966. Glazing agent: Hydrogenated poly-1-decene (WHO Food Additives Series 44)

INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

WORLD HEALTH ORGANIZATION

SAFETY EVALUATION OF CERTAIN FOOD
ADDITIVES AND CONTAMINANTS

WHO FOOD ADDITIVES SERIES: 44

Prepared by the Fifty-third meeting of the Joint FAO/WHO
Expert Committee on Food Additives (JECFA)

World Health Organization, Geneva, 2000
IPCS - International Programme on Chemical Safety

GLAZING AGENT

HYDROGENATED POLY-1-DECENE¹

First draft prepared by E. Vavasour

Chemical Hazard Assessment Division, Bureau of Chemical Safety, Food
Directorate, Health Protection Branch, Health Canada, Ottawa, Ontario,
Canada

Explanation
Biological data
Biochemical aspects
Absorption, distribution, and excretion
Toxicological studies
Acute toxicity
Short-term studies of toxicity
Genotoxicity
Observations in humans
Comments
Evaluation
References

1. EXPLANATION

Hydrogenated poly-1-decene is a mixture of synthetic
branched-chain hydrocarbons (isoparaffins) which are produced by the
oligomerization of 1-decene to the tri-, tetra-, and penta-decene
molecules followed by hydrogena-tion to full saturation of the
oligomer. Hydrogenated poly-1-decene has been proposed for use in
foods as a substitute for white mineral oil in its use as a glazing or
polishing agent for dried fruits and certain sugar confectionery, such
as fruit gums and jellies. Other uses are as a release ('non-stick')
coating in bread tins, as a lubricant in dough-dividing machines, as
an anti-dusting and anti-foaming agent, and as a plasticizer in films
that are to be used in contact with food.

Since hydrogenated poly-1-decene is a synthetic product, its
composition is well defined. The oligomer distribution of the product
is 16-35% trimer, 42-61% tetramer, 12-23% pentamer, and 1-9% hexamer;
the dimer concentration is less than 1%.

¹ The Committee gratefully acknowledges the contribution of Dr H.
Blumenthal, who prepared the working paper on this substance
before the forty-ninth meeting. That working paper was
incorporated into this monograph.

Hydrogenated poly-1-decene was evaluated by the Committee at its
forty-ninth meeting, when the results of two studies of 28 and 90
days' duration in rats given repeated doses were reviewed (Annex 1,
reference 131) and considered to be inadequate to support use of the
product as a food additive. In view of the potentially high intake
from its use, the Committee concluded that adequate data were required
to establish that the oily coats observed on rats fed hydrogenated
poly-1-decene were not the result of systemic absorption. It also
requested data that clearly demonstrated the lack of absorption of
this substance in humans. In the absence of these data, the Committee
noted that 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. The
only study submitted was an investigation of the distribution and
excretion of hydrogenated poly-1-decene and of the origin of the oily
coats on rats in the 90-day study. All relevant data, including those
reviewed at the forty-ninth meeting, were evaluated at the present
meeting.

2. BIOLOGICAL DATA

2.1 Biochemical aspects

2.1.1 Absorption, distribution, and excretion

A study was conducted with ³H-radiolabelled hydrogenated
poly-1-decene (purity not stated; oligomer distribution: 18% trimer,
56% tetramer, 29% pentamer, 5% hexamer) to determine its absorption,
pharmacokinetics in plasma, distribution in a limited number of
tissues, and excretion after oral ingestion. In the main study, single
oral doses of 30, 210, or 1500 mg/rat were administered 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,
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
hydrogenated poly-1-decene intravenously and in three rats that
received an oral dose of 210 mg per 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 ³H-hydrogenated poly-1-decene was
similar whether it 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 urine, 70% in
faeces, and 25% in the gut contents. After oral administration of
hydrogenated poly-1-decene, the radiolabel in plasma showed a large
increase during the first 4-8 h in all treated groups. In the groups

given 30 or 210 mg, the maximum concentration (C_max) 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-liveswere 81 h at 210 mg and 93 h at 1500 mg.
Most of the plasma radiolabel was associated with ³H₂O after 8 h at
30 mg, 4 h at 210 mg, and 2 h at 1500 mg. The authors reported that
the half-lives of plasma radiolabel were similar to those of ³H₂O in
the body water, 3.5 days. The plasma concentrations of radiolabel
measured 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 T_max for each dose; at lower doses, the amount of
radiolabel in liver remained high at 24 h while that in the lymph
nodes started 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 was 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. At
the higher dose, all rats showed oiliness of the fur 1 h after dosing,
and at 4 h the oiliness was clearly apparent and oily 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 highest 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 on the fur at 4 h. At the
intermediate dose, the largest amount appearing on the fur was 1.1% of
that administered 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 (AUC₁₆₈) for total plasma radiolabel was
1:2.3:7.6 (Runacres, 1999).

2.2 Toxicological studies

2.2.1 Acute toxicity

The results of studies of the toxicity of single doses of
hydrogenated poly-1-decene are shown in Table 1.

2.2.2 Short-term studies of toxicity

Rats

A 28-day range-finding study was conducted to establish an
appropriate range of doses for a 90-day study in rats. Diets
containing 0, 8000, 20 000, or 50 000 mg/kg (0, 0.8, 2, and 5%)
hydrogenated poly-1-decene (32% trimer, 47% tetramer, 17% pentamer, 4%
hexamer) were fed to groups of five male and five female Fischer 344
rats for 29 days, resulting in intakes of test material equal to 0,
1000, 2500, and 6200 mg/kg bw per day for males and 0, 1000, 2500, and
6800 mg/kg bw per day for females, respectively. Five animals of each
sex were housed per cage, observed twice daily for clinical signs, and
palpated weekly; body weights were measured twice weekly, and mean
weekly food consumption was measured for each cage. Gross autopsy at
sacrifice included an extensive inventory of the weights of the
kidney, liver, heart, spleen, and mandibular and mesenteric lymph
nodes from all animals; the liver and mesenteric lymph nodes of all
controls and all animals at the highdosewere examined histologically
but with no special staining techniques or use of polarized light to
allow visualization of accumulated material.

Table 1. Acute toxicity of hydrogenated poly-1-decene

Species^a Route Chain length LD₅₀
(mg/kg bw)

Rat Oral C10-11 > 10 000
Rat Oral C11-13 > 10 000
Rat Oral C9-11 > 34 600
Rat Oral C10-13 > 34 600
Rat Oral C9-12 > 25 000

Rabbit Dermal C10-11 > 3 200
Rabbit Dermal C11-13 > 3 200
Rabbit Dermal C9-11 15 400
Rabbit Dermal C10-13 15 000
Rabbit Dermal C9-12 > 5 000

From Mullion et al. (1990)

^a Sex unspecified

No clinical signs or deaths related to treatment were observed
during the study. The body weights were not affected by treatment, but
female rats at the high dose showed slightly elevated food
consumption, with no effect on food conversion efficiency, probably
due to compensation for the reduced nutritional quality of the diet. A
dose-related decrease in the absolute and relative weights of the

mandibular lymph nodes was seen in both male and female rats, which
was statistically significant ( p < 0.05) in females at the high
dose. A slight, dose-related decrease in the weights of the mesenteric
lymph nodes was also noted which was more pronounced in female rats.
There were no macroscopic or microscopic findings in the liver or
mesenteric lymph nodes that were related to treatment (Cooper, 1994).

Diets containing 0, 1000, 7000, or 50 000 mg/kg (0, 0.1, 0.7, and
5%) hydrogenated poly-1-decene, equal to 0, 78, 550, or 4200 mg/kg bw
per day in males and 0, 86, 610, and 4600 mg/kg bw per day in females,
respectively, 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 four-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 measured for each cage.
Ophthalmoscopic examination was made before treatment of all animals
and at week 12 for the control and high-dose animals. 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.
Histopatho-logical 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 it
was not related to dose, and females at the high dose were more
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 haemoglobin and erythrocyte

counts, but only the increase in haemoglobin count 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 count of males and females at the
high dose was 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
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 node were not assessed. The only
histopatho-logical findings were made females at the high dose, which
had a low incidence of necrosis of individual hepatocytes in the
livers (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 tissue.

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).

2.2.3 Genotoxicity

The results of studies of the genotoxicity of hydrogenated
poly-1-decene are shown in Table 2.

2.3 Observations in humans

Semi-occluded patch testing was carried out in humans with 50%
solutions in petrolatum of materials of chain lengths of C10-11,
C11-12, and C12-15. Defatting of the skin and irritation were seen,
but there was no evidence of sensitization, phototoxicity, or
photosensitization in over 100 test subjects (cited by Mullin et al.,
1990).

3. COMMENTS

³H-Hydrogenated poly-1-decene (97% radiochemical purity),
administered as a single oral dose of 30, 210, or 1500 mg/kg bw to
rats, was eliminated almost entirely in the faeces, with 0.2, 0.05,
and 0.6%, respectively, excreted in the urine; 0.07% was eliminated in
the urine of rats pretreated with 210 mg/kg bw per day for 14 days.

Negligible amounts were detected in the bile. The very low
concentrations of radiolabel in plasma and tissues did not increase in
direct proportion to dose, suggesting limited absorption of high
doses. After 8 h, 60-80% of the ³H in plasma was present as ³H₂O,
so that the label had a half-life of 80-90 h. The ratio of ³H in
liver or lymph nodes (site unspecified) to that in plasma was
approximately 5, indicating that the material within these tissues was
not simply ³H₂O and further suggesting that the material had been
absorbed from the gastrointestinal tract through the lymphatic system.
The absorbed 3H was not characterized further, and the results of
administration of an intravenous dose did not provide useful
information on the disposition of the parent compound through the
circulation. The study indicated very little absorption of
hydrogenated poly-1-decene in rats after oral administration but was
uninformative with regard to the disposition of any of the compound
that was absorbed intact. The study established that the oiliness of
the fur observed within 1-6 h of dosing was associated with
radiolabelled material originating from the anal region which was
spread by grooming activity.

In the 90-day study, rats of each sex that received diets
containing hydrogenated poly-1-decene at a concentration of 50 000
mg/kg of feed had ungroomed coats during the second week of treatment
and then oily coats from the third week of treatment to the first week
of the recovery period. The animals also showed hair loss during the
treatment period, which persisted throughout recovery for animals at
the high dose. Some marginal effects on haematological parameters were
noted. Treatment with hydrogenated poly-1-decene was associated with a
significant, but reversible, reduction in the weights of the livers of
males at the high dose, which was not associated with any unusual
histopathological observations. Treatment of females with the high
dose resulted in necrosis of individual hepatocytes and in a decrease
in the fat content of hepatocytes, as assessed histologically, with no
effect on liver weights. A dose-related decrease in the weights of
mandibular lymph nodes was noted in the 28-day study, which reached
statistical significance in females at the high dose but was not
associated with histopathological changes. This parameter was not
evaluated in the 90-day study. Accumulation of saturated hydrocarbons
was not observed in lymphoid, gastrointestinal, hepatic, or splenic
tissue.

4. EVALUATION

The Committee noted that the study of the disposition of
hydrogenated poly-1-decene did not allow clear definition of the fate
or deposition of any absorbed material. Therefore, the Committee was
unable to establish an ADI. The Committee requested an adequate study
of the absorption and deposition of hydrogenated poly-1-decene in
order to determine whether further studies were required.

Table 2. Results of assays for genotoxicity with some low-molecular-mass isoparaffins

Test system Test object Chain Concentration Results Reference
length

In vitro

Reverse S. typhimurium C11-13 7.7-77 000 µg/ Negative Xerox Corp.
mutation^a TA98, TA100, plate (1981)
TA1535, TA1537,
TA1538

Reverse S. typhimurium C10-11 7.5-75 000 µg/ Negative Xerox Corp.
mutation^a TA98, TA100, plate (1983)
TA1535, TA1537,
TA1538

Reverse S. typhimurium C10-13 < 10 000 µg/ Negative Phillips
mutation^a TA98, TA100, plate Petroleum
TA1535, TA1537, Co (1990)
TA1538

DNA E. coli, Pol A+/A- C11-13 7.7-77 000 µg/ Negative Xerox Corp.
damage plate (1981)

DNA E. coli, Pol A+/A- C10-11 7.5-75 000 µg/ Negative Xerox Corp.
damage plate (1981)

Reverse E. coli, WP2 C10-11 7.5 -75 000 µg/ Negative Xerox Corp.
mutation^a plate (1981)

Cell Mouse lymphoma C10-13 < 1000 µg/ml Negative Phillips Petroleum
mutation^a L5178Y cells, Co. (1990)
Tk+/- locus

Sister Chinese hamster C10-13 < 50 µg/ml Negative Phillips
chromatid ovary cells Petroleum
exchange^a Co. (1990)

Table 2. (continued)

Test system Test object Chain Concentration Results Reference
length

In vivo

Micronucleus Mouse bone C10-11 19 g/kg bw, Negative Xerox Corp.
formation^b marrow intraperitoneally (1983)

Dominant Sprague-Dawley C10-11 0, 300, 900 ppm, Negative Exxon Corp.
lethal rat 6 h/day, 5 d, by (1978)
mutation inhalation

^a In the presence and absence of Arochlor-induced rat liver microsomal fraction
^b Sacrificed at 48 and 72 h

No studies of genotoxicity have been conducted with the test
material; however, the results of tests for genotoxicity with related
isoparaffinic compounds of lower molecular mass showed that they had
no effect on a variety of end-points. Consequently, the Committee
concluded that tests for the genotoxicity of hydrogenated
poly-1-decene were not required.

Patch tests on human skin with the same low-molecular-mass
isoparaffins did not indicate sensitization.

5. REFERENCES

Cooper, S. (1994) NEXBASE 2006 FG: Preliminary toxicity study by
dietary administration to F-344 rats for four weeks. Unpublished
report No. 93/1140 from Pharmaco-LSR Ltd, Eye, Suffolk, United
Kingdom. Submitted to WHO by Neste Alfa OY, Espoo, Finland.

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.

Exxon Corp. (1978) Cited by Mullin et al. (1990).

Mullin, L.S., Ader, A.W., Daughtrey, W.C., Frost, D.Z. & Greenwood,
M.R. (1990) Toxicology update: Isoparaffinic hydrocarbons: A summary
of physical properties, toxicity studies and human exposure data.
J. Appl. Toxicol., 10, 135-142.

Phillips Petroleum Co. (1990) Unpublished data submitted to WHO by
Neste Alfa OY, Espoo, 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 Alfa OY, Espoo, Finland.

Xerox Corporation (1981) Unpublished data submitted to WHO by Neste
Alfa OY, Espoo, Finland.

Xerox Corporation (1983) Unpublished data submitted to WHO by Neste
Alfa OY, Espoo, Finland.

    See Also:
       Toxicological Abbreviations
       Glazing agent: Hydrogenated poly-1-decene (JECFA Food Additives Series 48)