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REACH

MoVNbTe mixed oxide

EC number: 888-364-4 | CAS number: 146569-48-4

Life Cycle description
Uses advised against

Toxicological information

Repeated dose toxicity: inhalation

Administrative data

Endpoint:: short-term repeated dose toxicity: inhalation
Type of information:: experimental study
Adequacy of study:: key study
Study period:: 26 April 2021 to 25 August 2021
Reliability:: 1 (reliable without restriction)
Rationale for reliability incl. deficiencies:: guideline study

Data source

Reference

Reference Type:: study report
Title:: Unnamed
Year:: 2022
Report date:: 2022

Materials and methods

Test guideline

Qualifier:: according to guideline
Guideline:: OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
Version / remarks:: adopted on 25 June 2018
Deviations:: no

GLP compliance:: yes (incl. QA statement)
Limit test:: no

Test material

Test material information

Test material form:: solid

Specific details on test material used for the study:: SOURCE OF TEST MATERIAL
- Batch No.of test material: EX.14402.600
- Expiration date of the lot/batch: No change of properties known over time (endless)

Test animals

Species:: rat
Strain:: Sprague-Dawley
Details on species / strain selection:: Rat is the preferred laboratory rodent species for inhalation toxicity assessment and is also recommended by various regulatory guidelines.
Sex:: male/female
Details on test animals or test system and environmental conditions:: TEST ANIMALS
- Source: In-house bred animals
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 7-8 weeks at the time of randomization
- Weight at study initiation: Males: 121.32 g to 137.50 g
Females: 111.62 g to 126.34 g
- Fasting period before study: No
- Housing: polypropylene cage (size: L 430 x B 285 x H 150 mm) with stainless steel mesh top grill having facilities for holding pelleted feed and water bottle
- Diet (e.g. ad libitum): Yes
- Water (e.g. ad libitum): Yes
- Acclimation period: 26 April 2021 to 02 May 2021

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.4°C to 23.0°C
- Humidity (%): 43% to 66%
- Air changes (per hr): 12 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light and 12 hours dark cycle

IN-LIFE DATES: From: 26 April 2021 To: 14 June 2021

Administration / exposure

Route of administration:: inhalation: aerosol
Type of inhalation exposure:: nose only
Vehicle:: air
Mass median aerodynamic diameter (MMAD):: > 1.67 - <= 2.05 µm
Geometric standard deviation (GSD):: 2.98
Details on inhalation exposure:: GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: CH Technologies, USA
- Method of holding animals in test chamber: Restrainer
- Source and rate of air: compressor air and 20 lt per min
- Method of conditioning air: filter air
- System of generating particulates/aerosols: Rotating Brush Generator
- Temperature, humidity, pressure in air chamber: 21.5 to 23.2, 51.4 to 57.8%, 60 psi
- Air flow rate: 20 lt/min
- Air change rate: 12-15 air changes
- Method of particle size determination: cascade impactor
- Treatment of exhaust air: distilled water

TEST ATMOSPHERE
- Brief description of analytical method used: Actual aerosol concentration of active ingredients of test item during exposure (first week and last week of exposure) was determined by ICPMS method. The results of first week of exposure and fourth week of exposure were found within ±20% of nominal target dose
- Samples taken from breathing zone: yes
Analytical verification of doses or concentrations:: yes
Details on analytical verification of doses or concentrations:: Actual aerosol concentration of active ingredients of test item during exposure (first week and last week of exposure) was determined by ICPMS method. The results of first week of exposure and fourth week of exposure were found within ±20% of nominal target dose.
Group Nominal Conc. (mg) Obtained Conc. (mg) Time (min) [A] Air flow rate (L/Min)
[B] Mean Conc. (mg) [C] BZC=
C/A B
(mg/L of air)
Date of Analysis: 28/04/2021
Sample G2 0.5 0.42 1 0.84 0.42 0.50
Sample G3 1.5 1.27 1 0.84 1.27 1.51
Sample G4 5.0 4.20 1 0.84 4.20 5.0
Date of Analysis: 04/05/2021
G2 Sample 1 A 0.43 0.43 1 0.84 0.43 0.51
G2 Sample 1 B 0.44 0.42 1 0.84
G2 Sample 1 C 0.42 0.43 1 0.84
G3 Sample 2 A 1.28 1.29 1 0.84 1.29 1.54
G3 Sample 2 B 1.26 1.28 1 0.84
G3 Sample 2 C 1.28 1.29 1 0.84
G4 Sample 3 A 4.22 4.29 1 0.84 4.22 5.02
G4 Sample 3 B 4.23 4.21 1 0.84
G4 Sample 3 C 4.21 4.17 1 0.84
Date of Analysis: 25/05/2021
G2 Sample 1 A 0.44 0.41 1 0.84 0.42 0.50
G2 Sample 1 B 0.42 0.42 1 0.84
G2 Sample 1 C 0.43 0.43 1 0.84
G3 Sample 2 A 1.26 1.30 1 0.84 1.30 1.55
G3 Sample 2 B 1.28 1.31 1 0.84
G3 Sample 2 C 1.27 1.29 1 0.84
G4 Sample 3 A 4.23 4.22 1 0.84 4.25 5.06
G4 Sample 3 B 4.22 4.24 1 0.84
G4 Sample 3 C 4.20 4.30 1 0.84
Refer Appendix 22
Note: 0.5 mg/L = 500 mg/m3; 1.5 mg/L = 1500 mg/m3; 5.0 mg/L = 5000 mg/m3.
Duration of treatment / exposure:: 6 hours/day for five days/ week
Frequency of treatment:: 6 hours/day

Doses / concentrationsopen all close all

Doses / concentrations 1

Dose / conc.:: 0.5 mg/L air (nominal)
Remarks:: 0.52 mg/L achieved

Doses / concentrations 2

Dose / conc.:: 1.5 mg/L air (nominal)
Remarks:: 1.51 mg/L achieved

Doses / concentrations 3

Dose / conc.:: 5 mg/L air (nominal)
Remarks:: 5.02 mg/L achieved

No. of animals per sex per dose:: 5 males and 5 females/dose
Control animals:: yes, concurrent no treatment
Details on study design:: - Dose selection rationale:
- Rationale for animal assignment (if not random): randomisation done
- Post-exposure recovery period in satellite groups: 14 days

Examinations

Observations and examinations performed and frequency:: CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily once
- Cage side observations checked in table [No.1] were included.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly once

BODY WEIGHT: Yes
- Time schedule for examinations: weekly once

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: before first exposure and week 4
- Dose groups that were examined: G1 and G4, G1R and G4R

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Day 27 for main group and Day 43 for recovery group
- Anaesthetic used for blood collection: Yes
- Animals fasted: Yes
- How many animals: 40 main study and 20 recovery
- Parameters checked in table [No.6] were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Day 27 for main group and Day 43 for recovery group
- Animals fasted: Yes
- How many animals: 40 main study and 20 recovery
- Parameters checked in table [No.8] were examined.

URINALYSIS: Yes
- Time schedule for collection of urine: Day 27 for main group and Day 43 for recovery group
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked in table [No.9] were examined.

NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: week 4 for main group and week 6 for recovery group
- Dose groups that were examined: G1 and G4, G1R and G4R
- Battery of functions tested: sensory activity / grip strength / motor activity / other: all

BRONCHO ALVEOLAR LAVAGE FLUID
At the end of treatment and recovery periods, all animals were fasted overnight (water
was available ad libitum), and the next day, blood, urine, and Broncho alveolar lavage
fluid (BALF) samples were collected and analysed. Subsequently, the animals were
sacrificed and subjected to gross pathological examination, and the organs were
collected, weighed, and preserved. The tissues/organs in vehicle control and high dose
group animals including recovery animals were subjected to histopathological
examinations.
Sacrifice and pathology:: GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Statistics:: The raw data were subjected to statistical analysis. The computer printout of the data (in the form of the appendix) was verified with the original raw data. After verification, the data were subjected to statistical analysis using SPSS Software version 22. Body weight, percent change in body weight with respect to Day 1, feed consumption, FOB (Foot splay, Actimeter, Grip strength and body temperature), organ weight ratios, hematology, and clinical chemistry estimations, urine volume, pH, and specific gravity were subjected to statistical analysis. One-way ANOVA followed by Dunnett’s post-test was done for different treatment groups comparing with the control group data. All analyses and comparisons were evaluated at the 95% level of confidence (P<0.05)

Results and discussion

Results of examinations

Clinical signs:: no effects observed
Description (incidence and severity):: No clinical signs of toxicity or mortality/morbidity were noted in any of the treated and recovery group animals. During exposure, black faeces was observed, from 3rd hour to end of exposure period, and during post exposure 30-40 minutes and 1 hour in G4/G4R group animals from days 2 to 5, days 9 to 12, days 16 to 19, days 23 to 26 and on days 6, 13, 20, 27. The coloration of faeces is because of the colouration of test item, hence considered as non-adverse
Mortality:: no mortality observed
Body weight and weight changes:: no effects observed
Description (incidence and severity):: No treatment related variations in the mean body weight were noted, however in males lower percent change in body weight with respect to day 1 was noted in G4 groups during days 1-5, 1-8, 1-15 and in females during days 1-12 (G2 and G4), days 1-15 (G4), days 1-22 (G2 and G4), days 1-26 (G4) when compared to control group. The noted variation is considered incidental as the mean body weights were unaffected and also no concomitant variations in feed consumption was noted
Food efficiency:: no effects observed
Ophthalmological findings:: no effects observed
Haematological findings:: effects observed, non-treatment-related
Description (incidence and severity):: No toxicologically significant treatment related changes in haematology parameters were noted. However, the following statistically significant variations were noted.
In main group males, decrease in Platelets (G2, G3 and G4) was noted. In main group females, decrease in absolute eosinophils (G2 and G4) and APTT (G4) was noted. In recovery group females (G4R), increase in percent lymphocytes and decrease in percent eosinophils (G4R); decrease in absolute eosinophils (G4R) was noted.
Decrease in platelets in main group males is incidental as all the values are within historical range of the species and similar changes were not noted in females; also, the significance attained is because of higher values in control (two animals have higher counts than the historical range). All other changes noted in main group are considered incidental in the absence of dose responsiveness. Variations noted at the end of recovery period are considered incidental as no such variations were noted at the end of treatment period or in other sex i.e., recovery males
Clinical biochemistry findings:: effects observed, non-treatment-related
Description (incidence and severity):: No toxicologically significant changes were observed in clinical chemistry parameters when compared to the vehicle control group. However, the following statistically significant variations were noted.
In main group males, decrease in Albumin (G3 and G4), increase in Urea, ALT, Total bilirubin and BUN (G4) was noted. In females decrease in Creatinine (G4) and increase in Total bilirubin (G4) was noted.
In recovery group males, decrease in ALT (G4R) was noted. In females, decrease in creatinine, total protein, AST, globulin and sodium (G4) was noted.
The variations noted in high dose main groups were not associated with any macroscopic or microscopic in related organs – liver and kidney; hence, all the noted changes are considered incidental and could be due to random biological variation
Urinalysis findings:: no effects observed
Behaviour (functional findings):: effects observed, non-treatment-related
Description (incidence and severity):: No adverse effects during neurological/functional examinations were observed. However, the following statistically significant variations were noted.
- Increased movement counts (G4R males)
- Decreased body temperature (G4R males)
The increase in movement counts and decreased body temperature were minimal in nature and also, in the absence of changes in all other neuromuscular parameters, the noted changes are considered incidental
Organ weight findings including organ / body weight ratios:: effects observed, non-treatment-related
Description (incidence and severity):: The following statistically significant variations were noted in organ weights and its ratios.
In main group males, decrease in relative and absolute weight of heart (G3 and G4) was noted.
In recovery group males, decrease in absolute and relative weight of heart (G4R) was noted; in females increase in absolute weight of kidneys (G4R) was noted.
Relative weight changes (relative to brain weight)
In main group males, decrease in relative weight of heart (G3 and G4) was noted.
In recovery group males, decrease in relative weight of heart and spleen (G4R) and in females, increase in relative weight of adrenals (G4R) was noted.
The variations noted in organ weights and its ratios were not associated with any macroscopic changes in all related organs or any microscopic changes in high dose main groups and hence considered not to be test item related and incidental
Gross pathological findings:: effects observed, non-treatment-related
Description (incidence and severity):: Grossly, blackish discoloration of lungs in mid (Male: 3/5, Female: 4/5), high (Male: 5/5, Female: 5/5) and high dose recovery (Male: 5/5, Female: 5/5) group of rats in both sexes and blackish contents in caecum of high dose (Male: 5/5, Female: 5/5) rats was observed. This blackish discoloration was attributed to physical appearance (solid black) of inhaled test item which might have imparted discoloration to the tissues
Histopathological findings: non-neoplastic:: effects observed, non-treatment-related
Description (incidence and severity):: Microscopically, test item-related changes were observed in lungs and are summarized as follows.
Incidences of test item-related microscopic lesions in lungs of males
Sex Males
Group G1 G2 G3 G4 G1R G4R
Number of Animals Examined 5 5 5 5 5 5
Lungs (left lobe)
Pigment, blackish brown - - 5 5 - 5
Incidences of test item-related microscopic lesions in lungs of Females
Sex Females
Group G1 G2 G3 G4 G1R G4R
Number of Animals Examined 5 5 5 5 5 5
Lungs (left lobe)
Pigment, blackish brown - - 4 5 - 5
In lungs, minimal to mild, multifocal, variably sized, pigmented (blackish brown) granular material was observed throughout the parenchyma of lung at mid, high and high dose recovery groups of rats. This pigment was distributed both in alveolar and bronchiolar spaces with no accompanying inflammation or tissue destruction to the lung parenchyma. This pigment was suggestive of inhaled test item particles as the physical appearance of test item was also black coloured powder. In the absence of cellular changes to lung parenchyma, mere presence of pigment in lungs could be considered as non-adverse effect up to the dose level of 5000 mg/m3 . (Nikula KJ et.al., 2014).
Few microscopic findings observed in this study such as ultimobranchial cyst in thyroid gland, epithelial cysts in thymus and all other findings were considered incidental as they occurred randomly across the dose groups including concurrent controls and/or were expected for laboratory rats of this age
Histopathological findings: neoplastic:: effects observed, non-treatment-related
Description (incidence and severity):: Few microscopic findings observed in this study such as ultimobranchial cyst in
thyroid gland, epithelial cysts in thymus and all other findings were considered
incidental as they occurred randomly across the dose groups including concurrent
controls and/or were expected for laboratory rats of this age.
Other effects:: no effects observed
Description (incidence and severity):: During BALF analysis, few significant changes were noted in the differential counts
and WBC counts which are considered to be secondary to the accumulation of test
item particles in the lungs, however, they are considered non adverse in the absence of
any adverse microscopic changes in the lungs.

Effect levels

Dose descriptor:: NOAEC
Effect level:: 5 040 mg/m³ air (analytical)
Based on:: test mat.
Sex:: male/female
Basis for effect level:: behaviour (functional findings); body weight and weight gain; clinical biochemistry; clinical signs; gross pathology; haematology; histopathology: neoplastic; histopathology: non-neoplastic; mortality; ophthalmological examination; organ weights and organ / body weight ratios

Target system / organ toxicity

Critical effects observed:: no

Any other information on results incl. tables

APPENDIX 2. INDIVIDUAL ANIMAL BODY WEIGHTS (g)RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Body Weight (g) on Days
Group, Sex & Concentration (mg/m³)	Animal No.	1	5	8	12	15	22	26
G1, M & 0	Rf5151	153.93	159.72	168.23	179.62	192.30	200.16	213.59
	Rf5152	165.38	172.23	185.47	196.33	209.03	216.49	229.85
	Rf5153	161.20	170.10	183.01	196.54	208.13	215.38	224.30
	Rf5154	158.75	164.09	176.24	188.41	202.93	210.50	219.67
	Rf5155	158.10	167.23	178.92	190.24	205.30	212.36	222.10
G2, M & 500	Rf5156	154.24	157.05	169.23	180.08	194.79	202.69	214.27
	Rf5157	153.29	160.04	173.49	186.28	200.07	208.54	219.43
	Rf5158	163.84	170.09	175.02	184.79	197.65	205.80	216.99
	Rf5159	164.80	171.03	183.46	195.53	205.00	212.12	221.37
	Rf5160	167.01	173.81	184.29	197.06	209.12	217.29	226.72
G3, M & 1500	Rf5161	145.00	149.03	162.05	173.58	186.12	193.12	205.66
	Rf5162	148.25	152.69	165.72	176.84	184.03	192.10	202.49
	Rf5163	153.28	160.24	175.29	188.22	195.39	183.55	192.13
	Rf5164	170.16	175.23	186.43	198.47	206.55	213.30	223.45
	Rf5165	183.11	187.95	198.43	211.58	218.36	226.97	235.12
G4, M & 5000	Rf5166	156.06	152.39	165.09	177.79	186.17	194.60	206.02
	Rf5167	149.37	151.29	165.03	178.38	187.12	198.49	209.98
	Rf5168	150.70	148.72	160.54	173.08	185.44	191.55	203.66
	Rf5169	160.01	162.43	175.02	185.96	192.15	199.30	206.59
	Rf5170	191.10	188.07	199.23	211.46	218.53	225.72	234.38
G1, F & 0	Rf5181	133.59	135.23	143.84	157.39	164.50	170.33	175.90
	Rf5182	136.46	140.01	147.76	159.45	166.37	172.60	179.78
	Rf5183	137.75	139.23	148.04	160.77	167.11	173.94	179.12
	Rf5184	142.73	146.04	155.95	165.23	175.36	180.43	187.84
	Rf5185	144.10	150.01	158.73	167.08	176.46	182.52	188.52
G2, F & 500	Rf5186	127.87	129.23	138.29	146.79	153.25	159.36	167.14
	Rf5187	134.68	136.51	145.72	152.96	161.83	166.12	172.92
	Rf5188	147.77	151.05	160.72	169.84	177.18	183.07	189.33
	Rf5189	148.98	152.64	159.84	168.23	177.98	182.54	189.10
	Rf5190	147.93	150.04	158.73	166.92	175.96	181.39	188.20
G3, F & 1500	Rf5191	128.33	131.37	140.85	150.08	157.30	163.96	169.33
	Rf5192	135.35	139.24	148.76	156.61	168.21	174.54	179.20
	Rf5193	144.63	146.72	155.76	163.54	172.86	177.20	182.65
	Rf5194	151.96	154.09	163.77	171.44	178.14	184.66	189.98
	Rf5195	152.47	156.11	166.04	175.21	182.09	187.55	193.53
G4, F & 5000	Rf5196	135.41	137.23	145.23	154.29	161.07	166.26	171.14
	Rf5197	140.85	143.41	151.29	159.66	167.29	173.73	178.22
	Rf5198	146.67	144.72	153.76	160.77	168.37	174.51	180.38
	Rf5199	146.13	148.23	156.94	165.38	172.80	178.25	183.67
	Rf5200	146.20	149.04	157.37	164.59	171.55	177.81	182.94

M: Male; F: Female.

APPENDIX 2 (Contd…). INDIVIDUAL ANIMAL BODY WEIGHTS (g) RECORD

Group, Sex & Concentration (mg/m³)	Animal No.		Body Weight (g) on Days
Group, Sex & Concentration (mg/m³)	Animal No.	1		5		8		12		15		22		29		36		42
G1R, M & 0	Rf5171		155.92		162.57		175.23		184.66		198.73		206.07		224.35		242.56		263.01
	Rf5172		157.21		162.77		173.49		185.17		196.55		205.34		223.59		245.23		265.01
	Rf5173		165.25		170.21		182.55		193.88		202.21		211.55		223.44		250.45		270.90
	Rf5174		164.81		170.62		184.07		195.92		206.56		212.11		231.77		252.76		272.77
	Rf5175		168.70		172.84		185.11		198.29		208.60		217.68		238.29		256.22		276.46
G4R, M & 5000	Rf5176		155.70		159.27		171.29		183.69		192.15		200.08		222.48		236.51		256.96
	Rf5177		144.03		150.23		162.55		174.66		183.35		191.84		212.66		228.63		248.52
	Rf5178		175.58		171.63		183.47		196.03		205.40		213.69		234.52		249.61		270.06
	Rf5179		152.70		150.49		163.32		175.11		184.80		192.91		214.67		233.71		253.18
	Rf5180		181.76		182.65		195.44		206.99		215.81		223.12		244.38		260.43		281.18
G1R, F & 0	Rf5201		137.60		140.23		147.86		155.92		165.58		171.39		183.54		200.65		215.43
	Rf5202		141.01		146.21		154.29		162.48		170.81		176.54		189.77		206.72		221.61
	Rf5203		146.57		150.41		158.93		167.51		175.67		180.59		192.89		210.55		224.44
	Rf5204		141.58		143.72		150.96		159.45		167.81		173.16		188.33		204.09		218.95
	Rf5205		143.50		145.05		154.72		162.21		170.56		176.60		188.16		201.44		217.33
G4R, F & 5000	Rf5206		142.10		147.21		156.76		165.83		173.70		179.97		192.63		204.76		219.54
	Rf5207		151.01		153.41		161.09		168.41		177.31		182.34		195.74		210.07		224.76
	Rf5208		143.79		142.42		151.33		159.56		168.78		174.12		188.49		201.64		215.53
	Rf5209		139.28		141.81		152.17		160.28		168.07		175.66		188.36		200.96		215.17
	Rf5210		151.08		153.01		160.44		168.93		176.91		182.60		195.89		210.45		226.24

M: Male; F: Female; R: Recovery.

APPENDIX 3. INDIVIDUAL ANIMAL PERCENT CHANGE IN BODY WEIGHT WITH RESPECT TO DAY 1 RECORD

Group, Sex & Concentration (mg/m³)	Animal No.		Percent Change in Body Weight (%) during Days
Group, Sex & Concentration (mg/m³)	Animal No.	1 to 5		1 to 8		1 to 12		1 to 15		1 to 22		1 to 26
G1, M & 0	Rf5151		3.76		9.29		16.69		24.93		30.03		38.76
	Rf5152		4.14		12.15		18.71		26.39		30.90		38.98
	Rf5153		5.52		13.53		21.92		29.11		33.61		39.14
	Rf5154		3.36		11.02		18.68		27.83		32.60		38.37
	Rf5155		5.77		13.17		20.33		29.85		34.32		40.48
G2, M & 500	Rf5156		1.82		9.72		16.75		26.29		31.41		38.92
	Rf5157		4.40		13.18		21.52		30.52		36.04		43.15
	Rf5158		3.81		6.82		12.79		20.64		25.61		32.44
	Rf5159		3.78		11.32		18.65		24.39		28.71		34.33
	Rf5160		4.07		10.35		17.99		25.21		30.11		35.75
G3, M & 1500	Rf5161		2.78		11.76		19.71		28.36		33.19		41.83
	Rf5162		2.99		11.78		19.28		24.13		29.58		36.59
	Rf5163		4.54		14.36		22.79		27.47		19.75		25.35
	Rf5164		2.98		9.56		16.64		21.39		25.35		31.32
	Rf5165		2.64		8.37		15.55		19.25		23.95		28.40
G4, M & 5000	Rf5166		-2.35		5.79		13.92		19.29		24.70		32.01
	Rf5167		1.29		10.48		19.42		25.27		32.88		40.58
	Rf5168		-1.31		6.53		14.85		23.05		27.11		35.14
	Rf5169		1.51		9.38		16.22		20.09		24.55		29.11
	Rf5170		-1.59		4.25		10.65		14.35		18.12		22.65
G1, F & 0	Rf5181		1.23		7.67		17.82		23.14		27.50		31.67
	Rf5182		2.60		8.28		16.85		21.92		26.48		31.75
	Rf5183		1.07		7.47		16.71		21.31		26.27		30.03
	Rf5184		2.32		9.26		15.76		22.86		26.41		31.61
	Rf5185		4.10		10.15		15.95		22.46		26.66		30.83
G2, F & 500	Rf5186		1.06		8.15		14.80		19.85		24.63		30.71
	Rf5187		1.36		8.20		13.57		20.16		23.34		28.39
	Rf5188		2.22		8.76		14.94		19.90		23.89		28.12
	Rf5189		2.46		7.29		12.92		19.47		22.53		26.93
	Rf5190		1.43		7.30		12.84		18.95		22.62		27.22
G3, F & 1500	Rf5191		2.37		9.76		16.95		22.57		27.76		31.95
	Rf5192		2.87		9.91		15.71		24.28		28.95		32.40
	Rf5193		1.45		7.70		13.07		19.52		22.52		26.29
	Rf5194		1.40		7.77		12.82		17.23		21.52		25.02
	Rf5195		2.39		8.90		14.91		19.43		23.01		26.93
G4, F & 5000	Rf5196		1.34		7.25		13.94		18.95		22.78		26.39
	Rf5197		1.82		7.41		13.35		18.77		23.34		26.53
	Rf5198		-1.33		4.83		9.61		14.80		18.98		22.98
	Rf5199		1.44		7.40		13.17		18.25		21.98		25.69
	Rf5200		1.94		7.64		12.58		17.34		21.62		25.13

M: Male; F: Female.

APPENDIX 3 (Contd…). INDIVIDUAL ANIMAL PERCENT CHANGE IN BODY WEIGHT WITH RESPECT TO DAY 1 RECORD

Group, Sex & Concentration (mg/m³)	Animal No.		Percent Change in Body Weight (%) during Days
Group, Sex & Concentration (mg/m³)	Animal No.	1 to 5		1 to 8		1 to 12		1 to 15		1 to 22		1 to 29		1 to 36		1 to 42
G1R, M & 0	Rf5171		4.27		12.38		18.43		27.46		32.16		43.89		55.57		68.68
	Rf5172		3.54		10.36		17.79		25.02		30.62		42.22		55.99		68.57
	Rf5173		3.00		10.47		17.33		22.37		28.02		35.21		51.56		63.93
	Rf5174		3.53		11.69		18.88		25.33		28.70		40.63		53.36		65.51
	Rf5175		2.45		9.73		17.54		23.65		29.03		41.25		51.88		63.88
G4R, M & 5000	Rf5176		2.29		10.01		17.98		23.41		28.50		42.89		51.90		65.04
	Rf5177		4.30		12.86		21.27		27.30		33.19		47.65		58.74		72.55
	Rf5178		-2.25		4.49		11.65		16.98		21.71		33.57		42.16		53.81
	Rf5179		-1.45		6.95		14.68		21.02		26.33		40.58		53.05		65.80
	Rf5180		0.49		7.53		13.88		18.73		22.76		34.45		43.28		54.70
G1R, F & 0	Rf5201		1.91		7.46		13.31		20.33		24.56		33.39		45.82		56.56
	Rf5202		3.69		9.42		15.23		21.13		25.20		34.58		46.60		57.16
	Rf5203		2.62		8.43		14.29		19.85		23.21		31.60		43.65		53.13
	Rf5204		1.51		6.63		12.62		18.53		22.31		33.02		44.15		54.65
	Rf5205		1.08		7.82		13.04		18.86		23.07		31.12		40.38		51.45
G4R, F & 5000	Rf5206		3.60		10.32		16.70		22.24		26.65		35.56		44.10		54.50
	Rf5207		1.59		6.68		11.52		17.42		20.75		29.62		39.11		48.84
	Rf5208		-0.95		5.24		10.97		17.38		21.09		31.09		40.23		49.89
	Rf5209		1.82		9.25		15.08		20.67		26.12		35.24		44.28		54.49
	Rf5210		1.28		6.20		11.81		17.10		20.86		29.66		39.30		49.75

M: Male; F: Female; R: Recovery.

APPENDIX 4. INDIVIDUAL ANIMAL FEED CONSUMPTION RECORD (g/rat/day)

Group, Sex & Concentration (mg/m³)	Animal No.	Week 1	Week 2	Week 3	Week 4	Week 5	Week 6
G1, M & 0	Rf5151 to Rf5153	16.3	16.3	16.3	28.3	-	-
G1, M & 0	Rf5154 & Rf5155	20.5	20.4	20.3	35.8	-	-
G2, M & 500	Rf5156 to Rf5158	16.4	16.4	16.6	28.9	-	-
G2, M & 500	Rf5159 & Rf5160	20.2	20.1	19.9	35.0	-	-
G3, M & 1500	Rf5161 to Rf5163	16.7	16.4	16.2	28.3	-	-
G3, M & 1500	Rf5164 & Rf5165	20.3	20.3	20.0	34.8	-	-
G4, M & 5000	Rf5166 to Rf5168	16.2	16.3	16.3	28.7	-	-
G4, M & 5000	Rf5169 & Rf5170	19.8	20.0	19.9	34.8	-	-
G1, F & 0	Rf5181 to Rf5183	12.9	12.9	13.0	22.7	-	-
G1, F & 0	Rf5184 & Rf5185	15.3	15.2	15.0	26.4	-	-
G2, F & 500	Rf5186 to Rf5188	13.0	13.1	12.9	22.5	-	-
G2, F & 500	Rf5189 & Rf5190	15.0	15.1	14.7	25.4	-	-
G3, F & 1500	Rf5191 to Rf5193	12.8	12.8	12.6	22.0	-	-
G3, F & 1500	Rf5194 & Rf5195	15.0	15.0	14.8	25.9	-	-
G4, F & 5000	Rf5196 to Rf5198	12.7	12.7	12.6	22.6	-	-
G4, F & 5000	Rf5199 & Rf5200	14.7	14.7	14.9	25.6	-	-
G1R, M & 0	Rf5171 to Rf5173	16.3	16.3	16.2	16.3	16.6	19.0
G1R, M & 0	Rf5174 & Rf5175	20.7	20.5	20.2	20.4	20.5	23.3
G4R, M & 5000	Rf5176 to Rf5178	16.1	16.2	16.2	16.4	16.4	19.1
G4R, M & 5000	Rf5179 & Rf5180	20.2	20.1	20.0	20.3	20.5	23.5
G1R, F & 0	Rf5201 to Rf5203	12.9	12.9	12.8	13.0	13.2	15.1
G1R, F & 0	Rf5204 & Rf5205	15.2	15.2	15.0	15.4	15.3	17.7
G4R, F & 5000	Rf5206 to Rf5208	12.7	12.7	12.8	12.9	13.0	15.0
G4R, F & 5000	Rf5209 & Rf5210	14.8	14.7	15.0	15.1	15.4	17.8

M: MaleF: Female; R: Recovery; -: Not applicable.

APPENDIX 5. INDIVIDUAL ANIMAL NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD

Week 4
Group & Concentration (mg/m³): G1 & 0
Sex		Male					Female
Parameters↓ Animal Nos. →		Rf5151	Rf5152	Rf5153	Rf5154	Rf5155	Rf5181	Rf5182	Rf5183	Rf5184	Rf5185
Home cage observations
Home Cage posture		1	1	1	1	1	1	1	1	1	1
Respiratory pattern		1	1	1	1	1	1	1	1	1	1
Clonic involuntary movements		1	1	1	1	1	1	1	1	1	1
Tonic involuntary movements		1	1	1	1	1	1	1	1	1	1
Vocalization		1	1	1	1	1	1	1	1	1	1
Palpebral Closure		1	1	1	1	1	1	1	1	1	1
Handling observation
Ease of removal from the cage		2	2	2	2	2	2	2	2	2	2
Ease of handling animal in hand		2	2	2	2	2	2	2	2	2	2
Red or crusty deposits	Eyes	1	1	1	1	1	1	1	1	1	1
	Nose	1	1	1	1	1	1	1	1	1	1
	Mouth	1	1	1	1	1	1	1	1	1	1
Lacrimation		1	1	1	1	1	1	1	1	1	1
Salivation		1	1	1	1	1	1	1	1	1	1
Fur Appearance		1	1	1	1	1	1	1	1	1	1
Piloerection		1	1	1	1	1	1	1	1	1	1
Eye Prominence		1	1	1	1	1	1	1	1	1	1
Muscle Tone		1	1	1	1	1	1	1	1	1	1
Home cage observations: Home cage posture- 1=Normal,Respiratory Pattern -1=Normal,Clonic involuntary movements -1=None/Normal,Tonic involuntary movements -1=None/Normal,Vocalization -1=Absent (Normal),Palpebral closure -1=Eyelids wide open (Normal),Handling observation : Ease of removal from the cage -2=Normal,Ease of handling animal in hand -2=Normal,Red/Crusty deposits -1=Absent,Lacrimation- 1=None,Salivation-1=Absent (Normal),Fur Appearance -1=Normal,Piloerection -1=None, Eye Prominence -1=Normal,Muscle tone -1=Normal

APPENDIX 5 (Contd...). INDIVIDUAL ANIMAL NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD

Week 4
Group & Concentration (mg/m³): G1 & 0
Sex	Male					Female
Parameters↓ Animal Nos. →	Rf5151	Rf5152	Rf5153	Rf5154	Rf5155	Rf5181	Rf5182	Rf5183	Rf5184	Rf5185
Open field observation
Mobility	1	1	1	1	1	1	1	1	1	1
Gait	1	1	1	1	1	1	1	1	1	1
Arousal	3	3	3	3	3	3	3	3	3	3
Number of Rearing	7	6	5	4	6	10	7	9	8	8
Numbers of Urination	1	1	2	1	1	1	1	1	2	2
Number of Defecation	1	1	1	1	1	1	1	2	1	1
Clonic involuntary movement	1	1	1	1	1	1	1	1	1	1
Tonic involuntary movement	1	1	1	1	1	1	1	1	1	1
Stereotype Behaviour	1	1	1	1	1	1	1	1	1	1
Excessive Grooming	4	5	6	5	5	8	7	6	5	5
Sensory Observations
Approach Response	2	2	2	2	2	2	2	2	2	2
Auditory Response	2	2	2	2	2	2	2	2	2	2
Touch Response	2	2	2	2	2	2	2	2	2	2
Pupil Reflex	2	2	2	2	2	2	2	2	2	2
Tail Pinch Response	2	2	2	2	2	2	2	2	2	2
Righting Reflex	1	1	1	1	1	1	1	1	1	1
Physiological observation
Body temperature (°F)	96.8	96.7	96.5	97.2	97.3	98.3	98.5	98.7	98.5	98.8
Open field Observation: Mobility -1=Normal,Gait -1=Normal,Arousal -3=Normal,Clonic involuntary movements -1=None/Normal,Tonic involuntary movements -1=None/Normal,Stereotype Behaviour -1=Absent,Sensory Observations: Approach response -2=Normal,Auditory Response -2=Normal,Touch Response -2=Normal,Pupil Reflex -2=Normal,Tail Pinch Response -2=Normal,Righting Reflex -1=Present

APPENDIX 5 (Contd...). INDIVIDUAL ANIMAL NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD

Week 4
Group & Concentration (mg/m³): G4 & 5000
Sex		Male					Female
Parameters↓ Animal Nos. →		Rf5166	Rf5167	Rf5168	Rf5169	Rf5170	Rf5196	Rf5197	Rf5198	Rf5199	Rf5200
Home cage observations
Home Cage posture		1	1	1	1	1	1	1	1	1	1
Respiratory pattern		1	1	1	1	1	1	1	1	1	1
Clonic involuntary movements		1	1	1	1	1	1	1	1	1	1
Tonic involuntary movements		1	1	1	1	1	1	1	1	1	1
Vocalization		1	1	1	1	1	1	1	1	1	1
Palpebral Closure		1	1	1	1	1	1	1	1	1	1
Handling observation
Ease of removal from the cage		2	2	2	2	2	2	2	2	2	2
Ease of handling animal in hand		2	2	2	2	2	2	2	2	2	2
Red or crusty deposits	Eyes	1	1	1	1	1	1	1	1	1	1
	Nose	1	1	1	1	1	1	1	1	1	1
	Mouth	1	1	1	1	1	1	1	1	1	1
Lacrimation		1	1	1	1	1	1	1	1	1	1
Salivation		1	1	1	1	1	1	1	1	1	1
Fur Appearance		1	1	1	1	1	1	1	1	1	1
Piloerection		1	1	1	1	1	1	1	1	1	1
Eye Prominence		1	1	1	1	1	1	1	1	1	1
Muscle Tone		1	1	1	1	1	1	1	1	1	1
Home cage observations: Home cage posture- 1=Normal,Respiratory Pattern -1=Normal,Clonic involuntary movements -1=None/Normal,Tonic involuntary movements -1=None/Normal,Vocalization -1=Absent (Normal),Palpebral closure -1=Eyelids wide open (Normal),Handling observation : Ease of removal from the cage -2=Normal,Ease of handling animal in hand -2=Normal,Red/Crusty deposits -1=Absent,Lacrimation- 1=None,Salivation-1=Absent (Normal),Fur Appearance -1=Normal,Piloerection -1=None, Eye Prominence -1=Normal,Muscle tone -1=Normal

APPENDIX 5 (Contd...). INDIVIDUAL ANIMAL NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD

Week 4
Group & Concentration (mg/m³): G4 & 5000
Sex	Male					Female
Parameters↓ Animal Nos. →	Rf5166	Rf5167	Rf5168	Rf5169	Rf5170	Rf5196	Rf5197	Rf5198	Rf5199	Rf5200
Open field observation
Mobility	1	1	1	1	1	1	1	1	1	1
Gait	1	1	1	1	1	1	1	1	1	1
Arousal	3	3	3	3	3	3	3	3	3	3
Number of Rearing	6	5	6	7	4	10	9	8	6	9
Numbers of Urination	1	1	1	1	1	1	1	2	1	2
Number of Defecation	1	1	0	1	2	2	1	1	1	1
Clonic involuntary movement	1	1	1	1	1	1	1	1	1	1
Tonic involuntary movement	1	1	1	1	1	1	1	1	1	1
Stereotype Behaviour	1	1	1	1	1	1	1	1	1	1
Excessive Grooming	4	5	6	5	5	8	8	6	5	6
Sensory Observations
Approach Response	2	2	2	2	2	2	2	2	2	2
Auditory Response	2	2	2	2	2	2	2	2	2	2
Touch Response	2	2	2	2	2	2	2	2	2	2
Pupil Reflex	2	2	2	2	2	2	2	2	2	2
Tail Pinch Response	2	2	2	2	2	2	2	2	2	2
Righting Reflex	1	1	1	1	1	1	1	1	1	1
Physiological observation
Body temperature (°F)	96.8	96.2	97.0	97.1	96.3	98.3	98.5	98.6	98.5	98.5
Open field Observation: Mobility -1=Normal,Gait -1=Normal,Arousal -3=Normal,Clonic involuntary movements -1=None/Normal,Tonic involuntary movements -1=None/Normal,Stereotype Behaviour -1=Absent,Sensory Observations: Approach response -2=Normal,Auditory Response -2=Normal,Touch Response -2=Normal,Pupil Reflex -2=Normal,Tail Pinch Response -2=Normal,Righting Reflex -1=Present

APPENDIX 5 (Contd...). INDIVIDUAL ANIMAL NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD

Week 6
Group & Concentration (mg/m³): G1R & 0
Sex		Male					Female
Parameters↓ Animal Nos. →		Rf5171	Rf5172	Rf5173	Rf5174	Rf5175	Rf5201	Rf5202	Rf5203	Rf5204	Rf5205
Home cage observations
Home Cage posture		1	1	1	1	1	1	1	1	1	1
Respiratory pattern		1	1	1	1	1	1	1	1	1	1
Clonic involuntary movements		1	1	1	1	1	1	1	1	1	1
Tonic involuntary movements		1	1	1	1	1	1	1	1	1	1
Vocalization		1	1	1	1	1	1	1	1	1	1
Palpebral Closure		1	1	1	1	1	1	1	1	1	1
Handling observation
Ease of removal from the cage		2	2	2	2	2	2	2	2	2	2
Ease of handling animal in hand		2	2	2	2	2	2	2	2	2	2
Red or crusty deposits	Eyes	1	1	1	1	1	1	1	1	1	1
	Nose	1	1	1	1	1	1	1	1	1	1
	Mouth	1	1	1	1	1	1	1	1	1	1
Lacrimation		1	1	1	1	1	1	1	1	1	1
Salivation		1	1	1	1	1	1	1	1	1	1
Fur Appearance		1	1	1	1	1	1	1	1	1	1
Piloerection		1	1	1	1	1	1	1	1	1	1
Eye Prominence		1	1	1	1	1	1	1	1	1	1
Muscle Tone		1	1	1	1	1	1	1	1	1	1
Home cage observations: Home cage posture- 1=Normal,Respiratory Pattern -1=Normal,Clonic involuntary movements -1=None/Normal,Tonic involuntary movements -1=None/Normal,Vocalization -1=Absent (Normal),Palpebral closure -1=Eyelids wide open (Normal),Handling observation : Ease of removal from the cage -2=Normal,Ease of handling animal in hand -2=Normal,Red/Crusty deposits -1=Absent,Lacrimation- 1=None,Salivation-1=Absent (Normal),Fur Appearance -1=Normal,Piloerection -1=None, Eye Prominence -1=Normal,Muscle tone -1=Normal

R: Recovery

APPENDIX 5 (Contd...). INDIVIDUAL ANIMAL NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD

Week 6
Group & Concentration (mg/m³): G1R & 0
Sex	Male					Female
Parameters↓ Animal Nos. →	Rf5171	Rf5172	Rf5173	Rf5174	Rf5175	Rf5201	Rf5202	Rf5203	Rf5204	Rf5205
Open field observation
Mobility	1	1	1	1	1	1	1	1	1	1
Gait	1	1	1	1	1	1	1	1	1	1
Arousal	3	3	3	3	3	3	3	3	3	3
Number of Rearing	7	8	9	7	7	9	10	8	8	7
Numbers of Urination	1	1	2	0	2	1	2	2	1	1
Number of Defecation	1	2	1	1	1	1	2	1	1	1
Clonic involuntary movement	1	1	1	1	1	1	1	1	1	1
Tonic involuntary movement	1	1	1	1	1	1	1	1	1	1
Stereotype Behaviour	1	1	1	1	1	1	1	1	1	1
Excessive Grooming	3	4	4	5	4	6	5	5	6	4
Sensory Observations
Approach Response	2	2	2	2	2	2	2	2	2	2
Auditory Response	2	2	2	2	2	2	2	2	2	2
Touch Response	2	2	2	2	2	2	2	2	2	2
Pupil Reflex	2	2	2	2	2	2	2	2	2	2
Tail Pinch Response	2	2	2	2	2	2	2	2	2	2
Righting Reflex	1	1	1	1	1	1	1	1	1	1
Physiological observation
Body temperature (°F)	98.6	97.9	98.4	97.8	98.3	98.9	98.5	98.5	98.7	98.8
Open field Observation: Mobility -1=Normal,Gait -1=Normal,Arousal -3=Normal,Clonic involuntary movements -1=None/Normal,Tonic involuntary movements -1=None/Normal,Stereotype Behaviour -1=Absent,Sensory Observations: Approach response -2=Normal,Auditory Response -2=Normal,Touch Response -2=Normal,Pupil Reflex -2=Normal,Tail Pinch Response -2=Normal,Righting Reflex -1=Present

R: Recovery

APPENDIX 5 (Contd...). INDIVIDUAL ANIMAL NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD

Week 6
Group & Concentration (mg/m³): G4R & 5000
Sex		Male					Female
Parameters↓ Animal Nos. →		Rf5176	Rf5177	Rf5178	Rf5179	Rf5180	Rf5206	Rf5207	Rf5208	Rf5209	Rf5210
Home cage observations
Home Cage posture		1	1	1	1	1	1	1	1	1	1
Respiratory pattern		1	1	1	1	1	1	1	1	1	1
Clonic involuntary movements		1	1	1	1	1	1	1	1	1	1
Tonic involuntary movements		1	1	1	1	1	1	1	1	1	1
Vocalization		1	1	1	1	1	1	1	1	1	1
Palpebral Closure		1	1	1	1	1	1	1	1	1	1
Handling observation
Ease of removal from the cage		2	2	2	2	2	2	2	2	2	2
Ease of handling animal in hand		2	2	2	2	2	2	2	2	2	2
Red or crusty deposits	Eyes	1	1	1	1	1	1	1	1	1	1
	Nose	1	1	1	1	1	1	1	1	1	1
	Mouth	1	1	1	1	1	1	1	1	1	1
Lacrimation		1	1	1	1	1	1	1	1	1	1
Salivation		1	1	1	1	1	1	1	1	1	1
Fur Appearance		1	1	1	1	1	1	1	1	1	1
Piloerection		1	1	1	1	1	1	1	1	1	1
Eye Prominence		1	1	1	1	1	1	1	1	1	1
Muscle Tone		1	1	1	1	1	1	1	1	1	1
Home cage observations: Home cage posture- 1=Normal,Respiratory Pattern -1=Normal,Clonic involuntary movements -1=None/Normal,Tonic involuntary movements -1=None/Normal,Vocalization -1=Absent (Normal),Palpebral closure -1=Eyelids wide open (Normal),Handling observation : Ease of removal from the cage -2=Normal,Ease of handling animal in hand -2=Normal,Red/Crusty deposits -1=Absent,Lacrimation- 1=None,Salivation-1=Absent (Normal),Fur Appearance -1=Normal,Piloerection -1=None, Eye Prominence -1=Normal,Muscle tone -1=Normal

R: Recovery

APPENDIX 5 (Contd...). INDIVIDUAL ANIMAL NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD

Week 6
Group & Concentration (mg/m³): G4R & 5000
Sex	Male					Female
Parameters↓ Animal Nos. →	Rf5176	Rf5177	Rf5178	Rf5179	Rf5180	Rf5206	Rf5207	Rf5208	Rf5209	Rf5210
Open field observation
Mobility	1	1	1	1	1	1	1	1	1	1
Gait	1	1	1	1	1	1	1	1	1	1
Arousal	3	3	3	3	3	3	3	3	3	3
Number of Rearing	7	8	5	6	6	10	9	8	8	6
Numbers of Urination	1	1	2	1	2	1	2	2	1	1
Number of Defecation	1	0	2	1	1	1	1	1	2	1
Clonic involuntary movement	1	1	1	1	1	1	1	1	1	1
Tonic involuntary movement	1	1	1	1	1	1	1	1	1	1
Stereotype Behaviour	1	1	1	1	1	1	1	1	1	1
Excessive Grooming	4	5	5	6	5	6	7	8	6	5
Sensory Observations
Approach Response	2	2	2	2	2	2	2	2	2	2
Auditory Response	2	2	2	2	2	2	2	2	2	2
Touch Response	2	2	2	2	2	2	2	2	2	2
Pupil Reflex	2	2	2	2	2	2	2	2	2	2
Tail Pinch Response	2	2	2	2	2	2	2	2	2	2
Righting Reflex	1	1	1	1	1	1	1	1	1	1
Physiological observation
Body temperature (°F)	97.7	97.9	98.0	97.4	97.8	98.7	98.8	98.9	98.5	98.5
Open field Observation: Mobility -1=Normal,Gait -1=Normal,Arousal -3=Normal,Clonic involuntary movements -1=None/Normal,Tonic involuntary movements -1=None/Normal,Stereotype Behaviour -1=Absent,Sensory Observations: Approach response -2=Normal,Auditory Response -2=Normal,Touch Response -2=Normal,Pupil Reflex -2=Normal,Tail Pinch Response -2=Normal,Righting Reflex -1=Present

R: Recovery

APPENDIX 6. INDIVIDUAL ANIMAL HIND LIMB FOOT SPLAY (cm) RECORD

#Week 4 & 6
Group, Sex & Concentration (mg/m³)	Animal No.	R1	R2	R3	Average
Group, Sex & Concentration (mg/m³)	Animal No.	R1	R2	R3	Average
G1, M & 0	Rf5151	5.2	7.4	7.6	6.7
	Rf5152	5.5	4.7	4.6	4.9
	Rf5153	5.6	5.2	6.1	5.6
	Rf5154	6.9	6.4	5.6	6.3
	Rf5155	5.9	5.7	5.2	5.6
G4, M & 5000	Rf5166	4.0	4.4	5.5	4.6
	Rf5167	4.8	4.9	4.5	4.7
	Rf5168	5.0	4.7	4.8	4.8
	Rf5169	4.5	4.2	5.5	4.7
	Rf5170	8.0	8.7	7.2	8.0
G1, F & 0	Rf5181	5.2	4.9	5.1	5.1
	Rf5182	3.4	3.8	3.9	3.7
	Rf5183	3.4	3.8	3.5	3.6
	Rf5184	5.9	6.0	5.9	5.9
	Rf5185	3.7	4.4	3.6	3.9
G4, F & 5000	Rf5196	4.2	4.5	3.8	4.2
	Rf5197	4.5	4.4	4.9	4.6
	Rf5198	4.9	5.0	5.2	5.0
	Rf5199	5.0	5.2	5.0	5.1
	Rf5200	5.4	5.2	5.8	5.5
G1R, M & 0	Rf5171	6.3	7.3	6.3	6.6
	Rf5172	5.6	6.4	5.3	5.8
	Rf5173	7.1	6.6	6.3	6.7
	Rf5174	5.6	6.0	6.3	6.0
	Rf5175	6.4	6.6	6.0	6.3
G4R, M & 5000	Rf5176	7.9	6.2	6.5	6.9
	Rf5177	6.7	7.0	6.6	6.8
	Rf5178	4.4	4.7	4.9	4.7
	Rf5179	6.5	5.4	5.2	5.7
	Rf5180	6.2	6.7	6.2	6.4
G1R, F & 0	Rf5201	4.7	4.6	5.1	4.8
	Rf5202	4.4	4.4	4.7	4.5
	Rf5203	5.2	6.3	5.2	5.6
	Rf5204	4.4	4.5	5.2	4.7
	Rf5205	4.9	4.4	4.8	4.7
G4R, F & 5000	Rf5206	5.9	5.2	5.5	5.5
	Rf5207	5.4	4.7	4.8	5.0
	Rf5208	5.5	4.9	4.7	5.0
	Rf5209	4.9	5.2	4.7	4.9
	Rf5210	5.6	4.7	4.8	5.0

M: Male; F: Female; R: Recovery; #: Week 4 for main group animals and week 6 for recovery group animals.

APPENDIX 7. INDIVIDUAL ANIMAL ACTIMETER READING RECORD

#Week 4 & 6
Group, Sex & Concentration (mg/m³)	Animal No.	Movement Counts (no.)
Group, Sex & Concentration (mg/m³)	Animal No.	Movement Counts (no.)
G1, M & 0	Rf5151	2303
	Rf5152	2422
	Rf5153	2365
	Rf5154	2309
	Rf5155	2372
G4, M & 5000	Rf5166	2292
	Rf5167	2259
	Rf5168	2231
	Rf5169	2252
	Rf5170	2591
G1, F & 0	Rf5181	2160
	Rf5182	2135
	Rf5183	2218
	Rf5184	2187
	Rf5185	2097
G4, F & 5000	Rf5196	2148
	Rf5197	2178
	Rf5198	2216
	Rf5199	2159
	Rf5200	2154
G1R, M & 0	Rf5171	2139
	Rf5172	2172
	Rf5173	2184
	Rf5174	2172
	Rf5175	2178
G4R, M & 5000	Rf5176	2199
	Rf5177	2184
	Rf5178	2195
	Rf5179	2199
	Rf5180	2218
G1R, F & 0	Rf5201	2294
	Rf5202	2297
	Rf5203	2305
	Rf5204	2301
	Rf5205	2315
G4R, F & 5000	Rf5206	2303
	Rf5207	2311
	Rf5208	2320
	Rf5209	2274
	Rf5210	2288

M: Male; F: Female; R: Recovery; #: Week 4 for main group animals and week 6 for recovery group animals.

APPENDIX 8. INDIVIDUAL ANIMAL GRIP STRENGTH (kgf) MEASUREMENT RECORD

Week 4
Group, Sex & Concentration (mg/m³)	Animal No.	Fore limb			Average	Hind limb			Average
Group, Sex & Concentration (mg/m³)	Animal No.	R1	R2	R3	Average	R1	R2	R3	Average
G1, M & 0	Rf5151	1.483	1.587	1.488	1.519	0.397	0.572	0.575	0.515
	Rf5152	1.395	1.522	1.503	1.473	0.973	0.587	0.497	0.686
	Rf5153	1.612	1.468	1.527	1.536	0.525	0.475	0.407	0.469
	Rf5154	1.502	1.575	1.586	1.554	0.403	0.487	0.587	0.492
	Rf5155	1.428	1.398	1.463	1.430	0.474	0.522	0.506	0.501
G4, M & 5000	Rf5166	1.472	1.575	1.412	1.486	0.366	0.485	0.495	0.449
	Rf5167	1.408	1.509	1.488	1.468	0.416	0.572	0.376	0.455
	Rf5168	1.601	1.485	1.503	1.530	0.588	0.463	0.421	0.491
	Rf5169	1.478	1.563	1.549	1.530	0.401	0.501	0.507	0.470
	Rf5170	1.409	1.390	1.439	1.413	0.498	0.508	0.483	0.496
G1, F & 0	Rf5181	1.349	1.507	1.497	1.451	0.376	0.488	0.397	0.420
	Rf5182	1.463	1.478	1.509	1.483	0.291	0.379	0.372	0.347
	Rf5183	1.359	1.396	1.427	1.394	0.371	0.403	0.376	0.383
	Rf5184	1.375	1.403	1.398	1.392	0.479	0.391	0.403	0.424
	Rf5185	1.497	1.373	1.474	1.448	0.523	0.404	0.489	0.472
G4, F & 5000	Rf5196	1.459	1.431	1.377	1.422	0.362	0.279	0.419	0.353
	Rf5197	1.368	1.359	1.471	1.399	0.473	0.403	0.462	0.446
	Rf5198	1.348	1.429	1.401	1.393	0.298	0.287	0.309	0.298
	Rf5199	1.387	1.423	1.381	1.397	0.391	0.389	0.377	0.386
	Rf5200	1.463	1.369	1.504	1.445	0.313	0.423	0.493	0.410

M: Male: Female; R1, R2 and R3 denote repetitions;

APPENDIX 8 (Contd…). INDIVIDUAL ANIMAL GRIP STRENGTH (kgf) MEASUREMENT RECORD

Week 6
Group, Sex & Concentration (mg/m³)	Animal No.	Fore limb			Average	Hind limb			Average
Group, Sex & Concentration (mg/m³)	Animal No.	R1	R2	R3	Average	R1	R2	R3	Average
G1R, M & 0	Rf5171	1.562	1.614	1.607	1.594	0.523	0.561	0.560	0.548
	Rf5172	1.601	1.577	1.582	1.587	0.495	0.544	0.505	0.515
	Rf5173	1.574	1.582	1.539	1.565	0.600	0.592	0.585	0.592
	Rf5174	1.586	1.499	1.568	1.551	0.481	0.589	0.561	0.544
	Rf5175	1.479	1.520	1.495	1.498	0.585	0.499	0.529	0.538
G4R, M & 5000	Rf5176	1.597	1.553	1.589	1.580	0.577	0.479	0.486	0.514
	Rf5177	1.509	1.584	1.575	1.556	0.590	0.574	0.577	0.580
	Rf5178	1.592	1.490	1.545	1.542	0.512	0.502	0.582	0.532
	Rf5179	1.544	1.574	1.588	1.569	0.430	0.488	0.529	0.482
	Rf5180	1.536	1.583	1.479	1.533	0.516	0.507	0.590	0.538
G1R, F & 0	Rf5201	1.411	1.295	1.386	1.364	0.375	0.410	0.305	0.363
	Rf5202	1.483	1.480	1.322	1.428	0.289	0.305	0.388	0.327
	Rf5203	1.377	1.399	1.475	1.417	0.307	0.299	0.315	0.307
	Rf5204	1.482	1.387	1.300	1.390	0.395	0.387	0.367	0.383
	Rf5205	1.396	1.475	1.385	1.419	0.388	0.406	0.366	0.387
G4R, F & 5000	Rf5206	1.495	1.288	1.407	1.397	0.408	0.420	0.377	0.402
	Rf5207	1.466	1.500	1.277	1.414	0.388	0.395	0.391	0.391
	Rf5208	1.507	1.465	1.309	1.427	0.276	0.316	0.349	0.314
	Rf5209	1.399	1.397	1.407	1.401	0.394	0.428	0.379	0.400
	Rf5210	1.386	1.493	1.276	1.385	0.398	0.295	0.360	0.351

M: Male: Female; R: Recovery; R1, R2 and R3 denote repetitions;

APPENDIX 10. INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Total Leucocyte Count	Total Erythrocyte Count	Hemoglobin	Haematocrit	Mean Corpuscular Volume	Mean Corpuscular Hemoglobin	Mean Corpuscular Hemoglobin Concentration	Platelet Count	Mean Platelet Volume
		(WBC)	(RBC)	(HGB)	(HCT)	(MCV)	(MCH)	(MCHC)	(PLT)	(MPV)
		(10³cells/µL)	(10⁶cells/µL)	(g/dL)	(%)	(fL)	(pg)	(g/dL)	(10³cells/µL)	(fL)
G1, M & 0	Rf5151	11.41	8.05	15.5	46.1	57.2	19.3	33.7	1182	6.5
	Rf5152	11.22	8.43	16.4	49.6	58.8	19.4	33.1	1058	6.1
	Rf5153	9.28	8.40	16.3	49.4	58.8	19.4	33.0	1191	6.2
	Rf5154	19.69	8.37	15.4	46.2	55.2	18.4	33.4	1029	6.3
	Rf5155	10.59	8.72	16.2	49.9	57.2	18.6	32.6	1159	6.2
G2, M & 500	Rf5156	8.57	7.99	15.5	46.3	57.9	19.4	33.5	939	6.1
	Rf5157	12.87	8.01	15.3	46.0	57.4	19.0	33.2	919	6.3
	Rf5158	10.66	7.55	15.6	46.2	61.2	20.7	33.7	893	6.5
	Rf5159	8.70	7.32	16.3	41.2	56.3	22.3	39.6	853	6.3
	Rf5160	9.07	9.01	16.8	50.9	56.4	18.6	33.0	1083	6.2
G3, M & 1500	Rf5161	6.24	8.23	15.3	47.1	57.3	18.6	32.4	968	6.2
	Rf5162	9.46	8.94	16.1	49.3	55.1	18.0	32.7	918	6.0
	Rf5163	10.42	8.69	15.7	47.6	54.8	18.0	32.9	835	6.8
	Rf5164	10.07	8.75	15.9	48.1	54.9	18.2	33.1	891	6.1
	Rf5165	9.24	7.78	15.3	45.9	59.1	19.7	33.3	957	6.2
G4, M & 5000	Rf5166	10.60	8.61	15.5	47.0	54.6	18.0	33.0	805	6.5
	Rf5167	10.70	7.99	15.2	45.6	57.1	19.0	33.3	1102	6.8
	Rf5168	10.34	8.44	15.5	46.0	54.5	18.4	33.8	738	6.6
	Rf5169	11.49	8.54	15.3	46.7	54.6	18.0	32.9	867	6.6
	Rf5170	12.31	9.07	16.4	49.7	54.8	18.0	33.0	959	6.0

M: Male.

APPENDIX 10 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Reticulocyte Count	Neutrophils	Lymphocytes	Monocytes	Eosinophils	Basophils	Absolute Reticulocyte Count
		(Retic)	(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(Retic)
		(%)	(%)	(%)	(%)	(%)	(%)	(10⁹cells/L)
G1, M & 0	Rf5151	3.19	19.0	76.4	2.9	0.5	0.3	256.8
	Rf5152	2.73	19.7	74.1	4.9	0.3	0.3	230.6
	Rf5153	3.14	26.3	67.4	4.6	0.5	0.4	263.5
	Rf5154	2.78	13.9	82.1	2.2	0.7	0.4	232.8
	Rf5155	3.21	36.6	56.7	4.2	1.3	0.5	279.6
G2, M & 500	Rf5156	2.83	17.5	75.5	4.8	1.0	0.4	225.9
	Rf5157	3.14	21.3	72.8	3.3	1.2	0.6	251.4
	Rf5158	2.61	15.5	79.2	3.7	0.5	0.3	196.9
	Rf5159	1.78	28.3	65.4	3.7	0.7	0.2	130.7
	Rf5160	1.72	18.2	75.1	4.1	0.9	0.7	155.0
G3, M & 1500	Rf5161	2.68	27.5	65.3	5.1	0.9	0.3	220.1
	Rf5162	2.79	24.3	69.3	4.8	0.4	0.3	249.9
	Rf5163	1.76	18.8	74.4	4.8	0.5	0.4	153.0
	Rf5164	2.69	25.8	68.0	4.4	0.4	0.4	235.3
	Rf5165	2.69	16.8	76.3	4.7	0.8	0.3	209.2
G4, M & 5000	Rf5166	2.23	18.7	74.9	3.5	0.7	0.3	192.0
	Rf5167	2.93	19.8	72.8	4.2	0.3	0.6	233.9
	Rf5168	2.23	19.2	75.1	3.3	0.7	0.6	188.5
	Rf5169	3.32	16.3	78.0	3.8	0.5	0.5	283.9
	Rf5170	1.87	13.5	82.3	2.5	0.3	0.5	169.6

M: Male.

APPENDIX 10 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Absolute Neutrophils	Absolute Lymphocytes	Absolute Monocytes	Absolute Eosinophils	Absolute Basophils	Prothrombin Time	Activated Prothrombin Time
		(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(PT)	(APTT)
		(10³cells/µL)	(10³cells/µL)	(10³cells/µL)	(10³cells/µL)	(10³cells/µL)	(Seconds)	(Seconds)
G1, M & 0	Rf5151	2.16	8.72	0.33	0.06	0.04	15.8	22.7
	Rf5152	2.21	8.31	0.55	0.03	0.03	17.8	22.2
	Rf5153	2.44	6.25	0.43	0.05	0.03	21.1	23.8
	Rf5154	2.74	16.17	0.44	0.13	0.07	17.0	20.7
	Rf5155	3.88	6.00	0.45	0.13	0.05	24.8	30.9
G2, M & 500	Rf5156	1.50	6.47	0.41	0.08	0.04	11.7	26.5
	Rf5157	2.75	9.37	0.43	0.16	0.07	19.6	25.8
	Rf5158	1.65	8.45	0.40	0.05	0.03	18.2	25.7
	Rf5159	2.46	5.68	0.32	0.06	0.02	17.2	22.7
	Rf5160	1.65	6.81	0.37	0.09	0.07	23.4	25.3
G3, M & 1500	Rf5161	1.72	4.07	0.32	0.06	0.02	21.1	34.0
	Rf5162	2.30	6.56	0.46	0.04	0.03	15.7	25.4
	Rf5163	1.96	7.76	0.50	0.05	0.04	18.6	20.7
	Rf5164	2.60	6.85	0.44	0.04	0.04	25.8	21.2
	Rf5165	1.56	7.05	0.44	0.07	0.03	28.2	20.7
G4, M & 5000	Rf5166	1.98	7.94	0.37	0.07	0.04	22.4	25.6
	Rf5167	2.11	7.79	0.45	0.04	0.06	18.4	30.4
	Rf5168	1.98	7.77	0.34	0.08	0.07	16.9	25.9
	Rf5169	1.87	8.96	0.43	0.06	0.06	16.5	24.1
	Rf5170	1.66	10.13	0.31	0.03	0.06	21.1	24.0

M: Male.

APPENDIX 10 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Total Leucocyte Count	Total Erythrocyte Count	Hemoglobin	Haematocrit	Mean Corpuscular Volume	Mean Corpuscular Hemoglobin	Mean Corpuscular Hemoglobin Concentration	Platelet Count	Mean Platelet Volume
		(WBC)	(RBC)	(HGB)	(HCT)	(MCV)	(MCH)	(MCHC)	(PLT)	(MPV)
		(10³cells/µL)	(10⁶cells/µL)	(g/dL)	(%)	(fL)	(pg)	(g/dL)	(10³cells/µL)	(fL)
G1, F & 0	Rf5181	9.92	8.82	16.0	48.9	55.4	18.1	32.7	1201	6.9
	Rf5182	10.85	8.98	16.4	49.1	54.7	18.3	33.4	1128	6.0
	Rf5183	11.07	8.60	15.5	46.6	54.2	18.0	33.3	976	6.5
	Rf5184	14.87	7.77	14.1	42.5	54.7	18.2	33.2	1325	6.5
	Rf5185	10.85	8.76	16.0	47.8	54.6	18.3	33.5	1081	6.0
G2, F & 500	Rf5186	7.39	7.63	14.4	42.8	56.2	18.9	33.7	902	6.5
	Rf5187	7.71	8.27	15.4	45.4	54.8	18.6	33.8	1042	6.7
	Rf5188	8.35	8.82	15.9	46.9	53.2	18.0	33.9	1076	6.5
	Rf5189	8.39	7.75	14.5	44.3	57.1	18.7	32.8	1439	6.5
	Rf5190	7.65	8.53	15.7	45.9	53.8	18.4	34.1	1170	6.2
G3, F & 1500	Rf5191	11.15	8.39	15.4	47.6	56.7	18.4	32.5	1010	6.7
	Rf5192	12.86	8.06	15.7	47.4	58.8	19.5	33.2	990	6.6
	Rf5193	14.61	8.57	15.6	52.7	61.5	18.2	29.6	835	7.8
	Rf5194	8.63	8.87	16.0	49.0	55.3	18.0	32.6	1055	6.2
	Rf5195	6.62	8.51	15.4	45.9	53.9	18.1	33.5	902	6.8
G4, F & 5000	Rf5196	6.62	8.31	15.0	45.7	55.0	18.1	32.8	1000	6.2
	Rf5197	5.51	8.41	15.0	45.5	54.1	17.9	33.0	1088	6.5
	Rf5198	15.80	8.23	15.2	45.2	55.0	18.4	33.5	926	6.2
	Rf5199	9.07	7.97	15.0	47.1	59.0	18.8	31.8	1091	7.0
	Rf5200	10.47	6.84	12.0	39.9	58.4	17.5	30.0	827	8.1

F: Female.

APPENDIX 10 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Reticulocyte Count	Neutrophils	Lymphocytes	Monocytes	Eosinophils	Basophils	Absolute Reticulocyte Count
		(Retic)	(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(Retic)
		(%)	(%)	(%)	(%)	(%)	(%)	(10⁹cells/L)
G1, F & 0	Rf5181	3.18	26.9	68.1	2.5	0.7	0.5	280.8
	Rf5182	2.56	29.5	63.3	3.5	2.1	0.7	230.0
	Rf5183	2.84	18.4	76.0	2.9	1.5	0.4	244.6
	Rf5184	2.31	17.2	78.1	1.8	1.4	0.3	179.6
	Rf5185	2.45	28.7	64.4	3.2	2.3	0.5	214.1
G2, F & 500	Rf5186	2.56	29.7	65.0	2.1	1.8	0.3	195.5
	Rf5187	2.47	23.0	72.0	2.5	1.5	0.2	204.4
	Rf5188	1.64	24.5	68.2	4.6	1.3	0.4	144.9
	Rf5189	2.54	19.8	75.2	2.6	1.0	0.3	196.7
	Rf5190	1.55	34.8	58.2	4.9	1.1	0.3	132.5
G3, F & 1500	Rf5191	3.11	16.6	73.5	6.5	1.5	0.8	261.1
	Rf5192	4.16	19.1	75.0	3.6	1.1	0.3	335.3
	Rf5193	1.51	17.7	74.3	6.0	0.5	0.7	129.3
	Rf5194	1.59	25.4	68.5	3.3	1.5	0.4	141.1
	Rf5195	1.57	25.7	69.8	1.4	1.9	0.4	133.8
G4, F & 5000	Rf5196	1.73	38.1	53.9	4.9	1.5	0.3	143.6
	Rf5197	1.82	29.8	63.4	3.5	1.7	0.3	152.8
	Rf5198	2.40	15.5	80.4	2.4	0.5	0.3	197.8
	Rf5199	3.84	21.0	72.9	3.8	1.1	0.3	306.1
	Rf5200	13.56	16.8	78.5	2.8	0.9	0.3	926.5

F: Female.

APPENDIX 10 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Absolute Neutrophils	Absolute Lymphocytes	Absolute Monocytes	Absolute Eosinophils	Absolute Basophils	Prothrombin Time	Activated Prothrombin Time
		(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(PT)	(APTT)
		(10³cells/µL)	(10³cells/µL)	(10³cells/µL)	(10³cells/µL)	(10³cells/µL)	(Seconds)	(Seconds)
G1, F & 0	Rf5181	2.67	6.76	0.25	0.07	0.05	17.3	37.7
	Rf5182	3.20	6.86	0.39	0.23	0.08	15.1	37.3
	Rf5183	2.04	8.42	0.33	0.17	0.05	16.7	27.8
	Rf5184	2.56	11.62	0.27	0.20	0.04	18.9	24.7
	Rf5185	3.11	6.99	0.35	0.25	0.06	17.7	22.8
G2, F & 500	Rf5186	2.19	4.80	0.15	0.14	0.02	19.4	20.7
	Rf5187	1.77	5.55	0.20	0.12	0.02	16.9	22.5
	Rf5188	2.05	5.69	0.38	0.11	0.03	17.9	20.2
	Rf5189	1.67	6.31	0.21	0.09	0.03	17.7	29.2
	Rf5190	2.66	4.45	0.37	0.09	0.02	17.2	26.7
G3, F & 1500	Rf5191	1.86	8.20	0.73	0.17	0.09	16.6	27.6
	Rf5192	2.46	9.65	0.46	0.14	0.04	17.6	27.7
	Rf5193	2.59	10.85	0.88	0.07	0.10	29.8	39.8
	Rf5194	2.19	5.92	0.28	0.13	0.03	30.9	21.6
	Rf5195	1.70	4.62	0.09	0.12	0.03	15.8	21.9
G4, F & 5000	Rf5196	2.52	3.57	0.32	0.10	0.02	24.6	25.7
	Rf5197	1.64	3.49	0.19	0.10	0.02	16.4	17.0
	Rf5198	2.45	12.70	0.37	0.07	0.05	19.4	19.4
	Rf5199	1.91	6.61	0.35	0.10	0.03	18.7	19.5
	Rf5200	1.76	8.22	0.30	0.10	0.03	16.7	17.5

F: Female.

APPENDIX 10 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Total Leucocyte Count	Total Erythrocyte Count	Hemoglobin	Haematocrit	Mean Corpuscular Volume	Mean Corpuscular Hemoglobin	Mean Corpuscular Hemoglobin Concentration	Platelet Count	Mean Platelet Volume
		(WBC)	(RBC)	(HGB)	(HCT)	(MCV)	(MCH)	(MCHC)	(PLT)	(MPV)
		(10³cells/µL)	(10⁶cells/µL)	(g/dL)	(%)	(fL)	(pg)	(g/dL)	(10³cells/µL)	(fL)
G1R, M & 0	Rf5171	6.35	8.56	15.0	46.3	54.1	17.5	32.4	1023	6.8
	Rf5172	8.20	8.52	16.1	48.9	57.4	18.9	33.0	332	7.2
	Rf5173	12.10	8.29	15.8	49.1	59.2	19.1	32.3	785	6.4
	Rf5174	6.94	8.32	16.1	48.2	57.9	19.4	33.5	953	6.2
	Rf5175	6.36	8.59	14.9	46.5	54.1	17.4	32.1	992	6.8
G4R, M & 5000	Rf5176	8.19	8.92	16.4	51.1	57.3	18.4	32.1	900	6.6
	Rf5177	10.65	8.04	15.2	48.1	59.8	18.9	31.5	497	6.7
	Rf5178	10.26	7.59	14.1	43.8	57.7	18.6	32.2	936	6.4
	Rf5179	13.65	8.50	15.5	47.9	56.4	18.2	32.3	982	6.4
	Rf5180	9.31	8.57	14.9	46.1	53.8	17.4	32.4	890	6.0
G1R, F & 0	Rf5201	7.51	8.18	15.8	48.1	58.8	19.3	32.9	719	6.4
	Rf5202	6.15	8.26	15.4	47.0	56.9	18.7	32.8	937	6.3
	Rf5203	5.68	8.82	16.3	48.1	54.5	18.5	33.8	439	6.6
	Rf5204	10.22	8.99	16.5	49.2	54.7	18.4	33.6	131	9.7
	Rf5205	10.87	8.35	15.8	47.2	56.6	18.9	33.4	971	6.5
G4R, F & 5000	Rf5206	14.41	7.77	14.8	43.6	56.2	19.1	34.0	864	6.8
	Rf5207	9.36	8.53	15.7	47.0	55.1	18.5	33.5	1019	6.6
	Rf5208	10.11	8.83	15.6	46.5	52.7	17.7	33.6	1088	6.3
	Rf5209	8.46	8.45	15.9	46.7	55.3	18.9	34.2	885	6.5
	Rf5210	7.47	8.54	16.0	47.7	55.9	18.7	33.5	900	6.9

M: Male; F: Female; R: Recovery.

APPENDIX 10 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Reticulocyte Count	Neutrophils	Lymphocytes	Monocytes	Eosinophils	Basophils	Absolute Reticulocyte Count
		(Retic)	(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(Retic)
		(%)	(%)	(%)	(%)	(%)	(%)	(10⁹cells/L)
G1R, M & 0	Rf5171	2.62	20.2	74.0	3.5	1.4	0.3	224.5
	Rf5172	2.84	33.5	59.7	3.2	2.4	0.5	241.6
	Rf5173	4.24	20.9	73.3	3.6	0.5	0.4	351.5
	Rf5174	3.46	22.5	70.7	4.2	1.3	0.4	287.7
	Rf5175	2.44	21.6	73.1	3.1	1.2	0.2	209.7
G4R, M & 5000	Rf5176	3.91	21.2	73.0	3.8	0.6	0.4	348.7
	Rf5177	3.56	19.5	73.2	4.4	1.8	0.2	286.1
	Rf5178	5.28	40.1	56.0	2.0	0.8	0.3	400.9
	Rf5179	3.09	46.5	46.3	5.7	0.5	0.4	262.8
	Rf5180	3.67	29.3	63.6	3.7	1.8	0.4	314.7
G1R, F & 0	Rf5201	3.25	26.3	64.4	5.9	1.5	0.6	266.1
	Rf5202	2.49	34.7	58.2	3.1	2.6	0.5	205.7
	Rf5203	2.13	25.5	67.0	2.8	3.4	0.3	188.2
	Rf5204	2.02	32.3	62.3	1.1	3.0	0.7	181.6
	Rf5205	2.29	22.1	71.4	3.0	1.7	0.4	191.2
G4R, F & 5000	Rf5206	4.45	29.7	66.1	1.8	1.0	0.4	345.8
	Rf5207	2.00	23.3	69.8	4.1	1.4	0.4	170.3
	Rf5208	2.46	19.2	76.8	2.3	0.6	0.4	217.4
	Rf5209	2.63	19.0	75.8	2.7	0.9	0.5	222.3
	Rf5210	3.28	20.8	74.0	2.9	0.8	0.3	280.4

M: Male; F: Female; R: Recovery.

APPENDIX 10 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Absolute Neutrophils	Absolute Lymphocytes	Absolute Monocytes	Absolute Eosinophils	Absolute Basophils	Prothrombin Time	Activated Prothrombin Time
		(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(PT)	(APTT)
		(10³cells/µL)	(10³cells/µL)	(10³cells/µL)	(10³cells/µL)	(10³cells/µL)	(Seconds)	(Seconds)
G1R, M & 0	Rf5171	1.28	4.70	0.22	0.09	0.02	17.4	21.3
	Rf5172	2.75	4.89	0.26	0.19	0.04	19.9	39.8
	Rf5173	2.53	8.86	0.43	0.07	0.05	10.7	26.5
	Rf5174	1.56	4.90	0.29	0.09	0.03	12.5	27.3
	Rf5175	1.38	4.65	0.20	0.08	0.01	15.2	18.4
G4R, M & 5000	Rf5176	1.73	5.98	0.31	0.05	0.03	14.9	22.5
	Rf5177	2.07	7.80	0.46	0.19	0.03	14.8	39.5
	Rf5178	4.11	5.74	0.21	0.08	0.03	16.6	37.3
	Rf5179	6.35	6.32	0.78	0.07	0.05	13.6	30.1
	Rf5180	2.72	5.92	0.34	0.17	0.04	13.3	27.3
G1R, F & 0	Rf5201	1.97	4.83	0.44	0.11	0.04	18.4	22.3
	Rf5202	2.14	3.58	0.19	0.16	0.03	18.5	23.5
	Rf5203	1.45	3.80	0.16	0.19	0.02	17.5	21.1
	Rf5204	3.30	6.37	0.12	0.31	0.08	17.2	27.7
	Rf5205	2.40	7.76	0.32	0.18	0.05	19.5	35.7
G4R, F & 5000	Rf5206	4.28	9.52	0.26	0.14	0.06	16.6	16.0
	Rf5207	2.18	6.53	0.38	0.13	0.04	19.2	24.1
	Rf5208	1.94	7.76	0.23	0.06	0.04	17.5	28.5
	Rf5209	1.61	6.42	0.23	0.08	0.04	18.4	10.3
	Rf5210	1.55	5.53	0.22	0.06	0.03	16.9	31.5

M: Male; F: Female; R: Recovery.

APPENDIX 11. INDIVIDUAL ANIMAL BALF RECORD

Group, Sex & Concentration (mg/m3)	Animal No.	Total Leucocyte Count	Neutrophils	Lymphocytes	Monocytes	Eosinophils	Basophils	Absolute Neutrophils
		(WBC)	(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(Neut)
		(10³cells/µL)	(%)	(%)	(%)	(%)	(%)	(10³cells/µL)
G1, M & 0	Rf5151	0.65	25.8	62.0	4.8	3.3	4.4	0.17
	Rf5152	1.42	71.3	18.4	2.7	1.5	4.1	1.01
	Rf5153	O2.39	10.9	86.3	0.9	0.1	O13.9	0.26
	Rf5154	0.68	33.1	52.7	2.6	0.8	4.9	0.22
	Rf5155	0.82	16.9	73.7	3.2	0.4	0.7	0.14
G2, M & 500	Rf5156	0.54	26.5	27.3	2.5	0.4	1.7	0.14
	Rf5157	0.53	11.1	57.9	0.4	0.2	1.2	0.06
	Rf5158	0.60	22.5	53.0	1.8	0.4	3.5	0.14
	Rf5159	0.46	28.1	59.9	2.2	1.0	1.9	0.13
	Rf5160	0.63	30.0	58.9	4.9	3.9	8.4	0.19
G3, M & 1500	Rf5161	O1.66	68.7	14.5	5.1	10.2	7.0	O1.14
	Rf5162	0.39	57.2	24.6	7.6	8.7	5.7	0.23
	Rf5163	O3.16	38.1	51.7	4.1	3.5	1.3	O1.2
	Rf5164	1.08	52.5	35.1	4.8	5.2	5.9	0.57
	Rf5165	0.81	56.7	15.7	O15.9	6.1	2.6	0.46
G4, M & 5000	Rf5166	0.88	68.1	14.9	5.9	6.9	11.8	0.60
	Rf5167	0.55	62.3	24.3	5.1	6.5	6.7	0.34
	Rf5168	0.40	46.3	36.7	2.0	11.2	3.1	0.18
	Rf5169	0.63	46.3	22.6	3.5	3.3	5.5	0.29
	Rf5170	0.75	39.0	45.2	8.2	4.0	9.4	0.29

M: Male. O: Outlier value.

APPENDIX 11 (Contd…). INDIVIDUAL ANIMAL BALF RECORD

Group, Sex & Concentration (mg/m3)	Animal No.	Absolute Lymphocytes	Absolute Monocytes	Absolute Eosinophils	Absolute Basophils	Lactate Dehydrogenase	Total Protein
		(Lymph)	(Mono)	(Eos)	(Baso)	(LDH)	(TPR)
		(10³cells/µL)	(10³cells/µL)	(10³cells/µL)	(10³cells/µL)	(u/L)	(µg/ml)
G1, M & 0	Rf5151	0.40	0.03	0.02	0.03	75.0	267.583
	Rf5152	0.26	0.04	0.02	0.06	49.9	379.835
	Rf5153	O2.06	0.02	0.00	O0.33	55.6	293.631
	Rf5154	0.36	0.02	0.01	0.03	53.1	409.708
	Rf5155	0.61	0.03	0.00	0.01	70.1	O811.692
G2, M & 500	Rf5156	0.15	0.01	0.00	0.01	56.7	388.675
	Rf5157	0.31	0.00	0.00	0.01	66.6	220.545
	Rf5158	0.32	0.01	0.00	0.02	49.8	387.522
	Rf5159	0.27	0.01	0.00	0.01	61.8	134.960
	Rf5160	0.37	0.03	0.02	0.05	53.3	462.536
G3, M & 1500	Rf5161	0.24	0.08	O0.17	0.12	119.5	141.228
	Rf5162	0.10	0.03	0.03	0.02	60.6	175.519
	Rf5163	O1.63	O0.13	0.11	0.04	O182.1	297.713
	Rf5164	0.38	0.05	0.06	0.06	92.1	264.451
	Rf5165	0.13	O0.13	0.05	0.02	99.1	409.921
G4, M & 5000	Rf5166	0.13	0.05	0.06	0.10	49.6	176.061
	Rf5167	0.13	0.03	0.04	0.04	68.3	522.235
	Rf5168	0.15	0.01	0.04	0.01	92.4	171.228
	Rf5169	0.14	0.02	0.02	0.03	73.5	298.561
	Rf5170	0.34	0.06	0.03	0.07	21.9	437.998

M: Male; O: Outlier value.

APPENDIX 11 (Contd…). INDIVIDUAL ANIMAL BALF RECORD

Group, Sex & Concentration (mg/m3)	Animal No.	Total Leucocyte Count	Neutrophils	Lymphocytes	Monocytes	Eosinophils	Basophils	Absolute Neutrophils
		(WBC)	(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(Neut)
		(10³cells/µL)	(%)	(%)	(%)	(%)	(%)	(10³cells/µL)
G1, F & 0	Rf5181	0.19	22.1	64.2	4.2	2.4	2.9	0.04
	Rf5182	0.75	47.5	30.6	5.1	3.7	1.5	0.36
	Rf5183	0.41	34.6	58.1	3.2	0.5	7.0	0.14
	Rf5184	0.31	36.6	49.1	4.4	2.6	4.3	0.11
	Rf5185	0.46	38.4	38.9	2.7	3.2	3.9	0.18
G2, F & 500	Rf5186	1.04	55.9	23.7	3.1	2.2	0.6	0.58
	Rf5187	0.43	13.7	66.5	2.1	1.0	2.0	0.06
	Rf5188	0.29	23.7	64.6	1.9	1.2	3.1	0.07
	Rf5189	0.33	20.6	66.1	4.1	1.4	3.7	0.07
	Rf5190	0.26	14.9	68.1	2.1	0.4	3.8	0.04
G3, F & 1500	Rf5191	1.43	39.9	47.9	5.0	6.4	5.4	0.57
	Rf5192	1.47	20.7	36.3	O40	1.7	O10.7	0.30
	Rf5193	0.60	61.9	20.3	6.3	O10.5	3.0	0.37
	Rf5194	O2.68	72.0	16.6	4.5	3.5	2.9	O1.93
	Rf5195	0.52	34.5	35.4	5.6	O21.9	5.1	0.18
G4, F & 5000	Rf5196	O4.49	73.6	10.6	O12.7	2.3	2.9	O3.31
	Rf5197	0.58	67.0	13.0	4.2	6.6	2.7	0.39
	Rf5198	0.53	57.2	27.3	7.9	3.4	2.3	0.30
	Rf5199	O2.61	75.1	7.7	O12.8	1.8	1.8	O1.96
	Rf5200	0.28	36.6	50.1	2.8	4.4	4.7	0.10

F: Female; O: Outlier value.

APPENDIX 11 (Contd…). INDIVIDUAL ANIMAL BALF RECORD

Group, Sex & Concentration (mg/m3)	Animal No.	Absolute Lymphocytes	Absolute Monocytes	Absolute Eosinophils	Absolute Basophils	Lactate Dehydrogenase	Total Protein
		(Lymph)	(Mono)	(Eos)	(Baso)	(LDH)	(TPR)
		(10³cells/µL)	(10³cells/µL)	(10³cells/µL)	(10³cells/µL)	(u/L)	(µg/ml)
G1, F & 0	Rf5181	0.12	0.01	0.00	0.01	98.3	335.149
	Rf5182	0.23	0.04	0.03	0.01	42.5	313.635
	Rf5183	0.24	0.01	0.00	0.03	55.1	123.016
	Rf5184	0.15	0.01	0.01	0.01	44.5	222.150
	Rf5185	0.18	0.01	0.01	0.02	60.2	358.050
G2, F & 500	Rf5186	0.25	0.03	0.02	0.01	79.1	244.040
	Rf5187	0.29	0.01	0.00	0.01	39.6	124.717
	Rf5188	0.19	0.01	0.00	0.01	52.9	160.186
	Rf5189	0.22	0.01	0.00	0.01	42.1	297.665
	Rf5190	0.18	0.01	0.00	0.01	77.9	241.718
G3, F & 1500	Rf5191	O0.69	0.07	0.09	0.08	O249.9	463.058
	Rf5192	O0.53	O0.59	0.02	O0.16	82.6	160.841
	Rf5193	0.12	0.04	0.06	0.02	O150.5	317.163
	Rf5194	0.44	0.12	0.09	0.08	75.6	274.012
	Rf5195	0.18	0.03	0.11	0.03	O202.4	75.773
G4, F & 5000	Rf5196	O0.48	O0.57	0.10	O0.13	69.7	297.157
	Rf5197	0.08	0.02	0.04	0.02	67.5	146.953
	Rf5198	0.14	0.04	0.02	0.01	94.5	373.659
	Rf5199	0.2	O0.34	0.05	0.05	59.0	378.589
	Rf5200	0.14	0.01	0.01	0.01	61.6	449.427

F: Female; O: Outlier value.

APPENDIX 11 (Contd…). INDIVIDUAL ANIMAL BALF RECORD

Group, Sex & Concentration (mg/m3)	Animal No.	Total Leucocyte Count	Neutrophils	Lymphocytes	Monocytes	Eosinophils	Basophils	Absolute Neutrophils
		(WBC)	(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(Neut)
		(10³cells/µL)	(%)	(%)	(%)	(%)	(%)	(10³cells/µL)
G1R, M & 0	Rf5171	1.37	29.4	43.2	2.1	1.4	3.2	0.40
	Rf5172	0.77	24.3	40.2	5.9	6.9	1.9	0.19
	Rf5173	0.40	15.8	74.7	3.4	0.0	0.6	0.06
	Rf5174	0.14	17.3	68.8	3.3	0.8	1.6	0.02
	Rf5175	0.40	19.4	72.8	2.0	2.0	1.7	0.08
G4R, M & 5000	Rf5176	0.74	38.8	39.2	7.0	5.2	2.2	0.29
	Rf5177	1.06	41.2	45.7	3.9	3.2	4.7	0.44
	Rf5178	0.49	37.5	35.3	O12.8	6.4	5.2	0.18
	Rf5179	1.40	43.7	40.3	4.9	5.6	3.0	0.61
	Rf5180	2.76	37.0	55.6	3.3	1.9	5.2	O1.02
G1R, F & 0	Rf5201	0.60	22.4	24.0	1.0	0.4	3.9	0.13
	Rf5202	0.28	6.5	84.6	1.2	0.4	2.0	0.02
	Rf5203	0.21	16.1	50.8	0.0	1.0	5.2	0.03
	Rf5204	0.46	18.1	49.0	2.0	0.7	2.4	0.08
	Rf5205	0.39	17.0	58.8	1.4	0.0	6.4	0.07
G4R, F & 5000	Rf5206	1.18	49.2	37.1	4.8	5.1	0.7	O0.58
	Rf5207	0.57	39.4	39.6	2.6	3.9	7.2	0.22
	Rf5208	0.61	18.6	68.8	3.3	4.4	6.3	0.11
	Rf5209	O1.76	O81.1	5.1	5.0	1.8	O13.3	O1.43
	Rf5210	0.84	32.0	43.9	4.2	O13.4	2.1	0.27

M: Male; F: Female; R: Recovery; O: Outlier value.

APPENDIX 11 (Contd…). INDIVIDUAL ANIMAL BALF RECORD

Group, Sex & Concentration (mg/m3)	Animal No.	Absolute Lymphocytes	Absolute Monocytes	Absolute Eosinophils	Absolute Basophils	Lactate Dehydrogenase	Total Protein
		(Lymph)	(Mono)	(Eos)	(Baso)	(LDH)	(TPR)
		(10³cells/µL)	(10³cells/µL)	(10³cells/µL)	(10³cells/µL)	(u/L)	(µg/ml)
G1R, M & 0	Rf5171	0.59	0.03	0.02	0.04	18.0	382.680
	Rf5172	0.31	0.05	0.05	0.01	O831.7	509.889
	Rf5173	0.30	0.01	0.00	0.00	46.1	398.573
	Rf5174	0.09	0.00	0.00	0.00	64.5	360.625
	Rf5175	0.29	0.01	0.01	0.01	18.1	164.321
G4R, M & 5000	Rf5176	0.29	0.05	0.04	0.02	16.4	291.905
	Rf5177	0.48	0.04	0.03	0.05	71.2	O599.369
	Rf5178	0.17	0.06	0.03	0.03	115.3	297.749
	Rf5179	0.57	0.07	0.08	0.04	43.4	310.126
	Rf5180	O1.54	0.09	0.05	O0.14	50.2	163.859
G1R, F & 0	Rf5201	0.14	0.01	0.00	0.02	14.0	193.782
	Rf5202	0.23	0.00	0.00	0.01	29.1	316.092
	Rf5203	0.11	0.00	0.00	0.01	41.5	170.756
	Rf5204	0.23	0.01	0.00	0.01	18.5	213.753
	Rf5205	0.23	0.01	0.00	0.03	33.8	390.005
G4R, F & 5000	Rf5206	0.44	0.06	0.06	0.01	31.1	379.224
	Rf5207	0.22	0.01	0.02	0.04	32.1	307.121
	Rf5208	0.42	0.02	0.03	0.04	15.2	249.449
	Rf5209	0.09	O0.09	0.03	O0.23	14.2	241.473
	Rf5210	0.37	0.03	O0.11	0.02	17.2	O643.554

M: Male; F: Female; R: Recovery; O: Outlier value.

APPENDIX 12. INDIVIDUAL ANIMAL CLINICAL CHEMISTRY RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Glucose	Urea	Creatinine	Total Cholesterol	Triglycerides	Total Protein	Albumin	Alanine aminotransferase	Aspartate aminotransferase
		(GLU)		(CRE)	(CHO)	(TRI)	(TPR)	(ALB)	(ALT)	(AST)
		(mg/dL)	(mg/dL)	(mg/dL)	(mg/dL)	(mg/dL)	(g/dL)	(g/dL)	(U/L)	(U/L)
G1, M & 0	Rf5151	92	30.7	0.47	58	33	7.3	3.41	62	131
	Rf5152	93	37.4	0.49	53	34	7.4	3.53	59	112
	Rf5153	80	29.9	0.46	40	32	7.4	3.55	50	108
	Rf5154	77	35.5	0.48	46	20	7.4	3.56	63	116
	Rf5155	82	30.5	0.50	51	69	7.3	3.64	46	110
G2, M & 500	Rf5156	78	34.6	0.40	50	35	7.1	3.35	59	132
	Rf5157	85	33.5	0.48	67	48	7.7	3.54	64	115
	Rf5158	98	36.8	0.46	45	27	7.1	3.46	60	120
	Rf5159	81	31.6	0.50	48	23	7.5	3.53	68	131
	Rf5160	95	28.0	0.49	56	45	8.3	3.61	44	109
G3, M & 1500	Rf5161	71	31.4	0.44	72	53	7.4	3.33	62	139
	Rf5162	113	27.1	0.40	55	25	6.6	3.06	46	119
	Rf5163	88	36.5	0.45	43	31	7.4	3.28	62	124
	Rf5164	91	38.3	0.47	47	31	7.1	3.39	56	130
	Rf5165	104	39.2	0.46	62	38	7.6	3.54	71	117
G4, M & 5000	Rf5166	114	39.8	0.48	34	23	7.2	3.22	79	133
	Rf5167	79	37.0	0.43	53	26	7.1	3.22	88	205
	Rf5168	108	39.8	0.44	46	34	6.9	3.32	74	120
	Rf5169	86	42.0	0.42	52	31	7.7	3.34	69	98
	Rf5170	102	38.5	0.44	67	35	7.6	3.45	84	111

M: Male.

APPENDIX 12 (Contd…). INDIVIDUAL ANIMAL CLINICAL CHEMISTRY RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Alkaline phosphatase	Total Bilirubin	Calcium	Phosphorous	Globulin	Blood Urea Nitrogen	Sodium	Potassium	Chloride
		(ALP)	(BIT)	(CAL)	(PHO)	(GLO)	(BUN)	(Na)	(K)	(CLO)
		(U/L)	(mg/dL)	(mg/dL)	(mg/dL)	(g/dL)	(mg/dL)	(mmol/L)	(mmol/L)	(mmol/L)
G1, M & 0	Rf5151	326	0.01	9.8	6.9	3.89	14.33	142.8	3.29	103.9
	Rf5152	221	0.01	10.4	6.4	3.87	17.45	142.6	3.49	103.9
	Rf5153	158	0.02	10.0	6.7	3.85	13.95	142.9	3.57	103.4
	Rf5154	259	0.02	10.1	6.8	3.84	16.57	140.4	3.74	103.2
	Rf5155	297	0.02	10.2	6.9	3.66	14.23	143.6	3.50	103.2
G2, M & 500	Rf5156	207	0.00	10.1	7.6	3.75	16.15	142.3	3.85	103.9
	Rf5157	233	0.03	10.6	7.9	4.16	15.63	142.9	4.03	104.1
	Rf5158	238	0.00	10.2	6.7	3.64	17.17	141.7	3.71	103.3
	Rf5159	321	0.03	9.8	7.3	3.97	14.75	144.5	3.23	106.4
	Rf5160	176	0.02	10.1	6.9	4.69	13.07	143.8	3.32	105.1
G3, M & 1500	Rf5161	226	0.02	10.2	6.4	4.07	14.65	141.2	3.50	101.4
	Rf5162	249	0.00	8.8	5.4	3.54	12.65	143.9	3.39	104.7
	Rf5163	266	0.03	9.8	6.6	4.12	17.03	142.5	3.38	105.1
	Rf5164	223	0.03	9.7	6.7	3.71	17.87	141.6	3.73	104.7
	Rf5165	234	0.03	10.1	6.2	4.06	18.29	141.0	3.94	104.1
G4, M & 5000	Rf5166	238	0.06	9.8	7.5	3.98	18.57	142.4	3.16	103.3
	Rf5167	350	0.03	9.5	6.8	3.88	17.27	142.5	4.08	107.0
	Rf5168	187	0.10	10.2	6.7	3.58	18.57	142.8	3.64	104.3
	Rf5169	153	0.11	10.1	6.7	4.36	19.60	141.8	3.61	103.7
	Rf5170	194	0.08	10.1	6.8	4.15	17.97	141.9	3.26	103.9

M: Male.

APPENDIX 12 (Contd…). INDIVIDUAL ANIMAL CLINICAL CHEMISTRY RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Glucose	Urea	Creatinine	Total Cholesterol	Triglycerides	Total Protein	Albumin	Alanine aminotransferase	Aspartate aminotransferase
		(GLU)		(CRE)	(CHO)	(TRI)	(TPR)	(ALB)	(ALT)	(AST)
		(mg/dL)	(mg/dL)	(mg/dL)	(mg/dL)	(mg/dL)	(g/dL)	(g/dL)	(U/L)	(U/L)
G1, F & 0	Rf5181	111	45.5	0.54	56	43	7.9	3.65	50	113
	Rf5182	73	44.8	0.52	105	47	7.8	3.67	83	170
	Rf5183	102	41.1	0.49	87	34	8.2	3.41	77	141
	Rf5184	88	49.0	0.51	47	54	7.8	3.28	58	129
	Rf5185	100	31.9	0.51	67	63	7.8	3.62	53	112
G2, F & 500	Rf5186	113	49.3	0.51	52	36	7.6	3.41	54	112
	Rf5187	106	39.3	0.47	76	35	7.9	3.90	45	108
	Rf5188	80	29.4	0.45	58	53	7.7	3.39	53	100
	Rf5189	96	34.3	0.50	60	39	8.1	3.71	60	108
	Rf5190	95	39.8	0.51	77	55	8.1	3.89	46	91
G3, F & 1500	Rf5191	94	36.1	0.56	69	38	7.5	3.47	47	132
	Rf5192	98	37.3	0.47	76	42	8.5	3.67	51	110
	Rf5193	76	38.4	0.48	64	38	8.4	3.76	56	149
	Rf5194	93	36.6	0.45	87	34	7.8	3.60	47	108
	Rf5195	112	36.4	0.48	53	48	8.0	3.84	45	107
G4, F & 5000	Rf5196	79	45.0	0.44	61	41	7.9	3.34	77	118
	Rf5197	86	37.4	0.44	56	61	7.2	3.29	59	82
	Rf5198	92	38.7	0.42	49	24	7.8	3.47	61	108
	Rf5199	74	38.3	0.41	51	21	7.5	3.19	96	119
	Rf5200	80	33.6	0.40	72	31	7.2	3.26	85	126

F: Female.

APPENDIX 12 (Contd…). INDIVIDUAL ANIMAL CLINICAL CHEMISTRY RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Alkaline phosphatase	Total Bilirubin	Calcium	Phosphorous	Globulin	Blood Urea Nitrogen	Sodium	Potassium	Chloride
		(ALP)	(BIT)	(CAL)	(PHO)	(GLO)	(BUN)	(Na)	(K)	(CLO)
		(U/L)	(mg/dL)	(mg/dL)	(mg/dL)	(g/dL)	(mg/dL)	(mmol/L)	(mmol/L)	(mmol/L)
G1, F & 0	Rf5181	182	0.01	10.3	7.5	4.25	21.23	140.9	3.78	103.9
	Rf5182	170	0.02	10.4	6.7	4.13	20.91	141.0	3.19	104.1
	Rf5183	157	0.01	10.1	6.2	4.79	19.18	141.2	3.33	103.1
	Rf5184	171	0.00	10.5	7.4	4.52	22.87	143.0	3.61	104.6
	Rf5185	153	0.00	10.5	6.1	4.18	14.89	141.5	3.78	103.1
G2, F & 500	Rf5186	164	0.01	10.1	6.9	4.19	23.01	141.5	3.33	104.0
	Rf5187	108	0.02	10.6	5.4	4.00	18.34	141.3	3.35	102.5
	Rf5188	114	0.01	10.1	6.6	4.31	13.72	141.5	3.62	102.5
	Rf5189	137	0.02	10.9	5.9	4.39	16.01	141.1	3.20	101.4
	Rf5190	138	0.01	10.6	5.7	4.21	18.57	140.5	3.14	100.7
G3, F & 1500	Rf5191	202	0.01	9.6	7.1	4.03	16.85	141.9	4.31	106.2
	Rf5192	126	0.02	10.6	6.2	4.83	17.41	141.5	3.03	103.2
	Rf5193	167	0.12	10.1	6.8	4.64	17.92	143.5	3.11	103.8
	Rf5194	114	0.01	10.7	6.5	4.20	17.08	142.4	3.44	101.3
	Rf5195	187	0.01	10.3	6.3	4.16	16.99	143.4	3.44	103.8
G4, F & 5000	Rf5196	205	0.11	10.2	7.2	4.56	21.00	142.4	3.70	104.2
	Rf5197	109	0.07	10.1	6.6	3.91	17.45	140.5	3.45	101.6
	Rf5198	128	0.07	9.9	6.7	4.33	18.06	141.1	3.47	103.6
	Rf5199	239	0.08	10.1	6.2	4.31	17.87	142.1	3.54	103.5
	Rf5200	101	0.17	10.3	6.8	3.94	15.68	142.1	3.67	104.6

F: Female.

APPENDIX 12 (Contd…). INDIVIDUAL ANIMAL CLINICAL CHEMISTRY RECORD

Group, Sex & Concentration (mg/m³)	Animal No.		Glucose		Urea		Creatinine		Total Cholesterol		Triglycerides		Total Protein		Albumin		Alanine aminotransferase		Aspartate aminotransferase
		(GLU)				(CRE)		(CHO)		(TRI)		(TPR)		(ALB)		(ALT)		(AST)
		(mg/dL)		(mg/dL)		(mg/dL)		(mg/dL)		(mg/dL)		(g/dL)		(g/dL)		(U/L)		(U/L)
G1R, M & 0	Rf5171		61		39.2		0.45		49		40		7.1		3.30		60		126
	Rf5172		73		34.5		0.49		52		55		6.8		3.29		65		115
	Rf5173		68		37.0		0.51		57		44		7.8		3.31		61		113
	Rf5174		91		31.8		0.46		57		42		7.2		3.13		53		106
	Rf5175		78		30.0		0.42		60		56		7.3		3.45		58		108
G4R, M & 5000	Rf5176		79		32.2		0.46		56		31		7.1		3.36		45		95
	Rf5177		65		31.0		0.46		61		39		7.7		3.34		52		118
	Rf5178		81		27.2		0.44		68		59		7.0		3.25		54		104
	Rf5179		67		30.7		0.41		56		44		7.1		3.24		54		94
	Rf5180		81		32.6		0.42		57		41		7.0		3.22		55		104
G1R, F & 0	Rf5201		79		32.9		0.49		44		40		7.8		3.46		88		135
	Rf5202		83		37.3		0.54		60		24		7.9		3.61		47		119
	Rf5203		92		32.0		0.57		59		41		8.0		3.82		44		112
	Rf5204		87		44.3		0.50		63		26		7.8		3.58		47		96
	Rf5205		82		39.8		0.51		64		46		7.5		3.58		55		101
G4R, F & 5000	Rf5206		97		47.5		0.46		75		64		6.9		3.15		50		95
	Rf5207		78		35.0		0.51		87		35		7.5		3.70		40		89
	Rf5208		87		40.2		0.50		65		39		7.6		3.57		45		96
	Rf5209		78		41.8		0.45		66		27		7.0		3.15		39		86
	Rf5210		77		34.8		0.44		57		33		7.1		3.39		32		85

M: Male; F: Female; R: Recovery.

APPENDIX 12 (Contd…). INDIVIDUAL ANIMAL CLINICAL CHEMISTRY RECORD

Group, Sex & Concentration (mg/m³)	Animal No.		Alkaline phosphatase		Total Bilirubin		Calcium		Phosphorous		Globulin		Blood Urea Nitrogen		Sodium		Potassium		Chloride
		(ALP)		(BIT)		(CAL)		(PHO)		(GLO)		(BUN)		(Na)		(K)		(CLO)
		(U/L)		(mg/dL)		(mg/dL)		(mg/dL)		(g/dL)		(mg/dL)		(mmol/L)		(mmol/L)		(mmol/L)
G1R, M & 0	Rf5171		270		0.07		9.9		7.2		3.80		18.29		144.4		3.58		105.8
	Rf5172		206		0.06		9.6		7.3		3.51		16.10		143.9		3.65		106.1
	Rf5173		217		0.09		9.2		6.4		4.49		17.27		143.3		3.75		105.2
	Rf5174		165		0.06		9.6		5.9		4.07		14.84		142.5		3.82		106.1
	Rf5175		357		0.05		9.5		7.5		3.85		14.00		143.8		3.95		104.1
G4R, M & 5000	Rf5176		221		0.05		9.5		7.0		3.74		15.03		143.2		3.82		105.6
	Rf5177		300		0.06		9.5		7.3		4.36		14.47		143.3		3.87		105.8
	Rf5178		429		0.09		8.8		6.2		3.75		12.69		141.7		3.81		104.5
	Rf5179		234		0.05		9.7		7.3		3.86		14.33		142.5		4.00		103.4
	Rf5180		224		0.06		9.2		6.7		3.78		15.21		143.0		4.10		105.7
G1R, F & 0	Rf5201		117		0.06		9.6		6.3		4.34		15.35		141.9		3.67		105.4
	Rf5202		94		0.08		9.3		5.6		4.29		17.41		142.4		3.97		105.5
	Rf5203		130		0.05		9.8		4.9		4.18		14.93		142.4		3.73		106.1
	Rf5204		199		0.05		9.6		5.6		4.22		20.67		143.7		3.51		107.9
	Rf5205		119		0.06		10.2		6.1		3.92		18.57		143.4		3.37		104.6
G4R, F & 5000	Rf5206		161		0.06		9.3		6.8		3.75		22.17		140.2		4.94		104.2
	Rf5207		95		0.05		10.0		6.3		3.80		16.33		142.1		3.82		105.9
	Rf5208		95		0.09		9.6		6.1		4.03		18.76		140.8		3.89		103.8
	Rf5209		110		0.06		9.1		6.0		3.85		19.51		141.5		4.09		104.4
	Rf5210		87		0.07		8.9		6.2		3.71		16.24		141.3		4.03		102.7

M: Male; F: Female; R: Recovery.

APPENDIX 13. INDIVIDUAL ANIMAL URINALYSIS RECORD

Group, Sex & Concentration (mg/m³)

Animal No.

Chemical Examination

Urobilinogen (UBG) (mg/dL)

Bilirubin (BIL) (mg/dL)

Ketones (KET) (mg/dL)

Blood (BLD) (Ery/µL)

Protein (PRO) (mg/dL)

Nitrite (NIT)

Leucocytes (LEU) (Leu/µL)

Glucose (GLU) (mg/dL)

Specific gravity (SG)

Microalbumin (MALB) (mg/dL)

G1, M & 0

Rf5151

0.2

Neg

Pos

Neg

<=1.005

8.5

Rf5152

0.2

Neg

Ca10

Pos

Ca15

Neg

1.010

8.5

>15

Rf5153

0.2

Neg

>=Ca200

Neg

1.010

7.5

Rf5154

0.2

Neg

Ca25

Trace

Neg

Ca15

Neg

<=1.005

8.5

>15

Rf5155

0.2

Neg

>=Ca200

Trace

Neg

Ca15

Neg

1.010

7.5

>15

G2, M & 500

Rf5156

0.2

Neg

Ca25

Trace

Neg

1.015

7.5

>15

Rf5157

0.2

Neg

Ca25

Trace

Neg

Ca15

Neg

1.015

7.5

>15

Rf5158

0.2

Neg

Trace

Pos

Ca15

Neg

1.010

8.5

>15

Rf5159

0.2

Neg

>=Ca200

Neg

Ca15

Neg

1.010

7.5

Rf5160

0.2

Neg

Ca80

Neg

1.010

8.0

G3, M & 1500

Rf5161

0.2

Neg

Ca10

Trace

Pos

Ca15

Neg

1.015

7.5

>15

Rf5162

0.2

Neg

Ca25

Trace

Pos

Ca15

Neg

1.015

7.5

>15

Rf5163

0.2

Neg

Ca80

Trace

Neg

Ca15

Neg

1.010

8.0

>15

Rf5164

0.2

Neg

Ca80

Neg

Ca15

Neg

1.010

8.0

Rf5165

0.2

Neg

Trace

Pos

Neg

1.010

8.0

>15

G4, M & 5000

Rf5166

0.2

Neg

Ca80

Neg

<=1.005

7.5

Neg

Rf5167

0.2

Neg

Ca25

Neg

Ca15

Neg

1.010

7.5

Neg

Rf5168

0.2

Neg

Ca80

Neg

Ca15

Neg

1.010

8.0

Rf5169

0.2

Neg

Ca25

Trace

Pos

Ca70

Neg

1.010

8.0

>15

Rf5170

0.2

Neg

Ca10

Neg

1.010

7.5

Neg

M: Male; Neg: Negative; Pos: Positive; Ca: Calculated Approximately; >=: More than equal to; <=: Less than or equal to; >: More than.

APPENDIX 13 (Contd…). INDIVIDUAL ANIMAL URINALYSISRECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Physical Examination			Microscopic Examination
Group, Sex & Concentration (mg/m³)	Animal No.	Color	Volume (mL)	Apperance	Epi Cells	Casts	Crystals
G1, M & 0	Rf5151	PY	7.0	Clear	0-1	A	P
	Rf5152	PY	4.5	Clear	0	A	P
	Rf5153	PY	7.5	Clear	0	A	P
	Rf5154	PY	5.0	Clear	0-1	A	P
	Rf5155	PY	4.5	Clear	0-1	A	P
G2, M & 500	Rf5156	PY	4.0	Clear	0	A	P
	Rf5157	Y	6.5	Turbid	1-2	A	P
	Rf5158	PY	4.5	Clear	0-1	A	P
	Rf5159	PY	5.0	Clear	0-1	A	P
	Rf5160	PY	5.5	Clear	0	A	P
G3, M & 1500	Rf5161	PY	5.5	Clear	0-1	A	P
	Rf5162	PY	4.0	Clear	0-1	A	P
	Rf5163	PY	4.0	Clear	0	A	P
	Rf5164	PY	5.0	Clear	0	A	P
	Rf5165	PY	4.5	Clear	0-1	A	P
G4, M & 5000	Rf5166	PY	7.5	Clear	0-1	A	P
	Rf5167	PY	4.5	Clear	0	A	P
	Rf5168	PY	5.0	Clear	0-1	A	P
	Rf5169	Y	6.5	Turbid	2-3	A	P
	Rf5170	PY	4.0	Clear	0	A	P

M: Male; A: Absent, P: Present; PY: Pale Yellow; Y: Yellow.

APPENDIX 13 (Contd…). INDIVIDUAL ANIMAL URINALYSISRECORD

Group, Sex & Concentration (mg/m³)

Animal No.

Chemical Examination

Urobilinogen (UBG) (mg/dL)

Bilirubin (BIL) (mg/dL)

Ketones (KET) (mg/dL)

Blood (BLD) (Ery/µL)

Protein (PRO) (mg/dL)

Nitrite (NIT)

Leucocytes (LEU) (Leu/µL)

Glucose (GLU) (mg/dL)

Specific gravity (SG)

Microalbumin (MALB) (mg/dL)

G1, F & 0

Rf5181

0.2

Neg

Ca10

Neg

1.010

7.5

Rf5182

0.2

Neg

Ca25

Neg

Ca70

Neg

>=1.030

6.5

>15

Rf5183

0.2

Neg

Pos

Neg

1.010

7.0

Rf5184

0.2

Neg

Ca80

Trace

Pos

Ca15

Neg

1.020

7.0

>15

Rf5185

0.2

Neg

Ca10

Neg

Pos

Neg

1.010

7.5

Neg

G2, F & 500

Rf5186

0.2

Neg

Pos

Ca15

Neg

<=1.005

8.5

>15

Rf5187

0.2

Neg

Ca125

Neg

1.015

6.5

>15

Rf5188

0.2

Neg

1.010

8.0

Rf5189

0.2

Neg

Pos

Neg

1.010

8.0

Rf5190

0.2

Neg

Ca10

Neg

1.015

7.5

G3, F & 1500

Rf5191

0.2

Neg

Pos

Neg

1.010

7.5

Neg

Rf5192

0.2

Neg

Ca25

Neg

Pos

Neg

<=1.005

7.5

Neg

Rf5193

0.2

Neg

Ca80

Neg

Pos

Neg

1.015

7.0

Neg

Rf5194

0.2

Neg

Ca10

Trace

Neg

Ca15

Neg

1.010

8.5

>15

Rf5195

0.2

Neg

1.010

8.0

Neg

G4, F & 5000

Rf5196

0.2

Neg

Pos

Neg

<=1.005

8.5

Neg

Rf5197

0.2

Neg

1.010

8.5

Rf5198

0.2

Neg

Pos

Neg

<=1.005

8.5

Neg

Rf5199

0.2

Ca10

100

Neg

Ca15

Neg

1.025

7.0

>15

Rf5200

0.2

Neg

Ca10

Trace

Pos

Ca15

Neg

1.020

7.0

>15

F: Female; Neg: Negative; Ca: Calculated Approximately; >=: More than equal to; <=: Less than or equal to; >: More than.

APPENDIX 13 (Contd…). INDIVIDUAL ANIMAL URINALYSISRECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Physical Examination			Microscopic Examination
Group, Sex & Concentration (mg/m³)	Animal No.	Color	Volume (mL)	Appearance	Epi Cells	Casts	Crystals
G1, F & 0	Rf5181	PY	4.0	Clear	0-1	A	P
	Rf5182	Y	3.0	Turbid	1-2	A	P
	Rf5183	PY	4.0	Clear	0	A	P
	Rf5184	PY	3.5	Clear	0-1	A	P
	Rf5185	PY	4.0	Clear	0-1	A	P
G2, F & 500	Rf5186	PY	3.5	Clear	0	A	P
	Rf5187	PY	4.5	Clear	0-1	A	P
	Rf5188	PY	3.5	Clear	1-2	A	P
	Rf5189	PY	3.5	Clear	0-1	A	P
	Rf5190	PY	4.5	Clear	0	A	P
G3, F & 1500	Rf5191	PY	4.5	Clear	0-1	A	P
	Rf5192	PY	3.5	Clear	0	A	P
	Rf5193	PY	5.5	Clear	1-2	A	P
	Rf5194	PY	3.0	Clear	0-1	A	P
	Rf5195	PY	5.5	Clear	0	A	P
G4, F & 5000	Rf5196	PY	4.0	Clear	0	A	P
	Rf5197	Y	5.0	Turbid	1-2	A	P
	Rf5198	PY	4.0	Clear	0	A	P
	Rf5199	Y	3.5	Turbid	2-3	A	P
	Rf5200	PY	3.0	Clear	0-1	A	P

F: Female; A: Absent, P: Present; PY: Pale Yellow; Y: Yellow.

APPENDIX 13 (Contd…). INDIVIDUAL ANIMAL URINALYSISRECORD

Group, Sex & Concentration (mg/m³)

Animal No.

Chemical Examination

Urobilinogen (UBG) (mg/dL)

Bilirubin (BIL) (mg/dL)

Ketones (KET) (mg/dL)

Blood (BLD) (Ery/µL)

Protein (PRO) (mg/dL)

Nitrite (NIT)

Leucocytes (LEU) (Leu/µL)

Glucose (GLU) (mg/dL)

Specific gravity (SG)

Microalbumin (MALB) (mg/dL)

G1R, M & 0

Rf5171

0.2

Neg

Ca80

Neg

Ca15

Neg

1.010

7.0

Rf5172

0.2

Neg

Ca25

Trace

Neg

Ca15

Neg

1.010

8.0

>15

Rf5173

0.2

Neg

Ca25

Trace

Neg

Ca15

Neg

<=1.005

8.5

>15

Rf5174

0.2

Neg

Ca25

Neg

1.010

7.5

Neg

Rf5175

0.2

Neg

Ca25

Neg

Ca15

Neg

1.010

7.5

Neg

G4R, M & 5000

Rf5176

0.2

Neg

Ca25

Neg

Ca15

Neg

1.010

7.5

Rf5177

0.2

Neg

Ca70

Neg

1.010

8.5

>15

Rf5178

0.2

Neg

Ca25

Trace

Neg

Ca70

Neg

1.015

7.5

>15

Rf5179

0.2

Neg

Ca25

Trace

Neg

Ca15

Neg

1.010

8.5

>15

Rf5180

0.2

Neg

Ca25

Trace

Neg

Ca70

Neg

1.010

7.5

>15

G1R, F & 0

Rf5201

0.2

Neg

Ca10

Neg

Ca15

Neg

1.010

7.5

Rf5202

0.2

Neg

1.010

7.5

Neg

Rf5203

0.2

Neg

Pos

Neg

<=1.005

8.0

Neg

Rf5204

0.2

Neg

1.010

8.0

Neg

Rf5205

0.2

Neg

Pos

Ca15

Neg

1.015

7.0

G4R, F & 5000

Rf5206

0.2

Neg

Ca10

Trace

Pos

Ca70

Neg

1.010

8.5

>15

Rf5207

0.2

Neg

Ca10

Neg

Ca15

Neg

1.010

7.5

Neg

Rf5208

0.2

Neg

Ca10

Neg

Ca15

Neg

1.010

7.5

Neg

Rf5209

0.2

Neg

Ca10

Neg

<=1.005

7.5

Neg

Rf5210

0.2

Neg

Ca10

Neg

Ca15

Neg

1.015

7.5

M: Male; F: Female; R: Recovery; Neg: Negative; Ca: Calculated Approximately; >=: More than equal to; <=: Less than or equal to; >: More than.

APPENDIX 13 (Contd…). INDIVIDUAL ANIMAL URINALYSISRECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Physical Examination			Microscopic Examination
Group, Sex & Concentration (mg/m³)	Animal No.	Color	Volume (mL)	Appearance	Epi Cells	Casts	Crystals
G1R, M & 0	Rf5171	PY	6.5	Clear	0	A	P
	Rf5172	PY	8.0	Clear	0	A	P
	Rf5173	PY	6.0	Clear	0	A	P
	Rf5174	PY	7.5	Clear	0	A	P
	Rf5175	PY	7.0	Clear	0	A	P
G4R, M & 5000	Rf5176	PY	6.5	Clear	0-1	A	P
	Rf5177	PY	9.0	Clear	0	A	P
	Rf5178	Y	8.5	Clear	0	A	P
	Rf5179	PY	8.0	Clear	0	A	P
	Rf5180	PY	6.0	Clear	0	A	P
G1R, F & 0	Rf5201	Y	7.5	Clear	0-1	A	P
	Rf5202	PY	6.5	Clear	0	A	P
	Rf5203	PY	9.5	Clear	0	A	P
	Rf5204	PY	6.5	Clear	1-2	A	P
	Rf5205	PY	7.0	Clear	0	A	P
G4R, F & 5000	Rf5206	PY	8.5	Clear	0	A	P
	Rf5207	Y	8.0	Clear	0	A	P
	Rf5208	PY	6.5	Clear	0-1	A	P
	Rf5209	PY	8.0	Clear	0	A	P
	Rf5210	PY	7.0	Clear	0	A	P

M: Male; F: Female; R: Recovery; A: Absent, P: Present; PY: Pale Yellow; Y: Yellow.

APPENDIX 14. INDIVIDUAL ANIMAL ABSOLUTE ORGAN WEIGHT (g) RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Adrenals	Thymus	Spleen	Testes	Heart	Kidneys	Brain	Liver	Lungs
G1, M & 0	Rf5151	0.0523	0.3452	0.4215	2.9272	0.7775	1.5710	1.7540	6.4481	0.6215
	Rf5152	0.0587	0.2406	0.3637	2.9999	0.8677	1.6080	1.7700	6.3915	0.6139
	Rf5153	0.0463	0.3259	0.4925	3.1379	0.8588	1.6942	1.8531	6.5506	0.5788
	Rf5154	0.0608	0.3064	0.5580	2.6671	0.9168	1.6053	1.8309	6.9824	0.5561
	Rf5155	0.0726	0.1769	0.4409	3.0801	0.9809	1.5651	1.8252	7.2496	0.7211
G2, M & 500	Rf5156	0.0537	0.2634	0.3919	2.5411	0.7432	1.7923	1.8153	6.3285	0.5401
	Rf5157	0.0326	0.1883	0.6190	2.8588	0.8178	1.6939	1.8890	6.8429	0.4552
	Rf5158	0.0721	0.4313	0.3995	3.0012	0.7925	1.8727	1.8978	6.8341	0.4821
	Rf5159	0.0423	0.1452	0.2420	3.3214	0.7453	1.4531	1.8027	5.4238	0.5285
	Rf5160	0.0494	0.4223	0.3221	2.9071	0.8472	1.5993	1.7108	6.1794	0.7049
G3, M & 1500	Rf5161	0.0512	0.2106	0.4652	3.3737	0.7668	1.8271	1.8363	7.1458	0.4516
	Rf5162	0.0386	0.1341	0.2731	2.1441	0.6234	1.4675	1.8042	4.9567	0.5679
	Rf5163	0.0427	0.1464	0.3125	2.7339	0.5776	1.2572	1.5723	5.1224	0.4175
	Rf5164	0.0501	0.1640	0.3049	2.8845	0.7142	1.5728	1.7088	5.6457	0.4454
	Rf5165	0.0503	0.1674	0.3773	3.2006	0.8328	1.8016	1.7859	7.0728	0.5948
G4, M & 5000	Rf5166	0.0569	0.2736	0.3739	3.1586	0.6995	1.5582	1.7031	6.2373	0.7015
	Rf5167	0.0391	0.1701	0.2756	2.8112	0.6611	1.5492	1.6748	5.8618	0.5257
	Rf5168	0.0630	0.1538	0.4049	2.8425	0.7572	1.9896	1.9215	7.4396	0.6023
	Rf5169	0.0550	0.1716	0.3641	2.6731	0.7124	1.4863	1.8044	5.9102	0.6687
	Rf5170	0.0633	0.1912	0.3837	2.8323	0.7207	1.6468	1.9135	5.9985	0.5309

M: Male.

APPENDIX 14 (Contd…). INDIVIDUAL ANIMAL ABSOLUTE ORGAN WEIGHT (g)RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Adrenals	Thymus	Spleen	Ovaries	Uterus	Heart	Kidneys	Brain	Liver	Lungs
G1, F & 0	Rf5181	0.0627	0.2727	0.4355	0.0703	0.3680	0.7216	1.1707	1.7332	5.2469	0.4523
	Rf5182	0.0467	0.2719	0.3892	0.0952	0.3066	0.5869	1.0631	1.8246	4.9587	0.4259
	Rf5183	0.0446	0.2982	0.3591	0.0641	0.2446	0.7039	1.1857	1.7911	5.2877	0.4754
	Rf5184	0.0688	0.2698	0.4555	0.1481	0.4757	0.8243	1.7370	1.7856	6.1931	0.4935
	Rf5185	0.0638	0.2828	0.3286	0.0791	0.7852	0.5967	1.1023	1.8123	5.0291	0.5211
G2, F & 500	Rf5186	0.0398	0.2170	0.3114	0.0994	0.4581	0.7307	1.2521	1.7187	5.1613	0.4172
	Rf5187	0.0613	0.3195	0.3345	0.1211	0.5537	0.6342	1.1971	1.6207	5.2594	0.6319
	Rf5188	0.0695	0.0715	0.3634	0.1041	0.4064	0.5851	1.2441	1.5873	5.3437	0.4361
	Rf5189	0.0675	0.3013	0.4770	0.1288	0.3710	0.8555	1.3172	1.6906	6.4350	0.4422
	Rf5190	0.0598	0.2123	0.3944	0.1493	0.8869	0.6259	1.1501	1.8692	5.5141	0.4102
G3, F & 1500	Rf5191	0.0631	0.2336	0.4570	0.0747	0.3270	0.5694	1.0944	1.6441	4.9366	0.5001
	Rf5192	0.0517	0.2890	0.6075	0.0862	0.2735	0.6071	1.2818	1.6935	5.6107	0.4379
	Rf5193	0.0630	0.0988	0.7025	0.1110	0.2622	0.6084	1.3305	1.7586	5.5879	0.4305
	Rf5194	0.0754	0.2635	0.3421	0.1104	0.3566	0.6933	1.3881	1.8196	5.9902	0.5514
	Rf5195	0.0687	0.1831	0.3659	0.1088	0.3563	0.7418	1.3133	1.7733	5.6710	0.4188
G4, F & 5000	Rf5196	0.0387	0.1719	0.2808	0.0766	0.2821	0.5742	1.1476	1.7826	4.3365	0.3901
	Rf5197	0.0461	0.1475	0.3542	0.1335	0.3953	0.6151	1.1496	1.6536	4.7440	0.3454
	Rf5198	0.0712	0.2889	0.4586	0.0813	0.2966	0.6698	1.3060	1.7927	5.2314	0.5821
	Rf5199	0.0549	0.1671	0.5928	0.0897	0.2951	0.5872	1.2040	1.6936	5.7579	0.4602
	Rf5200	0.0379	0.1961	0.8220	0.0772	0.1344	0.5857	1.1239	1.3843	5.1377	0.4132

F: Female.

APPENDIX 14 (Contd…). INDIVIDUAL ANIMAL ABSOLUTE ORGAN WEIGHT (g)RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Adrenals	Thymus	Spleen	Testes	Heart	Kidneys	Brain	Liver	Lungs
G1R, M & 0	Rf5171	0.0554	0.1482	0.4478	2.7035	0.9877	1.8251	1.7724	7.6153	0.5528
	Rf5172	0.0519	0.2118	0.5105	3.0125	0.9528	1.1625	1.8637	7.6415	0.5121
	Rf5173	0.0651	0.2958	0.5681	2.9951	0.9360	1.7284	1.8528	8.3163	0.4995
	Rf5174	0.0541	0.3421	0.5636	3.3021	1.0402	2.0883	1.9121	8.9425	0.6823
	Rf5175	0.0530	0.3179	0.5054	3.2659	1.0935	2.1651	1.9127	9.0251	0.6255
G4R, M & 5000	Rf5176	0.0529	0.2951	0.4995	3.1029	0.8728	1.9059	1.8418	8.1562	0.5721
	Rf5177	0.0584	0.2382	0.4678	2.8251	0.8682	1.6995	1.7925	7.9521	0.5623
	Rf5178	0.0572	0.2357	0.4298	2.9523	0.8751	1.8105	1.8257	7.8998	0.7421
	Rf5179	0.0528	0.2856	0.4762	2.9674	0.8762	1.7680	1.9651	7.5144	0.5313
	Rf5180	0.0674	0.2451	0.4325	2.9954	0.8399	1.8329	1.8467	8.0215	0.6160

M: Male; R: Recovery.

APPENDIX 14 (Contd…). INDIVIDUAL ANIMAL ABSOLUTE ORGAN WEIGHT (g)RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Adrenals	Thymus	Spleen	Ovaries	Uterus	Heart	Kidneys	Brain	Liver	Lungs
G1R, F & 0	Rf5201	0.0412	0.2851	0.5246	0.1186	0.8009	0.8559	1.5396	1.7032	6.6895	0.5723
	Rf5202	0.0525	0.2845	0.4251	0.1187	0.6095	0.7239	1.2771	1.8125	5.9523	0.4251
	Rf5203	0.0592	0.2583	0.4521	0.1128	0.9951	0.7451	1.3854	1.8025	6.5462	0.5401
	Rf5204	0.0521	0.2458	0.4258	0.1227	0.6451	0.7953	1.4453	1.7952	6.1051	0.4221
	Rf5205	0.0592	0.2805	0.4819	0.1425	0.7333	0.7137	1.2794	1.8215	6.7544	0.4799
G4R, F & 5000	Rf5206	0.0628	0.2944	0.3999	0.0960	0.6251	0.7178	1.6625	1.7251	6.6669	0.4417
	Rf5207	0.0600	0.2972	0.3830	0.0976	0.6102	0.8188	1.4272	1.7526	7.0354	0.5717
	Rf5208	0.0581	0.2805	0.5307	0.1128	0.8992	0.8022	1.5326	1.8373	7.2589	0.6101
	Rf5209	0.0592	0.3021	0.4526	0.1705	0.6022	0.7468	1.5823	1.7912	6.5921	0.6452
	Rf5210	0.0596	0.2682	0.5230	0.1144	0.7292	0.7949	1.4980	1.6369	5.8619	0.6031

F: Female R: Recovery.

APPENDIX 15. INDIVIDUAL ANIMAL ORGAN WEIGHT RELATIVE TO FASTING BODY WEIGHT (%) RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Fasting Body Weight (g)	Adrenals	Thymus	Spleen	Testes	Heart	Kidneys	Brain	Liver	Lungs
G1, M & 0	Rf5151	203.38	0.0257	0.1697	0.2072	1.4393	0.3823	0.7724	0.8624	3.1705	0.3056
	Rf5152	218.45	0.0269	0.1101	0.1665	1.3733	0.3972	0.7361	0.8103	2.9258	0.2810
	Rf5153	212.22	0.0218	0.1536	0.2321	1.4786	0.4047	0.7983	0.8732	3.0867	0.2727
	Rf5154	209.12	0.0291	0.1465	0.2668	1.2754	0.4384	0.7676	0.8755	3.3389	0.2659
	Rf5155	213.94	0.0339	0.0827	0.2061	1.4397	0.4585	0.7316	0.8531	3.3886	0.3371
G2, M & 500	Rf5156	203.55	0.0264	0.1294	0.1925	1.2484	0.3651	0.8805	0.8918	3.1091	0.2653
	Rf5157	205.87	0.0158	0.0915	0.3007	1.3886	0.3972	0.8228	0.9176	3.3239	0.2211
	Rf5158	202.60	0.0356	0.2129	0.1972	1.4813	0.3912	0.9243	0.9367	3.3732	0.2380
	Rf5159	209.68	0.0202	0.0692	0.1154	1.5840	0.3554	0.6930	0.8597	2.5867	0.2521
	Rf5160	214.39	0.0230	0.1970	0.1502	1.3560	0.3952	0.7460	0.7980	2.8823	0.3288
G3, M & 1500	Rf5161	194.29	0.0264	0.1084	0.2394	1.7364	0.3947	0.9404	0.9451	3.6779	0.2324
	Rf5162	193.60	0.0199	0.0693	0.1411	1.1075	0.3220	0.7580	0.9319	2.5603	0.2933
	Rf5163	183.44	0.0233	0.0798	0.1704	1.4904	0.3149	0.6853	0.8571	2.7924	0.2276
	Rf5164	211.87	0.0236	0.0774	0.1439	1.3614	0.3371	0.7423	0.8065	2.6647	0.2102
	Rf5165	222.60	0.0226	0.0752	0.1695	1.4378	0.3741	0.8093	0.8023	3.1774	0.2672
G4, M & 5000	Rf5166	196.12	0.0290	0.1395	0.1906	1.6105	0.3567	0.7945	0.8684	3.1803	0.3577
	Rf5167	198.96	0.0197	0.0855	0.1385	1.4129	0.3323	0.7786	0.8418	2.9462	0.2642
	Rf5168	194.59	0.0324	0.0790	0.2081	1.4608	0.3891	1.0225	0.9875	3.8232	0.3095
	Rf5169	198.38	0.0277	0.0865	0.1835	1.3475	0.3591	0.7492	0.9096	2.9792	0.3371
	Rf5170	223.16	0.0284	0.0857	0.1719	1.2692	0.3230	0.7379	0.8575	2.6880	0.2379

M: Male.

APPENDIX 15 (Contd…). INDIVIDUAL ANIMAL ORGAN WEIGHT RELATIVE TO FASTING BODY WEIGHT (%) RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Fasting Body Weight (g)	Adrenals	Thymus	Spleen	Ovaries	Uterus	Heart	Kidneys	Brain	Liver	Lungs
G1, F & 0	Rf5181	163.43	0.0384	0.1669	0.2665	0.0430	0.2252	0.4415	0.7163	1.0605	3.2105	0.2768
	Rf5182	167.11	0.0279	0.1627	0.2329	0.0570	0.1835	0.3512	0.6362	1.0919	2.9673	0.2549
	Rf5183	166.27	0.0268	0.1793	0.2160	0.0386	0.1471	0.4233	0.7131	1.0772	3.1802	0.2859
	Rf5184	176.62	0.0390	0.1528	0.2579	0.0839	0.2693	0.4667	0.9835	1.0110	3.5065	0.2794
	Rf5185	175.93	0.0363	0.1607	0.1868	0.0450	0.4463	0.3392	0.6266	1.0301	2.8586	0.2962
G2, F & 500	Rf5186	156.35	0.0255	0.1388	0.1992	0.0636	0.2930	0.4673	0.8008	1.0993	3.3011	0.2668
	Rf5187	161.46	0.0380	0.1979	0.2072	0.0750	0.3429	0.3928	0.7414	1.0038	3.2574	0.3914
	Rf5188	177.21	0.0392	0.0403	0.2051	0.0587	0.2293	0.3302	0.7020	0.8957	3.0155	0.2461
	Rf5189	178.27	0.0379	0.1690	0.2676	0.0722	0.2081	0.4799	0.7389	0.9483	3.6097	0.2481
	Rf5190	175.55	0.0341	0.1209	0.2247	0.0850	0.5052	0.3565	0.6551	1.0648	3.1410	0.2337
G3, F & 1500	Rf5191	159.62	0.0395	0.1463	0.2863	0.0468	0.2049	0.3567	0.6856	1.0300	3.0927	0.3133
	Rf5192	167.80	0.0308	0.1722	0.3620	0.0514	0.1630	0.3618	0.7639	1.0092	3.3437	0.2610
	Rf5193	170.11	0.0370	0.0581	0.4130	0.0653	0.1541	0.3577	0.7821	1.0338	3.2849	0.2531
	Rf5194	177.65	0.0424	0.1483	0.1926	0.0621	0.2007	0.3903	0.7814	1.0243	3.3719	0.3104
	Rf5195	180.09	0.0381	0.1017	0.2032	0.0604	0.1978	0.4119	0.7292	0.9847	3.1490	0.2326
G4, F & 5000	Rf5196	160.36	0.0241	0.1072	0.1751	0.0478	0.1759	0.3581	0.7156	1.1116	2.7042	0.2433
	Rf5197	166.62	0.0277	0.0885	0.2126	0.0801	0.2372	0.3692	0.6900	0.9924	2.8472	0.2073
	Rf5198	168.15	0.0423	0.1718	0.2727	0.0483	0.1764	0.3983	0.7767	1.0661	3.1112	0.3462
	Rf5199	171.43	0.0320	0.0975	0.3458	0.0523	0.1721	0.3425	0.7023	0.9879	3.3587	0.2684
	Rf5200	170.24	0.0223	0.1152	0.4828	0.0453	0.0789	0.3440	0.6602	0.8131	3.0179	0.2427

F: Female.

APPENDIX 15 (Contd…). INDIVIDUAL ANIMAL ORGAN WEIGHT RELATIVE TO FASTING BODY WEIGHT (%) RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Fasting Body Weight (g)	Adrenals	Thymus	Spleen	Testes	Heart	Kidneys	Brain	Liver	Lungs
G1R, M & 0	Rf5171	253.54	0.0219	0.0585	0.1766	1.0663	0.3896	0.7198	0.6991	3.0036	0.2180
	Rf5172	254.89	0.0204	0.0831	0.2003	1.1819	0.3738	0.4561	0.7312	2.9980	0.2009
	Rf5173	261.64	0.0249	0.1131	0.2171	1.1447	0.3577	0.6606	0.7081	3.1785	0.1909
	Rf5174	263.76	0.0205	0.1297	0.2137	1.2519	0.3944	0.7917	0.7249	3.3904	0.2587
	Rf5175	266.99	0.0199	0.1191	0.1893	1.2232	0.4096	0.8109	0.7164	3.3803	0.2343
G4R, M & 5000	Rf5176	247.61	0.0214	0.1192	0.2017	1.2531	0.3525	0.7697	0.7438	3.2940	0.2310
	Rf5177	239.74	0.0244	0.0994	0.1951	1.1784	0.3621	0.7089	0.7477	3.3170	0.2345
	Rf5178	260.28	0.0220	0.0906	0.1651	1.1343	0.3362	0.6956	0.7014	3.0351	0.2851
	Rf5179	243.20	0.0217	0.1174	0.1958	1.2201	0.3603	0.7270	0.8080	3.0898	0.2185
	Rf5180	271.48	0.0248	0.0903	0.1593	1.1034	0.3094	0.6752	0.6802	2.9547	0.2269

M: Male; R: Recovery.

APPENDIX 15 (Contd…). INDIVIDUAL ANIMAL ORGAN WEIGHT RELATIVE TO FASTING BODY WEIGHT (%) RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Fasting Body Weight (g)	Adrenals	Thymus	Spleen	Ovaries	Uterus	Heart	Kidneys	Brain	Liver	Lungs
G1R, F & 0	Rf5201	207.55	0.0199	0.1374	0.2528	0.0571	0.3859	0.4124	0.7418	0.8206	3.2231	0.2757
	Rf5202	213.50	0.0246	0.1333	0.1991	0.0556	0.2855	0.3391	0.5982	0.8489	2.7880	0.1991
	Rf5203	216.91	0.0273	0.1191	0.2084	0.0520	0.4588	0.3435	0.6387	0.8310	3.0179	0.2490
	Rf5204	211.49	0.0246	0.1162	0.2013	0.0580	0.3050	0.3760	0.6834	0.8488	2.8867	0.1996
	Rf5205	209.45	0.0283	0.1339	0.2301	0.0680	0.3501	0.3407	0.6108	0.8697	3.2248	0.2291
G4R, F & 5000	Rf5206	211.63	0.0297	0.1391	0.1890	0.0454	0.2954	0.3392	0.7856	0.8151	3.1503	0.2087
	Rf5207	216.76	0.0277	0.1371	0.1767	0.0450	0.2815	0.3777	0.6584	0.8085	3.2457	0.2637
	Rf5208	208.02	0.0279	0.1348	0.2551	0.0542	0.4323	0.3856	0.7368	0.8832	3.4895	0.2933
	Rf5209	207.92	0.0285	0.1453	0.2177	0.0820	0.2896	0.3592	0.7610	0.8615	3.1705	0.3103
	Rf5210	218.36	0.0273	0.1228	0.2395	0.0524	0.3339	0.3640	0.6860	0.7496	2.6845	0.2762

F: Female; R: Recovery.

APPENDIX 16.INDIVIDUAL ANIMAL ORGAN WEIGHT RELATIVE TO BRAIN WEIGHT (%) RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Adrenals	Thymus	Spleen	Testes	Heart	Kidneys	Liver	Lungs
G1, M & 0	Rf5151	2.9818	19.6807	24.0308	166.8871	44.3273	89.5667	367.6226	35.4333
	Rf5152	3.3164	13.5932	20.5480	169.4859	49.0226	90.8475	361.1017	34.6836
	Rf5153	2.4985	17.5867	26.5771	169.3325	46.3440	91.4252	353.4941	31.2341
	Rf5154	3.3208	16.7349	30.4768	145.6715	50.0737	87.6782	381.3644	30.3730
	Rf5155	3.9776	9.6921	24.1563	168.7541	53.7421	85.7495	397.1948	39.5080
G2, M & 500	Rf5156	2.9582	14.5100	21.5887	139.9824	40.9409	98.7330	348.6201	29.7527
	Rf5157	1.7258	9.9682	32.7687	151.3393	43.2927	89.6718	362.2499	24.0974
	Rf5158	3.7991	22.7263	21.0507	158.1410	41.7589	98.6774	360.1064	25.4031
	Rf5159	2.3465	8.0546	13.4243	184.2459	41.3435	80.6069	300.8709	29.3171
	Rf5160	2.8875	24.6844	18.8274	169.9264	49.5207	93.4826	361.1994	41.2029
G3, M & 1500	Rf5161	2.7882	11.4687	25.3336	183.7227	41.7579	99.4990	389.1412	24.5929
	Rf5162	2.1395	7.4327	15.1369	118.8394	34.5527	81.3380	274.7312	31.4766
	Rf5163	2.7158	9.3112	19.8753	173.8790	36.7360	79.9593	325.7902	26.5535
	Rf5164	2.9319	9.5974	17.8429	168.8027	41.7954	92.0412	330.3897	26.0651
	Rf5165	2.8165	9.3734	21.1266	179.2150	46.6320	100.8791	396.0356	33.3053
G4, M & 5000	Rf5166	3.3410	16.0648	21.9541	185.4618	41.0722	91.4920	366.2322	41.1896
	Rf5167	2.3346	10.1564	16.4557	167.8529	39.4734	92.5006	350.0000	31.3888
	Rf5168	3.2787	8.0042	21.0721	147.9313	39.4067	103.5441	387.1767	31.3453
	Rf5169	3.0481	9.5101	20.1785	148.1434	39.4813	82.3709	327.5438	37.0594
	Rf5170	3.3081	9.9922	20.0523	148.0167	37.6640	86.0622	313.4831	27.7450

M: Male

APPENDIX 16 (Contd…). INDIVIDUAL ANIMAL ORGAN WEIGHT RELATIVE TO BRAIN WEIGHT (%) RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Adrenals	Thymus	Spleen	Ovaries	Uterus	Heart	Kidneys	Liver	Lungs
G1, F & 0	Rf5181	3.6176	15.7339	25.1269	4.0561	21.2324	41.6340	67.5456	302.7291	26.0962
	Rf5182	2.5595	14.9019	21.3307	5.2176	16.8037	32.1660	58.2648	271.7692	23.3421
	Rf5183	2.4901	16.6490	20.0491	3.5788	13.6564	39.2999	66.1995	295.2208	26.5423
	Rf5184	3.8530	15.1098	25.5096	8.2941	26.6409	46.1638	97.2782	346.8358	27.6378
	Rf5185	3.5204	15.6045	18.1317	4.3646	43.3262	32.9250	60.8233	277.4982	28.7535
G2, F & 500	Rf5186	2.3157	12.6258	18.1183	5.7834	26.6539	42.5147	72.8516	300.3026	24.2742
	Rf5187	3.7823	19.7137	20.6392	7.4721	34.1643	39.1312	73.8631	324.5141	38.9893
	Rf5188	4.3785	4.5045	22.8942	6.5583	25.6032	36.8613	78.3784	336.6534	27.4743
	Rf5189	3.9927	17.8221	28.2148	7.6186	21.9449	50.6033	77.9132	380.6341	26.1564
	Rf5190	3.1992	11.3578	21.0999	7.9874	47.4481	33.4849	61.5290	294.9979	21.9452
G3, F & 1500	Rf5191	3.8380	14.2084	27.7964	4.5435	19.8893	34.6329	66.5653	300.2615	30.4179
	Rf5192	3.0528	17.0652	35.8725	5.0901	16.1500	35.8488	75.6894	331.3079	25.8577
	Rf5193	3.5824	5.6181	39.9465	6.3118	14.9096	34.5957	75.6568	317.7471	24.4797
	Rf5194	4.1438	14.4812	18.8008	6.0673	19.5977	38.1018	76.2860	329.2042	30.3034
	Rf5195	3.8741	10.3254	20.6338	6.1355	20.0925	41.8316	74.0597	319.7992	23.6170
G4, F & 5000	Rf5196	2.1710	9.6432	15.7523	4.2971	15.8252	32.2114	64.3779	243.2683	21.8838
	Rf5197	2.7879	8.9199	21.4199	8.0733	23.9054	37.1976	69.5210	286.8892	20.8878
	Rf5198	3.9717	16.1154	25.5815	4.5351	16.5449	37.3626	72.8510	291.8168	32.4706
	Rf5199	3.2416	9.8666	35.0024	5.2964	17.4244	34.6717	71.0912	339.9799	27.1729
	Rf5200	2.7378	14.1660	59.3802	5.5768	9.7089	42.3102	81.1890	371.1406	29.8490

F: Female

APPENDIX 16 (Contd…). INDIVIDUAL ANIMAL ORGAN WEIGHT RELATIVE TO BRAIN WEIGHT (%) RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Adrenals	Thymus	Spleen	Testes	Heart	Kidneys	Liver	Lungs
G1R, M & 0	Rf5171	3.1257	8.3615	25.2652	152.5333	55.7267	102.9734	429.6603	31.1893
	Rf5172	2.7848	11.3645	27.3917	161.6408	51.1241	62.3759	410.0177	27.4776
	Rf5173	3.5136	15.9650	30.6617	161.6526	50.5181	93.2858	448.8504	26.9592
	Rf5174	2.8293	17.8913	29.4754	172.6949	54.4009	109.2150	467.6795	35.6833
	Rf5175	2.7710	16.6205	26.4234	170.7482	57.1705	113.1960	471.8513	32.7025
G4R, M & 5000	Rf5176	2.8722	16.0224	27.1202	168.4711	47.3884	103.4803	442.8385	31.0620
	Rf5177	3.2580	13.2887	26.0976	157.6067	48.4351	94.8117	443.6318	31.3696
	Rf5178	3.1330	12.9101	23.5417	161.7078	47.9323	99.1674	432.6998	40.6474
	Rf5179	2.6869	14.5336	24.2329	151.0050	44.5881	89.9700	382.3928	27.0368
	Rf5180	3.6498	13.2723	23.4202	162.2028	45.4811	99.2527	434.3694	33.3568

M: Male; R: Recovery.

APPENDIX 16 (Contd…). INDIVIDUAL ANIMAL ORGAN WEIGHT RELATIVE TO BRAIN WEIGHT (%) RECORD

Group, Sex & Concentration (mg/m³)	Animal No.	Adrenals	Thymus	Spleen	Ovaries	Uterus	Heart	Kidneys	Liver	Lungs
G1R, F & 0	Rf5201	2.4190	16.7391	30.8008	6.9634	47.0233	50.2525	90.3946	392.7607	33.6015
	Rf5202	2.8966	15.6966	23.4538	6.5490	33.6276	39.9393	70.4607	328.4028	23.4538
	Rf5203	3.2843	14.3301	25.0818	6.2580	55.2067	41.3370	76.8599	363.1734	29.9639
	Rf5204	2.9022	13.6921	23.7188	6.8349	35.9347	44.3015	80.5091	340.0791	23.5127
	Rf5205	3.2501	15.3994	26.4562	7.8232	40.2580	39.1820	70.2388	370.8153	26.3464
G4R, F & 5000	Rf5206	3.6404	17.0657	23.1813	5.5649	36.2356	41.6092	96.3712	386.4646	25.6043
	Rf5207	3.4235	16.9577	21.8532	5.5689	34.8168	46.7192	81.4333	401.4265	32.6201
	Rf5208	3.1622	15.2670	28.8848	6.1394	48.9414	43.6619	83.4159	395.0852	33.2063
	Rf5209	3.3050	16.8658	25.2680	9.5188	33.6199	41.6927	88.3374	368.0270	36.0205
	Rf5210	3.6410	16.3846	31.9506	6.9888	44.5476	48.5613	91.5144	358.1098	36.8440

F: Female; R: Recovery

Applicant's summary and conclusion

Conclusions:

Based on the observed results, it is concluded that the No Observed Adverse Effect Concentration (NOAEC) of test item was found to be 5000 mg/m3 when exposed for 6 hours/day 5 days/week, for 4 weeks by flow-past nose-only inhalation route to Sprague Dawley rats. The actual (analytically verified) mean concentration was 5040 mg/m3 (6 hrs/day, 5 days/week) equal to an actual exposure concentration in males and females.

Executive summary:

The objective of this study was to determine the toxic potential of the test item, when administered for 6 hours/day, 5 days per week, for 4 consecutive weeks by flow-past nose-only inhalation route to Sprague Dawley rats. This study provides information on toxic effects, target organs, the possibility of cumulative effects, the reversibility of effects (after 14 days recovery period), and an estimate of the No Observed Adverse Effects Concentration (NOAEC).

A total of 60 (30 males + 30 females) healthy young Sprague Dawley rats were distributed to four groups viz., control (G1), low dose (G2), mid dose (G3), high dose (G4) and two recovery groups [(G1R (Air only) and G4R (high dose)]. Each main and recovery group comprised of 10 animals (5 males and 5 females). Animals allocated to groups G2, G3 and G4/G4R were exposed to test item for 6 hours per day, 5 days per week, for 4 consecutive weeks., at a nominal target concentration of 500, 1500 and 5000 mg/m3. Animals of the control group (G1/G1R) received air only inhalation for 6 hours/day for 04 consecutive weeks. The inhalation exposure of test item/air was achieved by a flow-past, nose-only dynamic inhalation exposure system supplied by CH Technologies, USA.

Addionally to the usual set of endpoints, at the end of treatment and recovery periods all animals were fasted overnight (water was availablead libitum), and the next day, blood, urine, and Broncho alveolar lavage fluid (BALF) samples were collected and analysed. Subsequently, the animals were sacrificed and subjected to gross pathological examination, and the organs were collected, weighed, and preserved. The tissues/organs in vehicle control and high dose group animals including recovery animals were subjected to histopathological examinations.

No clinical signs of toxicity or mortality/morbidity were noted in any of the treated and recovery group animals. During exposure, black faeces was observed, from 3rd hour to end of exposure period and during post exposure 30-40 minutes and 1 hour in G4/G4R group animals from days 2 to 5, days 9 to 12, days 16 to 19, days 23 to 26 and on days 6, 13, 20, 27. The coloration of faeces is because of the colouration of test item, hence considered as non-adverse.

No treatment-related changes in body weight, percent change in body weight with respect to day 1, feed consumption,or ophthalmology were noted.No adverse effects were observed in the neurological/functional examination tests.No adverse effects were observed in haematology, clinical chemistry, coagulationor urinalysis parameters.

During BALF analysis, few significant changes were noted in the differential counts and WBC counts which are considered to be secondary to the accumulation of test item particles in the lungs, however, they are considered non adverse in the absence of any adverse microscopic changes in the lungs.

No toxicologically significant changes were observed infasting body weight,organ weight and its ratios.

During gross pathology, blackish discoloration of lungs in mid (Male: 3/5, Female: 4/5), high (Male: 5/5, Female: 5/5) and high dose recovery (Male: 5/5, Female: 5/5) group of rats in both sexes and blackish contents in caecum of high dose (Male: 5/5, Female: 5/5) rats was observed. This blackish discoloration was attributed to physical appearance (solid black)of inhaled test item which might have imparted discoloration to the tissues.

Microscopically, test item-related changes were observed in lungs. In lungs, minimal to mild, multifocal, variably sized, pigmented (blackish brown) granular material was observed throughout the parenchyma of lung at mid, high and high dose recovery groups of rats. This pigment was distributed both in alveolar and bronchiolar spaces with no accompanying inflammation or tissue destruction to the lung parenchyma. This pigment was suggestive of inhaled test item particles as the physical appearance of test item was also black coloured powder. In the absence of cellular changes to lung parenchyma, mere presence of pigment in lungs could be considered as non-adverse effect up to the dose level of 5000 mg/m3(Nikula KJet.al., 2014)

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MoVNbTe mixed oxide

Repeated dose toxicity: inhalation

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