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The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area re-evaluated isoflurane [26675-46-7] and a maximum concentration at the workplace (MAK value) of 2 ml/m3 has been set for isoflurane. The substance is used as a volatile anaesthetic, and absorption of isoflurane at the workplace is by inhalation. Human studies are not available to derive a quantitative relationship between the internal dose and the critical toxic effects of isoflurane (neurotoxicity and liver toxicity, effects on reproductive organs). Three studies on surgical employees show a linear correlation between the concentration of isoflurane in the air and urine concentration. In correlation to the MAK value of 2 ml/m3, a biological tolerance value (BAT value) of 4 µg isoflurane/l urine was established. Sampling time is at the end of exposure or end of shift. There are no studies in neonatal or juvenile animals at non-anaesthetic concentrations to derive a no observed adverse effect concentration (NOAEC) for developmental neurotoxic effects of isoflurane. Therefore, isoflurane was assigned to Pregnancy Risk Group D. Since the BAT value was derived in correlation to the MAK value, Pregnancy Risk Group D also applies to the BAT value.

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area re-evaluated isoflurane [26675-46-7] and a maximum concentration at the workplace (MAK value) of 2 ml/m3 has been set for isoflurane. The substance is used as a volatile anaesthetic, and absorption of isoflurane at the workplace is by inhalation. Human studies are not available to derive a quantitative relationship between the internal dose and the critical toxic effects of isoflurane (neurotoxicity and liver toxicity, effects on reproductive organs). Three studies on surgical employees show a linear correlation between the concentration of isoflurane in the air and urine concentration. In correlation to the MAK value of 2 ml/m3, a biological tolerance value (BAT value) of 4 µg isoflurane/l urine was established. Sampling time is at the end of exposure or end of shift. There are no studies in neonatal or juvenile animals at non-anaesthetic concentrations to derive a no observed adverse effect concentration (NOAEC) for developmental neurotoxic effects of isoflurane. Therefore, isoflurane was assigned to Pregnancy Risk Group D. Since the BAT value was derived in correlation to the MAK value, Pregnancy Risk Group D also applies to the BAT value

In 2012, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area re-evaluated the maximum workplace concentration (MAK value) of isopropylbenzene (cumene) [98-82-8]. If the MAK value of 10 ml iso-propylbenzene/m3 (50 mg/m3) is observed, no prenatal toxic effects are to be expected. Therefore, Pregnancy Risk Group C was confirmed. In 2013, the biological tolerance value (BAT value) of 10 mg 2-phenyl-2-propanol (after hydrolysis)/g creatinine was derived in correlation to the MAK value. Pregnancy Risk Group C is also similarly valid for the BAT value. In adherence with the BAT value of 10 mg 2-phenyl-2-propanol (after hydrolysis)/g creatinine, no prenatal toxic effects are to be expected.

In 2005, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area re-evaluated the maximum workplace concentration (MAK value) of hydrogen fluoride [7664-39-3] and fluorides [16984-48-8]. If the MAK values of 1 ml hydrogen fluoride/m3 (0.83 mg/m3) or 1 mg fluoride/m3, respectively, are not exceeded, prenatal toxic effects are not to be expected. Therefore, hydrogen fluoride and fluorides were classified in Pregnancy Risk Group C. In 2013, the biological tolerance value (BAT value) for hydrogen fluoride and inorganic fluorine compounds (fluorides) of 4 mg fluoride/l urine was established which protects against the long-term effects of fluoride such as skeletal fluorosis. The BAT value was not derived in correlation to the MAK value. For this reason, it is to be evaluated whether no prenatal toxic effects are to be expected when the BAT value is adhered to. By extrapolating the NOAEL (no observed adverse effect level) for developmental toxicity in rodent studies to fluoride concentrations in urine it could be concluded that Pregnancy Risk Group C is also valid for the BAT value.

In 2005, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area re-evaluated the maximum workplace concentration (MAK value) of hydrogen fluoride [7664-39-3] and fluorides [16984-48-8]. If the MAK values of 1 ml hydrogen fluoride/m3 (0.83 mg/m3) or 1 mg fluoride/m3, respectively, are not exceeded, prenatal toxic effects are not to be expected. Therefore, hydrogen fluoride and fluorides were classified in Pregnancy Risk Group C. In 2013, the biological tolerance value (BAT value) for hydrogen fluoride and inorganic fluorine compounds (fluorides) of 4 mg fluoride/l urine was established which protects against the long-term effects of fluoride such as skeletal fluorosis. The BAT value was not derived in correlation to the MAK value. For this reason, it is to be evaluated whether no prenatal toxic effects are to be expected when the BAT value is adhered to. By extrapolating the NOAEL (no observed adverse effect level) for developmental toxicity in rodent studies to fluoride concentrations in urine it could be concluded that Pregnancy Risk Group C is also valid for the BAT value.

In 2012, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area re-evaluated the maximum workplace concentration (MAK value) of 1,2-epoxypropane (propylene oxide) [75-56-9]. If the MAK value of 2 ml 1,2-epoxypropane/m3 (4.8 mg/m3) is observed, no prenatal toxic effects are to be expect ed. 1,2-epoxypropane was therefore classified in Pregnancy Risk Group C. In 2014, the biological tolerance value (BAT value) of 2500 pmol N-(2-hydroxypropyl)valine/g globin was derived in correlation to the MAK value. As a result, Pregnancy Risk Group C is likewise valid for the BAT value. No prenatal toxic effects are to be expected by compliance with the BAT value of 2500 pg N-(2-hydroxypropyl)valine/g globin

In 2018, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area re-evaluated and confirmed the maximum workplace concentration (MAK value) of 2-propanol [67-63-0]. If the MAK value of 200 ml 2-propanol/m3 (500 mg/m3) is observed, no prenatal toxic effects are to be expected. Therefore, Pregnancy Risk Group C was likewise confirmed. In 2010, biological tolerance values (BAT values) of 25 mg acetone/l blood and 25 mg acetone/l urine were derived in correlation to the MAK value. Pregnancy Risk Group C is therefore similarly valid for the BAT value. In adherence with the BAT values of 25 mg acetone/l blood and 25 mg acetone/l urine, no prenatal toxic effects are to be expected

In 2011, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area re-evaluated the maximum workplace concentration (MAK value) of ethylbenzene [100-41-4]. If the MAK value of 20 ml ethylbenzene/m3 (88 mg/m3) is observed, no prenatal toxic effects are to be expected. Therefore, ethylbenzene was classified in Pregnancy Risk Group C. In 2015, the biological tolerance value (BAT value) of 250 mg mandelic acid plus phenylglyoxylic acid/g creatinine was derived in correlation to the MAK value. Pregnancy Risk Group C is therefore similarly valid for the BAT value. In adherence with the BAT value of 250 mg mandelic acid plus phenylglyoxylic acid/g creatinine, no prenatal toxic effects are to be expected.

In 2018, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area re-evaluated and confirmed the maximum workplace concentration (MAK value) of 2-propanol [67-63-0]. If the MAK value of 200 ml 2-propanol/m3 (500 mg/m3) is observed, no prenatal toxic effects are to be expected. Therefore, Pregnancy Risk Group C was likewise confirmed. In 2010, biological tolerance values (BAT values) of 25 mg acetone/l blood and 25 mg acetone/l urine were derived in correlation to the MAK value. Pregnancy Risk Group C is therefore similarly valid for the BAT value. In adherence with the BAT values of 25 mg acetone/l blood and 25 mg acetone/l urine, no prenatal toxic effects are to be expected.

In 2012, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area re-evaluated the maximum workplace concentration (MAK value) of 1,2-epoxypropane (propylene oxide) [75-56-9]. If the MAK value of 2 ml 1,2-epoxypropane/m3 (4.8 mg/m3) is observed, no prenatal toxic effects are to be expect ed. 1,2-epoxypropane was therefore classified in Pregnancy Risk Group C. In 2014, the biological tolerance value (BAT value) of 2500 pmol N-(2-hydroxypropyl)valine/g globin was derived in correlation to the MAK value. As a result, Pregnancy Risk Group C is likewise valid for the BAT value. No prenatal toxic effects are to be expected by compliance with the BAT value of 2500 pg N-(2-hydroxypropyl)valine/g globin

In 2011, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area re-evaluated the maximum workplace concentration (MAK value) of ethylbenzene [100-41-4]. If the MAK value of 20 ml ethylbenzene/m3 (88 mg/m3) is observed, no prenatal toxic effects are to be expected. Therefore, ethylbenzene was classified in Pregnancy Risk Group C. In 2015, the biological tolerance value (BAT value) of 250 mg mandelic acid plus phenylglyoxylic acid/g creatinine was derived in correlation to the MAK value. Pregnancy Risk Group C is therefore similarly valid for the BAT value. In adherence with the BAT value of 250 mg mandelic acid plus phenylglyoxylic acid/g creatinine, no prenatal toxic effects are to be expected

In 2012, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area re-evaluated the maximum workplace concentration (MAK value) of isopropylbenzene (cumene) [98-82-8]. If the MAK value of 10 ml iso-propylbenzene/m3 (50 mg/m3) is observed, no prenatal toxic effects are to be expected. Therefore, Pregnancy Risk Group C was confirmed. In 2013, the biological tolerance value (BAT value) of 10 mg 2-phenyl-2-propanol (after hydrolysis)/g creatinine was derived in correlation to the MAK value. Pregnancy Risk Group C is also similarly valid for the BAT value. In adherence with the BAT value of 10 mg 2-phenyl-2-propanol (after hydrolysis)/g creatinine, no prenatal toxic effects are to be expected.

In 2022, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has withdrawn the exposure equivalents for carcinogenic substances (EKA) for vinyl chloride [75-01-4] based on urinary excretion of thiodiglycolic acid (TdAA) because of its poor reliability at low exposure. Therefore, also the biological reference value (BAR) has to be re-evaluated. To this end, the existing literature was updated and taken into account. Four published studies showed that the excretion of TdAA in humans occupationally exposed to vinyl chloride and non-exposed persons largely overlaps, especially in the exposure range < 5 ml/m3. This may lead to a situation where unexposed persons may falsely be considered exposed to vinyl chloride as well as – on the other hand – real exposures may not be identified. Nevertheless, in order to keep an instrument for the assessment of higher exposures, notably after accidents or leakages, the Commission decided to confirm the existing BAR of 1.5 mg TdAA/l urine, however with the additional remark “This BAR is not suitable for the assessment of vinyl chloride exposures < 5 ml/m3”. Owing to the different excretion characteristics after hig vs. low vinyl chloride exposures, it is further recommended to obtain two separate urinesamples after 12–18 and 48 hours, respectively, after an accidental exposure.

In 2022, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has withdrawn the exposure equivalents for carcinogenic substances (EKA) for vinyl chloride [75-01-4] based on urinary excretion of thiodiglycolic acid (TdAA) because of its poor reliability at low exposure. Therefore, also the biological reference value (BAR) has to be re-evaluated. To this end, the existing literature was updated and taken into account. Four published studies showed that the excretion of TdAA in humans occupationally exposed to vinyl chloride and non-exposed persons largely overlaps, especially in the exposure range < 5 ml/m3. This may lead to a situation where unexposed persons may falsely be considered exposed to vinyl chloride as well as – on the other hand – real exposures may not be identified. Nevertheless, in order to keep an instrument for the assessment of higher exposures, notably after accidents or leakages, the Commission decided to confirm the existing BAR of 1.5 mg TdAA/l urine, however with the additional remark “This BAR is not suitable for the assessment of vinyl chloride exposures < 5 ml/m3”. Owing to the different excretion characteristics after high vs. low vinyl chloride exposures it is further recommended to obtain two separate urine samples after 12–18 and 48 hours, respectively, after an accidental exposure.