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Directorate-General for Health and Food Safety
1. Introduction
In discussions in 1994 about the revision of the Drinking Water Directive the Commission requested advice from the CSTE on "... the levels of organohalogen compounds in drinking water."
On 7 July 1994, the CSTE stated:
"The Committee agreed that the present guide concentration level of 1µg/l should be replaced by the consideration of a small list of substances selected as significant amongst the principal groups of organohalogen compounds, to be applied as indicators or because of their serious toxic properties."
In particular, "For aliphatic halogens of natural origin or due to pollution from industrial sources, trichlorethene and tetrachlorethene were selected as examples. Acceptable values for these substances should be as low as possible, and the maximum level should be determined on toxicological grounds and by reference to what is technologically achievable."
2. Questions to the Commission
In February 1997, the Commission again raised the matter and asked three specific questions:
The Commission had followed this advice, and proposed that standards for trichlorethene and tetrachlorethene should be included in the proposal for a revision of the Drinking Water Directive. Furthermore, bearing in mind that the Commission had utilised the 1993 WHO Guidelines for Drinking Water Quality as the basis for its toxicological standards, and in the absence of any other toxicologically based guidelines, the Commission adopted the WHO Guideline values for trichlorethene and tetrachlorethene, namely 70µg/l and 40 µg/l respectively.
During the European Parliament's first reading consideration of the Proposal there were several attempts, both in the Committee and in the Plenary to propose amendments to these standards. It was argued by some MEPs that the proposed standards were too lenient, particularly in view of the recent decision by the International Association for Research on Cancer (IARC) to reclassify these substances to Class 2A carcinogens.
The amendments proposed ranged from the replacement of the proposed standards by the old guide level standards of 1µg/l for each substance, to a new parameter for a list of five specified organochlorine substances with a standard of 10µg/l. This latter proposal was eventually adopted at the Plenary meeting of Parliament on 11 and 12 December, by a substantial majority.
In the light of these developments, the Commission would like to invite the Scientific Committee to provide advice on the following specific questions:-
1) Do the Commission's proposed standards for Trichlorethene and Tetrachlorethene represent a reasonable level of health protection, and which is commensurate with the standards adopted for the other Annex 1 Part B (chemical) substances?
2) If not, does the European Parliament's amendment number 53* represent a reasonable level of health protection, and which is commensurate with the standards adopted for the other Annex I Part B (chemical) substances?
* The parameters Trichlorethene and Tetrachlorethene should be replaced with a standard of 10µg/l for the total value for: trichlorethene, tetrachlorethene, tetrachloromethane, 1,1,1-trichlorethane and dichlormethane.
3) If not, what would be the most appropriate parameter(s) and parametric value(s) that could be proposed in the revision of the Drinking Water Directive which is commensurate with the standards adopted for the other Annex I Part B (chemical) substances?
Trichlorethene
3. The WHO Guideline value for trichlorethene of 70µg/l was derived in 1993, as shown in Appendix 1.
4. Since then, IARC has reconsidered its previous evaluation of trichlorethene (TCE) and has moved it from Group IIB to Group IIA for the reasons stated in Appendix 2.
The Specialised Experts under the CPL regulations have recently (1997) concluded that TCE should be regarded as a Category 2 chemical.
5. The response of the CSTE to the Commission's questions first required a discussion of whether TCE in drinking water should be considered as representing a carcinogenic risk to man.
6. Genotoxicity and Carcinogenicity of TCE in Animals and Man
6.1 Genotoxicity
IARC describes positive results in in vivo tests when impure preparations were used (epoxide stabilisers etc.) and negative results with pure TCE. Studies in vivo have given conflicting results; the majority of tests in vivo have been negative, but a positive has been claimed in 1 inhalation micronucleus test in the rat and in a non-standard assay of single strand breaks in DNA in the mouse. In a comprehensive inhalation test in the rat there were no chromosome aberrations and an IP micronucleus test in the mouse gave a negative result.
In a study in human cells TCE was shown to produce a small increase in SCE and UDS. In other experiments, including some in mammalian cells, TCE has given a mixture of positive and negative findings from which no conclusions can be drawn.
It was agreed that there was no definitive experimental evidence that TCE was an in vivo genotoxicant in animals, and there were no findings to suggest genotoxicity in humans.
6.2 Experimental Carcinogenicity
TCE has been associated with renal tumours in the rat and liver neoplasms in the mouse, as well as leukaemia and interstitial cell tumours in the rat and pulmonary neoplasms in the mouse. Many mechanistic investigations have shown considerable differences in the metabolism of TCE in human tissues and in rats and mice. The tumorigenicity in mice and rats may be due to specific processes not considered to represent human health risks.
Thus, the experimental results provide limited suggestions about the carcinogenic potential of TCE in humans.
6.3 Epidemiology
IARC has concluded that there is limited evidence in humans of the carcinogenicity of TCE.
Other epidemiologists have stated that the published studies are of inadequate quality or power to support the interpretation of carcinogenic risk to man.
(see CSTE 24/97/2 - Add 3 and Appendix 3; Committee on Carcinogenicity 1997).
7. Conclusions about Human Health Risks of TCE
The evidence from various laboratory studies and epidemiology surveys, which has been extensively reviewed by many expert groups, does not show that it represents a genotoxic carcinogenic risk to man.
Accordingly, a guideline value for exposure to TCE in drinking water can be proposed by the conventional application of safety (uncertainty) factors.
8. Permissible Guideline Level of TCE in Drinking Water
8.1 Present value
The present directive, now being revised, presents the parametric value of 1µg/l for TCE.
Two alternative proposals were suggested by the CSTE.
8.2 New proposal - 1
Taking the WHO provisional level (1993) of 70µg/l as the starting point, and noting how it was derived, it is apparent that the calculation does not allow for the volatility of TCE and the likelihood of additional respiratory uptake whilst washing etc.
Based on reports from the US EPA about respiratory uptake in this way, an additional safety factor of 2 is suggested.
The proposed Guideline value would then be 35µg/l; for convenience it could be rounded down to 30µg/l.
8.3 New proposal - 2
Because the limited knowledge of the carcinogenicity of TCE, it was suggested that, whilst the application of safety factors to the published toxicity data was acceptable, an additional factor of 10 would be appropriate to reflect concern about its carcinogenic potential. This would result in a guideline value of 3µg/l.
Tetrachlorethene (PCE)
9. The WHO guideline value (1993) for PCE is 40µg/l as shown in Annex I.
10. Since then, IARC has reconsidered its previous evaluation of PCE and has moved it from Group IIB to Group IIA for the reasons stated in Appendix 3.
The Specialised Experts under the CPL regulations have recently (1997) concluded that PCE should be regarded as a Category 2 chemical
11. The response of the CSTE to the Commission's questions first required a discussion of whether PCE in drinking water should be considered as representing a carcinogenic risk to man.
12. Genotoxicity and Carcinogenicity of PCE in Animals and Man
12.1 Genotoxicity
PCE has not been shown to be an in vivo genotoxic agent in animals.
12.2 Experimental carcinogenicity
PCE has been shown to produce liver tumours in the mouse and to be associated with leukaemia in one study in the rat.
The occurrence of these specific types of neoplasms is not at present considered to indicate a carcinogenic risk to humans.
12.3 Epidemiology
IARC has concluded that there is limited evidence in humans of the carcinogenicity of PCE.
Other epidemiologists have stated that the published studies are of inadequate quality or power to support the interpretation of carcinogenic risk to man.
(see CSTE 24/97/2 - Add 3 and Appendix 3; Committee on Carcinogenicity 1997).
13. Conclusions
The evidence from various laboratory studies and epidemiology surveys, which has been extensively reviewed by many expert groups, do not show that it represents a genotoxic carcinogenic risk to man.
Accordingly, a guideline value for exposure to PCE in drinking water can be proposed by the conventional application of safety (uncertainty) factors.
14. Permissible guideline level of PCE in drinking water
14.1 Present value
The present directive, now being revised, presents the parametric value of 1µg/l for PCE.
Two alternative proposals were advanced by the CSTE
14.2 New proposal - 1
Taking the WHO provisional level (1993) of 40µg/l as the starting point, and noting how it was derived, it is apparent that the calculation does not allow for the volatility of PCE and the likelihood of additional respiratory uptake whilst washing etc.
Based on reports from the US EPA about respiratory uptake in this way, an additional safety factor of 2 is suggested.
The proposed Guideline value would then be 20µg/l.
14.3 New proposal - 2
Because of limited knowledge of the carcinogenicity of PCE, it was suggested that, whilst the application of safety factors to the published toxicity data was acceptable, an additional factor of 10 would be appropriate to reflect concern about its carcinogenic potential. This would result in a guideline value of 2µg/l.
The CSTE is aware that new information about the toxicity of both substances is becoming available. These proposals should be reconsidered as soon as there are sufficient data for evaluation
Guideline Values for Trichlorethene (TCE) and Tetrachlorethene (PCE) in Drinking Water
Opinion of the CSTE
Responses to the Commission's questions:
1) Do the Commission's proposed standards for Trichlorethene and Tetrachlorethene represent a reasonable level of health protection, and which is commensurate with the standards adopted for the other Annex 1 Part B (chemical) substances?
No.
2) If not, does the European Parliament's amendment number 53* represent a reasonable level of health protection, and which is commensurate with the standards adopted for the other Annex 1 Part B (chemical) substances?
No because this suggestion does not have the same scientific basis as the other proposed parametric values.
3) If not, what would be the most appropriate parameter(s) and parametric value(s) that could be proposed in the revision of the Drinking Water Directive which is commensurate with the standards adopted for the other Annex 1 Part B (chemical) substances?
The CSTE concluded that:
Trichlorethene (TCE)
a) It was considered that the approach adopted in the WHO Guidelines for Drinking Water (1993) was appropriate but the guideline value proposed there was too high. Reconsideration of the data, including reassessment of the additional potential for respiratory exposure of people shows that a maximum guideline value of 30µg/l is appropriate.
b) It was also held that there was insufficient reassurance that TCE did not pose a carcinogenic risk to man. For that reason, and because of concern about its carcinogenic potential, they felt that an additional ten fold safety factor should be applied to the value proposed by the WHO in 1993. On that basis a guideline value of 3µg/l was suggested.
Tetrachlorethene (PCE)
As regards Tetrachlorethene the same considerations apply. The only differences are in the guideline values which, in this case are respectively:
a) 20µg/l and,
b) 2µg/l.
CONCLUSIONS
The CSTE held that the provisional guideline values should be:
a) Trichlorethene (TCE): 3µg/l
b) Tetrachlorethene (PCE): 2µg/l
The CSTE is aware that new information about the toxicity of both substances is becoming available. These proposals should be reconsidered as soon as there are sufficient data for evaluation
In discussions in 1994 about the revision of the Drinking Water Directive the Commission requested advice from the CSTE on "... the levels of organohalogen compounds in drinking water."
On 7 July 1994, the CSTE stated:
"The Committee agreed that the present guide concentration level of 1µg/l should be replaced by the consideration of a small list of substances selected as significant amongst the principal groups of organohalogen compounds, to be applied as indicators or because of their serious toxic properties."
In particular, "For aliphatic halogens of natural origin or due to pollution from industrial sources, trichlorethene and tetrachlorethene were selected as examples. Acceptable values for these substances should be as low as possible, and the maximum level should be determined on toxicological grounds and by reference to what is technologically achievable."
2. Questions to the Commission
In February 1997, the Commission again raised the matter and asked three specific questions:
The Commission had followed this advice, and proposed that standards for trichlorethene and tetrachlorethene should be included in the proposal for a revision of the Drinking Water Directive. Furthermore, bearing in mind that the Commission had utilised the 1993 WHO Guidelines for Drinking Water Quality as the basis for its toxicological standards, and in the absence of any other toxicologically based guidelines, the Commission adopted the WHO Guideline values for trichlorethene and tetrachlorethene, namely 70µg/l and 40 µg/l respectively.
During the European Parliament's first reading consideration of the Proposal there were several attempts, both in the Committee and in the Plenary to propose amendments to these standards. It was argued by some MEPs that the proposed standards were too lenient, particularly in view of the recent decision by the International Association for Research on Cancer (IARC) to reclassify these substances to Class 2A carcinogens.
The amendments proposed ranged from the replacement of the proposed standards by the old guide level standards of 1µg/l for each substance, to a new parameter for a list of five specified organochlorine substances with a standard of 10µg/l. This latter proposal was eventually adopted at the Plenary meeting of Parliament on 11 and 12 December, by a substantial majority.
In the light of these developments, the Commission would like to invite the Scientific Committee to provide advice on the following specific questions:-
1) Do the Commission's proposed standards for Trichlorethene and Tetrachlorethene represent a reasonable level of health protection, and which is commensurate with the standards adopted for the other Annex 1 Part B (chemical) substances?
2) If not, does the European Parliament's amendment number 53* represent a reasonable level of health protection, and which is commensurate with the standards adopted for the other Annex I Part B (chemical) substances?
* The parameters Trichlorethene and Tetrachlorethene should be replaced with a standard of 10µg/l for the total value for: trichlorethene, tetrachlorethene, tetrachloromethane, 1,1,1-trichlorethane and dichlormethane.
3) If not, what would be the most appropriate parameter(s) and parametric value(s) that could be proposed in the revision of the Drinking Water Directive which is commensurate with the standards adopted for the other Annex I Part B (chemical) substances?
Trichlorethene
3. The WHO Guideline value for trichlorethene of 70µg/l was derived in 1993, as shown in Appendix 1.
4. Since then, IARC has reconsidered its previous evaluation of trichlorethene (TCE) and has moved it from Group IIB to Group IIA for the reasons stated in Appendix 2.
The Specialised Experts under the CPL regulations have recently (1997) concluded that TCE should be regarded as a Category 2 chemical.
5. The response of the CSTE to the Commission's questions first required a discussion of whether TCE in drinking water should be considered as representing a carcinogenic risk to man.
6. Genotoxicity and Carcinogenicity of TCE in Animals and Man
6.1 Genotoxicity
IARC describes positive results in in vivo tests when impure preparations were used (epoxide stabilisers etc.) and negative results with pure TCE. Studies in vivo have given conflicting results; the majority of tests in vivo have been negative, but a positive has been claimed in 1 inhalation micronucleus test in the rat and in a non-standard assay of single strand breaks in DNA in the mouse. In a comprehensive inhalation test in the rat there were no chromosome aberrations and an IP micronucleus test in the mouse gave a negative result.
In a study in human cells TCE was shown to produce a small increase in SCE and UDS. In other experiments, including some in mammalian cells, TCE has given a mixture of positive and negative findings from which no conclusions can be drawn.
It was agreed that there was no definitive experimental evidence that TCE was an in vivo genotoxicant in animals, and there were no findings to suggest genotoxicity in humans.
6.2 Experimental Carcinogenicity
TCE has been associated with renal tumours in the rat and liver neoplasms in the mouse, as well as leukaemia and interstitial cell tumours in the rat and pulmonary neoplasms in the mouse. Many mechanistic investigations have shown considerable differences in the metabolism of TCE in human tissues and in rats and mice. The tumorigenicity in mice and rats may be due to specific processes not considered to represent human health risks.
Thus, the experimental results provide limited suggestions about the carcinogenic potential of TCE in humans.
6.3 Epidemiology
IARC has concluded that there is limited evidence in humans of the carcinogenicity of TCE.
Other epidemiologists have stated that the published studies are of inadequate quality or power to support the interpretation of carcinogenic risk to man.
(see CSTE 24/97/2 - Add 3 and Appendix 3; Committee on Carcinogenicity 1997).
7. Conclusions about Human Health Risks of TCE
The evidence from various laboratory studies and epidemiology surveys, which has been extensively reviewed by many expert groups, does not show that it represents a genotoxic carcinogenic risk to man.
Accordingly, a guideline value for exposure to TCE in drinking water can be proposed by the conventional application of safety (uncertainty) factors.
8. Permissible Guideline Level of TCE in Drinking Water
8.1 Present value
The present directive, now being revised, presents the parametric value of 1µg/l for TCE.
Two alternative proposals were suggested by the CSTE.
8.2 New proposal - 1
Taking the WHO provisional level (1993) of 70µg/l as the starting point, and noting how it was derived, it is apparent that the calculation does not allow for the volatility of TCE and the likelihood of additional respiratory uptake whilst washing etc.
Based on reports from the US EPA about respiratory uptake in this way, an additional safety factor of 2 is suggested.
The proposed Guideline value would then be 35µg/l; for convenience it could be rounded down to 30µg/l.
8.3 New proposal - 2
Because the limited knowledge of the carcinogenicity of TCE, it was suggested that, whilst the application of safety factors to the published toxicity data was acceptable, an additional factor of 10 would be appropriate to reflect concern about its carcinogenic potential. This would result in a guideline value of 3µg/l.
Tetrachlorethene (PCE)
9. The WHO guideline value (1993) for PCE is 40µg/l as shown in Annex I.
10. Since then, IARC has reconsidered its previous evaluation of PCE and has moved it from Group IIB to Group IIA for the reasons stated in Appendix 3.
The Specialised Experts under the CPL regulations have recently (1997) concluded that PCE should be regarded as a Category 2 chemical
11. The response of the CSTE to the Commission's questions first required a discussion of whether PCE in drinking water should be considered as representing a carcinogenic risk to man.
12. Genotoxicity and Carcinogenicity of PCE in Animals and Man
12.1 Genotoxicity
PCE has not been shown to be an in vivo genotoxic agent in animals.
12.2 Experimental carcinogenicity
PCE has been shown to produce liver tumours in the mouse and to be associated with leukaemia in one study in the rat.
The occurrence of these specific types of neoplasms is not at present considered to indicate a carcinogenic risk to humans.
12.3 Epidemiology
IARC has concluded that there is limited evidence in humans of the carcinogenicity of PCE.
Other epidemiologists have stated that the published studies are of inadequate quality or power to support the interpretation of carcinogenic risk to man.
(see CSTE 24/97/2 - Add 3 and Appendix 3; Committee on Carcinogenicity 1997).
13. Conclusions
The evidence from various laboratory studies and epidemiology surveys, which has been extensively reviewed by many expert groups, do not show that it represents a genotoxic carcinogenic risk to man.
Accordingly, a guideline value for exposure to PCE in drinking water can be proposed by the conventional application of safety (uncertainty) factors.
14. Permissible guideline level of PCE in drinking water
14.1 Present value
The present directive, now being revised, presents the parametric value of 1µg/l for PCE.
Two alternative proposals were advanced by the CSTE
14.2 New proposal - 1
Taking the WHO provisional level (1993) of 40µg/l as the starting point, and noting how it was derived, it is apparent that the calculation does not allow for the volatility of PCE and the likelihood of additional respiratory uptake whilst washing etc.
Based on reports from the US EPA about respiratory uptake in this way, an additional safety factor of 2 is suggested.
The proposed Guideline value would then be 20µg/l.
14.3 New proposal - 2
Because of limited knowledge of the carcinogenicity of PCE, it was suggested that, whilst the application of safety factors to the published toxicity data was acceptable, an additional factor of 10 would be appropriate to reflect concern about its carcinogenic potential. This would result in a guideline value of 2µg/l.
The CSTE is aware that new information about the toxicity of both substances is becoming available. These proposals should be reconsidered as soon as there are sufficient data for evaluation
Guideline Values for Trichlorethene (TCE) and Tetrachlorethene (PCE) in Drinking Water
Opinion of the CSTE
Responses to the Commission's questions:
1) Do the Commission's proposed standards for Trichlorethene and Tetrachlorethene represent a reasonable level of health protection, and which is commensurate with the standards adopted for the other Annex 1 Part B (chemical) substances?
No.
2) If not, does the European Parliament's amendment number 53* represent a reasonable level of health protection, and which is commensurate with the standards adopted for the other Annex 1 Part B (chemical) substances?
No because this suggestion does not have the same scientific basis as the other proposed parametric values.
3) If not, what would be the most appropriate parameter(s) and parametric value(s) that could be proposed in the revision of the Drinking Water Directive which is commensurate with the standards adopted for the other Annex 1 Part B (chemical) substances?
The CSTE concluded that:
Trichlorethene (TCE)
a) It was considered that the approach adopted in the WHO Guidelines for Drinking Water (1993) was appropriate but the guideline value proposed there was too high. Reconsideration of the data, including reassessment of the additional potential for respiratory exposure of people shows that a maximum guideline value of 30µg/l is appropriate.
b) It was also held that there was insufficient reassurance that TCE did not pose a carcinogenic risk to man. For that reason, and because of concern about its carcinogenic potential, they felt that an additional ten fold safety factor should be applied to the value proposed by the WHO in 1993. On that basis a guideline value of 3µg/l was suggested.
Tetrachlorethene (PCE)
As regards Tetrachlorethene the same considerations apply. The only differences are in the guideline values which, in this case are respectively:
a) 20µg/l and,
b) 2µg/l.
CONCLUSIONS
The CSTE held that the provisional guideline values should be:
a) Trichlorethene (TCE): 3µg/l
b) Tetrachlorethene (PCE): 2µg/l
The CSTE is aware that new information about the toxicity of both substances is becoming available. These proposals should be reconsidered as soon as there are sufficient data for evaluation
