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非常感謝樓上的兄弟。。。我可以很肯定在- r$ L: K7 q" {& i: R6 S( J
Hazardous Products (Toys) Regulations (C.R.C., c. 931)3 D! ?, r2 {, Y# s
裡沒有找到這句話,不知道你是在哪裡看的到呢?可以上傳嗎?以下是我看到的,看來我們看的不是同一份標准,謝謝你了 !!!!
: m( j1 E* C4 c, V4 b1 w' @4 E SCHEDULE I
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, F2 k% |9 K5 b. h K+ q/ { (ss. 10 and 14)
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/ x; Y4 l- ?0 N0 n2 u4 G kPERMISSIBLE LIMITS OF TOXICITY
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1. (1) For the purposes of paragraphs 10(c) and 14(c) of the Regulations, a substance shall be considered excessively toxic for humans if
3 }% \5 U6 o8 ]# ~5 J- H. w(a) the acute oral LD50 value thereof for rat is 5 grams or less per kilogram body weight;
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9 ?/ T1 e% v6 ]$ X0 o% E(b) the acute dermal LD50 value for rabbit is 2 grams or less per kilogram body weight; and $ t" U% S! f% V
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(c) where gas, vapour, mist or dust is likely to be encountered when the substance is used in any reasonably foreseeable manner, the LC50 value thereof for a one-hour exposure determined using rats, is 20,000 parts per million by volume of gas or vapor or less, or 200 milligrams per litre by volume of mist or dust or less. + }" x+ w% C* F6 g6 d9 `, Y8 k
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(2) LD50 values are to be determined in conformity with good toxicological practice. & L& w7 N: t" F }; U6 {8 ]
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(3) The number of deaths during a 14-day period following dosage shall be used as the basis for calculation of the LD50 value. $ Z+ ^( S- i, ]# f" V& c {
M* t; Y3 k$ {" R8 q6 v(4) Sufficient animals shall be used to give a statistically significant result, which result shall be calculated using methods based upon good statistical practice.
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(5) The methods used by C. I. Bliss (1938) and J. T. Litchfield and W. F. Wilcoxon (1949) are acceptable but other methods giving similar results may also be accepted. 8 ^; M1 m/ F0 v( U3 M; t. J: E
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+ B* a4 s$ t& l! y2 b; T3 z2. The dermal LD50 value shall be determined in the following manner: 8 @/ w% Q8 d) R% ?
In the acute exposures the agent is held in contact with the skin by means of a sleeve for periods varying up to 24 hours. The sleeve, made of rubber dam or other impervious material, is so constructed that the ends are reinforced with additional strips and should fit snugly around the trunk of the animal. The ends of the sleeve are tucked, permitting the central portion to “balloon” and furnish a reservoir for the dose. The reservoir must have sufficient capacity to contain the dose without pressure. The dimensions of sleeves and the approximate body surface exposed to the test substance are given in the following table:
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# i7 T* ?. t$ Q8 l) tDIMENSIONS OF SLEEVES FOR ACUTE DERMAL TOXICITY TEST ; B F& G* p7 Z
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(Test Animal Rabbits) & b' r. p) Q, M- y2 D2 O
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Measurements in centimetres Average
! P( B1 L+ d4 v, t( K) G5 J- BRange of Average percentage
3 n# S1 N1 |9 s3 u( x! a weight of area of of total
/ F$ B2 W, U" W6 N8 G6 LDiameter Overall animals exposure body ! W8 Z9 e$ M N4 h
at ends length (grams) (cm.2) surface 9 A' ?& w% w2 J1 K$ O9 d* D/ R
7.0 12.5 2,500 — 3,500 240 10.7
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The sleeves may vary in size to accommodate smaller or larger subjects. In the testing of unctuous materials that adhere readily to the skin, mesh wire screen may be employed instead of the sleeve. The screen is padded and raised approximately 2 centimetres from the exposed skin. In the case of dry powder preparations, the skin and substance are moistened with physiological saline prior to exposure. The sleeve or screen is then slipped over the gauze which holds the dose applied to the skin. In the case of finely divided powders the measured dose is evenly distributed on cotton gauze, which is then secured to the area of exposure.
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8 O1 l# s3 c. S* lThe animals are prepared by clipping the skin of the trunk free of hair. Approximately one half of the animals are further prepared by making epidermal abrasions every 2 centimetres or 3 centimetres longitudinally over the area of exposure. The abrasions are sufficiently deep to penetrate the stratum corneum (horny layer of the epidermis), but not to disturb the derma — that is, not to obtain bleeding.
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The sleeve is slipped onto the animal, that is then placed in a comfortable but immobilized position in a multiple animal holder. Selected doses of liquids and solutions are introduced under the sleeve. If there is slight leakage from the sleeve, which may occur during the first few hours of exposure, it is collected and reapplied. Dosage levels are adjusted in subsequent exposures (if necessary) to enable a calculation of a dose that would be fatal to 50 per cent of the animals. This can be determined from mortality ratios obtained at various doses employed. At the end of 24 hours the sleeves or screens are removed, the volume of unabsorbed material, if any, is measured, and the skin reactions are noted. The subjects are cleaned by thorough wiping, observed for gross symptoms of poisoning, and then observed for two weeks.
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4 E- J; G7 F5 y1 Q4 X3. For the purposes of this schedule, “LD50" means the dose that will kill 50 per cent of test animals under the specified conditions of test; and “LC50" means the concentration of gas and vapour that will kill 50 per cent of test animals under the specified conditions of test.
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4. The methods referred to in subsection 1(5) are described in publications as follows: / R& d! a7 Q2 B7 l
(a) C.I. Bliss, The determination of the dosage-mortality curve from small numbers, Quarterly Journal of Pharmacy and Pharmacology, 1939, Volume 11, page 192; and
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(b) J.T. Litchfield and W.F. Wilcoxon, A simplified method of evaluating dose-effect experiments, Journal of Pharmacology and Experimental Therapeutics, 1949, Volume 96, page 99. |
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