Hydrogenated poly-1-decene was first evaluated as a glazing and releasing agent by the Committee at its forty-ninth meeting (Annex 1, reference 131). A 28-day range-finding study and a 90-day study in rats that were available at that time were considered inadequate to support use of this product as a food additive. Data were requested to demonstrate that the oily coats observed on rats fed hydrogenated poly-1-decene in the 90-day study were not the result of systemic absorption of the material. In addition, the Committee suggested that the results of a study demonstrating lack of absorption in humans be provided. In the absence of such data, the results of long-term studies of toxicity and reproductive toxicity and information on the metabolism, distribution, and excretion of hydrogenated poly-1-decene would be required.

At its fifty-third meeting, the Committee reviewed a study of the distribution and excretion of [³H]hydrogenated poly-1-decene (Annex 1, reference 143). This study established that the oiliness of the fur of rats observed within 1–6 h of their receiving a bolus dose was associated with radiolabelled material originating from the anal region, which was spread by grooming. However, while the study indicated that very little hydrogenated poly-1-decene was absorbed after oral administration, it did not allow clear definition of the fate or disposition of any absorbed compound. The Committee was therefore unable to establish an ADI and wished to see an adequate study of the absorption and deposition of hydrogenated poly-1-decene in order to determine whether further studies were required.

At its present meeting, the Committee re-evaluated the results of the study of absorption, distribution, and excretion. Although no new study was submitted, arguments were drawn to the Committee’s attention that underlined the validity of the previous study. In addition, a study of the effect of hydrogenated poly-1-decene on the absorption, distribution, and excretion of linoleic acid and glycerol trioleate had been submitted for consideration.

Hydrogenated poly-1-decene is obtained by catalytic hydrogenation of mixtures of trimers, tetramers, pentamers, and hexamers of 1-decenes, produced by oligomerization of 1-decene in the presence of a catalyst. The product is purified by filtration through activated clay. Hydrogenated poly-1-decene consists of a mixture of branched isomeric hydrocarbons predominantly with carbon numbers higher than 30. Minor amounts of molecules with lower carbon numbers may be present.

At its present meeting, the Committee revised the existing specifications in order to take into account the decrease from 3% to 1.5% in the concentration of molecules with carbon numbers below 30 in products on the market for food additive use.

2.1.1 Absorption, distribution, and excretion

[³H]Hydrogenated poly-1-decene (purity not stated; oligomer distribution: 18% trimer, 56% tetramer, 29% pentamer, 5% hexamer) was administered at a single oral dose of 30, 210, or 1500 mg to groups of 33 male Fischer 344 rats weighing 200–250 g, and radiolabel was determined in plasma, tissues (fat, kidney, liver, lymph node, spleen, and gut wall and contents), urine, faeces, carcass, skin, and fur for 168 h after dosing. In three additional studies, radiolabel was determined in plasma for 168 h after dosing in three rats that received 30 mg of hydrogenated poly-1-decene intravenously and in three rats that received an oral dose of 210 mg/day of unlabelled compound for 14 days followed by a single oral dose of labelled compound; and biliary excretion of hydrogenated poly-1-decene was determined for 168 h in three rats that received a single oral dose of 210 mg.

The pattern of excretion of radiolabel was similar whether the compound was administered as a single dose or for 15 days. After 168 h, less than 1% of the administered dose had been excreted in urine, whereas 92–102% was excreted in the faeces, and the total recovered was 93–102%. Biliary excretion accounted for only 0.01% of the 210-mg dose at 48 h, while 0.16% was present in the urine, 70% in faeces, and 25% in the gut contents. After oral administration of hydrogenated poly-1-decene, the radiolabel in plasma increased during the first 4–8 h in all treated groups. In the groups given 30 or 210 mg, the maximum concentration was achieved after 8 and 4 h, respectively, while in the group given 1500 mg the plasma concentration of radiolabel continued to rise slightly over the next 24–72 h. The half-times were 81 h at 210 mg and 93 h at 1500 mg. Most of the plasma radiolabel was associated with H₂O after 8 h at 30 mg, 4 h at 210 mg, and 2 h at 1500 mg. The authors reported that the half-time of plasma radiolabel, 3.5 days, was similar to that in the body water. The plasma concentrations of radiolabel in rats given 30 mg hydrogenated poly-1-decene intravenously were similar to or lower than those measured in rats receiving the same dose orally, but no further comment was made on this result.

A large proportion of the administered radiolabel was associated with the gut and its contents during the first 4–24 h after dosing. The liver and lymph nodes had higher concentrations of radiolabel than plasma at the time of maximal concentration for each dose; at lower doses, the amount of radiolabel in liver remained high at 24 h, while that in the lymph nodes stared to decline. At the high dose, the amount of radiolabel in the liver remained high at 72 h, but the trend in accumulation of radiolabel in the lymph nodes at this dose could not be ascertained as it was measured only at 72 h. The concentrations of radiolabel in fat, spleen, and kidneys were similar to that in plasma. Animals at 210 or 1500 mg had transient oiliness of the fur. In those at 210 mg, the oiliness was generally restricted to the base of the tail, became apparent about 6 h after dosing and had disappeared within 24 h. All rats at the higher dose showed oily fur 1 h after dosing; at 4 h, the oiliness was clearly apparent and oil patches were observed over the entire body. The oiliness decreased during 48–72 h after dosing and had disappeared by 96 h. The radiolabel was distributed over the fur, but the largest amounts were found in the lower parts of the body, especially in animals at the high dose in which radiolabel was clearly distributed on the lower abdomen > mid-abdomen > thorax > head. The proportion of radiolabel found on the fur was much higher in animals at the high dose, with a maximum of 11% of the administered dose found at 4 h. At the intermediate dose, the largest amount appearing on the fur was 1.1% of that administered, which was found 8 h after dosing. It is likely that the continued small increase in plasma radiolabel in rats at the high dose seen after 8 h was due to reingestion of radiolabel during grooming. The presence of a larger proportion of the administered radiolabel on the fur of rats at the high dose indicates limited absorption of the test material and is consistent with the observation that the increase in plasma radiolabel with dose was not proportional to the dose itself; thus, the ratio of dose was 1:7:50, while the area under the curve of concentration–time at 168 h for total plasma radiolabel was 1:2.3:7.6 (Runacres, 1999).

2.1.2 Effects on enzymes and other biochemical parameters

The effects of dietary administration of hydrogenated poly-1-decene on the absorption and excretion of [¹⁴C]linoleic acid and [¹⁴C]glycerol trioleate were investigated in a study compliant with GLP standards (European Commission, OECD, United Kingdom). Groups of six Fischer CDF/CrlBR (344) rats of each sex were fed a powdered control diet or the control diet containing 50 000 ppm (5.0%) hydrogenated poly-1-decene, equivalent to 4900 and 4800 mg/kg bw per day for males and females, respectively, for 18 days. On day 15, groups of three rats of each sex per group were given 1 mg/kg [¹⁴C]linoleic acid (radiochemical purity, 99.4%) or 0.5 mg/kg [¹⁴C]glycerol trioleate (radiochemical purity, 99.8%) by gavage. Urine, faeces, expired air, and cage washes were collected over the following 3 days. At sacrifice on day 18, blood, plasma, and tissues (liver, abdominal fat, skin, and residual carcass) were collected and processed, and aliquots were analysed for radioactivity.

The body weights of treated animals were unaffected. The food consumption in groups fed hydrogenated poly-1-decene tended to be higher, although the differences were statistically significant only for groups receiving [¹⁴C]linoleic acid. No comment was made about the condition of the animals’ coats.

The total recovery of radiolabel during 72 h after dosing with [¹⁴C]linoleic acid ranged from 45 to 69%. The largest fraction of the recovered radiolabel was retained in the body. While urinary excretion of radiolabel was less than 1% in all groups, faecal excretion tended to be higher in males and females fed hydrogenated poly-1-decene than in the controls: means of 7.3 (2.1, 8.5, 11)% and 2.0 (1.4, 1.5, 3.0)% in treated versus 3.3 (1.2, 3.5, 5.3)% and 1.5 (0.58, 1.2, 2.8)% in control males and females, respectively. Similarly, the recovery of radiolabel from [¹⁴C]linoleic acid was higher in expired air (CO₂ and volatile organics) from rats fed hydrogenated poly-1-decene (27%) than from controls (21%). However, none of the differences was statistically significant. The tissue concentrations of radiolabel 72 h after administration of [¹⁴C]linoleic acid were similar in liver, skin, carcass, blood, and plasma of male and female rats fed diets with and without added hydrogenated poly-1-decene. In fat, higher concentrations were detected in male and female rats fed hydrogenated poly-1-decene (2400 and 2300 ng/g expressed as equivalents, respectively) than in controls (1700 and 1500 ng/g); however, there were large individual variations, and the differences were not statistically significant.

The total recoveries of radiolabel during the 72 h after dosing with [¹⁴C]glycerol trioleate ranged from 82 to 86%. Recovery in expired air accounted for the largest fraction of radiolabel (35–50%). While the recoveries in expired air were higher for males fed hydrogenated poly-1-decene than for the controls (45% and 35%, respectively), the same was not true for the females (45% and 50%). Urinary excretion accounted for 1–2% of the administered dose, and the percentage was unaffected by administration of hydrogenated poly-1-decene. Faecal excretion of radiolabel tended to be higher in treated males and females than in controls: means of 11 (5.4, 9.4, 19)% and 7.0 (2.9, 8.2, 9.9)% versus 6.8 (1.8, 3.4,15)% and 1.9 (1.1 1.9, 2.7)% in males and females, respectively. None of the differences in the percentages of the dose expired or excreted was statistically significant. Among females, there were no differences in tissue concentrations of radiolabel 72 h after administration of [¹⁴C]glycerol trioleate that could be attributed to treatment with hydrogenated poly-1-decene; however, male rats fed the control diet had higher concentrations of radiolabel in fat and residual carcass (statistically significant at p < 0.01) than those fed hydrogenated poly-1-decene: 1700 versus 1100 ng/g for fat and 220 versus 130 ng/g for residual carcass in control and treated males, respectively (expressed as equivalents).

The low recovery of radiolabel, particularly with administration of [¹⁴C]linoleic acid, prompted an additional study in which one female on the control diet was given 0.5 mg/kg of [¹⁴C]linoleic acid by gavage. Unlike in the main study, in which solutions of trapped expired CO₂ were analysed about 1 week after collection, expired air samples from this female were analysed ‘soon’ after collection. The recovery of radiolabel in the expired air accounted for 60% of the administered dose. The investigator concluded that the production of high concentrations of ¹⁴CO₂ over a short time in the main study may have impeded accurate analytical determination. Such an underestimate of ¹⁴CO₂ would account for the low recoveries observed in the study with [¹⁴C]linoleic acid. The author concluded that dietary hydrogenated poly-1-decene had no adverse effect on the uptake of [¹⁴C]linoleic acid or [¹⁴C]glycerol trioleate by rats of either sex. There was some evidence that hydrogenated poly-1-decene may have decreased retention of the radiolabel in the carcass of males receiving [¹⁴C]glycerol trioleate (Kemp, 2001). The Committee noted that there was a trend towards increased faecal excretion of both [¹⁴C]linoleic and [¹⁴C]glycerol trioleate in hydrogenated poly-1-decene-treated rats, which may indicate a decrease in absorption, but the large individual variations and small group size prevented definitive conclusions being drawn.

Diets containing hydrogenated poly-1-decene, at a concentration of 0, 1000, 7000, or 50 000 mg/kg (0, 0.1, 0.7, and 5.0%), equal to 0, 78, 550, or 4200 mg/kg bw per day for males and 0, 86, 610, and 4600 mg/kg bw per day for females, were fed to groups of 10 Fischer 344 rats of each sex for 13 weeks. Additional groups of five rats of each sex received the control and high-dose diets for 13 weeks, after which they were put on control diets for a 4-week recovery period. Five animals of each sex were housed per cage, observed twice daily for clinical signs of toxicity, and palpated weekly; body weights were recorded weekly, and mean weekly food consumption was measure in each cage. Ophthalmoscopic examinations were made before treatment of all animals and at week 12 for the controls and animals at the high dose. At week 12 of treatment, blood samples were collected from 10 animals of each sex per group and assessed for clinical chemical parameters; however, serum vitamin E and other lipid-soluble nutrients were not measured. Bone-marrow samples were collected from the femur at sacrifice. Urine samples were collected from 10 animals of each sex per group for analysis after 11 weeks of treatment. Gross autopsy at sacrifice included an extensive inventory of the weights of the kidney, liver, heart, spleen, and mesenteric lymph nodes from all animals. Histopathological examination was made of 20 tissues and organs. Samples of liver, kidneys, duodenum, jejunum, ileum, caecum, rectum, heart, spleen, Peyer patches, and mandibular and mesenteric lymph nodes were stained with oil red ‘O’ and examined for accumulation of oil [sic].

No unscheduled deaths occurred during the study. Animals of each sex at the high dose appeared ungroomed during the second week of treatment, and the coats of all of these animals were oily from week 3 to the end of the study. Several animals at the intermediate dose also had oily coats. Hair loss was seen in all treated groups, although the effect was not related to dose; females at the high dose were most severely affected. During the first week of the recovery period, rats at the high dose, and particularly females, had oily coats, and the females still had hair loss and appeared ungroomed. Animals of each sex at the high dose and occasionally females at the intermediate dose had soft faeces from the second week of treatment. The body weights of treated animals were comparable to those of controls. The food consumption of rats at the high dose was slightly increased during treatment. The food conversion efficiency was slightly reduced in these groups throughout treatment and increased only slightly during the recovery period. The increased consumption was probably due to the reduced nutritional content of the high-dose diet. Male rats at all doses showed significantly increased haemogloblin and erythrocyte count, but only the increase in haemaglobin concentration was dose-related. The lymphocyte counts were reduced in all treated females, but significantly so only at the low and intermediate doses, with no dose-related trend. The platelet counts of males and females at the high dose were also significantly increased. After the recovery period, no such changes were seen. The myeloid:erythroid ratio and the cellularity and composition of the bone marrow were comparable in all groups. None of the haematological changes was considered to be toxicologically significant, as they were slight and fell within the reference ranges. Clinical chemical and urinary parameters showed no effect of treatment. After 13 weeks, both the absolute weight of the liver and that relative to body weight were significantly lower in males at the high dose than in controls, but the difference had disappeared after the recovery period. A non-significant decrease in the weight of mesenteric lymph nodes was seen in males at the intermediate and high doses and in females at the high dose, and the effect persisted in females at the end of the recovery period. The weights of the mandibular lymph nodes were not assessed. The only histopathological findings were made in females at the high dose, which had a low incidence of necrosis of individual hepatocytes in the liver (3/10 vs 0/10) and a significant decrease in fat retention by hepatocytes in the right caudal lobe of the liver (2/10 vs 8/10). No accumulation of test material was reported in lymphoid, gastrointestinal, hepatic or splenic tissues. The NOEL was 7000 mg/kg, equal to 550 mg/kg bw per day, on the basis of effects on the condition of coats, the reversible effects on liver weight in males and histopathological observations in the livers of females at the high dose (Cooper, 1995).

Hydrogenated poly-1-decene can be used as a release agent in the preparation of bread in commercial baking operations at 300–500 mg/kg and in glazed fruit at 2000 mg/kg. Use of the budget method to assess whether incorporation of an additive should be restricted to specific food groups indicated that the theoretical maximum concentration of hydrogenated poly-1-decene would be 240 mg/kg, assuming its use in half the solid food supply and an ADI of 0–6 mg/kg bw. As the theoretical maximum level is lower than the known use of this compound in bread and in glazed fruit, further assessment is required.

The main contribution to intake of hydrogenated poly-1-decene is probably from bread, as glazed fruit are not consumed in large quantities. If the additive were used in bread alone at 500 mg/kg, a maximum of 720 g bread could be consumed per day by a 60-kg individual before the ADI was exceeded. However, it is considered unlikely that a person would consume this amount of commercially prepared leavened bread containing hydrogenated poly-1-decene at the maximum level of use.

Reference to the WHO GEMS/Food regional diets indicated that mean per capita consumption of white and wholemeal bread is 18 g/day in the African diet and 320 g/day in the Middle Eastern diet (Table 1). In many regions, but particularly in the Middle East where bread consumption is high, unleavened bread is often eaten. As unleavened and home-baked bread do not contain hydrogenated poly-1-decene, the intake of the additive would be much lower than that predicted when assuming that all bread consumed contained the additive at maximum levels of use.

In its re-evaluation, the Committee accepted that equivalent information can be obtained with ³H and ¹⁴C, provided that the label is located in a metabolically stable position, as is the case for [³H]hydrogenated poly-1-decene. It also accepted that, for technical reasons, use of ¹⁴C-labelled hydrogenated poly-1-decene might be less appropriate, since the synthetic ¹⁴C-labelled compound might be different from the substance used in the studies of toxicity.

The results of the study of absorption, distribution, and excretion indicated that < 1% of the dose of [³H]hydrogenated poly-1-decene was absorbed from the gastrointestinal tract. The absorbed radiolabel was present largely as ³H₂O, probably arising from tritium exchange between the labelled substance and body water. The Committee concluded that absorption of hydrogenated poly-1-decene was negligible. This conclusion was corroborated by the results of the 90-day study in rats, which provided no evidence of its accumulation in tissues, and the revised specification of the substance requires that it contain a maximum of 1.5% of compounds with fewer than 30 carbon atoms.

Consequently, the available studies were considered adequate to assess the toxicity and safety of hydrogenated poly-1-decene.

An additional study in rats submitted for consideration by the Committee suggested that hydrogenated poly-1-decene may decrease the bioavailability of linoleic acid, an essential fatty acid. However, for intake of hydrogenated poly-1-decene at the level of the ADI, i.e., a maximum of 360 mg/person per day, the Committee concluded that a nutritionally relevant decrease in bioavailability would not occur.

Hydrogenated poly-1-decene can be used as a release agent in bread prepared in commercial baking operations at 300–500 mg/kg and in glazed fruit at 2000 mg/kg. Bread is expected to be the major contributor to total intake of this compound. If use only in bread is assumed, a reverse budget calculation would indicate that a maximum of 720 g of bread containing hydrogenated poly-1-decene at 500 mg/kg could be consumed by a 60-kg person before the ADI of 0–6 mg/kg bw would be exceeded. However, it was considered highly unlikely that a person would consume this amount of bread containing hydrogenated poly-1-decene at the maximum level of use each day.

An ADI of 0–6 mg/kg bw was established on the basis of the NOEL of 550 mg/kg bw per day in the 90-day study in rats for effects on coat condition, liver weight, and histological appearance, and a safety factor of 100.

Cooper, S. (1995) NEXBASE 2006 FG: Toxicity study by dietary administration to F-344 rats for 13 weeks followed by a four week reversibility period. Unpublished report No. 95/NEY002/0090 from Pharmaco-LSR Ltd, Eye, Suffolk, United Kingdom. Submitted to WHO by Neste Alfa OY, Espoo, Finland.

Kemp, L. (2001) Hydrogenated poly-1-decene (NEXBASE 2006 FG). Absorption, distribution and excretion of ¹⁴C-linoleic acid and ¹⁴C-glycerol trioleate after dietary administration of NEXBASE 2005 FG. Unpublished report No. NEY 019/004138 from Huntingdon Life Sciences, Huntingdon, Cambridgeshire, United Kingdom. Submitted to WHO by Fortum Base Oils, Fortum, Finland.

Runacres, S. (1999) ³H-NEXBASE 2006 FG (³H-hydrogenated poly-1-decene). Absorption study in the rat after single and repeated doses. Unpublished report No. NEY 014/984811 from Huntingdon Life Sciences, Huntingdon, Cambridgeshire, United Kingdom. Submitted to WHO by Neste Alf OY, Espoo, Finland.

    See Also:
       Toxicological Abbreviations
       Glazing agent: Hydrogenated poly-1-decene (WHO Food Additives Series 44)