Annex C Derivation of Toxicity Reference Dose for Marine Mammals
Toxicological effects data were reviewed from various scientific literature, database and guidelines, including toxicological profiles of ATSDR, Sample et al. (1996), IRIS Database, WHO (2000) and NHMRC (2004). As toxicological data are not available specifically for dolphins or porpoises, it was necessary to use toxicological data for surrogate species. The toxicological data reviewed were summarized at the end of this Annex.
The following rules are adopted to derive COC-specific toxicity reference dose (equivalent to a chronic No Observable Adverse Effect Level (NOAEL)) for marine mammals from the toxicological data reviewed, based on the hierarchy described in SSDS/EIAS DRA (1998):
· Rule 1: Toxicity data shall be ecologically relevant to the Study
o Ecological endpoint: ecologically relevant endpoint such as reproduction, development and survival (desired endpoint) shall be used when available
· Rule 2: For exposure duration, chronic exposure is preferred to subchronic exposure; subchronic exposure is preferred to acute exposure
· Rule 3: The following framework shall be followed for selection of study endpoint:
o If highest reported NOAEL is below all available LOAELs (Lowest Observed Adverse Effect Level) across all species for the desired endpoints à the highest NOAEL is selected
o If a LOAEL for a test species is same to or below the highest NOAEL (either from the same test species or another species) à the highest NOAEL is not selected; the highest NOAEL which fells below the lowest LOAEL is selected
o If the lowest NOAEL is greater than the lowest LOAEL (of a different study) à the lowest available LOAEL is selected
o If only one NOAEL and LOAEL are available à the lowest of the two values is selected
· Rule 4: UF shall be applied to convert a toxicity endpoint (not a chronic NOAEL) to a chronic NOAEL (adopted from USEPA (1999b)):
o Chronic LOAEL should be multiplied by a UF of 0.1
o Subchronic NOAEL should be multiplied by a UF of 0.1
o Acute lethal value (such as LD50) should be multiplied by an UF of 0.01
· Rule 5: UF shall be applied to extrapolate a NOAEL for one type of organism to another:
o NOAEL = NOAEL of organism in different family but same order x 0.5
o NOAEL = NOAEL of organism in different order but same class x 0.5
o NOAEL = NOAEL of organism which is non-protected species x 0.5
The derived toxicity reference doses are presented in Table 1.
Table 1 Toxicity Reference Doses
|
COC |
Toxicological Data Adopted (mg/kg/d) |
UF Used |
Toxicity Reference Dose Derived (mg/kg/d) |
|
Bromoform |
100, chronic NOAEL (reproductive effect) for mouse |
0.5 x 0.5 x 0.5 = 0.125 |
12.5 |
|
Chloroform |
30, chronic NOAEL (reproductive effect) for dog |
0.5 x 0.5 x 0.5 = 0.125 |
3.75 |
|
Dibromochloromethane |
80, chronic NOAEL (reproductive effect) for rat |
0.5 x 0.5 x 0.5 = 0.125 |
10.0 |
|
Dibromoacetic acid |
2, subchronic NOAEL (reproductive effect) for rat |
0.5 x 0.5 x 0.5 x 0.1 = 0.0125 |
0.025 |
|
Chloroacetic acid |
15, chronic LOAEL (decreased survival) for rat |
0.5 x 0.5 x 0.5 x 0.1 = 0.0125 |
0.1875 |
|
COC |
Toxicological Data Adopted (mg/kg/d) |
UF Used |
Toxicity Reference Dose Derived (mg/kg/d) |
|
Dichloroacetic acid |
7.6, subchronic NOAEL for mice |
0.5 x 0.5 x 0.5 x 0.1 = 0.0125 |
0.095 |
|
Trichloroacetic acid |
36, subchronic NOAEL for rat |
0.5 x 0.5 x 0.5 x 0.1 = 0.0125 |
0.45 |
|
Total residual chlorine |
15, chronic NOAEL for rats and mice |
0.5 x 0.5 x 0.5 = 0.125 |
1.875 |
|
Tetrachloroethylene |
386, chronic LOAEL for mouse |
0.5 x 0.5 x 0.5 x 0.1 = 0.0125 |
4.825 |
|
Trichloroethylene |
500, chronic LOAEL for rat |
0.5 x 0.5 x 0.5 x 0.1 = 0.0125 |
6.25 |
|
2,4,6-trichlorophenol |
1300, chronic NOAEL for mouse |
0.5 x 0.5 x 0.5 = 0.125 |
162.5 |
|
Hexachlorobenzene |
11, chronic LOAEL for dog |
0.5 x 0.5 x 0.5 x 0.1 = 0.0125 |
0.1375 |
|
Beta-BHC |
0.2, chronic NOAEL for rat |
0.5 x 0.5 x 0.5 = 0.125 |
0.025 |
|
Gamma-BHC |
32, chronic LOAEL for rat |
0.5 x 0.5 x 0.5 x 0.1 = 0.0125 |
0.4 |
|
Aluminum |
49, chronic NOAEL for mouse |
0.5 x 0.5 x 0.5 x 0.1 = 0.125 |
6.125 |
|
Antimony |
1.25, chronic LOAEL for mouse |
0.5 x 0.5 x 0.5 x 0.1 = 0.0125 |
0.015625 |
|
Barium |
15, chronic NOAEL for rat |
0.5 x 0.5 x 0.5 = 0.125 |
1.875 |
|
Chromium (III) |
2,737, chronic NOAEL for rat |
0.5 x 0.5 x 0.5 = 0.125 |
342.125 |
|
Copper |
12, chronic NOAEL for mink |
0.5 x 0.5 x 0.5 = 0.125 |
1.5 |
|
Lead |
8, chronic NOAEL for rat |
0.5 x 0.5 x 0.5 = 0.125 |
1 |
|
Nickel |
40, chronic NOAEL for rat |
0.5 x 0.5 x 0.5 = 0.125 |
5 |
|
Selenium |
0.21, chronic NOAEL for rat |
0.5 x 0.5 x 0.5 = 0.125 |
0.02625 |
|
Silver |
222.2, chronic LOAEL for rat |
0.5 x 0.5 x 0.5 x 0.1 = 0.0125 |
2.7775 |
|
Tin |
23.4, chronic NOAEL for mouse |
0.5 x 0.5 x 0.5 = 0.125 |
2.925 |
|
Vanadium |
2.1, chronic LOAEL for rat |
0.5 x 0.5 x 0.5 x 0.1 = 0.0125 |
0.02625 |
|
Zinc |
160, chronic NOAEL for rat |
0.5 x 0.5 x 0.5 = 0.125 |
20 |
|
Ammonia |
412, subchronic NOAEL for rat |
0.5 x 0.5 x 0.5 x 0.1 = 0.0125 |
5.15 |
|
Dioxins and furans (TEQ) |
7.1E-5, chronic NOAEL for rat |
0.5 x 0.5 x 0.5 = 0.125 |
8.875E-6 |
|
Toluene |
260, chronic LOAEL for mouse |
0.5 x 0.5 x 0.5 x 0.1 = 0.0125 |
3.25 |
|
Diazinon |
12, chronic NOAEL for rat |
0.5 x 0.5 x 0.5 = 0.125 |
1.5 |
|
Malathion |
359, chronic LOAEL for rat |
0.5 x 0.5 x 0.5 x 0.1 = 0.0125 |
4.4875 |
Toxicological Data of COCs Reviewed
|
|
NOAEL (mg/kg/d) |
LOAEL (mg/kg/d) |
Source |
|
Bromoform |
||||
|
Rat (Fischer-344) male 103wk, 5d/wk (chronic) |
|
200 (decreased survival) |
ATSDR |
|
|
Rat (Fischer-344) male 103wk, 5d/wk (chronic) |
100 (reproductive) |
200 (reproductive) |
||
|
Rat (Fischer-344) female 103wk, 5d/wk (chronic) |
200 (reproductive) |
|
||
|
Mouse (B6C3F1) male 103wk, 5d/wk (chronic) |
100 (reproductive) |
|
||
|
Mouse (B6C3F1) female 103wk, 5d/wk (chronic) |
200 (reproductive) |
|
||
|
Rat, subchronic oral gavage bioassay |
17.9 (hepatic lesions) |
35.7 (hepatic lesions) |
IRIS |
|
|
Rat, 13 weeks oral gavage bioassay (subchronic) |
25 (hepatic lesions) |
|
WHO EHC 216 |
|
|
Chloroform |
||||
|
Rat (Osborne-Mendel), male 78wk, 5d/wk, 1 time/d (chronic) |
180 (reproductive) |
90 (decreased survival) |
ATSDR |
|
|
Rat (Osborne-Mendel), female 78wk, 5d/wk, 1 time/d (chronic) |
200 (reproductive) |
100 (decreased survival) |
||
|
Mouse (B6C3F1), female 78wk, 5d/wk, 1 time/d (chronic) |
477 (reproductive) |
477 (decreased survival) |
||
|
Mouse (B6C3F1), male 78wk, 5d/wk, 1 time/d (chronic) |
277 (reproductive) |
|
||
|
Dog (Beagle) 7.5yr, 6d/wk (chronic) |
30 (reproductive) |
|
||
|
Dog Chronic oral bioassay |
|
12.9 (moderate/marked fatty cyst formation in the liver and elevated SGPT) |
IRIS |
|
|
Mice 3 weeks, administration in corn oil (subchronic) |
10 (cytolethality and regenerative hyperplasia) |
|
WHO EHC 216 |
|
|
Rat 13 wk (subchronic) |
15 (liver, kidney gonad condition) |
41 (liver, kidney gonad condition) |
ORNL |
|
|
Dibromochloromethane |
||||
|
Mouse (B6C3F1) 105wk, 5d/wk (chronic) |
|
100 (decreased survival) |
ATSDR |
|
|
Rat (Fischer-344) 2yr, 5d/wk (chronic) |
80 (reproductive) |
|
||
|
Mouse (B6C3F1) 105wk, 5d/wk (chronic) |
100 (reproductive) |
|
||
|
Rat Subchronic gavage bioassay |
21.4 (hepatic lesions) |
42.9 (hepatic lesions) |
IRIS |
|
|
Rat 13 week corn oil gavage (subchronic) |
30 (hisopathological effect) |
|
WHO EHC 216 |
|
|
|
NOAEL (mg/kg/d) |
LOAEL (mg/kg/d) |
Source |
|
|
Dibromoacetic acid |
||||
|
Rat, male 79 days (subchronic) |
2 (reproductive) |
|
WHO EHC 216 |
|
|
Chloroacetic acid |
||||
|
Rat 2-year (chronic) |
|
15 (decreased survival) |
NHMRC |
|
|
Dichloroacetic acid |
||||
|
Mice 90-day (subchronic) |
7.6 |
|
NHMRC |
|
|
Dog Subchronic oral |
|
12.5 (lesions in the testes, cerebrum, cerebellum, and liver) |
IRIS |
|
|
Mice 8 weeks (subchronic) |
40 (hepatomegaly and glycogen accumulation) |
100 (hepatomegaly and glycogen accumulation) |
WHO EHC 216 |
|
|
Trichloroacetic acid |
||||
|
Rat, male 90-day (subchronic) |
36 |
|
NHMRC |
|
|
Mice Long-term study |
40 (hepatic toxicity) |
|
WHO EHC 216 |
|
|
Total residual chlorine |
||||
|
Rat Chronic drinking water study |
14.4 |
|
IRIS |
|
|
Rats and mice 2-year drinking water study (chronic) |
15 |
|
NHMRC, WHO EHC 216 |
|
|
Tetrachloroethylene |
||||
|
Rat (Subchronic test) |
14 (hepatotoxicity) |
|
IRIS |
|
|
Rat (Subchronic test) |
14 |
|
NHMRC |
|
|
Rat, male (Chronic test) |
|
471 (decreased survival) |
ATSDR |
|
|
Rat, female (Chronic test) |
|
474 (decreased survival) |
||
|
Mouse, female (Chronic test) |
|
386 (reduced survival) |
||
|
Mouse, male (Chronic test) |
|
536 (reduced survival) |
||
|
Rat (Chronic test) |
941 (systematic effect) |
|
||
|
Rat, male (Chronic test) |
|
471 (renal nephropathy) |
||
|
Rat, female (Chronic test) |
|
474 (renal nephropathy) |
||
|
Mouse (Chronic test) |
1,072 (systematic effect) |
|
||
|
Mouse, female (Chronic test) |
|
386 (renal nephropathy) |
||
|
Mouse, male (Chronic test) |
|
536 (renal nephropathy) |
||
|
Mouse (Subchronic test) |
1.4 (hepatotoxicity) |
7 (hepatotoxicity) |
ORNL |
|
|
|
NOAEL (mg/kg/d) |
LOAEL (mg/kg/d) |
Source |
|
|
Trichloroethylene |
|
|||
|
Mouse (Subchronic test) |
|
100 (minor effect on relative liver weight) |
IRIS |
|
|
Rat, male (Chronic test) |
|
1,097 (decreased survival) |
ATSDR |
|
|
Rat, female (Chronic test) |
|
549 (decreased survival) |
|
|
|
Rat, male (Chronic test) |
|
500 (decreased survival) |
|
|
|
Rat, female (Chronic test) |
|
500 (decreased survival) |
|
|
|
Mouse, female (Chronic test) |
|
869 (decreased survival) |
|
|
|
Mouse, male (Chronic test) |
|
1,000 (decreased survival) |
|
|
|
Rat (Chronic test) |
250 (systematic effect) |
|
|
|
|
Rat, male (Chronic test) |
50 (renal effect) |
250 (renal effect) |
|
|
|
Rat (Chronic test) |
1,097 (systematic effect) |
|
|
|
|
Rat (Chronic test) |
|
549 (toxic nephrosis, proximal tubular epithelium alterations) |
|
|
|
Rat (Chronic test) |
|
549 (alopecia, roughening of hair coat, sores) |
|
|
|
Rat (Chronic test) |
|
549 (squinting, red discharge) |
|
|
|
Rat, male (Chronic test) |
549 (body weight decreased) |
1,097 (body weight decreased) |
|
|
|
Rat, female (Chronic test) |
|
549 (body weight decreased) |
|
|
|
Rat (Chronic test) |
1,000 (systematic effect) |
|
|
|
|
Rat (Chronic test) |
|
500 (toxic nephrosis, cytomegaly) |
|
|
|
Rat, male (Chronic test) |
|
500 (body weight decreased) |
|
|
|
Rat (Chronic test) |
1,000 (systematic effect) |
|
|
|
|
Rat (Chronic test) |
|
500 (toxic nephrosis, cytomegaly) |
|
|
|
Rat, male (Chronic test) |
500 (body weight decreased) |
1,000 (body weight decreased) |
|
|
|
Mouse, male (Chronic test) |
2,239 (systematic effect) |
1,160 (toxic nephrosis) |
|
|
|
Mouse, female (Chronic test) |
|
569 (alopecia, skin sores) |
|
|
|
Mouse (Chronic test) |
1,000 (systematic effect) |
1,000 (alight to moderate toxic nephrosis, cytomegaly) |
|
|
|
Mouse, male (Chronic test) |
|
1,000 (decreased body weight) |
|
|
|
Mouse (Subchronic test) |
0.7 (hepatotoxicity) |
7 (hepatotoxicity) |
ORNL |
|
|
|
NOAEL (mg/kg/d) |
LOAEL (mg/kg/d) |
Source |
||
|
2,4,6-trichlorophenol |
|||||
|
Rat (Chronic test) |
4.5 |
|
NHMRC |
||
|
Rat (Chronic effect) |
500 (systematic effect) |
250 (bone marrow hyperplasia) |
ATSDR |
||
|
Rat, female (Chronic effect) |
|
500 (decreased body weight) |
|||
|
Mouse, male (Chronic effect) |
1,300 (systematic effect) |
650 (hepatic hyperplasia) |
|||
|
Mouse (Chronic effect) |
1,356 (systematic effect) |
|
|||
|
Mouse, female (Chronic effect) |
|
658 (reduced body weight) |
|||
|
Rat (Chronic test) |
500 (immuno / lymphor effect) |
|
|||
|
Rat (Chronic effect) |
500 (neurological effect) |
|
|||
|
Mouse, female (Chronic test) |
1,356 (neurological effect) |
|
|||
|
Rat (Chronic test) |
500 (reproductive) |
|
|||
|
Mouse, male (Chronic test) |
1,300 (reproductive) |
|
|||
|
Mouse, female (Chronic test) |
1,356 (reproductive) |
|
|||
|
Hexachlorobenzene |
|||||
|
Rat (Chronic test) |
0.08 (liver effect) |
|
IRIS |
||
|
Mouse (Chronic test) |
|
24 (decreased survival) |
ATSDR |
||
|
Dog, female (Chronic test) |
|
11 (decrease survival) |
|||
|
Rat (Chronic test) |
0.05 (hepatic effect) |
0.25 (mitochondrial swelling and elongation) |
|||
|
Rat, female (Chronic test) |
|
7 (systematic effect) |
|||
|
Rat (Chronic test) |
|
10 (systematic effect) |
|||
|
Rat, female (Chronic effect) |
|
10 (hepatic effect) |
|||
|
Rat, female (Chronic effect) |
10 (decreased body weight) |
|
|||
|
Mouse, male (Chronic test) |
|
13 (hepatic effect) |
|||
|
Hamster, male (Chronic test) |
|
16 (decreased in weight gain) |
|||
|
Dog (Chronic test) |
11 (Cardiovascular system) |
110 (arteriopathy) |
|||
|
Dog (Chronic test) |
1 (Gastro effect) |
11 (diarrhea, necrotic and inflammatory lesions of the omentum and abdominal serosa) |
|||
|
Dog (Chronic test) |
1 (hemato effect) |
110 (anemia) |
|||
|
|
NOAEL (mg/kg/d) |
LOAEL (mg/kg/d) |
Source |
||
|
Hexachlorobenzene (Con’t) |
|||||
|
Dog (Chronic test) |
1 (hepatic effect)
|
11 (hepatomegaly, bile duct hyperplasia, pericholangitis, perioportal fibrosis) |
|
||
|
Dog (Chronic test) |
1 (decreased body weight) |
11 (decreased body weight) |
|||
|
Dog (Chronic test) |
|
0.1 (immuno / lymphoret effect) |
|||
|
Mouse (Chronic test) |
|
24 (tremors, convulsions) |
|||
|
b-BHC |
|||||
|
Rat, female (Chronic test) |
5 (hemato effect) |
|
ATSDR |
||
|
Rat, male (Chronic test) |
|
22.5 (decreased red blood cells, leukocyte and hemoglobin concentrations) |
|||
|
Rat, male (Chronic test) |
|
4.5 (hyalinization of centrilobular cells) |
|||
|
Rat, male (Chronic test) |
4.5 (renal effect) |
22.5 (calcinosis) |
|||
|
Rat, female (Chronic test) |
5 (decreased in body weight) |
|
|||
|
Mouse, female (Chronic test) |
20 (hepatic effect) |
|
|||
|
Mouse, male (Chronic test) |
|
54 (nuclear irregularities in foci of enlarged hepatocytes) |
|||
|
Mouse, male (Chronic test) |
|
45 (centrilobular hypertrophy) |
|||
|
Rat, female (Chronic test) |
5 (immuno / lymphoret effect) |
|
|||
|
Rat, male (Chronic test) |
|
22.5 (cortical atrophy in thymus) |
|||
|
Rat, female (Chronic test) |
5 (neurological effect) |
|
|||
|
Rat, male (Chronic test) |
|
22.5 (ataxia, coma) |
|||
|
Rat, male (Chronic test) |
0.9 (reproductive) |
22.5 (atrophy of testes) |
|||
|
Rat, female (Chronic test) |
0.2 (reproductive) |
25 (atrophy of ovary) |
|||
|
|
NOAEL (mg/kg/d) |
LOAEL (mg/kg/d) |
Source |
||
|
g-BHC |
|||||
|
Rat, female (Chronic test) |
|
32 (increased mortality rate) |
ATSDR |
||
|
Rat, male (Chronic test)
|
|
7 (hepatic effect) |
|||
|
Rat, female (Chronic test) |
32 (renal effect) |
|
|||
|
Rat, female (Chronic test) |
4 (systematic effect) |
|
|||
|
Rat, male (Chronic test) |
|
112 (moderate microscopic damage of hepactic cell) |
|||
|
Rat, female (Chronic test) |
64 (decreased body weight gain) |
|
|||
|
Rat, male (Chronic test) |
|
112 (decreased body weight gain) |
|||
|
Rat (Chronic test) |
9 (hepatic effect) |
|
|||
|
Rat (Chronic test) |
8 (reproductive effect) |
|
ORNL |
||
|
Antimony |
|||||
|
Rat (Chronic test) |
|
0.35 (longevity, blood glucose, and cholesterol) |
IRIS |
||
|
Rat (Chronic test) |
6 (decreased body weight gain and reduced food and water intake) |
|
WHO (2004) |
||
|
Rat (Chronic test) |
|
0.262 (decreased lifespan) |
ATSDR |
||
|
Mouse, female (Chronic test) |
|
0.35 (decreased lifespan) |
|||
|
Rat (Chronic test) |
0.262 (cardio effect) |
0.262 (decreased nonfasting serum glucose, increased serum cholesterol) |
|||
|
Mouse (Chronic test) |
0.35 (hepatic effect) |
|
|||
|
Mouse (Chronic test) |
|
1.25 (longevity) |
ORNL |
||
|
|
NOAEL (mg/kg/d) |
LOAEL (mg/kg/d) |
Source |
|
Barium |
|||
|
Mouse, male (Chronic test) |
|
160 (increased mortality) |
ATSDR |
|
Rat, male (Chronic test) |
15 (systematic effect) |
|
|
|
Rat (Chronic test) |
60 (systematic effect) |
|
|
|
Rat, female (Chronic test) |
0.17 (cardio effect) |
7.2 (depressed rates of cardiac contraction and electrical conductivity) |
|
|
Rat, female (Chronic test) |
|
0.8 (increased blood pressure) |
|
|
Mouse, male (Chronic test) |
160 (systematic effect) |
|
|
|
Mouse, male (Chronic test) |
75 (renal effect) |
160 (marked nephropathy) |
|
|
Mouse, male (Chronic test) |
75 (body weight) |
160 (weight loss) |
|
|
Rat, male (Chronic test) |
15 (immuno/lymphoret effect) |
|
|
|
Rat, male (Chronic test) |
60 (immuno/lymphoret effect) |
|
|
|
Mouse, male (Chronic test) |
75 (immuno/lymphoret effect) |
160 (lymphoid depletion in the spleen and decreased relative and absolute spleen weight) |
|
|
Rat, male (Chronic test) |
15 (immuno/lymphoret effect) |
|
|
|
Rat, male (Chronic test) |
60 (immuno/lymphoret effect) |
|
|
|
Mouse, male (Chronic test |
160 (immuno/lymphoret effect) |
|
|
|
Rat, male (Chronic test) |
15 (reproductive effect) |
|
|
|
Rat, male (Chronic test) |
60 (reproductive effect) |
|
|
|
Rat, female (Chronic test) |
75 (reproductive effect) |
|
|
|
Mouse, male (Chronic test) |
160 (reproductive effect) |
|
|
|
Mouse, female (Chronic test) |
200 (reproductive effect) |
|
|
|
Rat (Chronic test) |
5.1 (growth) |
|
ORNL |
|
Rat (Chronic test) |
|
19.8 (mortality) |
|
|
|
NOAEL (mg/kg/d) |
LOAEL (mg/kg/d) |
Source |
|
Chromium |
|||
|
Rat (Chronic test) |
1,468 |
|
IRIS |
|
Rat (Chronic test) |
2,040 (systematic effect) |
|
ATSDR |
|
Rat (Chronic test) |
3.6 (systematic effect) |
|
|
|
Rat (Chronic test) |
0.46 (systematic effect) |
|
|
|
Rat (Chronic test) |
2,737 (longevity) |
|
ORNL |
|
Copper |
|||
|
Mouse, male (Chronic test) |
42 (decrease in body weight) |
|
ATSDR |
|
Rat, male (Subchronic test) |
66 (reproductive effect) |
|
|
|
Rat, female (Subchronic test) |
68 (reproductive effect) |
|
|
|
Mink (Subchronic test) |
12 (reproductive effect) |
|
|
|
Mink (Chronic test) |
11.7 (reproductive effect) |
15.14 (reproductive effect) |
ORNL |
|
Lead |
|||
|
Rat (Chronic test) |
8 (reproductive effect) |
80 (reproductive effect) |
ORNL |
|
Nickel |
|||
|
Rat (Chronic test) |
5 (decreased body and organ weights) |
|
IRIS, WHO (2004) |
|
Rat (Chronic test) |
187.5 (systematic effect) |
|
ATSDR |
|
Rat (Chronic test) |
7.5 (decrease in body weight) |
187.5 (decreased body weight gain) |
|
|
Dog (Chronic test) |
25 (respiratory effect) |
62.5 (cholesterol granulomas, emphysema, bronchiolectasis) |
|
|
Dog (Chronic test) |
62.5 (systematic effect) |
|
|
|
Dog (Chronic test) |
25 (hemato effect) |
62.5 (decreased hemaocrit and hemoglobin levels) |
|
|
Dog (Chronic test) |
25 (renal effect) |
62.5 (increased kidney weight) |
|
|
Dog (Chronic test) |
25 (decreased in body weight gain) |
62.5 (decreased in body weight gain) |
|
|
Rat (Chronic test) |
187.5 (immuno/lymphoret effect) |
|
|
|
Dog (Chronic test) |
62.5 (immuno/lymphoret effect) |
|
|
|
Rat (Chronic test) |
187.5 (neurological effect) |
|
|
|
Dog (Chronic test) |
62.5 (neurological effect) |
|
|
|
Rat (Chronic test) |
40 (reproductive effect) |
80 (reproductive effect) |
ORNL |
|
|
NOAEL (mg/kg/d) |
LOAEL (mg/kg/d) |
Source |
|
Selenium |
|||
|
Rat (Chronic test) |
|
0.5 (reduced longevity) |
ATSDR |
|
Rat (Chronic test) |
0.1 (muscular/skeletal effect) |
0.2 (soft bones) |
|
|
Rat (Chronic test) |
0.025 (hepatic effect) |
0.1 (hyperplastic lesions) |
|
|
Rat (Chronic test) |
0.025 (renal effect) |
0.1 (nephritis) |
|
|
Rat, female (Chronic test) |
0.5 (systematic effect) |
|
|
|
Rat, female (Chronic test) |
|
0.25 (slight to moderate cirrhosis) |
|
|
Mouse (Chronic test) |
|
0.57 (amyloidosis) |
|
|
Mouse (Chronic test) |
0.57 (decrease in body weight) |
|
|
|
Rat (Chronic test) |
0.21 (reproductive effect) |
1.05 (decreased fertility, maternal toxicity) |
|
|
Rat (Chronic test) |
0.20 (reproductive effect) |
0.33 (reproductive effect) |
ORNL |
|
Silver |
|||
|
Rat (Subhronic test) |
|
222.2 (decreased weight gain) |
ATSDR |
|
Mouse (Subhronic test) |
|
18.1 (hypoactivity) |
|
|
Tin |
|||
|
Rat (Chronic test) |
63 (systematic effect) |
|
ATSDR |
|
Rat (Chronic test) |
|
0.7 (systematic effect) |
|
|
Mouse (Chronic test) |
164 (systematic effect) |
|
|
|
Mouse (Chronic test) |
0.7 (decrease in body weight) |
|
|
|
Mouse (Chronic test) |
23.4 (reproductive effect) |
35 (reproductive effect) |
ORNL |
|
Vanadium |
|||
|
Rat (Chronic test) |
0.89 (decreased hair cystine) |
|
IRIS |
|
Rat (Chronic test) |
0.7 (systematic effect) |
|
ATSDR |
|
Mouse (Chronic test) |
4.1 (systematic effect) |
|
|
|
Mouse (Chronic test) |
0.54 (other effect) |
|
|
|
Rat (Chronic test) |
|
2.1 (reproductive effect) |
ORNL |
|
Zinc |
|||
|
Rat (Chronic test) |
160 (reproductive effect) |
320 (reproductive effect) |
ORNL |
|
|
NOAEL (mg/kg/d) |
LOAEL (mg/kg/d) |
Source |
|
Ammonia |
|||
|
Rat, female (Subchronic test) |
22 (decrease body weight) |
3,150 (reduction in body weight) |
ATSDR |
|
Rat (Subchronic test) |
22 (decrease body weight) |
3,102.2 (reduced body weight gain) |
|
|
Rat (Subchronic test) |
412 (renal effect) |
|
|
|
Rat, female (Subchronic test) |
79 (systematic effect) |
|
|
|
Dog (Subchronic test) |
|
337 (bone deformity and softening) |
|
|
Rat (Subchronic test) |
22 (neurological effect) |
3,102.2 (decreased binding of somatostatin to receptors in frontoparietal cortex and hippocampus) |
|
|
Rat (Subchronic test) |
|
4,293 (decreased body weight) |
|
|
|
NOAEL (mg/kg/d) |
LOAEL (mg/kg/d) |
Source |
|
Dioxins and Furans |
|||
|
Rat (Chronic test) |
|
0.1 (increased mortality) |
ATSDR |
|
Mouse (Chronic test) |
|
0.36 (increased mortality) |
|
|
Mouse, male (Chronic test) |
|
1 (decreased survival) |
|
|
Rat (Chronic test) |
0.01 (respiratory effect) |
0.1 (local alveolar hyperplasia) |
|
|
Rat (Chronic test) |
0.01 (cardio effect) |
0.1 (myocardial degeneration, periateritis) |
|
|
Rat (Chronic test) |
0.1 (gastro effect) |
|
|
|
Rat (Chronic test) |
0.01 (hemato effect) |
0.1 (decreased erythocytes) |
|
|
Rat (Chronic test) |
0.1 (muscular/skeletal effect) |
|
|
|
Rat (Chronic test) |
|
0.01 (severe and extensive hepatic nacrosis) |
|
|
Rat (Chronic test) |
0.1 (renal effect) |
|
|
|
Rat (Chronic test) |
|
0.1 (decreased in body weight gain) |
|
|
Rat (Chronic test) |
0.071 (systematic effect) |
|
|
|
Rat (Chronic test) |
0.0071 (hepatic effect) |
0.071 (toxic hepatitis) |
|
|
Rat (Chronic test) |
|
0.0014 (decrease in body weight gain) |
|
|
|
NOAEL (mg/kg/d) |
LOAEL (mg/kg/d) |
Source |
|
Dioxins and Furans (Con’t) |
|||
|
Rat (Chronic test) |
0.286 (systematic effect) |
|
ATSDR |
|
Rat (Chronic test) |
0.057 (decrease in weight gain) |
|
|
|
Rat, male (Chronic test) |
|
0.0286 (decreased weight gain) |
|
|
Mouse (Chronic test) |
|
0.36 (dermatitis) |
|
|
Mouse (Chronic test) |
|
0.36 (decreased weight gain) |
|
|
Mouse (Chronic test) |
0.3 (systematic effect) |
|
|
|
Mouse (Chronic test) |
0.0071 (renal effect) |
0.071 (lymphocytic inflammatory infiltration in kidney) |
|
|
Monkey (Chronic test) |
0.001 (immuno/lymphoret effect) |
|
|
|
Rat (Chronic test) |
0.01 (immuno/lymphoret effect) |
0.1 (thymic atrophy) |
|
|
Rat (Chronic test) |
0.071 (immuno/lymphoret effect) |
|
ATSDR |
|
Rat, male (Chronic test) |
0.286 (immuno/lymphoret effect) |
|
|
|
Mouse (Chronic test) |
0.3 (immuno/lymphoret effect) |
|
|
|
Mouse, female (Chronic test) |
|
0.03 (decrease in the effector and memory T cell phenotypes) |
|
|
Rat (Chronic test) |
0.01 (neurological effect) |
0.1 (hemorrhage in brain) |
|
|
Rat (Chronic test) |
0.071 (neurological effect) |
|
|
|
Mouse (Chronic test) |
0.3 (neurological effect) |
|
|
|
Rat (Chronic test) |
0.1 (reproductive effect) |
|
|
|
Rat (Chronic test) |
0.071 (reproductive effect) |
|
|
|
Mouse (Chronic test) |
0.3 (reproductive effect) |
|
|
|
|
NOAEL (mg/kg/d) |
LOAEL (mg/kg/d) |
Source |
||
|
Toluene |
|||||
|
Mouse (Chronic test) |
|
260 (reproductive effect) |
ORNL |
||
|
Diazinon |
|||||
|
Rat, male |
10 (systematic effect) |
|
ATSDR |
||
|
Rat, female |
12 (systematic effect) |
|
|||
|
Rat, male |
10 (immuno/lymphoret effect) |
|
|||
|
Rat, female |
12 (immuno/lymphoret effect) |
|
|||
|
Rat, male |
0.06 (neurological effect) |
5 (decrease in brain AChE) |
|||
|
Rat, female |
0.07 (neurological effect) |
6 (decrease in brain AChE) |
|||
|
Rat, male |
10 (reproductive effect) |
|
|||
|
Rat, female |
12 (reproductive effect) |
|
|||
|
|
NOAEL (mg/kg/d) |
LOAEL (mg/kg/d) |
Source |
|
Malathion |
|||
|
Rat, male (Chronic test) |
|
359 (significant increase in deaths) |
ATSDR |
|
Rat, male (Chronic test) |
|
166 (increased mortality) |
|
|
Rat, female (Chronic test) |
35 (systematic effect) |
415 (increased absolute and relative thyroid and parathyroid weight) |
|
|
Rat, male (Chronic test) |
|
359 (systematic effect) |
|
|
Rat (Chronic test) |
332 (systematic effect) |
|
|
|
Rat, male (Chronic test) |
|
166 (chronic inflammation of the stomach and stomach ulcers) |
|
|
Rat, female (Chronic test) |
|
166 (fatty metamorphosis of the liver) |
|
|
Mouse (Chronic test) |
2,980 (systematic effect) |
|
|
|
Mouse, male (Chronic test) |
17.4 (respiratory effect) |
1,476 (systematic effect) |
|
|
Mouse, female (Chronic test) |
167 (systematic effect) |
|
|
|
Rat, male (Chronic test) |
2 (neurological effect) |
359 (inhibition of plasma cholinesterase) |
|
|
Mouse, female (Chronic test) |
20.8 (neurological effect) |
|
|
|
Mouse, male (Chronic test) |
|
1,476 (inhibition of plasma and RBC cholinesterase activity) |
|
|
Mouse (Chronic test) |
|
1,490 (cystic endometrial hyperplasia) |
|
Note: Bolded value was used to derive toxicological reference dose