Synopsis on dioxins and PCBs

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Ranch Hand, a U.S. military operation during Vietnam war where antifoliant agents were spread over large areas to kill vegetation. One of the compounds used was Agent Orange, which contained mostly 2,4,5-T and was contaminated by PCDD/Fs. (See also chlorophenoxyacetic acid herbicides).

ribosome, a cell organelle where protein synthesis takes place. Ribosomes themselves are formed of several protein molecules.

risk assessment. See PCDD/F - risk assessment, conservative risk assessment.

RNA (ribonucleic acid), a nucleic acid similar to DNA (see this), but instead of thymine, one of the bases is uracil. There are three kinds of RNA. Messenger RNA is a copy of one gene copied during transcription from DNA, and it usually gives a code for one protein molecule. Transfer RNA transfers one amino acid at a time to a nascent protein in the ribosome. Ribosomal RNA functions in ribosomes. To learn more of these, grab any modern biology textbook.

Santotherm FR, a commercial PCB product. See PCB - trade names.

seven marker PCBs (Σ7PCB), a selection of PCB congeners. Σ7PCB denotes the sum of the seven marker PCBs. In a sample containing PCBs, there are often several dozens of different congeners. For practical reasons, all of them are not always measured, but the most important congeners are used as indicators. In Belgian chicken incident, only seven abundant congeners were usually measured: congeners with IUPAC numbers 28, 52, 101, 118, 138, 153, and 180 (2,4,4'-TriCB, 2,2',5,5'-TCB, 2,2',4,5,5'-PeCB, 2,3',4,4',5-PeCB, 2,2',3,4,4',5'-HxCB, 2,2',4,4',5,5'-HxCB, 2,2',3,4,4',5,5'-HpCB, respectively). The seven congeners are estimated to constitute about one third of all PCBs in the contaminated feed.

Seveso accident, the best-known dioxin accident in 1976 in Italy. In Seveso, 20 km north of Milan, a trichlorophenol production reactor in a chemical factory blew up and released kilogram quantities of TCDD to the environment. The cloud of chemicals spread as far as 6 km from the factory, and settled on the ground. Within 5 weeks the area was subdivided into three subareas based on soil concentrations: zone A (87 hectares, over 50 µg/m2 of TCDD), zone B (270 hectares, over 5 µg/m2), and zone R (1430 hectares, below 5 µg/m2). From zone A over 730 inhabitants were evacuated, and strict hygienic regulations were set for other zones. In a selected group of highly exposed persons, TCDD concentrations up to 56,000 ng/kg (TCDD in fat) were detected. In randomly sampled persons, the calculated median concentrations were 390 ng/kg (TCDD in fat) (zone A), 78 ng/kg (zone B) and in the reference population 5.5 ng/kg.
Chloracne was observed in a number of persons, most of them children. In 15-year follow-up studies, no increased total mortality was observed, but there was an increase of leukaemia (7 cases, 2.2 expected in zone B) in males, and myeloma (4 cases, 0.6 expected in zone B) in females. All-cancer mortality or mortality from the most common cancers were not increased (e.g. there were non-significantly less breast cancers than expected). There were no increases in zone A, but the population was too small for reliable analysis. One may conclude that, noting the relatively short period of observation, the increase of some cancers is likely to be real, but considering the high exposure, the risk is not very high (for details, see Bertazzi et al., Epidemiology 1997:8:646-652).

six marker PCBs (Σ6PCB), a selection of PCB congeners. Σ6PCB denotes the sum of the six marker PCBs. In a sample containing PCBs, there are often several dozens of different congeners. For practical reasons, all of them are not always measured, but the most important congeners are used as indicators: congeners with IUPAC numbers 28, 52, 101, 138, 153, and 180 (2,4,4'-TriCB, 2,2',5,5'-TCB, 2,2',4,5,5'-PeCB, 2,2',3,4,4',5'-HxCB, 2,2',4,4',5,5'-HxCB, 2,2',3,4,4',5,5'-HpCB, respectively).

sources of PCBs and PCDD/Fs. See PCDD/F - sources and PCB - sources.

Sovol, a commercial PCB product. See PCB - trade names.

spectrum of congeners. See profile of congeners.

steady state, the state during which the amount of chemical in the body stays constant, i.e. the same amount is eliminated per unit of time as is entering the body (see cumulation).

2,4,5-T (2,4,5-trichlorophenoxyacetic acid), a herbicide presently banned in many countries. See chlorophenoxyacetic acid herbicides.

TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin, the most potent of polychlorinated dibenzo-p-dioxins. For properties, see PCDD/F - specific items).

TDI, tolerable daily intake (see that).

TEF (TCDD equivalency factor, toxic equivalency factor), a relative toxicity factor of a PCDD/F or PCB congener as related to TCDD. TEF values vary from 1 to 0.00001 or 0 (Table 4; see also TEq). The latest re-evaluation of TEF values was that by WHO in 1998, and these TEF values have been used in this booklet as WHO-TEF for PCDD/Fs and PCB-TEF for PCBs. TEq = ΣTEFi*Ci, where Ci is the amount (or concentration) of congener i.

Table 4. Toxic equivalency factors for all PCDD/Fs and PCBs that have a TEF>0. Other congeners are not supposed to have dioxin-like effects. IUPAC numbers for PCBs are given in parenthesis.

Congener WHO-TEF
PCDDs
2,3,7,8-TCDD
1,2,3,7,8-PeCDD
1,2,3,4,7,8-HxCDD
1,2,3,6,7,8-HxCDD
1,2,3,7,8,9-HxCDD
1,2,3,4,6,7,8-HpCDD
OCDD

1
1
0.1
0.1
0.1
0.01
0.0001
PCDFs
2,3,7,8-TCDF
1,2,3,7,8-PeCDF
2,3,4,7,8-PeCDF
1,2,3,4,7,8-HxCDF
1,2,3,6,7,8-HxCDF
1,2,3,7,8,9-HxCDF
2,3,4,6,7,8-HxCDF
1,2,3,4,6,7,8-HpCDF
1,2,3,4,7,8,9-HpCDF
OCDF

0.1
0.05
0.5
0.1
0.1
0.1
0.1
0.01
0.01
0.0001
Non-ortho-PCBs
3,3’,4,4’-TCB (77)
3,4,4’,5-TCB (81)
3,3’,4,4’,5-PeCB (126)
3,3’,4,4’,5,5’-HxCB (169)

0.0001
0.0001
0.1
0.01
Mono-ortho-PCBs
2,3,3’,4,4’-PeCB (105)
2,3,4,4’,5-PeCB (114)
2,3’,4,4’,5-PeCB (118)
2’,3,4,4’,5-PeCB (123)
2,3,3’,4,4’,5-HxCB (156)
2,3,3’,4,4’,5’-HxCB (157)
2,3’,4,4’,5,5’-HxCB (167)
2,3,3’,4,4’,5,5’-HpCB (189)

0.0001
0.0005
0.0001
0.0001
0.0005
0.0005
0.00001
0.0001

TEq, TCDD equivalent quantity, toxicity equivalent (see also TEF). Different congeners of dibenzo-p-dioxins and dibenzofurans have many of the same biological effects but they are differently potent, meaning that different doses are needed to cause the same effect (Figure 8). E.g. 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (HxCDD) is one tenth as toxic as TCDD. To be able to assess the effects of a mixture, all congeners are "normalised" to the effects of TCDD, e.g. the amount or concentration of HxCDD is multiplied by the equivalency factor 0.1 (its TEF is 0.1). When all congeners are given as "equivalents of TCDD" they can be simply added and the sum gives the total toxicity of the mixture. Various TEq values have been developed, e.g. WHO-TEq, Nordic TEq and international TEq or I-TEq. WHO-TEq values are based on the most recent scientific consensus. The differences between the respective TEFs are not great. Also the most important dioxin-like PCBs have been given TEF values, but it should be appreciated that PCBs may have other effects that cannot be expressed by a TCDD-equivalency. (For more information on TEq concept and its use, see Ahlborg et al., Eur. J. Pharmacol. 1992:228:179-199; Van den Berg et al., Environ. Health Persp., 1998:106:775-792).


Figure 8. Congener profile of human milk samples (17 dioxin-like PCDD/Fs). A, weight basis (describes the amount); B WHO-TEq basis (describes the toxic potency).

tetra-, four. E.g., tetrachloro- four chlorine atoms in a molecule.

Times Beach, a village in Eastern Missouri where salvage oil containing over 30 mg/kg TCDD, was used to spray a horse arena and 23 miles of roadways as dust suppressant in 1971. Hundreds of birds and rodents died in the neighbourhood, as well as 48 of the 85 horses exercised in the arena. Three children and one adult developed chloracne. The source was ultimately traced to the distillation bottom sludges of a hexachlorophene manufacturer. The incident led to evacuation of the population and a buyout of the whole community by U.S. Federal Government.

tolerable daily intake dose (TDI), a theoretical concept of regulatory toxicology giving the highest dose of a chemical which can be assured to be safe even if one is exposed to the chemical through the whole lifetime. Most TDI values have been estimated on the basis of animal experiments. Usually the TDIs include safety margins to guarantee safety even if human being should be more sensitive than the animal. The safety margin is often 100-fold, but could be larger, if research data is not satisfactory. If the chemical is carcinogenic (see this), different methods are used in different countries. Some countries use large safety margin (e.g. 1000-fold), some use mathematical extrapolations (see this) to reach a level deemed safe (e.g. a maximum likelihood of one in a million chance of contracting cancer due to a lifetime exposure to the chemical). The important point is that the purpose of TDI is to serve regulators in administrative work, and not individual persons. It does not predict the likelihood of individual's health effect in any reliable way, if the limit is exceeded. TDIs of dioxins set by various authorities in different countries vary by more than thousandfold, which illustrates the difficulties in dioxin risk assessment. The latest recommendation for TDI for the sum of dioxins and dioxin-like PCBs is 1 to 4 pg/kg/day (WHO-TEq per b.w.), in other words, in 70-kg person 70 to 280 pg/day. This should be understood as the average intake over a long period of time (see cumulation).

toxicity in humans, see PCB - toxicity in humans, PCDD/F - toxicity in humans.

transcription, reading the genetic message from DNA (see this) to RNA.

transcription factor, a cell protein that can bind to specific sites at DNA (see this) or a member of a set of such proteins which after binding to DNA initiate a chain of events leading to expression of a particular gene. This usually leads to the synthesis of a protein determined by that gene.

translation, reading the message in messenger RNA (see RNA) to make a protein.

tri-, three. E.g., trichloro- three chlorine atoms in a molecule.

trophic levels, ecological levels of nutrition. In the Baltic Sea white-tailed eagle feeds on salmon, which feeds on herring, which feeds on small crustaceans and animal plankton, which feeds on phytoplankton. Chemicals may be transferred and bioconcentrated along such trophic levels.

units. Concentrations and amounts of dioxins and PCBs are very small, and therefore units to measure them do not belong to everyday vocabulary (Table 5.). One picogram per gram results, if 10 g (a spoonful of sugar) is dissolved in a lake 10 m deep and one square kilometre large. These small concentrations we are dealing with explain why rather small amounts of chemicals can contaminate large amounts of feed, for instance.
PCDD/F concentrations are often expressed as TEq (see this). PCB is usually expressed as sum of all PCBs (ΣPCBs) or as sum of marker PCBs analysed (e.g. Σ7PCBs, sum of seven marker PCBs [see this]).
Concentrations of PCBs or PCDD/Fs can be expressed per wet weight (w.w.) (e.g. in fish), per dry weight (d.w.) (e.g. in soil), per normalised cubic meter (Nm3) (e.g. in exhaust gases), or per fat. Many organisms contain about 10 % fat, then the difference between concentrations per fat and per wet weight is about tenfold. However, especially fish may be very different in their fat content, and usually PCBs and PCDD/Fs in fish are given per wet weight. Human PCBs and PCDD/Fs are mostly expressed per gram fat, because the concentrations are comparable regardless of if it was measured in serum, adipose tissue or milk. Human body contains about 15 % (10 -12 kg) fat, but the variation is large, especially upward. See also Common sources of errors and practical difficulties in General introduction.

Table 5. Weight units.

1 kg (kilogram) 1000 g  103 g
1 g (gram) 1 g 100 g
1 mg (milligram) 0.001 g  10-3 g
1 µg (microgram)  0.000,001 g 10-6 g
1 ng (nanogram) 0.000,000,001 g 10-9 g
1 pg (picogram) 0.000,000,000,001 g 10-12 g
1 fg (femtogram) 0.000,000,000,000,001 g 10-15 g

use of PCBs, see PCB - use.

xenobiotic, foreign chemical. See also metabolism.

Yu-Cheng incident, contamination of rice oil with PCB in Taiwan. In 1979, 2061 persons were determined to be victims of PCB poisoning, and the affected persons had been using rice-bran oil contaminated (53-99 mg/kg [ΣPCB in fat]) by PCBs used in heat transfer system. The PCB intake was estimated to be 700 to 1,800 mg (ΣPCB per person) and the average estimated PCDF intake 3.8 mg (ΣPCDD/F per person). Average blood levels were 50-100 µg/litre (ΣPCB). As in the earlier Yusho incident (see this) the main signs were eye problems (swelling, hypersecretion of Meibomian glands), abnormal pigmentation, decreased nerve conduction velocities, hyperpigmentation and tooth deformities of babies born to affected mothers.

Yusho incident, contamination of rice oil with PCB in Japan. In the year 1968, patients with chloracne came to the dermatology clinic in Fukuoka, and this disease was connected with the consumption of a batch of rice oil which was contaminated (2000-3000 mg/kg [ΣPCB in fat]) with Kanechlor 400, a PCB used in the heat exchanger leaking to the rice oil. The average estimated intake per person was 633 mg PCBs and 3.4 mg PCDFs among some other chemicals. This has been estimated to be 154,000 pg/kg/day (I-TEq per body weight per day) or 100,000 times higher than average background intake. The earliest signs of toxicity were enlargement and hypersecretion of Meibomian glands in the eyes, swelling of the eyelids and pigmentation of skin and mucous membranes. Many different skin problems followed, including darkening of the skin, hyperkeratosis and chloracne. Babies born to Yusho mothers were smaller than normal, they showed a dark brown pigmentation, and some of them had gingival hyperplasia and dentition at birth. The total number of patients was about 1,200 which is rather small number to evaluate effects on cancer reliably, but there seems to be an excess of cancer deaths among the male patients. Japanese research groups have concluded that the main signs and symptoms were due to the minor contaminants, i.e. PCDFs of the PCB contaminating rice oil. International Programme on Chemical safety concluded in 1993 that the intoxications of Yusho and Yu-Cheng were caused mainly by a combined effect of PCBs (especially coplanar ones) and PCDFs. For more information on Yusho see "Yusho; A human disaster caused by PCBs and related compounds", ed. By M. Kuratsune, H. Yoshimura, Y. Hori, M. Okumura, Y. Masuda, Kyushu Univ. Press, Fukuoka, 1996.

Σ (sigma), sum. Ordered alphabetically at the main entry disregarding the prefix.
 
 





 



Contents of the Synopsis

Synopsis main page

Information on the publication
General introduction

Burning produces dioxins
Dioxins and some PCBs cause multiple toxic effects.
Dioxins and PCBs accumulate in the human body.
Risk assessment is tricky.
Common sources of errors and practical difficulties.
Encyclopedia 
from A to C
from D to O
from P to Q
from R to Z
Tables and figures

Version 0.2 updated 17.9.1999 Jouni Tuomisto

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