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PROCESSING AND PACKAGING CONTAMINANTS 117 1183. Studies on stabilizers Springer, E. (1965). TierexperimenteUe Untersuchungen fiber die Toxizit~it eines Vinyl- chlorid-Vinylidenchlorid-Mischpolymerisats und yon zwei zur Stabilisierung der Dispersionen verwendbaren Substanzen. Z. ges. Hyg, 11,442. Gohlke, R. & Springer, E. (1965). iJber toxikologisch-histocheinische Untersuchungen eines PVC-Stabilisators. Z. ges. Hyg. 11, 437. "Stabilisator L" (I), an ethylene oxide-fatty alcohol adduct, finds its chief use as a stabil- izer in vinyl chloride-vinylidene chloride copolymers used for paper coating. These two papers report tests carried out in rats on a copolymer of this type ("Vinitex") both in the unstabilized state and containing 0.5 ~o of I, on I alone and on "Product FA" (II), an ethylene oxide-alkyl phenol stabilizer suspected of being toxicologically preferable to I. No adverse effects were elicited by either stabilized or unstabilized Vinitex when given orally in single doses of up to 24 g/kg or in daily doses of up to 1 g/kg for a 7-wk period (Springer, cited above), but the approximate lethal dose of I itself is about 10 g/kg (24 hr observation) and 250 mg/kg given daily for 7 wk increased mortality, reduced weight gain and caused liver changes, including fatty degeneration. Gohlke & Springer (cited above) found that daily administration of 50 mg I/kg for 7 wk did not retard growth or induce organ damage, but histochemical tests revealed enzymatic changes in the liver and adrenals, notably an increase in the activity of enzymes with functional thlol groups and a rise in 5- nucleotidase. The same authors reported that prolonged skin contact with I was without local effect and no internal changes resulted from percutaneous absorption. Results with II indicated that its use as a substitute for I was likely to have no toxico- logical advantage (Springer, cited above). II caused more skin damage than I and showed evidence of percutaneous absorption, and its approximate lethal dose was lower (7 g/kg with a 24-hr observation time; 4.7 g/kg when observation was extended to 96 hr). While all animals given 250 mg/kg daily for 7 wk survived, higher doses caused high mortality and fatty degeneration and other liver changes. 1184. Nephrotoxicity of ethylene glycol metabofites Bove, K. E. (1966). Ethylene glycol toxicity. Am. J. clin. Path. 45, 46. The nephrotoxic action of ethylene glycol (I) in rats appears to be mediated by the deposition of oxalate (II) stones in the kidney and the intermediary metabolism of I to II has been outlined previously (Cited in F.C.T. 1966, 4, 111). In the present study, oral doses of 1-6 g/kg of the three metabolites of I, namely glycol- aldehyde, glycollic acid and glyoxylic acid resulted in the deposition of oxalate stones in the rat kidney. Glycolaldehyde proved to be the least effective in this respect. However com- pared with I, all three metabolites were found to be more lethal. Based on histological examination of the convoluted tubular epithelium, the conclusion was drawn that renal failure is a consequence of cytotoxicity rather than simple mechanical obstruction of the tubular lumina by oxalate crystals. A rather unusual finding was the appearance of oxalate in the brain of a single rat given 9 g I/kg. This can be compared with the known effect seen in the meningeal vessels of several men poisoned by I. This phenomenon bears out the observed signs of early toxicity which indicate a functional disturbance of the central nervous system. 1185. Metabolism of 2-ethylhexyl sulphate Knaak, J. B., Kozbelt, Sarah J. & Sullivan, L. J. (1966). Metabolism of 2-ethylhexyl sulfate by the rat and rabbit. Toxic. appl. Pharmac. 8, 369. The metabolic fate of sodium 2-ethylhexyl sulphate (I), a surface-active agent, has been investigated in rats and rabbits given a single oral dose of I labelled with carbon-14 (14C) or sulphur-35 (35S). Within 4 days of administration of [14C]I to rats, 77.5 % of the 14C was

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PROCESSING AND PACKAGING CONTAMINANTS 117

1183. Studies on stabilizers Springer, E. (1965). TierexperimenteUe Untersuchungen fiber die Toxizit~it eines Vinyl- chlorid-Vinylidenchlorid-Mischpolymerisats und yon zwei zur Stabilisierung der Dispersionen verwendbaren Substanzen. Z. ges. Hyg, 11,442.

Gohlke, R. & Springer, E. (1965). iJber toxikologisch-histocheinische Untersuchungen eines PVC-Stabilisators. Z. ges. Hyg. 11, 437.

"Stabilisator L" (I), an ethylene oxide-fatty alcohol adduct, finds its chief use as a stabil- izer in vinyl chloride-vinylidene chloride copolymers used for paper coating. These two papers report tests carried out in rats on a copolymer of this type ("Vinitex") both in the unstabilized state and containing 0.5 ~o of I, on I alone and on "Product FA" (II), an ethylene oxide-alkyl phenol stabilizer suspected of being toxicologically preferable to I.

No adverse effects were elicited by either stabilized or unstabilized Vinitex when given orally in single doses of up to 24 g/kg or in daily doses of up to 1 g/kg for a 7-wk period (Springer, cited above), but the approximate lethal dose of I itself is about 10 g/kg (24 hr observation) and 250 mg/kg given daily for 7 wk increased mortality, reduced weight gain and caused liver changes, including fatty degeneration. Gohlke & Springer (cited above) found that daily administration of 50 mg I/kg for 7 wk did not retard growth or induce organ damage, but histochemical tests revealed enzymatic changes in the liver and adrenals, notably an increase in the activity of enzymes with functional thlol groups and a rise in 5- nucleotidase. The same authors reported that prolonged skin contact with I was without local effect and no internal changes resulted from percutaneous absorption.

Results with II indicated that its use as a substitute for I was likely to have no toxico- logical advantage (Springer, cited above). II caused more skin damage than I and showed evidence of percutaneous absorption, and its approximate lethal dose was lower (7 g/kg with a 24-hr observation time; 4.7 g/kg when observation was extended to 96 hr). While all animals given 250 mg/kg daily for 7 wk survived, higher doses caused high mortality and fatty degeneration and other liver changes.

1184. Nephrotoxicity of ethylene glycol metabofites Bove, K. E. (1966). Ethylene glycol toxicity. Am. J. clin. Path. 45, 46.

The nephrotoxic action of ethylene glycol (I) in rats appears to be mediated by the deposition of oxalate (II) stones in the kidney and the intermediary metabolism of I to II has been outlined previously (Cited in F.C.T. 1966, 4, 111).

In the present study, oral doses of 1-6 g/kg of the three metabolites of I, namely glycol- aldehyde, glycollic acid and glyoxylic acid resulted in the deposition of oxalate stones in the rat kidney. Glycolaldehyde proved to be the least effective in this respect. However com- pared with I, all three metabolites were found to be more lethal. Based on histological examination of the convoluted tubular epithelium, the conclusion was drawn that renal failure is a consequence of cytotoxicity rather than simple mechanical obstruction of the tubular lumina by oxalate crystals.

A rather unusual finding was the appearance of oxalate in the brain of a single rat given 9 g I/kg. This can be compared with the known effect seen in the meningeal vessels of several men poisoned by I. This phenomenon bears out the observed signs of early toxicity which indicate a functional disturbance of the central nervous system.

1185. Metabolism of 2-ethylhexyl sulphate Knaak, J. B., Kozbelt, Sarah J. & Sullivan, L. J. (1966). Metabolism of 2-ethylhexyl sulfate by the rat and rabbit. Toxic. appl. Pharmac. 8, 369.

The metabolic fate of sodium 2-ethylhexyl sulphate (I), a surface-active agent, has been investigated in rats and rabbits given a single oral dose of I labelled with carbon-14 (14C) or sulphur-35 (35S). Within 4 days of administration of [14C]I to rats, 77.5 % of the 14C was