Benzene, C15-16-alkyl derivs.

Endpoint summary

Description of key information

In cases where no data were available on the target substance, Benzene, C15-16-alkyl derivs., data were read across from a structurally related material (the test substance).
A series of toxicokinetic studies in rats indicates that a read-across source substance for Benzene, C15-16-alkyl derivs. is rapidly absorbed when the exposures are intravenous or oral, but poorly absorbed (8-10%) through the skin.   The test substance is then rapidly eliminated from the body, mostly via the urine and to a lesser extent in the faeces (in particular when the exposure is oral).  Metabolism is rapid and several metabolites have been resolved using TLC.  The test subtance was also rapidly eliminated from the majority of tissues, though some remained in the fatty tissues and tissues with high lipid content or with oily secretions.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

10

Additional information

In cases where no data were available on the target substance, Benzene, C15-16-alkyl derivs., data were read across from a structurally related material (the test substance).

A series of toxicokinetic studies in rats indicates that a read-across source substance for Benzene, C15-16-alkyl derivs. is rapidly absorbed when the exposures are intravenous or oral, but poorly absorbed (8-10%) through the skin. The test substance is then rapidly eliminated from the body, mostly via the urine and to a lesser extent in the faeces (in particular when the exposure is oral). Metabolism is rapid and several metabolites have been resolved using TLC. The test substance was also rapidly eliminated from the majority of tissues, though some remained in the fatty tissues and tissues with high lipid content or with oily secretions.

In the first key study (Whitby 1994a), a single intravenous dose of a read-across source substance for Benzene, C15-16-alkyl derivs. was given to five male and five female rats. Samples of urine and faeces were taken at pre-dose and 0.5, 4, 8, 24, 72, and 96 hrs post-dose. Whole body autoradiography was done for one animal of each sex at 0.5, 4, 8, 24, and 96 hrs after dosing. Liquid scintillation counting and TLC, urine and faeces were pooled by time point and sex. No clinical signs were observed during the study. Parent compound was a major component of radiation in the faeces. The test compound appeared to be rapidly eliminated from the body via the urine. Up to nine different metabolites were resolved by TLC. A volatile fraction that was most likely parent compound was noted at the first time point, but this was no longer evident at later time points. The test substance was rapidly eliminated from the majority of tissues, though some remained in fatty tissues. The highest levels were observed early in the liver and kidneys. The radioactivity was widely distributed early in the experiment, but was largely gone by 24 hrs after dosing. The stenos gland, however, still contained radioactivity. Tissues with high lipid content and those with oily secretions still showed low but persistent radioactivity. No radioactivity was noted in the blood after 4 hrs in males, and 8 hrs in females. A total of 79.88% of the test substance was excreted by male rats, and 85.87% by the female rats within 96 hrs. The main route of excretion was the urine (75.97% female, 57.94% males) and mostly within the first 24 hrs (72.15% female, and 53.19% males). The amount excreted in the feces was 8.865% for males and 5.285% in females.

In the second key study (Whitby 1994b), a single oral dose of the same test substance was given to five male and five female rats. Samples of urine and faeces were taken at pre-dose 4, 8, 24, 72, and 96 hrs post-dose. Whole body autoradiography was done for one animal of each sex at 4, 8, 24, and 96 hrs after dosing. No clinical signs were observed during the study. The test substance was rapidly absorbed (minimum of 50%) and eliminated from the majority of tissues, though some remained in fatty tissues. Metabolism of the test substance was rapid, and it was eliminated mostly through the urine. The highest levels of labeled material were observed early in the liver and kidneys. The radioactivity was widely distributed early in the experiment, but was largely gone by 24 hrs after dosing. The stenos gland, however, still contained radioactivity. Tissues with high lipid content and those with oily secretions still showed low but persistent radioactivity. Maximum rate of excretion was between 8 and 24 hrs. 74.99% was eliminated in males, and 88.52% in females. Most was eliminated via the urine (49.40% males, and 55.71% females). The amount excreted via the feces was 19.25% in males and 26.04% in females. Metabolites included either 4-phenyl pentanoic acid or 4-phenyl pentylthioamide. No clinical signs were observed during the experiment.

In the third study (Whitby 1994c), a single dermal dose of 200 uL of the same test substance was given to five male and five female rats. Samples of urine and faeces were taken at pre-dose 4, 8, 24, 72, and 96 hrs post-dose. Whole body autoradiography was done for one animal of each sex at 4, 8, 24, and 96 hrs after dosing. Cold traps were used to collect any test substance that volatilized. No clinical signs were observed during the study. The test substance was poorly absorbed through the skin, with only 8-10% being absorbed. The majority of the test substance remained on the skin through the end of the study. The test substance was rapidly eliminated from the majority of tissues, though some remained in fatty tissues. Metabolism of the test substance was rapid, and it was eliminated mostly through the urine. A total of 10.58% of the test substance was excreted in males, and 7.95% in females. About 7.668% was excreted through the urine in males, and 6.129% by females. The excretion rate in urine was greatest between 24 and 48 hrs post-dose. 2.004% was excreted through the feces in males, and 0.889% in females. The highest levels of radiation were found in the liver, gastro-intestinal tract, kidneys, and bladder. Levels increased through 24 hrs, then remained constant. Radioactivity continued to be found in tissues with high lipid content, such as the skeletal or brown fat tissues, and those with oily secretions throughout the study. Extensive and rapid metabolization occurred. Very little parent compound was found in the faeces and urine at any time point.