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Description of key information

MIPN isomer mixture [CAS no. 2953-36-9] is rapidly absorbed  from the gastro-intestinal tract, approx. 95 %/24 h after a single oral dose applied to rats. Excretion occurred predominantly via the urine, about 50 % of the dose within 24 h, 78 % after 96 h, while only 14 % were found in the faeces after 96 %. 

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

The toxicokinetic behaviour of MIPN isomer mixture has been examined in a comprehensive study programme with rats and rabbits receiving a single dose or several-fold doses of the target substance itself or the pure isomers, 1 - or 2 -isopropylnaphthalene (IPB). Most studies were carried out with 2 -IPB.

ABSORPTION, DISTRIBUTION, EXCRETION

More than 50% of the total dose of radioactivity (from isopropyl-[14C]naphthalene, isomer mixture) was excreted after 24 h via urine. After 96 h 78% of the total dose was excreted via urine. 14% of the total dose was excreted via faeces after 96 h. The excretion of radioactivity into the bile fluid was found to account for approx. 60% of the total dose. It was concluded that faecal excretion were the minor route of excretion of MIPN, but that enterohepatic circulation were important in the reabsorption of the metabolites excreted into the intestine via the bile (Kojima et al. 1981). Maximal levels of radioactivity in all tissues were reached after 4 h, except skin (6 h) and spleen (6 h). In blood the level kept nearly constant until 12 h after administration. Then levels decreased with time. The highest maximum level of radioactivity was found in adipose tissue followed in descending order by skin > liver, kidney >brain > spleen > muscle (Kojima et al. 1981).

More than 95% of total dose of 2-IPN was absorbed by the gastrointestinal tract after 24 h (Kojima and Maruyama 1979).

Maximal levels of 2-IPN in blood and in all tissues were reached after 2 h after single dose administration, except in adipose and skin tissues (4-6 h). In adipose and skin tissue the level decreased much more slowly than in blood and the other tissues. The highest maximum level of 2-IPN were found in adipose tissue followed in descending order by skin > muscle > liver > blood > kidney > brain > heart, spleen > muscle.

The amount of unchanged 2-IPN, excreted via faeces and urine after single dose administration was very small. Obviously the most of the applied 2-IPN was excreted as metabolites (Kojima and Maruyama 1979).

The disappearance of 2 -IPN from adipose tissue of rats after having fed a diet containing 0.1% 2 -IPN for 28 days:

Half-life time, 1st phase (0 - 7 d after post application of 2 -IPB):       male: 34 h; female: 31 h

Half-life time, 2nd phase (7 - 28 d post application of 2 -IPB):       male: 104 h; female: 113 h

(Kojima and Maruyama 1979)

METABOLISM, EXCRETION

Four metabolites from 2 -IPN were identified in conjugated and unconjugated form together with a small amount of unchanged 2-IPN in rats

(Kojima et al. 1980/1984):

- 2-(2-naphthyl)propionic acid

- 2-(2-naphthyl)-2-propanol

- 2-(2-naphthyl)-1,2-propandiol

- 2-(2-naphthyl)-2-hydroxypropionic acid

In the TL-chromatograms of an extract, two further not identified compounds were observed. Due to positive reactions with diazotised sulphonic acid, these compounds were considered as phenolic compounds (Kojima et al. 1980).

The metabolites of 2 -IPN in urine after 24 hours amounted to 23%, in bile to about 18% of the dose. The amount of unchanged 2 -IPN excreted via urine and bile was relatively small. 2-(2-naphthyl)-2-propanol was the major unconjugated metabolite found in both urine and bile. The major glucuronide conjugate identified in urinary and biliary excretions was 2-(2-naphthyl)-1,2-propandiol. The total urinary and biliary excretions of conjugated metabolites was much smaller than those of the unconjugated ones. Excretion patterns of urine and bile were almost similar (Kojima et al. 1984).

In the rabbit, also four metabolites from 2-IPB were identified in conjugated and unconjugated form together with a small amount of unchanged 2-IPN in urine:

- 2-(2-naphthyl) propionic acid (6.5 % plus 1.4 % conjugated) (after 24 h)

- 2-(2-naphthyl)-2-propanol (16 % plus 0.75 % conjugated) (after 24 h)

- 2-(2-naphthyl)-1,2-propandiol (minor)

- 2-(2-naphthyl)-2-hydroxypropionic acid (minor)

Further unconjugated metabolites, which were produced through oxidation of the naphthalene ring, were isolated and identified:

- 2-isopropylnaphthols

- 2-isopropyl-5,6 (or 7,8)- dihydronaphthalene-5,6 (or 7,8)-diol

The total urinary excretion of the metabolites (except 2 -isopropylnaphthols) within 24 h was about 29% of the dose.

Main facts

Overall, MIPN is absorbed and metabolised quite fast after administration and is not accumulated in organs even during repeated exposure. In fat, transiently elevated levels are attained. Thus, extended exposure will not result in continuing accumulation of MIPN. Based on dosage a maximal level (steady state) will be reached without further accumulation. After cessation of a 28 -d exposure via diet (rats), 2 -IPN was eliminated from the body at a half-life of 31 - 34 h (rapid phase) and of 104 - 113 h (second phase) (biphasic elimination characteristics).