Industrial chemicals and environmental contaminants

Experience

Within this group are the classic pesticides dichlordiphenyltrichlorethan (DDT), hexachlorbenzene (HCB), dieldrin , hexachlorcyclohexan (HCH), and “synthetic oils” made from polychlorinated biphenyls (PCBs) as well as the polychlorinated dioxins and furans .

Dioxins are considered a group of toxic chemicals with similar chemical structures and biologic characteristics. Exposure comes from environmental contamination from forest fires, backyard burning of trash, industrial activities and previous industrial burning of waste. Degradation of dioxins is slow and residuals persist from past man-made and natural events.

Almost all living things have been exposed to dioxins. Adverse health effects depend on level of exposure as well as when, how long and how often, an individual is exposed.

Of the organochlorine pesticides, only the short-lived χ-HCH ( lindane ) is still produced today (see Chapter 4.12 ). Other organochlorine pesticides such as DDT have been produced since the 1970s for export only to developing countries – at present there is a DDT “renaissance” for malaria prevention in Africa. For the most part, however, organochlorine pesticides have been replaced by carbamates , organophosphates , and pyrethroids . These substances are, to some extent, significantly more toxic, but they have a lesser tendency towards persistence and accumulation in nature.

Polychlorinated biphenyls were used as softeners and color additives. Since the 1970s they may only be used in closed systems, such as hydraulic fluid and transformer or condenser filling. Since the end of the 1980s the use of polychlorinated biphenyls has been banned in most countries, but the machines installed earlier still contain large quantities of these congeners.

Polychlorinated dibenzodioxins and -furans, among which group is the quadruply-chlorinated “seveso toxin” 2,3,7,8-TCDD , occur in connection with technical activities as by-products or impurities during the synthesis of organochlorine compounds, and when they are recycled and burned. Trash dumps and chlorinated additives in automobile fuel are among the most significant sources of dioxin in our environment.

Toxic symptoms in the infant as a result of organochlorine compounds in the mother’s milk have been described only after extreme exposure. The Turkish porphyria ( Pemba–Yarda syndrome ) occurred after consumption of seed grain treated with hexachlorbenzene . Apart from skin rash and weight loss, there were also lethal consequences for breastfed babies ( ). Yusho disease was caused by polychlorinated biphenyls in contaminated cooking oil. It caused muscular hypotonia, hyperexcitability, and apathy in the infants. The illness continued for many years ( ).

Concentrations in mothers’ milk

Safety levels for organochlorine compounds in mothers’ milk are aligned with the “no adverse effect level” (NOAEL) determined in animal studies. This is understood to be the amount of a contaminant per kg bodyweight, taken in daily, that no longer causes any toxic effect (for example, a weight increase of the liver with a rise in enzyme activity in the rat). Based on the NOAEL, and taking into consideration a safety factor (SF), the acceptable daily intake (ADI) of the contaminant involved is calculated for a human being (adult or infant). The safety factor should actually be of the magnitude of 100–1,000, but in practice, for PCBs in mothers’ milk, a factor of only 10 was occasionally calculated. This means that beyond a level 10 times the amount ingested by a breastfed infant per kg bodyweight daily, toxic effects can be expected in animal studies. Contamination of human milk with polychlorinated biphenyls is significantly greater than in cows’ milk. The term PCB covers some 200 congeners, among which the congeners 138, 153, and 180 predominate, and are frequently presented as a proxy for the entirety of PCB contamination.

The average dioxin load in mother’s milk is usually expressed in I-TEQ (International TCDD-equivalent) – i.e. the equivalent amount of seveso toxin 3,4,7,8-tetrachlordibenzodioxin that corresponds to the total amount of all dioxin- and furan-congeners in the analyzed specimen. According to the , the acceptable daily intake is 1–4 pg I-TEQ/kg bodyweight per day; the American Environmental Protection Agency (EPA) allows 0.1 pg/kg per day. These values are exceeded by nursing infants by up to 100-fold or more – for example, in Germany a fully breastfed infant receives on average 55 pg I-TEQ/kg per day. However, the acceptable dosages were defined for lifelong intake and not limited to the lactation period.

Regional differences in milk contamination

The different analytical methods used in different countries must be considered when comparing contamination in mothers’ milk. In general, significantly higher contamination with DDT and DDE can be observed in many so-called “developing countries” ( , ), while PCBs and dioxins are found at higher levels in industrialized countries. Corresponding differences were found between Eastern and Western Europe, with more PCBs in the West ( , ). Regional differences may also be explained by differences in nutrition of the studied cohorts ( ).

During the 1980s, DDT/DDE concentrations of, on average, 45 mg/kg milk fat were reported in Indonesia. Levels in South Africa, Kenya, Hong Kong, and India were between 10 and 20 mg/kg; in Europe, the USA, and Australia, levels were between 1 and 2 mg/kg. Depending on the analytical methodology, the average results for PCBs in Europe, Israel, and the USA were between 0.5 and 2.5 mg/kg milk fat (survey in ). In industrial nations, dioxins in human milk fat were between 15 and 25 ng I-TEQ/kg milk fat. Up to 1991, some authors still observed a rise in the average contamination in mothers’ milk ( ).

Since the early 1990s, a tendency towards declining levels of persistent organochlorine compounds has been noted in the milk. Today, PCB contamination has reduced to one-third of the values measured in Europe in the 1980s – in Germany, for example, more than 30,000 samples of human milk have been analyzed ( ) to come to this conclusion. The current data on dioxin contamination in mothers’ milk show that here, too, there has been a decline, from 37 pg/g fat in 1988 to 12 pg/g fat in 2002. Nevertheless, contamination levels in the Netherlands (18 pg/g fat) and Germany are still among the highest in Europe. Lower levels have been reported in Croatia and Spain, and also in Taiwan ( , ).

In another German publication on the development of contamination in mothers’ milk in Baden-Württemberg, it was reported that in 1988 a total of 14% of the milk samples contained at least one of the studied substances at levels above 10% of the NOAEL (mostly PCBs). In accordance with the recommendations that were in effect until 1996, mothers with such levels were advised not to breastfeed beyond 4 months. By 1996, only 2% of the milk samples exceeded this so-called SF-10 value. The number of milk samples studied every year was initially over 1000; by 1990 it reached its peak, with 1983 samples studied. By 1996, the number had declined to 280 ( ).

Persistently high PCB levels in mother’s milk were found in the Faroe Islands – the level was 2300 ng/g fat in 1987, and by 1999 it was still 1800 ng/g ( ).

Polybrominated diphenyl ethers

Increasing levels of polybrominated diphenyl ethers (PBDE) were observed in mothers’ milk on the Faroe Islands (rising from 2 ng/g fat in 1987 to 8 ng/g in 1999) ( ). PBDE contamination of breast milk was also found in other countries. PBDEs are a group of more than 200 structurally similar congeners that are used as flame-retardants in electrical appliances such as television sets and computers, as well as in carpets and furniture upholstery. Because these compounds can accumulate in human tissues and, in adequate concentrations, alter metabolic and physiologic functions, the European Union (EU) banned the production, use, and import of pentabromodiphenyl ether and octabromodiphenyl ether products in 2004. Decabromodiphenyl ether is still in use, and its main congener, deca-BDE 209, can be detected in breast milk. A German study of 89 lactating women found, on average, 1.65 ng/g milk fat among vegetarians and a significantly higher level (2.47 ng/g) among women eating a varied diet that included meat. As with organochlorines, the levels were lower in women who had breastfed many infants. However, no significant decrease was observed between the neonatal period and 3 months after birth. A fully breastfed child ingests, on average, 10 ng/kg bodyweight and, at maximum, 50 ng/kg. Considering the NOAEL for PBDE, this corresponds to a margin of safety (MOS) of >10 ⁴ . Therefore, health problems are not to be expected ( ). PBDE contamination in North America is one order of magnitude higher than that measured in Germany.

Levels measured in breastfed infants

It is estimated that breastfed infants receive one to two magnitudes more dioxins than adults. found the highest plasma concentrations after birth. At 6 months, regardless of the type of feeding, the lowest values were measured. Although the absolute amount of polychlorinated biphenyls and dioxins transferred with the milk is greater than that transferred by the placenta during pregnancy, the “dilution effect” that occurs as a result of the infant’s rapidly increasing fatty tissue appears to decrease the concentration in the infant’s plasma.

For dioxin, the elimination half-life of 4 months in newborns is significantly shorter than that in adults (5 years). This also contributes to the fact that although fully breastfed children have significantly higher TCDD concentrations in the blood and fatty tissue than do non-breastfed babies, the differences have completely leveled out after a few years ( ). A detailed model to predict dioxin levels in the body fat of infants, dependent on the duration of breastfeeding (no breastfeeding; and after 6 weeks, 6 months, 1 year, and 2 years), was presented by . According to this model that was validated with data from the study cohort of , breastfed infants reach peak values during their first months of life. Up to the age of 7–10 years, however, these levels approach those found in children who were not breastfed. For observed no difference between breastfed and formula-fed children at the age of 12 years.

Effects of average contamination on infant development

Among the numerous studies on persistent organochlorines in the “normal” environment, some present levels in maternal and infant blood, and in breast milk ( , , , , , , , ). Others focus on somatic and mental development (survey in ). There are mainly four larger research projects which have led to several publications, i.e. the studies in North Carolina, Michigan, The Netherlands and Germany. In North Carolina, 865 infants were enrolled in around 1980 to investigate their development until the age of 5 and at puberty ( ). Illnesses during childhood were not associated with exposure to PCB and DDE via breast milk. Furthermore, there was no significant correlation with mental and psychomotor development, or with somatic development and puberty.

The so-called Michigan study covered 240 children whose mothers regularly consumed PCB-contaminated fish from the Great Lakes (>11.8 kg over 6 years). The control group consisted of 71 children of mothers who did not consume such fish. Visual recognition at the age of 7 months was not affected. However, subtle differences of development were observed at the age of 4 years. These were more pronounced in children who had been breastfed for at least 1 year. Intelligence was not affected, at least up to the age of 11 years ( , , ).

A Dutch study with 100 breastfed and 100 formula-fed children focused on PCB and dioxins ( ). Higher levels in milk were associated with elevated TSH values at birth and at 3 months, indicating disturbance of thyroid function. Neurological examinations of 400 newborns and psychomotor and cognitive tests up to the age of 4 years, revealed no persisting effects of PCBs or dioxins (survey in ).

A German study on mental and motor development found a negative association between PCB levels in milk and performance of the Kaufman score at the age of 42 months. Other outcome parameters were uneventful in this study, which covered in total 171 mother–child-pairs ( ).

Other studies with smaller cohorts observed associations between dioxins, furans, and PCB in breast milk with lower levels of thyroid hormones, increased CD4+ lymphocytes, reduced CD8+ lymphocytes (T suppressor cells), slightly elevated liver enzymes, and lower platelet counts. In general, development was normal up to 6 months of age (survey in ). Even considering moderate contamination of breast milk, some authors suggest an overall positive effect of breastfeeding on psychomotor and cognitive development that compensates for potential impairments due to toxic contaminants ( , , ).

State governments, industry and the Environmental Protection Agency (EPA) have worked diligently to reduce known and measurable industrial emissions of dioxin. Air emissions of dioxin have been dramatically reduced by 90% and most Americans have low level exposures. The document “Reanalysis of Key Issues Related to Dioxin Toxicity” was released in February 2012 ( ). It contains a detailed and transparent description of the underlying data and analysis. The oral reference dose (RfD) for 2,3,7,8–Tetrachlorobenzo-p-Dioxin (TCDD) is 7 × 10 ⁻¹⁰ mg/kg-day, derived from two epidemiologic studies ( ).