2,6-diisopropylnaphthalene

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Objective of study:

toxicokinetics

Qualifier:

no guideline followed

Principles of method if other than guideline:

toxicokinetic study in rats; investigation of absorption, tissue distribution and elimination/excretions after oral administration of single doses

GLP compliance:

no

Radiolabelling:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 230 - 270 g
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on exposure:

2,6-DIPN was administered as solution in olive oil (40 mg/mL)

Duration and frequency of treatment / exposure:

Administration of one single dose

Dose / conc.:

100 mg/kg bw/day (nominal)

No. of animals per sex per dose / concentration:

3 to 5 animals

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, blood, liver, kidney, spleen, heart, brain, muscle, skin, adipose tissue
- Time and frequency of sampling: 2, 4, 6, 8, 14, 24, and 48 h after administration
- Other: rats were sacrificed at each designated time period by decapitation and the tissues collected

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled (delete / add / specify): urine, faeces, tissues, cage washes, bile
- Time and frequency of sampling:
- From how many animals: (samples pooled or not)
- Method type(s) for identification (e.g. GC-FID, GC-MS, HPLC-DAD, HPLC-MS-MS, HPLC-UV, Liquid scintillation counting, NMR, TLC)
- Limits of detection and quantification:
- Other:


TREATMENT FOR CLEAVAGE OF CONJUGATES (if applicable):

Details on absorption:

After a single dose, ca. 85 % of the dose administered was resorbed within 48 h. Maximal blood level were reached after ca. 2 h. The first-order rate constant for the gastrointestinal absorption of 2,6-DIPN was computed to be 0.170 per h. Overall, the gastrointestinal absorption of 2,6-DIPN appears to be considerably rapid.

Details on distribution in tissues:

Maximal levels of 2,6-DIPN in liver and kidney were reached after 2 h, as it was seen for the other tissues except skin and adipose tissue. Then 2,6-DIPN levels decreased with time. Maximum levels in skin and fat were reached after 10 hours and then levels decreased slowly. The highest maximum DIPN concentrations were found in adipose tissue followed in descending order by skin > liver > heart, kidney, brain > spleen > muscle.
Ca. 10 % (8 %) of the dose was transiently accumulated in adipose tissue after 10 h (24 h) p.a.

Details on excretion:

Excretion of unchanged 2,6-DIPN in feces amounted to ca 3.76 mg (about 15% of the dose) during 48 h. However, this fraction is not attributed to biliary excretion of ingested 2,6-DIPN.
Excretion of 2,6-DIPN in urine was marginal and most notable during the first 24 h.

Metabolites identified:

no

Conclusions:

Interpretation of results: low bioaccumulation potential based on study results
After oral administration, 2,6-DIPN is resorbed by 85% within 48 h. The remainder is excreted in feces. Peak levels in blood and most tissues are reached within 2 h and largely eliminated after 24 h. In adipose tissue and skin, maximum levels are obtained 10 h p.a. Elimination is slow. After 10 and 24 h ca. 10 % and 8 %, respectively, of the dose are transiently accumulated in adipose tissue.

Reference 2

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Objective of study:

toxicokinetics

Qualifier:

no guideline followed

Principles of method if other than guideline:

toxicokinetic study in rats; investigation of tissue distribution and elimination from tissues after oral administration of repeated doses for 17 or 31 days

GLP compliance:

no

Radiolabelling:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 130 - 160 g
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

rats were fed diet containing 0.1% or 0.2% 2,6-DIPN

Duration and frequency of treatment / exposure:

17 and 31 d; continuous uptake

Dose / conc.:

0.1 other: % test substance in diet

Dose / conc.:

0.2 other: % test substance in diet

No. of animals per sex per dose / concentration:

4

Control animals:

no

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: blood, liver, kidney, adiose tissue, skin (only for sampling group 2)
- Time and frequency of sampling:
1a: after 17 d and 31 d of treatment
1b: after 18 d and 32 d; 24 h feeding on normal diet after termination of treatment (day 17 and 31)
2: at day 0, 7, 14, 21, 28, and 35 after dosing with 0.1% test substance in diet for 14 days (starting at day 1, feed was control diet)

Details on distribution in tissues:

1a: Following continuous dosing in the feed, tissue levels increased in proportion of the dose and approached a steady state (no difference between tissue levels after 17 and 31 d). Levels in adipose tissue were 50 to 100 fold higher than that in other organs, corresponding to 200 and 550 µg DIPN/g fat tissue, related to the dose.
1b: When continuous dosing (17 and 31 d) was followed by a 24 h period feeding control diet, 2,6-DIPN concentrations in blood, liver, and kidney were greatly reduced by > 90% compared to levels immediately after the end of dosing. In contrast, 2,6-DIPN decrease in adipose tissue was only 10 to 30% within the 24 h period after cessation of DIPN administration.

Metabolites identified:

no

Elimination of 2,6-DIPN from various tissues after administration of 0.1% DIPN in diet for 14 days (dosing and sampling group 2)

 

Immediately after the end of administration (day 0), levels in blood, liver, and kidney were 0.25 ± 0.04, 2.46 ± 0.66, and 1.77 ± 0.30 (µg/mL or µg/g) respectively (n = 3 to 4). At day 7, no 2,6-DIPN could be detected any more in these tissues.

 

At day 0, levels in skin and adipose tissue were 23.41 ± 5.28 and 198.48 ± 4.69 µg/g respectively. After 28 days, still 10 % of the original concentration was left in skin. In adipose tissue, DIPN levels of 23.97 ± 8.30 and 4.09 ± 0.05 µg/g were detected after 7 and after 14 days. For the elimination of 2,6-DIPN from adiose tissue, a biphasic course was determined with a half-life of 55 h for the first phase (until ca. 21 days) and a half-life of 270 h for the second phase (from 21 to 35 days).

Conclusions:

Interpretation of results: low bioaccumulation potential based on study results
After continuous administration of 2,6-DIPN in feed for 17 and 21 days, DIPN levels in various tissues were elevated in proportion to the dose but were not affected by the difference of the administration period thus indicating approaching of a steady state. Levels in adipose tissue were 50 to 100 fold higher compared to other organs. Elimination from tissues except adipose tissue and skin was fast (> 90% within on day). Skin still retained about 10% of the starting concentration at day 28. For adipose tissue, a biphasic elimination was determined with half-lifes of 55 and 270 h.

Reference 3

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Objective of study:

metabolism

Qualifier:

no guideline followed

Principles of method if other than guideline:

Metabolic study by means of isolating metabolites from urine and bile and identification of structure using spectroscopic methods

GLP compliance:

no

Radiolabelling:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200 - 270 g urinary metabolites, repeated dose application; 200 -220 g biliary metabolites
- Individual metabolism cages: yes (Bollman cages)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on exposure:

Test substance was administered as solution in olive oil

Duration and frequency of treatment / exposure:

1: 15 d, daily for long time urine samples
2: single dose for 24 h urine and bile samples

Dose / conc.:

240 mg/kg bw/day (nominal)

Remarks:

Experiment 1: repeated doses, long term urine sampling

Dose / conc.:

100 mg/kg bw/day (nominal)

Remarks:

Experiment 2: single doses, 24 h sampling

No. of animals per sex per dose / concentration:

1: 6 animals
2: 3 to 6 animals

Control animals:

no

Details on dosing and sampling:

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine, bile
- Time and frequency of sampling: 1: urine samples from 15 days were combined; 2: individual 24 h samples
- From how many animals: 1: samples from 6 animals were pooled; 2: content of metabolites was individually determined
- Method type(s) for identification: GLC-FID, TLC
- Limits of detection and quantification: no data

TREATMENT FOR CLEAVAGE OF CONJUGATES (if applicable): The aqueous phase remaining after the extraction of unpolar metabolites was treated with beta-glucuronidase in order to cleave conjugates

Metabolites identified:

yes

Details on metabolites:

Main metabolic pathway was oxidation of the isopropyl side chain at the tertiary carbon and at the methyl group to alcohols and subsequently in some cases to carboxylic acids. Mono- di-, and trialcohols were formed as well as mixed alcohol-carboxylic acids and dicarboxylic acids. The metabolites identified were also excreted as glucuronides but to a much lower amount.
Two further metabolites were separated in the chloroform extract of urine by TLC. Both spots reacted with diazotized sulfanilic acid and are considered to be phenolic compounds. Their structure has not yet been elucidated.
Main metabolite excreted in urine was 2-[6-(1-hydroxy-1-methyl)ethylnaphth-2-yl-hydroxypropionic acid. In bile, two main metabolites were identified: 2,6-naphthalenedi(2-propan)-2-ol and 2,6-naphthalenedi-2-propionic acid

Results for 24 h samples

Total excretion (urine and bile) was about 40% of the dose administered within 24 h.

 

Urinary excretion was 23% of the dose after 24 h (19.4% not conjugated, 3.7% conjugated metabolites). Native 2,6-DIPN was less than 0.1%. Five metabolites were identified each also present as conjugate. Four of them amounted to less than 2 % each. The main component contributing ca. 17% of the dose applied (including glucuronide), was identified as 2-[6-(1-hydroxy-1-methyl)ethylnaphth-2-yl-hydroxypropionic acid (Kojima et al., 1982).

 

In bile after 24 h p.a., five unconjugated and conjugated metabolites were found as well, amounting to ca. 17% of the dose applied. Only ca. 1.5% were conjugated. Native DIPN was less than 0.1%. The metabolites identified in bile were the same as in urine, but the quantitative distribution was different. 2,6-naphthalenedi(2-propan)-2-ol and 2,6-naphthalenedi-2-propionic acid were the main metabolites accounting for ca. 13% of the dose applied (Kojima et al., 1985).

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Introduction  

There are some experimental data available in which the toxicokinetic behaviour of 2,6-Diisopropylnaphthalene (CAS No. 24157-81-1) has been assessed. The following summary has been prepared based on this experimental data.  Additionally, pharmacokinetic or toxicokinetic (PBTK) predictions have been made using actual and predicted physico-chemical properties of 2,6-Diisopropylnaphthalene and its degradation products. The main input variable for the majority of these algorithms is log octanol/water partition coefficient (log Kow). By using this, and other known or predicted physico-chemical properties of 2,6-Diisopropylnaphthalene and its degradation products, reasonable predictions or statements can be made about potential absorption, distribution, metabolism and excretion (ADME) properties.

Chemistry

2,6-Diisopropylnaphthalene has been shown to be metabolised in rats primarily by an oxidative pathway involving the isopropyl groups. Five metabolites were identified in urine and bile from rats given an oral dose of 2,6-Diisopropylnaphthalene (Kojima et al. 1982; Kojima et al. 1985). Details of the physico-chemical properties of 2,6-Diisopropylnaphthalene and the 5 metabolites are shown in Table 1.

Table 1 Summary of physico-chemical properties for 2,6-Diisopropylnaphthalene and its metabolites

Chemical	CAS number	Water solubility* (mol/L)	Log Kow*	Molecular weight* (g/mol)
2,6Diisopropylnaphthalene	24157-81-1	5.13 X10^-5	5.96 (predicted average)	212.33
2,6-Bis(2-hydroxy-2-propyl)naphthalene	24157-82-2	8.59 X10^-5(Predicted average)	3.05 (Predicted average)	244.33
2-Naphthaleneacetic acid, 6-(1-hydroxy-1-methylethyl)-alpha-methyl-	83162-89-4	1.97 (Predicted average)	3.0 (Predicted average)	258.317
2-[6-(1-carboxyethyl)naphthalen-2-yl]propanoic acid	83162-90-7	1.97 (Predicted average)	3.18 (Predicted average)	272.3
2-hydroxy-2-[6-(2-hydroxypropan-2-yl)naphthalen-2-yl]propanoic acid	83162-91-8	1.51 (Predicted average)	2.26 (Predicted average)	274.316
2-[6-(1-Hydroxy-1-methylethyl)naphthalen-2-yl]-1,2-propanediol	83162-92-9	3.50 (Predicted average)	1.71 (Predicted average)	260.33

*Figures obtained from the EPA CompTox database

Absorption is a function of the potential for a substance to diffuse across biological membranes. In addition to molecular weight, the most useful parameters providing information on this potential are the log Kow value and water solubility. The log Kow value provides information on the relative solubility of the substance in water and octanol and is a measure of lipophilicity. Log Kow values above zero indicate that the substance is more soluble in octanol compared with water (more lipophilic).

The low water solubility and high log Kow of 2,6-Diisopropylnaphthalene suggests that it is lipophilic and will have a high potential to be absorbed through biological membranes. With the exception of 2,6-Bis(2-hydroxy-2-propyl)naphthalene (CAS No. 24157-82-2) which has a similarly low predicted water solubility as the parent material, 2,6-Diisopropylnaphthalene, the predicted water solubility of the metabolites is judged to be moderate.  However, for the five metabolites, the lowest predicted log Kow is 1.71 (for 2-[6-(1-Hydroxy-1-methylethyl)naphthalen-2-yl]-1,2-propanediol (CAS No 83162-92-9)). It is therefore judged that all of the metabolites are sufficiently lipophilic to pass through biological membranes by passive diffusion efficiently.

The smaller the molecule, the more easily it is trans-dermally absorbed. In general, a molecular weight below 100 g/mol favours dermal absorption and above 500 g/mol, the molecule may be too large to be absorbed. Log Kow values between 1 and 4 favour dermal absorption particularly if water solubility is high (ECHA, 2017). Since 2,6-Diisopropylnaphthalene, has a low water solubility of 5.13 X10-5 mol/L, a molecular weight of 212.33 g/mol and a log Kow of 6.08, dermal absorption and subsequent metabolism is likely to be low.

Toxicokinetics

Absorption

Oral

The absorption, tissue distribution and excretion of 2,6-Diisopropylnaphthalene was investigated following a single oral administration in rats of 100 mg/kg bw (Kojima et al., 1978). Approximately 85% of the dose was absorbed from the gastrointestinal tract 48 hours after administration and only a small amount of the unchanged 2,6-Diisopropylnaphthalene was excreted in the urine.

2,6-Diisopropylnaphthalene was administered to male and female rats in a diet containing 0.1 or 0.2% for 14 or 31 days. Accumulation in various tissues was investigated. The 2,6-Diisopropylnaphthalene contents in blood, liver, kidneys and adipose tissue were increased in proportion to the dose, but were not affected by the difference in administrative periods (Kojima et al., 1979).

In the metabolite characterisation studies, rats were dosed orally with repeated doses of 240 mg/kg bw/day and single doses of 100 mg/kg bw (Kojima, 1982; Kojima, 1985). In both studies, the main metabolic pathway was identified as oxidation of the isopropyl side chain at the tertiary carbon and at the methyl group to alcohols and subsequently in some cases to carboxylic acids. Mono-, di-,and trialcohols were formed as well as mixed alcohol-carboxylic acids and dicarboxylic acids. The metabolites identified were also excreted as glucuronides, but to a much lower amount.

In an acute oral toxicity test in rats with 2,6-Diisopropylnaphthalene, an LD50 value of > 5 g/kg bw was determined (Wnorowski, 1997).

In a 90-day repeat dose dietary toxicity study, rats received 2,6-Diisopropylnaphthalene at concentration in the diet of 0, 750, 1500 and 3000 ppm (equivalent to 53.9, 104.6, and 207,6 mg/kg bw/day for males and 61.8, 121.4, and 244.7 mg/kg bw/day for females, respectively). No treatment-related, adverse effects were observed for all concentrations of 2,6-Diisopropylnaphthalene except pupil constriction at the mean and top dose. There were no test material-related effects noted during handling, open field observation, or on sensory reactivity assessment.  There were no mortalities; all animals survived the study period until the scheduled sacrifice. A no observed adverse effect level (NOAEL) of 105 mg/kg bw/day (105 and 121 mg/kg bw/day for males and females, respectively) was reported (Henwood, 1999).

No data on developmental toxicity with 2,6-Diisopropylnaphthalene are available. The endpoint, therefore, is assessed by means of read-across from the analogue source substance bis(isopropyl)naphthalene (CAS No.38640-62-9). A rat developmental study was conducted according to OECD guideline 414, with bis(isopropyl)naphthalene. In dams, there was no substance-related mortality. No significant clinical or toxic symptoms were observed, except a disproportionate reduction in feed consumption in the mean and high-dose group animals. No embryotoxic or teratogenic effects were observed at any dose level. The NOAEL for maternal toxicity was established as 100 mg/kg bw/day. Due to the absence of developmental effects, the highest dose (625 mg/kg bw/day) was reported to be the no observed effect level (NOEL) for embryo-/fetotoxicity and teratogenicity (Leuschner, 1993).

Overall, based on the findings from the toxicokinetic, acute and repeated dose oral toxicity studies with 2,6-Diisopropylnaphthalene and the analogue source substance bis(isopropyl)naphthalene, it can be concluded that the parent and the metabolites have the potential to be systemically absorbed via the oral route.  

Inhalation

2,6-Diisopropylnaphthalene is a solid material with a volatility of 0.005 hPa at 20ºC. It is therefore judged that inhalation will be via airborne particles rather than as a volatile material.

In an acute aerosol inhalation toxicity test with 5.64 mg/L air of the analogue source substance Bis(isopropyl)naphthalene, 5 rats/sex were exposed to an aerosol for 4 hours. Two of the female rats died at day 14 (mortality 2/10 total). The LC50 for acute inhalation toxicity was concluded to be > 5.64 mg/L air based on the mortality observed (Bernstein, 1988).

Based on the low volatility of 2,6-Diisopropylnaphthalene, and the absence of effects with the analogue source substance Bis(isopropyl)naphthalene in an acute inhalation study, it can be concluded that the parent material has a low potential to be absorbed via the inhalation route resulting in a low systemic toxicity hazard to both the parent material and metabolites.

Dermal

In an acute dermal toxicity test using only one dose (4500 mg/kg bw, limit test), 5 rats/sex were exposed to the analogue source substance Bis(isopropyl)naphthalene for 24 hours. No mortality and no clinical or gross pathological findings were observed. The LD50 for acute dermal toxicity was reported to be > 4500 mg/kg bw under the conditions of the study (Meisel, 1984).

In a primary skin irritation test in the rabbit, the analogue source substance Bis(isopropyl)naphthalene was found to be slightly irritating according to the scoring system of Draize (Meisel, 1982).

As discussed in the Chemistry section, the physico-chemical properties of 2,6-Diisopropylnaphthalene would indicate a low potential for skin penetration. In the acute dermal toxicity and acute dermal irritation study with the analogue source substance Bis(isopropyl)naphthalene neither mortalities nor significant signs of toxicity were observed. Is therefore judged that 2,6-Diisopropylnaphthalene has a low dermal absorption potential with a resulting low systemic and local toxicity hazard to both the intact parent material and any metabolites generated following oxidation via the dermal route.

Distribution

In a toxicokinetic study in rats, tissue distribution and elimination from tissues after oral administration of 2,6-Diisopropylnaphthalene following repeated doses of 0.1% or 0.2% in the diet for 17 or 31 days was investigated (Kojima et al., 1979). Following continuous dosing in the feed, levels in blood, liver, kidneys and adipose tissue increased in proportion to the dose and approached a steady state with no difference between tissue levels after 17 and 31 days. Levels in adipose tissue were 50 to 100 fold higher compared to other organs. Elimination from all tissues except adipose tissue and skin was rapid (> 90% within one day).

Following a single oral administration of 100 mg/kg bw 2,6-Diisopropylnaphthalene in rats, the test material was found in blood, liver, kidneys, spleen, heart, brain, muscle, skin and adipose tissue.  The order of the extent of the maximum levels in these tissues was adipose tissue > skin > liver > heart, kidney, brain > spleen > muscle (Kojima et al., 1978).

Metabolism

In the metabolite characterisation studies, the main metabolic pathway was oxidation of the isopropyl side chain at the tertiary carbon and at the methyl group to alcohols and subsequently in some cases to carboxylic acids. Mono-, di-, and trialcohols were formed as well as mixed alcohol-carboxylic acids and dicarboxylic acids. The metabolites identified were also excreted as glucuronides but to a much lower amount (Kojima et al., 1982; Kojima et al., 1985).  Five metabolites were identified in urine and bile from rats given an oral dose of 2, 6-Diisopropylnaphthalene (presented in Table 1).  

Excretion

In the metabolite characterisation studies, total excretion (via urine and bile) was about 40% of the dose administered within 24 hours.

Urinary excretion was 23% of the dose after 24 hours (19.4% not conjugated, 3.7% conjugated metabolites). Native 2,6-Diisopropylnaphthalene was less than 0.1%. Five metabolites were identified each also present as the conjugate. Four of them amounted to less than 2% each. The main component contributing around 17% of the dose applied (including glucuronide), was identified as 2-hydroxy-2-[6-(2-hydroxypropan-2-yl)naphthalen-2-yl]propanoic acid (CAS No. 83162-91-8) (Kojima et al., 1982).

In bile, 24 hours after administration of 2,6-Diisopropylnaphthalene, five unconjugated and conjugated metabolites were found as well, amounting to approximately 17% of the dose applied. Only approximately 1.5% were conjugated. Native 2,6-Diisopropylnaphthalene was less than 0.1%. While the metabolites identified in bile were the same as in urine, the quantitative distribution was different. 2,6-Bis(2-hydroxy-2-propyl)naphthalene (CAS No. 24157-82-2) and 2-[6-(1-Hydroxy-1-methylethyl)naphthalen-2-yl]-1,2-propanediol (CAS No.83162-92-9 ) were the main metabolites accounting for around 13% of the dose administered (Kojima et al., 1985).

References

Bernstein D (1988) unpublished report

CompTox Chemicals Dashboard https://comptox.epa.gov/dashboard accessed 9.10.2020

ECHA (2017) Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance

Henwood S (1999) unpublished report

Kojima S, Nakagawa M, Suzuki R, Horio M and Tanaka Y (1978). Alkylnaphthalenes. I. Absorption, tissue distribution and excretion of 2,6 Diisopropylnaphthalene in rats. Chem. Pharm. Bull. 26(10):3007-3009

Kojima S, Nakagawa M, Suzuki R, Horio M, Taniguchi Y and Tanaka Y (1979). Alkylnaphthalenes. II. Tissue accumulation of 2,6 Diisopropylnaphthalene administered continuously to rats. Eisie Kagaku (4):221-224

Kojima S, Honda T, Nakagawa M, Kiyozumi M and Takadate A (1982). Urinary metabolites of 2,6 Diisopropylnaphthalene in rats. Drug Mat. Disp. 10(4):429-433

Kojima S, Honda T and Kiyozumi (1985). Billary metabolites of 2,6 Diisopropylnaphthalene in rats. Bull. Environ. Contam. Toxicol. 35:745-749

Meisel M (1982) unpublished report

Meisel M (1984) unpublished report

Wnorowski G (1997) unpublished report