cis- and trans-decalin are metabolised in the rabbit to racemic secondary alcohols and excreted as ether glucuronides in amounts equal to about 60% of the dose administered.

Executive summary:

The metabolism of cis- and trans-decalin in the rabbit has been investigated.

Both hydrocarbons were oxidized to racemic secondary alcohols and excreted as ether glucuronides in amounts equal to about 60% of the dose administered. The principal glucuronides were isolated as triacetyl methyl esters and as sodium salts.

cis-Decalin gave rise mainly to (+/-)-cis-cis-2-decalol, together with a little cis-trans-2-decalol, and trans-decalin mainly to (+/-)-trans-cis-2-decalol and a small amount of trans-trans-2-decalol.

These results suggest that biological oxidation of the decalins does not occur via a free-radical mechanism. An attempt is made to explain why racemic alcohols are obtained, rather than the more typical optically active products of enzymic reaction, and a mechanism is proposed. It is suggested that enzymes similar to steroid hydroxylases are involved.

Description of key information

Short description of key information on bioaccumulation potential result: 
Experimental studies on metabolism and toxicokinetic in rats, mice, rabbits and dogs are available following inhalation or oral administration of decahydronaphthalene. Oxidative metabolism was reported with metabolites excreted only via urine and exclusively conjugated as glucuronidates or sulfats.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Rapid uptake, metabolism and elimination were reported for rats, mice, rabbits and dogs.

Accumulation was reported in kidney of young male rats only an decahydronapthalene accumulated as complex with alpha2u-globulin. This mechanism is generally regarded as sex and species specific with no relevance to humans or other animal species.