Octabromodiphenyl ether – isomer mixture 2,2',3,3',4,4',5',6-, 2,2',3,3',4,4',6,6'- and 2,2',3,4,4',5,5',6-  - ihalable fraction. Documentation   Jadwiga A. Szymańska, Elżbieta Bruchajzer Dibutyl phthalate –  ihalable fraction. Documentation   Anna Pałaszewska-Tkacz,  Sławomir Czerczak   Anhydrous sodium perborate and sodium perborate hexahydrate – inhalable fraction. Documentation   Małgorzata Kupczewska-Dobecka Styrene. Documentation   Andrzej Starek   1,1,2-Trichloroethane. Documentation   Karolina Bystry, Jan Stetkiewicz

Octabromodiphenyl ether – isomer mixture 2,2',3,3',4,4',5',6-, 2,2',3,3',4,4',6,6'- and 2,2',3,4,4',5,5',6-  - ihalable fraction. Documentation  
Jadwiga A. Szymańska, Elżbieta Bruchajzer

Octabromodiphenyl ether (octaBDE) is a white solid obtained by bromination of diphenyl ether. The most common form in which octabromodiphenyl ethers occurred were the technical (commercial) mixtures. These consisted of compounds of varying degrees of bromination.
Octabromodiphenyl ether was used as a flame retardant, often in combination with antimony trioxide. OctaBDE was used in the production of synthetic polymers such as ABS, HIPS and PBT, which were used in the automotive, electrical and electronic equipment industries.
Octabromodiphenyl ether, due to its physicochemical properties (such as a weak water solubility, thermal and chemical stability) and the ability to accumulate is a POP (persistent organic pollutant). The ban on the production and use of octaBDE was introduced in 2004.
Octabromodiphenyl ether has been found in the environment as a result of using and recycling equipment containing this compound. Concentrations of 6600 pg/m³ in the air were detected in a hall where hardware was dismantled (concentrations of the sum of polybrominated diphenyl ethers were 170 000 pg/m³).
So far, there have been no cases of people being poisoned.
Octabromodiphenyl ether in experiments on animals showed low acute toxicity. The mean lethal dose (LD50) for rats after oral administration was 5000 mg/kg body weight. This compound did not irritate the skin or eyes, and did not cause sensitization.
The toxic effects observed after short-term experiments and repeated administration of octaBDE to animals were similar. The most important role in the toxic effects of octabromodiphenyl ether are functional changes in the liver and thyroid, and after inhalation exposure - changes in the respiratory tract.
In short-term exposure (4-14 days of intragastric administration), the first symptoms of the toxicity (increase in relative liver weight, induction of PROD activity in the liver) were observed after  4-day exposure to octaBDE at 10 mg/kg/day. After higher doses (30 to 100 mg/kg/day) these effects are intensified. In addition, there were signs of the disturbance of thyroid function (decrease in the levels of T3 and T4 in the serum). A significant acceleration of hepatic metabolism was noted after 14-day administration of octaBDE at 80 mg/kg/day.
After repeated (28- and 90-day) intragastric exposure of rats to doses of 7–8 mg/kg/day the first symptoms of toxicity (increase in relative liver weight and histopathological changes in the liver) were observed. The 28 doses of 70-80 mg/kg/day caused a moderate hyperplasia of the thyroid, and after 90 days an increase in thyroid weight and its impaired function (reduction T4 levels in the serum). After higher doses of octabromodiphenyl ether (about 700 – 1000 mg/kg/day) the effects were intensified.
After subchronic (90 days) inhalation exposure of rats to octaBDE at the concentration of 1.1 mg/m³, no systemic toxicity was observed, only a slight increase in goblet cells in nasal mucosa (topical toxicity). Due to exposure to the compound at the concentration of 16 mg/m³, inflammation in the lungs, hyperplasia of hepatocytes and thyroid dysfunction (increase in TSH levels and decrease in T4 levels in the serum) were found. These symptoms were intensified after exposure to the compound at the concentration of 202 mg/m³; additionally, reproduction disorders were observed (absence of the corpus luteum in 30% of females and no normal cells in the seminiferous tubules or the presence of abnormal cells in the seminiferous tubules in the male).
Octabromodiphenyl ether was not mutagenic and genotoxic. In laboratory animals, adverse effects on fetal development were observed; causing, among other things, higher incidence of late resorptions, decreased fetal birth weight, changes in ossification and developmental disorders of limb bones, ribs and sternum.
Octabromodiphenyl ether is not classified as a carcinogen for humans, and the Environmental Protection Agency (EPA) classified it in Class D.
The mechanism of toxicity of polybrominated diphenyl ethers (PBDEs), including octabromodiphenyl ether, is associated with induction of hepatic microsomal enzymes, which may lead to changes in the metabolism of xenobiotics. Induction of microsomal enzymes, especially CYP 1A1 and CYP 1A2 (EROD) and CYP 2B (PROD), points to the Ah receptor binding and CAR. Changes in metabolism can affect thyroid hormone homeostasis, causing abnormal development of the central nervous system, mainly in young persons.
There is only a SCOEL proposal (2010) that the value was 0.2 mg/m³ OEL. The basis for the proposed value of the maximum admissible concentration (MAC) are literature data on the toxicity of 90-day inhalation exposure of rats. To calculate the MAC, we propose the NOAEL for systemic toxicity equal to 1.1 mg/m³. After determining the coefficients of uncertainty, adaption of the concentration of 0.1 mg/m³ for the MAC TWA value for octabromodiphenyl ether has been proposed. No MAC-STEL (NDSCh) values have been established. A "Ft" (fetotoxic substances) notation was recommended.

Dibutyl phthalate –  ihalable fraction. Documentation  
Anna Pałaszewska-Tkacz,  Sławomir Czerczak  

Dibutyl phthalate (DBP) is a clear, oily liquid with ester-like odour. It is used mostly as a plasticizer for resins and polymers such as polyvinyl chloride,  sealants and adhesives  and inks.
As far as occupational exposure is concerned, the inhalation route of exposure is important and, to a lesser extent, dermal contact. Because of low vapour pressure at room temperature, the high concentration of DBP may only occur during technological processes where the temperature is elevated or DBP aerosols are generated. Measurements done by a European company in the 1990s showed that during DBP production the mean concentration of this substance in the workplace was below 0.5 mg/m³, and only in a few workplaces 1.1 or 5 mg/m³. In a different plant, the mean DBP concentration was 0.04 mg/m³ in 1992  and 0.7 mg/m³ in 1995.
In 2007 and 2010, according to data of Polandʼs Chief Sanitary Inspectorate, no workers were occupationally exposed to DBP in concentrations in excess of Polish OEL values. According to the Polish inventory of occupational diseases of the Nofer Institute of Occupational Medicine (Lodz, Poland), in 2001-2010 there was only one case of skin disorder in a worker occupationally exposed to DBP.
DBP is absorbed in the respiratory and gastrointestinal tract, no significant accumulation has been recorded and it is excreted mainly in urine.
LD50  values derived from experiments with rodents revealed that DBP was a substance of relatively low acute toxicity. In most studies, the substance caused no irritation or sensitisation in human or in laboratory animals.
According to available data, subchronic and chronic toxicity of DBP was evaluated almost exclusively on the basis of studies on rats exposed orally. NOAEL values were equal to 176 – 353 mg/kg bw/d; the most often observed effects of exposure were decrease in body weight, changes in blood parameters and a relative increase in the weight of the liver and kidneys.
DBP is a compound of a confirmed reprotoxic activity. According to Regulation (EC) No. 1272/2008 of the European Parliament and of the Council, DBP is classified as Reprotoxic, category 1B with hazard statement H360Df (may damage the unborn child, suspected of damaging fertility). In the available studies on DBP reprotoxocity, the lowest described NOAELs were 50 mg/kg bw/d for fertility and 30 mg/kg bw/d for foetus effects.
In Poland, like in most European countries, the OEL value was set at the level equal to 5 mg/m³. This value is supposed to protect from burdensome working conditions connected with exposure to DBP aerosols expected due to its low vapour pressure. Taking into account the NOAEL values cited in the available literature, it was agreed that this level should also protect from toxic and reprotoxic DBP activity. It was agreed that the previous DBP OEL value of 5 mg/m³ should remain unchanged. Simultaneously, it was proposed that the previous STEL value of 10 mg/m³ should be removed from the Polish inventory of OELs as inaccurate due to no irritation activity of DBP confirmed in available studies. It is also recommended to label DBP, in the Polish inventory of OELs, with the letters ‘Ft’ – a substance toxic to the foetus.

Anhydrous sodium perborate and sodium perborate hexahydrate – inhalable fraction. Documentation  
Małgorzata Kupczewska-Dobecka

Anhydrous sodium perborate and sodium perborate hexahydrate conform to today’s knowledge on the dimeric nature of the peroxoboron anions. Sodium perborates are white, odorless crystalline powders. Due to the deliberation of active oxygen during degradation, sodium perborates are used as oxidising and bleaching agents mainly in detergents and also in cleaning and cosmetic preparations. Sodium perborate monohydrate should be classified as “Harmful if swallowed” due to the oral LD50 in rats of 1700 – 2700 mg/kg bw.  In an acute inhalation study, the LC50 was – 1164 mg/m³. Sodium perborate tetrahydrate should be classified as “Harmful by inhalation”. Sodium perborate caused strong eye irritation in animal studies, the effects were not reversible in most animals. The “Risk of serious damage to eyes” classification was proposed. Sodium perborate is assumed to be degraded to boric acid and H2O2 after oral application and to be excreted as boric acid via urine. Studies in animals on fertility are limited. However, evidence that sodium perborate is converted to boric acid suggests that sodium perborate may affect fertility. No effects in the lungs have been reported in spirometric examinations of workers in production plants. Maximal concentration of sodium peroxoborate during manufacturing was 12.1 mg/m³(reasonable worst case), and 1 mg/m³ was a typical value.  Workers did not show deterioration of the lung function measured as FVC and FEV1 compared to the general population for several years, even over 20. Considering this information , the NOAEC  for the effects on the lung may be in the range from  1 to 12 mg/m³. So, the MAC value of 4 mg/m³  and STEL of  8 mg/m³ for inhalable fraction of dust were established.

Styrene. Documentation  
Andrzej Starek  

Styrene monomer  is a colorless to yellow oily liquid with a sweet, sharp odor at concentrations on the order of 426 mg/m³. Styrene has been produced by catalytic dehydrogenation of ethyl benzene. This compound is manufactured on a large scale. It has been widely used in the manufacture of polystyrene plastics, protective coatings, styrenated polyesters, copolymer resins with acrylonitrile and butadiene, and as a chemical intermediate. In Poland in 2010 the number of workers exposed to styrene at concentration above MAC value (50 mg/m³) was 480. In 2001 to 2010 six cases of professional diseases caused by styrene was noted.
Results of animal studies revealed that styrene is a chemical of relatively low toxicity. In humans occupationally exposed to styrene an irritating effect to the eyes, both nose and throat mucosa, and central nervous system (CNS) disturbances (neurobehavioral, impairment of colour vision and hearing) were observed. Also, this chemical was caused hematological, hepatotoxic, andocrine, and immunological changes.
Styrene exerts genotoxic effects causing an increase of single-strand breaks of DNA and chromosomal aberrations. There is inadequate evidence in humans and limited evidence in experimental animals for the carcinogenicity of styrene. The International Agency for Research on Cancer (IARC) has classified styrene to Group 2B.  Styrene has shown neither  embryotoxic, fetotoxic, and teratogenec effects.
The recommended maximum admissible concentration (MAC) for styrene of 50 mg/m³ is based on the irritating effect and CNS disturbances in workers professionally exposed to this chemical. STEL value at 100 mg/m³, and “I” (irritating) notation has been proposed. Moreover, BEI value for sum of mandelic acid and phenylglyoxylic acid at level of 235 mg/g creatinine is recommended.

1,1,2-Trichloroethane. Documentation  
Karolina Bystry, Jan Stetkiewicz  

1,1,2-Trichloroethane (1,1,2 - TCE) is a colorless, inflammable liquid with a sweet odor, similar to the smell of chloroform. It is used as a solvent for fats, waxes, natural resins, alkaloids, and many other organic materials. It is also used as an intermediate in the production of vinylidene chloride, Teflon tubing and adhesives.
Over 95% of the compound produced in the USA is used in the production of vinylidene chloride. According to the Chief Sanitary Inspectorate in Poland, 1,1,2-trichloroethane workers have not been exposed to values over the TWA (45 mg/m³).
The median lethal dose of 1,1,2-trichloroethane for rats after administration to the stomach (LD50) is 837 mg/kg, after inhalation exposure (LC50) 9000 mg/m³. LD50 value for rabbits is 5.38 g / kg dose through the skin.
The substance is irritating to the skin, eyes, upper respiratory tract and stomach. Animal studies showed slight immunomodulatory properties of 1,1,2-trichlo-roethane.
This chemical compound is well absorbed into the body from all routes of exposure. 1,1,2-Trichloroethane is metabolized primarily in the liver and excreted from the body with the exhaled air, urine and faeces.
1,1,2-Trichloroethane was not mutagenic to Salmonella typhimurium TA1535, TA1537, TA1538, TA98, TA100, either with or without metabolic activation. Mutagenicity of 1,1,2-trichloroethane was found in Saccharomyces cerevisiae. This compound was shown to increase the number of micronuclei in human lymphocytes (in vitro).
There is no evidence of carcinogenic activity of 1,1,2-trichloroethane in humans. There is limited evidence of its carcinogenicity in animals.
1,1,2-Trichloroethane administered to B6C3F1 mice at doses of 195 or 390 mg/kg for 78 weeks caused liver cancer. Chromaffin adrenal tumors were observed only after administration of 1,1,2-trichloroethane at a dose of 390 mg/kg. In rats, 1,1,2-trichloroethane does not cause a significant increase in the number of cancers.
Information about embryotoxic, teratogenic and reproductive toxicity of 1,1,2-trichloroethane for humans has not been found in the available literature and specialist databases. No teratogenic effects were found for 1,1,2-trichloroethane in mice, either.
The IARC classified 1,1,2-trichloroethane to group 3 of carcinogenic compounds (a substance cannot be classified in terms of its carcinogenicity to humans).
NOAEL for 1,1,2-trichloroethane was established on the basis of a 90-day study in male and female mice given the compound in drinking water. The critical effect was the increase in alkaline phosphatase in serum in male and female mice given the highest dose of 1,1,2-trichloroethane, respectively, for females and males, 384 and 305 mg/kg bw/day. No changes in alkaline phosphatase in the serum of females were observed after a dose of 44 mg/kg/day of the compound, or in the serum of females after a dose of 46 mg/kg bw/day. The dose of 44 mg/kg bw/day in females was taken as the NOAEL and after applying appropriate  uncertainty  factors it is proposed to
adopt it for the value of 40 mg/m³ TWA 1,1,2-tri-chloroethane. The substance should be labelled  Carc. Cat. 3 - a possible carcinogen to humans. As 1,1,2-trichloroethane is absorbed through the skin, the "Sk" notation should be used. There is no factual basis for determining the maximum instantaneous concentration (TWA) or the admissible concentration in biological material (DSB).