This presentation describes animal testing safety end points in chemical industry according to REACH(registration,evaluation,authorisation & restriction of chemicals). REACH was established to control manufacturing and importing of chemicals in EU market & to minimize the risks to human health and environment.

1. ANIMAL TESTING SAFETY END POINTS IN CHEMICAL INDUSTRY (Precisely EU legislation on registration, evaluation & authorisation of chemicals or REACH) SUBMITTED BY-MIHIR PUJARA DEPT. OF PHARMACEUTICAL MANAGEMENT, NIPER,MOHALI

3. About REACH

4. REACH process in detail

5. What are “end points”?

6. Chart describing overall process related to chemical safety assessment

7. Testing involved in REACH proposal(annex V to X)

8. Acute toxicity tests

9. REACH-needed data of all the “end points”

10. Reproductive & developmental toxicology testing requirements

11. Examples

13. Numerous regulations

14. Numerous substances

15. Numerous stakeholders

16. Different authorities

17. Agencies from several countries

18. Many companies/competitiors

19. Traders

21. Animal tests were developed and testing demands increased along with increasing awareness and data of toxicity of chemicals in man.

22. Current legislation dictates that animal test data is still required to help assess potential health hazards of chemicals to humans.

23. The new European REACH and CLP Regulations take this further and require approval to be obtained from ECHA, the European Chemicals Agency, before any animal tests are carried out, for both substances and preparations.

25. To protect human health & environment from the use of chemicals

26. Understand & manage risk associated with chemicals & their use

27. To allow free movement of substances on EU market

28. To enhance innovation in and the competitiveness of the EU chemicals industry

29. To promote the use of alternative methods for the assessment of the hazardous properties of substances. e.g.QSAR

30. REACH foresees data sharing between registrants to gather the required information

31. The regulation applies to substances manufactured in, or imported to the EU in annual quantities of 1 tonne or more per company, unless the regulation indicates otherwise. WHAT IS REACH? PROPOSAL FOR SAFETY DRIVERS: WHY THERE IS SAFETY TESTING?

33. Pre registration

34. Applies from 1 june 2008

35. Chemicals currently on EU market are pre-registered between 1 june to 1 december,2008

36. Companies who pre-register their substances can benefit from extended registration deadlines

37. Late pre registration

38. It applies, when any company starts manufacturing or importing 1 tonne or more chemical substance per year after 1 dec,2008

39. Late pre-registration does not apply to companies that failed to meet the pre-registration deadline of 1 December 2008 for their substances

40. Chemicals manufactured or imported in large volumes have to register first NO DATA, NO MARKET

45. Main objective behind evaluation:-

46. Reliable & adequate data are produced

49. They can also ask for further information if required.

55. Step 3:Applications for authorisation (by industry)

56. Applicant have to provide chemical safety report, suitable alternatives or techniques to reduce overall risks & economically feasible.

57. Applicant can include socio-economic analysis in his application.

58. A fee has to be paid for each application.

59. For all applications, the Agency will provide expert opinions. The applicant can comment on these opinions.

60. Step 4: Granting of authorisations (by the European Commission)

61. If the risk associated with the use of substance is properly controlled authorisations will be granted.

62. If the risk is not adequately controlled, an authorisation may still be granted if it is proven that the socio-economic benefits outweigh the risks & there is no other option available.

66. Overall process related to information requirements and chemicals safety assessment under REACH Ref:-http://guidance.echa.europa.eu/docs/guidance document/information requirement r2 .pdf

68. Eye irritation (in vitro)

69. Skin sensitisation (Local Lymph Node Assay)

70. Mutagenicity (in vitro)

72. Eye irritation (in vivo)

73. Mutagenicity (in vitro)

74. Acute toxicity (in vivo by oral route and/or by inhalation and/or dermal route)

75. Repeated dose toxicity (28-day in vivo study, one species, male and female)

76. Reproductive toxicity (Screening for developmental toxicity in vivo, if there is no (Q)SAR estimates that the substance may be a developmental toxicant. A positive result in the screening should be confirmed by further in vivo tests)

77. Toxicokinetics – if it can be derived from the available information

78. Short term toxicity testing on fish

80. 28-day repeated dose toxicity or sub-chronic toxicity study (90-day, one species, rodent)

81. Developmental toxicity study (two species)

82. Two-generation reproductive toxicity study (in vivo, one species, male and female)

83. Long term toxicity testing on fish (fish early-life stage toxicity test or fish short term toxicity test on

84. embryo and sac-fry stages or fish juvenile growth test)

85. Accumulation in one aquatic species, preferably fish

86. Further studies on adsoption/desorption depending on results of studies required in Annex

87. If appropriate, further mutagenicity studies shall be proposed

88. A long term (12 month) repeated toxicity study may be proposed

89. Two generation reproductive toxicity study, one species, male and female, if not provided as part of

90. Annex VII requirements

91. A carcinogenicity study may be proposed by the applicant or requested by the competent authority

92. Long term or reproductive toxicity in birds Annex VIII – above 1,000 tonnes

95. Lethality has been the primary toxicological endpoint in acute toxicity tests, which have been in use for nearly 80 years but a large number of animals has been sacrificed.

96. For testing acute toxicity by the oral route, the LD50 method has been replaced in the OECD guidelines by other protocols which use fewer animals.

97. Fixed dose procedure

98. Up & down procedure

99. Acute toxic class method

100. For testing acute toxicity by inhalation or by the dermal (skin) route, LD50/LC50 tests are still most predominantly used.

101. These tests are highly criticised due to extent of animal suffering that it causes.All serve to provide an estimated LD50 value

102. Ref:-the report of CONAM/ecopa chemical policy working group, March 2007

103. REACH-NEEDED DATA :“PHYSICO-CHEMICAL ENDPOINTS”

104. TOXICOLOGICAL ENDPOINTS

108. EXAMPLE 1 Ref:-the report of CONAM/ecopa chemical policy working group, March 2007

109. EXAMPLE 2

111. It is about the hazards of chemical substances & mixtures & how to inform others about them.

112. NC3Rs-The National Centre for the Replacement, Refinement and Reduction of Animals in Research

113. Established by the UK Government, is an independent scientific organization

114. ECETOC-European Center for Ecotoxicology and Toxicology Of Chemicals

115. Concerned with the identification of research needs and provision of scientific rationale for the assessment of health effects and environmental impact, and thereby to justify industry's licence and freedom to operate.

116. EPAA-European Partnership for Alternative Approaches to Animal Testing

117. Accelerate the development, validation and acceptance of alternative approaches to further the reduction, refinement and replacement (3Rs) of animal use in regulatory testing.

118. CEFIC-European Chemical Industry Council