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EC number: 200-861-4 | CAS number: 75-33-2
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Not reported
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: This study was classified as reliable without restriction because it was well conducted and documented. The methods, timeframe and selection are the same as the OECD guidelines for subchronic inhalation, and it is compliant with GLP regulations.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 009
- Report date:
- 2009
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- GLP compliance:
- yes
- Limit test:
- yes
Test material
- Reference substance name:
- Butane-2-thiol
- EC Number:
- 208-165-2
- EC Name:
- Butane-2-thiol
- Cas Number:
- 513-53-1
- IUPAC Name:
- butane-2-thiol
- Details on test material:
- - Supplier: Tokyo Chemical Industry (ToKyo, Japan)
- Name of test material (as cited in study report): sec-Butanethiol
- Substance type: C2-C4 Alkyl Mercaptan
- Physical state: Liquid
- Analytical purity: Not reported
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Orient Bio Co. (Seoul, Republic of Korea)
- Age at study initiation: 6 weeks
- Housing: individually in wire-bottomed stainless-steel mesh cages that were placed in exposure chambers
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): 12-15
- Photoperiod (hrs dark / hrs light): 12 / 12
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Details on inhalation exposure:
- The test animals were either exposed to butane-1-thiol or fresh air for 6 h per day, 5 days a week for a period of 13 weeks. The inhalation
exposure was carried out from 10:00 to 16:00 in a stainless-steel chamber (1000 L). The experimental design was based on the usual working
schedule for workers, as well as the major exposure route for the test chemical.
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Gas Generator (Shibata Co. Japan) connected to a whole-body stainless steel exposure chamber (Shibata Co. Japan)
- Method of holding animals in test chamber: Animals were housed individually in wire-bottom stainless steel cages that were placed inside the exposure chambers.
- Source and rate of air: Not reported
- Method of conditioning air: Air mixed with sec-butanethiol vapors conditioned at 30°C by passage through a thermostatted condenser
- System of generating particulates/aerosols: Fresh air was bubbled through the liquid sec-butanethiol to generate sec-butanethiol vapor-air mixture.
TEST ATMOSPHERE
- Brief description of analytical method used: The apparatus and conditions used for detecting sec-butanethiol by gas chromatography (Shimadzu Co., Japan) were as follows: detector, flame ionization detector; column, 0.5 m silicon DC-200 15% chromosorb with a mesh of 80/100; detector temperature, 150°C; oven temperature, 130°C; oven temperature, 200°C; injector temperature, 200°C; and injection volume, 1 ml of sample gas.
- Samples taken from breathing zone: yes
VEHICLE (if applicable)
- Vehicle: Fresh air - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The mean concentration was measured by gas chromatography every 30 min for 6 h and was taken as the concentration value for each day. This was then averaged over the 13-week exposure period in order to obtain the mean and standard deviations.
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- 6 hrs per day, 5 days per week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 25 ppm
- Remarks:
- 92.6 mg/m³ air (analytical)
- Dose / conc.:
- 100 ppm
- Remarks:
- 367.4 mg/m³ air (analytical)
- Dose / conc.:
- 400 ppm
- Remarks:
- 1488.2 mg/m³ air (analytical)
- No. of animals per sex per dose:
- 10 per sex per dose
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Dose selection rationale: The experimental concentrations were selected based on the results of a preliminary dose-range finding study in which rats (5/sex/dose) were exposed to sec-butanethiol via whole-body inhalation at concentrations of 62.5, 125, 250, and 500 ppm for 2 weeks. At a concentration of 500 ppm, both males and females showed suppressed body weight gain and decreased food intake. A dose of 250 ppm produced only a slight decrease in body weight gain. On the contrary, there were no treatment-related effects of clinical signs, body weight, or food intake at =125 ppm. On the basis of these results, 400 ppm was used as the high dose, and the doses of 100 and 25 ppm were selected as medium and low doses, respectively, using a scaling factor of 4.
- Rationale for animal assignment (if not random): Random assignment
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily (before and after exposure)
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Twice daily (before and after exposure)
BODY WEIGHT: Yes
- Time schedule for examinations: Prior to beginning of exposure and once/week during the experimental period.
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes (The amounts of food were calculated before they were supplied to the cages, and the remnants were measured the next day in order to calculate the difference, which was regarded as daily food consumption (g/rat/day)).
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Prior to exposure and during the last week of the experimental period.
- Dose groups that were examined: All animals in each dose group
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Prior to sacrifice
- Anaesthetic used for blood collection: Yes (ether)
- Animals fasted: Yes
- How many animals: 10/sex/dose
- Parameters checked in table [No.1] in the results section were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Prior to sacrifice
- Animals fasted: Yes
- How many animals: 10/sex/dose
- Parameters checked in table [No.2] in the results section were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: During last week of exposure
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters such as specific gravity, pH, protein, glucose, ketone body, occult blood, bilirubin, urobilinogen, nitrite, and leukocyte contents were examined.
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
ORGAN WEIGHTS: Yes
400 ppm concentrations of sec-butanethiol and a vehicle control group exposed to
fresh air only. Each group consisted of 10 rats of each gender.
The absolute and relative (organ-to-body weight ratios) weights of the following organs were measured: brain, heart, thymus, lung, liver, spleen, kidney, adrenal, testis, epididymis, and/or ovary.
HISTOPATHOLOGY: Yes
The following tissues were obtained from all animals: skin, mammary gland, spleen, pancreas, jejunum, stomach, duodenum, ileum, cecum, colon, mesenteric lymph node, salivary gland, submandibular lymph node, ovaries, uterus, vagina, urinary bladder, epididymides, prostates, seminal vesicles, rectum, kidneys, adrenal glands, liver, sternum, thymus, heart, lung, trachea, esophagus, thyroids (including parathyroids), tongue, aorta, sciatic nerve, skeletal muscle, femur, thoracic spinal cord, Harderian glands, brain, pituitary gland, eyes, testes, nasal cavity, nasal turbinates, and Zymbal glands. Eyes and testes were preserved in Davidson’s ¿xative and Bouin’s ¿xative, respectively. Other tissues were ¿xed with a 10% neutral buffered formalin solution. The tissues were routinely processed, embedded in paraf¿n, and sectioned at 3–5 lm. The sections were stained with hematoxylin–eosin for microscopic examination. The nasal passages and nasal turbinates were decalci¿ed prior to being embedded and sectioned. The nasal cavity was sectioned at levels posterior to the upper incisors, the incisive papilla, the second palatine ridge, and the ¿rst molar teeth (Young, 1981). All the organs and tissues removed from the animals in the vehicle control group and the treatment groups were examined microscopically. All gross lesions, as de¿ned in the study of pathology, were also included in the examination. - Statistics:
- The variance of numerical data was checked using Bartlett’s test (1937). For homogeneous variances, data was subjected to a one-way analysis of variance (ANOVA) and, for non-homogenous variances; data was analyzed by Kruskal-Wallis’ non-parametric ANOVA (1952). If either of the tests showed a significant difference among the groups, the data was analyzed by the multiple comparison procedure of the Dunnett’s post-hoc test (1964). Clinical signs, necropsy findings, and histopathological findings were represented as frequencies, and were subjected to Fisher’s exact probability test (1970) where necessary. All statistical analyses were conducted with Statistical Analysis Software (SAS Institute, Inc., 1997). The significant probability values P < 0.05 (*) or P < 0.01 (**) are represented with asterisks.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No treatment-related toxic symptoms was observed in any of the animals treated with sec-butanethiol
- Mortality:
- no mortality observed
- Description (incidence):
- No mortality was observed in any of the animals treated with sec-butanethiol
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Although not statistically significant, the body weight of male rats was slightly lower in the 400 ppm group from Day 7 of the test to termination when compared to the control group. In contrast, the body weight of male rats was slightly higher in the 25 ppm group from Day 14 of the test to termination when compared with the control group. Statistically significant suppression of body weight gain was observed in female rats on days 28 and 42 to 90 of treatment in the 25 ppm group, and on days 14 through 90 of treatment in the 400 ppm group when compared to control animals.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- In males, the amount of food consumed was significantly lower on Days 0 and 7 of treatment in the 400 ppm group (11.7 ± 3.9 and 20.7 ± 1.5 g) than in the control group (22.6 ± 2.4 and 24.3 ± 2.3 g). In females, food consumption of the 400 ppm group was also decreased significantly on Days 0 and 7 of treatment (9.6 ± 3.5 and 13.6 ± 1.8 g) than in the control group (18.2 ± 2.7 and 18.8 ± 3.3 g).
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- Ophthalmologic examinations did not show any treatment-related ocular lesions in any of the animals.
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- (Table 1)
RBC, hemoglobin, and hematocrit in male rats were significantly lower in the 400 ppm group than in the control group. On the other hand, MCV was significantly higher, while RBC, hemoglobin, hematocrit, and MCHC were significantly lower in the 400 ppm group of female rats compared with the control group. - Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- (Table 2)
In males, the serum value of ALT in the 400 ppm group decreased significantly, while BUN levels in the 25 ppm group increased significantly compared to the control group. In females, the serum level of ALT decreased significantly, while the total bilirubin increased significantly in the 400 ppm group compared to the control group. - Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- No significant differences were apparent between the treatment groups and the controls for any urinary parameters examined.
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- (Table 3, attached picture)
In males, the relative weights of the liver and kidneys in the 400 ppm group increased significantly in a dose-dependent manner compared to those of the control group. In females, the relative weights of the kidneys, brain, lung, and heart in the 400 ppm group also significantly increased in a dose-dependent manner compared to those of the control group. - Gross pathological findings:
- not specified
- Description (incidence and severity):
- At the scheduled necropsy, there were no treatment-related gross findings in any of the treated animals.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- (Table 4, attached picture)
Histopathological changes were observed in the liver, kidneys, spleen, lung, heart, thymus, adrenals, and nasal turbinates in the treatment groups. Of the histopathological findings observed in this study, the incidences of tubular hyaline droplets, granular cast, pyelonephritis, and tubular degeneration/regeneration in the kidneys and hemosiderin pigment in the spleen were significantly higher in the males of the 400 ppm group than those in the control group, but not in the females of the group. The degree of the histopathological changes observed in the 400 ppm group was slight-to-moderate. The other histopathological findings observed in both genders of the treatment groups were also found in the control group or were determined to be spontaneous changes.
Effect levels
- Dose descriptor:
- NOAEC
- Effect level:
- 367 mg/m³ air (analytical)
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- haematology
- histopathology: non-neoplastic
- organ weights and organ / body weight ratios
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 1
Hematological results of male and female rats after inhalation of butane-2 -thiol for 13 weeks.a
Parameters |
Dosage (ppm) |
|
|
|
|
0 |
25 |
100 |
400 |
No. of rats |
10 |
10 |
10 |
10 |
Male |
||||
RBC (x1012/L) |
9.21 ± 0.55 |
9.15 ± 0.32 |
9.10 ± 0.33 |
8.46 ± 0.40** |
HB (g/dl) |
15.96 ± 0.54 |
15.82 ± 0.46 |
15.95 ± 0.49 |
15.11 ± 0.64** |
HCT (%) |
45.06 ± 2.55 |
44.06 ± 1.53 |
44.56 ± 1.61 |
42.22 ± 2.39* |
MCV (fl) |
48.95 ± 1.51 |
48.18 ± 1.42 |
48.97 ± 1.15 |
49.88 ± 1.40 |
MCH (pg) |
17.36 ± 0.75 |
17.29 ± 0.42 |
17.55 ± 0.54 |
17.87 ± 0.81 |
MCHC (g/dl) |
35.48 ± 1.13 |
35.94 ± 0.82 |
35.81 ± 0.70 |
35.81 ± 0.74 |
PLT (x109/L) |
1167.80 ± 154.88 |
1085.90 ± 75.83 |
1063.60 ± 100.15 |
1132.80 ± 211.73 |
WBC (x109/L) |
7.22 ± 1.43 |
6.91 ± 2.23 |
7.47 ± 1.49 |
6.60 ± 1.26 |
Female |
||||
RBC (x1012/L) |
8.78 ± 0.36 |
8.80 ± 0.33 |
8.72 ± 0.21 |
7.58 ± 0.49** |
HB (g/dl) |
16.47 ± 0.57 |
16.23 ± 0.57 |
16.27 ± 0.47 |
14.33 ± 1.47** |
HCT (%) |
45.48 ± 1.41 |
45.38 ± 1.55 |
45.17 ± 1.76 |
40.54 ± 3.48** |
MCV (fl) |
51.84 ± 1.17 |
51.55 ± 0.94 |
51.77 ± 1.15 |
53.42 ± 1.59** |
MCH (pg) |
18.76 ± 0.34 |
18.45 ± 0.41 |
18.66 ± 0.34 |
18.88 ± 0.95 |
MCHC (g/dl) |
36.18 ± 0.47 |
35.78 ± 0.59 |
36.04 ± 0.69 |
35.32 ± 0.86* |
PLT (x109/L) |
1263.80 ± 128.66 |
1230.60 ± 152.82 |
1084.50 ± 129.72 |
1239.20 ± 403.24 |
WBC (x109/L) |
4.80 ± 1.19 |
5.69 ± 1.43 |
5.85 ± 2.34 |
6.59 ± 2.98 |
RBC, red blood cells; HB, hemoglobin; HCT, hematocrit; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin
concentration; PLT, platelet; and WBC, white blood cells.
a Values are presented as means ± SD.
* Indicates a significant difference at P < 0.05 compared with the control group.
** Indicates a significant difference at P < 0.01 compared with the control group.
Table 2
Serum biochemical findings of male and female rats after inhalation of butane-2 -thiol for 13 weeks.a
Parameters |
Dosage (ppm) |
|
|
|
|
0 |
25 |
100 |
400 |
No. of rats |
10 |
10 |
10 |
10 |
Male |
||||
AST (IU/l) |
75.6 ± 16.45 |
76.5 ± 23.14 |
69.1 ± 8.27 |
65.9 ± 6.44 |
ALT (IU/dl) |
50.9 ± 19.89 |
51.6 ± 19.95 |
43.1 ± 7.77 |
34.2 ± 3.88* |
ALP (mg/dl) |
302.3 ± 76.52 |
313.6 ± 55.56 |
317.3 ± 53.31 |
306.8 ± 71.70 |
BUN (mg/dl) |
16.99 ± 14.8 |
19.35 ± 3.23* |
18.96 ± 2.00 |
19.04 ± 1.27 |
CRTN (mg/dl) |
0.62 ± 0.04 |
0.64 ± 0.05 |
0.66 ± 0.05 |
0.65 ± 0.08 |
GLU (mg/dl) |
225.2 ± 40.93 |
209.8 ± 31.48 |
212.1 ± 32.90 |
223.8 ± 40.27 |
LDH (IU/l) |
371.2 ± 217.67 |
323.6 ± 142.94 |
242.4 ± 134.77 |
382.2 ± 229.16 |
T-CHO (mg/dl) |
72.4 ± 8.92 |
84.2 ± 13.80 |
80.4 ± 11.86 |
71.2 ± 9.91 |
T-BIL182.4 ± 57.88(mg/dl) |
0.03 ± 0.01 |
0.04 ± 0.01 |
0.04 ± 0.01 |
0.04 ± 0.01 |
TP (g/dl) |
6.64 ± 0.31 |
6.82 ± 0.30 |
6.89 ± 0.36 |
6.93 ± 0.52 |
Female |
||||
AST (IU/l) |
97.2 ± 30.69 |
93.9 ± 23.95 |
96.8 ± 49.70 |
85.8 ± 36.82 |
ALT (IU/dl) |
65.3 ± 24.26 |
62.6 ± 16.80 |
52.9 ± 18.18 |
40.2 ± 11.03* |
ALP (mg/dl) |
189.7 ± 98.05 |
216.6 ± 81.05 |
203.9 ± 60.41 |
182.4 ± 57.88 |
BUN (mg/dl) |
16.83 ± 2.04 |
17.51 ± 2.38 |
17.94 ± 2.28 |
17.06 ± 2.31 |
CRTN (mg/dl) |
0.63 ± 0.05 |
0.61 ± 0.06 |
0.65 ± 0.05 |
0.60 ± 0.05 |
GLU (mg/dl) |
173.3 ± 27.20 |
181.0 ± 30.22 |
209.8 ± 35.18 |
196.4 ± 40.45 |
LDH (IU/l) |
359.6 ± 195.40 |
375.9 ± 208.35 |
320.9 ± 155.29 |
288.0 ± 162.82 |
T-CHO (mg/dl) |
115.5 ± 11.70 |
104.5 ± 11.94 |
104.8 ± 16.39 |
104.4 ± 13.41 |
T-BIL (mg/dl) |
0.03 ± 0.01 |
0.04 ± 0.00 |
0.04 ± 0.01 |
0.05 ± 0.02** |
TP (g/dl) |
7.54 ± 0.28 |
7.38 ± 0.30 |
7.25 ± 0.25 |
7.35 ± 0.47 |
AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; BUN, blood urea nitrogen; CRTN, creatinine; GLU, glucose; LDH, lactate dehydrogenase;
T-CHO, total cholesterol; T-BIL, total bilirubin; and TP, total protein.
aValues are presented as means ± SD.
* Indicates a significant difference at P < 0.05 compared with the control group.
** Indicates a significant difference at P < 0.01 compared with the control group.
Applicant's summary and conclusion
- Conclusions:
- Based on the treatment-related effects observed (erythrocyte, kidneys, liver, and nasal turbinates), the NOAEC is 0.37 mg/L (100 ppm).
- Executive summary:
In a 90-day inhalation toxicity study, butane-2 -thiol was administered to 10 sprague-dawly rats/sex/concentration by dynamic whole body exposure at target concentrations of 0, 25, 100 and 400 ppm (0, 92.6, 367.4 and 1488.2 mg/m3 analytical, respectively) for 6 hours per day, 5 days/week for a total of 91 days.
No treatment-related toxic symptoms or mortality were observed in any of the animals treated with butane-2 -thiol during the experimental period. In males, the amount of food consumed was significantly lower on Days 0 and 7 of treatment in the 400 ppm group (11.7 ± 3.9 and 20.7 ± 1.5 g) than in the control group (22.6 ± 2.4 and 24.3 ± 2.3 g). In females, food consumption of the group exposed to 400 ppm was also decreased significantly on Days 0 and 7 of treatment (9.6 ± 3.5 and 13.6 ± 1.8 g) than in the control group (18.2 ± 2.7 and 18.8 ± 3.3 g). Significant decreases in body weight gain were observed in females in the high concentration group and decreases in RBC, haemoglobin and hematocrit levels were reported in both male and female animals in the 400 ppm group. In males, the relative weights of the liver and kidneys in the 400 ppm group were increased significantly in a dose-dependent manner compared to those of the control group. In females, the relative weights of the kidneys, brain, lung, and heart in the 400 ppm group were also significantly increased in a dose-dependent manner compared to those of the control group. No gross pathological changes were observed at necropsy, however histopathological alterations observed predominantly in the 400 ppm group, included centrilobular hepatocyte hypertrophy in the liver of males (which corresponded with increased liver weights) and tubular hyaline droplets, granular cast, pyelonephritis, and tubular degeneration/regeneration in the kidneys (severe in male animals), extramedullary haematopoiesis and hemosiderin pigment in the spleen, and eosinophilic inclusions and mineralization in the nasal olfactory epithelium. Based on these findings the target organs of butane-2-thiol were determined to be the erythrocyte, kidneys, liver, and nasal turbinates in rats. The NOAEC is 100 ppm (367.4 mg/m3 analytical).
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